Bio

Bio


I am a postdoctoral research fellow focusing on infectious disease epidemiology, specifically tuberculosis, in the Division of Infectious Diseases and Geographic Medicine at Stanford University's School of Medicine under the mentorship of Dr. Jason Andrews.
My research focuses on
(i) deriving and validating meaningful and effective interventions to diagnose and prevent pediatric tuberculosis
(ii) furthering our understanding of tuberculosis transmission dynamics in high-burden settings, and
(iii) advocating for the implementation of effective health policy in low-income communities with a high tuberculosis burden

Honors & Awards


  • Rising Star Award, American Thoracic Society (2020)
  • Tuberculosis Research & Training Center TB Junior Investigator Award, University of Washington (2019)
  • Stephen Lawn TB-HIV Research Leadership Prize, TB Centre at LSHTM in London, UK, Desmond Tutu HIV Centre in Cape Town, South Africa, & The Union (2017)

Professional Education


  • BA, University of Arizona, Political Science, Spanish (2009)
  • MPH, Tulane University, School of Public Health and Tropical Medicine, Global Community Health and Behavioral Sciences (2012)
  • PhD, University of Georgia School of Public Health, Epidemiology (2017)

Publications

All Publications


  • The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis LANCET Martinez, L., Cords, O., Horsburgh, C., Andrews, J. R., Pediat TB Contact Studies 2020; 395 (10228): 973–84
  • 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

    Abstract

    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

  • Tuberculin skin test conversion and primary progressive tuberculosis disease in the first 5 years of life: a birth cohort study from Cape Town, South Africa The Lancet Child & Adolescent Health Martinez, L., le Roux, D. M., Barnett, W., Stadler, A., Nicol, M. P., Zar, H. J. 2018; 2 (1): 46-55.
  • Transmission of Mycobacterium Tuberculosis in Households and the Community: A Systematic Review and Meta-Analysis. American journal of epidemiology Martinez, L., Shen, Y., Mupere, E., Kizza, A., Hill, P. C., Whalen, C. C. 2017; 185 (12): 1327–39

    Abstract

    The individual- and population-level impact of household tuberculosis exposure on transmission is unclear but may have implications for the effectiveness and implementation of control interventions. We systematically searched for and included studies in which latent tuberculosis infection was assessed in 2 groups: children exposed and unexposed to a household member with tuberculosis. We also extracted data on the smear and culture status of index cases, the age and bacillus Calmette-Guérin vaccination status of contacts, and study design characteristics. Of 6,176 citations identified from our search strategy, 26 studies (13,999 children with household exposure to tuberculosis and 174,097 children without) from 1929-2015 met inclusion criteria. Exposed children were 3.79 (95% confidence interval (CI): 3.01, 4.78) times more likely to be infected than were their community counterparts. Metaregression demonstrated higher infection among children aged 0-4 years of age compared with children aged 10-14 years (ratio of odds ratios = 2.24, 95% CI: 1.43, 3.51) and among smear-positive versus smear-negative index cases (ratio of odds ratios = 5.45, 95% CI: 3.43, 8.64). At the population level, we estimated that a small proportion (<20%) of transmission was attributable to household exposure. Our results suggest that targeting tuberculosis prevention efforts to household contacts is highly effective. However, a large proportion of transmission at the population level may occur outside the household.

    View details for DOI 10.1093/aje/kwx025

    View details for PubMedID 28982226

  • Effectiveness of WHO's pragmatic screening algorithm for child contacts of tuberculosis cases in resource-constrained settings: a prospective cohort study in Uganda. The Lancet. Respiratory medicine Martinez, L., Shen, Y., Handel, A., Chakraburty, S., Stein, C. M., Malone, L. L., Boom, W. H., Quinn, F. D., Joloba, M. L., Whalen, C. C., Zalwango, S. 2017

    Abstract

    Tuberculosis is a leading cause of global childhood mortality; however, interventions to detect undiagnosed tuberculosis in children are underused. Child contact tracing has been widely recommended but poorly implemented in resource-constrained settings. WHO has proposed a pragmatic screening approach for managing child contacts. We assessed the effectiveness of this screening approach and alternative symptom-based algorithms in identifying secondary tuberculosis in a prospectively followed cohort of Ugandan child contacts.We identified index patients aged at least 18 years with microbiologically confirmed pulmonary tuberculosis at Old Mulago Hospital (Kampala, Uganda) between Oct 1, 1995, and Dec 31, 2008. Households of index patients were visited by fieldworkers within 2 weeks of diagnosis. Coprevalent and incident tuberculosis were assessed in household contacts through clinical, radiographical, and microbiological examinations for 2 years. Disease rates were compared among children younger than 16 years with and without symptoms included in the WHO pragmatic guideline (presence of haemoptysis, fever, chronic cough, weight loss, night sweats, and poor appetite). Symptoms could be of any duration, except cough (>21 days) and fever (>14 days). A modified WHO decision-tree designed to detect high-risk asymptomatic child contacts was also assessed, in which all asymptomatic contacts were classified as high risk (children younger than 3 years or immunocompromised [HIV-infected]) or low risk (aged 3 years or older and immunocompetent [HIV-negative]). We also assessed a more restrictive algorithm (ie, assessing only children with presence of chronic cough and one other tuberculosis-related symptom).Of 1718 household child contacts, 126 (7%) had coprevalent tuberculosis and 24 (1%) developed incident tuberculosis, diagnosed over the 2-year study period. Of these 150 cases of tuberculosis, 95 (63%) were microbiologically confirmed with a positive sputum culture. Using the WHO approach, 364 (21%) of 1718 child contacts had at least one tuberculosis-related symptom and 85 (23%) were identified as having coprevalent tuberculosis, 67% of all coprevalent cases detected (diagnostic odds ratio 9·8, 95% CI 6·8-14·5; p<0·0001). 1354 (79%) of 1718 child contacts had no symptoms, of whom 41 (3%) had coprevalent tuberculosis. The WHO approach was effective in contacts younger than 5 years: 70 (33%) of 211 symptomatic contacts had coprevalent disease compared with 23 (6%) of 367 asymptomatic contacts (p<0·0001). This approach was also effective in contacts aged 5 years and older: 15 (10%) of 153 symptomatic contacts had coprevalent disease compared with 18 (2%) of 987 asymptomatic contacts (p<0·0001). More coprevalent disease was detected in child contacts recommended for screening when the study population was restricted by HIV-serostatus (11 [48%] of 23 symptomatic HIV-seropositive child contacts vs two [7%] of 31 asymptomatic HIV-seropositive child contacts) or to only culture-confirmed cases (47 [13%] culture confirmed cases of 364 symptomatic child contacts vs 29 [2%] culture confirmed cases of 1354 asymptomatic child contacts). In the modified algorithm, high-risk asymptomatic child contacts were at increased risk for coprevalent disease versus low-risk asymptomatic contacts (14 [6%] of 224 vs 27 [2%] of 1130; p=0·0021). The presence of tuberculosis infection did not predict incident disease in either symptomatic or asymptomatic child contacts: in symptomatic contacts, eight (5%) of 169 infected contacts and six (5%) of 111 uninfected contacts developed incident tuberculosis (p=0·80). Among asymptomatic contacts, incident tuberculosis occurred in six (<1%) of 795 contacts infected at baseline versus four (<1%) of 518 contacts uninfected at baseline, respectively (p=1·00).WHO's pragmatic, symptom-based algorithm was an effective case-finding tool, especially in children younger than 5 years. A modified decision-tree identified 6% of asymptomatic child contacts at high risk for subclinical disease. Increasing the feasibility of child-contact tracing using these approaches should be encouraged to decrease tuberculosis-related paediatric mortality in high-burden settings, but this should be partnered with increasing access to microbiological point-of-care testing.National Institutes of Health, Tuberculosis Research Unit, AIDS International Training and Research Program of the Fogarty International Center, and the Center for AIDS Research.

