Jason Andrews is an Associate Professor in the Division of Infectious Diseases and Geographic Medicine and a practicing infectious diseases physician.

Clinical Focus

  • Infectious Disease

Honors & Awards

  • Fellow, Infectious Diseases Society of America (2018)
  • NIH Director's New Innovator Award, NIH (2016)
  • George Rosenkranz Prize for Healthcare Research In Developing Countries, Rosenkranz Prize (2015)
  • The Union Young Investigator Prize, International Union Against Tuberculosis and Lung Disease (2015)
  • Young Physician-Scientist Award, American Society of Clinical Investigation (2014)
  • Dean?s Community Service Award, Harvard Medical School (2012)
  • David Brudnoy Scholar Award, Massachusetts General Hospital (2011)
  • David Brudnoy Scholar Award, Massachusetts General Hospital (2010)
  • Award for Best International Health Thesis, Yale School of Medicine Award (2007)
  • Merck Book Award for Academic Excellence, Yale School of Medicine (2007)

Boards, Advisory Committees, Professional Organizations

  • Faculty Fellow, Stanford Center for Innovation in Global Health (2015 - Present)

Professional Education

  • Medical Education: Yale University Office of the Registrar (2007) CT
  • Board Certification, American Board of Internal Medicine, Infectious Diseases (2012)
  • Fellowship, Harvard Combined Program in Infectious Diseases (Massachusetts General and Brigham and Women's Hospitals), Infectious Diseases (2012)
  • DTM&H, Gorgas Memorial Institute of Tropical & Preventive Medicine (2012)
  • Board Certification, American Board of Internal Medicine, Internal Medicine (2010)
  • SM, Harvard School of Public Health (2012)
  • Residency, University of California, San Francisco (2009)
  • Internship, University of California, San Francisco (2008)
  • MD, Yale University (2007)
  • BA, Yale University (2002)

Research & Scholarship

Current Research and Scholarly Interests

Our laboratory aims to develop and test innovative approaches to the diagnosis, treatment and control of infectious diseases in resource-limited settings. We draw upon multiple fields including mathematical modeling, microbial genetics, field epidemiology, and statistical inference to work on challenging problems in infectious diseases, with an emphasis on tuberculosis and tropical diseases. Our current field research sites are in Brazil, South Africa, Nepal and India.

Clinical Trials

  • Single-Blind Study of a Single Dose of Peginterferon Lambda-1a Compared With Placebo in Outpatients With Mild COVID-19 Recruiting

    To evaluate the efficacy of a single dose of subcutaneous injections of 180 ug of Peginterferon Lambda-1a, compared with placebo in reducing the duration of viral shedding of SARS-CoV-2 virus in patients with uncomplicated COVID-19 disease.

    View full details


  • Strategies for tuberculosis control in Brazilian prisons, Stanford University and Federal University of Grande Dourados



  • Congregate Air Sampling for Population-Based Detection of Tuberculosis, Stanford University and University of Cape Town


    Cape Town, South Africa

  • Evaluating effectiveness of typhoid conjugate vaccine introduction in Navi Mumbai, India, Stanford


    Navi Mumbai, India

  • Surveillance for Enteric Fever in Asia Project (SEAP)



  • Evaluating novel diagnostic approaches for tuberculosis


    Campo Grande, Brazil

  • Host blood biomarkers for diagnosis, prognosis and treatment response of childhood tuberculosis, Stanford University and University of Cape Town


    Cape Town, South Africa

  • Sero-epidemiology and environmental surveillance for enteric fever, Stanford University and Sabin Vaccine Institute


    Dhulikhel, Nepal

  • Global Burden of Tuberculosis in Prisons, Stanford University


    Stanford, California

  • Surveillance of Enteric Fever in India (SEFI), Christian Medical College Vellore and Stanford University


    Vellore, India

  • Characterizing Infectiousness Of Subclinical TB And Identifying Novel Early Diagnostic Strategies for Preventing Transmission, Stanford & Fiocruz Mato Grosso do Sul


    Mato Grosso do Sul, Brazil

  • Preventing Covid-19 in Correctional Facilities, Stanford


    California, USA

  • Does phage predation shape typhoid ecology in urban environments, Stanford University & Child Health Research Foundation (Bangladesh)


    Dhaka, Bangladesh

  • Detection of asymptomatic Salmonella enterica serotype Typhi and Paratyphi A carriage by serum antibodies targeting YncE, Massachusetts General Hospital, Stanford University, Dhulikhel Hospital


    Dhulikhel, Nepal

  • Development and validation of molecular viability assays for SARS-CoV-2, Stanford


    Stanford, California

  • Modeling to inform the response to the Covid-19 epidemic, Stanford


    Stanford, California


Stanford Advisees


All Publications

  • The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis. Lancet (London, England) Martinez, L., Cords, O., Horsburgh, C. R., Andrews, J. R. 2020; 395 (10228): 973?84


    Tens of millions of children are exposed to Mycobacterium tuberculosis globally every year; however, there are no contemporary estimates of the risk of developing tuberculosis in exposed children. The effectiveness of contact investigations and preventive therapy remains poorly understood.In this systematic review and meta-analysis, we investigated the development of tuberculosis in children closely exposed to a tuberculosis case and followed for incident disease. We restricted our search to cohort studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase electronic databases. Individual-participant data and a pre-specified list of variables were requested from authors of all eligible studies. These included characteristics of the exposed child, the index case, and environmental characteristics. To be eligible for inclusion in the final analysis, a dataset needed to include: (1) individuals below 19 years of age; (2) follow-up for tuberculosis for a minimum of 6 months; (3) individuals with household or close exposure to an individual with tuberculosis; (4) information on the age and sex of the child; and (5) start and end follow-up dates. Studies assessing incident tuberculosis but without dates or time of follow-up were excluded. Our analysis had two primary aims: (1) estimating the risk of developing tuberculosis by time-period of follow-up, demographics (age, region), and clinical attributes (HIV, tuberculosis infection status, previous tuberculosis); and (2) estimating the effectiveness of preventive therapy and BCG vaccination on the risk of developing tuberculosis. We estimated the odds of prevalent tuberculosis with mixed-effects logistic models and estimated adjusted hazard ratios (HRs) for incident tuberculosis with mixed-effects Poisson regression models. The effectiveness of preventive therapy against incident tuberculosis was estimated through propensity score matching. The study protocol is registered with PROSPERO (CRD42018087022).In total, study groups from 46 cohort studies in 34 countries-29 (63%) prospective studies and 17 (37%) retrospective-agreed to share their data and were included in the final analysis. 137?647 tuberculosis-exposed children were evaluated at baseline and 130?512 children were followed for 429?538 person-years, during which 1299 prevalent and 999 incident tuberculosis cases were diagnosed. Children not receiving preventive therapy with a positive result for tuberculosis infection had significantly higher 2-year cumulative tuberculosis incidence than children with a negative result for tuberculosis infection, and this incidence was greatest among children below 5 years of age (19·0% [95% CI 8·4-37·4]). The effectiveness of preventive therapy was 63% (adjusted HR 0·37 [95% CI 0·30-0·47]) among all exposed children, and 91% (adjusted HR 0·09 [0·05-0·15]) among those with a positive result for tuberculosis infection. Among all children <5 years of age who developed tuberculosis, 83% were diagnosed within 90 days of the baseline visit.The risk of developing tuberculosis among exposed infants and young children is very high. Most cases occurred within weeks of contact investigation initiation and might not be preventable through prophylaxis. This suggests that alternative strategies for prevention are needed, such as earlier initiation of preventive therapy through rapid diagnosis of adult cases or community-wide screening approaches.National Institutes of Health.

    View details for DOI 10.1016/S0140-6736(20)30166-5

    View details for PubMedID 32199484

  • Evaluating strategies for control of tuberculosis in prisons and prevention of spillover into communities: An observational and modeling study from Brazil. PLoS medicine Mabud, T. S., de Lourdes Delgado Alves, M., Ko, A. I., Basu, S., Walter, K. S., Cohen, T., Mathema, B., Colijn, C., Lemos, E., Croda, J., Andrews, J. R. 2019; 16 (1): e1002737


    It has been hypothesized that prisons serve as amplifiers of general tuberculosis (TB) epidemics, but there is a paucity of data on this phenomenon and the potential population-level effects of prison-focused interventions. This study (1) quantifies the TB risk for prisoners as they traverse incarceration and release, (2) mathematically models the impact of prison-based interventions on TB burden in the general population, and (3) generalizes this model to a wide range of epidemiological contexts.We obtained individual-level incarceration data for all inmates (n = 42,925) and all reported TB cases (n = 5,643) in the Brazilian state of Mato Grosso do Sul from 2007 through 2013. We matched individuals between prisoner and TB databases and estimated the incidence of TB from the time of incarceration and the time of prison release using Cox proportional hazards models. We identified 130 new TB cases diagnosed during incarceration and 170 among individuals released from prison. During imprisonment, TB rates increased from 111 cases per 100,000 person-years at entry to a maximum of 1,303 per 100,000 person-years at 5.2 years. At release, TB incidence was 229 per 100,000 person-years, which declined to 42 per 100,000 person-years (the average TB incidence in Brazil) after 7 years. We used these data to populate a compartmental model of TB transmission and incarceration to evaluate the effects of various prison-based interventions on the incidence of TB among prisoners and the general population. Annual mass TB screening within Brazilian prisons would reduce TB incidence in prisons by 47.4% (95% Bayesian credible interval [BCI], 44.4%-52.5%) and in the general population by 19.4% (95% BCI 17.9%-24.2%). A generalized model demonstrates that prison-based interventions would have maximum effectiveness in reducing community incidence in populations with a high concentration of TB in prisons and greater degrees of mixing between ex-prisoners and community members. Study limitations include our focus on a single Brazilian state and our retrospective use of administrative databases.Our findings suggest that the prison environment, more so than the prison population itself, drives TB incidence, and targeted interventions within prisons could have a substantial effect on the broader TB epidemic.

    View details for PubMedID 30677013

  • Extensively Drug-Resistant Typhoid - Are Conjugate Vaccines Arriving Just in Time? The New England journal of medicine Andrews, J. R., Qamar, F. N., Charles, R. C., Ryan, E. T. 2018; 379 (16): 1493?95

    View details for PubMedID 30332569

  • Typhoid conjugate vaccines: a new tool in the fight against antimicrobial resistance. The Lancet. Infectious diseases Andrews, J. R., Baker, S., Marks, F., Alsan, M., Garrett, D., Gellin, B. G., Saha, S. K., Qamar, F. N., Yousafzai, M. T., Bogoch, I. I., Antillon, M., Pitzer, V. E., Kim, J., John, J., Gauld, J., Mogasale, V., Ryan, E. T., Luby, S. P., Lo, N. C. 2018


    Typhoid fever is an acute systemic infectious disease responsible for an estimated 12-20 million illnesses and over 150?000 deaths annually. In March, 2018, a new recommendation was issued by WHO for the programmatic use of typhoid conjugate vaccines in endemic countries. Health economic analyses of typhoid vaccines have informed funding decisions and national policies regarding vaccine rollout. However, by focusing only on averted typhoid cases and their associated costs, traditional cost-effectiveness analyses might underestimate crucial benefits of typhoid vaccination programmes, because the potential effect of typhoid vaccines on the treatment of patients with non-specific acute febrile illnesses is not considered. For every true case of typhoid fever, three to 25 patients without typhoid disease are treated with antimicrobials unnecessarily, conservatively amounting to more than 50 million prescriptions per year. Antimicrobials for suspected typhoid might therefore be an important selective pressure for the emergence and spread of antimicrobial resistance globally. We propose that large-scale, more aggressive typhoid vaccination programmes-including catch-up campaigns in children up to 15 years of age, and vaccination in lower incidence settings-have the potential to reduce the overuse of antimicrobials and thereby reduce antimicrobial resistance in many bacterial pathogens. Funding bodies and national governments must therefore consider the potential for broad reductions in antimicrobial use and resistance in decisions related to the rollout of typhoid conjugate vaccines.

    View details for PubMedID 30170987

  • Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study. The Lancet. Respiratory medicine Andrews, J. R., Nemes, E., Tameris, M., Landry, B. S., Mahomed, H., McClain, J. B., Fletcher, H. A., Hanekom, W. A., Wood, R., McShane, H., Scriba, T. J., Hatherill, M. 2017


    The value of quantitative interferon-? release assay results for predicting progression from Mycobacterium tuberculosis infection to active disease is unknown. We aimed to investigate the relation between QuantiFERON-TB Gold In-Tube (QFT) conversion interferon-? values and risk of subsequent active tuberculosis disease and of QFT reversion.We analysed data from a reported vaccine efficacy trial of the tuberculosis vaccine MVA85A in South Africa. QFT negative, HIV uninfected young children aged 18-24 weeks were enrolled. We stratified participants by quantitative QFT result (interferon-? <0·35 IU/mL, 0·35-4·00 IU/mL, and >4·00 IU/mL) at the intermediate study visit (day 336) and determined risk of progression to active tuberculosis disease over the subsequent 6-24 months. No QFT differences were observed between placebo and MVA85A groups at day 336 or end of study; therefore, both groups were included in analyses. Study clinicians were not masked to QFT values, but strict case definitions were used that excluded QFT results. We used generalised additive models to evaluate the quantitative relation between day 336 QFT value and subsequent disease risk, and we compared disease rates between QFT strata using a two-sample Poisson test.Among 2512 young children with QFT tests done at day 336, 172 (7%) were positive; 87 (7%) of 1267 in placebo group and 85 (7%) of 1245 in the MVA85A group (p=1·00). Compared with QFT non-converters (tuberculosis disease incidence 0·7 per 100 person-years [95% CI 0·4-1·1]), children with QFT conversion at interferon-? values between 0·35-4·00 IU/mL did not have significantly increased risk of disease (2·5 per 100 person-years [95% CI 0·4-9·4]; incidence rate ratio (IRR) 3·7 (95% CI 0·4-15·8; p=0·23). However, QFT conversion at interferon-? values higher than 4·00 IU/mL was associated with substantially increased disease incidence (28·0 per 100 person-years [95% CI 14·9-45·7]) compared with non-converters (IRR 42·5 [95% CI 17·2-99·7]; p<0·0001), and compared with children with interferon-? values between 0·35-4·00 IU/mL (IRR 11·4 [95% CI 2·4-107·2]; p=0·00047). Among 91 QFT converters who were given a repeat test, 53 (58%) reverted from positive to negative. QFT reversion risk was inversely associated with interferon-? value at QFT conversion and was highest with interferon-? values less than 4·00 IU/mL (47 [77%] of 61).In young children, tuberculosis disease risk was not significantly increased, and QFT reversion was common, following QFT conversion at interferon-? values up to 10 times the recommended test threshold (0·35 IU/mL). By contrast, QFT conversion at very high interferon-? values (>4·00 IU/mL) warrants intensified diagnostic and preventive intervention because of the extremely high risk of tuberculosis disease in these young children.Aeras, Wellcome Trust, and Oxford-Emergent Tuberculosis Consortium (OETC) were the funders of the MVA85A 020 Trial. National Institute of Allergy and Infectious Diseases supported this analysis.

    View details for DOI 10.1016/S2213-2600(17)30060-7

    View details for PubMedID 28215501

  • Assessment of global guidelines for preventive chemotherapy against schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study LANCET INFECTIOUS DISEASES Lo, N. C., Lai, Y., Karagiannis-Voules, D., Bogoch, I. I., Coulibaly, J. T., Bendavid, E., Utzinger, J., Vounatsou, P., Andrews, J. R. 2016; 16 (9): 1065-1075


    WHO guidelines recommend annual treatment for schistosomiasis or soil-transmitted helminthiasis when prevalence in school-aged children is at or above a threshold of 50% and 20%, respectively. Separate treatment guidelines are used for these two helminthiases, and integrated community-wide treatment is not recommended. We assessed the cost-effectiveness of changing prevalence thresholds and treatment guidelines under an integrated delivery framework.We developed a dynamic, age-structured transmission and cost-effectiveness model that simulates integrated preventive chemotherapy programmes against schistosomiasis and soil-transmitted helminthiasis. We assessed a 5-year treatment programme with praziquantel (40 mg/kg per treatment) against schistosomiasis and albendazole (400 mg per treatment) against soil-transmitted helminthiasis at 75% coverage. We defined strategies as highly cost-effective if the incremental cost-effectiveness ratio was less than the World Bank classification for a low-income country (gross domestic product of US$1045 per capita). We calculated the prevalence thresholds for cost-effective preventive chemotherapy of various strategies, and estimated treatment needs for sub-Saharan Africa.Annual preventive chemotherapy against schistosomiasis was highly cost-effective in treatment of school-aged children at a prevalence threshold of 5% (95% uncertainty interval [UI] 1·7-5·2; current guidelines recommend treatment at 50% prevalence) and for community-wide treatment at a prevalence of 15% (7·3-18·5; current recommendation is unclear, some community treatment recommended at 50% prevalence). Annual preventive chemotherapy against soil-transmitted helminthiasis was highly cost-effective in treatment of school-aged children at a prevalence of 20% (95% UI 5·4-30·5; current guidelines recommend treatment at 20% prevalence) and the entire community at 60% (35·3-85·1; no guidelines available). When both helminthiases were co-endemic, prevalence thresholds using integrated delivery were lower. Using this revised treatment framework, we estimated that treatment needs would be six times higher than WHO guidelines for praziquantel and two times higher for albendazole. An additional 21·3% (95% Bayesian credible interval 20·4-22·2) of the population changed from receiving non-integrated treatment under WHO guidelines to integrated treatment (both praziquantel and albendazole). Country-specific economic differences resulted in heterogeneity around these prevalence thresholds.Annual preventive chemotherapy programmes against schistosomiasis and soil-transmitted helminthiasis are likely to be highly cost-effective at prevalences lower than WHO recommendations. These findings support substantial treatment scale-up, community-wide coverage, integrated treatment in co-endemic settings that yield substantial cost synergies, and country-specific treatment guidelines.Doris Duke Charitable Foundation, Mount Sinai Hospital-University Health Network AMO Innovation Fund, and Stanford University Medical Scholars Programme.

    View details for DOI 10.1016/S1473-3099(16)30073-1

    View details for Web of Science ID 000381655200036

    View details for PubMedID 27286968

  • Comparison of community-wide, integrated mass drug administration strategies for schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study. The Lancet. Global health Lo, N. C., Bogoch, I. I., Blackburn, B. G., Raso, G., N'Goran, E. K., Coulibaly, J. T., Becker, S. L., Abrams, H. B., Utzinger, J., Andrews, J. R. 2015; 3 (10): e629-38


    More than 1·5 billion people are affected by schistosomiasis or soil-transmitted helminthiasis. WHO's recommendations for mass drug administration (MDA) against these parasitic infections emphasise treatment of school-aged children, using separate treatment guidelines for these two helminthiases groups. We aimed to evaluate the cost-effectiveness of expanding integrated MDA to the entire community in four settings in Côte d'Ivoire.We extended previously published, dynamic, age-structured models of helminthiases transmission to simulate costs and disability averted with integrated MDA (of praziquantel and albendazole) for schistosomiasis and soil-transmitted helminthiasis. We calibrated the model to data for prevalence and intensity of species-specific helminth infection from surveys undertaken in four communities in Côte d'Ivoire between March, 1997, and September, 2010. We simulated a 15-year treatment programme with 75% coverage in only school-aged children; school-aged children and preschool-aged children; adults; and the entire community. Treatment costs were estimated at US$0·74 for school-aged children and $1·74 for preschool-aged children and adults. The incremental cost-effectiveness ratio (ICER) was calculated in 2014 US dollars per disability-adjusted life-year (DALY) averted.Expanded community-wide treatment was highly cost effective compared with treatment of only school-aged children (ICER $167 per DALY averted) and WHO guidelines (ICER $127 per DALY averted), and remained highly cost effective even if treatment costs for preschool-aged children and adults were ten times greater than those for school-aged children. Community-wide treatment remained highly cost effective even when elimination of helminth infections was not achieved. These findings were robust across the four diverse communities in Côte d'Ivoire, only one of which would have received annual MDA for both schistosomiasis and soil-transmitted helminthiasis under the latest WHO guidelines. Treatment every 6 months was also highly cost effective in three out of four communities.Integrated, community-wide MDA programmes for schistosomiasis and soil-transmitted helminthiasis can be highly cost effective, even in communities with low disease burden in any helminth group. These results support an urgent need to re-evaluate current global guidelines for helminthiases control programmes to include community-wide treatment, increased treatment frequency, and consideration for lowered prevalence thresholds for integrated treatment.Stanford University Medical Scholars Programme, Mount Sinai Hospital-University Health Network AMO Innovation Fund.

    View details for DOI 10.1016/S2214-109X(15)00047-9

    View details for PubMedID 26385302

  • Integrating Social Contact and Environmental Data in Evaluating Tuberculosis Transmission in a South African Township JOURNAL OF INFECTIOUS DISEASES Andrews, J. R., Morrow, C., Walensky, R. P., Wood, R. 2014; 210 (4): 597-603


    Background.?Population models of tuberculosis transmission have not accounted for social contact structure and the role of the environment in which tuberculosis is transmitted.Methods.?We utilized extensions to the Wells-Riley model of tuberculosis transmission, using exhaled carbon dioxide as a tracer gas, to describe transmission patterns in an endemic community. Drawing upon social interaction data and carbon dioxide measurements from a South African township, we created an age-structured model of tuberculosis transmission in households, public transit, schools and workplaces. We fit the model to local data on latent tuberculosis prevalence by age.Results.?Most tuberculosis infections (84%) were estimated to occur outside of one's own household. 50% of infections among young adults (ages 15-19) occurred in schools, due to high contact rates and poor ventilation. Despite lower numbers of contacts in workplaces, assortative mixing among adults with high rates of smear-positive tuberculosis contributed to transmission in this environment. Households and public transit were important sites of transmission between age groups.Conclusions.?Consistent with molecular epidemiologic estimates, a minority of tuberculosis transmission was estimated to occur within households, which may limit the impact of contact investigations. Further work is needed to investigate the role of schools in tuberculosis transmission.

    View details for DOI 10.1093/infdis/jiu138

    View details for Web of Science ID 000340243500013

    View details for PubMedID 24610874

  • Risk of Progression to Active Tuberculosis Following Reinfection With Mycobacterium tuberculosis CLINICAL INFECTIOUS DISEASES Andrews, J. R., Noubary, F., Walensky, R. P., Cerda, R., Losina, E., Horsburgh, C. R. 2012; 54 (6): 784-791


    The risk of progression to active tuberculosis is greatest in the several years following initial infection. The extent to which latent tuberculosis infection reduces the risk of progressive disease following reexposure and reinfection is not known. Indirect estimates from population models have been highly variable.We reviewed prospective cohort studies of persons exposed to individuals with infectious tuberculosis that were published prior to the widespread treatment of latent tuberculosis to estimate the incidence of tuberculosis among individuals with latent tuberculosis infection (LTBI group) and without latent tuberculosis (uninfected; UI group). We calculated the incidence rate ratio (IRR) of tuberculosis disease following infection between these 2 groups. We then adjusted incidence for expected reactivation, proportion of each group that was infected, and median time of observation following infection during the study.We identified 18 publications reporting tuberculosis incidence among 23 paired cohorts of individuals with and without latent infection (total N = 19 886). The weighted mean adjusted incidence rate of tuberculosis in the LTBI and UI groups attributable to reinfection was 13.5 per 1000 person-years (95% confidence interval [CI]: 5.0-26.2 per 1000 person-years) and that attributable to primary infection was 60.1 per 1000 person-years (95% CI: 38.6-87.4 per 1000 person-years). The adjusted IRR for tuberculosis in the LTBI group compared with the UI group was 0.21 (95% CI: .14-.30).Individuals with latent tuberculosis had 79% lower risk of progressive tuberculosis after reinfection than uninfected individuals. The risk reduction estimated in this study is greater than most previous estimates made through population models.

    View details for DOI 10.1093/cid/cir951

    View details for Web of Science ID 000300790900009

    View details for PubMedID 22267721

  • Transmission dynamics and control of cholera in Haiti: an epidemic model LANCET Andrews, J. R., Basu, S. 2011; 377 (9773): 1248-1255


    Official projections of the cholera epidemic in Haiti have not incorporated existing disease trends or patterns of transmission, and proposed interventions have been debated without comparative estimates of their effect. We used a mathematical model of the epidemic to provide projections of future morbidity and mortality, and to produce comparative estimates of the effects of proposed interventions.We designed mathematical models of cholera transmission based on existing models and fitted them to incidence data reported in Haiti for each province from Oct 31, 2010, to Jan 24, 2011. We then simulated future epidemic trajectories from March 1 to Nov 30, 2011, to estimate the effect of clean water, vaccination, and enhanced antibiotic distribution programmes.We project 779,000 cases of cholera in Haiti (95% CI 599,000-914,000) and 11,100 deaths (7300-17,400) between March 1 and Nov 30, 2011. We expect that a 1% per week reduction in consumption of contaminated water would avert 105,000 cases (88,000-116,000) and 1500 deaths (1100-2300). We predict that the vaccination of 10% of the population, from March 1, will avert 63,000 cases (48,000-78,000) and 900 deaths (600-1500). The proposed extension of the use of antibiotics to all patients with severe dehydration and half of patients with moderate dehydration is expected to avert 9000 cases (8000-10,000) and 1300 deaths (900-2000).A decline in cholera prevalence in early 2011 is part of the natural course of the epidemic, and should not be interpreted as indicative of successful intervention. Substantially more cases of cholera are expected than official estimates used for resource allocation. Combined, clean water provision, vaccination, and expanded access to antibiotics might avert thousands of deaths.National Institutes of Health.

    View details for DOI 10.1016/S0140-6736(11)60273-0

    View details for Web of Science ID 000289597300031

    View details for PubMedID 21414658

  • Exogenous reinfection as a cause of multidrug-resistant and extensively drug-resistant tuberculosis in rural South Africa. Journal of Infectious Diseases Andrews, J. R., Gandhi, N. R., Prashini, M., N, S. S., Louise, B., Moll, A. P., Pillay, M., Friedland, G., Sturm, A. W. 2008; 198 (11): 1582-9
  • Primary Prophylaxis to Prevent Tuberculosis Infection in Prison Inmates: A Randomized, Double-Blind, Placebo-Controlled Trial. The American journal of tropical medicine and hygiene Dias de Oliveira, R., da Silva Santos, A., Reis, C. B., de Cássia Leite, A., Correia Sacchi, F. P., Araujo, R. P., Dos Santos, P. P., Rolla, V. C., Martinez, L., Andrews, J., Croda, J. 2020


    In many low- and middle-income countries, tuberculosis (TB) incidence in prisons is high, exposing incarcerated populations to an elevated risk of TB infection. We conducted a randomized, double-blind, placebo-controlled trial among HIV-negative male inmates of a high TB burden prison to determine whether isoniazid given twice weekly (900 mg) for 12 months prevents TB infection. The primary outcome was QuantiFERON-TB Gold in Plus (QFT) conversion to ? 0.35 international units per milliliter (IU/mL) at 6 months; secondary outcomes included alternative QFT thresholds (? 0.7, ? 2.0, and ? 4.0 IU/mL). In total, 467 participants were randomly assigned to intervention (N = 258) or control (N = 209). In an interim analysis of participants who had completed 6 months of follow-up (N = 170), QFT conversion occurred in 20.8% (19/91) and 21.5% (17/79) of participants in intervention and control arms (efficacy: 2.9%, P = 0.91), respectively. The trial was then stopped according to the trial protocol, and the remaining participants prematurely discontinued. In an analysis of secondary outcomes, the intervention arm had significantly lower rates of conversion at a cutoff of ? 2.0 IU/mL (efficacy: 82.6%, P < 0.01). In conclusion, 900 mg of isoniazid, administered twice a week, did not effectively prevent QFT conversion at a cutoff point ? 0.35 IU/mL in a trial of QFT-negative inmates. Higher QFT cutoffs are associated with sustained conversion and greater protection. Future clinical trials that evaluate protection for latent infection should use the highest cutoff than that recommended by the manufacturer.

    View details for DOI 10.4269/ajtmh.20-0110

    View details for PubMedID 32876010

  • Gold-standard cholera diagnostics are tarnished by lytic bacteriophage and antibiotics. Journal of clinical microbiology Nelson, E. J., Grembi, J. A., Chao, D. L., Andrews, J. R., Alexandrova, L., Rodriguez, P. H., Ramachandran, V. V., Sayeed, M. A., Wamala, J. F., Debes, A. K., Sack, D. A., Hryckowian, A. J., Haque, F., Khatun, S., Rahman, M., Chien, A., Spormann, A. M., Schoolnik, G. K. 2020


    A fundamental, clinical and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity. Cholera was chosen as a model disease to investigate this important question because cholera outbreaks enable large enrollment, field methods are well established, and the predatory relationship between lytic bacteriophage and the etiologic agent Vibrio cholerae share commonalities across bacterial taxa. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as a function of lytic bacteriophage detection and exposure to the first-line antibiotic azithromycin detected in stool samples by mass spectrometry. Among diarrheal samples positive by nanoliter quantitative PCR for V. cholerae (n=78/849), the odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by 89% (OR 0.108; 95%CI 0.002-0.872) and 87% (OR 0.130; 95%CI 0.022-0.649) when lytic bacteriophage were detected, respectively. The odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by more than 99% (OR 0.00; 95% CI: 0.00-0.28) and 89% (OR 0.11; 95% CI: 0.03-0.44) when azithromycin was detected, respectively. Analysis of additional samples from South Sudan found similar phage effects on RDTs; antibiotics were not assayed. Cholera burden estimates may improve by accommodating for the negative effects of lytic bacteriophage and antibiotic exposure on diagnostic positivity. One accommodation is using bacteriophage detection as proxy for pathogen detection. These findings have relevance for other diagnostic settings where bacterial pathogens are vulnerable to lytic bacteriophage predation.

