CAP Profiles

Bio

Bio

Since the early 2000s, I have devoted my efforts to better understanding the risk factors and long-term health consequences of arboviral infections, including Rift Valley fever, chikungunya, and dengue viruses. Currently, I have two large field projects ongoing in Kenya. As a physician-scientist, I split my time between research (75%) and clinical practice (25%), including travel clinic experience. In my current position, I balance a productive research career, a stimulating hospital-based clinical practice, and a rewarding family life.

My formal education included a bachelor’s degree in Biology (University of California at San Diego, 1996, Cum Laude), medical degree (Medical College of Wisconsin, 2000, AOA), pediatric residency-International Health track (Rainbow Babies & Children’s Hospital, CWRU, 2003), fellowship in pediatric infectious diseases (Rainbow Babies & Children’s Hospital, CWRU, 2006), and master’s degree in Clinical Research with a focus in epidemiology (CWRU, 2009).

Clinical Focus

  • Pediatric Infectious Diseases

Academic Appointments

Administrative Appointments

  • Co-Leader and Clinical Partner, Pediatrics Global Health Scholarly Concentration (2018 - Present)
  • Research Fellow, Windward Islands Researach and Education Foundation (WINDREF) (2017 - Present)
  • Affilated Faculty Member, Institute for Immunity, Transplantation, and Infection (2015 - Present)
  • Affiliated Faculty Member, Stanford Woods Institute for the Environment (2015 - Present)
  • Affiliated Faculty Member, Emmett Interdisciplinary Program in Environment & Resources (2015 - Present)
  • Faculty Fellow, Center for Innovation in Global Health (2015 - Present)

Honors & Awards

  • Postdoc Mentor Award, Stanford Department of Pediatrics (2018)
  • Women in Science Award, International Socieety for Antiviral Research (ISAR) (2018)
  • Bechtel Faculty Scholar Award, Stanford Child Health Research Institute (2015-2020)
  • New Investigator in Global Health Scholarship, Global Health Council (2010)
  • Fellowship in Infectious Diseases Award, Robert E. Shope (2008)
  • Women Faculty of the School of Medicine Junior Faculty Award, Case Western Reserve University (2008)
  • Loan Repayment Award (LRP), NIH Clinical Research (2004-2012)
  • American Medical Woman Award, American Medical Women's Association (2000)
  • Outstanding Academic Achievement, Merck Award (2000)
  • Alpha Omega, Alpha Honor Society (1999)

Boards, Advisory Committees, Professional Organizations

  • Core Member, Innovation and Integration of Eosystem-Human Health Science and Tools on the Natural Capital Project Platform Working Group, Stanford Program for Disease Ecology, Health, and the Environment (2018 - Present)
  • Expert Member, GloPID-R Chikungunya working group (2018 - Present)
  • Invited Learner, Stanford Leadership Development Program (2018 - Present)
  • Member, Infectious Disease Society of America (2018 - Present)
  • Member, Pediatric Infectious Diseases Society (2018 - Present)
  • Member, American Academy of Pediatrics (2018 - Present)
  • Chair, American Committee on Arthropod-Borne Viruses (2017 - Present)
  • Editorial Advisory Board Member, American Journal of Tropical Medicine and Hygiene (2017 - Present)
  • Member, WHO ZIKV IPD Consortium, Geneva, Switzerland (2017 - Present)
  • Chair, Ben Kean Travel Fellowship Award Committee, ASTMH (2016 - Present)
  • Chair- elect, American Committee on Arthropod-Borne Viruses (2016 - Present)
  • Chair-elect, American Committee on Arthropod-Borne Viruses (2016 - 2017)
  • Affiliated Faculty Member, Emmett Interdisciplinary Program in Environment & Resources, Stanford University (2015 - Present)
  • Affiliated Faculty Member, Woods Institute for the Environment, Stanford University (2015 - Present)
  • Co-Chair, Integrative Program Committee, Stanford University (2015 - Present)
  • Councilor, American Committee on Arthropod-Borne Viruses (2015 - Present)
  • Member, Institution Biosafety Committee, Stanford University (2015 - Present)
  • Member, Pediatric Infectious Disease Fellowship Program Evaluation Committee, Stanford University (2015 - Present)
  • Panelist, NIAID-WHO Gaps and Opportunities in Chikungunya Research: Expert Consultation on Chikungunya Disease in the Americas (2015 - Present)
  • Member, Adult Infectious Disease Search Committee, Stanford University (2015 - 2016)
  • Chair, CTropMedExam Working Group, ASTMH (2013 - Present)
  • Co-Chair, Other Viruses Research Section Symposium, ASTMH Meeting, Washington, DC (2013 - Present)
  • Invited PLoS Representative, WHO Informal Consultation on Dual Use Research of Concern, Geneva, Switzerland (2013 - Present)
  • Member, Dual Use Research of Concern Committee, PLoS Journals (2013 - Present)
  • Councilor, ASTMH (2012 - Present)
  • Director, Pediatric Resident's Research Seminar Series Hospital of Oakland (2012 - Present)
  • Member, Blue Ribbon Committee, ASTMH (2012 - Present)
  • Symposium Organizer / Chair, "Cultural Lessons Learned in Tropical Medicine: Pearls from the Pioneers" ASTMH Annual Meeting (2011 - Present)
  • Member, Ben Kean Travel Fellowship Award Committee, ASTMH (2011 - 2016)
  • Journal Editor Round Table Participant, National Science Advisory Board for Biosecurity (NSABB) (2010 - 2012)
  • Member, American Academy of Pediatrics International Research Award Selection Committee (2009 - Present)
  • Panelist, National Center for Foreign Animal and Zoonotic Disease Defense Advisory Group on Rift Valley Fever, Washington, DC (2009 - Present)
  • Member, ASTMH Travel Research Award Selection Ccommittee (2009 - 2017)
  • Deputy Editor, PLoS NTDs (2008 - Present)
  • Member, American Society for Tropical Medicine and Hygiene / Courses Committee (2008 - 2017)

Professional Education

  • Medical Education:Medical College Of Wisconsin Office of Graduate Medical Education (2000) WI
  • KL2 Scholar, National Institure of Health, Multidisciplinary Research (2009)
  • MS, Case Western Reserve University, Clinical Research (2009)
  • Board Certification: Pediatric Infectious Diseases, American Board of Pediatrics (2007)
  • Fellowship, Rainbow Babies & Children's Hospital, Cleveland, Ohio, Pediatric Infectious Disease (2006)
  • Pediatric Residency, Rainbow Babies & Children's Hospital, Cleveland, Ohio, International Health Track (2003)
  • Board Certification: Pediatrics, American Board of Pediatrics (2003)
  • Pediatric Internship, Rainbow Babies & Children's Hospital, Cleveland, Ohio, International Health Track (2001)
  • BS, University of California at San Diego, General Biology (1996)
  • Residency:University Hospitals of ClevelandOH
  • Fellowship:Rainbow Babies and Children's Hospital Pediatric Infectious DiseaseOH

Community and International Work

  • Neurodevelopment and Vector-borne Diseases: Building Research Capacity in the Tropics, Grenada

    Topic

    Building research capacity

    Partnering Organization(s)

    NIH

    Populations Served

    Children

    Location

    International

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Complex Data and Deep Learning for Disease Outbreak Prediction

    Topic

    Disease outbreak prediction

    Partnering Organization(s)

    Stanford Center for Innovation in Global Health

    Populations Served

    Children

    Location

    International

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Assessment of Cognitive Functioning in Children Exposed to the Zika Virus

    Topic

    Zika virus impact

    Partnering Organization(s)

    USAID Maternal and Child Survival Program

    Populations Served

    Children

    Location

    International

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Trash to Treasure: Collecting trash for profit to reduce vector breeding sites in Kwale County, Kenya, Kenya

    Topic

    Vector control

    Partnering Organization(s)

    Bova Network

    Populations Served

    Families

    Location

    International

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

  • Characterizing the Effects of Antenatal Parasitic Infection on Fetal Immune System Development

    Location

    Bay Area

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • The Spectrum of Zika Disease in Grenada, Grenada

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • Predicting dengue transmission in a changing climate to improve mosquito control, Kenya, Ecuador

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • Integrated Vector Management as a Strategy for Reduced Disease Risk in Dengue Fever

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • Characterization of Immune Factors of Severe and Chronic Chikungunya Disease, Grenada

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • Miniaturized Automated Whole Blood Cellular Analysis System, Kenya

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • Effects of Parasitic Infections on Vaccine Response, Kenya

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

  • Burden of Chikungunya and Dengue in Kenya, Kenya

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

Contact

  • Pediatric Infectious Diseases 300 Pasteur Dr Rm G312 MC 5208 Stanford, CA 94305
    • Tel: (650) 723-5682
    Fax: (650) 725-8040

Links

Research & Scholarship

Current Research and Scholarly Interests

Arthropod-borne viruses are emerging and re-emerging infections that are spreading throughout the world. Our laboratory investigates the epidemiology of arboviral infections, focusing on the burden of disease and the long-term complications on human health. In particular, Dr. LaBeaud investigates dengue, chikungunya, and Rift Valley fever viruses in Kenya, where outbreaks cause fever, arthritis, retinitis, encephalitis, and hemorrhagic fever. Our main research questions focus on the risk factors for arboviral infections, the development of diagnostic tests that can be administered in the field to quickly determine what kind of arboviral infection a person has, and the genetic and immunologic investigation of why different people respond differently to the same infection. Our long-term goals are to contribute to a deeper understanding of arboviral infections and their long-term health consequences and to optimize control strategies to prevent these emerging infections. Our laboratory also investigates the effects of antenatal and postnatal parasitic infections on vaccine responses, growth, and development of Kenyan children.

My lab at Stanford supports the field work that is ongoing in Kenya, but we also have several projects that are based locally. We strive to improve diagnostics of arboviral infections and are using Luminex technology to build a new screening assay. We also have created a Luminex based platform to assess vaccine responses against multiple pathogens.

Projects

  • Characterizing the Effects of Antenatal Parasitic Infection on Fetal Immune System Development, Stanford University, Case Western Reserve University, Ministry of Health- Kenya (1/1/2016 - 1/1/2017)

    Extensive resources are being committed to improve global childhood vaccination coverage, but the response to standard vaccination is often diminished in children from developing nations. The ineffectiveness of vaccination programs in developing communities has been blamed on cold chain lapses and lack of supportable infrastructure, but chronic infections also play a significant role. Multiple maternal parasitic infections affect the unborn infant and are potentially important vaccine response modifiers, but have not been well studied. Increasing evidence suggests that chronic parasitic infections in pregnant women, such as schistosomiasis, filariasis, intestinal helminths, and malaria, can suppress fetal and infant immune responses to subsequent infections and vaccinations. The mechanisms of parasite effects on immune responses are not well understood, although the lack of appropriate vaccine response in infants of parasite-infected mothers appears to be due to dysregulation of maternal immunity, with resultant impaired fetal immunity. The central hypothesis to be tested is that treatment of maternal and infant parasitic infections will enhance infant responses to vaccination. We propose a prospective study of pregnant Kenyan woman and their offspring to evaluate the effects of parasitic infections and prompt anti-parasitic treatment on infant vaccine responses to Streptococcus ppneumonia, Haemophilus influenzae, and diphtheria. We propose the following specific aims: 1) To determine the individual and combined influence of maternal parasitic infections on infant vaccine responses, and 2) To measure the impact of maternal and infant anti-parasitic treatment on infant vaccine responses. The long term goals of this project are to determine the value of specific antenatal and postnatal parasitic treatments and to develop novel approaches to optimizing vaccine program effectiveness.

    Location

    Kenya

    Collaborators

    • Scott Boyd, Associate Professor, Stanford
    • Holden Maecker, Associate Professor (Research) of Microbiology and Immunology, Stanford
  • Burden of Chikungunya and Dengue in Kenya, Kenya, Stanford University (7/1/2013 - 6/30/2018)

    Outbreaks of arthropod-borne viruses, such as dengue (DENV) and chikungunya (CHIKV) viruses, demonstrate the substantial cost and health burden of these emerging/re-emerging health threats to the developing and developed world. In sub-Saharan Africa, routine passive surveillance for these diseases detects only a fraction of their impact, given the high probability of misdiagnosis and unknown levels of transmission across different landscapes and within different susceptible populations. Known and unknown entomologic, environmental, and behavioral factors differentially drive transmission in different habitats. We hypothesize that a significant burden of human disease due to DENV and CHIKV is undetected in the clinical setting, leading to missed opportunities for prevention and heightened risk for large-scale outbreaks. Preliminary data demonstrate that Kenyan children and adults are frequently exposed to DENV and CHIKV, both between and during known outbreaks, although acute arboviral infections are rarely diagnosed in this setting. Our objectives are to assess the true burden of human disease related to DENV strains 1-4 and for CHIKV across Kenya, and then to determine the drivers of viral circulation, estimate the thresholds for outbreak initiation, and provide improved outbreak risk assessment. We will investigate transmission of CHIKV and DENV1-4 in two regions of Kenya that represent heterogeneous degrees of urbanization with varied landscape, climate, and populations. Using several novel approaches, we address the following aims: 1) Quantify the incidence of human infection and disease due to CHIKV and DENV1-4 and determine their relative contribution to acute febrile illness; 2) Measure the level of CHIKV and DENV1-4 circulation in Aedes mosquito vectors and estimate the amount of human-vector contact in Kenya; and 3) Detect and predict spatial and temporal patterns of CHIKV and DENV transmission in rural and urban settings by integrating data on circulation in humans (Aim 1) and vectors (Aim 2) with environmental and weather/climate data collected both in situ and using satellite imagery. This research involves cohorts in and near Msambweni (coastal) and Kisumu (western), Kenya, where there is year-round transmission of arboviruses, and is based on 10 years of collaborative longitudinal studies. Methodologies include analyses of the relationship between well-defined entomologic, clinical, epidemiologic, and climatologic findings and immune biomarkers of virus and mosquito exposure. These studies will fill knowledge gaps about the persistence of CHIKV and DENV in local habitats and the factors that contribute to persistence during inter-epidemic periods and to regional variation during epidemic periods. The data will also answer fundamental questions about arboviral etiologies in severe fever syndromes among at-risk populations while providing better estimates of related disease burden and long-term sequelae.

    Location

    Kenya

  • Integrated Vector Management as a Strategy for Reduced Disease Risk in a Newly Discovered Region of Dengue Fever in Africa, Stanford (9/1/2015 - 8/31/2020)

    The LaBeaud lab currently has an NIH R01 grant that studies acute dengue and chikungunya infection and disease in Kenyan children and measures circulation of these infections in vectors at all life stages (eggs, larvae, pupae, and adults). The planned study will capitalize on this data by allowing us to link child seroprevalence information with the control interventions to enable measurement of changes in disease incidence as a result of our planned child and community interventions. The ongoing vector sampling in our R01 study will allow us to easily perform the planned vector assessments (pupal and larval surveys) and maintain the highly trained human capital that will allow accurate measurement of our primary study outcome (pupal productivity). This study will transform years of successful field work into child and community focused benefits that will promote improved integrated vector management using sustainable grass-roots methods, results that will matter greatly to the study participants.
    Although the immediate benefits of this study will be for Kenyan children and their families, the methods employed will be generalizable to all children of the world, as children in Africa, Asia, and the Americas are all at risk for these infections. Although children are at greater risk for arboviral exposures than adults, previous surveys have rarely focused on this vulnerable population, yielding only imprecise estimates of disease burden among the pediatric (and general) population. CHIKV is now circulating in Florida and is likely to spread throughout the US. DENV has been circulating in Florida since 2009. The vectors for DENV and CHIKV have recently been identified locally in Hayward, Fresno and Menlo Park. Both mild and severe arboviral disease, including CHIKV, are known to cause chronic arthritic, neurologic and ocular sequelae in children. Cheap, sustainable methods of integrated vector management, as planned in this study, will be tested for their efficacy in preventing vector development and human virus exposure. Because there are no therapeutics or vaccines for these infections, vector control is the main strategy for prevention.
    This project is funded by The Bechtel Faculty Scholar Fund and Stanford Child Health Research Institute (CHRI).

    Location

    Kenya

    Collaborators

    • Jenna Forsyth, PhD Student, E-IPER, Stanford
    • Nicole Ardoin, Associate Professor of Education and Senior Fellow at the Woods Institute for the Environment, Stanford
  • Characterization of Immune Factors of Severe and Chronic Chikungunya Disease in Grenada, West Indies, Stanford (8/1/2015 - 7/31/2016)

    CHIKV, an infectious cause of long-term chronic arthritis, is a communicable disease that evolves into a disabling non-communicable disease that can last for years; therefore, understanding how CHIKV-related arthritis is mediated and how it can be prevented will result in large savings of human health burden and costs. CHIKV introduction into Grenada in 2014 led to large outbreaks with substantial chronic disease burden. We hypothesize that specific measurable host and viral factors underpin these chronic sequelae. Preliminary data demonstrate that both host and viral factors are essential to determine CHIKV human disease outcome, but the most important drivers of disease have not been elucidated. Severe disease is also linked to host factors such as comorbidities and specific host immune responses. In the proposed research, through combined studies of humans and viral isolates, we will determine the influential drivers of chronic chikungunya disease in the island country of Grenada, linking disease phenotype and long-term health consequences to viral strain, demography, and host immune response.