    View details for DOI 10.1016/S2213-2600(17)30497-6

    View details for PubMedID 29273539

  • Infectiousness of HIV-Seropositive Patients with Tuberculosis in a High-Burden African Setting AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE Martinez, L., Sekandi, J. N., Castellanos, M. E., Zalwango, S., Whalen, C. C. 2016; 194 (9): 1152-1163

    Abstract

    Policy recommendations on contact investigation of HIV-seropositive patients with tuberculosis have changed several times. Current epidemiologic evidence informing these recommendations is considered low quality, and few large studies investigating the infectiousness of HIV-seropositive and -seronegative index cases have been performed in sub-Saharan Africa.We assessed the infectiousness of HIV-seropositive and -seronegative patients with tuberculosis to their household contacts and examined potential modifiers of this relationship.Adults suffering from their first episode of pulmonary tuberculosis were identified in Kampala, Uganda. Field workers visited index households and enrolled consenting household contacts. Latent tuberculosis infection was measured through tuberculin skin testing, and relative risks were calculated using modified Poisson regression models. Standard assessments of interaction between latent tuberculosis infection, the HIV serostatus of index cases, and other variables were performed.Latent tuberculosis infection was found in 577 of 878 (65.7%) and 717 of 974 (73.6%) household contacts of HIV-seropositive and -seronegative tuberculosis cases (relative risk, 0.89; 95% confidence interval, 0.82-0.97). On further stratification, cavitary lung disease (P < 0.0001 for interaction) and smear status (P = 0.02 for interaction) of tuberculosis cases modified the infectiousness of HIV-seropositive indexes. Cough duration of index cases did not display interaction (P = 0.499 for interaction).This study suggests that HIV-seropositive tuberculosis cases may be less infectious than HIV-seronegative patients only when they are smear-negative or lack cavitary lung disease. These results may explain heterogeneity between prior studies and provide evidence suggesting that tuberculosis contact investigation should include HIV-seropositive index cases in high disease burden settings.

    View details for DOI 10.1164/rccm.201511-2146OC

    View details for Web of Science ID 000386866600018

    View details for PubMedID 27181053

    View details for PubMedCentralID PMC5114446

  • Predictors of Discordant Tuberculin Skin test and QuantiFERON-TB Gold In-Tube Results in Eastern China: A Population-based, Cohort Study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Lu, P., Liu, Q., Zhou, Y., Martinez, L., Kong, W., Ding, X., Peng, H., Zhu, T., Zhu, L., Lu, W. 2020

    Abstract

    BACKGROUND: Discordance between QuantiFERON-TB (QFT) Gold In-Tube and tuberculin skin tests (TST) is not well understood. To identify factors that determine discordance between TST and QFT tests when compared to either TST+QFT+ or TST-QFT- results in a medium tuberculosis burden setting.METHODS: We conducted a population-based study in Eastern China and administered TST and QFT tests to participants. We calculated kappa values while constructing multivariable logistic regression models to evaluate predictors of test discordance. We analyzed the predictive value of discordant and concordant test results for progression to tuberculosis over 6 years of follow-up.RESULTS: Overall, 5,405 participants were enrolled; 2,043 (37.8%) and 1,104 (20.4%) were TST and QFT positive. There was fair agreement between the TST and the QFT (kappa values between 0.30-0.39 at different TST cutoffs). Agreement was lower among BCG-vaccinated participants (kappa, 0.17 versus 0.47). TST+QFT- results were associated with decreasing age, smoking, undiagnosed diabetes, and BCG vaccination (adjusted Odds Ratio, 1.45, 95%CI, 1.11-1.90). TST-QFT+ results were associated with increasing age, male sex, smoking, and diagnosed diabetes. Compared to participants with TST-QFT- results, QFT+ and TST+QFT+ participants were 6.3 (95%CI, 1.9-20.4) and 7.5 (95%CI, 2.3-25.1) times more likely to progress to tuberculosis.CONCLUSIONS: In this population-based study of over 5000 participants from a medium tuberculosis burden region, test agreement between QFT and TST was fair overall, and we found multiple novel predictors of discordant QFT/TST test results. QFT provides a substantial improvement to the TST among these populations and was multi-fold better predictive of progression to tuberculosis.

    View details for DOI 10.1093/cid/ciaa519

    View details for PubMedID 32369577

  • Community Outbreak Investigation of SARS-CoV-2 Transmission Among Bus Riders in Eastern China. JAMA internal medicine Shen, Y., Li, C., Dong, H., Wang, Z., Martinez, L., Sun, Z., Handel, A., Chen, Z., Chen, E., Ebell, M. H., Wang, F., Yi, B., Wang, H., Wang, X., Wang, A., Chen, B., Qi, Y., Liang, L., Li, Y., Ling, F., Chen, J., Xu, G. 2020

    Abstract

    Evidence of whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be transmitted as an aerosol (ie, airborne) has substantial public health implications.To investigate potential transmission routes of SARS-CoV-2 infection with epidemiologic evidence from a COVID-19 outbreak.This cohort study examined a community COVID-19 outbreak in Zhejiang province. On January 19, 2020, 128 individuals took 2 buses (60 [46.9%] from bus 1 and 68 [53.1%] from bus 2) on a 100-minute round trip to attend a 150-minute worship event. The source patient was a passenger on bus 2. We compared risks of SARS-CoV-2 infection among at-risk individuals taking bus 1 (n = 60) and bus 2 (n = 67 [source patient excluded]) and among all other individuals (n = 172) attending the worship event. We also divided seats on the exposed bus into high-risk and low-risk zones according to the distance from the source patient and compared COVID-19 risks in each zone. In both buses, central air conditioners were in indoor recirculation mode.SARS-CoV-2 infection was confirmed by reverse transcription polymerase chain reaction or by viral genome sequencing results. Attack rates for SARS-CoV-2 infection were calculated for different groups, and the spatial distribution of individuals who developed infection on bus 2 was obtained.Of the 128 participants, 15 (11.7%) were men, 113 (88.3%) were women, and the mean age was 58.6 years. On bus 2, 24 of the 68 individuals (35.3% [including the index patient]) received a diagnosis of COVID-19 after the event. Meanwhile, none of the 60 individuals in bus 1 were infected. Among the other 172 individuals at the worship event, 7 (4.1%) subsequently received a COVID-19 diagnosis. Individuals in bus 2 had a 34.3% (95% CI, 24.1%-46.3%) higher risk of getting COVID-19 compared with those in bus 1 and were 11.4 (95% CI, 5.1-25.4) times more likely to have COVID-19 compared with all other individuals attending the worship event. Within bus 2, individuals in high-risk zones had moderately, but nonsignificantly, higher risk for COVID-19 compared with those in the low-risk zones. The absence of a significantly increased risk in the part of the bus closer to the index case suggested that airborne spread of the virus may at least partially explain the markedly high attack rate observed.In this cohort study and case investigation of a community outbreak of COVID-19 in Zhejiang province, individuals who rode a bus to a worship event with a patient with COVID-19 had a higher risk of SARS-CoV-2 infection than individuals who rode another bus to the same event. Airborne spread of SARS-CoV-2 seems likely to have contributed to the high attack rate in the exposed bus. Future efforts at prevention and control must consider the potential for airborne spread of the virus.