    View details for DOI 10.1128/JCM.00412-20

    View details for PubMedID 32611794

  • Oral swab testing by Xpert® MTB/RIF Ultra for mass tuberculosis screening in prisons. Journal of clinical tuberculosis and other mycobacterial diseases Lima, F., Santos, A. S., Oliveira, R. D., Silva, C. C., Gonçalves, C. C., Andrews, J. R., Croda, J. 2020; 19: 100148


    Diagnosis of pulmonary tuberculosis is usually achieved by testing sputum for presence of Mycobacterium tuberculosis by microscopy, culture or nucleic acid amplification tests. However, many individuals are unable to produce sputum, particularly early in the course of illness. Studies have reported that oral swabs, assayed by nucleic acid amplification tests, may be a suitable substitute or complement to sputum testing. To determine whether this method could be useful of case finding, in which bacillary load is often lower, we evaluated it in the setting of a mass tuberculosis screening study in prison inmates in Brazil. For this sub-study, we enrolled 128 individuals with pulmonary tuberculosis confirmed by sputum Xpert testing, and 128 controls who tested negative by sputum culture and Xpert. We collected two oral swabs by participant, prior to starting treatment. Swabs were collected from the tongue by brushing along the surface for 10 times. The sensitivity of a single oral swab was 43% (N = 55/128; 95% CI: 34-52%). Using two consecutive oral swabs the sensitivity increased to 51% (N = 66/128; 95% CI: 43-60%). The specificity was 100% (128/128). In participants with high mycobaterial load in the sputum, the combined sensitivity was 90% (N = 9/10). In the participants with medium mycobaterial load in the sputum, the combined sensitivity was 79% (N = 23/29). In the participants with low or very low mycobaterial load in the sputum, the combined sensitivity was 38% (N = 34/89). Our data suggest that oral swab sampling, assayed by Xpert, has comparable sensitivity to sputum in participants with high and medium mycobacterial load in the sputum. However, 70% (89/128) of individuals identified through our mass screening study (Carbone et al.) had detection number low or very low in their sputum. In this population, oral swab testing may not have sufficient sensitivity as currently performed. Further studies are needed to identify alternative non-sputum sampling strategies in this population.

    View details for DOI 10.1016/j.jctube.2020.100148

    View details for PubMedID 32099908

    View details for PubMedCentralID PMC7031315

  • Cost-Effectiveness of a Pharmacogenomic Test for Stratified Isoniazid Dosing in Treatment of Active Tuberculosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Rens, N. E., Uyl-de Groot, C. A., Goldhaber-Fiebert, J. D., Croda, J., Andrews, J. R. 2020


    There is marked interindividual variability in metabolism and resulting toxicity and effectiveness of drugs used for tuberculosis treatment. For isoniazid, mutations in the N-acetyltransferase-2 (NAT2) gene explain over 88% of pharmacokinetic variability. However, weight-based dosing remains the norm globally. The potential clinical impact and cost-effectiveness of pharmacogenomic-guided therapy (PGT) is unknown.We constructed a decision tree model to project lifetime costs and benefits of isoniazid PGT for drug-susceptible tuberculosis in Brazil, South Africa, and India. PGT was modeled to reduce isoniazid toxicity among slow NAT2 acetylators and reduce treatment failure among rapid acetylators. The genotyping test was assumed to cost the same as the GeneXpert test. The main outcomes were costs (2018 USD), quality adjusted life years (QALYs), and incremental cost-effectiveness ratios.In Brazil, PGT gained 19 discounted life years (23 QALYs) and cost $11,064 per 1,000 patients, a value of $476 per QALY gained. In South Africa, PGT gained 15 life years (19 QALYs) and cost $33,182 per 1,000 patients, a value of $1,780 per QALY gained. In India, PGT gained 20 life years (24 QALYs) and cost $13,195 per 1,000 patients, a value of $546 per QALY gained. One-way sensitivity analyses showed the cost-effectiveness to be robust to all input parameters. Probabilistic sensitivity analyses were below per capita GDP in all three countries in 99% of simulations.Isoniazid PGT improves health outcomes and would be cost-effective in the treatment of drug-susceptible tuberculosis in Brazil, South Africa, and India.

    View details for DOI 10.1093/cid/ciz1212

    View details for PubMedID 31905381

  • Clinical Validation of a Deep Learning Algorithm for Detection of Pneumonia on Chest Radiographs in Emergency Department Patients with Acute Febrile Respiratory Illness. Journal of clinical medicine Kim, J. H., Kim, J. Y., Kim, G. H., Kang, D., Kim, I. J., Seo, J., Andrews, J. R., Park, C. M. 2020; 9 (6)


    Early identification of pneumonia is essential in patients with acute febrile respiratory illness (FRI). We evaluated the performance and added value of a commercial deep learning (DL) algorithm in detecting pneumonia on chest radiographs (CRs) of patients visiting the emergency department (ED) with acute FRI. This single-centre, retrospective study included 377 consecutive patients who visited the ED and the resulting 387 CRs in August 2018-January 2019. The performance of a DL algorithm in detection of pneumonia on CRs was evaluated based on area under the receiver operating characteristics (AUROC) curves, sensitivity, specificity, negative predictive values (NPVs), and positive predictive values (PPVs). Three ED physicians independently reviewed CRs with observer performance test to detect pneumonia, which was re-evaluated with the algorithm eight weeks later. AUROC, sensitivity, and specificity measurements were compared between "DL algorithm" vs. "physicians-only" and between "physicians-only" vs. "physicians aided with the algorithm". Among 377 patients, 83 (22.0%) had pneumonia. AUROC, sensitivity, specificity, PPV, and NPV of the algorithm for detection of pneumonia on CRs were 0.861, 58.3%, 94.4%, 74.2%, and 89.1%, respectively. For the detection of 'visible pneumonia on CR' (60 CRs from 59 patients), AUROC, sensitivity, specificity, PPV, and NPV were 0.940, 81.7%, 94.4%, 74.2%, and 96.3%, respectively. In the observer performance test, the algorithm performed better than the physicians for pneumonia (AUROC, 0.861 vs. 0.788, p = 0.017; specificity, 94.4% vs. 88.7%, p < 0.0001) and visible pneumonia (AUROC, 0.940 vs. 0.871, p = 0.007; sensitivity, 81.7% vs. 73.9%, p = 0.034; specificity, 94.4% vs. 88.7%, p < 0.0001). Detection of pneumonia (sensitivity, 82.2% vs. 53.2%, p = 0.008; specificity, 98.1% vs. 88.7%; p < 0.0001) and 'visible pneumonia' (sensitivity, 82.2% vs. 73.9%, p = 0.014; specificity, 98.1% vs. 88.7%, p < 0.0001) significantly improved when the algorithm was used by the physicians. Mean reading time for the physicians decreased from 165 to 101 min with the assistance of the algorithm. Thus, the DL algorithm showed a better diagnosis of pneumonia, particularly visible pneumonia on CR, and improved diagnosis by ED physicians in patients with acute FRI.

    View details for DOI 10.3390/jcm9061981

    View details for PubMedID 32599874

  • The household secondary attack rate of SARS-CoV-2: A rapid review. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Fung, H. F., Martinez, L., Alarid-Escudero, F., Salomon, J. A., Studdert, D. M., Andrews, J. R., Goldhaber-Fiebert, J. D. 2020


    Although much of the public health effort to combat COVID-19 has focused on disease control strategies in public settings, transmission of SARS-CoV-2 within households remains an important problem. The nature and determinants of household transmission are poorly understood.To address this gap, we gathered and analyzed data from 22 published and pre-published studies from 10 countries (20,291 household contacts) that were available through September 2, 2020. Our goal was to combine estimates of the SARS-CoV-2 household secondary attack rate (SAR) and explore variation in estimates of the household SAR.The overall pooled random-effects estimate of the household SAR was 17.1% (95% CI: 13.7-21.2%). In study-level, random-effects meta-regressions stratified by testing frequency (1 test, 2 tests, >2 tests), SAR estimates were 9.2% (95% CI: 6.7-12.3%), 17.5% (95% CI: 13.9-21.8%), and 21.3% (95% CI: 13.8-31.3%), respectively. Household SAR tended to be higher among older adult contacts and among contacts of symptomatic cases.These findings suggest that SAR reported using a single follow-up test may be underestimated and that testing household contacts of COVID-19 cases on multiple occasions may increase the yield for identifying secondary cases.

    View details for DOI 10.1093/cid/ciaa1558

    View details for PubMedID 33045075

  • Interferon-gamma release assay for accurate detection of SARS-CoV-2 T cell response. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Murugesan, K., Jagannathan, P., Pham, T. D., Pandey, S., Bonilla, H. F., Jacobson, K., Parsonnet, J., Andrews, J. R., Weiskopf, D., Sette, A., Pinsky, B. A., Singh, U., Banaei, N. 2020


    We investigated feasibility and accuracy of an interferon-gamma release assay (IGRA) for detection of T cell responses to SARS-CoV-2. Whole blood IGRA accurately distinguished between convalescents and uninfected healthy blood donors with a predominantly CD4+ T cell response. SARS-CoV-2 IGRA may serve as a useful diagnostic tool in managing the COVID-19 pandemic.

    View details for DOI 10.1093/cid/ciaa1537

    View details for PubMedID 33035306

  • Deep learning-based automated detection algorithm for active pulmonary tuberculosis on chest radiographs: diagnostic performance in systematic screening of asymptomatic individuals. European radiology Lee, J. H., Park, S., Hwang, E. J., Goo, J. M., Lee, W. Y., Lee, S., Kim, H., Andrews, J. R., Park, C. M. 2020


    Performance of deep learning-based automated detection (DLAD) algorithms in systematic screening for active pulmonary tuberculosis is unknown. We aimed to validate DLAD algorithm for detection of active pulmonary tuberculosis and any radiologically identifiable relevant abnormality on chest radiographs (CRs) in this setting.We performed out-of-sample testing of a pre-trained DLAD algorithm, using CRs from 19.686 asymptomatic individuals (ages, 21.3 ± 1.9 years) as part of systematic screening for tuberculosis between January 2013 and July 2018. Area under the receiver operating characteristic curves (AUC) for diagnosis of tuberculosis and any relevant abnormalities were measured. Accuracy measures including sensitivities, specificities, positive predictive values (PPVs), and negative predictive values (NPVs) were calculated at pre-defined operating thresholds (high sensitivity threshold, 0.16; high specificity threshold, 0.46).All five CRs from four individuals with active pulmonary tuberculosis were correctly classified as having abnormal findings by DLAD with specificities of 0.959 and 0.997, PPVs of 0.006 and 0.068, and NPVs of both 1.000 at high sensitivity and high specificity thresholds, respectively. With high specificity thresholds, DLAD showed comparable diagnostic measures with the pooled radiologists (p values > 0.05). For the radiologically identifiable relevant abnormality (n = 28), DLAD showed an AUC value of 0.967 (95% confidence interval, 0.938-0.996) with sensitivities of 0.821 and 0.679, specificities of 0.960 and 0.997, PPVs of 0.028 and 0.257, and NPVs of both 0.999 at high sensitivity and high specificity thresholds, respectively.In systematic screening for tuberculosis in a low-prevalence setting, DLAD algorithm demonstrated excellent diagnostic performance, comparable with the radiologists in the detection of active pulmonary tuberculosis.? Deep learning-based automated detection algorithm detected all chest radiographs with active pulmonary tuberculosis with high specificities and negative predictive values in systematic screening. ? Deep learning-based automated detection algorithm had comparable diagnostic measures with the radiologists for detection of active pulmonary tuberculosis on chest radiographs. ? For the detection of radiologically identifiable relevant abnormalities on chest radiographs, deep learning-based automated detection algorithm showed excellent diagnostic performance in systematic screening.

    View details for DOI 10.1007/s00330-020-07219-4

    View details for PubMedID 32857202

  • The Surveillance for Enteric Fever in Asia Project (SEAP), Severe Typhoid Fever Surveillance in Africa (SETA), Surveillance of Enteric Fever in India (SEFI), and Strategic Typhoid Alliance Across Africa and Asia (STRATAA) Population-based Enteric Fever Studies: A Review of Methodological Similarities and Differences. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Carey, M. E., MacWright, W. R., Im, J., Meiring, J. E., Gibani, M. M., Park, S. E., Longley, A., Jeon, H. J., Hemlock, C., Yu, A. T., Soura, A., Aiemjoy, K., Owusu-Dabo, E., Terferi, M., Islam, S., Lunguya, O., Jacobs, J., Gordon, M., Dolecek, C., Baker, S., Pitzer, V. E., Yousafzai, M. T., Tonks, S., Clemens, J. D., Date, K., Qadri, F., Heyderman, R. S., Saha, S. K., Basnyat, B., Okeke, I. N., Qamar, F. N., Voysey, M., Luby, S., Kang, G., Andrews, J., Pollard, A. J., John, J., Garrett, D., Marks, F. 2020; 71 (Supplement_2): S102?S110


    Building on previous multicountry surveillance studies of typhoid and others salmonelloses such as the Diseases of the Most Impoverished program and the Typhoid Surveillance in Africa Project, several ongoing blood culture surveillance studies are generating important data about incidence, severity, transmission, and clinical features of invasive Salmonella infections in sub-Saharan Africa and South Asia. These studies are also characterizing drug resistance patterns in their respective study sites. Each study answers a different set of research questions and employs slightly different methodologies, and the geographies under surveillance differ in size, population density, physician practices, access to healthcare facilities, and access to microbiologically safe water and improved sanitation. These differences in part reflect the heterogeneity of the epidemiology of invasive salmonellosis globally, and thus enable generation of data that are useful to policymakers in decision-making for the introduction of typhoid conjugate vaccines (TCVs). Moreover, each study is evaluating the large-scale deployment of TCVs, and may ultimately be used to assess post-introduction vaccine impact. The data generated by these studies will also be used to refine global disease burden estimates. It is important to ensure that lessons learned from these studies not only inform vaccination policy, but also are incorporated into sustainable, low-cost, integrated vaccine-preventable disease surveillance systems.

    View details for DOI 10.1093/cid/ciaa367

    View details for PubMedID 32725221

  • Environmental Surveillance as a Tool for Identifying High-risk Settings for Typhoid Transmission. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Andrews, J. R., Yu, A. T., Saha, S., Shakya, J., Aiemjoy, K., Horng, L., Qamar, F., Garrett, D., Baker, S., Saha, S., Luby, S. P. 2020; 71 (Supplement_2): S71?S78


    Enteric fever remains a major cause of morbidity in developing countries with poor sanitation conditions that enable fecal contamination of water distribution systems. Historical evidence has shown that contamination of water systems used for household consumption or agriculture are key transmission routes for Salmonella Typhi and Salmonella Paratyphi A. The World Health Organization now recommends that typhoid conjugate vaccines (TCV) be used in settings with high typhoid incidence; consequently, governments face a challenge regarding how to prioritize typhoid against other emerging diseases. A key issue is the lack of typhoid burden data in many low- and middle-income countries where TCV could be deployed. Here we present an argument for utilizing environmental sampling for the surveillance of enteric fever organisms to provide data on community-level typhoid risk. Such an approach could complement traditional blood culture-based surveillance or even replace it in settings where population-based clinical surveillance is not feasible. We review historical studies characterizing the transmission of enteric fever organisms through sewage and water, discuss recent advances in the molecular detection of typhoidal Salmonella in the environment, and outline challenges and knowledge gaps that need to be addressed to establish environmental sampling as a tool for generating actionable data that can inform public health responses to enteric fever.

    View details for DOI 10.1093/cid/ciaa513

    View details for PubMedID 32725227

  • Genomic variant-identification methods may alter Mycobacterium tuberculosis transmission inferences. Microbial genomics Walter, K. S., Colijn, C., Cohen, T., Mathema, B., Liu, Q., Bowers, J., Engelthaler, D. M., Narechania, A., Lemmer, D., Croda, J., Andrews, J. R. 2020


    Pathogen genomic data are increasingly used to characterize global and local transmission patterns of important human pathogens and to inform public health interventions. Yet, there is no current consensus on how to measure genomic variation. To test the effect of the variant-identification approach on transmission inferences for Mycobacterium tuberculosis, we conducted an experiment in which five genomic epidemiology groups applied variant-identification pipelines to the same outbreak sequence data. We compared the variants identified by each group in addition to transmission and phylogenetic inferences made with each variant set. To measure the performance of commonly used variant-identification tools, we simulated an outbreak. We compared the performance of three mapping algorithms, five variant callers and two variant filters in recovering true outbreak variants. Finally, we investigated the effect of applying increasingly stringent filters on transmission inferences and phylogenies. We found that variant-calling approaches used by different groups do not recover consistent sets of variants, which can lead to conflicting transmission inferences. Further, performance in recovering true variation varied widely across approaches. While no single variant-identification approach outperforms others in both recovering true genome-wide and outbreak-level variation, variant-identification algorithms calibrated upon real sequence data or that incorporate local reassembly outperform others in recovering true pairwise differences between isolates. The choice of variant filters contributed to extensive differences across pipelines, and applying increasingly stringent filters rapidly eroded the accuracy of transmission inferences and quality of phylogenies reconstructed from outbreak variation. Commonly used approaches to identify M. tuberculosis genomic variation have variable performance, particularly when predicting potential transmission links from pairwise genetic distances. Phylogenetic reconstruction may be improved by less stringent variant filtering. Approaches that improve variant identification in repetitive, hypervariable regions, such as long-read assemblies, may improve transmission inference.

    View details for DOI 10.1099/mgen.0.000418

    View details for PubMedID 32735210

  • Yield, Efficiency and Costs of Mass Screening Algorithms for Tuberculosis in Brazilian Prisons. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Santos, A. d., Oliveira, R. D., Lemos, E. F., Lima, F., Cohen, T., Cords, O., Martinez, L., Gonçalves, C., Ko, A., Andrews, J. R., Croda, J. 2020


    Tuberculosis is a major cause of morbidity and mortality among incarcerated populations globally. We performed mass tuberculosis screening in three prisons and assessed yield, efficiency, and costs associated with various screening algorithms.Between 2017 and 2018, inmates from the three prisons in Brazil were screened for tuberculosis by symptom assessment, chest radiography, sputum testing by Xpert MTB/RIF 4th generation and culture. Chest radiographs were scored by an automated interpretation algorithm (CAD4TB) that was locally calibrated to establish a positivity threshold. Four diagnostic algorithms were evaluated. We assessed the yield (percent of total cases found) and efficiency (prevalence among those screened) for each algorithm. We performed unit costing to estimate the costs of each screening or diagnostic test and calculated the cost per case detected for each algorithm.We screened 5,387 prisoners, of whom 214 (3.9%) were diagnosed with tuberculosis. Compared to other screening strategies initiated with radiography or chest symptoms, the trial of all participants with a single Xpert MTB / RIF sputum test detected 74% of all tuberculosis cases at a cost of $ 249. Performing Xpert MTB/RIF screening tests only on those with symptoms had a similar cost per case diagnosed (US$ 255) but missed as many cases (73 vs 54) as screening all inmates.In this prospective study in three with prisons in high tuberculosis burden countries Brazilian prisons, we found that testing all participants with sputum Xpert MTB/RIF was sensitive approach, while remaining cost-efficient. These results support use of Xpert MTB/RIF for mass screening in tuberculosis-endemic prisons.

    View details for DOI 10.1093/cid/ciaa135

    View details for PubMedID 32064514

  • Seasonal drivers of tuberculosis: evidence from over 100 years of notifications in Cape Town. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Andrews, J. R., Cobelens, F., Horsburgh, C. R., Hatherill, M., Basu, S., Hermans, S., Wood, R. 2020; 24 (5): 477?84


    BACKGROUND: Tuberculosis incidence varies seasonally in many settings. However, the role of seasonal variation in reactivation vs. transmission is unclear.METHODS: We reviewed data on TB notifications in Cape Town, South Africa, from 1903 to 2017 (exclusive of 1995-2002, which were unavailable). Data from 2003 onward were stratified by HIV status, age and notification status (new vs. retreatment). We performed seasonal decomposition and time-dependent spectral analysis using wavelets to assess periodicity over time. We estimated monthly peak-to-peak seasonal amplitude of notifications as a percentage of the annual notification rate.RESULTS: A seasonal trend was intermittently detected between 1904 and 1994, particularly during periods of high notification rates, but was consistently and strongly evident between 2003 and 2017, with peaks in September through November, following winter. Among young children, a second, higher seasonal peak was observed in March. Seasonal variation was greater in children (<5 years, 54%, 95% CI 47-61; 5-14 years, 63%, 95% CI 58-69) than in adults (36%, 95% CI 33-39).CONCLUSIONS: Stronger seasonal effects were seen in children, in whom progression following recent infection is known to be the predominant driver of disease. These findings may support increased transmission in the winter as an important driver of TB in Cape Town.

    View details for DOI 10.5588/ijtld.19.0274

    View details for PubMedID 32398196

  • Identifying priorities for testing and treatment of latent tuberculosis infection in the United States. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Martinez, L., Andrews, J. R. 2020

    View details for DOI 10.1093/cid/ciaa850

    View details for PubMedID 32588882

  • Evaluation of a Rapid Point-of-Care Multiplex Immunochromatographic Assay for the Diagnosis of Enteric Fever. mSphere Kumar, S., Nodoushani, A., Khanam, F., DeCruz, A. T., Lambotte, P., Scott, R., Bogoch, I. I., Vaidya, K., Calderwood, S. B., Bhuiyan, T. R., Esfandiari, J., Ryan, E. T., Qadri, F., Andrews, J. R., Charles, R. C. 2020; 5 (3)


    There is a critical need for an improved rapid diagnostic for enteric fever. We have previously demonstrated that serum IgA responses targeting Salmonella enterica serovar Typhi hemolysin E (HlyE) and lipopolysaccharide (LPS) are able to discriminate patients with acute typhoid from healthy controls in areas where enteric fever is endemic (healthy endemic controls) and from patients with other bacterial infections. We now have data demonstrating that IgA antibody responses against these antigens also work well for identifying patients with acute S. Paratyphi A infection. To develop a test for acute enteric fever detection, we have adapted a point-of-care immunochromatographic dual-path platform technology (DPP), which improves on the traditional lateral flow technology by using separate sample and conjugate paths and a compact, portable reader, resulting in diagnostics with higher sensitivity and multiplexing abilities. In this analysis, we have compared our standard enzyme-linked immunosorbent assay (ELISA) method to the DPP method in detecting acute phase plasma/serum anti-HlyE and anti-LPS IgA antibodies in a cohort of patients with culture-confirmed S. Typhi (n?=?30) and Paratyphi A infection (n?=?20), healthy endemic controls (n?=?25), and febrile endemic controls (n?=?25). We found that the DPP measurements highly correlated with ELISA results, and both antigens had an area under the curve (AUC) of 0.98 (sensitivity of 92%, specificity of 94%) with all controls and an AUC of 0.98 (sensitivity of 90%, specificity of 96%) with febrile endemic controls. Our results suggest that the point-of-care DPP Typhoid System has high diagnostic accuracy for the rapid detection of enteric fever and warrants further evaluation.IMPORTANCE Enteric fever remains a significant global problem, and control programs are significantly limited by the lack of an optimal assay for identifying individuals with acute infection. This is especially critical considering the recently released World Health Organization (WHO) position paper endorsing the role of the typhoid conjugate vaccine in communities where enteric fever is endemic. A reliable diagnostic test is needed to assess and evaluate typhoid intervention strategies and determine which high-burden areas may benefit most from a vaccine intervention. Our collaborative team has developed and evaluated a point-of-care serodiagnostic assay based on detection of anti-HlyE and LPS IgA. Our finding of the high diagnostic accuracy of the DPP Typhoid System for the rapid detection of enteric fever has the potential to have significant public health impact by allowing for improved surveillance and for control and prevention programs in areas with limited laboratory capacity.

    View details for DOI 10.1128/mSphere.00253-20

    View details for PubMedID 32522777

  • Comparative accuracy of typhoid diagnostic tools: A Bayesian latent-class network analysis. PLoS neglected tropical diseases Arora, P., Thorlund, K., Brenner, D. R., Andrews, J. R. 2019; 13 (5): e0007303


    Typhoid fevers are infections caused by the bacteria Salmonella enterica serovar Typhi (Salmonella Typhi) and Paratyphi A, B and C (Salmonella Paratyphi). Approximately 17.8 million incident cases of typhoid fever occur annually, and incidence is highest in children. The accuracy of current diagnostic tests of typhoid fever is poorly understood. We aimed to determine the comparative accuracy of available tests for the pediatric population.We first conducted a systematic literature review to identify studies that compared diagnostic tests for typhoid fever in children (aged ?15 years) to blood culture results. We applied a Bayesian latent-class extension to a network meta-analysis model. We modelled known diagnostic properties of bone marrow culture and the relationship between bone marrow and blood culture as informative priors in a Bayesian framework. We tested sensitivities for the proportion of negative blood samples that were false as well as bone marrow sensitivity and specificity.We found 510 comparisons from 196 studies and 57 specific to the pediatric population. IgM-based tests outperformed their IgG-based counterparts for ELISA and Typhidot tests. The lateral flow IgG test performed comparatively well with 92% sensitivity (72% to 98% across scenario analyses) and 94% specificity. The most sensitive test of those investigated for the South Asian pediatric population was the Reverse Passive Hemagglutination Assay with 96% sensitivity (98% - 100% across scenario analyses). Adding a Widal slide test to other typhoid diagnostics did not substantially improve diagnostic performance beyond the single test alone, however, a lateral flow-based IgG rapid test combined with the typhoid/paratyphoid (TPT) assay yielded improvements in sensitivity without substantial declines in specificity and was the best performing combination test in this setting.In the pediatric population, lateral-flow IgG, TPT and Reverse Passive Hemagglutination tests had high diagnostic accuracy compared to other diagnostics. Combinations of tests may provide a feasible option to increase diagnostic sensitivity. South Asia has the most informed set of data on typhoid diagnostic testing accuracy, and the evidence base in other important regions needs to be expanded.

    View details for PubMedID 31067228

  • Epidemiology of Typhoid and Paratyphoid: Implications for Vaccine Policy. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Saha, S., Islam, M. S., Sajib, M. S., Saha, S., Uddin, M. J., Hooda, Y., Hasan, M., Amin, M. R., Hanif, M., Shahidullah, M., Islam, M., Luby, S. P., Andrews, J. R., Saha, S. K. 2019; 68 (Supplement_2): S117?S123


    Typhoid and paratyphoid remain the most common bloodstream infections in many resource-poor settings. The World Health Organization recommends typhoid conjugate vaccines for country-specific introduction, but questions regarding typhoid and paratyphoid epidemiology persist, especially regarding their severity in young children.We conducted enteric fever surveillance in Bangladesh from 2004 through 2016 in the inpatient departments of 2 pediatric hospitals and the outpatient departments of 1 pediatric hospital and 1 private consultation clinic. Blood cultures were conducted at the discretion of the treating physicians; cases of culture-confirmed typhoid/paratyphoid were included. Hospitalizations and durations of hospitalizations were used as proxies for severity in children <12 years old.We identified 7072 typhoid and 1810 paratyphoid culture-confirmed cases. There was no increasing trend in the proportion of paratyphoid over the 13 years. The median age in the typhoid cases was 60 months, and 15% of the cases occurred in children <24 months old. The median age of the paratyphoid cases was significantly higher, at 90 months (P < .001); 9.4% were in children <24 months old. The proportion of children (<12 years old) hospitalized with typhoid and paratyphoid (32% and 21%, respectively) decreased with age; there was no significant difference in durations of hospitalizations between age groups. However, children with typhoid were hospitalized for longer than those with paratyphoid.Typhoid and paratyphoid fever are common in Dhaka, including among children under 2 years old, who have equivalent disease severity as older children. Early immunization with typhoid conjugate vaccines could avert substantial morbidity, but broader efforts are required to reduce the paratyphoid burden.

    View details for PubMedID 30845325

  • Antibacterial mass drug administration for child mortality reduction: Opportunities, concerns, and possible next steps. PLoS neglected tropical diseases Bogoch, I. I., Utzinger, J., Lo, N. C., Andrews, J. R. 2019; 13 (5): e0007315

    View details for DOI 10.1371/journal.pntd.0007315

    View details for PubMedID 31120903

  • How Can the Typhoid Fever Surveillance in Africa and the Severe Typhoid Fever in Africa Programs Contribute to the Introduction of Typhoid Conjugate Vaccines? Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Jeon, H. J., Im, J., Haselbeck, A., Holm, M., Rakotozandrindrainy, R., Bassiahi, A. S., Panzner, U., Mogeni, O. D., Seo, H. J., Lunguya, O., Jacobs, J., Okeke, I. N., Terferi, M., Owusu-Dabo, E., Dougan, G., Carey, M., Steele, A. D., Kim, J. H., Clemens, J. D., Andrews, J. R., Park, S. E., Baker, S., Marks, F. 2019; 69 (Supplement_6): S417?S421


    The World Health Organization now recommends the use of typhoid conjugate vaccines (TCVs) in typhoid-endemic countries, and Gavi, the Vaccine Alliance, added TCVs into the portfolio of subsidized vaccines. Data from the Severe Typhoid Fever in Africa (SETA) program were used to contribute to TCV introduction decision-making processes, exemplified for Ghana and Madagascar.Data collected from both countries were evaluated, and barriers to and benefits of introduction scenarios are discussed. No standardized methodological framework was applied.The Ghanaian healthcare system differs from its Malagasy counterpart: Ghana features a functioning insurance system, antimicrobials are available nationwide, and several sites in Ghana deploy blood culture-based typhoid diagnosis. A higher incidence of antimicrobial-resistant Salmonella Typhi is reported in Ghana, which has not been identified as an issue in Madagascar. The Malagasy people have a low expectation of provided healthcare and experience frequent unavailability of medicines, resulting in limited healthcare-seeking behavior and extended consequences of untreated disease.For Ghana, high typhoid fever incidence coupled with spatiotemporal heterogeneity was observed. A phased TCV introduction through an initial mass campaign in high-risk areas followed by inclusion into routine national immunizations prior to expansion to other areas of the country can be considered. For Madagascar, a national mass campaign followed by routine introduction would be the introduction scenario of choice as it would protect the population, reduce transmission, and prevent an often-deadly disease in a setting characterized by lack of access to healthcare infrastructure. New, easy-to-use diagnostic tools, potentially including environmental surveillance, should be explored and improved to facilitate identification of high-risk areas.