    Location

    Grenada

  • Miniaturized Automated Whole Blood Cellular Analysis System, Stanford (6/23/2015 - 6/22/2020)

    Assays of cellular immunity are key to understanding the pathogenesis and mechanisms of control of viral and other infectious diseases. But such assays are difficult to perform as part of clinical studies because they are:

    Labile: They must either be performed on fresh blood, or on PBMC that are cryopreserved within a relatively short time after blood collection.
    Laborious: They require a lot of manual effort, as well as skills and equipment not commonly found at clinical sites.
    Sample-intensive: They tend to require large volumes of blood, particularly if performed on cryopreserved PBMCs.
    These challenges have limited the implementation of cellular immune function assays, particularly in children (where blood draw volumes are most limited) and in remote settings. Yet, children in remote settings are often the most affected by important infectious diseases, and stand the most to gain from advances in vaccines and other methods of control. Therefore, we propose to develop a sample-sparing and fully automated system for stimulation and stabilization of whole blood for functional cellular assays. This system will be based on the concepts pioneered by Smart Tube, Inc. in their existing whole blood stimulation system, but will use 80% less blood, and provide full automation, so that all pipetting steps are eliminated. It will withdraw blood directly from a collection tube, using as little as 2 cc, distribute the blood into multiple incubation chambers where it will be stimulated with lyophilized, pre-configured reagents (antigens, mitogens, etc.) to assay cellular function, then stabilized with a proteomic stabilizer for later analysis.

    The results of this study will not only validate the blood collection system’s performance, but will provide valuable biological data on the cellular response to these viruses in children. The blood collection system, in turn, will be useful for many different kinds of studies of cellular immunity, particularly in remote settings and situations where samples are limiting. The end result should be much more rapid advancement of our understanding of disease pathogenesis and of vaccine development for important infectious agents.

    Location

    Kenya

    Collaborators

    • Holden Maecker, Associate Professor (Research) of Microbiology and Immunology, Stanford
  • Complex Data and Deep Learning for Disease Outbreak Prediction, Stanford (1/1/2017 - 1/1/2018)

    Disease outbreaks are not easily predicted because they occur only when multiple factors trigger the rapid spread of disease. Key factors can often be identified, e.g., excess rainfall leading to outbreaks of Rift Valley fever virus (RVFV)1,2, but the complex circumstances that lead to outbreaks remain elusive for several reasons. First, gathering varied datasets (climatic, genetics, demographic, historical, and behavioral) is time consuming and expensive. Second, the computing capabilities to mine and analyze such varied and complex datasets has not been available until recently. In this application using RVFV as a case study, we propose to model the interplay between vectors, livestock, wildlife, climate, and humans. Large historic and modern datasets are accessible to the key investigators and will be aggregated into a repository. In collaboration with an industry partner, we will then apply machine learning to construct models for inference and prediction of RVFV outbreaks. We achieve broad applicability by separating data gathering from deep learning and execution. As such, once data curation and conversion of a dataset has been completed, one can take advantage of deep learning in the absence of a computer expert. As deep learning makes few assumptions about the data, this approach is transferable to other outbreak scenarios and diseases.
    Rift Valley fever (RVF) is a deadly vector-borne disease that infects livestock and humans3–6. Transmitted via mosquitoes to livestock7, it can decimate entire herds and cause catastrophic economic hardship8. Humans are exposed via vector and animal transmission: animal husbandry, slaughter and butchery, and ingesting diseased meat, milk, and blood9,10. RVFV is endemic throughout much of Africa, but has recently caused outbreaks the Middle East11,12 and has significant potential to spread to the EU and USA, where all the necessary vectors and hosts to allow transmission are present13–15. Our proposal initiates a new collaboration between faculty who are uniquely suited to investigate RVF and use DL and diverse datasets to predict RVF outbreaks. Dr. LaBeaud brings clinical expertise in RVF transmission and epidemiology3–6,16,17. Dr. Seetah brings expertise in historical climate, meat processing as ‘social and economic’ practice, and is a trained butcher. We collaborate with Dr. Kumm, CEO of insightAI, to adapt their GPU-based deep-learning platform to “learn” what triggers RVF outbreaks. All three have worked in Kenya and have established in-country networks. In addition, the team is in discussion with IBM who has recently acquired weather.com, providing access to a massive database of past climate. This transformative, cross-disciplinary research project meets all CIGH priority areas: climate change and global health, new solutions to improve health care delivery, new interdisciplinary collaborations among faculty, and is a high-impact, high-risk project that lends itself to implementation among stakeholders in both endemic and at risk regions of the world.

    Location

    Kenya

    Collaborators

    • Krish Seetah, Assistant Professor of Anthropology, Stanford University
  • Predicting dengue transmission in a changing climate to improve mosquito control, Stanford University (Depts of Biology and Pediatrics) (7/1/2016 - 6/30/2018)

    Dengue, Zika, chikungunya, and other Aedes aegypti-transmitted viruses are a major concern throughout the tropics and sub-tropics, and better mosquito control could dramatically reduce disease burden. Mosquito control is currently inefficient and poorly targeted in part because of a general lack of mosquito surveillance data in most places. Understanding the links between climate, mosquito abundance, and dengue infections would promote a more effective allocation of costly and sometimes environmentally damaging mosquito control resources, such as insecticides. This project will develop improved models that use satellite imagery to predict the climate suitability for dengue transmission, and integrate the improved models into current decision-making procedures on vector control.

    Location

    Kenya and Ecuador

    Collaborators

    • Erin Mordecai, Assistant Professor of Biology, Stanford
    • Eric Lambin, George and Setsuko Ishiyama Provostial Professor and Senior Fellow at the Woods Institute for the Environment, Stanford
  • The Spectrum of Zika Virus Disease in Grenada, Stanford (1/1/2017 - 1/1/2018)

    Arthropod-borne viruses (arboviruses) comprise many of the most important emerging pathogens due to their geographic expansion and their increasing impact on vulnerable populations. In 2015, Zika virus (ZIKV) became the newest emerging public health threat to Latin America, with more than 14,000 cases in Salvador, Brazil, and accruing substantial evidence of resultant Guillain-Barré and microcephaly. After severe outbreaks of chikungunya virus (CHIKV) wherein some islands experienced more than 90% of residents infected, the Caribbean islands are now witnessing large- scale ZIKV exposure and infection. We propose to determine the true incidence of ZIKV compared to CHIKV and dengue virus (DENV) disease in Grenada, and identify the demographic and ecological drivers for ZIKV transmission and disease. Serum collected from participants will be tested by ELISA and PCR to document acute ZIKV infection and characterize the spectrum of disease, severity and impact of ZIKV in Grenada. Participants, especially pregnant women, will be followed to determine long-term consequences of ZIKV disease, including any microcephaly resulting from antenatal ZIKV infection. Clinical manifestations of disease in those with and without prior DENV infection will be compared to determine if previous DENV exposure alters resultant Zika disease. This information will provide crucial data to determine the full spectrum and medical sequelae from ZIKV in a naïve population.

    Location

    Grenada

  • Neurodevelopment and Vector-borne Diseases: Building Research Capacity in the Tropics, Stanford (September 1, 2016 - 8/31/2018)

    Vector-borne diseases (VBD) pose a significant economic and public health threat throughout developing
    tropical regions worldwide, including the Caribbean. The introduction in December 2013 and rapid spread of
    the chikungunya virus (CHIKV) throughout all the Caribbean nations, and more recently the emergence of the
    zika virus in Suriname and Martinique highlights the need to develop regional capacity to investigate, predict,
    contain, and respond to VBD. For example, recent evidence from la Réunion suggests that CHIKV can
    negatively impact neurodevelopment among infants born to mothers who were infected with the virus during
    pregnancy. However, these results have not yet been replicated in other sites internationally – such as the
    Caribbean – nor have any longitudinal studies been carried out to follow children who have experienced
    neurocognitive delay related to CHIKV infection. To address the paucity of data while building VBD research
    capacity in tropical LMICs where these diseases are endemic and the burden of impaired neurodevelopment is
    felt most, researchers from St. George’s University (SGU) in Grenada will partner with researchers from
    Stanford University, Oxford University, and the Université de La Réunion to: (1) Determine the prevalence of
    mother to child transmission of CHIKV in Grenadian pregnant mothers; (2) Measure the neurodevelopment of
    children at 2 years of age exposed at different trimesters in utero to CHIKV and compare them with unexposed
    children; (3) Assess the burden of confounding factors to better understand the specific impact of VBD on
    neurodevelopment and inform public health priorities; (4) Build local capacity for arboviral and
    neurodevelopmental testing at SGU. To achieve Aim 1, 379 moms and their infants who were born during the
    CHIKV outbreak in Grenada, 473 moms and their infants who were born after the outbreak and may have been
    exposed to the virus in utero, and 190 moms and their infants who were born at least nine months after the
    outbreak (and thus, very unlikely to be exposed to the virus in utero) will complete a survey detailing the onset
    and symptoms related to their CHIKV infection and will then be tested for exposure to CHIKV by ELISA. Non
    CHIKV-exposed infants and moms, CHIKV-exposed moms but not infants, CHIKV-exposed moms and infants,
    and time of exposure during pregnancy will be used to divide groups for neurocognitive comparison at 2-years
    of age. To achieve Aims 2 and 3, we will administer the intergrowth 21st Neurodevelopment Assessment – a
    holistic assessment of early child development developed at Oxford University – while controlling for
    confounding neurodevelopmental factors. To achieve Aim 4, we will establish a Regional Center for Child
    Neurodevelopment while addressing seven key areas of needed research support: (1) Financial (i.e., granting);
    (2) Expertise; (3) On-the-ground human resources; (4) Student trainees to build local capacity; (5) Equipment,
    IT, and facilities support; (6) On-the-ground university and research institute administrative support; and (7)
    Local and regional government, relevant NGO, and professional/academic institutional support.

    Location

    Grenada

  • Trash to Treasure: Collecting trash for profit to reduce vector breeding sites in Kwale County, Bova Network (9/2018 - 8/2019)

    Location

    Kwale County, Kenya

  • Assessment of cognitive functioning in children exposed to the Zika virus, USAID (4/2018 - December 2018)

    Location

    Africa

Teaching

2018-19 Courses

Stanford Advisees

  • Postdoctoral Faculty Sponsor
    Amy Krystosik, Melisa Shah
  • Doctoral Dissertation Reader (NonAC)
    Haripriya Vaidehi Narayanan

Publications

All Publications

  • Making Pastoralists Count: Geospatial Methods for the Health Surveillance of Nomadic Populations. The American journal of tropical medicine and hygiene Wild, H., Glowacki, L., Maples, S., Mejia-Guevara, I., Krystosik, A., Bonds, M. H., Hiruy, A., LaBeaud, A. D., Barry, M. 2019

    Abstract

    Nomadic pastoralists are among the world's hardest-to-reach and least served populations. Pastoralist communities are difficult to capture in household surveys because of factors including their high degree of mobility over remote terrain, fluid domestic arrangements, and cultural barriers. Most surveys use census-based sampling frames which do not accurately capture the demographic and health parameters of nomadic populations. As a result, pastoralists are "invisible" in population data such as the Demographic and Health Surveys (DHS). By combining remote sensing and geospatial analysis, we developed a sampling strategy designed to capture the current distribution of nomadic populations. We then implemented this sampling frame to survey a population of mobile pastoralists in southwest Ethiopia, focusing on maternal and child health (MCH) indicators. Using standardized instruments from DHS questionnaires, we draw comparisons with regional and national data finding disparities with DHS data in core MCH indicators, including vaccination coverage, skilled birth attendance, and nutritional status. Our field validation demonstrates that this method is a logistically feasible alternative to conventional sampling frames and may be used at the population level. Geospatial sampling methods provide cost-affordable and logistically feasible strategies for sampling mobile populations, a crucial first step toward reaching these groups with health services.

    View details for DOI 10.4269/ajtmh.18-1009

    View details for PubMedID 31436151

  • Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children. BMJ open Wilder-Smith, A., Wei, Y., Araujo, T. V., VanKerkhove, M., Turchi Martelli, C. M., Turchi, M. D., Teixeira, M., Tami, A., Souza, J., Sousa, P., Soriano-Arandes, A., Soria-Segarra, C., Sanchez Clemente, N., Rosenberger, K. D., Reveiz, L., Prata-Barbosa, A., Pomar, L., Pela Rosado, L. E., Perez, F., Passos, S. D., Nogueira, M., Noel, T. P., Moura da Silva, A., Moreira, M. E., Morales, I., Miranda Montoya, M. C., Miranda-Filho, D. d., Maxwell, L., Macpherson, C. N., Low, N., Lan, Z., LaBeaud, A. D., Koopmans, M., Kim, C., Joao, E., Jaenisch, T., Hofer, C. B., Gustafson, P., Gerardin, P., Ganz, J. S., Dias, A. C., Elias, V., Duarte, G., Debray, T. P., Cafferata, M. L., Buekens, P., Broutet, N., Brickley, E. B., Brasil, P., Brant, F., Bethencourt, S., Benedetti, A., Avelino-Silva, V. L., Ximenes, R. A., Alves da Cunha, A., Alger, J., Zika Virus Individual Participant Data Consortium, Abreu de Carvalho, L. M., Batista, R., Bertozzi, A. P., Carles, G., Cotrim, D., Damasceno, L., Dimitrakis, L., Duarte Rodrigues, M. M., Estofolete, C. F., Fragoso da Silveira Gouvea, M. I., Fumado-Perez, V., Gazeta, R. E., Kaydos-Daniels, N., Gilboa, S., Krystosik, A., Lambert, V., Lopez-Hortelano, M. G., Mussi-Pinhata, M. M., Nelson, C., Nielsen, K., Oliani, D. M., Rabello, R., Ribeiro, M., Rockx, B., Rodrigues, L. C., Salgado, S., Silveira, K., Sulleiro, E., Tong, V., Valencia, D., De Souza, W. V., Villar Centeno, L. A., Zin, A. 2019; 9 (6): e026092

    Abstract

    INTRODUCTION: Zika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.METHODS AND ANALYSIS: We will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.ETHICS AND DISSEMINATION: The IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.TRIAL REGISTRATION NUMBER: PROSPERO International prospective register of systematic reviews (CRD42017068915).

    View details for DOI 10.1136/bmjopen-2018-026092

    View details for PubMedID 31217315

  • GloPID-R report on Chikungunya, O'nyong-nyong and Mayaro virus, part I: Biological diagnostics ANTIVIRAL RESEARCH Pezzi, L., Reusken, C. B., Weaver, S. C., Drexler, J. F., Busch, M., LaBeaud, A. D., Diamond, M. S., Vasilakis, N., Drebot, M. A., Siqueira, A. M., Ribeiro, G. S., Kohl, A., Lecuit, M., Ng, L. P., Gallian, P., de Lamballerie, X., Boyer, S., Brasil, P., Diallo, M., Failloux, A. B., Jaenisch, T., Lourenco-de-Oliveira, R., Neyts, J., Rios, M., Rodriguez-Morales, A. J., Rosa-Freitas, M. G., Sall, A., Simmons, G., Simon, F., Rua, A., GloPID-R Chikungunya O'nyong-n 2019; 166: 66–81

    View details for DOI 10.1016/j.antiviral.2019.03.009

    View details for Web of Science ID 000469522900007

  • Pediatric tropical medicine: The neglected diseases of children PLOS NEGLECTED TROPICAL DISEASES Hotez, P. J., John, A., LaBeaud, A. 2019; 13 (5)

    View details for DOI 10.1371/journal.pntd.0007008

    View details for Web of Science ID 000470188100003

  • The influence of raw milk exposures on Rift Valley fever virus transmission. PLoS neglected tropical diseases Grossi-Soyster, E. N., Lee, J., King, C. H., LaBeaud, A. D. 2019; 13 (3): e0007258

    Abstract

    Rift Valley fever virus (RVFV) is a zoonotic phlebovirus that can be transmitted to humans or livestock by mosquitoes or through direct contact with contaminated bodily fluids and tissues. Exposure to bodily fluids and tissues varies by types of behaviors engaged for occupational tasks, homestead responsibilities, or use in dietary or therapeutic capacities. While previous studies have included milk exposures in their analyses, their primary focus on livestock exposures has been on animal handling, breeding, and slaughter. We analyzed data from multiple field surveys in Kenya with the aim of associating RVFV infection to raw milk exposures from common animal species. Of those with evidence of prior RVFV infection by serology (n = 267), 77.2% engaged in milking livestock compared to 32.0% for 3,956 co-local seronegative individuals (p < 0.001), and 86.5% of seropositive individuals consumed raw milk compared to 33.4% seronegative individuals (p < 0.001). Individuals who milked and also consumed raw milk had greater odds of RVFV exposure than individuals whose only contact to raw milk was through milking. Increased risks were associated with exposure to milk sourced from cows (p < 0.001), sheep (p < 0.001), and goats (p < 0.001), but not camels (p = 0.98 for consuming, p = 0.21 for milking). Our data suggest that exposure to raw milk may contribute to a significant number of cases of RVFV, especially during outbreaks and in endemic areas, and that some animal species may be associated with a higher risk for RVFV exposure. Livestock trade is regulated to limit RVFV spread from endemic areas, yet further interventions designed to fully understand the risk of RVFV exposure from raw milk are imperative.