    View details for DOI 10.1001/jamainternmed.2020.5225

    View details for PubMedID 32870239

  • 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

    Abstract

    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

  • Transmission Dynamics in Tuberculosis Patients with Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis of 32 Observational Studies. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Martinez, L., Woldu, H., Chen, C., Hallowell, B. D., Castellanos, M. E., Lu, P., Liu, Q., Whalen, C. C., Zhu, L. 2020

    Abstract

    There are large knowledge gaps on the transmission dynamics of Mycobacterium tuberculosis in settings where both tuberculosis and HIV are endemic. We aimed to assess the infectiousness of tuberculosis patients coinfected with HIV.We systematically searched for studies of contacts of both HIV-positive and negative tuberculosis index cases. Our primary outcome was Mycobacterium tuberculosis infection in contacts. Data on sputum smear and lung cavitation status of index cases was extracted from each study to assess effect modification. Secondary outcomes included prevalent tuberculosis and HIV in contacts of HIV-positive and negative index cases.Of 5,255 original citations identified, 32 studies met inclusion criteria including 25 studies investigating M. tuberculosis infection (Nparticipants=36,893), 13 on tuberculosis (Nparticipants=18,853), and 12 on HIV positivity (Nparticipants=18,424). Risk of M. tuberculosis infection was lower in contacts of HIV-positive index cases (Odds Ratio [OR], 0.67, 95% CI, 0.58-0.77) but was heterogeneous (I2=75.1%). Two factors modified this relationship: the lung cavitary status of the index case and immunosuppression (measured through CD4 counts or HIV or AIDS diagnoses) among index patients living with HIV. Rates of HIV were consistently higher in contacts of coinfected index cases (OR, 4.9, 95% CI, 3.0-8.0). This was modified by whether the study was in sub-Saharan Africa (OR, 2.8, 1.6-4.9) or in another global region (OR, 9.8, 5.9-16.3).Tuberculosis patients coinfected with HIV are less infectious than HIV-uninfected cases when they have severe immunosuppression or paucibacillary disease. Contacts of coinfected index cases are almost five times more likely to also have HIV.

    View details for DOI 10.1093/cid/ciaa1146

    View details for PubMedID 32770236

  • A Cluster of Novel Coronavirus Disease 2019 Infections Indicating Person-to-Person Transmission Among Casual Contacts From Social Gatherings: An Outbreak Case-Contact Investigation. Open forum infectious diseases Shen, Y., Xu, W., Li, C., Handel, A., Martinez, L., Ling, F., Ebell, M., Fu, X., Pan, J., Ren, J., Gu, W., Chen, E. 2020; 7 (6): ofaa231

    Abstract

    Severe acute respiratory syndrome coronavirus 2, the pathogen causing novel coronavirus disease of 2019 (COVID-19), efficiently spreads from person to person in close contact settings. Transmission among casual contacts in settings such as during social gatherings is not well understood.We report several transmission events to both close and casual contacts from a cluster of 7 COVID-19 cases occurring from mid-January to early February 2020. A total of 539 social and family contacts of the index patient's, including members of a 2-day wedding and a family party, were contacted and screened through epidemiologic surveys. The clinical progression of all cases is described.We estimate the secondary attack rate among close contacts to be 29% (2 of 7) and for the casual contacts to be 0.6% (3 of 473). The incubation period of our case cluster was 4-12 days (median, 7 days).Transmission efficiency among close contacts was higher than among casual contacts; however, transmission from second-generation cases may help spread the virus during the incubation period.

    View details for DOI 10.1093/ofid/ofaa231

    View details for PubMedID 32613025

    View details for PubMedCentralID PMC7313868

  • 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

  • It Ain't Over Till It's Over: The Triple Threat of COVID-19, TB, and HIV. The American journal of tropical medicine and hygiene Kay, A. W., Ness, T. E., Martinez, L., Mandalakas, A. M. 2020

    Abstract

    It Ain't Over Till It's Over: The Triple Threat of COVID-19, TB, and HIV.

    View details for DOI 10.4269/ajtmh.20-1089

    View details for PubMedID 32876009

  • 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

    Abstract

    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

  • Collateral Impact of the Covid-19 Pandemic on Tuberculosis Control in Jiangsu Province, China. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Liu, Q., Lu, P., Shen, Y., Li, C., Wang, J., Zhu, L., Lu, W., Martinez, L. 2020

    Abstract

    The Covid-19 pandemic may impede global tuberculosis elimination goals. In Jiangsu Province, China, tuberculosis notifications dropped 52% in 2020 compared to 2015-2019. Treatment completion and screening for drug resistance decreased continuously in 2020. Urgent attention must be paid to tuberculosis control efforts during and after the Covid-19 pandemic.

    View details for DOI 10.1093/cid/ciaa1289

    View details for PubMedID 32857838

  • Monitoring the COVID-19 pandemic in sub-Saharan Africa: focusing on health facility admissions and deaths. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Harries, A. D., Martinez, L., Chakaya, J. M. 2020; 24 (5): 550–52

    View details for DOI 10.5588/ijtld.20.0176

    View details for PubMedID 32398216

  • Evidence for supercoughers in an analysis of six tuberculosis cohorts from China, Peru, The Gambia and Uganda INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE Handel, A., Martinez, L., Sekandi, J. N., Bellan, S. E., Zhu, L., Chen, C., Liu, Q., Donkor, S., Sutherland, J., Hill, P. C., Gilman, R. H., Grandjean, L., Whalen, C. C. 2019; 23 (12): 1286–92

    Abstract

    BACKGROUND: It is very difficult to observe tuberculosis (TB) transmission chains and thus, identify superspreaders. We investigate cough duration as a proxy measure of transmission to assess the presence of potential TB superspreaders.DESIGN: We analyzed six studies from China, Peru, The Gambia and Uganda, and determined the distribution of cough duration and compared it with several theoretical distributions. To determine factors associated with cough duration, we used linear regression and boosted regression trees to examine the predictive power of patient, clinical and environmental characteristics.RESULTS: We found within-study heterogeneity in cough duration and strong similarities across studies. Approximately 20% of patients contributed 50% of total cough days, and around 50% of patients contributed 80% of total cough days. The cough duration distribution suggested an initially increasing, and subsequently, decreasing hazard of diagnosis. While some of the exposure variables showed statistically significant associations with cough duration, none of them had a strong effect. Multivariate analyses of different model types did not produce a model that had good predictive power.CONCLUSION: We found consistent evidence for the presence of supercoughers, but no characteristics predictive of such individuals.

    View details for DOI 10.5588/ijtld.18.0819

    View details for Web of Science ID 000502329600010

    View details for PubMedID 31931913

  • A Risk Classification Model to Predict Mortality Among Laboratory-Confirmed Avian Influenza A H7N9 Patients: A Population-Based Observational Cohort Study. The Journal of infectious diseases Martinez, L., Cheng, W., Wang, X., Ling, F., Mu, L., Li, C., Huo, X., Ebell, M. H., Huang, H., Zhu, L., Li, C., Chen, E., Handel, A., Shen, Y. 2019

    Abstract

    BACKGROUND: Avian influenza A H7N9 (A/H7N9) is characterized by rapid progressive pneumonia and respiratory failure. Mortality among laboratory-confirmed cases is above 30%; however, the clinical course of disease is variable and patients at high risk for death are not well characterized.METHODS: We obtained demographic, clinical, and laboratory information on all A/H7N9 patients in Zhejiang province from China Centers for Disease Control and Prevention electronic databases. Risk factors for death were identified using logistic regression and a risk score was created using regression coefficients from multivariable models. We externally validated this score in an independent cohort from Jiangsu province.RESULTS: Among 305 A/H7N9 patients, 115 (37.7%) died. Four independent predictors of death were identified: older age, diabetes, bilateral lung infection, and neutrophil percentage. We constructed a score with 0-13 points. Mortality rates in low- (0-3), medium- (4-6), and high-risk (7-13) groups were 4.6%, 32.1%, and 62.7% (Ptrend < .0001). In a validation cohort of 111 A/H7N9 patients, 61 (55%) died. Mortality rates in low-, medium-, and high-risk groups were 35.5%, 55.8, and 67.4% (Ptrend = .0063).CONCLUSIONS: We developed and validated a simple-to-use, predictive risk score for clinical use, identifying patients at high mortality risk.