    View details for DOI 10.1093/cid/ciz629

    View details for PubMedID 31665772

  • Investigation of preanalytical variables impacting pathogen cell-free DNA in blood and urine. Journal of clinical microbiology Murugesan, K., Hogan, C. A., Palmer, Z., Reeve, B., Theron, G., Andama, A., Somoskovi, A., Steadman, A., Madan, D., Andrews, J., Croda, J., Sahoo, M. K., Cattamanchi, A., Pinsky, B. A., Banaei, N. 2019


    Pathogen cell-free DNA (pcfDNA) in blood and urine is an attractive biomarker; however, the impact of preanalytical factors is not well understood.Blood and urine samples from healthy donors spiked with cfDNA from Mycobacterium tuberculosis, Salmonella enterica, Aspergillus fumigatus and EBV, and samples from tuberculosis patients were used to evaluate the impact of blood collection tube, urine preservative, processing delay, processing method, freezing and thawing, and sample volume on pcfDNA. PCR cycle threshold (CT) was used to measure amplifiable cfDNA.In spiked samples, median CT for M. tuberculosis, S. enterica, and EBV cfDNA was significantly lower in blood collected in K2EDTA than Streck and PAXgene blood collection tubes, and significantly lower in EDTA-urine than Streck-urine. Blood and urine samples from TB patients preserved with K2EDTA and Tris-EDTA, respectively, showed significantly lower median M. tuberculosis CT compared with Streck blood collection tube and urine preservative. Processing delay increased median pathogen CT for Streck and PAXgene but not K2EDTA blood samples, and for urine preserved with Streck reagent but not EDTA. Double spin compared with single spin plasma separation increased median pathogen CT regardless of blood collection tube. No differences were observed between whole urine and supernatant, and between fresh and thawed plasma and urine after 24 weeks at -80 °C. Larger plasma and urine volume in contrived and patient samples showed a significantly lower median M. tuberculosis CT. These findings suggest large volume single spin K2EDTA-plasma and EDTA-whole urine with up to 24-hour processing delay may optimize pcfDNA detection.

    View details for DOI 10.1128/JCM.00782-19

    View details for PubMedID 31511335

  • Detection, survival and infectious potential of Mycobacterium tuberculosis in the environment: A review of the evidence and epidemiological implications. The European respiratory journal Martinez, L., Verma, R., Croda, J., Horsburgh, C. R., Walter, K. S., Degner, N., Middelkoop, K., Koch, A., Hermans, S., Warner, D., Wood, R., Cobelens, F., Andrews, J. R. 2019


    Much remains unknown about Mycobacterium tuberculosis transmission. Seminal experimental studies from the 1950s demonstrated that airborne expulsion of droplet nuclei from an infectious tuberculosis patient is the primary route of transmission. However, these findings did not rule out other routes of M. tuberculosis transmission. We reviewed historical scientific evidence from the late 19th and early 20th century and contemporary studies investigating the presence, persistence, and infectiousness of environmental M. tuberculosis We found evidence - both experimental and epidemiological - supporting the presence and viability of M. tuberculosis in multiple natural and built environments for months to years, presumably following contamination by a human source. Further, several studies confirm M. tuberculosis viability and virulence in the environment using guinea pig and mouse models. Most of this evidence was historical; however, several recent studies have reported consistent findings of M. tuberculosis detection and viability in the environment using modern methods. Whether or not M. tuberculosis in environments represents an infectious threat to humans, it may represent an untapped source of data with which to further understand M. tuberculosis transmission. We discuss potential opportunities for harnessing these data to generate new insights into tuberculosis transmission in congregate settings.

    View details for PubMedID 31048345

  • Building a tuberculosis-free world: The Lancet Commission on tuberculosis. Lancet (London, England) Reid, M. J., Arinaminpathy, N., Bloom, A., Bloom, B. R., Boehme, C., Chaisson, R., Chin, D. P., Churchyard, G., Cox, H., Ditiu, L., Dybul, M., Farrar, J., Fauci, A. S., Fekadu, E., Fujiwara, P. I., Hallett, T. B., Hanson, C. L., Harrington, M., Herbert, N., Hopewell, P. C., Ikeda, C., Jamison, D. T., Khan, A. J., Koek, I., Krishnan, N., Motsoaledi, A., Pai, M., Raviglione, M. C., Sharman, A., Small, P. M., Swaminathan, S., Temesgen, Z., Vassall, A., Venkatesan, N., van Weezenbeek, K., Yamey, G., Agins, B. D., Alexandru, S., Andrews, J. R., Beyeler, N., Bivol, S., Brigden, G., Cattamanchi, A., Cazabon, D., Crudu, V., Daftary, A., Dewan, P., Doepel, L. K., Eisinger, R. W., Fan, V., Fewer, S., Furin, J., Goldhaber-Fiebert, J. D., Gomez, G. B., Graham, S. M., Gupta, D., Kamene, M., Khaparde, S., Mailu, E. W., Masini, E. O., McHugh, L., Mitchell, E., Moon, S., Osberg, M., Pande, T., Prince, L., Rade, K., Rao, R., Remme, M., Seddon, J. A., Selwyn, C., Shete, P., Sachdeva, K. S., Stallworthy, G., Vesga, J. F., Vilc, V., Goosby, E. P. 2019

    View details for PubMedID 30904263

  • Identification of widespread antibiotic exposure in cholera patients correlates with clinically relevant microbiota changes. The Journal of infectious diseases Alexandrova, L., Haque, F., Rodriguez, P., Marrazzo, A. C., Grembi, J. A., Ramachandran, V., Hryckowian, A. J., Adams, C. M., Siddique, M. S., Khan, A. I., Qadri, F., Andrews, J. R., Rahman, M., Spormann, A. M., Schoolnik, G. K., Chien, A., Nelson, E. J. 2019


    A first step to combating antimicrobial resistance in enteric pathogens is to establish an objective assessment of antibiotic exposure. Our goal was to develop and evaluate a liquid chromatography-ion trap mass spectrometry (LC/MS) method to determine antibiotic exposure in cholera patients.A priority list for targeted LC/MS was generated from medication vendor surveys in Bangladesh. A study of cholera and non-cholera patients was conducted to collect and analyze paired urine and stool samples.Among 845 patients, 11% (n=90) were Vibrio cholerae positive; at least one antibiotic was detected in 86% and at least two in 52% of cholera stools. Among paired urine and stool (n=44), at least one antibiotic was detected in 98% and at least two in 84%, despite 55% self-reporting medication use. Compared to LC/MS, a low-cost antimicrobial detection bio-assay lacked sufficient negative predictive value (10%; 95% CI 6-16). Detection of guideline-recommended antibiotics in stool did (azithromycin; p=0.040) and did not (ciprofloxacin) correlate with V. cholerae suppression. A non-recommended antibiotic (metronidazole) was associated with decreases in anaerobes (Prevotella; p<0.001).The findings suggest there may be no true negative control group when attempting to account for antibiotic exposure in settings like those in this study.

    View details for DOI 10.1093/infdis/jiz299

    View details for PubMedID 31192364

  • Clinical evaluation for morbidity associated with soil-transmitted helminth infection in school-age children on Pemba Island, Tanzania. PLoS neglected tropical diseases Bogoch, I. I., Speich, B., Lo, N. C., Moser, W., Croll, D., Ali, S. M., Ame, S. M., Utzinger, J., Andrews, J. R., Keiser, J. 2019; 13 (7): e0007581


    More than 1.5 billion people are infected with soil-transmitted helminths (Ascaris lumbricoides, hookworm, Strongyloides stercoralis, and Trichuris trichiura), causing an estimated global burden in excess of 3 million disability-adjusted life years. However, the relationship between soil-transmitted helminth infection, adverse health consequences, and beneficial effects of deworming are not well understood.We pursued a detailed longitudinal clinical evaluation of school-age children to evaluate morbidity associated with soil-transmitted helminth infection and responses to treatment. This exploratory study was embedded into a randomized controlled trial. Overall, 434 children, aged 7-14 years, underwent a detailed medical history, physical examination, stool microscopy for soil-transmitted helminths, and hemoglobin (Hb) measurement at baseline. Medical history and stool examination were repeated at 3 and 18 weeks posttreatment. Additionally, Hb measurement was performed at the 18-week treatment follow-up. Logistic regression was employed to assess clinical factors associated with soil-transmitted helminth infection at baseline, and longitudinal data analysis to examine change in health outcomes following treatment over time.All enrolled children were infected with T. trichiura, and randomized into four different treatment interventions. None of the medical history, physical examination, and laboratory (i.e., Hb) findings were associated with A. lumbricoides, hookworm, or S. stercoralis infection at baseline. A composite of physical exam findings for anemia, including pallor of the conjunctiva, nail beds, and palmar creases predicted lower Hb values (-3.8 g/dl, 95% confidence interval (CI): -6.9, -0.6 g/dl). When examining longitudinal trends, we did not find improvements to Hb or face Wong-Baker Likert scale among children with soil-transmitted helminth infection compared to those without infection, although there was a slight trend toward improving Hb values after treating hookworm infection.Our study demonstrates the challenges of measuring morbidity in the context of soil-transmitted helminth infection and treatment, thus confirming the mainly subtle morbidity effects of infection.

    View details for DOI 10.1371/journal.pntd.0007581

    View details for PubMedID 31306433

  • Paediatric tuberculosis transmission outside the household: challenging historical paradigms to inform future public health strategies. The Lancet. Respiratory medicine Martinez, L., Lo, N. C., Cords, O., Hill, P. C., Khan, P., Hatherill, M., Mandalakas, A., Kay, A., Croda, J., Horsburgh, C. R., Zar, H. J., Andrews, J. R. 2019


    Tuberculosis is a major cause of death and disability among children globally, yet children have been neglected in global tuberculosis control efforts. Historically, tuberculosis in children has been thought of as a family disease, and because of this, household contact tracing of children after identification of an adult tuberculosis case has been emphasised as the principal public health intervention. However, the population-level effect of household contact tracing is predicated on the assumption that most paediatric tuberculosis infections are acquired within the household. In this Personal View, we focus on accumulating scientific evidence indicating that the majority of Mycobacterium tuberculosis transmission to children in high-burden settings occurs in the community, outside of households in which a person has tuberculosis. We estimate the population-attributable fraction of M tuberculosis transmission to children due to household exposures to be between 10% and 30%. M tuberculosis transmission from the household was low (<30%) even in children younger than age 5 years. We propose that an effective public health response to childhood tuberculosis requires comprehensive, community-based interventions, such as active surveillance in select settings, rather than contact tracing alone. Importantly, the historical paradigm that most paediatric transmission occurs in households should be reconsidered on the basis of the scientific knowledge presented.

    View details for PubMedID 31078497

  • Temporal trends in the prevalence of Mycobacterium tuberculosis infection in South African adolescents. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Bunyasi, E. W., Geldenhuys, H., Mulenga, H., Shenje, J., Luabeya, A. K., Tameris, M., Nemes, E., Mahomed, H., Rozot, V., Wood, R., Scriba, T., Andrews, J. R., Hatherill, M. 2019; 23 (5): 571?78


    SETTING South Africa. OBJECTIVE 1) To measure changes in the adolescent prevalence of latent tuberculous infection (LTBI) between 2005 and 2015, and 2) to evaluate medium-term impact of TB control measures on LTBI prevalence. DESIGN We compared baseline data from a cohort study (2005-2007) and a vaccine trial (2014-2015) which enrolled adolescents from the same eight South African high schools. LTBI was defined based on QuantiFERON®-TB Gold In-Tube test positivity. RESULTS We analysed data from 4880 adolescents between 2005 and 2007, and 1968 adolescents between 2014 and 2015, when the average LTBI prevalence was respectively 43.8% (95%CI 28.4-59.1) vs. 48.5% (95%CI 41.1-55.8). Age-specific LTBI prevalence increased between the ages 12 and 18 years by 13% only in lower socio-economic quintile schools, where the average LTBI prevalence was unchanged between the two periods (54% vs. 53%). In the highest socio-economic quintile schools, LTBI prevalence did not increase with age; however, the average LTBI prevalence increased from 20% to 38% between the two periods. CONCLUSION Adolescent LTBI prevalence remained high and constant over a decade, suggesting that Mycobacterium tuberculosis transmission to children was not impacted in the medium term by effective TB control efforts. Trends in adolescent LTBI prevalence should be interpreted in the context of the sociodemographic factors that affect the risk of transmission before and during adolescence. .

    View details for DOI 10.5588/ijtld.18.0283

    View details for PubMedID 31097065

  • The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet. Infectious diseases 2019


    Efforts to quantify the global burden of enteric fever are valuable for understanding the health lost and the large-scale spatial distribution of the disease. We present the estimates of typhoid and paratyphoid fever burden from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, and the approach taken to produce them.For this systematic analysis we broke down the relative contributions of typhoid and paratyphoid fevers by country, year, and age, and analysed trends in incidence and mortality. We modelled the combined incidence of typhoid and paratyphoid fevers and split these total cases proportionally between typhoid and paratyphoid fevers using aetiological proportion models. We estimated deaths using vital registration data for countries with sufficiently high data completeness and using a natural history approach for other locations. We also estimated disability-adjusted life-years (DALYs) for typhoid and paratyphoid fevers.Globally, 14·3 million (95% uncertainty interval [UI] 12·5-16·3) cases of typhoid and paratyphoid fevers occurred in 2017, a 44·6% (42·2-47·0) decline from 25·9 million (22·0-29·9) in 1990. Age-standardised incidence rates declined by 54·9% (53·4-56·5), from 439·2 (376·7-507·7) per 100?000 person-years in 1990, to 197·8 (172·0-226·2) per 100?000 person-years in 2017. In 2017, Salmonella enterica serotype Typhi caused 76·3% (71·8-80·5) of cases of enteric fever. We estimated a global case fatality of 0·95% (0·54-1·53) in 2017, with higher case fatality estimates among children and older adults, and among those living in lower-income countries. We therefore estimated 135·9 thousand (76·9-218·9) deaths from typhoid and paratyphoid fever globally in 2017, a 41·0% (33·6-48·3) decline from 230·5 thousand (131·2-372·6) in 1990. Overall, typhoid and paratyphoid fevers were responsible for 9·8 million (5·6-15·8) DALYs in 2017, down 43·0% (35·5-50·6) from 17·2 million (9·9-27·8) DALYs in 1990.Despite notable progress, typhoid and paratyphoid fevers remain major causes of disability and death, with billions of people likely to be exposed to the pathogens. Although improvements in water and sanitation remain essential, increased vaccine use (including with typhoid conjugate vaccines that are effective in infants and young children and protective for longer periods) and improved data and surveillance to inform vaccine rollout are likely to drive the greatest improvements in the global burden of the disease.Bill & Melinda Gates Foundation.

    View details for DOI 10.1016/S1473-3099(18)30685-6

    View details for PubMedID 30792131

  • Molecular mechanism of azithromycin resistance among typhoidal Salmonella stains in Bangladesh identified through passive pediatric surveillance. PLoS neglected tropical diseases Hooda, Y., Sajib, M. S., Rahman, H., Luby, S. P., Bondy-Denomy, J., Santosham, M., Andrews, J. R., Saha, S. K., Saha, S. 2019; 13 (11): e0007868


    With the rise in fluoroquinolone-resistant Salmonella Typhi and the recent emergence of ceftriaxone resistance, azithromycin is one of the last oral drugs available against typhoid for which resistance is uncommon. Its increasing use, specifically in light of the ongoing outbreak of extensively drug-resistant (XDR) Salmonella Typhi (resistant to chloramphenicol, ampicillin, cotrimoxazole, streptomycin, fluoroquinolones and third-generation cephalosporins) in Pakistan, places selective pressure for the emergence and spread of azithromycin-resistant isolates. However, little is known about azithromycin resistance in Salmonella, and no molecular data are available on its mechanism.We conducted typhoid surveillance in the two largest pediatric hospitals of Bangladesh from 2009-2016. All typhoidal Salmonella strains were screened for azithromycin resistance using disc diffusion and resistance was confirmed using E-tests. In total, we identified 1,082 Salmonella Typhi and Paratyphi A strains; among these, 13 strains (12 Typhi, 1 Paratyphi A) were azithromycin-resistant (MIC range: 32-64 ?g/ml) with the first case observed in 2013. We sequenced the resistant strains, but no molecular basis of macrolide resistance was identified by the currently available antimicrobial resistance prediction tools. A whole genome SNP tree, made using RAxML, showed that the 12 Typhi resistant strains clustered together within the sub-clade (H58 lineage 1). We found a non-synonymous single-point mutation exclusively in these 12 strains in the gene encoding AcrB, an efflux pump that removes small molecules from bacterial cells. The mutation changed the conserved amino acid arginine (R) at position 717 to a glutamine (Q). To test the role of R717Q present in azithromycin-resistant strains, we cloned acrB from azithromycin-resistant and sensitive strains, expressed them in E. coli, Typhi and Paratyphi A strains and tested their azithromycin susceptibility. Expression of AcrB-R717Q in E. coli and Typhi strains increased the minimum inhibitory concentration (MIC) for azithromycin by 11- and 3-fold respectively. The azithromycin-resistant Paratyphi A strain also contained a mutation at R717 (R717L), whose introduction in E. coli and Paratyphi A strains increased MIC by 7- and 3-fold respectively, confirming the role of R717 mutations in conferring azithromycin resistance.This report confirms 12 azithromycin-resistant Salmonella Typhi strains and one Paratyphi A strain. The molecular basis of this resistance is one mutation in the AcrB protein at position 717. This is the first report demonstrating the impact of this non-synonymous mutation in conferring macrolide resistance in a clinical setting. With increasing azithromycin use, strains with R717 mutations may spread and be acquired by XDR strains. An azithromycin-resistant XDR strain would shift enteric fever treatment from outpatient departments, where patients are currently treated with oral azithromycin, to inpatient departments to be treated with injectable antibiotics like carbapenems, thereby further burdening already struggling health systems in endemic regions. Moreover, with the dearth of novel antimicrobials in the horizon, we risk losing our primary defense against widespread mortality from typhoid. In addition to rolling out the WHO prequalified typhoid conjugate vaccine in endemic areas to decrease the risk of pan-resistant Salmonella Typhi strains, it is also imperative to implement antimicrobial stewardship and water sanitation and hygiene intervention to decrease the overall burden of enteric fever.

    View details for DOI 10.1371/journal.pntd.0007868

    View details for PubMedID 31730615

  • Global, regional, and national burden of tuberculosis, 1990-2016: results from the Global Burden of Diseases, Injuries, and Risk Factors 2016 Study LANCET INFECTIOUS DISEASES Kyu, H., Maddison, E. R., Henry, N. J., Ledesma, J. R., Wiens, K. E., Reiner, R., Biehl, M. H., Shields, C., Osgood-Zimmerman, A., Ross, J. M., Carter, A., Frank, T. D., Wang, H., Srinivasan, V., Abebe, Z., Agarwal, S., Alahdab, F., Alene, K., Ali, B., Alvis-Guzman, N., Andrews, J. R., Antonio, C. T., Atique, S., Atre, S. R., Awasthi, A., Ayele, H., Badali, H., Badawi, A., Barac, A., Bedi, N., Behzadifar, M., Behzadifar, M., Bekele, B., Belay, S., Bensenor, I. M., Butt, Z. A., Carvalho, F., Cercy, K., Christopher, D. J., Daba, A., Dandona, L., Dandona, R., Daryani, A., Demeke, F., Deribe, K., Dharmaratne, S., Doku, D., Dubey, M., Edessa, D., El-Khatib, Z., Enany, S., Fernandes, E., Fischer, F., Garcia-Basteiro, A. L., Gebre, A., Gebregergs, G., Gebremichael, T., Gelano, T., Geremew, D., Gona, P. N., Goodridge, A., Gupta, R., Bidgoli, H., Hailu, G., Hassen, H., Hedayati, M., Henok, A., Hostiuc, S., Hussen, M., Ilesanmi, O., Irvani, S., Jacobsen, K. H., Johnson, S. C., Jonas, J. B., Kahsay, A., Kant, S., Kasaeian, A., Kassa, T., Khader, Y., Khafaie, M., Khalil, I., Khan, E., Khang, Y., Kim, Y., Kochhar, S., Koyanagi, A., Krohn, K. J., Kumar, G., Lakew, A., Leshargie, C., Lodha, R., Macarayan, E., Majdzadeh, R., Martins-Melo, F., Melese, A., Memish, Z. A., Mendoza, W., Mengistu, D., Mengistu, G., Mestrovic, T., Moazen, B., Mohammad, K., Mohammed, S., Mokdad, A. H., Moosazadeh, M., Mousavi, S., Mustafa, G., Nachega, J. B., Long Hoang Nguyen, Son Hoang Nguyen, Trang Huyen Nguyen, Ningrum, D., Nirayo, Y., Vuong Minh Nong, Ofori-Asenso, R., Ogbo, F., Oh, I., Oladimeji, O., Olagunju, A. T., Oren, E., Pereira, D. M., Prakash, S., Qorbani, M., Rafay, A., Rai, R., Ram, U., Rubino, S., Safiri, S., Salomon, J. A., Samy, A. M., Sartorius, B., Satpathy, M., Seyedmousavi, S., Sharif, M., Silva, J., Silveira, D., Singh, J. A., Sreeramareddy, C. T., Tran, B., Tsadik, A., Ukwaja, K., Ullah, I., Uthman, O. A., Vlassov, V., Vollset, S., Vu, G., Weldegebreal, F., Werdecker, A., Yimer, E. M., Yonemoto, N., Yotebieng, M., Naghavi, M., Theo Vos, Hay, S. I., Murray, C. L., GBD TB Collaborators 2018; 18 (12): 1329?49


    Although a preventable and treatable disease, tuberculosis causes more than a million deaths each year. As countries work towards achieving the Sustainable Development Goal (SDG) target to end the tuberculosis epidemic by 2030, robust assessments of the levels and trends of the burden of tuberculosis are crucial to inform policy and programme decision making. We assessed the levels and trends in the fatal and non-fatal burden of tuberculosis by drug resistance and HIV status for 195 countries and territories from 1990 to 2016.We analysed 15?943 site-years of vital registration data, 1710 site-years of verbal autopsy data, 764 site-years of sample-based vital registration data, and 361 site-years of mortality surveillance data to estimate mortality due to tuberculosis using the Cause of Death Ensemble model. We analysed all available data sources, including annual case notifications, prevalence surveys, population-based tuberculin surveys, and estimated tuberculosis cause-specific mortality to generate internally consistent estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian meta-regression tool. We assessed how the burden of tuberculosis differed from the burden predicted by the Socio-demographic Index (SDI), a composite indicator of income per capita, average years of schooling, and total fertility rate.Globally in 2016, among HIV-negative individuals, the number of incident cases of tuberculosis was 9·02 million (95% uncertainty interval [UI] 8·05-10·16) and the number of tuberculosis deaths was 1·21 million (1·16-1·27). Among HIV-positive individuals, the number of incident cases was 1·40 million (1·01-1·89) and the number of tuberculosis deaths was 0·24 million (0·16-0·31). Globally, among HIV-negative individuals the age-standardised incidence of tuberculosis decreased annually at a slower rate (-1·3% [-1·5 to -1·2]) than mortality did (-4·5% [-5·0 to -4·1]) from 2006 to 2016. Among HIV-positive individuals during the same period, the rate of change in annualised age-standardised incidence was -4·0% (-4·5 to -3·7) and mortality was -8·9% (-9·5 to -8·4). Several regions had higher rates of age-standardised incidence and mortality than expected on the basis of their SDI levels in 2016. For drug-susceptible tuberculosis, the highest observed-to-expected ratios were in southern sub-Saharan Africa (13·7 for incidence and 14·9 for mortality), and the lowest ratios were in high-income North America (0·4 for incidence) and Oceania (0·3 for mortality). For multidrug-resistant tuberculosis, eastern Europe had the highest observed-to-expected ratios (67·3 for incidence and 73·0 for mortality), and high-income North America had the lowest ratios (0·4 for incidence and 0·5 for mortality).If current trends in tuberculosis incidence continue, few countries are likely to meet the SDG target to end the tuberculosis epidemic by 2030. Progress needs to be accelerated by improving the quality of and access to tuberculosis diagnosis and care, by developing new tools, scaling up interventions to prevent risk factors for tuberculosis, and integrating control programmes for tuberculosis and HIV.Bill & Melinda Gates Foundation.

    View details for DOI 10.1016/S1473-3099(18)30625-X

    View details for Web of Science ID 000450899900030

    View details for PubMedID 30507459

  • Phenotyping antibiotic resistance with single-cell resolution for the detection of heteroresistance SENSORS AND ACTUATORS B-CHEMICAL Lyu, F., Pan, M., Patil, S., Wang, J., Matin, A. C., Andrews, J. R., Tang, S. Y. 2018; 270: 396?404
  • Improving Tuberculosis Case Finding in Persons Living with Advanced HIV through New Diagnostic Algorithms. American journal of respiratory and critical care medicine Martinez, L., Andrews, J. R. 2018

    View details for PubMedID 30273498

  • Integrating Facility-Based Surveillance With Healthcare Utilization Surveys to Estimate Enteric Fever Incidence: Methods and Challenges. The Journal of infectious diseases Andrews, J. R., Barkume, C., Yu, A. T., Saha, S. K., Qamar, F. N., Garrett, D., Luby, S. P. 2018


    Cohort studies and facility-based sentinel surveillance are common approaches to characterizing infectious disease burden, but present trade-offs; cohort studies are resource-intensive and may alter disease natural history, while sentinel surveillance underestimates incidence in the population. Hybrid surveillance, whereby facility-based surveillance is paired with a community-based healthcare utilization assessment, represents an alternative approach to generating population-based disease incidence estimates with moderate resource investments. Here, we discuss this method in the context of the Surveillance for Enteric Fever in Asia Project (SEAP) study. We describe how data are collected and utilized to adjust enteric fever incidence for blood culture sensitivity, facility-based enrollment, and healthcare seeking, incorporating uncertainty in these parameters in the uncertainty around incidence estimates. We illustrate how selection of surveillance sites and their coverage may influence precision and bias, and we identify approaches in the study design and analysis to minimize and control for these biases. Rigorously designed hybrid surveillance systems can be an efficient approach to generating population-based incidence estimates for infectious diseases.

    View details for PubMedID 30184162

  • Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis. Proceedings of the National Academy of Sciences of the United States of America Lo, N. C., Gurarie, D., Yoon, N., Coulibaly, J. T., Bendavid, E., Andrews, J. R., King, C. H. 2018


    Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5-20%) and high-prevalence (25-50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, "hot spots" of transmission, and noncompliance to MDA.

    View details for PubMedID 29301964

  • Invasive Pomacea snails as important intermediate hosts of Angiostrongylus cantonensis in Laos, Cambodia and Vietnam: implications for outbreaks of eosinophilic meningitis. Acta tropica Lv, S., Guo, Y. H., Nguyen, H. M., Sinuon, M., Sayasone, S., Lo, N. C., Zhou, X. N., Andrews, J. R. 2018


    The rat lungworm Angiostrongylus cantonensis causes human eosinophilic meningitis and it is endemic in Southeast Asia, but little is known about its distribution in Laos, Cambodia and Vietnam. We conducted a multi-country survey for A. cantonensis in these countries to estimate its prevalence in snails along the Mekong River and the east coast of Vietnam. We identified Angiostrongylus species by morphological and molecular analysis. We found A. cantonensis in the invasive snail, Pomacea spp. The wide accessibility of Pomacea snails, along with their infection by A. cantonensis, indicates that this snail species could be used in surveillance for preventing outbreaks of eosinophilic meningitis.

    View details for PubMedID 29574000

  • Serum vitamin D levels and risk of prevalent tuberculosis, incident tuberculosis and tuberculin skin test conversion among prisoners. Scientific reports Maceda, E. B., Gonçalves, C. C., Andrews, J. R., Ko, A. I., Yeckel, C. W., Croda, J. 2018; 8 (1): 997


    Poor vitamin D status has been associated with tuberculosis (TB); whether poor status is cause or consequence of disease is uncertain. We conducted a case-control study and two nested case-control studies to determine whether vitamin D levels were associated with active TB, tuberculin skin test (TST) conversion, and risk of progression to the active TB in prisoners in Brazil. In multivariable conditional logistic regression, subnormal vitamin D levels (OR, 3.77; 95% CI, 1.04-13.64) were more likely in prisoners with active TB. In contrast, vitamin D was not found to be a risk factor for either TST conversion (OR, 2.49; 95% CI, 0.64-9.66) or progression to active disease (OR, 0.59; 95% CI, 0.13-2.62). Black race (OR, 11.52; 95% CI, 2.01-63.36), less than 4 years of schooling (OR, 2.70; 95% CI, 0.90-8.16), cigarette smoking (OR, 0.23; 95% CI, 0.06-0.79) were identified as risk factors for TST conversion. Risk of progression to active TB was found to be associated with cigarette smoking (OR, 7.42; 95% CI, 1.23-44.70). Our findings in the prison population show that poor vitamin D status is more common in individuals with active TB, but is not a risk factor for acquisition of latent TB or progression to active TB.