    View details for PubMedID 30893298

  • The influence of raw milk exposures on Rift Valley fever virus transmission PLOS NEGLECTED TROPICAL DISEASES Grossi-Soyster, E. N., Lee, J., King, C. H., LaBeaud, A. 2019; 13 (3)

    View details for DOI 10.1371/journal.pntd.0007258

    View details for Web of Science ID 000463799300050

  • Parasitic infections during pregnancy need not affect infant antibody responses to early vaccination against Streptococcus pneumoniae, diphtheria, or Haemophilus influenzae type B. PLoS neglected tropical diseases McKittrick, N. D., Malhotra, I. J., Vu, D. M., Boothroyd, D. B., Lee, J., Krystosik, A. R., Mutuku, F. M., King, C. H., LaBeaud, A. D. 2019; 13 (2): e0007172

    Abstract

    BACKGROUND: Globally, vaccine-preventable diseases remain a significant cause of early childhood mortality despite concerted efforts to improve vaccine coverage. One reason for impaired protection may be the influence of prenatal exposure to parasitic antigens on the developing immune system. Prior research had shown a decrease in infant vaccine response after in utero parasite exposure among a maternal cohort without aggressive preventive treatment. This study investigated the effect of maternal parasitic infections on infant vaccination in a more recent setting of active anti-parasitic therapy.METHODOLOGY/PRINCIPAL FINDINGS: From 2013-2015, 576 Kenyan women were tested in pregnancy for malaria, soil-transmitted helminths, filaria, and S. haematobium, with both acute and prophylactic antiparasitic therapies given. After birth, 567 infants received 10-valent S. pneumoniae conjugate vaccine and pentavalent vaccine for hepatitis B, pertussis, tetanus, H. influenzae type B (Hib) and C. diphtheriae toxoid (Dp-t) at 6, 10, and 14 weeks. Infant serum samples from birth, 10 and 14 weeks, and every six months until age three years, were analyzed using a multiplex bead assay to quantify IgG for Hib, Dp-t, and the ten pneumococcal serotypes. Antenatal parasitic prevalence was high; 461 women (80%) had at least one and 252 (43.6%) had two or more infections during their pregnancy, with the most common being malaria (44.6%), S. haematobium (43.9%), and hookworm (29.2%). Mixed models comparing influence of infection on antibody concentration revealed no effect of prenatal infection status for most vaccine outcomes. Prevalences of protective antibody concentrations after vaccination were similar among the prenatal exposure groups.CONCLUSIONS/SIGNIFICANCE: These findings are in contrast with results from our prior cohort study performed when preventive anti-parasite treatment was less frequently given. The results suggest that the treatment of maternal infections in pregnancy may be able to moderate the previously observed effect of antenatal maternal infections on infant vaccine responses.

    View details for PubMedID 30818339

  • Parasitic infections during pregnancy need not affect infant antibody responses to early vaccination against Streptococcus pneumoniae, diphtheria, or Haemophilus influenzae type B PLOS NEGLECTED TROPICAL DISEASES McKittrick, N. D., Malhotra, I. J., Vu, D. M., Boothroyd, D. B., Lee, J., Krystosik, A. R., Mutuku, F. M., King, C. H., LaBeaud, A. 2019; 13 (2)

    View details for DOI 10.1371/journal.pntd.0007172

    View details for Web of Science ID 000459970700056

  • Acute flavivirus and alphavirus infections among childdren in two different areas of Kenya, 2015 Am J Trop Med Hyg Hortion, L., Mutuku, F., Eyherabide, F., Vu, D., Boothroyd, D., Grossi-Soyster, E., King, C., Ndenga, B., LaBeaud, A. 2019; 100 (1): 170-173
  • Acute Flavivirus and Alphavirus Infections among Children in Two Different Areas of Kenya, 2015 AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Hortion, J., Mutuku, F. M., Eyherabide, A. L., Vu, D. M., Boothroyd, D. B., Grossi-Soyster, E. N., King, C. H., Ndenga, B. A., Desiree LaBeaud, A. 2019; 100 (1): 170–73

    View details for DOI 10.4269/ajtmh.18-0297

    View details for Web of Science ID 000455207700036

  • Early Childhood Anemia in a Birth Cohort in Coastal Kenya: Links to Infection and Nutrition. The American journal of tropical medicine and hygiene Kao, J., Mutuku, F., Martin, S., Lee, J., Muinde, J., Mukoko, D., Malhotra, I., King, C. H., LaBeaud, A. D. 2019

    Abstract

    Anemia is known to impact a child's growth and development, but not all anemias are caused by iron deficiency, and the CDC and WHO have emphasized investigating other contributors to anemia. This cross-sectional sub-study of a 2012-2016 maternal-child cohort in coastal Kenya evaluated 244 children and found 185 (76%) to have been anemic on at least one time point since birth. At the time of assessment in 2016, evaluation included a complete blood count, nutritional assessment, and testing for parasitic infections, focusing on the primary outcome of anemia, defined as hemoglobin (Hb) < 11 g/dL. The average age at assessment was 20.5 ± 7 months. Ninety-five percent had a lifetime average Hb in the anemic range. Adjusting for age and gender, prior or current malaria infection (prior: Hb β = -0.99, 95% CI: -1.49 to -0.49, P = 0.01), or having any current infection with hookworm, Trichuris, Strongyloides, Ascaris, and/or malaria (β = -0.84, 95% CI: -1.36 to -0.33, P = 0.01) was associated with decreased current Hb. Nutritional evaluation revealed that children with a declining Hb ate fewer vitamin-A-rich vegetables per week (P = 0.01) or eggs (P = 0.01), drank more milk (P = 0.07), and ate more bread (P = 0.01), and were more likely to live in a household that experienced food shortage (P = 0.05). The high prevalence of anemia, polyparasitism, and dietary insufficiency among children in rural coastal Kenya suggests that remedial interventions will need to address both diet and parasitic infections to effectively combat this significant health threat.

    View details for PubMedID 31074407

  • Pediatric tropical medicine: The neglected diseases of children. PLoS neglected tropical diseases Hotez, P. J., Odom John, A. R., LaBeaud, A. D. 2019; 13 (5): e0007008

    View details for PubMedID 31071087

  • Early Childhood Anemia in a Birth Cohort in Coastal Kenya: Links to Infection and Nutrition AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Kao, J., Mutuku, F., Martin, S., Lee, J., Mwandi, J., Mukoko, D., Malhotra, I., King, C. H., LaBeaud, A. 2019; 101 (1): 242–52

    View details for DOI 10.4269/ajtmh.17-0688

    View details for Web of Science ID 000476680300039

  • Malaria smear positivity among Kenyan children peaks at intermediate temperatures as predicted by ecological models. Parasites & vectors Shah, M. M., Krystosik, A. R., Ndenga, B. A., Mutuku, F. M., Caldwell, J. M., Otuka, V., Chebii, P. K., Maina, P. W., Jembe, Z., Ronga, C., Bisanzio, D., Anyamba, A., Damoah, R., Ripp, K., Jagannathan, P., Mordecai, E. A., LaBeaud, A. D. 2019; 12 (1): 288

    Abstract

    Ambient temperature is an important determinant of malaria transmission and suitability, affecting the life-cycle of the Plasmodium parasite and Anopheles vector. Early models predicted a thermal malaria transmission optimum of 31 °C, later revised to 25 °C using experimental data from mosquito and parasite biology. However, the link between ambient temperature and human malaria incidence remains poorly resolved.To evaluate the relationship between ambient temperature and malaria risk, 5833 febrile children (<18 years-old) with an acute, non-localizing febrile illness were enrolled from four heterogenous outpatient clinic sites in Kenya (Chulaimbo, Kisumu, Msambweni and Ukunda). Thick and thin blood smears were evaluated for the presence of malaria parasites. Daily temperature estimates were obtained from land logger data, and rainfall from National Oceanic and Atmospheric Administration (NOAA)'s Africa Rainfall Climatology (ARC) data. Thirty-day mean temperature and 30-day cumulative rainfall were estimated and each lagged by 30 days, relative to the febrile visit. A generalized linear mixed model was used to assess relationships between malaria smear positivity and predictors including temperature, rainfall, age, sex, mosquito exposure and socioeconomic status.Malaria smear positivity varied between 42-83% across four clinic sites in western and coastal Kenya, with highest smear positivity in the rural, western site. The temperature ranges were cooler in the western sites and warmer in the coastal sites. In multivariate analysis controlling for socioeconomic status, age, sex, rainfall and bednet use, malaria smear positivity peaked near 25 °C at all four sites, as predicted a priori from an ecological model.This study provides direct field evidence of a unimodal relationship between ambient temperature and human malaria incidence with a peak in malaria transmission occurring at lower temperatures than previously recognized clinically. This nonlinear relationship with an intermediate optimal temperature implies that future climate warming could expand malaria incidence in cooler, highland regions while decreasing incidence in already warm regions with average temperatures above 25 °C. These findings support efforts to further understand the nonlinear association between ambient temperature and vector-borne diseases to better allocate resources and respond to disease threats in a future, warmer world.

    View details for DOI 10.1186/s13071-019-3547-z

    View details for PubMedID 31171037

  • Strengthening the Interaction of the Virology Community with the International Committee on Taxonomy of Viruses (ICTV) by Linking Virus Names and Their Abbreviations to Virus Species. Systematic biology Calisher, C. H., Briese, T., Rodney Brister, J., Charrel, R. N., Durrwald, R., Ebihara, H., Fulhorst, C. F., Fu Gao, G., Groschup, M. H., Haddow, A. D., Hyndman, T. H., Junglen, S., Klempa, B., Klingstrom, J., Kropinski, A. M., Krupovic, M., LaBeaud, A. D., Maes, P., Nowotny, N., Roberto Teixeira Nunes, M., Payne, S. L., Radoshitzky, S. R., Rubbenstroth, D., Sabanadzovic, S., Sasaya, T., Stenglein, M. D., Varsani, A., Wahl, V., Weaver, S. C., Zerbini, F. M., Vasilakis, N., Kuhn, J. H. 2018

    Abstract

    The International Committee on Taxonomy of Viruses (ICTV) is tasked with classifying viruses into taxa (orders to species) and devising taxon names. Virus names and virus name abbreviations are currently not within the ICTV's official remit and are not regulated by an official entity. Many scientists, medical/veterinary professionals, and regulatory agencies do not address evolutionary questions nor are they concerned with the hierarchical organization of the viral world and therefore have limited use for ICTV-devised taxa. Instead, these professionals look to the ICTV as an expert point source that provides the most current taxonomic affiliations of viruses of interests to facilitate document writing. These needs are currently unmet as an ICTV-supported, easily-searchable database that includes all published virus names and abbreviations linked to their taxa is not available. In addition, in stark contrast to other biological taxonomic frameworks, virus taxonomy currently permits individual species to have several members. Consequently, confusion emerges among those who are not aware of the difference between taxa and viruses, and because certain well-known viruses cannot be located in ICTV publications or be linked to their species. In addition, the number of duplicate names and abbreviations has increased dramatically in the literature. To solve this conundrum, the ICTV could mandate listing all viruses of established species and all reported unclassified viruses in forthcoming online ICTV Reports and create a searchable webpage using this information. The International Union of Microbiology Societies could also consider changing the mandate of the ICTV to include the nomenclature of all viruses in addition to taxon considerations. With such a mandate expansion, official virus names and name abbreviations could be catalogued and virus nomenclature could be standardized. As a result, the ICTV would become an even more useful resource for all stakeholders in virology.

    View details for PubMedID 30597118

  • Neighborhood Violence Impacts Disease Control and Surveillance: Case Study of Cali, Colombia from 2014 to 2016 INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH Krystosik, A. R., Curtis, A., LaBeaud, A., Davalos, D. M., Pacheco, R., Buritica, P., Alvarez, A. A., Bhatta, M. P., Rojas Palacios, J., James, M. A. 2018; 15 (10)

    View details for DOI 10.3390/ijerph15102144

    View details for Web of Science ID 000448818100086

  • Neighborhood Violence Impacts Disease Control and Surveillance: Case Study of Cali, Colombia from 2014 to 2016. International journal of environmental research and public health Krystosik, A. R., Curtis, A., LaBeaud, A. D., Davalos, D. M., Pacheco, R., Buritica, P., Alvarez, A. A., Bhatta, M. P., Rojas Palacios, J. H., James, M. A. 2018; 15 (10)

    Abstract

    Arboviruses are responsible for a large burden of disease globally and are thus subject to intense epidemiological scrutiny. However, a variable notably absent from most epidemiological analyses has been the impact of violence on arboviral transmission and surveillance. Violence impedes surveillance and delivery of health and preventative services and affects an individual's health-related behaviors when survival takes priority. Moreover, low and middle-income countries bear a disproportionately high burden of violence and related health outcomes, including vector borne diseases. To better understand the epidemiology of arboviral outbreaks in Cali, Colombia, we georeferenced chikungunya (CHIKV), dengue (DENV), and Zika (ZIKV) viral cases from The National System of Surveillance in Public Health between October 2014 and April 2016. We extracted homicide data from the municipal monthly reports and kernel density of homicide distribution from IdeasPaz. Crucially, an overall higher risk of homicide is associated with increased risk of reported DENV, lower rates of acute testing, and higher rates of lab versus clinical discordance. In the context of high violence as a potential barrier to access to preventive health services, a community approach to improve health and peace should be considered.

    View details for PubMedID 30274270

  • Mother-to-child transmission of Chikungunya virus: A systematic review and meta-analysis. PLoS neglected tropical diseases Contopoulos-Ioannidis, D., Newman-Lindsay, S., Chow, C., LaBeaud, A. D. 2018; 12 (6): e0006510

    Abstract

    BACKGROUND: Chikungunya virus (CHIKV) is an emerging arboviral infection with a global distribution and may cause fetal and neonatal infections after maternal CHIKV-infections during gestation.METHODOLOGY: We performed a systematic review to evaluate the risk for: a) mother-to-child transmission (MTCT), b) antepartum fetal deaths (APFD), c) symptomatic neonatal disease, and d) neonatal deaths from maternal CHIKV-infections during gestation. We also recorded the neonatal clinical manifestations after such maternal infections (qualitative data synthesis). We searched PubMed (last search 3/2017) for articles, of any study design, with any of the above outcomes. We calculated the overall risk of MTCT, APFDs and risk of symptomatic neonatal disease by simple pooling. For endpoints with ≥5 events in more than one study, we also synthesized the data by random-effect-model (REM) meta-analysis.PRINCIPAL FINDINGS: Among 563 identified articles, 13 articles from 8 cohorts were included in the quantitative data synthesis and 33 articles in the qualitative data synthesis. Most cohorts reported data only on symptomatic rather than on all neonatal infections. By extrapolation also of these data, the overall pooled-MTCT-risk across cohorts was at least 15.5% (206/1331), (12.6% by REMs). The pooled APFD-risk was 1.7% (20/1203); while the risk of CHIKV-confirmed-APFDs was 0.3% (3/1203). Overall, the pooled-risk of symptomatic neonatal disease was 15.3% (203/1331), (11.9% by REMs). The pooled risk of symptomatic disease was 50.0% (23/46) among intrapartum vs 0% (0/712) among antepartum/peripartum maternal infections. Infected newborns, from maternal infections during gestation were either asymptomatic or presented within their first week of life, but not at birth, with fever, irritability, hyperalgesia, diffuse limb edema, rashes and occasionally sepsis-like illness and meningoencephalitis. The pooled-risk of neonatal death was 0.6% (5/832) among maternal infections and 2.8% (5/182) among neonatal infections; long-term neurodevelopmental delays occurred in 50% of symptomatic neonatal infections.CONCLUSIONS/SIGNIFICANCE: Published cohorts with data on the risk to the fetus and/or newborn from maternal CHIKV-infections during gestation were sparse compared to the number of recently reported CHIKV-infection outbreaks worldwide; however perinatal infections do occur, at high rates during intrapartum period, and can be related to neonatal death and long-term disabilities.