    View details for DOI 10.1093/infdis/jiz328

    View details for PubMedID 31622983

  • Towards a more holistic understanding of paediatric tuberculosis LANCET CHILD & ADOLESCENT HEALTH Martinez, L. 2019; 3 (4): 220–21
  • Undiagnosed Diabetes Mellitus and Tuberculosis Infection: A Population-based, Observational Study from Eastern China. Diabetes/metabolism research and reviews Liu, Q., Lu, P., Martinez, L., Peng, H., Zhu, T., Zhu, L., Wang, J., Lu, W. 2019: e3227

    Abstract

    China has the largest dual diabetes and tuberculosis epidemic globally. No studies from mainland China have assessed the relationship between tuberculosis infection and diabetes. We conducted a population-based, observational study in eastern China to further explore this relationship.A blood glucose, Quantiferon, and tuberculin skin test were administered at baseline. We compared tuberculosis infection in nondiabetics and diabetics. The cohort was additionally screened for tuberculosis progression over five years.Among 5405 participants, diabetics had elevated levels of Quantiferon and tuberculin positivity, largely driven by undiagnosed diabetics (compared to nondiabetics, Adjusted Odds Ratios of 1.53, 95% Confidence Interval [CI], 1.05-2.23 and 1.58, and 95% CI, 1.07-2.35 for tuberculin and Quantiferon positivity). During follow-up, the annual tuberculosis incidence was three times higher for diabetics compared to the entire cohort.These results suggest improving diabetic control through rapidly identifying undiagnosed diabetes may have indirect benefits to tuberculosis control. Targeting of preventive therapy to newly diagnosed diabetics at high-risk for progressive tuberculosis in China should be considered.

    View details for DOI 10.1002/dmrr.3227

    View details for PubMedID 31655015

  • 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

    Abstract

    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

  • Forecasting the seasonality and trend of pulmonary tuberculosis in Jiangsu Province of China using advanced statistical time-series analyses INFECTION AND DRUG RESISTANCE Liu, Q., Li, Z., Ji, Y., Martinez, L., Zia, U., Javaid, A., Lu, W., Wang, J. 2019; 12: 2311–22

    Abstract

    Forecasting the seasonality and trend of pulmonary tuberculosis is important for the rational allocation of health resources; however, this foresting is often hampered by inappropriate prediction methods. In this study, we performed validation research by comparing the accuracy of the autoregressive integrated moving average (ARIMA) model and the back-propagation neural network (BPNN) model in a southeastern province of China.We applied the data from 462,214 notified pulmonary tuberculosis cases registered from January 2005 to December 2015 in Jiangsu Province to modulate and construct the ARIMA and BPNN models. Cases registered in 2016 were used to assess the prediction accuracy of the models. The root mean square error (RMSE), mean absolute percentage error (MAPE), mean absolute error (MAE) and mean error rate (MER) were used to evaluate the model fitting and forecasting effect.During 2005-2015, the annual pulmonary tuberculosis notification rate in Jiangsu Province was 56.35/100,000, ranging from 40.85/100,000 to 79.36/100,000. Through screening and comparison, the ARIMA (0, 1, 2) (0, 1, 1)12 and BPNN (3-9-1) were defined as the optimal fitting models. In the fitting dataset, the RMSE, MAPE, MAE and MER were 0.3901, 6.0498, 0.2740 and 0.0608, respectively, for the ARIMA (0, 1, 2) (0, 1, 1)12 model, 0.3236, 6.0113, 0.2508 and 0.0587, respectively, for the BPNN model. In the forecasting dataset, the RMSE, MAPE, MAE and MER were 0.1758, 4.6041, 0.1368 and 0.0444, respectively, for the ARIMA (0, 1, 2) (0, 1, 1)12 model, and 0.1382, 3.2172, 0.1018 and 0.0330, respectively, for the BPNN model.Both the ARIMA and BPNN models can be used to predict the seasonality and trend of pulmonary tuberculosis in the Chinese population, but the BPNN model shows better performance. Applying statistical techniques by considering local characteristics may enable more accurate mathematical modeling.

    View details for DOI 10.2147/IDR.S207809

    View details for Web of Science ID 000477633300001

    View details for PubMedID 31440067

    View details for PubMedCentralID PMC6666376

  • A tuberculosis school outbreak in China, 2018: reaching an often overlooked adolescent population. Epidemiology and infection You, N. N., Zhu, L. M., Li, G. L., Martinez, L., Lu, W., Liu, Q., Yang, H. T. 2019; 147: e303

    Abstract

    Adolescents have been largely neglected from tuberculosis control efforts. In low- to medium burden settings much of the tuberculosis burden in this age group occurs from school outbreaks. We report on a large tuberculosis outbreak in adolescents from a boarding high school in Jiangsu Province, China. From March to June 2018, a tuberculosis outbreak occurred in a boarding high school. We conducted an outbreak investigation involving clinical diagnostic tests and molecular analysis to determine the outbreak origin. Cases were detected through symptom screening, tuberculin skin testing (TST), chest radiography, sputum smear, solid sputum culture and GeneXpert MTB/RIF. Mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) genotyping and spoligotyping methods were performed on Mycobacterium tuberculosis (M. tuberculosis) isolates to identify the outbreak origin. A total of 845 students and 131 teachers/staff attended a TST screening for tuberculosis infection. The prevalence of elevated tuberculin reactions at ≥5, ≥10 and ≥15 mm was 12.19% (119/976), 6.35% (62/976) and 3.28% (32/976), respectively. Radiographic abnormalities were present in 5.73% (56 of 976) individuals, 40 students and 16 teachers/staff. Of these, 12 students were diagnosed with confirmed tuberculosis. In total, 14 students (two index cases and 12 confirmed cases) were diagnosed and reported in the tuberculosis outbreak, an attack rate of 1.7% (14/847) among students (two index cases and 845 screened students). Results from MIRU-VNTR typing and spoligotyping analyses demonstrated that three M. tuberculosis strains belong to the Beijing family with corresponding MIRU-VNTR alleles. This school-based tuberculosis outbreak among adolescents demonstrates that transmission among individuals in this age group is common and must be prioritised. It suggests that identifying and timely diagnosis of smear-positive cases, especially in the early phase of outbreaks, is the key to preventing further spread among close contacts.

    View details for DOI 10.1017/S0950268819001882

    View details for PubMedID 31736459

    View details for PubMedCentralID PMC6873155

  • In reply to 'Interferon-gamma release assays have suboptimal sensitivity in both latent and active tuberculosis'. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Castellanos, M. E., Martinez, L., Whalen, C. C. 2019; 23 (6): 767

    View details for DOI 10.5588/ijtld.18.0749

    View details for PubMedID 31315714

  • Mycobacterium tuberculosis Beijing genotype strains and unfavourable treatment outcomes: a systematic review and meta-analysis. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases Liu, Q., Wang, D., Martinez, L., Lu, P., Zhu, L., Lu, W., Wang, J. 2019

    Abstract

    The Mycobacterium tuberculosis Beijing genotype was first described in 1995 and is now the predominant strain among patients with tuberculosis in many Asian countries. The rapid global spread of the Beijing genotype is receiving increasing attention because it can cause a higher risk of treatment failures. Our objective was to assess the association between the Beijing genotype and unfavourable treatment outcomes of tuberculosis.We searched for eligible studies through PubMed, Web of Science, Chinese National Knowledge Infrastructure and Wanfang Data. We included cohort studies that evaluated treatment outcomes and Beijing genotype strains. Participants were individuals with active pulmonary tuberculosis. The association between Beijing genotype and the risk of unfavourable treatment outcomes was assessed using the pooled odds ratios (ORs) with corresponding confidence intervals (CIs).In total, 7489 tuberculosis patients were involved in the analysis. Patients infected with the Beijing genotype were more likely to have unfavourable treatment outcomes, with the OR of 2.04 (95% CI 1.52-2.75). The pooled OR was 2.33 (95% CI 1.71-3.16) for recurrence, 2.36 (95% CI 1.69-3.30) for relapse and 2.62 (95% CI 1.90-3.61) for treatment failure, respectively. Subgroup analysis revealed that Beijing genotype was a significant risk factor for unfavourable treatment outcomes in Asians (OR 2.28, 95% CI 1.82-2.86) or in drug-susceptible TB patients (OR 2.11, 95% CI 1.31-3.39). No significant association was observed among non-Asian populations (OR 1.17, 95% CI 0.73-1.86) or patients with multidrug-resistant (MDR) tuberculosis (OR 0.97, 95% CI 0.48-1.94).Our results suggest that Mycobacterium tuberculosis Beijing genotype is associated with an increased risk of unfavourable treatment outcomes, including treatment failure and relapse.