    View details for PubMedID 29343733

  • Building capacity for advances in tuberculosis research; proceedings of the third RePORT international meeting. Tuberculosis (Edinburgh, Scotland) van der Heijden, Y. F., Abdullah, F., Andrade, B. B., Andrews, J. R., Christopher, D. J., Croda, J., Ewing, H., Haas, D. W., Hatherill, M., Horsburgh, C. R., Mave, V., Nakaya, H. I., Rolla, V., Srinivasan, S., Sugiyono, R. I., Ugarte-Gil, C., Hamilton, C. 2018; 113: 153?62


    RePORT International is a global network of research sites in India, Brazil, Indonesia, South Africa, China, and the Philippines dedicated to collaborative tuberculosis research in the context of HIV. A standardized research protocol (the Common Protocol) guides the enrollment of participants with active pulmonary tuberculosis and contacts into observational cohorts. The establishment of harmonized clinical data and bio-repositories will allow cutting-edge, large-scale advances in the understanding of tuberculosis, including identification of novel biomarkers for progression to active tuberculosis and relapse after treatment. The RePORT International infrastructure aims to support research capacity development through enabling globally-diverse collaborations. To that end, representatives from the RePORT International network sites, funding agencies, and other stakeholders gathered together in Brazil in September 2017 to present updates on relevant research findings and discuss ideas for collaboration. Presenters emphasized research involving biomarker identification for incipient tuberculosis, host immunity and pharmacogenomics, co-morbidities such as HIV and type 2 diabetes mellitus, and tuberculosis transmission in vulnerable and high-risk populations. Currently, 962 active TB participants and 670 household contacts have contributed blood, sputum, urine and microbes to in-country biorepositories. Cross-consortium collaborations have begun sharing data and specimens to analyze molecular and cytokine predictive patterns.

    View details for PubMedID 30514497

  • Phase I of the Surveillance for Enteric Fever in Asia Project (SEAP): An Overview and Lessons Learned. The Journal of infectious diseases Barkume, C., Date, K., Saha, S. K., Qamar, F. N., Sur, D., Andrews, J. R., Luby, S. P., Khan, M. I., Freeman, A., Yousafzai, M. T., Garrett, D. 2018


    The objective of Phase I of the Surveillance for Enteric Fever in Asia Project (SEAP), a multiphase surveillance study characterizing the burden of disease in South Asia, was to inform data collection for prospective surveillance and to capture clinical aspects of disease.Through a retrospective record review conducted at hospitals in Bangladesh, India, Nepal, and Pakistan, we examined laboratory and clinical records to assess the culture positivity rate for Salmonella Typhi and Salmonella Paratyphi, age and sex distribution, and antimicrobial susceptability in each country.Of all blood cultures performed in Bangladesh, India, Nepal, and Pakistan, 1.5%, 0.43%, 2%, and 1.49%, respectively, were positive for S. Typhi and 0.24%, 0.1%, 0.5%, and 0.67%, respectively, were positive for S. Paratyphi. A higher proportion of laboratory-confirmed infections in Bangladesh and Pakistan were aged ?5 years, while India and Nepal had a higher proportion of participants aged 15-25 years. In all countries, the sex of the majority of participants was male. The majority of isolates in all countries were resistant to fluoroquinolones, with a high proportion also resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole.Enteric fever remains endemic in South Asia. Data generated by this study can help inform strategies for implementation and evaluation of prevention and control measures.

    View details for PubMedID 30304505

  • Evaluating PCR-Based Detection of Salmonella Typhi and Paratyphi A in the Environment as an Enteric Fever Surveillance Tool. The American journal of tropical medicine and hygiene Saha, S., Tanmoy, A. M., Andrews, J. R., Sajib, M. S., Yu, A. T., Baker, S., Luby, S. P., Saha, S. K. 2018


    With prequalification of a typhoid conjugate vaccine by the World Health Organization, countries are deciding whether and at what geographic scale to provide the vaccine. Optimal local data to clarify typhoid risk are expensive and often unavailable. To determine whether quantitative real-time PCR can be used as a tool to detect typhoidal Salmonella DNA in the environment and approximate the burden of enteric fever, we tested water samples from urban Dhaka, where enteric fever burden is high, and rural Mirzapur, where enteric fever burden is low and sporadic. Sixty-six percent (38/59) of the water sources of Dhaka were contaminated with typhoidal Salmonella DNA, in contrast to none of 33 samples of Mirzapur. If these results can be replicated in larger scale in Bangladesh and other enteric fever endemic areas, drinking water testing could become a low-cost approach to determine the presence of typhoidal Salmonella in the environment that can, in turn, guide informed-design of blood culture-based surveillance and thus assist policy decisions on investing to control typhoid.

    View details for PubMedID 30426919

  • Assessing the Risk of Vaccine-derived Outbreaks After Reintroduction of Oral Poliovirus Vaccine in Postcessation Settings. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Fu, R., Altamirano, J., Sarnquist, C. C., Maldonado, Y. A., Andrews, J. R. 2018; 67 (suppl_1): S26?S34


    The Polio Eradication and Endgame Strategic Plan 2013-2018 calls for the gradual withdrawal of oral poliovirus vaccine (OPV) from routine immunization. We aimed to quantify the transmission potential of Sabin strains from OPV when it is reintroduced, accidentally or deliberately, in a community vaccinated with inactivated poliovirus vaccine alone.We built an individual-based stochastic epidemiological model that allows independent spread of 3 Sabin serotypes and differential transmission rates within versus between households. Model parameters were estimated by fitting to data from a prospective cohort in Mexico. We calculated the effective reproductive number for the Mexico cohort and simulated scenarios of Sabin strain resurgence under postcessation conditions, projecting the risk of prolonged circulation, which could lead to circulating vaccine-derived poliovirus (cVDPV).The estimated effective reproductive number for naturally infected individuals was about 1 for Sabin 2 and Sabin 3 (OPV2 and OPV3) in a postcessation setting. Most transmission events occurred between households. We estimated the probability of circulation for >9 months to be (1) <1% for all 3 serotypes when 90% of children <5 years of age were vaccinated in a hypothetical outbreak control campaign; (2) 45% and 24% for Sabin 2 and Sabin 3, respectively, when vaccine coverage dropped to 10%; (3) 37% and 8% for Sabin 2 and Sabin 3, respectively, when a single active shedder appeared in a community.Critical factors determining the risk of cVDPV emergence are the scale at which OPV is reintroduced and the between-household transmission rate for poliovirus, with intermediate values posing the greatest risk.

    View details for PubMedID 30376087

  • Assessment of Validity of a Blood-Based 3-Gene Signature Score for Progression and Diagnosis of Tuberculosis, Disease Severity, and Treatment Response JAMA Network Open Warsinske, H. C., Rao, A. M., Moreira, F. M., Santos, P. M., Liu, A. B., Scott, M., Malherbe, S. T., Ronacher, K., Walzl, G., Winter, J., Sweeney, T. E., Croda, J., Andrews, J. R., Khatri, P. 2018; 1 (6): e183779
  • Spatially targeted screening to reduce tuberculosis transmission in high-incidence settings. The Lancet. Infectious diseases Cudahy, P. G., Andrews, J. R., Bilinski, A., Dowdy, D. W., Mathema, B., Menzies, N. A., Salomon, J. A., Shrestha, S., Cohen, T. 2018


    As the leading infectious cause of death worldwide and the primary proximal cause of death in individuals living with HIV, tuberculosis remains a global concern. Existing tuberculosis control strategies that rely on passive case-finding appear insufficient to achieve targets for reductions in tuberculosis incidence and mortality. Active case-finding strategies aim to detect infectious individuals earlier in their infectious period to reduce onward transmission and improve treatment outcomes. Empirical studies of active case-finding have produced mixed results and determining how to direct active screening to those most at risk remains a topic of intense research. Our systematic review of literature evaluating the effects of geographically targeted tuberculosis screening interventions found three studies in low tuberculosis incidence settings, but none conducted in high tuberculosis incidence countries. We discuss open questions related to the use of spatially targeted approaches for active screening in countries where tuberculosis incidence is highest.

    View details for PubMedID 30554997

  • Advances in the understanding of Mycobacterium tuberculosis transmission in HIV-endemic settings. The Lancet. Infectious diseases Peters, J. S., Andrews, J. R., Hatherill, M., Hermans, S., Martinez, L., Schurr, E., van der Heijden, Y., Wood, R., Rustomjee, R., Kana, B. D. 2018


    Tuberculosis claims more human lives than any other infectious disease. This alarming epidemic has fuelled the development of novel antimicrobials and diagnostics. However, public health interventions that interrupt transmission have been slow to emerge, particularly in HIV-endemic settings. Transmission of tuberculosis is complex, involving various environmental, bacteriological, and host factors, among which concomitant HIV infection is important. Preventing person-to-person spread is central to halting the epidemic and, consequently, tuberculosis transmission is now being studied with renewed interest. In this Series paper, we review recent advances in the understanding of tuberculosis transmission, from the view of source-case infectiousness, inherent susceptibility of exposed individuals, appending tools for predicting risk of disease progression, the biophysical nature of the contagion, and the environments in which transmission occurs and is sustained in populations. We focus specifically on how HIV infection affects these features with a view to describing novel transmission blocking strategies in HIV-endemic settings.

    View details for PubMedID 30554995

  • Investigating spillover of multidrug-resistant tuberculosis from a prison: a spatial and molecular epidemiological analysis. BMC medicine Warren, J. L., Grandjean, L., Moore, D. A., Lithgow, A., Coronel, J., Sheen, P., Zelner, J. L., Andrews, J. R., Cohen, T. 2018; 16 (1): 122


    Congregate settings may serve as institutional amplifiers of tuberculosis (TB) and multidrug-resistant tuberculosis (MDR-TB). We analyze spatial, epidemiological, and pathogen genetic data prospectively collected from neighborhoods surrounding a prison in Lima, Peru, where inmates experience a high risk of MDR-TB, to investigate the risk of spillover into the surrounding community.Using hierarchical Bayesian statistical modeling, we address three questions regarding the MDR-TB risk: (i) Does the excess risk observed among prisoners also extend outside the prison? (ii) If so, what is the magnitude, shape, and spatial range of this spillover effect? (iii) Is there evidence of additional transmission across the region?The region of spillover risk extends for 5.47 km outside of the prison (95% credible interval: 1.38, 9.63 km). Within this spillover region, we find that nine of the 467 non-inmate patients (35 with MDR-TB) have MDR-TB strains that are genetic matches to strains collected from current inmates with MDR-TB, compared to seven out of 1080 patients (89 with MDR-TB) outside the spillover region (p values: 0.022 and 0.008). We also identify eight spatially aggregated genetic clusters of MDR-TB, four within the spillover region, consistent with local transmission among individuals living close to the prison.We demonstrate a clear prison spillover effect in this population, which suggests that interventions in the prison may have benefits that extend to the surrounding community.

    View details for PubMedID 30071850

  • Plasma IgA responses against two Salmonella Typhi antigens identify patients with typhoid fever. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Andrews, J. R., Khanam, F., Rahman, N., Hossain, M., Bogoch, I. I., Vaidya, K., Kelly, M., Calderwood, S. B., Bhuiyan, T. R., Ryan, E. T., Qadri, F., Charles, R. C. 2018


    There is a need for a reliable, simple diagnostic assay for typhoid fever. Available commercial serologic assays for typhoid fever have limited sensitivity and specificity. Using high-throughput immuno-screening technologies, we previously identified several immuno-reactive Salmonella Typhi antigens that appear promising for possible inclusion in a new diagnostic assay: hemolysin E (HlyE); cytolethal distending toxin (CdtB), S. Typhi LPS, and S. Typhi membrane preparation (MP).We assessed plasma antibody responses (IgM, IgA, and IgG) to these antigens via ELISA in patients with suspected enteric fever, controls with other febrile illnesses, and healthy controls in Dhaka, Bangladesh and performed Tubex, Typhidot, Widal and the Typhoid/Paratyphoid test (TPTest) on each patient. Using machine learning methods, we identified a parsimonious serology signature to distinguish acute typhoid cases from controls and then validated our findings in an independent test cohort from Nepal of culture-confirmed S. Typhi patients and controls with other bacteremic illnesses.We identified anti-MP IgG and IgA plasma responses to HlyE, LPS, and MP as important predictors of acute typhoid in the Bangladesh cohort. Using our Nepalese validation cohort, we demonstrated that the use of two antigens (HlyE and LPS) with one antibody isotype (IgA) could distinguish typhoid from other invasive bacterial infections (AUC 0.95; sensitivity 90%, specificity 92%). Use of a single antigen (HlyE) and isotype (IgA) had an AUC of 0.93.Our results suggest that development of a diagnostic assay for acute typhoid fever focused on detecting IgA responses against HlyE, with or without LPS, is warranted.

    View details for PubMedID 30020426

  • Suicide in Brazilian indigenous communities: clustering of cases in children and adolescents by household. Revista de saude publica Lazzarini, T. A., Gonçalves, C. C., Benites, W. M., Silva, L. F., Tsuha, D. H., Ko, A. I., Rohrbaugh, R., Andrews, J. R., Croda, J. 2018; 52: 56


    OBJECTIVE To estimate age and sex-specific suicide rates, compare suicide rates between indigenous communities, and quantify the frequency of intrafamilial suicide clustering. METHODS We performed a retrospective cohort study involving 14,666 indigenous individuals in reservations in Dourados, state of Mato Grosso do Sul, Brazil, from 2003 through 2013 using national and local census. RESULTS The overall suicide rate was 73.4 per 100,000 person-years. Adolescent males aged 15-19 and girls aged 10-14 had the highest rates for each sex at 289.3 (95%CI 187.5-391.2) and 85.3 (95%CI 34.9-135.7), respectively. Comparing the largest reservations, Bororo had a higher suicide rate than Jaguapiru (RR = 4.83, 95%CI 2.85-8.16) and had significantly lower socioeconomic indicators including income and access to electricity. Nine of 19 suicides among children under 15 occurred in household clusters. Compared with adult suicides, a greater proportion of child (OR = 5.12, 95%CI 1.89-13.86, p = 0.001) and adolescent (OR = 3.48, 95%CI 1.29-9.44, p = 0.017) suicides occurred within household clusters. CONCLUSIONS High rates of suicide occur among children and adolescents in these indigenous reservations, particularly in poor communities. Nearly half of child suicides occur within household clusters. These findings underscore the need for broad public health interventions and focused mental health interventions in households following a suicide.

    View details for PubMedID 29791676

  • What is the best immunization strategy for protecting African children against invasive Salmonella disease? Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Jeon, H. J., Pak, G. D., Im, J., Owusu-Dabo, E., Adu-Sarkodie, Y., Gassama Sow, A., Bassiahi, A. S., Gasmelseed, N., Keddy, K. H., Bjerregaard-Andersen, M., Konings, F., Aseffa, A., Crump, J. A., Chon, Y., Breiman, R. F., Park, S. E., Cruz Espinoza, L. M., Seo, H. J., May, J., Meyer, C. G., Andrews, J. R., Panzner, U., von Kalckreuth, V., Wierzba, T. F., Rakotozandrindrainy, R., Dougan, G., Levine, M. M., Hombach, J., Kim, J. H., Clemens, J. D., Baker, S., Marks, F. 2018


    The WHO recently prequalified a typhoid conjugate vaccine (TCV), recommending its use in persons aged ?6 months to 45 years residing in typhoid fever (TF)-endemic areas. We now need to consider how TCVs can have the greatest impact in the most vulnerable populations in Africa.The Typhoid Fever Surveillance in Africa Program (TSAP) in 10 sub-Saharan African countries included blood culture-based surveillance in febrile people presenting at healthcare-facilities originating from defined catchment areas. The TF/invasive non-typhoidal Salmonella (iNTS) disease incidences were estimated for 0-10 year-old children in yearly increments.Salmonella Typhi and iNTS were the most frequently isolated pathogens, 135 and 94 cases were identified, respectively. Isolates (12 and 4, respectively) from Ethiopia, Senegal and South Africa were excluded due to person-years of observation (PYO) data absence. 37/123 (30.1%) TF and 71/90 (78.9%) iNTS disease cases occurred among individuals aged <5 years. No TF and 8/90 (8.9%) iNTS-infections were observed in children aged <9 months. The TF incidences (/100,000 PYO) for children aged <1 year and 1-<2 years were 5 and 39, respectively; the highest incidence was 304/100,000 PYO in 4-<5 year-old children. The iNTS incidence in the defined age groups ranged between 81 and 233/100,000 PYO, with the highest incidence in 1-<2 year-old children. Higher TF/iNTS disease incidences were observed in West Africa.The high TF burden observed in TSAP merits TCV introductions. Considering the additional iNTS disease burden, a trivalent vaccine targeting S. Typhi, S. Typhimurium, and S. Enteritidis may be a future solution.

    View details for PubMedID 29746615

  • Drivers of seasonal variation in tuberculosis incidence: insights from a systematic review and mathematical model. Epidemiology (Cambridge, Mass.) Tedijanto, C., Hermans, S., Cobelens, F., Wood, R., Andrews, J. R. 2018


    Seasonality in tuberculosis incidence has been widely observed across countries and populations; however, its drivers are poorly understood. We conducted a systematic review of studies reporting seasonal patterns in tuberculosis to identify demographic and ecologic factors associated with timing and magnitude of seasonal variation.We identified studies reporting seasonal variation in tuberculosis incidence through PubMed and EMBASE and extracted incidence data and population metadata. We described key factors relating to seasonality and, when data permitted, quantified seasonal variation and its association with metadata. We developed a dynamic tuberculosis natural history and transmission model incorporating seasonal differences in disease progression and/or transmission rates to examine magnitude of variation required to produce observed seasonality in incidence.Fifty-seven studies met inclusion criteria. In the majority of studies (n=49), tuberculosis incidence peaked in spring or summer and reached a trough in late fall or winter. A standardized seasonal amplitude was calculated for 34 of the studies, resulting in a mean of 17.1% (range: 2.7-85.5%) after weighting by sample size. Across multiple studies, stronger seasonality was associated with younger patients, extrapulmonary disease, and latitudes farther from the Equator. The mathematical model was generally able to reproduce observed levels of seasonal case variation; however, substantial variation in transmission and/or disease progression risk was required to replicate several extreme values.We observed seasonal variation in tuberculosis, with consistent peaks occurring in spring, across countries with varying tuberculosis burden. Future research is needed to explore and quantify potential gains from strategically conducting mass screening interventions in the spring.

    View details for PubMedID 29870427

  • Deworming in pre-school age children: A global empirical analysis of health outcomes. PLoS neglected tropical diseases Lo, N. C., Snyder, J., Addiss, D. G., Heft-Neal, S., Andrews, J. R., Bendavid, E. 2018; 12 (5): e0006500


    There is debate over the effectiveness of deworming children against soil-transmitted helminthiasis (STH) to improve health outcomes, and current evidence may be limited in study design and generalizability. However, programmatic deworming continues throughout low and middle-income countries.We performed an empirical evaluation of the relationship between deworming in pre-school age children (ages 1-4 years) within the previous 6 months, as proxy-reported by the mother, and health outcomes of weight, height, and hemoglobin. We used nationally representative cross-sectional data from 45 countries using the Demographic and Health Surveys (DHS) during the period 2005-2016. We used logistic regression with coarsened exact matching, fixed effects for survey and year, and person-level covariates. We included data on 325,115 children in 45 STH-endemic countries from 66 DHS surveys. Globally in STH-endemic countries, children who received deworming treatment were less likely to be stunted (1.2 percentage point decline from mean of 36%; 95% CI [-1.9, -0.5%]; p<0.001), but we did not detect consistent associations between deworming and anemia or weight. In sub-Saharan Africa, we found that children who received deworming treatment were less likely to be stunted (1.1 percentage point decline from mean of 36%; 95% CI [-2.1, -0.2%]; p = 0.01) and less likely to have anemia (1.8 percentage point decline from mean of 58%; 95% CI [-2.8, -0.7%]; p<0.001), but we did not detect consistent associations between deworming and weight. These findings were robust across multiple statistical models, and we did not find consistently measurable associations with data from non-endemic settings.Among pre-school age children, we detected a robust and consistent association between deworming and reduced stunting, with additional evidence for reduced anemia in sub-Saharan Africa. We did not find a consistent relationship between deworming and improved weight. This global empirical analysis provides evidence to support the deworming of pre-school age children.

    View details for PubMedID 29852012

  • Comparison of Strategies and Incidence Thresholds for Vi Conjugate Vaccines Against Typhoid Fever: A Cost-effectiveness Modeling Study. The Journal of infectious diseases Lo, N. C., Gupta, R., Stanaway, J. D., Garrett, D. O., Bogoch, I. I., Luby, S. P., Andrews, J. R. 2018


    Typhoid fever remains a major public health problem globally. While new Vi conjugate vaccines hold promise for averting disease, the optimal programmatic delivery remains unclear. We aimed to identify the strategies and associated epidemiologic conditions under which Vi conjugate vaccines would be cost-effective.We developed a dynamic, age-structured transmission and cost-effectiveness model that simulated multiple vaccination strategies with a typhoid Vi conjugate vaccine from a societal perspective. We simulated 10-year vaccination programs with (1) routine immunization of infants (aged <1 year) through the Expanded Program on Immunization (EPI) and (2) routine immunization of infants through the EPI plus a 1-time catch-up campaign in school-aged children (aged 5-14 years). In the base case analysis, we assumed a 0.5% case-fatality rate for all cases of clinically symptomatic typhoid fever and defined strategies as highly cost-effective by using the definition of a low-income country (defined as a country with a gross domestic product of $1045 per capita). We defined incidence as the true number of clinically symptomatic people in the population per year.Vi conjugate typhoid vaccines were highly cost-effective when administered by routine immunization activities through the EPI in settings with an annual incidence of >50 cases/100000 (95% uncertainty interval, 40-75 cases) and when administered through the EPI plus a catch-up campaign in settings with an annual incidence of >130 cases/100000 (95% uncertainty interval, 50-395 cases). The incidence threshold was sensitive to the typhoid-related case-fatality rate, carrier contribution to transmission, vaccine characteristics, and country-specific economic threshold for cost-effectiveness.Typhoid Vi conjugate vaccines would be highly cost-effective in low-income countries in settings of moderate typhoid incidence (50 cases/100000 annually). These results were sensitive to case-fatality rates, underscoring the need to consider factors contributing to typhoid mortality (eg, healthcare access and antimicrobial resistance) in the global vaccination strategy.

    View details for PubMedID 29444257

  • Development of a new dipstick (Cholkit) for rapid detection of Vibrio cholerae O1 in acute watery diarrheal stools. PLoS neglected tropical diseases Sayeed, M. A., Islam, K., Hossain, M., Akter, N. J., Alam, M. N., Sultana, N., Khanam, F., Kelly, M., Charles, R. C., Ková?, P., Xu, P., Andrews, J. R., Calderwood, S. B., Amin, J., Ryan, E. T., Qadri, F. 2018; 12 (3): e0006286


    Recognizing cholera cases early, especially in the initial phase of an outbreak and in areas where cholera has not previously circulated, is a high public health priority. Laboratory capacity in such settings is often limited. To address this, we have developed a rapid diagnostic test (RDT) termed Cholkit that is based on an immunochromatographic lateral flow assay for the diagnosis of cholera cases using stool. Cholkit contains a monoclonal antibody (ICL-33) to the O-specific polysaccharide (OSP) component of V. cholerae O1 lipopolysaccharide, and recognizes both Inaba and Ogawa serotypes. We tested the Cholkit dipstick using fresh stool specimens of 76 adults and children presenting with acute watery diarrhea at the icddr,b hospital in Dhaka, Bangladesh. We compared Cholkit's performance with those of microbial culture, PCR (targeting the rfb and ctxA genes of V. cholerae) and the commercially available RDT, Crystal VC (Span Diagnostics; Surat, India). We found that all stool specimens with a positive culture for V. cholerae O1 (n = 19) were positive by Cholkit as well as Crystal VC. We then used Bayesian latent class modeling to estimate the sensitivity and specificity of each diagnostic assay. The sensitivity of Cholkit, microbiological culture, PCR and Crystal VC was 98% (95% CI: 88-100), 71% (95% CI: 59-81), 74% (95% CI: 59-86) and 98% (95% CI: 88-100), respectively. The specificity for V. cholerae O1 was 97% (95% CI: 89-100), 100%, 97% (95% CI: 93-99) and 98% (95% CI: 92-100), respectively. Of note, two Crystal VC dipsticks were positive for V. cholerae O139 but negative by culture and PCR in this area without known circulating epidemic V. cholerae O139. In conclusion, the Cholkit dipstick is simple to use, requires no dedicated laboratory capacity, and has a sensitivity and specificity for V. cholerae O1 of 98% and 97%, respectively. Cholkit warrants further evaluation in other settings.

    View details for PubMedID 29538377

  • Disease ecology, health and the environment: a framework to account for ecological and socio-economic drivers in the control of neglected tropical diseases PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Garchitorena, A., Sokolow, S. H., Roche, B., Ngonghala, C. N., Jocque, M., Lund, A., Barry, M., MORDECAI, E. A., Daily, G. C., Jones, J. H., Andrews, J. R., Bendavid, E., Luby, S. P., LaBeaud, A. D., Seetah, K., Guegan, J. F., Bonds, M. H., De Leo, G. A. 2017; 372 (1722)


    Reducing the burden of neglected tropical diseases (NTDs) is one of the key strategic targets advanced by the Sustainable Development Goals. Despite the unprecedented effort deployed for NTD elimination in the past decade, their control, mainly through drug administration, remains particularly challenging: persistent poverty and repeated exposure to pathogens embedded in the environment limit the efficacy of strategies focused exclusively on human treatment or medical care. Here, we present a simple modelling framework to illustrate the relative role of ecological and socio-economic drivers of environmentally transmitted parasites and pathogens. Through the analysis of system dynamics, we show that periodic drug treatments that lead to the elimination of directly transmitted diseases may fail to do so in the case of human pathogens with an environmental reservoir. Control of environmentally transmitted diseases can be more effective when human treatment is complemented with interventions targeting the environmental reservoir of the pathogen. We present mechanisms through which the environment can influence the dynamics of poverty via disease feedbacks. For illustration, we present the case studies of Buruli ulcer and schistosomiasis, two devastating waterborne NTDs for which control is particularly challenging.This article is part of the themed issue 'Conservation, biodiversity and infectious disease: scientific evidence and policy implications'.

    View details for DOI 10.1098/rstb.2016.0128

    View details for PubMedID 28438917

  • Determinants of severe dehydration from diarrheal disease at hospital presentation: Evidence from 22 years of admissions in Bangladesh. PLoS neglected tropical diseases Andrews, J. R., Leung, D. T., Ahmed, S., Malek, M. A., Ahmed, D., Begum, Y. A., Qadri, F., Ahmed, T., Faruque, A. S., Nelson, E. J. 2017; 11 (4)


    To take advantage of emerging opportunities to reduce morbidity and mortality from diarrheal disease, we need to better understand the determinants of life-threatening severe dehydration (SD) in resource-poor settings.We analyzed records of patients admitted with acute diarrheal disease over twenty-two years at the International Centre for Diarrhoeal Disease Research, Bangladesh (1993-2014). Patients presenting with and without SD were compared by multivariable logistic regression models, which included socio-demographic factors and pathogens isolated. Generalized additive models evaluated non-linearities between age or household income and SD. Among 55,956 admitted patients, 13,457 (24%) presented with SD. Vibrio cholerae was the most common pathogen isolated (12,405 patients; 22%), and had the strongest association with SD (AOR 4.77; 95% CI: 4.41-5.51); detection of multiple pathogens did not exacerbate SD risk. The highest proportion of severely dehydrated patients presented in a narrow window only 4-12 hours after symptom onset. Risk of presenting with SD increased sharply from zero to ten years of age and remained high throughout adolescence and adulthood. Adult women had a 38% increased odds (AOR 1.38; 95% CI: 1.30-1.46) of SD compared to adult men. The probability of SD increased sharply at low incomes. These findings were consistent across pathogens.There remain underappreciated populations vulnerable to life-threatening diarrheal disease that include adult women and the very poor. In addition to efforts that address diarrheal disease in young children, there is a need to develop interventions for these other high-risk populations that are accessible within 4 hours of symptom onset.