    View details for PubMedID 29897898

  • Mother-to-child transmission of Chikungunya virus: A systematic review and meta-analysis PLOS NEGLECTED TROPICAL DISEASES Contopoulos-Ioannidis, D., Newman-Lindsay, S., Chow, C., LaBeaud, A. 2018; 12 (6)

    View details for DOI 10.1371/journal.pntd.0006510

    View details for Web of Science ID 000437442000019

  • Cord Blood Antiparasite Interleukin 10 as a Risk Marker for Compromised Vaccine Immunogenicity in Early Childhood JOURNAL OF INFECTIOUS DISEASES Malhotra, I., Labeaud, A., Morris, N., Mckibben, M., Mungai, P., Muchiri, E., King, C. L., King, C. H. 2018; 217 (9): 1426–34

    Abstract

    Antenatal exposure to parasites can affect infants' subsequent responses to vaccination. The present study investigated how maternal prenatal infections and newborns' antiparasite cytokine profiles relate to immunoglobulin G (IgG) responses to standard vaccination during infancy.A total of 450 Kenyan women were tested for parasitic infections during pregnancy. Their newborns' responses to Plasmodium falciparum, schistosome, and filaria antigens were assessed in cord blood lymphocytes. Following standard neonatal vaccination, this infant cohort was followed biannually to age 30 months for measurement of circulating IgG levels against Haemophilus influenzae b (Hib), diphtheria toxoid (DT), hepatitis B virus (HBV), and tetanus toxoid.Trajectories of postvaccination IgG levels were classified by functional principal component (PC) analysis to assess each child's response profile. Two main components, PC1, reflecting height of response over time, and PC2, reflecting crossover from high to low responses or from low to high responses, were identified. Cord blood cytokine responses to schistosome and filarial antigens showed a significant association between augmented antihelminth interleukin 10 and reduced antibody levels, particularly to DT and HBV, and a more rapid postvaccination decline in circulating IgG levels against Hib.Antenatal sensitization to schistosomiasis or filariasis and related production of antiparasite interleukin 10 at birth are associated with reduced antivaccine IgG levels in infancy, with possibly impaired protection.

    View details for DOI 10.1093/infdis/jiy047

    View details for Web of Science ID 000430729300014

    View details for PubMedID 29390149

    View details for PubMedCentralID PMC5894090

  • Perinatal Case Fatality Rate Related to Congenital Zika Syndrome in Brazil: A Cross-Sectional Study PEDIATRIC NEUROLOGY Mendes Neto, N. N., da Silva Maia, J., Zacarkim, M., Queiroz, I., Labeaud, A., Aronoff, D. M. 2018; 81: 47–48

    View details for PubMedID 29526344

  • Nasopharyngeal Carriage of Streptococcus pneumoniae in Children in Coastal Kenya. The American journal of tropical medicine and hygiene Heath, C. J., Nayakwadi-Singer, M., King, C. H., Malhotra, I., Mutuku, F., Mukoko, D., LaBeaud, A. D. 2018; 98 (4): 1046–50

    Abstract

    Streptococcus pneumoniae (SP) is a leading cause of child mortality globally, killing around half a million children aged 5 years and less per year. Nasopharyngeal carriage of SP is a prerequisite to disease, and the prevalence of colonization reaches 100% within the first few years of life. Serotype prevalence varies geographically, impacting the serotype coverage of pneumococcal vaccines, and serotype prevalence data are limited from large regions of the world, including sub-Saharan Africa. We enrolled 323 unvaccinated children, aged 4-7 years from coastal Kenya and obtained nasopharyngeal swab samples before and after vaccination with the 10-valent pneumococcal vaccine. Vaccination did not reduce the overall prevalence of pneumococcal carriage in our cohort, with 65 (20%) children colonized before vaccination and 63 (19.4%) colonized postvaccination. However, the prevalence of vaccine-included serotypes (vaccine strains) declined from 43% to 19% of positive swabs, whereas non-vaccine serotypes increased from 46% to 73%. This study contributes to the few data available regarding pneumococcal carriage and serotype prevalence in Kenya and is in concordance with reports of dynamic serotype replacement, driven by vaccine pressure.

    View details for PubMedID 29488456

  • Nasopharyngeal Carriage of Streptococcus pneumoniae in Children in Coastal Kenya AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Heath, C. J., Nayakwadi-Singer, M., King, C. H., Malhotra, I., Mutuku, F., Mukoko, D., LaBeaud, A. 2018; 98 (4): 1046–50

    View details for DOI 10.4269/ajtmh.16-0813

    View details for Web of Science ID 000430958200014

  • Bunyavirus Taxonomy: Limitations and Misconceptions Associated with the Current ICTV Criteria Used for Species Demarcation AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Blitvich, B. J., Beaty, B. J., Blair, C. D., Brault, A. C., Dobler, G., Drebot, M. A., Haddow, A. D., Kramer, L. D., LaBeaud, A., Monath, T. P., Mossel, E. C., Plante, K., Powers, A. M., Tesh, R. B., Turell, M. J., Vasilakis, N., Weaver, S. C. 2018; 99 (1): 11–16

    Abstract

    The International Committee on Taxonomy of Viruses (ICTV) has implemented numerous changes to the taxonomic classification of bunyaviruses over the years. Whereas most changes have been justified and necessary because of the need to accommodate newly discovered and unclassified viruses, other changes are a cause of concern, especially the decision to demote scores of formerly recognized species to essentially strains of newly designated species. This practice was first described in the seventh taxonomy report of the ICTV and has continued in all subsequent reports. In some instances, viruses that share less than 75% nucleotide sequence identity across their genomes, produce vastly different clinical presentations, possess distinct vector and host associations, have different biosafety recommendations, and occur in nonoverlapping geographic regions are classified as strains of the same species. Complicating the matter is the fact that virus strains have been completely eliminated from ICTV reports; thus, critically important information on virus identities and their associated biological and epidemiological features cannot be readily related to the ICTV classification. Here, we summarize the current status of bunyavirus taxonomy and discuss the adverse consequences associated with the reclassification and resulting omission of numerous viruses of public health importance from ICTV reports. As members of the American Committee on Arthropod-borne Viruses, we encourage the ICTV Bunyavirus Study Group to reconsider their stance on bunyavirus taxonomy, to revise the criteria currently used for species demarcation, and to list additional strains of public and veterinary importance.

    View details for PubMedID 29692303

  • Clinical, Serological, and Molecular Observations from a Case Series Study during the Asian Lineage Zika Virus Outbreak in Grenada during 2016 CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY Brenciaglia, M., Noel, T. P., Fields, P. J., Bidaisee, S., Myers, T. E., Nelson, W. M., Venkateswaran, N., Venkateswaran, K., Parameswaran, N., Bahadoor, A., Yearwood, K., Mapp-Alexander, V., Mitchell, G., LaBeaud, A., Macpherson, C. L. 2018: 4635647

    Abstract

    This paper describes the spatial and temporal distribution of cases, demographic characteristics of patients, and clinical manifestations of Zika virus (ZIKV) during the 2016 outbreak in Grenada. The first reported case was recorded in St. Andrew Parish in April, and the last reported case was seen in November, with peak transmission occurring in the last week of June, based on test results. Data were collected from a total of 514 patients, of whom 207 (40%) tested positive for ZIKV. No evidence was found that testing positive for ZIKV infection was related to age, gender, or pregnancy status. Clinical presentation with rash (OR = 2.4, 95% CI = 1.5 to 3.7) or with lymphadenopathy (OR = 1.7, 95% CI = 1.0 to 2.9) were the only reported symptoms consistent with testing positive for ZIKV infection. During the Zika outbreak, the infection rate was 20 clinical cases per 10,000 in the population compared to 41 cases per 10,000 during the chikungunya outbreak in Grenada in 2014 and 17 cases per 10,000 during the dengue outbreak in 2001-2002. Even though the country has employed vector control programs, with no apparent decrease in infection rates, it appears that new abatement approaches are needed to minimize morbidity in future arbovirus outbreaks.

    View details for PubMedID 29623138

  • The Identification of Risk Factors for Chronic Chikungunya Arthralgia in Grenada, West Indies: A Cross-Sectional Cohort Study OPEN FORUM INFECTIOUS DISEASES Heath, C. J., Lowther, J., Noel, T. P., Mark-George, I., Boothroyd, D. B., Mitchell, G., MacPherson, C., LaBeaud, A. 2018; 5 (1): ofx234

    Abstract

    Chikungunya virus (CHIKV) is a re-emerging arboviral pathogen. In 2014, an explosive CHIKV outbreak occurred in Grenada, West Indies, infecting approximately 60% of the population. In approximately 50% of cases, CHIKV infection transitions to painful arthralgia that can persist for years. Elucidation of the risk factors for chronic disease is imperative to the development of effective risk management strategies and specific therapeutics.We conducted a cross-sectional study of 240 people who were tested for CHIKV during the outbreak. We administered questionnaires to examine demographic, behavioral, psychological, social, and environmental factors to identify associations with chronic disease. Physical examinations were performed and persistent symptoms were recorded.Ethnicity and socioeconomic status were not associated with risk of chronic joint pain. Female sex increased risk, and age was demonstrated to be predictive of chronic CHIKV sequelae. Mosquito avoidance behaviors did not reduce risk. Patients suffering joint pains, generalized body ache, and weakness in the extremities during acute infection were more likely to develop chronic arthralgia, and an increased duration of acute disease also increased risk.These data demonstrate that chronic CHIKV affects people across the ethnic and socioeconomic spectrum, and it is not reduced by vector avoidance activity. Increased duration of acute symptoms, in particular acute joint pain, was strongly correlated with the risk of persistent arthralgia, thus effective clinical management of acute CHIKV disease could reduce burden of chronic CHIKV.

    View details for PubMedID 29308412

  • Characteristics of Aedes aegypti adult mosquitoes in rural and urban areas of western and coastal Kenya PLOS ONE Ndenga, B., Mutuku, F., Ngugi, H., Mbakaya, J., Aswani, P., Musunzaji, P., Vulule, J., Mukoko, D., Kitron, U., LaBeaud, A. 2017; 12 (12): e0189971

    Abstract

    Aedes aegypti is the main vector for yellow fever, dengue, chikungunya and Zika viruses. Recent outbreaks of dengue and chikungunya have been reported in Kenya. Presence and abundance of this vector is associated with the risk for the occurrence and transmission of these diseases. This study aimed to characterize the presence and abundance of Ae. aegypti adult mosquitoes from rural and urban sites in western and coastal regions of Kenya. Presence and abundance of Ae. aegypti adult mosquitoes were determined indoors and outdoors in two western (urban Kisumu and rural Chulaimbo) and two coastal (urban Ukunda and rural Msambweni) sites in Kenya. Sampling was performed using quarterly human landing catches, monthly Prokopack automated aspirators and monthly Biogents-sentinel traps. A total of 2,229 adult Ae. aegypti mosquitoes were collected: 785 (35.2%) by human landing catches, 459 (20.6%) by Prokopack aspiration and 985 (44.2%) by Biogents-sentinel traps. About three times as many Ae. aegypti mosquitoes were collected in urban than rural sites (1,650 versus 579). Comparable numbers were collected in western (1,196) and coastal (1,033) sites. Over 80% were collected outdoors through human landing catches and Prokopack aspiration. The probability of collecting Ae. aegypti mosquitoes by human landing catches was significantly higher in the afternoon than morning hours (P<0.001), outdoors than indoors (P<0.001) and in urban than rural sites (P = 0.008). Significantly more Ae. aegypti mosquitoes were collected using Prokopack aspiration outdoors than indoors (P<0.001) and in urban than rural areas (P<0.001). Significantly more mosquitoes were collected using Biogents-sentinel traps in urban than rural areas (P = 0.008) and in western than coastal sites (P = 0.006). The probability of exposure to Ae. aegypti bites was highest in urban areas, outdoors and in the afternoon hours. These characteristics have major implications for the possible transmission of arboviral diseases and for the planning of surveillance and control programs.

    View details for PubMedID 29261766

  • Unrecognized Dengue Virus Infections in Children, Western Kenya, 2014-2015 EMERGING INFECTIOUS DISEASES Vu, D. M., Mutai, N., Heath, C. J., Vulule, J. M., Mutuku, F. M., Ndenga, B. A., LaBeaud, A. 2017; 23 (11): 1915–17

    Abstract

    We detected a cluster of dengue virus infections in children in Kenya during July 2014-June 2015. Most cases were serotype 1, but we detected all 4 serotypes, including co-infections with 2 serotypes. Our findings implicate dengue as a cause of febrile illness in this population and highlight a need for robust arbovirus surveillance.

    View details for DOI 10.3201/eid2311.170807

    View details for Web of Science ID 000413109500030

    View details for PubMedID 29048283

    View details for PubMedCentralID PMC5652413

  • Serological and spatial analysis of alphavirus and flavivirus prevalence and risk factors in a rural community in western Kenya PLOS NEGLECTED TROPICAL DISEASES Grossi-Soyster, E. N., Cook, E. J., de Glanville, W. A., Thomas, L. F., Krystosik, A. R., Lee, J., Wamae, C., Kariuki, S., Fevre, E. M., LaBeaud, A. 2017; 11 (10): e0005998

    Abstract

    Alphaviruses, such as chikungunya virus, and flaviviruses, such as dengue virus, are (re)-emerging arboviruses that are endemic in tropical environments. In Africa, arbovirus infections are often undiagnosed and unreported, with febrile illnesses often assumed to be malaria. This cross-sectional study aimed to characterize the seroprevalence of alphaviruses and flaviviruses among children (ages 5-14, n = 250) and adults (ages 15 ≥ 75, n = 250) in western Kenya. Risk factors for seropositivity were explored using Lasso regression. Overall, 67% of participants showed alphavirus seropositivity (CI95 63%-70%), and 1.6% of participants showed flavivirus seropositivity (CI95 0.7%-3%). Children aged 10-14 were more likely to be seropositive to an alphavirus than adults (p < 0.001), suggesting a recent transmission period. Alphavirus and flavivirus seropositivity was detected in the youngest participants (age 5-9), providing evidence of inter-epidemic transmission. Demographic variables that were significantly different amongst those with previous infection versus those without infection included age, education level, and occupation. Behavioral and environmental variables significantly different amongst those in with previous infection to those without infection included taking animals for grazing, fishing, and recent village flooding. Experience of recent fever was also found to be a significant indicator of infection (p = 0.027). These results confirm alphavirus and flavivirus exposure in western Kenya, while illustrating significantly higher alphavirus transmission compared to previous studies.

    View details for PubMedID 29040262

  • Principles, practices and knowledge of clinicians when assessing febrile children: a qualitative study in Kenya MALARIA JOURNAL Hooft, A. M., Ripp, K., Ndenga, B., Mutuku, F., Vu, D., Baltzell, K., Masese, L. N., Vulule, J., Mukoko, D., LaBeaud, A. 2017; 16: 381

    Abstract

    Clinicians in low resource settings in malaria endemic regions face many challenges in diagnosing and treating febrile illnesses in children. Given the change in WHO guidelines in 2010 that recommend malaria testing prior to treatment, clinicians are now required to expand the differential when malaria testing is negative. Prior studies have indicated that resource availability, need for additional training in differentiating non-malarial illnesses, and lack of understanding within the community of when to seek care play a role in effective diagnosis and treatment. The objective of this study was to examine the various factors that influence clinician behavior in diagnosing and managing children presenting with fever to health centres in Kenya.A total of 20 clinicians (2 paediatricians, 1 medical officer, 2 nurses, and 15 clinical officers) were interviewed, working at 5 different government-sponsored public clinic sites in two areas of Kenya where malaria is prevalent. Clinicians were interviewed one-on-one using a structured interview technique. Interviews were then analysed qualitatively for themes.The following five themes were identified: (1) Strong familiarity with diagnosis of malaria and testing for malaria; (2) Clinician concerns about community understanding of febrile illness, use of traditional medicine, delay in seeking care, and compliance; (3) Reliance on clinical guidelines, history, and physical examination to diagnose febrile illness and recognize danger signs; (4) Clinician discomfort with diagnosis of primary viral illness leading to increased use of empiric antibiotics; and (5) Lack of resources including diagnostic testing, necessary medications, and training modalities contributes to the difficulty clinicians face in assessing and treating febrile illness in children. These themes persisted across all sites, despite variation in levels of medical care. Within these themes, clinicians consistently expressed a need for reliable basic testing, especially haemograms and bacterial cultures. Clinicians discussed the use of counseling and education to improve community understanding of febrile illness in order to decrease preventable deaths in children.Results of this study suggest that since malarial testing has become more widespread, clinicians working in resource-poor environments still face difficulty when evaluating a child with fever, especially when malaria testing is negative. Improving access to additional diagnostics, continuing medical education, and ongoing evaluation and revision of clinical guidelines may lead to more consistent management of febrile illness by providers, and may potentially decrease prescription of unnecessary antibiotics. Additional interventions at the community level may also have an important role in managing febrile illness, however, more studies are needed to identify targets for intervention at both the clinic and community levels.