    View details for DOI 10.1016/j.cmi.2019.07.016

    View details for PubMedID 31336202

  • 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

  • Low Prevalence of Tuberculin Skin Test Boosting among Community Residents in Uganda. The American journal of tropical medicine and hygiene Sekandi, J. N., Zalwango, S., Nkwata, A. K., Martinez, L., Kakaire, R., Mutanga, J. N., Whalen, C. C., Kiwanuka, N. 2018

    Abstract

    Boosted tuberculin skin test (TST) reactions can be misclassified as new latent tuberculosis (TB) infection. To our knowledge, no study has evaluated the prevalence of TST boosting in a population-based sample in high TB burden settings. We determined the prevalence of TST boosting among urban residents in Uganda. We evaluated 99 participants with initial TST < 5 mm and repeated a skin test after 2 weeks. We found that only 2% had boosted TST reactions suggesting that most TST conversions could represent new TB infections in this high-burden setting.

    View details for DOI 10.4269/ajtmh.17-0591

    View details for PubMedID 29313483

  • 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

    Abstract

    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

  • Performance of the QuantiFERON®-TB Gold In-Tube assay in tuberculin skin test converters: a prospective cohort study. The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease Castellanos, M. E., Kirimunda, S., Martinez, L., Quach, T., Woldu, H., Kakaire, R., Handel, A., Zalwango, S., Kiwanuka, N., Whalen, C. C. 2018; 22 (9): 1000–1006

    Abstract

    To investigate diagnostic agreement of the QuantiFERON®-TB Gold In-Tube (QFT-GIT) test in adult tuberculin skin test (TST) converters in a high tuberculosis (TB) burden setting.We performed a case-cohort study from 2014 to 2016 in Uganda among residents who were not infected with Mycobacterium tuberculosis. Participants were followed up for 1 year, when they were retested to determine TST conversion. All TST converters and a random sample of participants from baseline were offered QFT-GIT testing.Of 368 enrolled participants, 61 (17%) converted their TST by 1 year. Among 61 converters, 42 were tested using QFT-GIT, 64% of whom were QFT-GIT-positive. Of 307 participants with a persistent negative TST, 48 were tested using QFT-GIT, 83% of whom were QFT-negative. Overall concordance of TST and QFT-GIT was moderate (κ = 0.48, 95%CI 0.30-0.66). Converters with a conversion of 15 mm had a higher proportion of concordant QFT-GIT results (79%) than converters with increments of 10-14.9 mm (52%).Concordance between TST and QFT-GIT was moderate among TST converters in this urban African population. These findings call for improved tests that more accurately measure conversion to tuberculous infection.

    View details for DOI 10.5588/ijtld.18.0073

    View details for PubMedID 30092864

    View details for PubMedCentralID PMC6482451

  • Tuberculin conversion and tuberculosis disease in infants and young children from the Drakenstein Child Health Study: A call to action. South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde Martinez, L., Zar, H. J. 2018; 108 (4): 247–48

    Abstract

    Although tuberculosis (TB) is widely acknowledged as a major driver of global morbidity and mortality in adults, the disease's impact on children has been underappreciated. Global estimates of mortality among children aged <5 years, derived largely from vital registration and verbal autopsy records, have excluded paediatric TB as a contributing cause.

    View details for DOI 10.7196/SAMJ.2017.v108i4.13169

    View details for PubMedID 29629670

  • Factors affecting time to sputum culture conversion and treatment outcome of patients with multidrug-resistant tuberculosis in China. BMC infectious diseases Liu, Q., Lu, P., Martinez, L., Yang, H., Lu, W., Ding, X., Zhu, L. 2018; 18 (1): 114

    Abstract

    Few prospective cohort studies, none in China, have investigated the relationship between treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) patients and sputum culture conversion. Factors affecting the time of the culture conversion throughout the whole course of the treatment have rarely been investigated.This study was performed in four cities in Jiangsu province, China. MDR-TB patients were consecutively enrolled between December 2011 and March 2014. Rates of sputum culture conversion were calculated and Cox proportional-hazards model was performed. Factors contributing to sputum culture conversion were investigated.In all, 139 MDR-TB patients with treatment outcomes were enrolled. Median time to culture conversion among those who converted was 91.5 days (interquartile range, 34.0-110.8 days). After multivariable analysis, smoking (HR = 0.44; 95% CI: 0.23-0.83), drinking (HR = 0.41; 95% CI: 0.21-0.81), ofloxacin resistance (HR = 0.43; 95% CI: 0.24-0.76) and sputum smear grade > 1 (HR = 0.51; 95% CI: 0.31-0.83) were less likely to have culture conversion.MDR-TB patients who smoke, drink, have ofloxacin resistance, or a high smear grade are less likely to respond to treatment and should be meticulously followed up.

    View details for DOI 10.1186/s12879-018-3021-0

    View details for PubMedID 29510666

  • Cognitive deficits and educational loss in children with schistosome infection-A systematic review and meta-analysis. PLoS neglected tropical diseases Ezeamama, A. E., Bustinduy, A. L., Nkwata, A. K., Martinez, L., Pabalan, N., Boivin, M. J., King, C. H. 2018; 12 (1): e0005524

    Abstract

    By means of meta-analysis of information from all relevant epidemiologic studies, we examined the hypothesis that Schistosoma infection in school-aged children (SAC) is associated with educational loss and cognitive deficits.This review was prospectively registered in the PROSPERO database (CRD42016040052). Medline, Biosis, and Web of Science were searched for studies published before August 2016 that evaluated associations between Schistosoma infection and cognitive or educational outcomes. Cognitive function was defined in four domains-learning, memory, reaction time, and innate intelligence. Educational outcome measures were defined as attendance and scholastic achievement. Risk of bias (ROB) was evaluated using the Newcastle-Ottawa quality assessment scale. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare cognitive and educational measures for Schistosoma infected /not dewormed vs. uninfected/dewormed children. Sensitivity analyses by study design, ROB, and sequential exclusion of individual studies were implemented. Thirty studies from 14 countries, including 38,992 SAC between 5-19 years old, were identified. Compared to uninfected children and children dewormed with praziquantel, the presence of Schistosoma infection and/or non-dewormed status was associated with deficits in school attendance (SMD = -0.36, 95%CI: -0.60, -0.12), scholastic achievement (SMD = -0.58, 95%CI: -0.96, -0.20), learning (SMD = -0.39, 95%CI: -0.70, -0.09) and memory (SMD = -0.28, 95%CI: -0.52, -0.04) tests. By contrast, Schistosoma-infected/non-dewormed and uninfected/dewormed children were similar with respect to performance in tests of reaction time (SMD = -0.06, 95%CI: -0.42, 0.30) and intelligence (SMD = -0.25, 95%CI: -0.57, 0.06). Schistosoma infection-associated deficits in educational measures were robust among observational studies, but not among interventional studies. The significance of infection-associated deficits in scholastic achievement was sensitive to ROB. Schistosoma infection-related deficits in learning and memory tests were invariant by ROB and study design.Schistosoma infection/non-treatment was significantly associated with educational, learning, and memory deficits in SAC. Early treatment of children in Schistosoma-endemic regions could potentially mitigate these deficits.ClinicalTrials.gov CRD42016040052.