    View details for DOI 10.1371/journal.pntd.0005512

    View details for PubMedID 28448489

  • A call to strengthen the global strategy against schistosomiasis and soil-transmitted helminthiasis: the time is now. The Lancet. Infectious diseases Lo, N. C., Addiss, D. G., Hotez, P. J., King, C. H., Stothard, J. R., Evans, D. S., Colley, D. G., Lin, W., Coulibaly, J. T., Bustinduy, A. L., Raso, G., Bendavid, E., Bogoch, I. I., Fenwick, A., Savioli, L., Molyneux, D., Utzinger, J., Andrews, J. R. 2017; 17 (2): e64-e69


    In 2001, the World Health Assembly (WHA) passed the landmark WHA 54.19 resolution for global scale-up of mass administration of anthelmintic drugs for morbidity control of schistosomiasis and soil-transmitted helminthiasis, which affect more than 1·5 billion of the world's poorest people. Since then, more than a decade of research and experience has yielded crucial knowledge on the control and elimination of these helminthiases. However, the global strategy has remained largely unchanged since the original 2001 WHA resolution and associated WHO guidelines on preventive chemotherapy. In this Personal View, we highlight recent advances that, taken together, support a call to revise the global strategy and guidelines for preventive chemotherapy and complementary interventions against schistosomiasis and soil-transmitted helminthiasis. These advances include the development of guidance that is specific to goals of morbidity control and elimination of transmission. We quantify the result of forgoing this opportunity by computing the yearly disease burden, mortality, and lost economic productivity associated with maintaining the status quo. Without change, we estimate that the population of sub-Saharan Africa will probably lose 2·3 million disability-adjusted life-years and US$3·5 billion of economic productivity every year, which is comparable to recent acute epidemics, including the 2014 Ebola and 2015 Zika epidemics. We propose that the time is now to strengthen the global strategy to address the substantial disease burden of schistosomiasis and soil-transmitted helminthiasis.

    View details for DOI 10.1016/S1473-3099(16)30535-7

    View details for PubMedID 27914852

    View details for PubMedCentralID PMC5280090

  • Increase in Tuberculosis Cases among Prisoners, Brazil, 2009-2014(1). Emerging infectious diseases Bourdillon, P. M., Gonçalves, C. C., Pelissari, D. M., Arakaki-Sanchez, D., Ko, A. I., Croda, J., Andrews, J. R. 2017; 23 (3): 496?99


    During 2009-2014, incarceration rates in Brazil rose 34%, and tuberculosis (TB) cases among prisoners rose 28.8%. The proportion of national TB cases that occurred among prisoners increased from 6.2% to 8.4% overall and from 19.3% to 25.6% among men 20-29 years of age.

    View details for DOI 10.3201/eid2303.161006

    View details for PubMedID 28221118

  • High Rates of Enteric Fever Diagnosis and Lower Burden of Culture-Confirmed Disease in Peri-urban and Rural Nepal. The Journal of infectious diseases Andrews, J. R., Vaidya, K., Bern, C., Tamrakar, D., Wen, S., Madhup, S., Shrestha, R., Karmacharya, B., Amatya, B., Koju, R., Adhikari, S. R., Hohmann, E., Ryan, E. T., Bogoch, I. I. 2017


    In South Asia, data on enteric fever are sparse outside of urban areas. We characterized enteric fever diagnosis patterns and the burden of culture-confirmed cases in peri-urban and rural Nepal.We used national reports to estimate enteric fever diagnosis rates over 20 years (1994-2014) and conducted a prospective study of patients presenting with a >72-hour history of fever to 4 peri-urban and rural healthcare facilities (during August 2013-June 2016). We compared clinical characteristics of patients with culture-confirmed Salmonella Typhi or Paratyphi infection to those of patients without enteric fever. We used generalized additive models with logistic link functions to evaluate associations of age and population density with culture positivity.National rates of enteric fever diagnosis were high, reaching 18.8 cases per 1000 during 2009-2014. We enrolled 4309 participants with acute febrile illness. Among those with a provisional clinical diagnosis, 55% (1334 of 2412) received a diagnosis of enteric fever; however, only 4.1% of these had culture-confirmed typhoidal Salmonella infection. Culture positivity was highest among young adults and was strongly associated with higher population density (P < .001).Enteric fever diagnosis rates were very high throughout Nepal, but in rural settings, few patients had culture-confirmed disease. Expanded surveillance may inform local enteric fever treatment and prevention strategies.

    View details for PubMedID 28961918

  • The benefits of mass deworming on health outcomes: new evidence synthesis, the debate persists. The Lancet. Global health Andrews, J. R., Bogoch, I. I., Utzinger, J. 2017; 5 (1): e4-e5

    View details for DOI 10.1016/S2214-109X(16)30333-3

    View details for PubMedID 27955787

  • Mobile phone and handheld microscopes for public health applications Lancet Public Health Bogoch, I. I., Lundin, J., Lo, N. C., Andrews, J. R. 2017; 2 (8): e355
  • The global burden of tuberculosis: results from the Global Burden of Disease Study 2015. The Lancet. Infectious diseases 2017


    An understanding of the trends in tuberculosis incidence, prevalence, and mortality is crucial to tracking of the success of tuberculosis control programmes and identification of remaining challenges. We assessed trends in the fatal and non-fatal burden of tuberculosis over the past 25 years for 195 countries and territories.We analysed 10?691 site-years of vital registration data, 768 site-years of verbal autopsy data, and 361 site-years of mortality surveillance data using the Cause of Death Ensemble model to estimate tuberculosis mortality rates. We analysed all available age-specific and sex-specific data sources, including annual case notifications, prevalence surveys, and estimated cause-specific mortality, to generate internally consistent estimates of incidence, prevalence, and mortality using DisMod-MR 2.1, a Bayesian meta-regression tool. We assessed how observed tuberculosis incidence, prevalence, and mortality differed from expected trends as predicted by the Socio-demographic Index (SDI), a composite indicator based on income per capita, average years of schooling, and total fertility rate. We also estimated tuberculosis mortality and disability-adjusted life-years attributable to the independent effects of risk factors including smoking, alcohol use, and diabetes.Globally, in 2015, the number of tuberculosis incident cases (including new and relapse cases) was 10·2 million (95% uncertainty interval 9·2 million to 11·5 million), the number of prevalent cases was 10·1 million (9·2 million to 11·1 million), and the number of deaths was 1·3 million (1·1 million to 1·6 million). Among individuals who were HIV negative, the number of incident cases was 8·8 million (8·0 million to 9·9 million), the number of prevalent cases was 8·9 million (8·1 million to 9·7 million), and the number of deaths was 1·1 million (0·9 million to 1·4 million). Annualised rates of change from 2005 to 2015 showed a faster decline in mortality (-4·1% [-5·0 to -3·4]) than in incidence (-1·6% [-1·9 to -1·2]) and prevalence (-0·7% [-1·0 to -0·5]) among HIV-negative individuals. The SDI was inversely associated with HIV-negative mortality rates but did not show a clear gradient for incidence and prevalence. Most of Asia, eastern Europe, and sub-Saharan Africa had higher rates of HIV-negative tuberculosis burden than expected given their SDI. Alcohol use accounted for 11·4% (9·3-13·0) of global tuberculosis deaths among HIV-negative individuals in 2015, diabetes accounted for 10·6% (6·8-14·8), and smoking accounted for 7·8% (3·8-12·0).Despite a concerted global effort to reduce the burden of tuberculosis, it still causes a large disease burden globally. Strengthening of health systems for early detection of tuberculosis and improvement of the quality of tuberculosis care, including prompt and accurate diagnosis, early initiation of treatment, and regular follow-up, are priorities. Countries with higher than expected tuberculosis rates for their level of sociodemographic development should investigate the reasons for lagging behind and take remedial action. Efforts to prevent smoking, alcohol use, and diabetes could also substantially reduce the burden of tuberculosis.Bill & Melinda Gates Foundation.

    View details for DOI 10.1016/S1473-3099(17)30703-X

    View details for PubMedID 29223583

  • Genetic Clustering of Tuberculosis in an Indigenous Community of Brazil. The American journal of tropical medicine and hygiene Correia Sacchi, F. P., Tatara, M. B., Camioli de Lima, C., Ferreia da Silva, L., Cunha, E. A., Simonsen, V., Ferrazoli, L., Gomes, H. M., Gonçalves Vasconcellos, S. E., Suffys, P. N., Andrews, J. R., Croda, J. 2017


    We conducted a population-based study of tuberculosis (TB) from 2009 to 2015 in an indigenous community of Brazil, the largest in the country, to investigate risk factors associated with recent TB transmission. The clinical isolates of Mycobacterium tuberculosis were genotyped by IS6110-RFLP (restriction fragment length polymorphism) and spoligotyping analysis. Among 67 isolates typed by RFLP, 69% fell into fifteen clusters, and 91% of TB cases with shared IS6110-RFLP pattern were diagnosed within 2 years of another case in the cluster. Individual risk factors associated with genetic clustering were domestic overcrowding (odds ratio [OR]: 6.10; 95% confidence interval [CI]: 1.50-24.88) and low social class (OR: 3.72; 95% CI: 1.00-13.98). Most reported contacts (76%) were identified within the household of the index TB case, but most of the genetic clustering of M. tuberculosis occurred outside of household (79%). Expanded contacts investigation and prophylaxis outside of household should be considered as a priority for TB control programs in this population.

    View details for PubMedID 29210353

  • Schistosoma haematobium Egg Excretion does not Increase after Exercise: Implications for Diagnostic Testing. The American journal of tropical medicine and hygiene Coulibaly, J. T., Andrews, J. R., Lo, N. C., N'Goran, E. K., Utzinger, J., Keiser, J., Bogoch, I. I. 2017


    Children are frequently invited to exercise before micturition, as it is believed that this will result in higher Schistosoma haematobium egg excretion, and hence, increases sensitivity of microscopic diagnoses. However, the evidence of this recommendation is scant. In the study presented here, 257 children, aged 2-15 years from south Côte d'Ivoire, provided urine samples for microscopy on consecutive days; one sample without prior exercise and one sample after exercise. Comparing the same individuals without and with prior exercise, sample positivity for S. haematobium (25.7% versus 23.0%, P = 0.31) and mean egg counts (10.2 eggs/10 mL versus 8.5 eggs/10 mL, P = 0.45) did not differ. Exercise before urine collection does not appear to increase S. haematobium egg excretion.

    View details for PubMedID 29260647

  • Drivers of Tuberculosis Transmission. The Journal of infectious diseases Mathema, B., Andrews, J. R., Cohen, T., Borgdorff, M. W., Behr, M., Glynn, J. R., Rustomjee, R., Silk, B. J., Wood, R. 2017; 216 (suppl_6): S644?S653


    Measuring tuberculosis transmission is exceedingly difficult, given the remarkable variability in the timing of clinical disease after Mycobacterium tuberculosis infection; incident disease can result from either a recent (ie, weeks to months) or a remote (ie, several years to decades) infection event. Although we cannot identify with certainty the timing and location of tuberculosis transmission for individuals, approaches for estimating the individual probability of recent transmission and for estimating the fraction of tuberculosis cases due to recent transmission in populations have been developed. Data used to estimate the probable burden of recent transmission include tuberculosis case notifications in young children and trends in tuberculin skin test and interferon ?-release assays. More recently, M. tuberculosis whole-genome sequencing has been used to estimate population levels of recent transmission, identify the distribution of specific strains within communities, and decipher chains of transmission among culture-positive tuberculosis cases. The factors that drive the transmission of tuberculosis in communities depend on the burden of prevalent tuberculosis; the ways in which individuals live, work, and interact (eg, congregate settings); and the capacity of healthcare and public health systems to identify and effectively treat individuals with infectious forms of tuberculosis. Here we provide an overview of these factors, describe tools for measurement of ongoing transmission, and highlight knowledge gaps that must be addressed.

    View details for PubMedID 29112745

  • Identification of Novel Serodiagnostic Signatures of Typhoid Fever Using a Salmonella Proteome Array. Frontiers in microbiology Darton, T. C., Baker, S., Randall, A., Dongol, S., Karkey, A., Voysey, M., Carter, M. J., Jones, C., Trappl, K., Pablo, J., Hung, C., Teng, A., Shandling, A., Le, T., Walker, C., Molina, D., Andrews, J., Arjyal, A., Basnyat, B., Pollard, A. J., Blohmke, C. J. 2017; 8: 1794


    Current diagnostic tests for typhoid fever, the disease caused by Salmonella Typhi, are poor. We aimed to identify serodiagnostic signatures of typhoid fever by assessing microarray signals to 4,445 S. Typhi antigens in sera from 41 participants challenged with oral S. Typhi. We found broad, heterogeneous antibody responses with increasing IgM/IgA signals at diagnosis. In down-selected 250-antigen arrays we validated responses in a second challenge cohort (n = 30), and selected diagnostic signatures using machine learning and multivariable modeling. In four models containing responses to antigens including flagellin, OmpA, HlyE, sipC, and LPS, multi-antigen signatures discriminated typhoid (n = 100) from other febrile bacteremia (n = 52) in Nepal. These models contained combinatorial IgM, IgA, and IgG responses to 5 antigens (ROC AUC, 0.67 and 0.71) or 3 antigens (0.87), although IgA responses to LPS also performed well (0.88). Using a novel systematic approach we have identified and validated optimal serological diagnostic signatures of typhoid fever.

    View details for PubMedID 28970824

    View details for PubMedCentralID PMC5609549

  • Optimization and Interpretation of Serial QuantiFERON Testing to Measure Acquisition of M. tuberculosis Infection. American journal of respiratory and critical care medicine Nemes, E., Rozot, V., Geldenhuys, H., Bilek, N., Mabwe, S., Abrahams, D., Makhethe, L., Erasmus, M., Keyser, A., Toefy, A., Cloete, Y., Ratangee, F., Blauenfeldt, T., Ruhwald, M., Walzl, G., Smith, B., Loxton, A. G., Hanekom, W. A., Andrews, J. R., Lempicki, M. D., Ellis, R., Ginsberg, A. M., Hatherill, M., Scriba, T. J. 2017


    Conversion from a negative to positive QuantiFERON-TB test is indicative of Mycobacterium tuberculosis (M.tb) infection, which predisposes to tuberculosis disease. Interpretation of serial tests is confounded by immunological and technical variability.To improve consistency of serial QuantiFERON-TB testing algorithms and provide a data-driven definition of conversion.Sources of QuantiFERON-TB variability were assessed and optimal procedures identified. Distributions of IFN? response levels were analysed in healthy adolescents, M.tb-unexposed controls, and pulmonary tuberculosis patients.Individuals with no known M.tb exposure had IFN? values <0.2 IU/mL. Among individuals with IFN? values <0.2, 0.2-0.34, 0.35-0.7, and >0.7 IU/mL, tuberculin skin test positivity was 15%, 53%, 66% and 91% (p<0.005), respectively. Together, these findings suggest that values <0.2 IU/mL were true negatives. In short-term serial testing, "uncertain" conversions, with at least one value within the uncertainty zone (0.2-0.7 IU/mL), were partly explained by technical assay variability. Individuals who had a change in QuantiFERON-TB IFN? values from <0.2 to >0.7 IU/mL had 10-fold higher tuberculosis incidence rates than those who maintained values <0.2 IU/mL over 2 years (p=0.0003). By contrast, "uncertain" converters were not at higher risk than non-converters (p=0.229). Eighty-seven percent of active TB patients had IFN? values >0.7 IU/mL, suggesting that these values are consistent with established M.tb infection.Implementation of optimized procedures and a more rigorous QuantiFERON-TB conversion definition, an increase from IFN? <0.2 to >0.7 IU/mL, would allow more definitive detection of recent M.tb infection and potentially improve identification of those more likely to develop disease.

    View details for PubMedID 28737960

  • Evaluation of a Mobile Phone-Based Microscope for Screening of Schistosoma haematobium Infection in Rural Ghana. The American journal of tropical medicine and hygiene Bogoch, I. I., Koydemir, H. C., Tseng, D., Ephraim, R. K., Duah, E., Tee, J., Andrews, J. R., Ozcan, A. 2017; 96 (6): 1468?71


    AbstractSchistosomiasis affects over 170 million people in Africa. Here we compare a novel, low-cost mobile phone microscope to a conventional light microscope for the label-free diagnosis of Schistosoma haematobium infections in a rural Ghanaian school setting. We tested the performance of our handheld microscope using 60 slides that were randomly chosen from an ongoing epidemiologic study in school-aged children. The mobile phone microscope had a sensitivity of 72.1% (95% confidence interval [CI]: 56.1-84.2), specificity of 100% (95% CI: 75.9-100), positive predictive value of 100% (95% CI: 86.3-100), and a negative predictive value of 57.1% (95% CI: 37.4-75.0). With its modest sensitivity and high specificity, this handheld and cost-effective mobile phone-based microscope is a stepping-stone toward developing a powerful tool in clinical and public health settings where there is limited access to conventional laboratory diagnostic support.

    View details for PubMedID 28719262

  • Eosinophilic Meningitis Caused by Angiostrongylus cantonensis. ACS chemical neuroscience Lv, S., Zhou, X. N., Andrews, J. R. 2017


    Rat lungworm, Angiostrongylus cantonensis, is one major cause of human eosinophilic meningitis. This helminth is endemic in Southeast Asia, Pacific Islands, and the Caribbean and has recently expanded to South America. The infection is characterized by an elevated eosinophil count in cerebrospinal fluid. Common symptoms and signs include headache, neck stiffness, paresthesia and nausea/vomiting. The unique history of eating freshwater and land snails or slugs within 2 weeks before onset is helpful for diagnosis. Antihelminthic agents have not shown efficacy in human infection; treatment involves supportive care with management of inflammation and intracranial pressure.

    View details for PubMedID 28704038

  • Mobile-phone and handheld microscopy for neglected tropical diseases. PLoS neglected tropical diseases Rajchgot, J., Coulibaly, J. T., Keiser, J., Utzinger, J., Lo, N. C., Mondry, M. K., Andrews, J. R., Bogoch, I. I. 2017; 11 (7): e0005550

    View details for PubMedID 28683127

  • Evaluation of a Smartphone Decision-Support Tool for Diarrheal Disease Management in a Resource-Limited Setting. PLoS neglected tropical diseases Haque, F., Ball, R. L., Khatun, S., Ahmed, M., Kache, S., Chisti, M. J., Sarker, S. A., Maples, S. D., Pieri, D., Vardhan Korrapati, T., Sarnquist, C., Federspiel, N., Rahman, M. W., Andrews, J. R., Rahman, M., Nelson, E. J. 2017; 11 (1)


    The emergence of mobile technology offers new opportunities to improve clinical guideline adherence in resource-limited settings. We conducted a clinical pilot study in rural Bangladesh to evaluate the impact of a smartphone adaptation of the World Health Organization (WHO) diarrheal disease management guidelines, including a modality for age-based weight estimation. Software development was guided by end-user input and evaluated in a resource-limited district and sub-district hospital during the fall 2015 cholera season; both hospitals lacked scales which necessitated weight estimation. The study consisted of a 6 week pre-intervention and 6 week intervention period with a 10-day post-discharge follow-up. Standard of care was maintained throughout the study with the exception that admitting clinicians used the tool during the intervention. Inclusion criteria were patients two months of age and older with uncomplicated diarrheal disease. The primary outcome was adherence to guidelines for prescriptions of intravenous (IV) fluids, antibiotics and zinc. A total of 841 patients were enrolled (325 pre-intervention; 516 intervention). During the intervention, the proportion of prescriptions for IV fluids decreased at the district and sub-district hospitals (both p < 0.001) with risk ratios (RRs) of 0.5 and 0.2, respectively. However, when IV fluids were prescribed, the volume better adhered to recommendations. The proportion of prescriptions for the recommended antibiotic azithromycin increased (p < 0.001 district; p = 0.035 sub-district) with RRs of 6.9 (district) and 1.6 (sub-district) while prescriptions for other antibiotics decreased; zinc adherence increased. Limitations included an absence of a concurrent control group and no independent dehydration assessment during the pre-intervention. Despite limitations, opportunities were identified to improve clinical care, including better assessment, weight estimation, and fluid/ antibiotic selection. These findings demonstrate that a smartphone-based tool can improve guideline adherence. This study should serve as a catalyst for a randomized controlled trial to expand on the findings and address limitations.

    View details for DOI 10.1371/journal.pntd.0005290

    View details for PubMedID 28103233

  • Poor Validity of Noninvasive Hemoglobin Measurements by Pulse Oximetry Compared with Conventional Absorptiometry in Children in Cote d'Ivoire AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Bogoch, I. I., Coulibaly, J. T., Rajchgot, J., Andrews, J. R., Kovac, J., Utzinger, J., Panic, G., Keiser, J. 2017; 96 (1): 217-220


    Anemia remains a major public health issue in many African communities. We compared a novel, commercially available noninvasive hemoglobin (Hb)-measuring device to direct Hb measurements by finger-prick samples in a pediatric cohort in rural Côte d'Ivoire. Noninvasive Hb measurements were attempted in 191 children 2-15 years of age and obtained in 102 (53.5%) children. The median Hb for the 102 children was 12.0 g/dL (interquartile range [IQR] = 11.3-12.7 g/dL) for conventional absorptiometry and 13.3 g/dL (IQR = 12.1-14.2 g/dL) for noninvasive measurements. A Bland-Altman analysis demonstrated a median bias of +1.1 g/dL (IQR = 0.4-2.0 g/dL), with greater overestimation of Hb by noninvasive testing occurring at low Hb values. This overestimation of the noninvasive Hb-measuring device to direct Hb measurements persisted across preschool- and school-aged children, and both sexes. The Pearson correlation coefficient was 0.50 for children 4-9 years of age, and 0.33 for children 10-15 years of age. Further study and development of noninvasive Hb devices is necessary prior to implementation in African pediatric populations.

    View details for DOI 10.4269/ajtmh.16-0505

    View details for Web of Science ID 000397822900040

    View details for PubMedID 28077748

  • Evaluation of Malaria Diagnoses Using a Handheld Light Microscope in a Community-Based Setting in Rural Cote d'Ivoire AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Coulibaly, J. T., Ouattara, M., Keiser, J., Bonfoh, B., N'Goran, E. K., Andrews, J. R., Bogoch, I. I. 2016; 95 (4): 831-834


    Portable microscopy may facilitate quality diagnostic care in resource-constrained settings. We compared a handheld light microscope (Newton Nm1) with a mobile phone attachment to conventional light microscopy for the detection of Plasmodium falciparum in a cross-sectional study in rural Côte d'Ivoire. Single Giemsa-stained thick blood film from 223 individuals were prepared and read by local laboratory technicians on both microscopes under 1,000× magnification with oil. Of the 223 samples, 162 (72.6%) were P. falciparum positive, and the overall mean parasite count was 1,392/?L of blood. Sensitivity and specificity of the handheld microscope was 80.2% (95% confidence interval [CI]: 73.1-85.9%) and 100.0% (95% CI: 92.6-100.0%), respectively, with a positive and negative predictive value of 100.0% (95% CI: 96.4-100.0%) and 65.6% (95% CI: 54.9-74.9%), respectively. If sensitivity can be improved, handheld light microscopy may become a valuable public health tool for P. falciparum diagnosis.

    View details for DOI 10.4269/ajtmh.16-0328

    View details for Web of Science ID 000400206500021

    View details for PubMedID 27527637

  • Risk of self-reported symptoms or diagnosis of active tuberculosis in relationship to low body mass index, diabetes and their co-occurrence. Tropical medicine & international health Prince, L., Andrews, J. R., Basu, S., Goldhaber-Fiebert, J. D. 2016; 21 (10): 1272-1281


    Globally, tuberculosis prevalence has declined, but its risk factors have varied across place and time - low body mass index (BMI) has persisted while diabetes has increased. Using India's National Family Health Survey (NFHS), wave 3 and World Health Survey (WHS) data, we examined their relationships to support projection of future trends and targeted control efforts.Multivariate logistic regressions at the individual level with and without diabetes/BMI interactions assessed the relationship between tuberculosis, diabetes and low BMI and the importance of risk factor co-occurrence. Population-level analyses examined how tuberculosis incidence and prevalence varied with diabetes/low BMI co-occurrence.In NFHS, diabetic individuals had higher predicted tuberculosis risks (diabetic vs. non-diabetic: 2.50% vs. 0.63% at low BMI; 0.81% vs. 0.20% at normal BMI; 0.37% vs. 0.09% at high BMI), which were not significantly different when modelled independently or allowing for risk modification with diabetes/low BMI co-occurrence. WHS findings were generally consistent. Population-level analysis found that diabetes/low BMI co-occurrence may be associated with elevated tuberculosis risk, although its predicted effect on tuberculosis incidence/prevalence was generally ?0.2 percentage points and not robustly statistically significant.Concerns about the additional elevation of tuberculosis risk from diabetes/low BMI co-occurrence and hence the need to coordinate tuberculosis control efforts around the nexus of co-occurring diabetes and low BMI may be premature. However, study findings robustly support the importance of individually targeting low BMI and diabetes as part of ongoing tuberculosis control efforts.

    View details for DOI 10.1111/tmi.12763

    View details for PubMedID 27495971

  • Advances in diagnosis, treatment, and prevention of invasive Salmonella infections. Current opinion in infectious diseases MacFadden, D. R., Bogoch, I. I., Andrews, J. R. 2016; 29 (5): 453-458


    Typhoidal and nontyphoidal Salmonella enterica serotypes are among the most common bacterial causes of acute febrile illnesses in the developing world. In this review, we discuss new advances in understanding of the burden, diagnostic approaches, treatment and vaccines for invasive Salmonella infections.Recent estimates of the global burden of typhoidal and nontyphoidal Salmonella not only affirm the importance of these infections but also highlight the paucity of systematic incidence data from many regions. New data from Africa indicate that typhoidal Salmonella may be more common than previously considered. Novel diagnostic techniques for Salmonella include new serologic, molecular and metabolomic approaches, but blood culture - although slow and insensitive - remains the primary means of establishing a diagnosis. Antibiotic resistance, particularly to fluoroquinolones, continues to emerge and threatens to undermine treatment success for these infections. New vaccines for typhoid, including conjugate vaccines with longer duration of immunity than prior vaccines, represent a promising tool for prevention of enteric fever.Invasive Salmonella infections are a major cause of morbidity and mortality worldwide. Increasing antibiotic resistance in Salmonella is concerning, and empiric oral options are being rapidly eroded. Where new effective antimicrobials are lacking, developments in vaccines offer hope for reducing the burden of Salmonella infections globally.

    View details for DOI 10.1097/QCO.0000000000000302

    View details for PubMedID 27479027

  • Evaluation of a Urine Pooling Strategy for the Rapid and Cost-Efficient Prevalence Classification of Schistosomiasis. PLoS neglected tropical diseases Lo, N. C., Coulibaly, J. T., Bendavid, E., N'Goran, E. K., Utzinger, J., Keiser, J., Bogoch, I. I., Andrews, J. R. 2016; 10 (8)


    A key epidemiologic feature of schistosomiasis is its focal distribution, which has important implications for the spatial targeting of preventive chemotherapy programs. We evaluated the diagnostic accuracy of a urine pooling strategy using a point-of-care circulating cathodic antigen (POC-CCA) cassette test for detection of Schistosoma mansoni, and employed simulation modeling to test the classification accuracy and efficiency of this strategy in determining where preventive chemotherapy is needed in low-endemicity settings.We performed a cross-sectional study involving 114 children aged 6-15 years in six neighborhoods in Azaguié Ahoua, south Côte d'Ivoire to characterize the sensitivity and specificity of the POC-CCA cassette test with urine samples that were tested individually and in pools of 4, 8, and 12. We used a Bayesian latent class model to estimate test characteristics for individual POC-CCA and quadruplicate Kato-Katz thick smears on stool samples. We then developed a microsimulation model and used lot quality assurance sampling to test the performance, number of tests, and total cost per school for each pooled testing strategy to predict the binary need for school-based preventive chemotherapy using a 10% prevalence threshold for treatment.The sensitivity of the urine pooling strategy for S. mansoni diagnosis using pool sizes of 4, 8, and 12 was 85.9%, 79.5%, and 65.4%, respectively, when POC-CCA trace results were considered positive, and 61.5%, 47.4%, and 30.8% when POC-CCA trace results were considered negative. The modeled specificity ranged from 94.0-97.7% for the urine pooling strategies (when POC-CCA trace results were considered negative). The urine pooling strategy, regardless of the pool size, gave comparable and often superior classification performance to stool microscopy for the same number of tests. The urine pooling strategy with a pool size of 4 reduced the number of tests and total cost compared to classical stool microscopy.This study introduces a method for rapid and efficient S. mansoni prevalence estimation through examining pooled urine samples with POC-CCA as an alternative to widely used stool microscopy.

    View details for DOI 10.1371/journal.pntd.0004894

    View details for PubMedID 27504954

    View details for PubMedCentralID PMC4978437

  • Accuracy of Mobile Phone and Handheld Light Microscopy for the Diagnosis of Schistosomiasis and Intestinal Protozoa Infections in Cote d'Ivoire PLOS NEGLECTED TROPICAL DISEASES Coulibaly, J. T., Ouattara, M., D'Ambrosio, M. V., Fletcher, D. A., Keiser, J., Utzinger, J., N'Goran, E. K., Andrews, J. R., Bogoch, I. I. 2016; 10 (6)


    Handheld light microscopy using compact optics and mobile phones may improve the quality of health care in resource-constrained settings by enabling access to prompt and accurate diagnosis.Laboratory technicians were trained to operate two handheld diagnostic devices (Newton Nm1 microscope and a clip-on version of the mobile phone-based CellScope). The accuracy of these devices was compared to conventional light microscopy for the diagnosis of Schistosoma haematobium, S. mansoni, and intestinal protozoa infection in a community-based survey in rural Côte d'Ivoire. One slide of 10 ml filtered urine and a single Kato-Katz thick smear from 226 individuals were subjected to the Newton Nm1 microscope and CellScope for detection of Schistosoma eggs and compared to conventional microscopy. Additionally, 121 sodium acetate-acetic acid-formalin (SAF)-fixed stool samples were examined by the Newton Nm1 microscope and compared to conventional microscopy for the diagnosis of intestinal protozoa.The prevalence of S. haematobium, S. mansoni, Giardia intestinalis, and Entamoeba histolytica/E. dispar, as determined by conventional microscopy, was 39.8%, 5.3%, 20.7%, and 4.9%, respectively. The Newton Nm1 microscope had diagnostic sensitivities for S. mansoni and S. haematobium infection of 91.7% (95% confidence interval (CI) 59.8-99.6%) and 81.1% (95% CI 71.2-88.3%), respectively, and specificities of 99.5% (95% CI 97.0-100%) and 97.1% (95% CI 92.2-99.1%), respectively. The CellScope demonstrated sensitivities for S. mansoni and S. haematobium of 50.0% (95% CI 25.4-74.6%) and 35.6% (95% CI 25.9-46.4%), respectively, and specificities of 99.5% (95% CI 97.0-100%) and 100% (95% CI 86.7-100%), respectively. For G. intestinalis and E. histolytica/E. dispar, the Newton Nm1 microscope had sensitivity of 84.0% (95% CI 63.1-94.7%) and 83.3% (95% CI 36.5-99.1%), respectively, and 100% specificity.Handheld diagnostic devices can be employed in community-based surveys in resource-constrained settings after minimal training of laboratory technicians to diagnose intestinal parasites.