    View details for PubMedID 28931399

  • Current Status of Rift Valley Fever Vaccine Development VACCINES Faburay, B., LaBeaud, A., McVey, D., Wilson, W. C., Richt, J. A. 2017; 5 (3)

    View details for DOI 10.3390/vaccines5030029

    View details for Web of Science ID 000411994000014

  • Characterization and productivity profiles of Aedes aegypti (L.) breeding habitats across rural and urban landscapes in western and coastal Kenya PARASITES & VECTORS Ngugi, H. N., Mutuku, F. M., Ndenga, B. A., Musunzaji, P. S., Mbakaya, J. O., Aswani, P., Irungu, L. W., Mukoko, D., Vulule, J., Kitron, U., LaBeaud, A. D. 2017; 10: 331

    Abstract

    Aedes aegypti, the principal vector for dengue and other emerging arboviruses, breeds preferentially in various man-made and natural container habitats. In the absence of vaccine, epidemiological surveillance and vector control remain the best practices for preventing dengue outbreaks. Effective vector control depends on a good understanding of larval and adult vector ecology of which little is known in Kenya. In the current study, we sought to characterize breeding habitats and establish container productivity profiles of Ae. aegypti in rural and urban sites in western and coastal Kenya.Twenty sentinel houses in each of four study sites (in western and coastal Kenya) were assessed for immature mosquito infestation once a month for a period of 24 months (June 2014 to May 2016). All water-holding containers in and around the households were inspected for Ae. aegypti larvae and pupae.Collections were made from a total of 22,144 container visits: Chulaimbo (7575) and Kisumu (8003) in the west, and from Msambweni (3199) and Ukunda (3367) on the coast. Of these, only 4-5.6% were positive for Ae. aegypti immatures. In all four sites, significantly more positive containers were located outdoors than indoors. A total of 17,537 Ae. aegypti immatures were sampled from 10 container types. The most important habitat types were buckets, drums, tires, and pots, which produced over 75% of all the pupae. Key outdoor containers in the coast were buckets, drums and tires, which accounted for 82% of the pupae, while pots and tires were the only key containers in the western region producing 70% of the pupae. Drums, buckets and pots were the key indoor containers, producing nearly all of the pupae in the coastal sites. No pupae were collected indoors in the western region. The coastal region produced significantly more Ae. aegypti immatures than the western region both inside and outside the sentinel houses.These results indicate that productive Ae. aegypti larval habitats are abundant outdoors and that only a few containers produce a majority of the pupae. Although the numbers were lower, productive habitats were detected within households. Targeting source reduction efforts towards these productive containers both inside and outside homes is likely to be a cost-effective way to reduce arboviral transmission in these regions.

    View details for PubMedID 28701194

  • The sero-epidemiology of Rift Valley fever in people in the Lake Victoria Basin of western Kenya PLOS NEGLECTED TROPICAL DISEASES Cook, E., Grossi-Soyster, E., de Glanville, W., Thomas, L., Kariuki, S., Bronsvoort, B., Wamae, C., LaBeaud, A., Fevre, E. 2017; 11 (7): e0005731

    Abstract

    Rift Valley fever virus (RVFV) is a zoonotic arbovirus affecting livestock and people. This study was conducted in western Kenya where RVFV outbreaks have not previously been reported. The aims were to document the seroprevalence and risk factors for RVFV antibodies in a community-based sample from western Kenya and compare this with slaughterhouse workers in the same region who are considered a high-risk group for RVFV exposure. The study was conducted in western Kenya between July 2010 and November 2012. Individuals were recruited from randomly selected homesteads and a census of slaughterhouses. Structured questionnaire tools were used to collect information on demographic data, health, and risk factors for zoonotic disease exposure. Indirect ELISA on serum samples determined seropositivity to RVFV. Risk factor analysis for RVFV seropositivity was conducted using multi-level logistic regression. A total of 1861 individuals were sampled in 384 homesteads. The seroprevalence of RVFV in the community was 0.8% (95% CI 0.5-1.3). The variables significantly associated with RVFV seropositivity in the community were increasing age (OR 1.2; 95% CI 1.1-1.4, p<0.001), and slaughtering cattle at the homestead (OR 3.3; 95% CI 1.0-10.5, p = 0.047). A total of 553 slaughterhouse workers were sampled in 84 ruminant slaughterhouses. The seroprevalence of RVFV in slaughterhouse workers was 2.5% (95% CI 1.5-4.2). Being the slaughterman, the person who cuts the animal's throat (OR 3.5; 95% CI 1.0-12.1, p = 0.047), was significantly associated with RVFV seropositivity. This study investigated and compared the epidemiology of RVFV between community members and slaughterhouse workers in western Kenya. The data demonstrate that slaughtering animals is a risk factor for RVFV seropositivity and that slaughterhouse workers are a high-risk group for RVFV seropositivity in this environment. These risk factors have been previously reported in other studies providing further evidence for RVFV circulation in western Kenya.

    View details for PubMedID 28686589

  • 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)

    Abstract

    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

  • Parasitic Infections in Pregnancy Decrease Placental Transfer of Antipneumococcus Antibodies. Clinical and vaccine immunology McKittrick, N. D., Vu, D. M., Malhotra, I., King, C. H., Mutuku, F., LaBeaud, A. D. 2017; 24 (6)

    Abstract

    Many factors can influence maternal placental antibody transfer to the fetus, which confers important immune protection to the newborn infant. However, little is known about the effect of maternal parasitic infection on placental antibody transfer. To investigate this, we selected, from a parent study of 576 pregnant Kenyan women, four groups of women with term deliveries (≥37 weeks), including uninfected women (N=30) and women with solo infections of malaria (N=30), hookworm (N=30), or schistosomiasis (N=10). Maternal plasma at delivery and infant cord blood were tested via multiplex fluorescent bead assay for IgG against ten pneumococcal serotypes (PnPs 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F), diphtheria toxoid, and Haemophilus influenzae type B. Infants born to mothers with prenatal malaria, hookworm, or S. haematobium infections were associated with a significantly reduced ratio of maternal:infant cord blood antibody concentration for S. pneumoniae serotypes 1, 4, 5, 6B, 7F, 9V, and 18C compared to infants of uninfected mothers. Anti-diphtheria toxoid and anti-H. influenzae type B IgG ratios were not significantly different among infection groups. Prenatal parasitic infections decrease the transfer of maternal IgG antibodies to infants for several serotypes of S. pneumoniae.

    View details for DOI 10.1128/CVI.00039-17

    View details for PubMedID 28404574

  • Chikungunya Virus. Clinics in laboratory medicine Vu, D. M., Jungkind, D., Angelle Desiree LaBeaud 2017; 37 (2): 371-382

    Abstract

    For chikungunya virus (CHIKV), the long-term sequelae from infection are yet ill-defined. The prolonged debilitating arthralgia associated with CHIKV infection has tremendous potential for impacting the global economy and should be considered when evaluating the human burden of disease and the allocation of resources. There is much still unknown about CHIKV and the illnesses that it causes. Developing a better understanding of the pathogenesis of CHIKV infection is a priority and forms the basis for developing effective strategies at infection prevention and disease control.

    View details for DOI 10.1016/j.cll.2017.01.008

    View details for PubMedID 28457355

  • Malaria and Chikungunya Detected Using Molecular Diagnostics Among Febrile Kenyan Children OPEN FORUM INFECTIOUS DISEASES Waggoner, J., Brichard, J., Mutuku, F., Ndenga, B., Heath, C., Mohamed-Hadley, A., Sahoo, M. K., Vulule, J., Lefterova, M., BanaeiA, N., Mukoko, D., Pinsky, B. A., LaBeaud, A. 2017; 4 (3): ofx110

    Abstract

    In sub-Saharan Africa, malaria is frequently overdiagnosed as the cause of an undifferentiated febrile illness, whereas arboviral illnesses are presumed to be underdiagnosed.Sera from 385 febrile Kenyan children, who presented to 1 of 4 clinical sites, were tested using microscopy and real-time molecular assays for dengue virus (DENV), chikungunya virus (CHIKV), malaria, and Leptospira.Malaria was the primary clinical diagnosis for 254 patients, and an arboviral infection (DENV or CHIKV) was the primary diagnosis for 93 patients. In total, 158 patients (41.0%) had malaria and 32 patients (8.3%) had CHIKV infections. Compared with real-time polymerase chain reaction, microscopy demonstrated a percent positive agreement of 49.7%. The percentage of malaria cases detected by microscopy varied significantly between clinical sites. Arboviral infections were the clinical diagnosis for patients on the Indian Ocean coast (91 of 238, 38.2%) significantly more often than patients in the Lake Victoria region (2 of 145, 1.4%; P < .001). However, detection of CHIKV infections was significantly higher in the Lake Victoria region (19 of 145 [13.1%] vs 13 of 239 [5.4%]; P = .012).The clinical diagnosis of patients with an acute febrile illness, even when aided by microscopy, remains inaccurate in malaria-endemic areas, contributing to inappropriate management decisions.

    View details for PubMedID 28702473

  • Pneumococcal Vaccine Response After Exposure to Parasites in Utero, in Infancy, or Mid-Childhood PEDIATRICS Singer, M. N., Heath, C., Muinde, J., Gildengorin, V., Mutuku, F. M., Vu, D., Mukoko, D., King, C. L., Malhotra, I. J., King, C. H., LaBeaud, A. D. 2017; 139 (4)

    Abstract

    Streptococcus pneumoniae is a leading cause of mortality before age 5, but few studies examine details of childhood response to pneumococcal vaccine in less-developed settings. Although malnutrition, HIV, and concurrent infections can impair response, evidence suggests that chronic parasitic infections can also contribute to poor vaccination results. The objective of this study was to determine whether response to pneumococcal vaccine varied among children either exposed to parasitic infections in utero, previously infected in infancy, or infected at the time of immunization.Children from a 2006 to 2010 maternal-infant cohort were eligible for the current study. Children were screened for malaria, schistosomiasis, filariasis, intestinal helminths, and protozoa. Data on in utero exposure and early life infections were linked, and baseline antipneumococcal immunoglobulin G levels and nasopharyngeal carrier status were determined. Participants received decavalent pneumococcal vaccine, and 4 weeks later, serology was repeated to assess vaccine response.A total of 281 children were included. Preimmunity was associated with greater postvaccination increments in anti-pneumococcal polysaccharide immunoglobulin G, especially serotypes 4, 7, 9, 18C, and 19. Present-day growth stunting was independently associated with weaker responses to 1, 4, 6B, 7, 9V, and 19. Previous exposure to Trichuris was associated with stronger responses to 1, 5, 6B, 7, 18C, and 23, but other parasite exposures were not consistently associated with response.In our cohort, hyporesponsiveness to pneumococcal conjugate vaccine was associated with growth stunting but not parasite exposure. Parasite-related vaccine response deficits identified before age 3 do not persist into later childhood.

    View details for DOI 10.1542/peds.2016-2781

    View details for Web of Science ID 000398602400023

    View details for PubMedID 28302673

  • Clinical aspects of Zika virus. Current opinion in pediatrics Grossi-Soyster, E. N., LaBeaud, A. D. 2017; 29 (1): 102-106

    Abstract

    Zika virus (ZIKV) is a mosquito-borne flavivirus that has caused a sudden and explosive outbreak in South America and the Caribbean in the last year, and has been declared a public health emergency by the WHO. As ZIKV afflicts previously naive populations, more severe clinical presentations and sequelae have been observed. A specific emphasis has been placed on the neurological effects in infants resulting from viral exposure in utero.Acute onset of ZIKV disease is seen in approximately 20% of cases, whereas most individuals (80%) exposed are asymptomatic. Presentation of illness is typically mild, with disease spectrum ranging from arthralgia and rash to encephalitis, myelitis, and Guillain-Barré syndrome. Infants have been uniquely impacted by the current outbreak with significant congenital exposure resulting in permanent neurological defects and developmental complications.The current ZIKV outbreak has illustrated the emergent capabilities of mosquito-borne viruses and the teratogenic nature of ZIKV. Causality and risk factors associated with severe manifestations, as well as chronic sequelae, have yet to be determined. Extensive research is required to understand the molecular mechanisms of infection, develop improved assays for differential diagnosis, and improve overall knowledge of the spectrum of ZIKV disease in order to develop modes of prevention and treatment.

    View details for DOI 10.1097/MOP.0000000000000449

    View details for PubMedID 27870688

  • Dengue and West Nile Virus Transmission in Children and Adults in Coastal Kenya AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Vu, D. M., Banda, T., Teng, C. Y., Heimbaugh, C., Muchiri, E. M., Mungai, P. L., Mutuku, F. M., Brichard, J., Gildengorin, G., Borland, E. M., Powers, A. M., Kitron, U., King, C. H., LaBeaud, A. D. 2017; 96 (1): 141-143

    Abstract

    Dengue virus (DENV) and West Nile virus (WNV) are important reemerging arboviruses that are under-recognized in many parts of Africa due to lack of surveillance. As a part of a study on flavivirus, alphavirus, and parasite exposure in coastal Kenya, we measured neutralizing antibody against DENV and, to evaluate assay specificity, WNV in serum samples that tested positive for serum anti-DENV IgG by enzyme-linked immunosorbent assay. Of 830 anti-DENV IgG-positive samples that were tested for neutralizing activity, 488 (58.8%) neutralized DENV and 94 (11.3%) neutralized WNV. Of children ≤ 10 years of age, 23% and 17% had serum neutralizing antibody to DENV and WNV, respectively, indicating that DENV and WNV transmission has occurred in this region within the past decade. The results suggest that ongoing DENV and WNV transmission continues on the coast of Kenya and supports a need for routine arboviral surveillance in the area to detect and respond to future outbreaks.

    View details for DOI 10.4269/ajtmh.16-0562

    View details for Web of Science ID 000397822900025

  • Current Status of Rift Valley Fever Vaccine Development. Vaccines Faburay, B., LaBeaud, A. D., McVey, D. S., Wilson, W. C., Richt, J. A. 2017; 5 (3)

    Abstract

    Rift Valley Fever (RVF) is a mosquito-borne zoonotic disease that presents a substantial threat to human and public health. It is caused by Rift Valley fever phlebovirus (RVFV), which belongs to the genus Phlebovirus and the family Phenuiviridae within the order Bunyavirales. The wide distribution of competent vectors in non-endemic areas coupled with global climate change poses a significant threat of the transboundary spread of RVFV. In the last decade, an improved understanding of the molecular biology of RVFV has facilitated significant progress in the development of novel vaccines, including DIVA (differentiating infected from vaccinated animals) vaccines. Despite these advances, there is no fully licensed vaccine for veterinary or human use available in non-endemic countries, whereas in endemic countries, there is no clear policy or practice of routine/strategic livestock vaccinations as a preventive or mitigating strategy against potential RVF disease outbreaks. The purpose of this review was to provide an update on the status of RVF vaccine development and provide perspectives on the best strategies for disease control. Herein, we argue that the routine or strategic vaccination of livestock could be the best control approach for preventing the outbreak and spread of future disease.

    View details for PubMedID 28925970

  • Rift Valley Fever Seroprevalence in Coastal Kenya AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Grossi-Soyster, E. N., Banda, T., Teng, C. Y., Muchiri, E. M., Mungai, P. L., Mutuku, F. M., Gildengorin, G., Kitron, U., King, C. H., Labeaud, A. 2017; 97 (1): 115–20

    Abstract

    Rift Valley fever virus (RVFV) causes severe disease in both animals and humans, resulting in significant economic and public health damages. The objective of this study was to measure RVFV seroprevalence in six coastal Kenyan villages between 2009 and 2011, and characterize individual-, household-, and community-level risk factors for prior RVFV exposure. Sera were tested for anti-RVFV IgG via enzyme-linked immunosorbent assay. Overall, 51 (1.8%; confidence interval [CI95] 1.3-2.3) of 2,871 samples were seropositive for RVFV. Seroprevalence differed significantly among villages, and was highest in Jego Village (18/300; 6.0%; CI95 3.6-9.3) and lowest in Magodzoni (0/248). Adults were more likely to be seropositive than children (P < 0.001). Seropositive subjects were less likely to own land or a motor vehicle (P < 0.01), suggesting exposure is associated with lower socioeconomic standing (P = 0.03). RVFV exposure appears to be low in coastal Kenya, although with some variability among villages.