    View details for DOI 10.1371/journal.pntd.0005524

    View details for PubMedID 29329293

  • ) in urban school microenvironments near a contaminated beach with mine tailings, Chañaral, Chile. Environmental geochemistry and health Mesías Monsalve, S., Martínez, L., Yohannessen Vásquez, K., Alvarado Orellana, S., Klarián Vergara, J., Martín Mateo, M., Costilla Salazar, R., Fuentes Alburquenque, M., Cáceres Lillo, D. D. 2017

    Abstract

    Air quality in schools is an important public health issue because children spend a considerable part of their daily life in classrooms. Particulate size and chemical composition has been associated with negative health effects. We studied levels of trace element concentrations in fine particulate matter (PM2.5) in indoor versus outdoor school settings from six schools in Chañaral, a coastal city with a beach severely polluted with mine tailings. Concentrations of trace elements were measured on two consecutive days during the summer and winter of 2012 and 2013 and determined using X-ray fluorescence. Source apportionment and element enrichment were measured using principal components analysis and enrichment factors. Trace elements were higher in indoor school spaces, especially in classrooms compared with outdoor environments. The most abundant elements were Na, Cl, S, Ca, Fe, K, Mn, Ti, and Si, associated with earth's crust. Conversely, an extremely high enrichment factor was determined for Cu, Zn, Ni and Cr; heavy metals associated with systemic and carcinogenic risk effects, whose probably origin sources are industrial and mining activities. These results suggest that the main source of trace elements in PM2.5 from these school microenvironments is a mixture of dust contaminated with mine tailings and marine aerosols. Policymakers should prioritize environmental management changes to minimize further environmental damage and its direct impact on the health of children exposed.

    View details for DOI 10.1007/s10653-017-9980-z

    View details for PubMedID 28536962

  • Time to sputum culture conversion and treatment outcome of patients with multidrug-resistant tuberculosis: a prospective cohort study from urban China EUROPEAN RESPIRATORY JOURNAL Lu, P., Liu, Q., Martinez, L., Yang, H., Lu, W., Ding, X., Zhu, L. 2017; 49 (3)

    View details for DOI 10.1183/13993003.01558-2016

    View details for Web of Science ID 000397931500014

    View details for PubMedID 28331033

    View details for PubMedCentralID PMC5380874

  • Innovative Methods to Manage, Detect, and Prevent Tuberculosis. American journal of respiratory and critical care medicine Martinez, L., Castellanos, M. E., Hallowell, B. D., Whalen, C. C. 2017; 195 (4): 530-532

    View details for DOI 10.1164/rccm.201608-1657RR

    View details for PubMedID 27911589

  • Delays and Pathways to Final Tuberculosis Diagnosis in Patients from a Referral Hospital in Urban China. The American journal of tropical medicine and hygiene Martinez, L., Xu, L., Chen, C., Sekandi, J. N., Zhu, Y., Zhang, C., Whalen, C. C., Zhu, L. 2017

    Abstract

    AbstractChina is among the countries with the largest epidemic of drug susceptible and resistant tuberculosis globally. We investigated the locations tuberculosis patients visited before being diagnosed, total diagnostic delay, and risk factors associated with total delay from a large tuberculosis referral hospital in Nanjing, China. We conducted a retrospective cohort study among tuberculosis patients who initiated anti-tuberculosis treatment within 3 months prior to the study date. Patient information regarding time and locations visited while seeking care for tuberculosis-related symptoms was collected through face-to-face interviews. Crude and adjusted Cox proportional hazard ratios of factors associated with time to diagnosis were calculated. Of 179 bacteriologically confirmed patients, 37% were women and median age was 41 (interquartile range [IQR], 26-62). Public hospitals were the most commonly visited health-care institution and repeated visits to them were common. The mean days to tuberculosis diagnosis were 50.3. Female patients (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.04-1.48) or patients who contacted a health-care provider 2 weeks after becoming symptomatic (HR, 1.59; 95% CI, 1.43-1.70) were significantly less likely to have a timely diagnosis. In a referral hospital in urban China, we found that female tuberculosis patients took significantly more time to reach diagnosis than males and patients often cycled in public hospitals for multiple visits before reaching final diagnosis. Health professionals at public hospitals in Nanjing should be encouraged to refer potential tuberculosis patients as soon as possible to avoid nosocomial transmission.

    View details for DOI 10.4269/ajtmh.16-0358

    View details for PubMedID 28193742

    View details for PubMedCentralID PMC5417195

  • Diagnostic Performance of the GenoType MTBDRplus and MTBDRsl Assays to Identify Tuberculosis Drug Resistance in Eastern China. Chinese medical journal Liu, Q., Li, G. L., Chen, C., Wang, J. M., Martinez, L., Lu, W., Zhu, L. M. 2017; 130 (13): 1521–28

    Abstract

    The WHO recently has recommended the GenoType MTBDRplus version 1.0 and MTBDRsl version 1.0 assays for widespread use in countries endemic with drug-resistant tuberculosis. Despite this, these assays have rarely been evaluated in China, where the burden of drug-resistant tuberculosis is among the highest globally.Mycobacterium tuberculosis clinical isolates were obtained between January 2008 and December 2008. Isolates were tested for drug resistance against rifampicin (RFP) and isoniazid (INH) using the GenoType MTBDRplus assay and drug resistance against ethambutol (EMB), ofloxacin (OFX), and kanamycin (KM) using the Genotype MTBDRsl assay. These results were compared with conventional drug-susceptibility testing (DST).Readable results were obtained from 235 strains by GenoType MTBDRplus assay. Compared to DST, the sensitivity of GenoType MTBDRplus assay to detect RFP, INH, and multidrug resistance was 97.7%, 69.9%, and 69.8%, respectively, whereas the specificity for detecting RFP, INH, and multidrug resistance was 66.7%, 69.2%, and 76.8%, respectively. The sensitivity and specificity of the GenoType MTBDRsl assay were 90.9% and 95.2% for OFX, 77.8% and 99.5% for KM, 63.7% and 86.4% for EMB, respectively. Mutations in codon S531L of the rpoB gene and codon S315T1 of KatG gene were dominated in multidrug-resistant tuberculosis (MDR-TB) strains.In combination with DST, application of the GenoType MTBDRplus and MTBDRsl assays may be a useful supplementary tool to allow a rapid and safe diagnosis of multidrug resistance and extensively drug-resistant tuberculosis.

    View details for DOI 10.4103/0366-6999.208248

    View details for PubMedID 28639565

  • Mediating Effect of Repeated Tuberculosis Exposure on the Risk of Transmission to Household Contacts of Multidrug-Resistant Tuberculosis Patients. The American journal of tropical medicine and hygiene Lu, P., Ding, X., Liu, Q., Lu, W., Martinez, L., Sun, J., Lu, F., Zhong, C., Jiang, H., Miao, C., Zhu, L., Yang, H. 2017

    Abstract

    Primary Mycobacterium tuberculosis transmission is an important driver of the global epidemic of resistance to tuberculosis drugs. A few studies have compared tuberculosis infection in contacts of index cases with different drug-resistant profiles, suggesting that contacts of multidrug-resistant (MDR) tuberculosis cases are at higher risk. Repeated tuberculosis exposure in contacts of MDR tuberculosis patients through recurrent tuberculosis may modify this relationship. We compared tuberculosis infection in household contacts of MDR and drug-susceptible (DS) tuberculosis patients from six cities in southeastern China and investigated whether repeated tuberculosis exposure was a mediating factor. Tuberculosis infection was defined as a tuberculin skin test induration ≥ 10 mm. In all, 111 (28.0%) of 397 household contacts of MDR tuberculosis patients and 165 (24.7%) of 667 contacts of DS tuberculosis index cases were infected with tuberculosis. In a multivariate model not including the previous tuberculosis exposure, contacts of MDR tuberculosis patients had a higher likelihood of tuberculosis infection (adjusted odds ratio [AOR] = 1.37; 95% confidence interval [CI] = 1.01-1.84; P = 0.041). In a separate multivariate model adjusted for the previous tuberculosis exposure, the odds ratio of tuberculosis infection flipped and contacts of MDR cases were now at lower risk for tuberculosis infection (AOR = 0.55; 95% CI = 0.38-0.81; P = 0.003). These findings suggest prior tuberculosis exposure in contacts strongly mediates the relationship between tuberculosis infection and the index drug resistance profile. Prior studies showing lower risk of developing tuberculosis among contacts of MDR tuberculosis patients may be partially explained by a lower rate of tuberculosis infection at baseline.