    View details for DOI 10.1371/journal.pntd.0004768

    View details for Web of Science ID 000379346200031

    View details for PubMedID 27348755

  • Diagnosis of Opisthorchis viverrini Infection with Handheld Microscopy in Lao People's Democratic Republic. American journal of tropical medicine and hygiene Bogoch, I. I., Sayasone, S., Vonghachack, Y., Meister, I., Utzinger, J., Odermatt, P., Andrews, J. R., Keiser, J. 2016; 94 (1): 158-160


    Opisthorchis viverrini infection is a neglected tropical disease, yet it is of considerable public health importance in southeast Asia given the predilection for chronically infected persons to develop cholangiocarcinoma. We evaluated a handheld microscope for the diagnosis of O. viverrini in a community-based setting in Lao People's Democratic Republic compared with conventional light microscopy. In stool samples collected from 104 individuals, handheld microscopy revealed a sensitivity of 70.6% and a specificity of 89.5% for O. viverrini infection. Pearson's correlation for quantitative fecal egg counts between the two devices was 0.98 (95% confidence interval: 0.98-0.99). With small adjustments to further increase diagnostic sensitivity, a handheld microscope may become a helpful tool to screen for O. viverrini and other helminth infections in public health settings.

    View details for DOI 10.4269/ajtmh.15-0525

    View details for PubMedID 26526923

  • Comparison of the Performance of the TPTest, Tubex, Typhidot and Widal Immunodiagnostic Assays and Blood Cultures in Detecting Patients with Typhoid Fever in Bangladesh, Including Using a Bayesian Latent Class Modeling Approach. PLoS neglected tropical diseases Islam, K., Sayeed, M. A., Hossen, E., Khanam, F., Charles, R. C., Andrews, J., Ryan, E. T., Qadri, F. 2016; 10 (4): e0004558


    There is an urgent need for an improved diagnostic assay for typhoid fever. In this current study, we compared the recently developed TPTest (Typhoid and Paratyphoid Test) with the Widal test, blood culture, and two commonly used commercially available kits, Tubex and Typhidot.For analysis, we categorized 92 Bangladeshi patients with suspected enteric fever into four groups: S. Typhi bacteremic patients (n = 28); patients with a fourfold change in Widal test from day 0 to convalescent period (n = 7); patients with Widal titer ?1:320 (n = 13) at either acute or convalescent stage of disease; and patients suspected with enteric fever, but with a negative blood culture and Widal titer (n = 44). We also tested healthy endemic zone controls (n = 20) and Bangladeshi patients with other febrile illnesses (n = 15). Sample size was based on convenience to facilitate preliminary analysis.Of 28 S. Typhi bacteremic patients, 28 (100%), 21 (75%) and 18 (64%) patients were positive by TPTest, Tubex and Typhidot, respectively. In healthy endemic zone controls, the TPTest method was negative in all, whereas Tubex and Typhidot were positive in 3 (15%) and 5 (25%), respectively. We then estimated sensitivity and specificity of all diagnostic tests using Bayesian latent class modeling. The sensitivity of TPTest, Tubex and Typhidot were estimated at 96.0% (95% CI: 87.1%-99.8%), 60.2% (95% CI: 49.3%-71.2%), and 59.6% (95% CI: 50.1%-69.3%), respectively. Specificity was estimated at 96.6% (90.7%-99.2%) for TPTest, 89.9% (79.6%-96.8%) for Tubex, and 80.0% (67.7%-89.7%) for Typhidot.These results suggest that the TPTest is highly sensitive and specific in diagnosing individuals with typhoid fever in a typhoid endemic setting, outperforming currently available and commonly used alternatives.

    View details for PubMedID 27058877

  • Impact of mass-screening on tuberculosis incidence in a prospective cohort of Brazilian prisoners. BMC infectious diseases Paião, D. S., Lemos, E. F., Carbone, A. d., Sgarbi, R. V., Junior, A. L., da Silva, F. M., Brandão, L. M., Dos Santos, L. S., Martins, V. S., Simionatto, S., Motta-Castro, A. R., Pompílio, M. A., Urrego, J., Ko, A. I., Andrews, J. R., Croda, J. 2016; 16 (1): 533


    Globally, prison inmates are a high-risk population for tuberculosis (TB), but the specific drivers of disease and impact of mass screening interventions are poorly understood.We performed a prospective cohort study to characterize the incidence and risk factors for tuberculosis infection and disease in 12 Brazilian prisons, and to investigate the effect of mass screening on subsequent disease risk. After recruiting a stratified random sample of inmates, we administered a questionnaire to ascertain symptoms and potential risk factors for tuberculosis; performed tuberculin skin testing (TST); collected sera for HIV testing; and obtained two sputum samples for smear microscopy and culture, from participants reporting a cough of any duration. We repeated the questionnaire and all tests for inmates who remained incarcerated after 1 year. TST conversion was defined as TST ?10 mm and an induration increase of at least 6 mm in an individual with a baseline TST <10 mm. Cox proportional hazard models were performed to identify risk factors associated with active TB. To evaluate the impact of screening on subsequent risk of disease, we compared TB notifications over one year among individuals randomized to screening for active TB with those not randomized to screening.Among 3,771 inmates recruited, 3,380 (89.6 %) were enrolled in the study, and 1,422 remained incarcerated after one year. Among 1,350 inmates (94.9 %) with paired TSTs at baseline and one-year follow-up, 25.7 % (272/1060) converted to positive. Among those incarcerated for the year, 10 (0.7 %) had TB at baseline and 25 (1.8 %) were diagnosed with TB over the subsequent year. Cases identified through active screening were less likely to be smear-positive than passively detected cases (10.0 % vs 50.9 %; p?

    View details for DOI 10.1186/s12879-016-1868-5

    View details for PubMedID 27716170

  • Efficacy and safety of praziquantel against light infections of Opisthorchis viverrini: a randomised parallel single blind dose-ranging trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Sayasone, S., Meister, I., Andrews, J. R., Odermatt, P., Vonghachack, Y., Xayavong, S., Senggnam, K., Phongluxa, K., Hattendorf, J., Bogoch, I. I., Keiser, J. 2016


    The liver fluke Opisthorchis viverrini, highly prevalent in Southeast Asia, is an important public health burden, including a risk factor for developing an aggressive bile duct cancer, cholangiocarcinoma, in chronically infected patients. Praziquantel, administered at single 40 mg/kg in preventive chemotherapy programs and 3 x 25 mg/kg for individual treatment is the drug of choice, yet information on the nature of the dose-response relationship is lacking.We performed a randomized, parallel, single blind dose-ranging Phase 2 trial in Lao PDR in O. viverrini-infected adults. Patients were randomly assigned to 30, 40, 50, 3 x 25 mg/kg praziquantel or placebo. Adverse events were recorded at baseline, 3 and 24 hours post-treatment. Cure rates and egg reduction rates were estimated 3 weeks after drug administration using available case analysis. Dose-response curves were predicted using Emax models.Two-hundred and seventeen O. viverrini-infected patients were assigned to the five treatment arms. The majority (94.3%) of patients harbored light infections. The Emax model predicted a high efficacy among the observed dose range. We observed cure rates ranging from 92.7-93.3% and egg reduction rates above 99.5% for all praziquantel-treatment groups. Adverse events were mild but higher in the standard treatment group (3x25 mg/kg) than in the single dose treatment arms.Single dose praziquantel appear to be as efficacious as the standard 3x25 mg/kg regimen for the treatment of O. viverrini infections, while presenting fewer adverse events. Further studies are necessary in moderate and heavy O. viverrini infections.

    View details for DOI 10.1093/cid/ciw785

    View details for PubMedID 27927864

  • The mass miniature chest radiography programme in Cape Town, South Africa, 1948 - 1994: The impact of active tuberculosis case finding. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde Hermans, S. M., Andrews, J. R., Bekker, L. G., Wood, R. 2016; 106 (12): 1263?69


    Tuberculosis (TB) control programmes rely mainly on passive detection of symptomatic individuals. The resurgence of TB has rekindled interest in active case finding. Cape Town (South Africa) had a mass miniature radiography (MMR) screening programme from 1948 to 1994.To evaluate screening coverage, yield and secular trends in TB notifications during the MMR programme.We performed an ecological analysis of the MMR programme and TB notification data from the City of Cape Town Medical Officer of Health reports for 1948 - 1994.Between 1948 and 1962, MMR screening increased to 12% of the population per annum with yields of 14 cases per 1 000 X-rays performed, accounting for >20% of total annual TB notifications. Concurrent with increasing coverage (1948 - 1965), TB case notification decreased in the most heavily TB-burdened non-European population from 844/100 000 population to 415/100 000. After 1966, coverage declined and TB notifications that initially remained stable (1967 - 1978) subsequently increased to 525/100 000. MMR yields remained low in the European population but declined rapidly in the non-European population after 1966, coincidental with forced removals from District 6. An inverse relationship between screening coverage and TB notification rates was observed in the non-European adult population. Similar secular trends occurred in infants and young children who were not part of the MMR screening programme.MMR of a high-burdened population may have significantly contributed to TB control and was temporally associated with decreased transmission to infants and children. These historical findings emphasise the importance of re-exploring targeted active case finding strategies as part of population TB control.

    View details for DOI 10.7196/SAMJ.2016.v106.i12.10744

    View details for PubMedID 27917775

  • Improving helminth treatment access: costs and opportunities. The Lancet. Infectious diseases Lo, N. C., Andrews, J. R., Bogoch, I. I. 2016; 16 (7): 762?64

    View details for PubMedID 27352742

  • Achieving high treatment success for multidrug-resistant TB in Africa: initiation and scale-up of MDR TB care in Ethiopia-an observational cohort study. Thorax Meressa, D., Hurtado, R. M., Andrews, J. R., Diro, E., Abato, K., Daniel, T., Prasad, P., Prasad, R., Fekade, B., Tedla, Y., Yusuf, H., Tadesse, M., Tefera, D., Ashenafi, A., Desta, G., Aderaye, G., Olson, K., Thim, S., Goldfeld, A. E. 2015; 70 (12): 1181-1188


    In Africa, fewer than half of patients receiving therapy for multidrug-resistant TB (MDR TB) are successfully treated, with poor outcomes reported for HIV-coinfected patients.A standardised second-line drug (SLD) regimen was used in a non-governmental organisation-Ministry of Health (NGO-MOH) collaborative community and hospital-based programme in Ethiopia that included intensive side effect monitoring, adherence strategies and nutritional supplementation. Clinical outcomes for patients with at least 24?months of follow-up were reviewed and predictors of treatment failure or death were evaluated by Cox proportional hazards models.From February 2009 to December 2014, 1044 patients were initiated on SLD. 612 patients with confirmed or presumed MDR TB had ?24?months of follow-up, 551 (90.0%) were confirmed and 61 (10.0%) were suspected MDR TB cases. 603 (98.5%) had prior TB treatment, 133 (21.7%) were HIV coinfected and median body mass index (BMI) was 16.6. Composite treatment success was 78.6% with 396 (64.7%) cured, 85 (13.9%) who completed treatment, 10 (1.6%) who failed, 85 (13.9%) who died and 36 (5.9%) who were lost to follow-up. HIV coinfection (adjusted HR (AHR): 2.60, p<0.001), BMI (AHR 0.88/kg/m(2), p=0.006) and cor pulmonale (AHR 3.61, p=0.003) and confirmed MDR TB (AHR 0.50, p=0.026) were predictive of treatment failure or death.We report from Ethiopia the highest MDR TB treatment success outcomes so far achieved in Africa, in a setting with severe resource constraints and patients with advanced disease. Intensive treatment of adverse effects, nutritional supplementation, adherence interventions and NGO-MOH collaboration were key strategies contributing to success. We argue these approaches should be routinely incorporated into programmes.

    View details for DOI 10.1136/thoraxjnl-2015-207374

    View details for PubMedID 26506854

  • The Impact of Ventilation and Early Diagnosis on Tuberculosis Transmission in Brazilian Prisons AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Urrego, J., Ko, A. I., Santos Carbone, A. d., Guimaraes Paiao, D. S., Enne Sgarbi, R. V., Yeckel, C. W., Andrews, J. R., Crodat, J. 2015; 93 (4): 739-746


    Prisoners have among the highest incidence of tuberculosis (TB) globally. However, the contribution of the prison environment on transmission is not well understood and structural characteristics have received little attention as effective epidemiological interventions in TB control. We evaluated architectural characteristics and estimated ventilation rates in 141 cells in three prisons in central west Brazil using steady-state exhaled carbon dioxide (CO2) levels. We used a modified Wells-Riley equation to estimate the probability of infection for inmates sharing a cell with an infectious case and projected the impact of interventions, including early diagnosis and improved ventilation. Overall, prison cells were densely populated (mean 2.1 m(2) per occupant) and poorly ventilated, with only three cells meeting World Health Organization (WHO) standards for per-person ventilation (60 L/s) applied in infection control settings. In the absence of interventions, projected median risk of infection was 78.0% during a 6-month period. Decreasing time-to-diagnosis by 25% reduced transmission risk by 8.3%. Improving ventilation to WHO standards decreased transmission by 38.2%, whereas optimizing cross-ventilation reduced transmission by 64.4%. Prison environments promote high infection risk over short-time intervals. In this context, enhanced diagnostics have a limited impact on reducing transmission. Improving natural ventilation may be required to effectively control TB in prisons.

    View details for DOI 10.4269/ajtmh.15-0166

    View details for Web of Science ID 000362311800014

    View details for PubMedID 26195459

  • Changes to Initial Postexposure Prophylaxis Regimens Between the Emergency Department and Clinic. Journal of acquired immune deficiency syndromes (1999) Bogoch, I. I., Siemieniuk, R. A., Andrews, J. R., Scully, E. P., Mayer, K. H., Bell, C. M., Zachary, K. C., Yawetz, S. 2015; 69 (5): e182-4

    View details for DOI 10.1097/QAI.0000000000000680

    View details for PubMedID 25967272

  • Is a Cholera Outbreak Preventable in Post-earthquake Nepal? PLoS neglected tropical diseases Nelson, E. J., Andrews, J. R., Maples, S., Barry, M., Clemens, J. D. 2015; 9 (8)

    View details for DOI 10.1371/journal.pntd.0003961

    View details for PubMedID 26270343

  • Diagnostics for invasive Salmonella infections: Current challenges and future directions. Vaccine Andrews, J. R., Ryan, E. T. 2015; 33: C8-15


    Invasive Salmonellosis caused by Salmonella enterica serotype Typhi or Paratyphi A, B, C, or invasive non-typhoidal Salmonella serotypes, is an immensely important disease cluster for which reliable, rapid diagnostic tests are not available. Blood culture remains the gold standard but is insensitive, slow, and resource-intensive. Existing molecular diagnostics have poor sensitivity due to the low organism burden in bodily fluids. Commercially available serologic tests for typhoidal Salmonella have had limited sensitivity and specificity. In high burden, resource-limited settings, reliance on clinical diagnosis or inaccurate tests often results in frequent, unnecessary treatment, which contributes selective pressure for the emergence of antimicrobial resistance. This practice also results in inadequate therapy for other etiologies of acute febrile illnesses, including leptospirosis and rickettsial infections. A number of novel serologic, molecular, transcriptomic and metabolomic approaches to diagnostics are under development. Target product profiles that outline specific needs may focus development and investment, and establish benchmarks for accuracy, cost, speed, and portability of new diagnostics. Of note, a critical barrier to diagnostic assay rollout will be the low cost and low perceived harm of empiric therapy on behalf of providers and patients, which leaves few perceived incentives to utilize diagnostics. Approaches that align incentives with societal goals of limiting inappropriate antimicrobial use, such as subsidizing diagnostics, may be essential for stimulating development and uptake of such assays in resource-limited settings. New diagnostics for invasive Salmonellosis should be developed and deployed alongside diagnostics for alternative etiologies of acute febrile illnesses to improve targeted use of antibiotics.

    View details for DOI 10.1016/j.vaccine.2015.02.030

    View details for PubMedID 25937611

  • Towards sustainable public health surveillance for enteric fever. Vaccine Luby, S. P., Saha, S., Andrews, J. R. 2015; 33: C3-7


    Enteric fever that results from infection by the typhoidal Salmonellas (Salmonella Typhi and Salmonella Paratyphi A, B and C) is a life-threatening preventable illness. Surveillance of enteric fever is important to understand current burden of disease, to track changes in human health burden from increasing antimicrobial resistance and to assess the impact of efforts to reduce disease burden. Since enteric fever occurs predominantly in low income communities, expensive surveillance is not sustainable. Traditional hospital-based surveillance does not estimate population burden and intensive community-based cohort studies do not capture the severe disease that is crucial to policy decisions. While cohort studies have been considered the gold standard for incidence estimates, the resources required to conduct them are great; as a consequence, estimates of enteric fever burden have been highly geographically and temporally restricted. A hybrid approach combining laboratory diagnosis that is already being conducted in healthcare centers with community-based surveillance of health care facility use offers a low-cost, sustainable approach to generate policy relevant data.

    View details for DOI 10.1016/j.vaccine.2015.02.054

    View details for PubMedID 25912287

  • Diagnosis of Schistosoma haematobium Infection with a Mobile Phone-Mounted Foldscope and a Reversed-Lens CellScope in Ghana AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Ephraim, R. K., Duah, E., Cybulski, J. S., Prakash, M., D'Ambrosio, M. V., Fletcher, D. A., Keiser, J., Andrews, J. R., Bogoch, I. I. 2015; 92 (6): 1253-1256


    We evaluated two novel, portable microscopes and locally acquired, single-ply, paper towels as filter paper for the diagnosis of Schistosoma haematobium infection. The mobile phone-mounted Foldscope and reversed-lens CellScope had sensitivities of 55.9% and 67.6%, and specificities of 93.3% and 100.0%, respectively, compared with conventional light microscopy for diagnosing S. haematobium infection. With conventional light microscopy, urine filtration using single-ply paper towels as filter paper showed a sensitivity of 67.6% and specificity of 80.0% compared with centrifugation for the diagnosis of S. haematobium infection. With future improvements to diagnostic sensitivity, newer generation handheld and mobile phone microscopes may be valuable tools for global health applications.

    View details for DOI 10.4269/ajtmh.14-0741

    View details for Web of Science ID 000355785400028

    View details for PubMedID 25918211

  • The epidemiological advantage of preferential targeting of tuberculosis control at the poor INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE Andrews, J. R., Basu, S., Dowdy, D. W., Murray, M. B. 2015; 19 (4): 375-380


    Tuberculosis (TB) remains disproportionately concentrated among the poor, yet known determinants of TB reactivation may fail to explain observed disparities in disease rates according to wealth. Reviewing data on TB disparities in India and the wealth distribution of known TB risk factors, we describe how social mixing patterns could be contributing to TB disparities. Wealth-assortative mixing, whereby individuals are more likely to be in contact with others from similar socio-economic backgrounds, amplifies smaller differences in risk of TB, resulting in large population-level disparities. As disparities and assortativeness increase, TB becomes more difficult to control, an effect that is obscured by looking at population averages of epidemiological parameters, such as case detection rates. We illustrate how TB control efforts may benefit from preferential targeting toward the poor. In India, an equivalent-scale intervention could have a substantially greater impact if targeted at those living below the poverty line than with a population-wide strategy. In addition to potential efficiencies in targeting higher-risk populations, TB control efforts would lead to a greater reduction in secondary TB cases per primary case diagnosed if they were preferentially targeted at the poor. We highlight the need to collect programmatic data on TB disparities and explicitly incorporate equity considerations into TB control plans.

    View details for DOI 10.5588/ijtld.14.0423

    View details for Web of Science ID 000351967800004

    View details for PubMedID 25859990

  • The Dynamics of QuantiFERON-TB Gold In-Tube Conversion and Reversion in a Cohort of South African Adolescents. American journal of respiratory and critical care medicine Andrews, J. R., Hatherill, M., Mahomed, H., Hanekom, W. A., Campo, M., Hawn, T. R., Wood, R., Scriba, T. J. 2015; 191 (5): 584-591


    Rationale: Interferon-gamma release assays are used to diagnose tuberculosis infection. In developed countries, high rates of reversion following conversion have been described. Objectives: Assess QuantiFERON® TB Gold In-tube (QFT) conversion and reversion dynamics in a tuberculosis-endemic setting. Methods. Adolescents aged 12-18 residing near Cape Town were recruited. Tuberculin skin testing (TST) and QFT were performed at baseline and after 2 years of follow-up; half also had TST and QFT performed at additional time points. Participants were observed for incident tuberculosis disease for up to five years. Measurements and Main Results. Among 5,357 participants, 2,751 (51.4%) and 2,987 (55.8%) were positive by QFT and TST at baseline. Annualized QFT and TST conversion risks were 14.0% and 13.0%, respectively; reversion risks were 5.1% and 4.1%. Concordance was excellent for conversions (? = 0.74), but poor for reversions (? = 0.12). Among recent QFT converters, magnitude of QFT value was strongly inversely associated with risk of reversion (p<0.0001). When longitudinal QFT data were analyzed in a cross-sectional manner, the annual risk of infection was 7.3%, whereas inclusion of reversions in the analysis showed that the actual risk of infection was 14.0%. Incident tuberculosis was 8-fold higher among QFT reverters, compared with persons with all negative QFT results (1.47 vs. 0.18 cases/100 person-years, p=0.011). Conclusions. In this tuberculosis-endemic setting, annual risk of infection was extremely high, while QFT and TST conversion concordance were higher and QFT reversion rates were lower than reported from low-burden settings.

    View details for DOI 10.1164/rccm.201409-1704OC

    View details for PubMedID 25562578

  • Prisons as Reservoir for Community Transmission of Tuberculosis, Brazil EMERGING INFECTIOUS DISEASES Sacchi, F. P., Praca, R. M., Tatara, M. B., Simonsen, V., Ferrazoli, L., Croda, M. G., Suffys, P. N., Ko, A. I., Andrews, J. R., Croda, J. 2015; 21 (3): 452-455


    We conducted a population-based study of tuberculosis (TB) cases in Dourados, Brazil, to assess the relationship between incarceration and TB in the general population. Incarceration was associated with TB in an urban population; 54% of Mycobacterium tuberculosis strains were related to strains from persons in prisons. TB control in prisons is critical for reducing disease prevalence.

    View details for DOI 10.3201/eid2103.140896

    View details for Web of Science ID 000350269300009

    View details for PubMedID 25642998

  • Treating multidrug-resistant tuberculosis in community settings: a wise investment. international journal of tuberculosis and lung disease Andrews, J. R., Stout, J. E. 2015; 19 (2): 127-?

    View details for DOI 10.5588/ijtld.14.0761

    View details for PubMedID 25574906

  • Active and latent tuberculosis in Brazilian correctional facilities: a cross-sectional study. BMC infectious diseases Carbone, A. d., Paião, D. S., Sgarbi, R. V., Lemos, E. F., Cazanti, R. F., Ota, M. M., Junior, A. L., Bampi, J. V., Elias, V. P., Simionatto, S., Motta-Castro, A. R., Pompílio, M. A., de Oliveira, S. M., Ko, A. I., Andrews, J. R., Croda, J. 2015; 15: 24-?


    BackgroundTuberculosis (TB) rates among prisoners are more than 20 times that of the general population in Brazil, yet there are limited data available to facilitate the development of effective interventions in this high-transmission setting. We aimed to assess risk factors for TB infection and evaluate the yield of mass screening for active disease among inmates.MethodsWe administered a questionnaire and tuberculin skin test (TST) to a population-based sample of inmates from 12 prisons in Central-West Brazil and collected sera for HIV testing and two sputum samples for smear microscopy and culture from participants reporting a cough of any duration. Hierarchical Poisson regression models were used to evaluate factors associated with latent tuberculosis infection (LTBI).ResultsWe recruited 3,380 inmates, of which 2,861 (84.6%) were males from 8 prisons, and 519 (15.4%) were females from 4 prisons. Among the 1,020 (30%) subjects who reported a cough, we obtained sputum from 691 (68%) and identified 31 cases of active TB for a point prevalence of 917 (95% CI, 623¿1302) per 100,000 prisoners. Evaluation of the two sputum smear samples failed to identify 74% of the TB cases, and 29% of the cases reported less than 2 weeks of symptoms. Obtaining a second culture identified an additional 7 (24%) cases. The prevalences of LTBI were 22.5% and 11.7% for male and female prisoners, respectively and duration of incarceration (in years) was associated with LTBI in male and female in the multivariable model (1.04, 95% CI, 1.01-1.07 and 1.34, 95% CI, 1.06-1.70, respectively). The prevalence of LTBI is 8.6% among newly incarcerated inmates, among whom LTBI prevalence significantly increased by 5% with each year of incarceration.ConclusionsAlthough the overall LTBI prevalence among inmates in Central-West Brazil is low, tuberculosis incidence is high (>1,800/100,00), likely due to the high force of infection among a largely susceptible inmate population. Efforts to reduce transmission in prisons may require mass screening for active TB, utilizing sputum culture in case-detection protocols.

    View details for DOI 10.1186/s12879-015-0764-8

    View details for PubMedID 25608746

  • A Cross-Sectional Survey of HIV Testing and Prevalence in Twelve Brazilian Correctional Facilities. PloS one Sgarbi, R. V., Carbone, A. d., Paião, D. S., Lemos, E. F., Simionatto, S., Puga, M. A., Motta-Castro, A. R., Pompilio, M. A., Urrego, J., Ko, A. I., Andrews, J. R., Croda, J. 2015; 10 (10): e0139487


    Prior studies have reported higher HIV prevalence among prisoners than the general population in Brazil, but data have been derived from single prisons. The aim of this study was to evaluate HIV testing practices, prevalence and linkage to care among inmates in a network of 12 prisons.We administered a questionnaire to a population-based sample of inmates from 12 prisons in Central-West Brazil and collected sera for HIV and syphilis testing from January to December 2013. We evaluated factors associated with HIV testing and infection using multivariable logistic regression models. Six months after HIV testing, we assessed whether each HIV-infected prisoner was engaged in clinical care and whether they had started antiretroviral therapy.We recruited 3,362 inmates, of whom 2,843 (85%) were men from 8 prisons, and 519 (15%) were women from 4 prisons. Forty-five percent of participants reported never having been tested for HIV previously. In multivariable analysis, the variables associated with previous HIV testing were lack of a stable partner (adjusted odds ratio [AOR]: 1.38; 95% CI: 1.18-1.60), completed more than four years of schooling (AOR 1.40; 95% CI: 1.20-1.64), history of previous incarceration (AOR: 1.68; 95% CI: 1.43-1.98), history of mental illness (AOR 1.52; 95% CI: 1.31-1.78) and previous surgery (AOR 1.31; 95% CI: 1.12-1.52). Fifty-four (1.6%) of all participants tested positive for HIV; this included 44 (1.54%) men and 10 (1.92%) women. Among male inmates, HIV infection was associated with homosexuality (AOR 6.20, 95% CI: 1.73-22.22), self-report of mental illness (AOR 2.18, 95% CI: 1.13-4.18), history of sexually transmitted infections (AOR 3.28, 95% CI: 1.64-6.56), and syphilis sero-positivity (AOR 2.54, 95% CI: 1.20-5.39). Among HIV-infected individuals, 34 (63%) were unaware of their HIV status; only 23 of these 34 (68%) newly diagnosed participants could be reached at six month follow-up, and 21 of 23 (91%) were engaged in HIV care.HIV testing rates among prison inmates are low, and the majority of HIV-infected inmates were unaware of their HIV diagnosis. Incarceration can be an opportunity for diagnosis and treatment of HIV among vulnerable populations who have poor access to health services, but further work is needed on transitional HIV care for released inmates.

    View details for PubMedID 26466312

  • Quantitative evaluation of a handheld light microscope for field diagnosis of soil-transmitted helminth infection. The American journal of tropical medicine and hygiene Bogoch, I. I., Andrews, J. R., Speich, B., Ame, S. M., Ali, S. M., Stothard, J. R., Utzinger, J., Keiser, J. 2014; 91 (6): 1138-1141


    We evaluated the Newton Nm1, a commercially available handheld light microscope and compared it with conventional light microscopy for the diagnosis of soil-transmitted helminth infections. A total of 91 Kato-Katz thick smears were examined by experienced microscopists and helminth eggs were counted and expressed as eggs per gram of stool (EPG). Mean egg counts were significantly higher with the conventional light microscope (5,190.0 EPG versus 2,385.8 EPG for Ascaris lumbricoides; 826.3 versus 455.7 for Trichuris trichiura; both P < 0.05). Using regression coefficients and accounting for intensity of infection, we found that the agreement between the two devices was excellent for both species (? = 0.90, 95% confidence interval = 0.82-0.99 for A. lumbricoides and ? = 0.96, 95% CI = 0.91-1.00 for T. trichiura). The Newton Nm1 microscope may be a useful tool for the detection and quantification of soil-transmitted helminth infection in clinical, epidemiologic, and public health settings.