    View details for DOI 10.4269/ajtmh.17-0104

    View details for Web of Science ID 000409523900020

    View details for PubMedID 28719329

    View details for PubMedCentralID PMC5508922

  • Development of a Real-Time Reverse Transcription Polymerase Chain Reaction for O'nyong-nyong Virus and Evaluation with Clinical and Mosquito Specimens from Kenya AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Waggoner, J., Heath, C., Ndenga, B., Mutuku, F., Sahoo, M. K., Mohamed-Hadley, A., Vulule, J., Mukoko, D., LaBeaud, A., Pinsky, B. A. 2017; 97 (1): 121–24

    Abstract

    O'nyong-nyong virus (ONNV), an alphavirus closely related to chikungunya virus (CHIKV), has been the documented cause of two large outbreaks in east Africa; however, little is known about the contribution of ONNV to cases of acute febrile illness during interepidemic periods. An ONNV real-time reverse transcription polymerase chain reaction (rRT-PCR) was developed and evaluated using clinical and mosquito pool samples. The ONNV rRT-PCR linear range extended from 8.0 to 2.0 log10 copies/μL, and the lower limit of 95% detection was 22.4 copies/μL. No cases of ONNV infection were identified in serum from 385 Kenyan children who presented with an acute febrile illness. Additionally, ONNV was not detected in 120 mosquito pools collected in coastal and western Kenya. The ONNV rRT-PCR demonstrated good analytical sensitivity when performed in monoplex or as a component of an ONNV-CHIKV duplex assay. This assay should provide a useful diagnostic for the detection of ONNV in surveillance studies.

    View details for PubMedID 28719301

  • Dengue and West Nile Virus Transmission in Children and Adults in Coastal Kenya AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Vu, D. M., Banda, T., Teng, C. Y., Heimbaugh, C., Muchiri, E. M., Mungai, P. L., Mutuku, F. M., Brichard, J., Gildengorin, G., Borland, E. M., Powers, A. M., Kitron, U., King, C. H., LaBeaud, A. D. 2017; 96 (1): 141-143

    View details for DOI 10.4269/ajtmh.16-0562

    View details for Web of Science ID 000401757800025

  • Dengue and West Nile Virus Transmission in Children and Adults in Coastal Kenya. American journal of tropical medicine and hygiene Vu, D. M., Banda, T., Teng, C. Y., Heimbaugh, C., Muchiri, E. M., Mungai, P. L., Mutuku, F. M., Brichard, J., Gildengorin, G., Borland, E. M., Powers, A. M., Kitron, U., King, C. H., LaBeaud, A. D. 2016

    Abstract

    Dengue virus (DENV) and West Nile virus (WNV) are important reemerging arboviruses that are under-recognized in many parts of Africa due to lack of surveillance. As a part of a study on flavivirus, alphavirus, and parasite exposure in coastal Kenya, we measured neutralizing antibody against DENV and, to evaluate assay specificity, WNV in serum samples that tested positive for serum anti-DENV IgG by enzyme-linked immunosorbent assay. Of 830 anti-DENV IgG-positive samples that were tested for neutralizing activity, 488 (58.8%) neutralized DENV and 94 (11.3%) neutralized WNV. Of children ≤ 10 years of age, 23% and 17% had serum neutralizing antibody to DENV and WNV, respectively, indicating that DENV and WNV transmission has occurred in this region within the past decade. The results suggest that ongoing DENV and WNV transmission continues on the coast of Kenya and supports a need for routine arboviral surveillance in the area to detect and respond to future outbreaks.

    View details for PubMedID 27821697

  • Clinical and Serological Insights from the Asian Lineage Chikungunya Outbreak in Grenada, 2014: An Observational Study. American journal of tropical medicine and hygiene Macpherson, C., Noël, T., Fields, P., Jungkind, D., Yearwood, K., Simmons, M., Widjaja, S., Mitchell, G., Noel, D., Bidaisee, S., Myers, T. E., LaBeaud, A. D. 2016; 95 (4): 890-893

    Abstract

    Chikungunya virus (CHIKV) spread rapidly throughout the Caribbean region in 2014, and the first serologically confirmed case was seen in Grenada in July. This study investigated the outbreak of CHIKV in Grenada to identify the distinguishing clinical manifestations and the symptoms that corresponded the closest with serological test results. Sera were tested by IgM enzyme-linked immunosorbent assay and polymerase chain reaction to distinguish between cases positive or negative for CHIKV. Of 493 cases, 426 (86%) tested positive for CHIKV. The diagnostic decision rule, "Define as CHIKV positive a patient presenting with joint pain and any combination of the fever, body pain, or rash," produced the closest agreement (85%) with the serological test results (Cohen's kappa, κ = 0.289, P value < 0.001). When laboratory facilities are not available for diagnostic confirmation, syndromic surveillance using these four symptoms could be useful to define cases during a CHIKV outbreak when CHIKV is the predominant circulating arbovirus.

    View details for PubMedID 27527629

  • Congenital Zika syndrome: time to move from case series to case-control studies and data sharing. BMJ (Clinical research ed.) Gérardin, P., Randrianaivo, H., Schaub, B., Césaire, R., Doray, B., LaBeaud, A. D. 2016; 354: i4850

    View details for DOI 10.1136/bmj.i4850

    View details for PubMedID 27629599

  • Use of prospective hospital surveillance data to define spatiotemporal heterogeneity of malaria risk in coastal Kenya MALARIA JOURNAL Bisanzio, D., Mutuku, F., LaBeaud, A. D., Mungai, P. L., Muinde, J., Busaidy, H., Mukoko, D., King, C. H., Kitron, U. 2015; 14

    Abstract

    Malaria in coastal Kenya shows spatial heterogeneity and seasonality, which are important factors to account for when planning an effective control system. Routinely collected data at health facilities can be used as a cost-effective method to acquire information on malaria risk for large areas. Here, data collected at one specific hospital in coastal Kenya were used to assess the ability of such passive surveillance to capture spatiotemporal heterogeneity of malaria and effectiveness of an augmented control system.Fever cases were tested for malaria at Msambweni sub-County Referral Hospital, Kwale County, Kenya, from October 2012 to March 2015. Remote sensing data were used to classify the development level of each monitored community and to identify the presence of rice fields nearby. An entomological study was performed to acquire data on the seasonality of malaria vectors in the study area. Rainfall data were obtained from a weather station located in proximity of the study area. Spatial analysis was applied to investigate spatial patterns of malarial and non-malarial fever cases. A space-time Bayesian model was performed to evaluate risk factors and identify locations at high malaria risk. Vector seasonality was analysed using a generalized additive mixed model (GAMM).Among the 25,779 tested febrile cases, 28.7 % were positive for Plasmodium infection. Malarial and non-malarial fever cases showed a marked spatial heterogeneity. High risk of malaria was linked to patient age, community development level and presence of rice fields. The peak of malaria prevalence was recorded close to rainy seasons, which correspond to periods of high vector abundance. Results from the Bayesian model identified areas with significantly high malaria risk. The model also showed that the low prevalence of malaria recorded during late 2012 and early 2013 was associated with a large-scale bed net distribution initiative in the study area during mid-2012.The results indicate that the use of passive surveillance was an effective method to detect spatiotemporal patterns of malaria risk in coastal Kenya. Furthermore, it was possible to estimate the impact of extensive bed net distribution on malaria prevalence among local fever cases over time. Passive surveillance based on georeferenced malaria testing is an important tool that control agencies can use to improve the effectiveness of interventions targeting malaria (and other causes of fever) in such high-risk locations.

    View details for DOI 10.1186/s12936-015-1006-7

    View details for PubMedID 26625721

  • Seroepidemiological Study of Interepidemic Rift Valley Fever Virus Infection among Persons with Intense Ruminant Exposure in Madagascar and Kenya AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Gray, G. C., Anderson, B. D., LaBeaud, A. D., Heraud, J., Fevre, E. M., Andriamandimby, S. F., Cook, E. A., Dahir, S., de Glanville, W. A., Heil, G. L., Khan, S. U., Muiruri, S., Olive, M., Thomas, L. F., Merrill, H. R., Merrill, M. L., Richt, J. A. 2015; 93 (6): 1364-1370

    Abstract

    In this cross-sectional seroepidemiological study we sought to examine the evidence for circulation of Rift Valley fever virus (RVFV) among herders in Madagascar and Kenya. From July 2010 to June 2012, we enrolled 459 herders and 98 controls (without ruminant exposures) and studied their sera (immunoglobulin G [IgG] and IgM through enzyme-linked immunosorbent assay [ELISA] and plaque reduction neutralization test [PRNT] assays) for evidence of previous RVFV infection. Overall, 59 (12.9%) of 459 herders and 7 (7.1%) of the 98 controls were positive by the IgG ELISA assay. Of the 59 ELISA-positive herders, 23 (38.9%) were confirmed by the PRNT assay (21 from eastern Kenya). Two of the 21 PRNT-positive study subjects also had elevated IgM antibodies against RVFV suggesting recent infection. Multivariate modeling in this study revealed that being seminomadic (odds ratio [OR] = 6.4, 95% confidence interval [CI] = 2.1-15.4) was most strongly associated with antibodies against RVFV. Although we cannot know when these infections occurred, it seems likely that some interepidemic RVFV infections are occurring among herders. As there are disincentives regarding reporting RVFV outbreaks in livestock or wildlife, it may be prudent to conduct periodic, limited, active seroepidemiological surveillance for RVFV infections in herders, especially in eastern Kenya.

    View details for DOI 10.4269/ajtmh.15-0383

    View details for Web of Science ID 000366540800040

    View details for PubMedID 26458775

    View details for PubMedCentralID PMC4674260

  • Parasitism in Children Aged Three Years and Under: Relationship between Infection and Growth in Rural Coastal Kenya PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D., Singer, M. N., McKibben, M., Mungai, P., Muchiri, E. M., McKibben, E., Gildengorin, G., Sutherland, L. J., King, C. H., King, C. L., Malhotra, I. 2015; 9 (5)

    Abstract

    Parasitic infections, which are among the most common infections worldwide, disproportionately affect children; however, little is known about the impact of parasitic disease on growth in very early childhood. Our objective was to document the prevalence of parasitic infections and examine their association with growth during the first three years of life among children in coastal Kenya.Children enrolled in a maternal-child cohort were tested for soil transmitted helminths (STHs: Ascaris, Trichuris, hookworm, Strongyloides), protozoa (malaria, Entamoeba histolytica and Giardia lamblia), filaria, and Schistosoma infection every six months from birth until age three years. Anthropometrics were measured at each visit. We used generalized estimating equation (GEE) models to examine the relationship between parasitic infections experienced in the first three years of life and growth outcomes (weight, length and head circumference). Of 545 children, STHs were the most common infection with 106 infections (19%) by age three years. Malaria followed in period prevalence with 68 infections (12%) by three years of age. Filaria and Schistosoma infection occurred in 26 (4.8%) and 16 (2.9%) children, respectively. Seven percent were infected with multiple parasites by three years of age. Each infection type (when all STHs were combined) was documented by six months of age. Decreases in growth of weight, length and head circumference during the first 36 months of life were associated with hookworm, Ascaris, E. histolytica, malaria and Schistosoma infection. In a subset analysis of 180 children who followed up at every visit through 24 months, infection with any parasite was associated with decelerations in weight, length and head circumference growth velocity. Multiple infections were associated with greater impairment of linear growth.Our results demonstrate an under-recognized burden of parasitism in the first three years of childhood in rural Kenya. Parasitic infection and polyparasitism were common, and were associated with a range of significant growth impairment in terms of weight, length and/or head circumference.

    View details for DOI 10.1371/journal.pntd.0003721

    View details for Web of Science ID 000355303600014

    View details for PubMedID 25996157

    View details for PubMedCentralID PMC4440755

  • Association of Symptoms and Severity of Rift Valley Fever with Genetic Polymorphisms in Human Innate Immune Pathways PLOS NEGLECTED TROPICAL DISEASES Hise, A. G., Traylor, Z., Hall, N. B., Sutherland, L. J., Dahir, S., Ermler, M. E., Muiruri, S., Muchiri, E. M., Kazura, J. W., LaBeaud, A. D., King, C. H., Stein, C. M. 2015; 9 (3)

    Abstract

    Multiple recent outbreaks of Rift Valley Fever (RVF) in Africa, Madagascar, and the Arabian Peninsula have resulted in significant morbidity, mortality, and financial loss due to related livestock epizootics. Presentation of human RVF varies from mild febrile illness to meningoencephalitis, hemorrhagic diathesis, and/or ophthalmitis with residual retinal scarring, but the determinants for severe disease are not understood. The aim of the present study was to identify human genes associated with RVF clinical disease in a high-risk population in Northeastern Province, Kenya.We conducted a cross-sectional survey among residents (N = 1,080; 1-85 yrs) in 6 villages in the Sangailu Division of Ijara District. Participants completed questionnaires on past symptoms and exposures, physical exam, vision testing, and blood collection. Single nucleotide polymorphism (SNP) genotyping was performed on a subset of individuals who reported past clinical symptoms consistent with RVF and unrelated subjects. Four symptom clusters were defined: meningoencephalitis, hemorrhagic fever, eye disease, and RVF-not otherwise specified. SNPs in 46 viral sensing and response genes were investigated. Association was analyzed between SNP genotype, serology and RVF symptom clusters. The meningoencephalitis symptom phenotype cluster among seropositive patients was associated with polymorphisms in DDX58/RIG-I and TLR8. Having three or more RVF-related symptoms was significantly associated with polymorphisms in TICAM1/TRIF, MAVS, IFNAR1 and DDX58/RIG-I. SNPs significantly associated with eye disease included three different polymorphisms TLR8 and hemorrhagic fever symptoms associated with TLR3, TLR7, TLR8 and MyD88.Of the 46 SNPs tested, TLR3, TLR7, TLR8, MyD88, TRIF, MAVS, and RIG-I were repeatedly associated with severe symptomatology, suggesting that these genes may have a robust association with RVFV-associated clinical outcomes. Studies of these and related genetic polymorphisms are warranted to advance understanding of RVF pathogenesis.

    View details for DOI 10.1371/journal.pntd.0003584

    View details for PubMedID 25756647

  • Factors Associated with Severe Human Rift Valley Fever in Sangailu, Garissa County, Kenya PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D., Pfeil, S., Muiruri, S., Dahir, S., Sutherland, L. J., Traylor, Z., Gildengorin, G., Muchiri, E. M., Morrill, J., Peters, C. J., Hise, A. G., Kazura, J. W., King, C. H. 2015; 9 (3)

    Abstract

    Mosquito-borne Rift Valley fever virus (RVFV) causes acute, often severe, disease in livestock and humans. To determine the exposure factors and range of symptoms associated with human RVF, we performed a population-based cross-sectional survey in six villages across a 40 km transect in northeastern Kenya.A systematic survey of the total populations of six Northeastern Kenyan villages was performed. Among 1082 residents tested via anti-RVFV IgG ELISA, seroprevalence was 15% (CI95%, 13-17%). Prevalence did not vary significantly among villages. Subject age was a significant factor, with 31% (154/498) of adults seropositive vs. only 2% of children ≤15 years (12/583). Seroprevalence was higher among men (18%) than women (13%). Factors associated with seropositivity included a history of animal exposure, non-focal fever symptoms, symptoms related to meningoencephalitis, and eye symptoms. Using cluster analysis in RVFV positive participants, a more severe symptom phenotype was empirically defined as having somatic symptoms of acute fever plus eye symptoms, and possibly one or more meningoencephalitic or hemorrhagic symptoms. Associated with this more severe disease phenotype were older age, village, recent illness, and loss of a family member during the last outbreak. In multivariate analysis, sheltering livestock (aOR = 3.5 CI95% 0.93-13.61, P = 0.065), disposing of livestock abortus (aOR = 4.11, CI95% 0.63-26.79, P = 0.14), and village location (P = 0.009) were independently associated with the severe disease phenotype.Our results demonstrate that a significant proportion of the population in northeastern Kenya has been infected with RVFV. Village and certain animal husbandry activities were associated with more severe disease. Older age, male gender, herder occupation, killing and butchering livestock, and poor visual acuity were useful markers for increased RVFV infection. Formal vision testing may therefore prove to be a helpful, low-technology tool for RVF screening during epidemics in high-risk rural settings.

