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Angelle Desiree LaBeaud

Associate Professor of Pediatrics (Infectious Diseases) and, by courtesy, of Health Research and Policy (Epidemiology) at the Lucile Salter Packard Children's Hospital

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).
Pediatric Infectious Disease
Academic Appointments: 
Associate Professor - Med Center Line, Pediatrics - Infectious Diseases
Associate Professor - Med Center Line (By courtesy), Health Research & Policy
Member, Bio-X
Administrative Appointments: 
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)
Professional Organizations: 
Chair- elect, American Committee on Arthropod-Borne Viruses (2016 - Present)
Deputy Editor, PLoS NTDs (2008 - Present)
Education: 
MS, Case Western Reserve University, Clinical Research (2009)
Residency:University Hospitals of ClevelandOH
Fellowship:Rainbow Babies and Children's Hospital Pediatric Infectious DiseaseOH
Board Certification: Pediatric Infectious Disease, American Board of Pediatrics (2007)
Board Certification: Pediatrics, American Board of Pediatrics (2003)
Medical Education:Medical College Of Wisconsin (2000) WI
Community and International Work: 
Characterizing the Effects of Antenatal Parasitic Infection on Fetal Immune System Development
The Spectrum of Zika Disease in Grenada, Grenada
Predicting dengue transmission in a changing climate to improve mosquito control, Kenya, Ecuador
Integrated Vector Management as a Strategy for Reduced Disease Risk in Dengue Fever
Characterization of Immune Factors of Severe and Chronic Chikungunya Disease, Grenada
Miniaturized Automated Whole Blood Cellular Analysis System, Kenya
Effects of Parasitic Infections on Vaccine Response, Kenya
Burden of Chikungunya and Dengue in Kenya, Kenya
Academic and Contact Information
Clinical Offices: 
Clinical Practices: 
Research & Scholarship
Current Research 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)
Title: 
Characterizing the Effects of Antenatal Parasitic Infection on Fetal Immune System Development
Detail: 

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, Assistant 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)
Title: 
Burden of Chikungunya and Dengue in Kenya, Kenya
Detail: 

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)
Title: 
Integrated Vector Management as a Strategy for Reduced Disease Risk in a Newly Discovered Region of Dengue Fever in Africa
Detail: 

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)
Title: 
Characterization of Immune Factors of Severe and Chronic Chikungunya Disease in Grenada, West Indies
Detail: 

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)
Title: 
Miniaturized Automated Whole Blood Cellular Analysis System
Detail: 

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)
Title: 
Complex Data and Deep Learning for Disease Outbreak Prediction
Detail: 

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
Predicting dengue transmission in a changing climate to improve mosquito control, Stanford University (Depts of Biology and Pediatrics) (7/1/2016 - 6/30/2018)
Title: 
Predicting dengue transmission in a changing climate to improve mosquito control
Detail: 

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)
Title: 
The Spectrum of Zika Virus Disease in Grenada
Detail: 

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)
Title: 
Neurodevelopment and Vector-borne Diseases: Building Research Capacity in the Tropics
Detail: 

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

Teaching
Courses Taught: 
Academic Year: 
2016-17
Independent Study Courses: 
Directed Reading in Environment and Resources
ENVRES 398 (Aut, Win, Spr, Sum)
Directed Research in Environment and Resources
ENVRES 399 (Aut, Win, Spr, Sum)
Early Clinical Experience
PEDS 280 (Win, Spr)
Graduate Research
HRP 399 (Win, Spr)
Graduate Research
PEDS 399 (Win, Spr)
Medical Scholars Research
PEDS 370 (Aut, Win, Spr)
Advisees: 
Postdoctoral Advisees: 
Publications
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

Parasitic Infections in Pregnancy Decrease Placental Transfer of Anti-Pneumococcal Antibodies. Clinical and vaccine immunology : CVI McKittrick, N. D., Vu, D. M., Malhotra, I., King, C. H., Mutuku, F., LaBeaud, A. D. 2017

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

Pneumococcal Vaccine Response After Exposure to Parasites in Utero, in Infancy, or Mid-Childhood. Pediatrics Nayakwadi Singer, M., 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

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 PubMedID 28302673

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

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

View details for Web of Science ID 000365795500009

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

View details for DOI 10.4269/ajtmh.15-0383

View details for Web of Science ID 000366540800040

View details for PubMedID 26458775

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

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 Web of Science ID 000352199400052

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 Web of Science ID 000352199400027

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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