    View details for DOI 10.4269/ajtmh.14-0253

    View details for PubMedID 25246697

  • Evaluation of portable microscopic devices for the diagnosis of Schistosoma and soil-transmitted helminth infection PARASITOLOGY Bogoch, I. I., Coulibaly, J. T., Andrews, J. R., Speich, B., Keiser, J., Stothard, J. R., N'Goran, E. K., Utzinger, J. 2014; 141 (14): 1811-1818


    SUMMARY The diagnosis of parasitic worm (helminth) infections requires specialized laboratory settings, but most affected individuals reside in locations without access to such facilities. We tested two portable microscopic devices for the diagnosis of helminth infections in a cross-sectional survey in rural Côte d'Ivoire. We examined 164 stool samples under a light microscope and then re-examined with a commercial portable light microscope and an experimental mobile phone microscope for the diagnosis of Schistosoma mansoni and soil-transmitted helminths. Additionally, 180 filtered urine samples were examined by standard microscopy and compared with the portable light microscope for detection of Schistosoma haematobium eggs. Conventional microscopy was considered the diagnostic reference standard. For S. mansoni, S. haematobium and Trichuris trichiura, the portable light microscope showed sensitivities of 84·8%, 78·6% and 81·5%, respectively, and specificities of 85·7%, 91·0% and 93·0%, respectively. For S. mansoni and T. trichiura, we found sensitivities for the mobile phone microscope of 68·2% and 30·8%, respectively, and specificities of 64·3% and 71·0%, respectively. We conclude that the portable light microscope has sufficient diagnostic yield for Schistosoma and T. trichiura infections, while the mobile phone microscope has only modest sensitivity in its current experimental set-up. Development of portable diagnostic technologies that can be used at point-of-sample collection will enhance diagnostic coverage in clinical and epidemiological settings.

    View details for DOI 10.1017/S0031182014000432

    View details for Web of Science ID 000346740700005

    View details for PubMedID 24776232

  • Isoniazid preventive therapy in medium-incidence settings: the price is right. international journal of tuberculosis and lung disease Stout, J. E., Andrews, J. R. 2014; 18 (12): 1388-?

    View details for DOI 10.5588/ijtld.14.0760

    View details for PubMedID 25517800

  • Strengthening Nepal's Female Community Health Volunteer network: a qualitative study of experiences at two years BMC HEALTH SERVICES RESEARCH Schwarz, D., Sharma, R., Bashyal, C., Schwarz, R., Baruwal, A., Karelas, G., Basnet, B., Khadka, N., Brady, J., Silver, Z., Mukherjee, J., Andrews, J., Maru, D. S. 2014; 14


    Nepal's Female Community Health Volunteer (FCHV) program has been described as an exemplary public-sector community health worker program. However, despite its merits, the program still struggles to provide high-quality, accessible services nation-wide. Both in Nepal and globally, best practices for community health worker program implementation are not yet known: there is a dearth of empiric research, and the research that has been done has shown inconsistent results.Here we evaluate a pilot program designed to strengthen the Nepali government's FCHV network. The program was structured with five core components: 1) improve local FCHV leadership; 2) facilitate structured weekly FCHV meetings and 3) weekly FCHV trainings at the village level; 4) implement a monitoring and evaluation system for FCHV patient encounters; and 5) provide financial compensation for FCHV work. Following twenty-four months of program implementation, a retrospective programmatic evaluation was conducted, including qualitative analysis of focus group discussions and semi-structured interviews.Qualitative data analysis demonstrated that the program was well-received by program participants and community members, and suggests that the five core components of this program were valuable additions to the pre-existing FCHV network. Analysis also revealed key challenges to program implementation including geographic limitations, literacy limitations, and limitations of professional respect from healthcare workers to FCHVs. Descriptive statistics are presented for programmatic process metrics and costs throughout the first twenty four months of implementation.The five components of this pilot program were well-received as a mechanism for strengthening Nepal's FCHV program. To our knowledge, this is the first study to present such data, specifically informing programmatic design and management of the FCHV program. Despite limitations in its scope, this study offers tangible steps forward for further research and community health worker program improvement, both within Nepal and globally.

    View details for DOI 10.1186/1472-6963-14-473

    View details for Web of Science ID 000349638000001

    View details for PubMedID 25301105

  • Ultra-Low-Cost Urine Filtration for Schistosoma haematobium Diagnosis: A Proof-of-Concept Study. American journal of tropical medicine and hygiene Ephraim, R. K., Duah, E., Andrews, J. R., Bogoch, I. I. 2014; 91 (3): 544-546


    Simple, efficient, and cost-effective strategies are needed for urine sample preparation in the field diagnosis of infection with Schistosoma haematobium. In this proof-of-concept study, we evaluated inexpensive and widely available paper products (paper towels, school workbook paper, and newspaper) to gravity-filter urine containing 60 eggs/mL of Schistosoma haematobium. Eggs were reliably visualized by light microscopy by using single-ply paper towels as urine filters. This filtration method has broad applicability in clinical and public health settings in resource-constrained environments.

    View details for DOI 10.4269/ajtmh.14-0221

    View details for PubMedID 24980496

  • The Importance of Implementation Strategy in Scaling Up Xpert MTB/RIF for Diagnosis of Tuberculosis in the Indian Health-Care System: A Transmission Model PLOS MEDICINE Salje, H., Andrews, J. R., Deo, S., Satyanarayana, S., Sun, A. Y., Pai, M., Dowdy, D. W. 2014; 11 (7)


    India has announced a goal of universal access to quality tuberculosis (TB) diagnosis and treatment. A number of novel diagnostics could help meet this important goal. The rollout of one such diagnostic, Xpert MTB/RIF (Xpert) is being considered, but if Xpert is used mainly for people with HIV or high risk of multidrug-resistant TB (MDR-TB) in the public sector, population-level impact may be limited.We developed a model of TB transmission, care-seeking behavior, and diagnostic/treatment practices in India and explored the impact of six different rollout strategies. Providing Xpert to 40% of public-sector patients with HIV or prior TB treatment (similar to current national strategy) reduced TB incidence by 0.2% (95% uncertainty range [UR]: -1.4%, 1.7%) and MDR-TB incidence by 2.4% (95% UR: -5.2%, 9.1%) relative to existing practice but required 2,500 additional MDR-TB treatments and 60 four-module GeneXpert systems at maximum capacity. Further including 20% of unselected symptomatic individuals in the public sector required 700 systems and reduced incidence by 2.1% (95% UR: 0.5%, 3.9%); a similar approach involving qualified private providers (providers who have received at least some training in allopathic or non-allopathic medicine) reduced incidence by 6.0% (95% UR: 3.9%, 7.9%) with similar resource outlay, but only if high treatment success was assured. Engaging 20% of all private-sector providers (qualified and informal [providers with no formal medical training]) had the greatest impact (14.1% reduction, 95% UR: 10.6%, 16.9%), but required >2,200 systems and reliable treatment referral. Improving referrals from informal providers for smear-based diagnosis in the public sector (without Xpert rollout) had substantially greater impact (6.3% reduction) than Xpert scale-up within the public sector. These findings are subject to substantial uncertainty regarding private-sector treatment patterns, patient care-seeking behavior, symptoms, and infectiousness over time; these uncertainties should be addressed by future research.The impact of new diagnostics for TB control in India depends on implementation within the complex, fragmented health-care system. Transformative strategies will require private/informal-sector engagement, adequate referral systems, improved treatment quality, and substantial resources. Please see later in the article for the Editors' Summary.

    View details for DOI 10.1371/journal.pmed.1001674

    View details for Web of Science ID 000340617400007

    View details for PubMedID 25025235

  • A User-Friendly, Open-Source Tool to Project Impact and Cost of Diagnostic Tests for Tuberculosis ELIFE Dowdy, D. W., Andrews, J. R., Dodd, P. J., Gilman, R. H. 2014; 3


    Most existing models of infectious diseases, including tuberculosis (TB), do not allow end-users to customize results to local conditions. We created a dynamic transmission model to project TB incidence, TB mortality, multidrug-resistant (MDR) TB prevalence, and incremental costs over five years after scale-up of nine alternative diagnostic strategies including combinations of sputum smear microscopy, Xpert MTB/RIF, microcolony-based culture, and same-day diagnosis. We developed a corresponding web-based interface that allows users to specify local costs and epidemiology. Full model code - including the ability to change any input parameter - is also included. The impact of improved diagnostic testing was greater for mortality and MDR-TB prevalence than TB incidence, and was maximized in high-incidence, low-HIV settings. More costly interventions generally had greater impact. In settings with little capacity for up-front investment, same-day microscopy had greatest impact on TB incidence and became cost-saving within five years if feasible to deliver at $10/test. In settings where more initial investment was possible, population-level scale-up of either Xpert MTB/RIF or microcolony-based culture offered substantially greater benefits, often averting ten times more TB cases than narrowly-targeted diagnostic strategies at minimal incremental long-term cost. Where containing MDR-TB is the overriding concern, Xpert for smear-positives has reasonable impact on MDR-TB incidence, but at substantial price and little impact on overall TB incidence and mortality. This novel, user-friendly modeling framework improves decision-makers' ability to evaluate the impact of TB diagnostic strategies, accounting for local conditions.

    View details for DOI 10.7554/eLife.02565

    View details for Web of Science ID 000336837300004

    View details for PubMedID 24898755

  • Patient Attrition Between the Emergency Department and Clinic Among Individuals Presenting for HIV Nonoccupational Postexposure Prophylaxis CLINICAL INFECTIOUS DISEASES Bogoch, I. I., Scully, E. P., Zachary, K. C., Yawetz, S., Mayer, K. H., Bell, C. M., Andrews, J. R. 2014; 58 (11): 1618-1624


    Background.?Nonoccupational postexposure prophylaxis (nPEP) is recommended after a sexual or parenteral exposure to human immunodeficiency virus (HIV). Patients frequently seek care in an emergency department (ED) after an exposure and are usually referred to an HIV clinic for further management. There have been few data on determinants of attrition after presentation to EDs for nPEP. Methods.?From July 2010 to June 2011, we prospectively recorded all referrals to nPEP programs from 2 large EDs at 2 academic medical centers in Boston, Massachusetts. Data were recorded on patient demographics, nature of potential HIV exposures, referrals to and attendance at HIV clinics, and reported completion of 28 days of antiretroviral therapy (ART). Multivariable logistic regression was used to evaluate risk factors for (1) patient attrition between the ED and HIV clinic follow-up and (2) documented completion of ART. Results.?Of 180 individuals who were referred to clinic follow-up for nPEP care from the ED, 98 (54.4%) attended a first nPEP clinic visit and 43 (23.9%) had documented completion of a 28-day course of ART. Multivariable analysis revealed older age (adjusted odds ratio [aOR], 0.96; 95% confidence interval [CI], .93-.99) and self-payment (aOR, 0.32; 95% CI, .11-.97) were significant predictors for failing to attend an initial HIV clinic appointment. Women were less likely than men to complete a 28-day ART regimen (aOR, 0.34; 95% CI, .15-.79). Conclusions.?Commonly used nPEP delivery models may not be effective for all patients who present with nonoccupational exposures to HIV. Interventions are needed to improve rates of follow-up and completion of nPEP to reduce the risk of preventable HIV infections.

    View details for DOI 10.1093/cid/ciu118

    View details for Web of Science ID 000337031200020

    View details for PubMedID 24723288

  • Timing of Tuberculosis Transmission and the Impact of Household Contact Tracing An Agent-based Simulation Model AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Kasaie, P., Andrews, J. R., Kelton, W. D., Dowdy, D. W. 2014; 189 (7): 845-852


    Rationale: Household contact tracing has recently been endorsed for global tuberculosis (TB) control, but its potential population-level impact remains uncertain. Objectives: To project the maximum impact of household contact tracing for TB in a moderate-burden setting. Methods: We developed a stochastic, agent-based simulation model of a simplified TB epidemic, calibrated to a setting of moderate TB incidence. We used data from the literature to generate "community-driven" and "household-driven" scenarios in which 22% and 50% of TB transmission occurred within the household respectively. In each scenario, we simulated an intervention in which the household members are screened and treated for TB at the time of an index patient's active TB diagnosis. Measurements and Main Results: By the time of TB diagnosis, 75-95% of initial household infections had already occurred, but only 1.5-3.0% of contacts had sufficient time to progress to active TB. With 100% sensitive tracing of all contacts for five consecutive years, TB incidence declined by 10-15%: a mean year-over-year decline of 2%/year. Effects were sustained for many years after stopping the intervention. Providing preventive therapy with contact tracing nearly doubled this impact (17-27% decline in incidence). Impact was proportional to sensitivity and coverage; thus, if 50% of contacts were screened with a 50% sensitive test, TB incidence declined by only 0.5%/year. Conclusions: Household contact tracing is unlikely to transform TB epidemiology in isolation but has the potential - especially with provision of preventive therapy - to augment a comprehensive package of interventions that could substantially reduce the population-level burden of TB.

    View details for DOI 10.1164/rccm.201310-1846OC

    View details for Web of Science ID 000333565600014

    View details for PubMedID 24559425

  • Quantification of shared air: a social and environmental determinant of airborne disease transmission. PloS one Wood, R., Morrow, C., Ginsberg, S., Piccoli, E., Kalil, D., Sassi, A., Walensky, R. P., Andrews, J. R. 2014; 9 (9)


    Tuberculosis is endemic in Cape Town, South Africa where a majority of the population become tuberculosis infected before adulthood. While social contact patterns impacting tuberculosis and other respiratory disease spread have been studied, the environmental determinants driving airborne transmission have not been quantified.Indoor carbon dioxide levels above outdoor levels reflect the balance of exhaled breath by room occupants and ventilation. We developed a portable monitor to continuously sample carbon dioxide levels, which were combined with social contact diary records to estimate daily rebreathed litres. A pilot study established the practicality of monitor use up to 48-hours. We then estimated the daily volumes of air rebreathed by adolescents living in a crowded township.One hundred eight daily records were obtained from 63 adolescents aged between 12- and 20-years. Forty-five lived in wooden shacks and 18 in brick-built homes with a median household of 4 members (range 2-9). Mean daily volume of rebreathed air was 120.6 (standard error: 8.0) litres/day, with location contributions from household (48%), school (44%), visited households (4%), transport (0.5%) and other locations (3.4%). Independent predictors of daily rebreathed volumes included household type (p?=?0.002), number of household occupants (p?=?0.021), number of sleeping space occupants (p?=?0.022) and winter season (p<0.001).We demonstrated the practical measurement of carbon dioxide levels to which individuals are exposed in a sequence of non-steady state indoor environments. A novel metric of rebreathed air volume reflects social and environmental factors associated with airborne infection and can identify locations with high transmission potential.

    View details for DOI 10.1371/journal.pone.0106622

    View details for PubMedID 25181526

  • Challenges in Evaluating the Cost-effectiveness of New Diagnostic Tests for HIV-Associated Tuberculosis CLINICAL INFECTIOUS DISEASES Andrews, J. R., Lawn, S. D., Dowdy, D. W., Walensky, R. P. 2013; 57 (7): 1021-1026


    With an emerging array of rapid diagnostic tests for tuberculosis, cost-effectiveness analyses are needed to inform scale-up in various populations and settings. Human immunodeficiency virus (HIV)-associated tuberculosis poses unique challenges in estimating and interpreting the cost-effectiveness of novel diagnostic tools. First, gains in sensitivity and specificity do not directly correlate with impact on clinical outcomes. Second, the cost-effectiveness of implementing tuberculosis diagnostics in HIV-infected populations is heavily influenced by downstream costs of HIV care. As a result, tuberculosis diagnostics may appear less cost-effective in this population than among HIV-uninfected individuals, raising important ethical and policy questions about the design and interpretation of cost-effectiveness analyses in this setting. Third, conventional cost-effectiveness benchmarks may be inadequate for making decisions about whether to adopt new diagnostics. If we are to appropriately deploy novel diagnostics for tuberculosis to people living with HIV in resource-constrained settings, these challenges in measuring cost-effectiveness must be more widely recognized and addressed.

    View details for DOI 10.1093/cid/cit412

    View details for Web of Science ID 000326027400015

    View details for PubMedID 23788239

  • Complexity in mathematical models of public health policies: a guide for consumers of models. PLoS medicine Basu, S., Andrews, J. 2013; 10 (10)


    Sanjay Basu and colleagues explain how models are increasingly used to inform public health policy yet readers may struggle to evaluate the quality of models. All models require simplifying assumptions, and there are tradeoffs between creating models that are more "realistic" versus those that are grounded in more solid data. Indeed, complex models are not necessarily more accurate or reliable simply because they can more easily fit real-world data than simpler models can. Please see later in the article for the Editors' Summary.

    View details for DOI 10.1371/journal.pmed.1001540

    View details for PubMedID 24204214

    View details for PubMedCentralID PMC3812083

  • Evaluation of an Electricity-free, Culture-based Approach for Detecting Typhoidal Salmonella Bacteremia during Enteric Fever in a High Burden, Resource-limited Setting PLOS NEGLECTED TROPICAL DISEASES Andrews, J. R., Prajapati, K. G., Eypper, E., Shrestha, P., Shakya, M., Pathak, K. R., Joshi, N., Tiwari, P., Risal, M., Koirala, S., Karkey, A., Dongol, S., Wen, S., Smith, A. B., Maru, D., Basnyat, B., Baker, S., Farrar, J., Ryan, E. T., Hohmann, E., Arjyal, A. 2013; 7 (6)


    In many rural areas at risk for enteric fever, there are few data on Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi) incidence, due to limited laboratory capacity for microbiologic culture. Here, we describe an approach that permits recovery of the causative agents of enteric fever in such settings. This approach involves the use of an electricity-free incubator based upon use of phase-change materials. We compared this against conventional blood culture for detection of typhoidal Salmonella.Three hundred and four patients with undifferentiated fever attending the outpatient and emergency departments of a public hospital in the Kathmandu Valley of Nepal were recruited. Conventional blood culture was compared against an electricity-free culture approach. Blood from 66 (21.7%) patients tested positive for a Gram-negative bacterium by at least one of the two methods. Sixty-five (21.4%) patients tested blood culture positive for S. Typhi (30; 9.9%) or S. Paratyphi A (35; 11.5%). From the 65 individuals with culture-confirmed enteric fever, 55 (84.6%) were identified by the conventional blood culture and 60 (92.3%) were identified by the experimental method. Median time-to-positivity was 2 days for both procedures. The experimental approach was falsely positive due to probable skin contaminants in 2 of 239 individuals (0.8%). The percentages of positive and negative agreement for diagnosis of enteric fever were 90.9% (95% CI: 80.0%-97.0%) and 96.0% (92.7%-98.1%), respectively. After initial incubation, Salmonella isolates could be readily recovered from blood culture bottles maintained at room temperature for six months.A simple culture approach based upon a phase-change incubator can be used to isolate agents of enteric fever. This approach could be used as a surveillance tool to assess incidence and drug resistance of the etiologic agents of enteric fever in settings without reliable local access to electricity or local diagnostic microbiology laboratories.

    View details for DOI 10.1371/journal.pntd.0002292

    View details for Web of Science ID 000321201300043

    View details for PubMedID 23853696

    View details for PubMedCentralID PMC3694822

  • Short Report: Mobile Phone Microscopy for the Diagnosis of Soil-Transmitted Helminth Infections: A Proof-of-Concept Study AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Bogoch, I. I., Andrews, J. R., Speich, B., Utzinger, J., Ame, S. M., Ali, S. M., Keiser, J. 2013; 88 (4): 626-629


    We created a mobile phone microscope and assessed its accuracy for the diagnosis of soil-transmitted helminths compared with conventional microscopy. Mobile phone microscopy has a sensitivity of 69.4% for detecting any helminth egg and sensitivities of 81.0%, 54.4%, and 14.3% for the diagnosis of Ascaris lumbricoides, Trichuris trichiura and hookworm respectively.

    View details for DOI 10.4269/ajtmh.12-0742

    View details for Web of Science ID 000317024700005

  • Modeling the Role of Public Transportation in Sustaining Tuberculosis Transmission in South Africa AMERICAN JOURNAL OF EPIDEMIOLOGY Andrews, J. R., Morrow, C., Wood, R. 2013; 177 (6): 556-561


    Current tuberculosis notification rates in South Africa are among the highest ever recorded. Although the human immunodeficiency virus epidemic has been a critical factor, the density of respiratory contacts in high-risk environments may be an important and underappreciated driver. Using a modified Wells-Riley model for airborne disease transmission, we estimated the risk of tuberculosis transmission on 3 modes of public transit (minibus taxis, buses, and trains) in Cape Town, South Africa, using exhaled carbon dioxide as a natural tracer gas to evaluate air exchange. Carbon dioxide measurements were performed between October and December of 2011. Environmental risk, reflected in the rebreathed fraction of air, was highest in minibus taxis and lowest in trains; however, the average number of passengers sharing an indoor space was highest in trains and lowest in minibus taxis. Among daily commuters, the annual risk of tuberculosis infection was projected to be 3.5%-5.0% and was highest among minibus taxi commuters. Assuming a duration of infectiousness of 1 year, the basic reproductive number attributable to transportation was more than 1 in all 3 modes of transportation. Given its poor ventilation and high respiratory contact rates, public transportation may play a critical role in sustaining tuberculosis transmission in South African cities.

    View details for DOI 10.1093/aje/kws331

    View details for Web of Science ID 000316374500009

    View details for PubMedID 23423215

  • Is Passive Diagnosis Enough? The Impact of Subclinical Disease on Diagnostic Strategies for Tuberculosis AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Dowdy, D. W., Basu, S., Andrews, J. R. 2013; 187 (5): 543-551


    Tuberculosis (TB) is characterized by a subclinical phase (symptoms absent or not considered abnormal); prediagnostic phase (symptoms noticed but diagnosis not pursued); and clinical phase (care actively sought). Diagnostic capacity during these phases is limited.To estimate the population-level impact of TB case-finding strategies in the presence of subclinical and prediagnostic disease.We created a mathematical epidemic model of TB, calibrated to global incidence. We then introduced three prototypical diagnostic interventions: increased sensitivity of diagnosis in the clinical phase by 20% ("passive"); early diagnosis during the prediagnostic phase at a rate of 10% per year ("enhanced"); and population-based diagnosis of 5% of undiagnosed prevalent cases per year ("active").If the subclinical phase was ignored, as in most models, the passive strategy was projected to reduce TB incidence by 18% (90% uncertainty range [UR], 11-32%) by year 10, compared with 23% (90% UR, 14-35%) for the enhanced strategy and 18% (90% UR, 11-28%) for the active strategy. After incorporating a subclinical phase into the model, consistent with population-based prevalence surveys, the active strategy still reduced 10-year TB incidence by 16% (90% UR, 11-28%), but the passive and enhanced strategies' impact was attenuated to 11% (90% UR, 8-25%) and 6% (90% UR, 4-13%), respectively. The degree of attenuation depended strongly on the transmission rate during the subclinical phase.Subclinical disease may limit the impact of current diagnostic strategies for TB. Active detection of undiagnosed prevalent cases may achieve greater population-level TB control than increasing passive case detection.

    View details for DOI 10.1164/rccm.201207-1217OC

    View details for Web of Science ID 000315977200014

    View details for PubMedID 23262515

  • Clinical predictors for the aetiology of peripheral lymphadenopathy in HIV-infected adults HIV MEDICINE Bogoch, I. I., Andrews, J. R., Nagami, E. H., Rivera, A. M., Gandhi, R. T., Stone, D. 2013; 14 (3): 182-186


    The aim of the study was to determine the aetiology and clinical predictors of peripheral lymphadenopathy in HIV-infected individuals during the antiretroviral (ARV) era in a nontuberculosis endemic setting.A multicentred, retrospective cohort study of peripheral lymph node biopsies in HIV-positive adults was carried out. A total of 107 charts were identified and reviewed for clinical features, lymphadenopathy size, and ARV use and duration. Biopsy results were categorized, and multivariate logistic regression determined independent predictors of lymphadenopathy aetiology.Evaluation of 107 peripheral lymph node biopsies revealed that 42.9% of peripheral lymphadenopathy was attributable to malignancy, 49.5% to reactive changes, and 7.5% to infections, with only 2.8% of all cases secondary to tuberculosis. Fevers, weight loss, ARV use, and lower viral loads are significantly associated with nonreactive lymphadenopathy.Lymphadenopathy is likely to be reactive or malignant in nontuberculosis endemic regions. Readily available clinical features can aid clinicians in predicting the underlying aetiology, those at risk for malignancy, and who to biopsy.

    View details for DOI 10.1111/j.1468-1293.2012.01035.x

    View details for Web of Science ID 000314469500008

    View details for PubMedID 22805116

  • Diagnosis of influenza from lower respiratory tract sampling after negative upper respiratory tract sampling VIRULENCE Bogoch, I. I., Andrews, J. R., Zachary, K. C., Hohmann, E. L. 2013; 4 (1): 82-84


    In this retrospective cohort study, we demonstrate that PCR-confirmed diagnoses of influenza were made solely by lower respiratory sampling in 6.9% of cases, as traditional upper respiratory tract tests were negative, indeterminate or not performed. Clinical features of these cases are presented. Clinicians should consider lower respiratory tract sampling in select cases of influenza-like illness for diagnosis.

    View details for DOI 10.4161/viru.22466

    View details for Web of Science ID 000313566000005

    View details for PubMedID 23135351

  • Crossing the quality chasm in resource-limited settings GLOBALIZATION AND HEALTH Maru, D. S., Andrews, J., Schwarz, D., Schwarz, R., Acharya, B., Ramaiya, A., Karelas, G., Rajbhandari, R., Mate, K., Shilpakar, S. 2012; 8


    Over the last decade, extensive scientific and policy innovations have begun to reduce the "quality chasm"--the gulf between best practices and actual implementation that exists in resource-rich medical settings. While limited data exist, this chasm is likely to be equally acute and deadly in resource-limited areas. While health systems have begun to be scaled up in impoverished areas, scale-up is just the foundation necessary to deliver effective healthcare to the poor. This perspective piece describes a vision for a global quality improvement movement in resource-limited areas. The following action items are a first step toward achieving this vision: 1) revise global health investment mechanisms to value quality; 2) enhance human resources for improving health systems quality; 3) scale up data capacity; 4) deepen community accountability and engagement initiatives; 5) implement evidence-based quality improvement programs; 6) develop an implementation science research agenda.

    View details for DOI 10.1186/1744-8603-8-41

    View details for Web of Science ID 000312600500001

    View details for PubMedID 23193968

  • Simple questionnaire and urine reagent strips compared to microscopy for the diagnosis of Schistosoma haematobium in a community in northern Ghana TROPICAL MEDICINE & INTERNATIONAL HEALTH Bogoch, I. I., Andrews, J. R., Dadzie Ephraim, R. K., Utzinger, J. 2012; 17 (10): 1217-1221


    To evaluate the utility of a simple questionnaire and urine reagent strip testing for the rapid diagnosis of Schistosoma haematobium in rural northern Ghana.Cross-sectional parasitological and questionnaire survey in a community in northern Ghana. Participants provided two urine specimens that were examined under a microscope using a centrifugation method. The first urine sample was additionally subjected to reagent strip testing. A short questionnaire was administered to all participants.Microscopy of urine samples obtained from 208 individuals aged 1-77 years revealed an S. haematobium prevalence of 6.8%. The presence of any blood or protein on a urine reagent strip was 100% and 42% sensitive, and 93% and 80% specific for S. haematobium diagnosis. Questionnaires were completed by 198 individuals. Self-reported haematuria showed a sensitivity of 53% and a specificity of 85%. A dichotomous two-question panel was helpful in S. haematobium diagnosis, with working and playing near the river significantly associated with S. haematobium infection (P?

    View details for DOI 10.1111/j.1365-3156.2012.03054.x

    View details for Web of Science ID 000308714200007

    View details for PubMedID 22863035

  • Projecting the Benefits of Antiretroviral Therapy for HIV Prevention: The Impact of Population Mobility and Linkage to Care JOURNAL OF INFECTIOUS DISEASES Andrews, J. R., Wood, R., Bekker, L., Middelkoop, K., Walensky, R. P. 2012; 206 (4): 543-551


    Recent mathematical models suggested that frequent human immunodeficiency virus (HIV) testing with immediate initiation of antiretroviral therapy (ART) to individuals with a positive test result could profoundly curb transmission. The debate about ART as prevention has focused largely on parameter values. We aimed to evaluate structural assumptions regarding linkage to care and population mobility, which have received less attention.We modified the linkage structure of published models of ART as prevention, such that individuals who decline initial testing or treatment do not link to care until late-stage HIV infection. We then added population mobility to the models. We populated the models with demographic, clinical, immigration, emigration, and linkage data from a South African township.In the refined linkage model, elimination of HIV transmission (defined as an incidence of <0.1%) did not occur by 30 years, even with optimistic assumptions about the linkage rate. Across a wide range of estimates, models were more sensitive to structural assumptions about linkage than to parameter values. Incorporating population mobility further attenuated the reduction in incidence conferred by ART as prevention.Linkage to care and population mobility are critical features of ART-as-prevention models. Clinical trials should incorporate relevant data on linkage to care and migration to evaluate the impact of this strategy.