    View details for DOI 10.4269/ajtmh.17-0325

    View details for PubMedID 29210348

  • Glycemic Control and the Prevalence of Tuberculosis Infection: A Population-based Observational Study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Martinez, L., Zhu, L., Castellanos, M. E., Liu, Q., Chen, C., Hallowell, B. D., Whalen, C. C. 2017; 65 (12): 2060–68

    Abstract

    Several cohort studies demonstrate that diabetics are at increased risk for active tuberculosis, and poor glycemic control may exacerbate this risk. A higher prevalence of tuberculosis infection at baseline among diabetics may partially explain these results; however, no population-based studies have investigated this association. Furthermore, whether glycemic control modifies the relationship between diabetes and tuberculosis infection, as it does with active tuberculosis, is unknown.Diabetics were diagnosed through physician evaluation and using 3 laboratory tests including hemoglobin A1C (HbA1C), fasting plasma glucose (FPG), or 2-hour plasma glucose (PG). Tuberculosis infection was diagnosed through tuberculin skin tests, and glycemic control was assessed linearly and categorically using recommended targets.Among 4215 participants, the prevalence of tuberculosis infection was 4.1%, 5.5%, and 7.6% in nondiabetic, prediabetic, and diabetic participants (Ptrend = .012). In multivariate analysis, diabetes was associated with tuberculosis infection (adjusted odds ratio [AOR], 1.5; 95% confidence interval [CI], 1.0-2.2). Compared to nondiabetics, diabetics who were undiagnosed (AOR, 2.2 and 1.2 in diagnosed diabetics), FPG >130 mg/dL (AOR, 2.6 and 1.3 in diabetics with FPG ≤130 mg/dL), or not on insulin (AOR, 1.7 and 0.8 in diabetics on insulin) had elevated tuberculosis infection rates. In a linear dose-response analysis, increasing values of FPG (AOR, 1.02 per 1-mg/dL; 95% CI, 1.01-1.03), PG (AOR, 1.02 per 1-mg/dL; 95% CI, 1.01-1.04), and HbA1C (AOR, 1.13 per 1%; 95% CI, 1.04-1.22) all predicted tuberculosis infection.Our results suggest glycemic control may modify the relationship between tuberculosis infection and diabetes.

    View details for DOI 10.1093/cid/cix632

    View details for PubMedID 29059298

  • A Prospective Validation of a Clinical Algorithm to Detect Tuberculosis in Child Contacts. American journal of respiratory and critical care medicine Martinez, L., Handel, A., Shen, Y., Chakraburty, S., Quinn, F. D., Stein, C. M., Malone, L. L., Zalwango, S., Whalen, C. C. 2017

    View details for DOI 10.1164/rccm.201706-1210LE

    View details for PubMedID 29035095

  • Four Degrees of Separation: Social Contacts and Health Providers Influence the Steps to Final Diagnosis of Active Tuberculosis Patients in Urban Uganda BMC INFECTIOUS DISEASES Sekandi, J. N., Zalwango, S., Martinez, L., Handel, A., Kakaire, R., Nkwata, A. K., Ezeamama, A. E., Kiwanuka, N., Whalen, C. C. 2015; 15

    Abstract

    Delay in tuberculosis (TB) diagnosis adversely affects patients' outcomes and prolongs transmission in the community. The influence of social contacts on steps taken by active pulmonary TB patients to seek a diagnosis has not been well examined.A retrospective study design was use to enroll TB patients on treatment for 3 months or less and aged ≥18 years from 3 public clinics in Kampala, Uganda, from March to July 2014. Social network analysis was used to collect information about social contacts and health providers visited by patients to measure the number of steps and time between onset of symptoms and final diagnosis of TB.Of 294 TB patients, 58 % were male and median age was 30 (IQR: 24-38) years. The median number of steps was 4 (IQR: 3, 7) corresponding to 70 (IQR: 28,140) days to diagnosis. New patients had more steps and time to diagnosis compared retreatment patients (5 vs. 3, P < 0.0001; 84 vs. 46 days P < 0.0001). Fifty-eight percent of patients first contacted persons in their social network. The first step to initiate seeking care accounted for 41 % of the patients' time to diagnosis while visits to non-TB providers and TB providers (without a TB diagnosis) accounted for 34 % and 11 % respectively. New TB patients vs. retreatment (HR: 0.66, 95 % CI; 1.11, 1.99), those who first contacted a non-TB health provider vs. contacting social network (HR: 0.72 95 % CI; 0.55, 0.95) and HIV seronegative vs. seropositive patients (HR: 0.70, 95 % CI; 0.53, 0.92) had a significantly lower likelihood of a timely final diagnosis.There were four degrees of separation between the onset of symptoms in a TB patient and a final diagnosis. Both social and provider networks of patients influenced the diagnostic pathways. Most delays occurred in the first step which represents decisions to seek help, and through interactions with non-TB health providers. TB control programs should strengthen education and active screening in the community and in health care settings to ensure timely diagnosis of TB.

    View details for DOI 10.1186/s12879-015-1084-8

    View details for Web of Science ID 000359764700005

    View details for PubMedID 26293293

    View details for PubMedCentralID PMC4546132

  • Age, sex, and nutritional status modify the CD4+T-cell recovery rate in HIV-tuberculosis co-infected patients on combination antiretroviral therapy INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES Ezeamama, A. E., Mupere, E., Oloya, J., Martinez, L., Kakaire, R., Yin, X., Sekandi, J. N., Whalen, C. C. 2015; 35: 73-79

    Abstract

    Baseline age and combination antiretroviral therapy (cART) were examined as determinants of CD4+ T-cell recovery during 6 months of tuberculosis (TB) therapy with/without cART. It was determined whether this association was modified by patient sex and nutritional status.This longitudinal analysis included 208 immune-competent, non-pregnant, ART-naive HIV-positive patients from Uganda with a first episode of pulmonary TB. CD4+ T-cell counts were measured using flow cytometry. Age was defined as ≤24, 25-29, 30-34, and 35-39 vs. ≥40 years. Nutritional status was defined as normal (>18.5kg/m(2)) vs. underweight (≤18.5kg/m(2)) using the body mass index (BMI). Multivariate random effects linear mixed models were fitted to estimate differences in CD4+ T-cell recovery in relation to specified determinants.cART was associated with a monthly rise of 15.7 cells/μl (p<0.001). Overall, age was not associated with CD4+ T-cell recovery during TB therapy (p = 0.655). However, among patients on cART, the age-associated CD4+ T-cell recovery rate varied by sex and nutritional status, such that age <40 vs. ≥40 years predicted superior absolute CD4+ T-cell recovery among females (p=0.006) and among patients with a BMI ≥18.5kg/m(2) (p<0.001).TB-infected HIV-positive patients aged ≥40 years have a slower rate of immune restoration given cART, particularly if BMI is >18.5kg/m(2) or they are female. These patients may benefit from increased monitoring and nutritional support during cART.

    View details for DOI 10.1016/j.ijid.2015.04.008

    View details for Web of Science ID 000358004000017

    View details for PubMedID 25910854

    View details for PubMedCentralID PMC4497838

  • The Epidemiology and Geographic Distribution of Nontuberculous Mycobacteria Clinical Isolates from Sputum Samples in the Eastern Region of China PLOS NEGLECTED TROPICAL DISEASES Shao, Y., Chen, C., Song, H., Li, G., Liu, Q., Li, Y., Zhu, L., Martinez, L., Lu, W. 2015; 9 (3)

    Abstract

    Nontuberculous mycobacteria (NTM) have been reported to be increasing worldwide and its geographic distribution differs by region. The aim of this study was to describe the epidemiology and distribution of NTM in the eastern part of China.Sputum samples were collected from 30 surveillance sites for tuberculosis drug resistance test from May 1, 2008 to December 31, 2008. Identification was performed using a biochemical test, multiplex PCR and GenoType Mycobacterium CM/AS assay.A total of 1779 smear positive clinical isolates were obtained, of which 60 (3.37%) were NTM. Five species/complex of NTM were identified; M. intracellulare was the predominated species (68.33%), followed by M. abscessus-M. immunogenum (13.33%), Mycobacterium spec. (10.00%), M. Kansasii (6.67%) and M. peregrinum-M. alvei-M. septicum (1.67%).M. intracellulare was the main species of NTM in the eastern part of China and clinical physicians should pay more attention to NTM induced pulmonary disease.

    View details for DOI 10.1371/journal.pntd.0003623

    View details for Web of Science ID 000352199400081

    View details for PubMedID 25775117

    View details for PubMedCentralID PMC4361326

  • Diagnostic Value of GeneChip for Detection of Resistant Mycobacterium tuberculosis in Patients with Differing Treatment Histories JOURNAL OF CLINICAL MICROBIOLOGY Zhu, L., Liu, Q., Martinez, L., Shi, J., Chen, C., Shao, Y., Zhong, C., Song, H., Li, G., Ding, X., Zhou, Y., Zhu, L., Whalen, C. C., Lu, W. 2015; 53 (1): 131-135

    Abstract

    The increasing burden of drug-resistant tuberculosis (TB) poses an escalating threat to national TB control programs. To assist appropriate treatment for TB patients, accurate and rapid detection of drug resistance is critical. The GeneChip test is a novel molecular tool for the diagnosis of TB drug resistance. Performance-related data on GeneChip are limited, and evaluation in new and previously treated TB cases has never been performed. We evaluated the diagnostic performance of GeneChip in detecting resistance to rifampin (RMP) and isoniazid (INH) and in detecting multidrug-resistant tuberculosis (MDR-TB) in comparison with standard drug susceptibility testing (DST) and compared the results in a group of previously treated and newly detected TB patients in an urban area in southeastern China. One thousand one hundred seventy-three (83.8%) new cases and 227 (16.2%) previously treated cases were collected between January 2011 and September 2013. The GeneChip showed a specificity of 97.8% and a sensitivity of 94.8% for detection of RMP resistance and 97.3% and 70.9%, respectively, for INH resistance in new cases. For previously treated cases, the overall sensitivity, specificity, and agreement rate are 94.6%, 91.3%, and 92.1%, respectively, for detection of RMP resistance and 69.7%, 95.4%, and 86.8%, respectively, for INH resistance. The sensitivity and specificity of MDR-TB were 81.8% and 99.0% in new cases and 77.8% and 93.4% in previously treated cases, respectively. The GeneChip system provides a simple, rapid, reliable, and accurate clinical assay for the detection of TB drug resistance, and it is a potentially important diagnostic tool in a high-prevalence area.

    View details for DOI 10.1128/JCM.02283-14

    View details for Web of Science ID 000346502200021

    View details for PubMedID 25355771

    View details for PubMedCentralID PMC4290911

  • Changes in Tuberculin Skin Test Positivity Over 20 Years in Periurban Shantytowns in Lima, Peru AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Martinez, L., Arman, A., Haveman, N., Lundgren, A., Cabrera, L., Evans, C. A., Pelly, T. F., Saito, M., Callacondo, D., Oberhelman, R., Collazo, G., Carnero, A. M., Gilman, R. H. 2013; 89 (3): 507-515

    Abstract

    A cross-sectional, community-based study was performed in 2012 with 428 residents of periurban shantytowns in Lima, Peru to study risk factors for and changes in latent tuberculosis infection in age-stratified groups compared with our data from the same region in 1990 (N = 219) and 2005 (N = 103). Tuberculin skin test positivity in these communities was highly prevalent at 52% overall, increased with age (P < 0.01) and was similar to 2005 (53%) and 1990 (48%). From 1990 to 2012, the prevalence of tuberculin positivity decreased in 5-14 and 15-24 year old groups (to 17% and 34%, respectively, both P < 0.05). However, this may be explained by cessation of Bacille Calmette-Guérin revaccination during this period, because Bacille Calmette-Guérin revaccination doubled tuberculin positivity. Over the same 22-year period, tuberculin positivity in the ≥ 25 year old group remained high (71%, P = 0.3), suggesting that prevalent latent tuberculosis infection persists in the adult population despite improving medical care and socioeconomic development in this region.

    View details for DOI 10.4269/ajtmh.13-0005

    View details for Web of Science ID 000326129900019

    View details for PubMedID 23878185

    View details for PubMedCentralID PMC3771290

  • Cutaneous Leishmaniasis "Chiclero's Ulcer" in Subtropical Ecuador AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Calvopina, M., Martinez, L., Hashiguchi, Y. 2013; 89 (2): 195-196

    Abstract

    An 18-year-old female presented with a severe ulcerative lesion on her right ear of 6 weeks duration. Her right ear was edematous and erythematous with a large, painless ulcerative lesion covering a third of the pinna and satellite papular lesions on the posterior. She was diagnosed with chiclero's ulcer. A skin smear stained with Diff-quik showed abundant Leishmania parasites. Chiclero's ulcer is a rare clinical presentation and is typically severe and difficult to treat. Physicians in Ecuador recommend administering prolonged intramuscular Glucantime. Side effects are common and can be severe resulting in low patient compliance. Because of preferences of the patient and the large volume needed for her weight, we recommended topical treatment with a lotion of Glucantime mixed half and half with white Merthiolate. After applying this lotion to the lesion 3 to 4 times a day for 6 weeks, the lesion healed.

    View details for DOI 10.4269/ajtmh.12-0690

    View details for Web of Science ID 000322683100001

    View details for PubMedID 23926136

    View details for PubMedCentralID PMC3741233

  • Free-ranging chickens in households in a periurban shantytown in Peru--attitudes and practices 10 years after a community-based intervention project. The American journal of tropical medicine and hygiene Martinez, L., Collazo, G., Cabrera, L., Bernabe-Ortiz, A., Ramos-Peña, Y., Oberhelman, R. 2013; 89 (2): 229-231

    Abstract

    Free-ranging chickens are often found in periurban communities in developing countries, and their feces can pose a significant public health sanitation problem. Corralling chickens raised in these periurban areas in chicken coops has been proposed previously as an intervention to address this problem. Aims of this study were to revisit households in a corralling intervention study conducted in 2000-2001 to compare poultry-raising practices and investigate current attitudes regarding the impact of raising chickens in a periurban environment. Sociobehavioral questionnaires were given sequentially to all study participants; 30 families (58%) ceased raising poultry of any kind, whereas 42 (81%) do not raise chickens in their home. This finding indicates a significant reduction in poultry-raising in our study population since 2000-2001, possibly because of acculturation and/or change in socioeconomic status. However, attitudes about corral use for raising poultry were overwhelmingly positive, and the most common reason cited was cleanliness of the home.

    View details for DOI 10.4269/ajtmh.12-0760

    View details for PubMedID 23817335

    View details for PubMedCentralID PMC3741241

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