    View details for DOI 10.1371/journal.pntd.0003548

    View details for PubMedID 25764399

  • Cross-Sectional Survey of Rift Valley Fever Virus Exposure in Bodhei Village Located in a Transitional Coastal Forest Habitat in Lamu County, Kenya AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Muiruri, S., Kabiru, E. W., Muchiri, E. M., Hussein, H., Kagondu, F., LaBeaud, A. D., Kingt, C. H. 2015; 92 (2): 394-400

    Abstract

    Few studies have focused on Rift Valley fever virus (RVFV) transmission in less arid, transitional landscapes surrounding known high-risk regions. The objective of this study was to identify evidence of RVFV exposure in Bodhei Village in a forested area at the edge of the RVFV-epidemic Garissa region. In a household cluster-based survey conducted between epidemics in early 2006, 211 participants were enrolled. Overall seroprevalence for anti-RVFV was high (18%) and comparable with rates in the more arid, dense brush regions farther north. Seroprevalence of adults was 28%, whereas that of children was significantly lower (3%; P < 0.001); the youngest positive child was age 3 years. Males were more likely to be seropositive than females (25% versus 11%; P < 0.01), and animal husbandry activities (birthing, sheltering, and butchering) were strongly associated with seropositivity. The results confirm that significant RVFV transmission occurs outside of recognized high-risk areas and independent of known epidemic periods.

    View details for DOI 10.4269/ajtmh.14-0440

    View details for Web of Science ID 000349065400036

    View details for PubMedID 25535309

    View details for PubMedCentralID PMC4347346

  • High Rates of O'Nyong Nyong and Chikungunya Virus Transmission in Coastal Kenya PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D., Banda, T., Brichard, J., Muchiri, E. M., Mungai, P. L., Mutuku, F. M., Borland, E., Gildengorin, G., Pfeil, S., Teng, C. Y., Long, K., Heise, M., Powers, A. M., Kitron, U., King, C. H. 2015; 9 (2)

    Abstract

    Chikungunya virus (CHIKV) and o'nyong nyong virus (ONNV) are mosquito-borne alphaviruses endemic in East Africa that cause acute febrile illness and arthritis. The objectives of this study were to measure the seroprevalence of CHIKV and ONNV in coastal Kenya and link it to demographics and other risk factors.Demographic and exposure questionnaires were administered to 1,848 participants recruited from two village clusters (Milalani-Nganja and Vuga) in 2009. Sera were tested for alphavirus exposure using standardized CHIKV IgG ELISA protocols and confirmed with plaque reduction neutralization tests (PRNT). Logistic regression models were used to determine the variables associated with seropositivity. Weighted K test for global clustering of houses with alphavirus positive participants was performed for distance ranges of 50-1,000 meters, and G* statistic and kernel density mapping were used to identify locations of higher seroprevalence.486 (26%) participants were seropositive by IgG ELISA. Of 443 PRNT confirmed positives, 25 samples (6%) were CHIKV+, 250 samples (56%) were ONNV+, and 168 samples (38%) had high titers for both. Age was significantly associated with seropositivity (OR 1.01 per year, 95% C.I. 1.00-1.01); however, younger adults were more likely to be seropositive than older adults. Males were less likely to be seropositive (p<0.05; OR 0.79, 95% C.I. 0.64-0.97). Adults who owned a bicycle (p<0.05; OR 1.37, 95% C.I. 1.00-1.85) or motor vehicle (p<0.05; OR 4.64, 95% C.I. 1.19-18.05) were more likely to be seropositive. Spatial analysis demonstrated hotspots of transmission within each village and clustering among local households in Milalani-Nganja, peaking at the 200-500m range.Alphavirus exposure, particularly ONNV exposure, is common in coastal Kenya with ongoing interepidemic transmission of both ONNV and CHIKV. Women and adults were more likely to be seropositive. Household location may be a defining factor for the ecology of alphaviral transmission in this region.

    View details for DOI 10.1371/journal.pntd.0003436

    View details for Web of Science ID 000350992500014

    View details for PubMedID 25658762

    View details for PubMedCentralID PMC4319898

  • Effect of Antenatal Parasitic Infections on Anti-vaccine IgG Levels in Children: A Prospective Birth Cohort Study in Kenya PLOS NEGLECTED TROPICAL DISEASES Malhotra, I., McKibben, M., Mungai, P., McKibben, E., Wang, X., Sutherland, L. J., Muchiri, E. M., King, C. H., King, C. L., LaBeaud, A. D. 2015; 9 (1)

    Abstract

    Parasitic infections are prevalent among pregnant women in sub-Saharan Africa. We investigated whether prenatal exposure to malaria and/or helminths affects the pattern of infant immune responses to standard vaccinations against Haemophilus influenzae (Hib), diphtheria (DT), hepatitis B (Hep B) and tetanus toxoid (TT).450 Kenyan women were tested for malaria, schistosomiasis, lymphatic filariasis (LF), and intestinal helminths during pregnancy. After three standard vaccinations at 6, 10 and 14 weeks, their newborns were followed biannually to age 36 months and tested for absolute levels of IgG against Hib, DT, Hep B, and TT at each time point. Newborns' cord blood (CB) lymphocyte responses to malaria blood-stage antigens, soluble Schistosoma haematobium worm antigen (SWAP), and filaria antigen (BMA) were also assessed. Three immunophenotype categories were compared: i) tolerant (those having Plasmodium-, Schistosoma-, or Wuchereria-infected mothers but lacking respective Th1/Th2-type recall responses at birth to malaria antigens, SWAP, or BMA); ii) sensitized (those with infected/uninfected mothers and detectable Th1/Th2-type CB recall response to respective parasite antigen); or iii) unexposed (no evidence of maternal infection or CB recall response). Overall, 78.9% of mothers were infected with LF (44.7%), schistosomiasis (32.4%), malaria (27.6%) or hookworm (33.8%). Antenatal maternal malaria, LF, and hookworm were independently associated with significantly lower Hib-specific IgG. Presence of multiple maternal infections was associated with lower infant IgG levels against Hib and DT antigens post-vaccination. Post-vaccination IgG levels were also significantly associated with immunophenotype: malaria-tolerized infants had reduced response to DT, whereas filaria-tolerized infants showed reduced response to Hib.There is an impaired ability to develop IgG antibody responses to key protective antigens of Hib and diphtheria in infants of mothers infected with malaria and/or helminths during pregnancy. These findings highlight the importance of control and prevention of parasitic infections among pregnant women.

    View details for DOI 10.1371/journal.pntd.0003466

    View details for Web of Science ID 000349318100051

    View details for PubMedID 25590337

    View details for PubMedCentralID PMC4295886

  • Predicting the Mosquito Species and Vertebrate Species Involved in the Theoretical Transmission of Rift Valley Fever Virus in the United States PLOS NEGLECTED TROPICAL DISEASES Golnar, A. J., Turell, M. J., LaBeaud, A. D., Kading, R. C., Hamer, G. L. 2014; 8 (9)

    Abstract

    Rift Valley fever virus (RVFV) is a mosquito-borne virus in the family Bunyaviridiae that has spread throughout continental Africa to Madagascar and the Arabian Peninsula. The establishment of RVFV in North America would have serious consequences for human and animal health in addition to a significant economic impact on the livestock industry. Published and unpublished data on RVFV vector competence, vertebrate host competence, and mosquito feeding patterns from the United States were combined to quantitatively implicate mosquito vectors and vertebrate hosts that may be important to RVFV transmission in the United States. A viremia-vector competence relationship based on published mosquito transmission studies was used to calculate a vertebrate host competence index which was then combined with mosquito blood feeding patterns to approximate the vector and vertebrate amplification fraction, defined as the relative contribution of the mosquito or vertebrate host to pathogen transmission. Results implicate several Aedes spp. mosquitoes and vertebrates in the order Artiodactyla as important hosts for RVFV transmission in the U.S. Moreover, this study identifies critical gaps in knowledge which would be necessary to complete a comprehensive analysis identifying the different contributions of mosquitoes and vertebrates to potential RVFV transmission in the U.S. Future research should focus on (1) the dose-dependent relationship between viremic exposure and the subsequent infectiousness of key mosquito species, (2) evaluation of vertebrate host competence for RVFV among North American mammal species, with particular emphasis on the order Artiodactyla, and (3) identification of areas with a high risk for RVFV introduction so data on local vector and host populations can help generate geographically appropriate amplification fraction estimates.

    View details for DOI 10.1371/journal.pntd.0003163

    View details for Web of Science ID 000342796600044

    View details for PubMedID 25211133

    View details for PubMedCentralID PMC4161329

  • The Largest Drought in American History: Funding for Science Is Drying Up PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D., McKeating, H. 2013; 7 (8)

    View details for DOI 10.1371/journal.pntd.0002351

    View details for Web of Science ID 000323941500018

    View details for PubMedID 24009785

    View details for PubMedCentralID PMC3757073

  • Epidemiology, outcomes and predictors of recovery in childhood encephalitis: a hospital-based study. Pediatric infectious disease journal Dubray, K., Anglemyer, A., LaBeaud, A. D., Flori, H., Bloch, K., Joaquin, K. S., Messenger, S., Preas, C., Sheriff, H., Glaser, C. 2013; 32 (8): 839-844

    Abstract

    Pediatric encephalitis is a devastating diagnosis with little guidance regarding prognostic indicators early in the hospitalization.This is a retrospective cohort study of patients with encephalitis referred to the California Encephalitis Project from Children's Hospital & Research Center Oakland from 1998 to 2010. Demographic, clinical, laboratory and neuroimaging data were collected by California Encephalitis Project and chart review. Outcomes were classified into "recovery" or "incomplete recovery" and evaluated at discharge and other times (7-10 days postadmission, 3 and 12 months postdischarge). Using logistic regression, predictors associated with recovery were identified.Of 190 patients with outcomes available at discharge, 128 patients (67.4%) recovered, whereas 62 (32.6%) had an incomplete recovery, including 13 deaths (6.8%). Variables predictive of outcomes at discharge in the bivariate and multivariable analyses included Asian/Pacific Islander race, neuroimaging results and Glasgow Coma Score. Asian/Pacific Islander patients were less likely to recover than patients of other races (adjusted odds ratio = 0.43, P = 0.046). Patients with normal neuroimaging studies were more likely to recover than patients with abnormal neuroimaging (adjusted odds ratio = 2.54, P = 0.008). Patients with Glasgow Coma Score ≥7 were more likely to recover than patients with Glasgow Coma Score <7 (adjusted odds ratio = 5.82, P < 0.001). In a multivariable analysis, similar statistically significant findings were noted at all other analyzed times. Results were similar using a different population for validation, however, due to the small number of Asian/Pacific Islander patients; this finding could not be validated.This study is unique in identification of race/ethnicity as an independent predictor of pediatric encephalitis outcomes. Additional variables may be useful ancillary tools in determining prognosis.

    View details for DOI 10.1097/INF.0b013e318290614f

    View details for PubMedID 23518823

  • Comparison Of Moderate And Severe Hospitalized Pediatric 2009 H1N1 Influenza Cases PEDIATRIC INFECTIOUS DISEASE JOURNAL LaBeaud, A. D., Wentworth, B., Gildengorin, G., Tam, K., Guardia-LaBar, L., Petru, A. 2013; 32 (2): E90-E93

    Abstract

    Since its discovery in 2009, H1N1 influenza (H1N1) has spread globally. Predictive factors for severe disease in children are not well defined. Our retrospective data collection and logistic regression analysis on 137 patients hospitalized between April 2009 and February 2010 at Children's Hospital and Research Center Oakland describe clinical and epidemiologic features of H1N1 in children and determines predictors of severe disease.

    View details for DOI 10.1097/INF.0b013e31827882f9

    View details for Web of Science ID 000313874500007

    View details for PubMedID 23080289

  • Painful Arthritis and Extremity Rash in an 8-Year-Old Boy CLINICAL INFECTIOUS DISEASES Islam, S., Cooney, T., Singh, A., Petru, A. M., LaBeaud, A. D. 2012; 54 (10): 1473-?

    View details for DOI 10.1093/cid/cir1007

    View details for Web of Science ID 000304049300019

    View details for PubMedID 22527963

  • Postepidemic Analysis of Rift Valley Fever Virus Transmission in Northeastern Kenya: A Village Cohort Study PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D., Muiruri, S., Sutherland, L. J., Dahir, S., Gildengorin, G., Morrill, J., Muchiri, E. M., Peters, C. J., King, C. H. 2011; 5 (8)

    Abstract

    In endemic areas, Rift Valley fever virus (RVFV) is a significant threat to both human and animal health. Goals of this study were to measure human anti-RVFV seroprevalence in a high-risk area following the 2006-2007 Kenyan Rift Valley Fever (RVF) epidemic, to identify risk factors for interval seroconversion, and to monitor individuals previously exposed to RVFV in order to document the persistence of their anti-RVFV antibodies.We conducted a village cohort study in Ijara District, Northeastern Province, Kenya. One hundred two individuals tested for RVFV exposure before the 2006-2007 RVF outbreak were restudied to determine interval anti-RVFV seroconversion and persistence of humoral immunity since 2006. Ninety-two additional subjects were enrolled from randomly selected households to help identify risk factors for current seropositivity. Overall, 44/194 or 23% (CI(95%):17%-29%) of local residents were RVFV seropositive. 1/85 at-risk individuals restudied in the follow-up cohort had seroconverted since early 2006. 27/92 (29%, CI(95%): 20%-39%) of newly tested individuals were seropositive. All 13 individuals with positive titers (by plaque reduction neutralization testing (PRNT₈₀) in 2006 remained positive in 2009. After adjustment in multivariable logistic models, age, village, and drinking raw milk were significantly associated with RVFV seropositivity. Visual impairment (defined as ≤ 20/80) was much more likely in the RVFV-seropositive group (P<0.0001).Our results highlight significant variability in RVFV exposure in two neighboring villages having very similar climate, terrain, and insect density. Among those with previous exposure, RVFV titers remained at > 1∶40 for more than 3 years. In concordance with previous studies, residents of the more rural village were more likely to be seropositive and RVFV seropositivity was associated with poor visual acuity. Raw milk consumption was strongly associated with RVFV exposure, which may represent an important new focus for public health education during future RVF outbreaks.

    View details for DOI 10.1371/journal.pntd.0001265

    View details for Web of Science ID 000294479800020

    View details for PubMedID 21858236

    View details for PubMedCentralID PMC3156691

  • Serologic evidence of arboviral infections among humans in Kenya. American journal of tropical medicine and hygiene Sutherland, L. J., Cash, A. A., Huang, Y. S., Sang, R. C., Malhotra, I., Moormann, A. M., King, C. L., Weaver, S. C., King, C. H., LaBeaud, A. D. 2011; 85 (1): 158-161

    Abstract

    Outbreaks of arthropod-borne viral infections occur periodically across Kenya. However, limited surveillance takes place during interepidemic periods. Using serum samples obtained from asymptomatic persons across Kenya in 2000-2004, we assessed (by indirect immunofluorescent assay) prevalence of IgG against yellow fever virus (YFV), West Nile virus (WNV), tick-borne encephalitis virus (TBEV), dengue virus serotypes 1-4 (DENV1-4), and chikungunya virus (CHIKV). Older persons on the Indian Ocean coast were more likely to be seropositive than children inland: YFV = 42% versus 6%, WNV = 29% versus 6%, TBEV = 16% versus 6%, DENV-1 = 63% versus 9%, DENV-2 = 67% versus 7%, DENV-3 = 55% versus 6%, DENV-4 = 44% versus 8%, and CHIKV = 37% versus 20%. Among inland samples, children in lowlands were more likely to be seropositive for CHIKV (42% versus 0%) than children in highlands. In Kenya, transmission of arboviral infection continues between known epidemics and remains common across the country.

    View details for DOI 10.4269/ajtmh.2011.10-0203

    View details for PubMedID 21734142

    View details for PubMedCentralID PMC3122361

  • Rift Valley Fever Virus Infection in African Buffalo (Syncerus caffer) Herds in Rural South Africa: Evidence of Interepidemic Transmission AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LaBeaud, A. D., Cross, P. C., Getz, W. M., Glinka, A., King, C. H. 2011; 84 (4): 641-646

    Abstract

    Rift Valley fever virus (RVFV) is an emerging biodefense pathogen that poses significant threats to human and livestock health. To date, the interepidemic reservoirs of RVFV are not well defined. In a longitudinal survey of infectious diseases among African buffalo during 2000-2006, 550 buffalo were tested for antibodies against RVFV in 820 capture events in 302 georeferenced locations in Kruger National Park, South Africa. Overall, 115 buffalo (21%) were seropositive. Seroprevalence of RVFV was highest (32%) in the first study year, and decreased progressively in subsequent years, but had no detectable impact on survival. Nine (7%) of 126 resampled, initially seronegative animals seroconverted during periods outside any reported regional RVFV outbreaks. Seroconversions for RVFV were detected in significant temporal clusters during 2001-2003 and in 2004. These findings highlight the potential importance of wildlife as reservoirs for RVFV and interepidemic RVFV transmission in perpetuating regional RVFV transmission risk.

    View details for DOI 10.4269/ajtmh.2011.10-0187

    View details for Web of Science ID 000289023600024

    View details for PubMedID 21460024

    View details for PubMedCentralID PMC3062463

  • Arbovirus Prevalence in Mosquitoes, Kenya EMERGING INFECTIOUS DISEASES LaBeaud, A. D., Sutherland, L. J., Muiruri, S., Muchiri, E. M., Gray, L. R., Zimmerman, P. A., Hise, A. G., King, C. H. 2011; 17 (2): 233-241

    Abstract

    Few studies have investigated the many mosquito species that harbor arboviruses in Kenya. During the 2006-2007 Rift Valley fever outbreak in North Eastern Province, Kenya, exophilic mosquitoes were collected from homesteads within 2 affected areas: Gumarey (rural) and Sogan-Godud (urban). Mosquitoes (n = 920) were pooled by trap location and tested for Rift Valley fever virus and West Nile virus. The most common mosquitoes trapped belonged to the genus Culex (75%). Of 105 mosquito pools tested, 22% were positive for Rift Valley fever virus, 18% were positive for West Nile virus, and 3% were positive for both. Estimated mosquito minimum infection rates did not differ between locations. Our data demonstrate the local abundance of mosquitoes that could propagate arboviral infections in Kenya and the high prevalence of vector arbovirus positivity during a Rift Valley fever outbreak.

    View details for DOI 10.3201/eid1702.091666

    View details for Web of Science ID 000287436400011

    View details for PubMedID 21291594

    View details for PubMedCentralID PMC3204744

  • Measuring the burden of arboviral diseases: the spectrum of morbidity and mortality from four prevalent infections POPULATION HEALTH METRICS LaBeaud, A. D., Bashir, F., King, C. H. 2011; 9

    Abstract

    Globally, arthropod-borne virus infections are increasingly common causes of severe febrile disease that can progress to long-term physical or cognitive impairment or result in early death. Because of the large populations at risk, it has been suggested that these outcomes represent a substantial health deficit not captured by current global disease burden assessments.We reviewed newly available data on disease incidence and outcomes to critically evaluate the disease burden (as measured by disability-adjusted life years, or DALYs) caused by yellow fever virus (YFV), Japanese encephalitis virus (JEV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV). We searched available literature and official reports on these viruses combined with the terms "outbreak(s)," "complication(s)," "disability," "quality of life," "DALY," and "QALY," focusing on reports since 2000. We screened 210 published studies, with 38 selected for inclusion. Data on average incidence, duration, age at onset, mortality, and severity of acute and chronic outcomes were used to create DALY estimates for 2005, using the approach of the current Global Burden of Disease framework.Given the limitations of available data, nondiscounted, unweighted DALYs attributable to YFV, JEV, CHIKV, and RVFV were estimated to fall between 300,000 and 5,000,000 for 2005. YFV was the most prevalent infection of the four viruses evaluated, although a higher proportion of the world's population lives in countries at risk for CHIKV and JEV. Early mortality and long-term, related chronic conditions provided the largest DALY components for each disease. The better known, short-term viral febrile syndromes caused by these viruses contributed relatively lower proportions of the overall DALY scores.Limitations in health systems in endemic areas undoubtedly lead to underestimation of arbovirus incidence and related complications. However, improving diagnostics and better understanding of the late secondary results of infection now give a first approximation of the current disease burden from these widespread serious infections. Arbovirus control and prevention remains a high priority, both because of the current disease burden and the significant threat of the re-emergence of these viruses among much larger groups of susceptible populations.

    View details for DOI 10.1186/1478-7954-9-1

    View details for Web of Science ID 000300215200001

    View details for PubMedID 21219615

    View details for PubMedCentralID PMC3024945

  • Planning for Rift Valley fever virus: use of geographical information systems to estimate the human health threat of white-tailed deer (Odocoileus virginianus)-related transmission GEOSPATIAL HEALTH Kakani, S., LaBeaud, A. D., King, C. H. 2010; 5 (1): 33-43

    Abstract

    Rift Valley fever (RVF) virus is a mosquito-borne phlebovirus of the Bunyaviridae family that causes frequent outbreaks of severe animal and human disease in sub-Saharan Africa, Egypt and the Arabian Peninsula. Based on its many known competent vectors, its potential for transmission via aerosolization, and its progressive spread from East Africa to neighbouring regions, RVF is considered a high-priority, emerging health threat for humans, livestock and wildlife in all parts of the world. Introduction of West Nile virus to North America has shown the potential for "exotic" viral pathogens to become embedded in local ecological systems. While RVF is known to infect and amplify within domestic livestock, such as taurine cattle, sheep and goats, if RVF virus is accidentally or intentionally introduced into North America, an important unknown factor will be the role of local wildlife in the maintenance or propagation of virus transmission. We examined the potential impact of RVF transmission via white-tailed deer (Odocoileus virginianus) in a typical north-eastern United States urban-suburban landscape, where livestock are rare but where these potentially susceptible, ungulate wildlife are highly abundant. Model results, based on overlap of mosquito, human and projected deer densities, indicate that a significant proportion (497/1186 km(2), i.e. 42%) of the urban and peri-urban landscape could be affected by RVF transmission during the late summer months. Deer population losses, either by intervention for herd reduction or by RVF-related mortality, would substantially reduce these likely transmission zones to 53.1 km(2), i.e. by 89%.

    View details for Web of Science ID 000284089600004

    View details for PubMedID 21080319

    View details for PubMedCentralID PMC3140430

  • Neglected Funding for Vector-Borne Diseases: A Near Miss This Time, a Possible Disaster the Next Time PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D., Aksoy, S. 2010; 4 (10)

    View details for DOI 10.1371/journal.pntd.0000847

    View details for Web of Science ID 000283559600001

    View details for PubMedID 21049011

    View details for PubMedCentralID PMC2964300

  • Advances in Rift Valley fever research: insights for disease prevention CURRENT OPINION IN INFECTIOUS DISEASES LaBeaud, A. D., Kazura, J. W., King, C. H. 2010; 23 (5): 403-408

    Abstract

    The purpose was to review recent research on Rift Valley fever virus (RVFV) infection, encompassing four main areas: epidemiology and outbreak prediction, viral pathogenesis, human diagnostics and therapeutics, and vaccine and therapeutic candidates.RVFV continues to extend its range in Africa and the Middle East. Better definition of RVFV-related clinical syndromes and human risk factors for severe disease, combined with early-warning systems based on remote-sensing, simplified rapid diagnostics, and tele-epidemiology, hold promise for earlier deployment of effective outbreak control measures. Advances in understanding of viral replication pathways and host cell-related pathogenesis suggest means for antiviral therapeutics and for more effective vaccination strategies based on genetically engineered virus strains or subunit vaccines.RVFV is a significant health and economic burden in many areas of Africa, and remains a serious threat to other parts of the world. Development of more effective methods for RVFV outbreak prevention and control remains a global health priority.

    View details for DOI 10.1097/QCO.0b013e32833c3da6

    View details for Web of Science ID 000281653400001

    View details for PubMedID 20613512

    View details for PubMedCentralID PMC3126654

  • Facets of the Rift Valley fever outbreak in Northeastern Province, Kenya, 2006-2007. American journal of tropical medicine and hygiene King, C. H., Kahlon, S. S., Muiruri, S., LaBeaud, A. D. 2010; 82 (3): 363-?

    View details for DOI 10.4269/ajtmh.2010.09-0800

    View details for PubMedID 20207854

    View details for PubMedCentralID PMC2829890

  • Pulmonary Tuberculosis Presenting as Fever Without Source in a Pediatric Patient With Acute Lymphoblastic Leukemia PEDIATRIC BLOOD & CANCER Lancioni, C., LaBeaud, A. D., Esper, F., Abughali, N., Auletta, J. 2009; 53 (7): 1318-1320

    Abstract

    Children who undergo treatment for malignancies are at high for infection with both typical and opportunistic pathogens. Fever in these children prompts extensive evaluation and empiric treatment with broad-spectrum antimicrobials. In the United States (US), tuberculosis is an infrequently reported cause of fever in the pediatric cancer patient and has not been well described. In this report we describe a case of primary pulmonary tuberculosis (TB) in a boy with precursor B-cell acute lymphoblastic leukemia (ALL) and review the pertinent literature.

    View details for DOI 10.1002/pbc.22155

    View details for Web of Science ID 000271363800026

    View details for PubMedID 19618457

  • CANDIDA SKIN TESTING IS A POOR ADJUNCT TO TUBERCULIN SKIN TESTING IN INTERNATIONAL ADOPTEES PEDIATRIC INFECTIOUS DISEASE JOURNAL Yeo, K. T., Zhu, X., Kirchner, H. L., LaBeaud, A. D., Mandalakas, A. 2009; 28 (11): 1020-1021

    Abstract

    We conducted a prospective longitudinal study evaluating Candida skin testing among international adoptees presenting to our clinic between 2000 and 2006. Nineteen (17%) and 17 (15%) children had negative tests at presentation and at 6 months, respectively--only 3 were negative at both points. Our study suggests that Candida skin test reactivity is an unstable measure of anergy among international adoptees.

    View details for DOI 10.1097/INF.0b013e3181a909d3

    View details for Web of Science ID 000271253800018

    View details for PubMedID 19820428

    View details for PubMedCentralID PMC3133951

  • School-Based Health Promotion for Mosquito-Borne Disease Prevention in Children JOURNAL OF PEDIATRICS LaBeaud, A. D., Glinka, A., Kippes, C., King, C. H. 2009; 155 (4): 590-592

    Abstract

    We enrolled 345 fourth-grade students in a classroom-randomized, controlled trial to evaluate a school-based West Nile virus health education program's impact on knowledge, attitudes, and personal protective behavior use. Immediate and sustained improvements in West Nile virus knowledge and greater frequencies of reported personal protective behaviors resulted from the educational intervention.

    View details for DOI 10.1016/j.jpeds.2009.03.009

    View details for Web of Science ID 000270497800031

    View details for PubMedID 19773005

    View details for PubMedCentralID PMC3104726

  • Do Antenatal Parasite Infections Devalue Childhood Vaccination? PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D., Malhotra, I., King, M. J., King, C. L., King, C. H. 2009; 3 (5)

    Abstract

    On a global basis, both potent vaccine efficacy and high vaccine coverage are necessary to control and eliminate vaccine-preventable diseases. Emerging evidence from animal and human studies suggest that neglected tropical diseases (NTDs) significantly impair response to standard childhood immunizations. A review of efficacy and effectiveness studies of vaccination among individuals with chronic parasitic infections was conducted, using PUBMED database searches and analysis of data from the authors' published and unpublished studies. Both animal models and human studies suggest that chronic trematode, nematode, and protozoan infections can result in decreased vaccine efficacy. Among pregnant women, who in developing countries are often infected with multiple parasites, soluble parasite antigens have been shown to cross the placenta and prime or tolerize fetal immune responses. As a result, antenatal infections can have a significant impact on later vaccine responses. Acquired childhood parasitic infections, most commonly malaria, can also affect subsequent immune response to vaccination. Additional data suggest that antiparasite therapy can improve the effectiveness of several human vaccines. Emerging evidence demonstrates that both antenatal and childhood parasitic infections alter levels of protective immune response to routine vaccinations. Successful antiparasite treatment may prevent immunomodulation caused by parasitic antigens during pregnancy and early childhood and may improve vaccine efficacy. Future research should highlight the varied effects that different parasites (alone and in combination) can have on human vaccine-related immunity. To optimize vaccine effectiveness in developing countries, better control of chronic NTDs may prove imperative.

    View details for DOI 10.1371/journal.pntd.0000442

    View details for Web of Science ID 000267268000014

    View details for PubMedID 19478847

    View details for PubMedCentralID PMC2682196

  • Interepidemic Rift Valley fever virus seropositivity, northeastern Kenya EMERGING INFECTIOUS DISEASES LaBeaud, A. D., Muchiri, E. M., Ndzovu, M., Mwanje, M. T., Muiruri, S., Peters, C. J., King, C. H. 2008; 14 (8): 1240-1246

    Abstract

    Most outbreaks of Rift Valley fever (RVF) occur in remote locations after floods. To determine environmental risk factors and long-term sequelae of human RVF, we examined rates of previous Rift Valley fever virus (RVFV) exposure by age and location during an interepidemic period in 2006. In a randomized household cluster survey in 2 areas of Ijara District, Kenya, we examined 248 residents of 2 sublocations, Gumarey (village) and Sogan-Godud (town). Overall, the RVFV seropositivity rate was 13% according to immunoglobulin G ELISA; evidence of interepidemic RVFV transmission was detected. Increased seropositivity was found among older persons, those who were male, those who lived in the rural village (Gumarey), and those who had disposed of animal abortus. Rural Gumarey reported more mosquito and animal exposure than Sogan-Godud. Seropositive persons were more likely to have visual impairment and retinal lesions; other physical findings did not differ.

    View details for DOI 10.3201/eid1408.080082

    View details for Web of Science ID 000258216900008

    View details for PubMedID 18680647

    View details for PubMedCentralID PMC2600406

  • Why Arboviruses Can Be Neglected Tropical Diseases PLOS NEGLECTED TROPICAL DISEASES LaBeaud, A. D. 2008; 2 (6)

    View details for DOI 10.1371/journal.pntd.0000247

    View details for Web of Science ID 000261807000001

    View details for PubMedID 18575597

    View details for PubMedCentralID PMC2427179

  • Rapid GIS-based profiling of West Nile virus transmission: defining environmental factors associated with an urban-suburban outbreak in Northeast Ohio, USA GEOSPATIAL HEALTH LaBeaud, A. D., Gorman, A., Koonce, J., Kippes, C., McLeod, J., Lynch, J., Gallagher, T., King, C. H., Mandalakas, A. M. 2008; 2 (2): 215-225

    Abstract

    Human West Nile virus (WNV) infection was first detected in Cuyahoga county, Ohio, USA, in 2002. During that year's extensive epidemic/epizootic among non-immune human and bird populations, the county experienced 155 cases of severe human West Nile neurological disease (WNND, incidence = 11.1 cases/100,000), with 11 fatalities. Structured serosurveys indicated that 1.9%, or approximately 26,000 of county residents (population = 1,372,303) were infected that year. In early 2003, in order to better focus monitoring and control efforts, we used a geographical information system (GIS) approach and spatial statistical analysis to identify the association of environmental factors and human population structure with the observed local risk for WNV transmission. Within the varied range of urban/suburban/ rural habitats across the 1186 km2 county, exploratory analysis indicated significant clustering of WNND risk in inner-ring suburbs. Subsequent discriminant factor analysis based on inputs of census and land-use/land cover data was found to effectively classify sub-areas of the county having low, medium and high WNV risk. On a 1036 ha quadrat scale of resolution, higher risk of human infection was significantly associated with higher-income areas, increased fractionation of habitat and older housing, while it was negatively associated with areas of agricultural land, wetland or forest. The areal classification of WNV transmission risk has been validated over time through detection of increased local Culex spp. mosquito density (2002-2006), and increased frequency of WNV positive mosquito pools within the medium- and high-risk quadrats. This timely working identification of the transmission scale effectively focused control interventions against newly invasive WNV in a complex North American habitat.

    View details for Web of Science ID 000258662200008

    View details for PubMedID 18686270

    View details for PubMedCentralID PMC3140769

  • Spectrum of rift valley fever virus transmission in Kenya: Insights from three distinct regions AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LaBeaud, A. D., Ochiai, Y., Peters, C. J., Muchiri, E. M., King, C. H. 2007; 76 (5): 795-800

    Abstract

    Rift Valley fever virus (RVFV) is an emerging pathogen that maintains high biodefense priority based on its threat to livestock, its ability to cause human hemorrhagic fever, and its potential for aerosol spread. To define the range of human transmission during inter-epidemic and epidemic periods in Kenya, we tested archived sera from defined populations (N = 1,263) for anti-RVFV IgG by ELISA and plaque reduction neutralization testing. RVFV seroprevalence was 10.8% overall and varied significantly by location, sex, and age. In NW Kenya, high seroprevalence among those born before 1980 indicates that an undetected epidemic may have occurred then. Seroconversion documented in highland areas suggests previously unsuspected inter-epidemic transmission. RVFV seroprevalence is strikingly high in certain Kenyan areas, suggesting endemic transmission patterns that may preclude accurate estimation of regional acute outbreak incidence. The extent of both epidemic and inter-epidemic RVFV transmission in Kenya is greater than previously documented.

    View details for Web of Science ID 000246326300003

    View details for PubMedID 17488893

    View details for PubMedCentralID PMC2367216

  • Index of suspicion PEDIATRICS IN REVIEW Eneli, I., West, M., Sigal, Y., Martel, J. N., Lazerson, J., Halthore, S. N., LaBeaud, A. D., Leonard, E. G., McComsey, G. A. 2006; 27 (10): 389-394

    View details for Web of Science ID 000242176700005

    View details for PubMedID 17012490