    View details for DOI 10.1093/infdis/jis401

    View details for Web of Science ID 000306667000012

    View details for PubMedID 22711905

    View details for PubMedCentralID PMC3491737

  • Comparative Performance of Private and Public Healthcare Systems in Low- and Middle-Income Countries: A Systematic Review PLOS MEDICINE Basu, S., Andrews, J., Kishore, S., Panjabi, R., Stuckler, D. 2012; 9 (6)


    Private sector healthcare delivery in low- and middle-income countries is sometimes argued to be more efficient, accountable, and sustainable than public sector delivery. Conversely, the public sector is often regarded as providing more equitable and evidence-based care. We performed a systematic review of research studies investigating the performance of private and public sector delivery in low- and middle-income countries.Peer-reviewed studies including case studies, meta-analyses, reviews, and case-control analyses, as well as reports published by non-governmental organizations and international agencies, were systematically collected through large database searches, filtered through methodological inclusion criteria, and organized into six World Health Organization health system themes: accessibility and responsiveness; quality; outcomes; accountability, transparency, and regulation; fairness and equity; and efficiency. Of 1,178 potentially relevant unique citations, data were obtained from 102 articles describing studies conducted in low- and middle-income countries. Comparative cohort and cross-sectional studies suggested that providers in the private sector more frequently violated medical standards of practice and had poorer patient outcomes, but had greater reported timeliness and hospitality to patients. Reported efficiency tended to be lower in the private than in the public sector, resulting in part from perverse incentives for unnecessary testing and treatment. Public sector services experienced more limited availability of equipment, medications, and trained healthcare workers. When the definition of "private sector" included unlicensed and uncertified providers such as drug shop owners, most patients appeared to access care in the private sector; however, when unlicensed healthcare providers were excluded from the analysis, the majority of people accessed public sector care. "Competitive dynamics" for funding appeared between the two sectors, such that public funds and personnel were redirected to private sector development, followed by reductions in public sector service budgets and staff.Studies evaluated in this systematic review do not support the claim that the private sector is usually more efficient, accountable, or medically effective than the public sector; however, the public sector appears frequently to lack timeliness and hospitality towards patients.

    View details for DOI 10.1371/journal.pmed.1001244

    View details for Web of Science ID 000305946200015

    View details for PubMedID 22723748

  • The cost-effectiveness of routine tuberculosis screening with Xpert MTB/RIF prior to initiation of antiretroviral therapy: a model-based analysis AIDS Andrews, J. R., Lawn, S. D., Rusu, C., Wood, R., Noubary, F., Bender, M. A., Horsburgh, C. R., Losina, E., Freedberg, K. A., Walensky, R. P. 2012; 26 (8): 987-995


    In settings with high tuberculosis (TB) prevalence, 15-30% of HIV-infected individuals initiating antiretroviral therapy (ART) have undiagnosed TB. Such patients are usually screened by symptoms and sputum smear, which have poor sensitivity.To project the clinical and economic outcomes of using Xpert MTB/RIF(Xpert), a rapid TB/rifampicin-resistance diagnostic, to screen individuals initiating ART.We used a microsimulation model to evaluate the clinical impact and cost-effectiveness of alternative TB screening modalities - in all patients or only symptomatic patients - for hypothetical cohorts of individuals initiating ART in South Africa (mean CD4 cell count = 171 cells/?l; TB prevalence 22%). We simulated no active screening and four diagnostic strategies, smear microscopy (sensitivity 23%); smear and culture (sensitivity, 100%); one Xpert sample (sensitivity in smear-negative TB: 43%); two Xpert samples (sensitivity in smear-negative TB: 62%). Outcomes included projected life expectancy, lifetime costs (2010 US$), and incremental cost-effectiveness ratios (ICERs). Strategies with ICERs less than $7100 (South African gross domestic product per capita) were considered very cost-effective.Compared with no screening, life expectancy in TB-infected patients increased by 1.6 months using smear in symptomatic patients and by 6.6 months with two Xpert samples in all patients. At 22% TB prevalence, the ICER of smear for all patients was $2800 per year of life saved (YLS), and of Xpert (two samples) for all patients was $5100/YLS. Strategies involving one Xpert sample or symptom screening were less efficient.Model-based analysis suggests that screening all individuals initiating ART in South Africa with two Xpert samples is very cost-effective.

    View details for DOI 10.1097/QAD.0b013e3283522d47

    View details for Web of Science ID 000303656000010

    View details for PubMedID 22333751

  • On partnership. Narrative inquiry in bioethics Schwarz, R., Maru, D. S., Schwarz, D., Acharya, B., Acharya, B., Rajbhandari, R., Andrews, J., Karelas, G., Sharma, R., Arnoldy, M. 2012; 2 (2): 101-106

    View details for DOI 10.1353/nib.2012.0036

    View details for PubMedID 24406829

  • Social and News Media Enable Estimation of Epidemiological Patterns Early in the 2010 Haitian Cholera Outbreak AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Chunara, R., Andrews, J. R., Brownstein, J. S. 2012; 86 (1): 39-45


    During infectious disease outbreaks, data collected through health institutions and official reporting structures may not be available for weeks, hindering early epidemiologic assessment. By contrast, data from informal media are typically available in near real-time and could provide earlier estimates of epidemic dynamics. We assessed correlation of volume of cholera-related HealthMap news media reports, Twitter postings, and government cholera cases reported in the first 100 days of the 2010 Haitian cholera outbreak. Trends in volume of informal sources significantly correlated in time with official case data and was available up to 2 weeks earlier. Estimates of the reproductive number ranged from 1.54 to 6.89 (informal sources) and 1.27 to 3.72 (official sources) during the initial outbreak growth period, and 1.04 to 1.51 (informal) and 1.06 to 1.73 (official) when Hurricane Tomas afflicted Haiti. Informal data can be used complementarily with official data in an outbreak setting to get timely estimates of disease dynamics.

    View details for DOI 10.4269/ajtmh.2012.11-0597

    View details for Web of Science ID 000299065200013

    View details for PubMedID 22232449

  • Risk factors for mortality among MDR- and XDR-TB patients in a high HIV prevalence setting INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE Gandhi, N. R., Andrews, J. R., Brust, J. C., Montreuil, R., Weissman, D., Heo, M., Moll, A. P., Friedland, G. H., Shah, N. S. 2012; 16 (1): 90-97


    Recent studies suggest that the prevalence of drug-resistant tuberculosis (TB) in sub-Saharan Africa may be rising. This is of concern, as human immunodeficiency virus (HIV) co-infection in multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB has been associated with exceedingly high mortality rates.To identify risk factors associated with mortality in MDR- and XDR-TB patients co-infected with HIV in South Africa.Case-control study of patients who died of all causes within 2 years of diagnosis with MDR- or XDR-TB.Among 123 MDR-TB patients, 78 (63%) died following diagnosis. CD4 count ? 50 (HR 4.64, P = 0.01) and 51-200 cells/mm(3) (HR 4.17, P = 0.008) were the strongest independent risk factors for mortality. Among 139 XDR-TB patients, 111 (80%) died. CD4 count ? 50 cells/mm(3) (HR 4.46, P = 0.01) and resistance to all six drugs tested (HR 2.54, P = 0.04) were the principal risk factors. Use of antiretroviral therapy (ART) was protective (HR 0.34, P = 0.009).Mortality due to MDR- and XDR-TB was associated with greater degree of immunosuppression and drug resistance. Efforts to reduce mortality must focus on preventing the amplification of resistance by strengthening TB treatment programs, as well as reducing the pool of immunosuppressed HIV-infected patients through aggressive HIV testing and ART initiation.

    View details for DOI 10.5588/ijtld.11.0153

    View details for Web of Science ID 000298726700017

    View details for PubMedID 22236852

  • Implementing a systems-oriented morbidity and mortality conference in remote rural Nepal for quality improvement BMJ QUALITY & SAFETY Schwarz, D., Schwarz, R., Gauchan, B., Andrews, J., Sharma, R., Karelas, G., Rajbhandari, R., Acharya, B., Mate, K., Bista, A., Bista, M. G., Sox, C., Maru, D. S. 2011; 20 (12): 1082-1088


    In hospitals in rural, resource-limited settings, there is an acute need for simple, practical strategies to improve healthcare quality.A district hospital in remote western Nepal.To provide a mechanism for systems-level reflection so that staff can identify targets for quality improvement in healthcare delivery. Strategies for change To develop a morbidity and mortality conference (M&M) quality improvement initiative that aims to facilitate structured analysis of patient care and identify barriers to providing quality care, which can subsequently be improved.The authors designed an M&M involving clinical and non-clinical staff in conducting root-cause analyses of healthcare delivery at their hospital. Weekly conferences focus on seven domains of causal analysis: operations, supply chain, equipment, personnel, outreach, societal, and structural. Each conference focuses on assessing the care provided, and identifying ways in which services can be improved in the future.Staff reception of the M&Ms was positive. In these M&Ms, staff identified problem areas in healthcare delivery and steps for improvement. Subsequently, changes were made in hospital workflow, supply procurement, and on-site training.While widely practiced throughout the world, M&Ms typically do not involve both clinical and non-clinical staff members and do not take a systems-level approach. The authors' experience suggests that the adapted M&M conference is a simple, feasible tool for quality improvement in resource-limited settings. Senior managerial commitment is crucial to ensure successful implementation of M&Ms, given the challenging logistics of implementing these programmes in resource-limited health facilities.

    View details for DOI 10.1136/bmjqs-2011-000273

    View details for Web of Science ID 000297619300013

    View details for PubMedID 21949441

  • Pandemic H1N1 Influenza Infection in Adult Transplant Recipients TRANSPLANTATION Bogoch, I. I., Andrews, J. R., Hohmann, E. L., Kotton, C. N., Marty, F. M. 2011; 91 (12): E80-E81

    View details for DOI 10.1097/TP.0b013e31821c1eac

    View details for Web of Science ID 000291430500001

    View details for PubMedID 21654492

  • HIV-1 and 2009 H1N1 Influenza A in Adults JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES Bogoch, I. I., Andrews, J. R., Marty, F. M., Hohmann, E. L. 2011; 56 (4): E111-E113

    View details for DOI 10.1097/QAI.0b013e31820a9afb

    View details for Web of Science ID 000287740700003

    View details for PubMedID 21350357

  • Visceral Leishmaniasis in Far Western Nepal: Another Case and Concerns about a New Area of Endemicity AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Schwarz, D., Andrews, J., Gauchan, B. 2011; 84 (3): 508-508

    View details for DOI 10.4269/ajtmh.2011.11-0021

    View details for Web of Science ID 000287995600027

    View details for PubMedID 21363996

  • Tuberculosis and HIV Co-Infection Screening and Treatment Strategies DRUGS Venkatesh, K. K., Swaminathan, S., Andrews, J. R., Mayer, K. H. 2011; 71 (9): 1133-1152


    Globally, tuberculosis (TB) and HIV interact in deadly synergy. The high burden of TB among HIV-infected individuals underlies the importance of TB diagnosis, treatment and prevention for clinicians involved in HIV care. Despite expanding access to antiretroviral therapy (ART) to treat HIV infection in resource-limited settings, many individuals in need of therapy initiate ART too late and have already developed clinically significant TB by the time they present for care. Many co-infected individuals are in need of concurrent ART and anti-TB therapy, which dramatically improves survival, but also raises several management challenges, including drug interactions, shared drug toxicities and TB immune reconstitution inflammatory syndrome (IRIS). Due to the survival benefits of promptly initiating ART among all HIV-infected individuals, including those with TB, it is recommended that co-infected individuals receive treatment for both diseases, regardless of CD4+ cell count. We review current screening and treatment strategies for TB and HIV co-infection. Recent findings and ongoing studies will assist clinicians in managing the prevention and treatment of TB and HIV co-infection, which remains a major global health challenge.

    View details for Web of Science ID 000293101200003

    View details for PubMedID 21711060

  • Kaposi's Sarcoma-Associated Herpesvirus-Related Solid Lymphoma Involving the Heart and Brain. AIDS research and treatment Andrews, J. R., Cho-Park, Y. A., Ferry, J., Abramson, J. S., Robbins, G. K. 2011; 2011: 729854-?


    Since its discovery in 1994, Kaposi's sarcoma-associated herpesvirus (KSHV) has been associated with lymphoproliferative disorders, particularly in patients infected with human immunodeficiency virus (HIV). The disorders most strongly linked to KSHV are multicentric Castleman's Disease (MCD), primary effusion lymphoma, and diffuse large B-cell lymphomas. We report an unusual case of KSHV-associated lymphoma in an HIV-infected patient manifesting with myocardial and central nervous system involvement. We discuss this case in the context of increasing array of KSHV-associated lymphomas. In the HIV-infected patient with a mass lesion, a history of cutaneous Kaposi's sarcoma and prolonged immunosuppression should alert clinicians as to the possibility of KSHV-associated lymphoproliferative disorders, in order to establish a timely diagnosis.

    View details for DOI 10.1155/2011/729854

    View details for PubMedID 21541215

  • Predictors of Multidrug- and Extensively Drug-Resistant Tuberculosis in a High HIV Prevalence Community PLOS ONE Andrews, J. R., Shah, N. S., Weissman, D., Moll, A. P., Friedland, G., Gandhi, N. R. 2010; 5 (12)


    Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) have emerged in high-HIV-prevalence settings, which generally lack laboratory infrastructure for diagnosing TB drug resistance. Even where available, inherent delays with current drug-susceptibility testing (DST) methods result in clinical deterioration and ongoing transmission of MDR and XDR-TB. Identifying clinical predictors of drug resistance may aid in risk stratification for earlier treatment and infection control.We performed a retrospective case-control study of patients with MDR (cases), XDR (cases) and drug-susceptible (controls) TB in a high-HIV-prevalence setting in South Africa to identify clinical and demographic risk factors for drug-resistant TB. Controls were selected in a 1:1:1 ratio and were not matched. We calculated odds ratios (OR) and performed multivariate logistic regression to identify independent predictors.We enrolled 116, 123 and 139 patients with drug-susceptible, MDR, and XDR-TB. More than 85% in all three patient groups were HIV-infected. In multivariate analysis, MDR and XDR-TB were each strongly associated with history of TB treatment failure (adjusted OR 51.7 [CI 6.6-403.7] and 51.5 [CI 6.4-414.0], respectively) and hospitalization more than 14 days (aOR 3.8 [CI 1.1-13.3] and 6.1 [CI 1.8-21.0], respectively). Prior default from TB treatment was not a risk factor for MDR or XDR-TB. HIV was a risk factor for XDR (aOR 8.2, CI 1.3-52.6), but not MDR-TB. Comparing XDR with MDR-TB patients, the only significant risk factor for XDR-TB was HIV infection (aOR 5.3, CI 1.0-27.6).In this high-HIV-prevalence and drug-resistant TB setting, a history of prolonged hospitalization and previous TB treatment failure were strong risk factors for both MDR and XDR-TB. Given high mortality observed among patients with HIV and drug-resistant TB co-infection, previously treated and hospitalized patients should be considered for empiric second-line TB therapy while awaiting confirmatory DST results in settings with a high-burden of MDR/XDR-TB.

    View details for DOI 10.1371/journal.pone.0015735

    View details for Web of Science ID 000285793200047

    View details for PubMedID 21209951

  • Turning a blind eye: the mobilization of radiology services in resource-poor regions. Globalization and health Maru, D. S., Schwarz, R., Jason, A., Basu, S., Sharma, A., Moore, C. 2010; 6: 18-?


    While primary care, obstetrical, and surgical services have started to expand in the world's poorest regions, there is only sparse literature on the essential support systems that are required to make these operations function. Diagnostic imaging is critical to effective rural healthcare delivery, yet it has been severely neglected by the academic, public, and private sectors. Currently, a large portion of the world's population lacks access to any form of diagnostic imaging. In this paper we argue that two primary imaging modalities--diagnostic ultrasound and X-Ray--are ideal for rural healthcare services and should be scaled-up in a rapid and standardized manner. Such machines, if designed for resource-poor settings, should a) be robust in harsh environmental conditions, b) function reliably in environments with unstable electricity, c) minimize radiation dangers to staff and patients, d) be operable by non-specialist providers, and e) produce high-quality images required for accurate diagnosis. Few manufacturers are producing ultrasound and X-Ray machines that meet the specifications needed for rural healthcare delivery in resource-poor regions. A coordinated effort is required to create demand sufficient for manufacturers to produce the desired machines and to ensure that the programs operating them are safe, effective, and financially feasible.

    View details for DOI 10.1186/1744-8603-6-18

    View details for PubMedID 20946643

  • HIV Coinfection in Multidrug- and Extensively Drug-Resistant Tuberculosis Results in High Early Mortality AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Gandhi, N. R., Shah, N. S., Andrews, J. R., Vella, V., Moll, A. P., Scott, M., Weissman, D., Marra, C., Lalloo, U. G., Friedland, G. H. 2010; 181 (1): 80-86


    The multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) epidemics are rapidly expanding in South Africa. Our initial report of HIV-associated XDR TB in South Africa revealed rapid and near complete mortality. Lower mortality has been described in the literature, but few of these patients have been HIV coinfected.To characterize mortality from MDR and XDR TB in a setting with high HIV-coinfection rates.We conducted a retrospective observational study among 654 MDR and XDR TB cases diagnosed in Tugela Ferry, South Africa, from 2005 to 2007. Demographics and HIV status were abstracted from available medical records.Survival was determined from the date of sputum collection until October 2008 and correlated with year of diagnosis and drug-susceptibility test results. From 2005 to 2007, 272 MDR TB and 382 XDR TB cases were diagnosed; HIV-coinfection rates were 90 and 98%, respectively. One-year mortality was 71% for MDR and 83% for XDR TB patients; 40% of MDR TB and 51% of XDR TB cases died within 30 days of sputum collection. One-year mortality among both MDR and XDR TB patients improved from 2005 to 2007; however, the majority of deaths still occurred within the first 30 days. One-year and 30-day mortality rates were worse with greater degree of drug resistance (P < 0.001).Mortality from MDR and XDR TB in this high HIV-prevalence region is extraordinarily high, particularly within the first 30 days. Efforts to reduce mortality must focus on earlier diagnosis and early initiation of second-line TB and antiretroviral therapy.

    View details for DOI 10.1164/rccm.200907-0989OC

    View details for Web of Science ID 000273147100015

    View details for PubMedID 19833824

  • Global Health Delivery 2.0: Using Open-Access Technologies for Transparency and Operations Research PLOS MEDICINE Maru, D. S., Sharma, A., Andrews, J., Basu, S., Thapa, J., Oza, S., Bashyal, C., Acharya, B., Schwarz, R. 2009; 6 (12)

    View details for DOI 10.1371/journal.pmed.1000158

    View details for Web of Science ID 000273060600001

    View details for PubMedID 19956665

  • Averting epidemics of extensively drug-resistant tuberculosis PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Basu, S., Friedland, G. H., Medlock, J., Andrews, J. R., Shah, N. S., Gandhi, N. R., Moll, A., Moodley, P., Sturm, A. W., Galvani, A. P. 2009; 106 (18): 7672-7677


    Extensively drug-resistant tuberculosis (XDR TB) has been detected in most provinces of South Africa, particularly in the KwaZulu-Natal province where several hundred cases have been reported since 2004. We analyzed the transmission dynamics of XDR TB in the region using mathematical models, and observed that nosocomial transmission clusters of XDR TB may emerge into community-based epidemics under the public health conditions of many South African communities. The effective reproductive number of XDR TB in KwaZulu-Natal may be around 2. Intensified community-based case finding and therapy appears critical to curtailing transmission. In the setting of delayed disease presentation and high system demand, improved diagnostic approaches may need to be employed in community-based programs rather than exclusively at tertiary hospitals. Using branching process mathematics, we observed that early, community-based drug-susceptibility testing and effective XDR therapy could help curtail ongoing transmission and reduce the probability of XDR TB epidemics in neighboring territories.

    View details for DOI 10.1073/pnas.0812472106

    View details for Web of Science ID 000265783600073

    View details for PubMedID 19365076

  • Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis LANCET INFECTIOUS DISEASES Orenstein, E. W., Basu, S., Shah, N. S., Andrews, J. R., Friedland, G. H., Moll, A. P., Gandhi, N. R., Galvani, A. P. 2009; 9 (3): 153-161


    Multidrug-resistant (MDR) tuberculosis is a growing clinical and public-health concern. To evaluate existing evidence regarding treatment regimens for MDR tuberculosis, we used a Bayesian random-effects meta-analysis of the available therapeutic studies to assess how the reported proportion of patients treated successfully is influenced by differences in treatment regimen design, study methodology, and patient population. Successful treatment outcome was defined as cure or treatment completion. 34 clinical reports with a mean of 250 patients per report met the inclusion criteria. Our analysis shows that the proportion of patients treated successfully improved when treatment duration was at least 18 months, and if patients received directly observed therapy throughout treatment. Studies that combined both factors had significantly higher pooled success proportions (69%, 95% credible interval [CI] 64-73%) than other studies of treatment outcomes (58%, 95% CI 52-64%). Individualised treatment regimens had higher treatment success (64%, 95% CI 59-68%) than standardised regimens (54%, 95% CI 43-68%), although the difference was not significant. Treatment approaches and study methodologies were heterogeneous across studies. Many important variables, including patients' HIV status, were inconsistently reported between studies. These results underscore the importance of strong patient support and treatment follow-up systems to develop successful MDR tuberculosis treatment programmes.

    View details for Web of Science ID 000263787500014

    View details for PubMedID 19246019

  • Multidrug-resistant and extensively drug-resistant tuberculosis: Implications for the HIV epidemic and antiretroviral therapy rollout in South Africa JOURNAL OF INFECTIOUS DISEASES Andrews, J. R., Shah, N. S., Gandhi, N., Moll, T., Friedland, G. 2007; 196: S482-S490


    Drug-resistant tuberculosis (TB) is emerging as a major clinical and public health challenge in areas of sub-Saharan Africa where there is a high prevalence of human immunodeficiency virus (HIV) infection. TB drug-resistance surveillance in this region has been limited by laboratory capacity and the public health infrastructure; however, with the maturation of the HIV epidemic, the burden of drug-resistant TB is increasing rapidly. The recent discovery of large numbers of cases of multidrug-resistant (MDR) TB and extensively drug-resistant (XDR) TB in South Africa likely represents an unrecognized and evolving epidemic rather than sporadic, localized outbreaks. The combination of a large population of HIV-infected susceptible hosts with poor TB treatment success rates, a lack of airborne infection control, limited drug-resistance testing, and an overburdened MDR-TB treatment program provides ideal conditions for an MDR-TB and XDR-TB epidemic of unparalleled magnitude. In the present article, we review the history of drug-resistant TB in South Africa, describe its interaction with the HIV epidemic and the resultant consequences, and suggest measures necessary for controlling MDR-TB and XDR-TB in this context. A successful response to the emergence of MDR-TB and XDR-TB will necessitate increased resources for and collaboration between TB and HIV programs.

    View details for DOI 10.1086/521121

    View details for Web of Science ID 000251398100007

    View details for PubMedID 18181698

  • Prevention of nosocomial transmission of extensively drug-resistant tuberculosis in rural South African district hospitals: an epidemiological modelling study LANCET Basu, S., Andrews, J. R., Poolman, E. M., Gandhi, N. R., Shah, N. S., Moll, A., Moodley, P., Galvani, A. P., Friedland, G. H. 2007; 370 (9597): 1500-1507


    Extensively drug-resistant (XDR) tuberculosis has spread among hospitalised patients in South Africa, but the epidemic-level effect of hospital-based infection control strategies remains unknown. We modelled the plausible effect of rapidly available infection control strategies on the overall course of the XDR tuberculosis epidemic in a rural area of South Africa.We investigated the effect of administrative, environmental, and personal infection control measures on the epidemic trajectory of XDR tuberculosis in the rural community of Tugela Ferry. Assessments were done with a mathematical model incorporating over 2 years of longitudinal inpatient and community-based data. The model simulated inpatient airborne tuberculosis transmission, community tuberculosis transmission, and the effect of HIV and antiretroviral therapy.If no new interventions are introduced, about 1300 cases of XDR tuberculosis are predicted to occur in the area of Tugela Ferry by the end of 2012, more than half of which are likely to be nosocomially transmitted. Mask use alone would avert fewer than 10% of cases in the overall epidemic, but could prevent a large proportion of cases of XDR tuberculosis in hospital staff. The combination of mask use with reduced hospitalisation time and a shift to outpatient therapy could prevent nearly a third of XDR tuberculosis cases. Supplementing this approach with improved ventilation, rapid drug resistance testing, HIV treatment, and tuberculosis isolation facilities could avert 48% of XDR tuberculosis cases (range 34-50%) by the end of 2012. However, involuntary detention could result in an unexpected rise in incidence due to restricted isolation capacity.A synergistic combination of available nosocomial infection control strategies could prevent nearly half of XDR tuberculosis cases, even in a resource-limited setting. XDR tuberculosis transmission will probably continue in the community, indicating the need to develop and implement parallel community-based programmes.

    View details for Web of Science ID 000250487000027

    View details for PubMedID 17964351

  • XDR-TB in South Africa: Theory and practice PLOS MEDICINE Andrews, J., Basu, S., Scales, D., Maru, D. S., Subbaraman, R. 2007; 4 (4): 770-771

    View details for DOI 10.1371/journal.pmed.0040163

    View details for Web of Science ID 000245947000028

    View details for PubMedID 17455998

  • Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa LANCET Gandhi, N. R., Moll, A., Sturm, A. W., Pawinski, R., Govender, T., Lalloo, U., Zeller, K., Andrews, J., Friedland, G. 2006; 368 (9547): 1575-1580


    The epidemics of HIV-1 and tuberculosis in South Africa are closely related. High mortality rates in co-infected patients have improved with antiretroviral therapy, but drug-resistant tuberculosis has emerged as a major cause of death. We assessed the prevalence and consequences of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis in a rural area in KwaZulu Natal, South Africa.We undertook enhanced surveillance for drug-resistant tuberculosis with sputum culture and drug susceptibility testing in patients with known or suspected tuberculosis. Genotyping was done for isolates resistant to first-line and second-line drugs.From January, 2005, to March, 2006, sputum was obtained from 1539 patients. We detected MDR tuberculosis in 221 patients, of whom 53 had XDR tuberculosis. Prevalence among 475 patients with culture-confirmed tuberculosis was 39% (185 patients) for MDR and 6% (30) for XDR tuberculosis. Only 55% (26 of 47) of patients with XDR tuberculosis had never been previously treated for tuberculosis; 67% (28 of 42) had a recent hospital admission. All 44 patients with XDR tuberculosis who were tested for HIV were co-infected. 52 of 53 patients with XDR tuberculosis died, with median survival of 16 days from time of diagnosis (IQR 6-37) among the 42 patients with confirmed dates of death. Genotyping of isolates showed that 39 of 46 (85%, 95% CI 74-95) patients with XDR tuberculosis had similar strains.MDR tuberculosis is more prevalent than previously realised in this setting. XDR tuberculosis has been transmitted to HIV co-infected patients and is associated with high mortality. These observations warrant urgent intervention and threaten the success of treatment programmes for tuberculosis and HIV.

    View details for DOI 10.1016/S0140-6736(06)69573-1

    View details for Web of Science ID 000242180900026

    View details for PubMedID 17084757

  • Populations who test drugs should benefit from them NATURE Basu, S., Andrews, J., Smith-Rohrberg, D. 2006; 440 (7084): 605-605

    View details for DOI 10.1038/440605d

    View details for Web of Science ID 000236350400021

    View details for PubMedID 16572144

  • Research in the ranks - vulnerable subjects, coercible collaborotionl and the hepatitis E vaccine trial in Nepal PERSPECTIVES IN BIOLOGY AND MEDICINE Andrews, J. 2006; 49 (1): 35-51


    Concern over the diminished autonomy of members of the armed forces has resulted in the classification of these groups as "vulnerable" in many international codes of research ethics, a designation that places the onus on researchers to provide special justification for the inclusion of these persons in research. This paper examines the application of these ethical requirements to a recent trial carried out by U.S. Army researchers among soldiers of the Royal Nepal Army (RNA) and concludes that the requirements to justify conducting research in this population were not met. Furthermore, noting the human rights abuses rampant in the RNA, it is appropriate to question the choice of this institution as both a partner and a subject pool for U.S. state-sponsored research. This case study raises another important ethical question about the vulnerability to coerced collaboration of groups or institutions. In response, I propose the idea of "institutional vulnerability" as an extension of the idea of individual "juridic vulnerability." The recent military and financial assistance that the RNA received from the U.S. Army, in light of their partnership in this biomedical research trial, constitutes an appropriate and revealing context in which to ground this discussion.

    View details for Web of Science ID 000235107900004

    View details for PubMedID 16489275

  • US military sponsored vaccine trials and La resistance in Nepal AMERICAN JOURNAL OF BIOETHICS Andrews, J. 2005; 5 (3): W1-W3

    View details for DOI 10.1080/15265160591002962

    View details for Web of Science ID 000231019400028

    View details for PubMedID 16006352

  • How do international trade agreements influence the promotion of public health?--An introduction to the issue. Yale journal of health policy, law, and ethics Andrews, J., Chaifetz, S. 2004; 4 (2): 339-340

    View details for PubMedID 15536915

Footer Links:

Stanford Medicine Resources: