Children with Congenital Zika Syndrome and microcephaly are at high risk for epilepsy; however, the risk is unclear in normocephalic children with prenatal Zika virus (ZIKV) exposure [Exposed Children (EC)]. In this prospective cohort... more
Children with Congenital Zika Syndrome and microcephaly are at high risk for epilepsy; however, the risk is unclear in normocephalic children with prenatal Zika virus (ZIKV) exposure [Exposed Children (EC)]. In this prospective cohort study, we performed epilepsy screening in normocephalic EC alongside a parallel group of normocephalic unexposed children [Unexposed Children (UC)]. We compared the incidence rate of epilepsy among EC and UC at one year of life to global incidence rates. Pregnant women were recruited from public health centers during the ZIKV outbreak in Grenada, West Indies and assessed for prior ZIKV infection using a plasmonic-gold platform that measures IgG antibodies in serum. Normocephalic children born to mothers with positive ZIKV results during pregnancy were classified as EC and those born to mothers with negative ZIKV results during and after pregnancy were classified as UC. Epilepsy screening procedures included a pediatric epilepsy screening questionnaire ...
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Additional File 1. Socioeconomic Status Survey. The 84-question socioeconomic status and family planning survey used to determine SES using WAMI index and PCA asset score. Adapted from Psaki et al.
Additional file 1: Figure S1. Correlation of HOBO logger temperature data between nearest clinical sites and with Weather Underground data. Left panel: comparison of HOBO logger temperature data between nearest clinical site (top:... more
Additional file 1: Figure S1. Correlation of HOBO logger temperature data between nearest clinical sites and with Weather Underground data. Left panel: comparison of HOBO logger temperature data between nearest clinical site (top: Msambweni and Ukunda; bottom: Kisumu and Chulaimbo). Middle and right panels: comparison of HOBO logger temperature data at a clinical site and Weather Underground data from the nearest weather station (weather station code for Msambweni and Ukunda is HKMO and for Kisumu and Chulaimbo is HKKI). Dashed black lines indicate the regression line where y = x; blue lines indicate the linear regression between the two data sets (y = mx + b). The linear regression equations (blue lines) were used to adjust source data to fill in missing data. Figure S2. The nonlinear effect of temperature on malaria smear positivity. The plot shows the nonlinear effect of temperature alone on the odds of malaria smear positivity using a structured additive regression model (R2Baye...
Additional file 2. Consent for Participation in Study.
Additional file 1. Semi-structured interview guide (modified and reproduced from Baltzell et al. [5] with permission).
Abstract: On a global basis, both potent vaccine efficacy and high vaccine coverage are necessary to control and eliminate vaccine-preventable diseases. Emerging evi-dence from animal and human studies suggest that neglected tropical... more
Abstract: On a global basis, both potent vaccine efficacy and high vaccine coverage are necessary to control and eliminate vaccine-preventable diseases. Emerging evi-dence 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 conduct-ed, 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
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BackgroundRift Valley fever virus (RVFV) is a lethal threat to humans and livestock in many parts of Africa, the Arabian Peninsula, and the Indian Ocean. This systematic review’s objective was to consolidate understanding of RVFV... more
BackgroundRift Valley fever virus (RVFV) is a lethal threat to humans and livestock in many parts of Africa, the Arabian Peninsula, and the Indian Ocean. This systematic review’s objective was to consolidate understanding of RVFV epidemiology during 1999-2021 and highlight knowledge gaps relevant to plans for human vaccine trials.Methodology/Principal FindingsThe review is registered with PROSPERO (CRD42020221622). Reports of RVFV infection or exposure among humans, animals, and/or vectors in Africa, the Arabian Peninsula, and the Indian Ocean during the period January 1999 to June 2021 were eligible for inclusion. Online databases were searched for publications, and supplemental materials were recovered from official reports and research colleagues. Exposures were classified into five groups: 1) acute human RVF cases, 2) acute animal cases, 3) human RVFV sero-surveys, 4) animal sero-surveys, and 5) arthropod infections. Human risk factors, circulating RVFV lineages, and surveillanc...
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Climate change and variability influence temperature and rainfall, which impact vector abundance and the dynamics of vector-borne disease transmission. Climate change is projected to increase the frequency and intensity of extreme climate... more
Climate change and variability influence temperature and rainfall, which impact vector abundance and the dynamics of vector-borne disease transmission. Climate change is projected to increase the frequency and intensity of extreme climate events. Mosquito-borne diseases, such as dengue fever, are primarily transmitted by Aedes aegypti mosquitoes. Freshwater availability and temperature affect dengue vector populations via a variety of biological processes and thus influence the ability of mosquitoes to effectively transmit disease. However, the effect of droughts, floods, heat waves, and cold waves is not well understood. Using vector, climate, and dengue disease data collected between 2013 and 2019 in Kenya, this retrospective cohort study aims to elucidate the impact of extreme rainfall and temperature on mosquito abundance and the risk of arboviral infections. To define extreme periods of rainfall and land surface temperature (LST), we calculated monthly anomalies as deviations f...
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The goal of this study was to systematically review the published data on dengue virus (DENV) seroprevalence in Sudan and to estimate disease burden through meta-analysis. We searched, reviewed, and extracted online available reports on... more
The goal of this study was to systematically review the published data on dengue virus (DENV) seroprevalence in Sudan and to estimate disease burden through meta-analysis. We searched, reviewed, and extracted online available reports on DENV in Sudan. Among 168 identified records, 19 were selected. Dengue infections were documented in 11/18 states. The overall seroprevalence of DENV in Sudan was estimated to be 27%, while the prevalence of dengue IgM was 22% and IgG was 38%. The prevalence of dengue estimated from community and hospital-based cross-sectional studies were 26% and 30% respectively. Additionally, one cohort study and a single PCR-based study reported a prevalence of 1% and 4%, respectively. Regional analysis revealed that the variation in seroprevalence in East, North, West, and Central Sudan was 23%, 24%, 36% and 43%, respectively. Interestingly, we found that DENV is circulating countrywide with a significant spatiotemporal variation in the disease seroprevalence. Fu...
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Climate drives population dynamics through multiple mechanisms, which can lead to seemingly context-dependent effects of climate on natural populations. For climate-sensitive diseases such as dengue, chikungunya, and Zika, climate appears... more
Climate drives population dynamics through multiple mechanisms, which can lead to seemingly context-dependent effects of climate on natural populations. For climate-sensitive diseases such as dengue, chikungunya, and Zika, climate appears to have opposing effects in different contexts. Here we show that a model, parameterized with laboratory measured climate-driven mosquito physiology, captures three key epidemic characteristics across ecologically and culturally distinct settings in Ecuador and Kenya: the number, timing, and duration of outbreaks. The model generates a range of disease dynamics consistent with observed Aedes aegypti abundances and laboratory-confirmed arboviral incidence with variable accuracy (28 – 85% for vectors, 44 – 88% for incidence). The model predicted vector dynamics better in sites with a smaller proportion of young children in the population, lower mean temperature, and homes with piped water and made of cement. Models with limited calibration that robus...
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Background Congenital Zika Syndrome (CZS) has a broad spectrum of clinical presentations that are still being described. This cohort study aimed to describe the orthopedic complications in children with microcephaly (MCP) related to Zika... more
Background Congenital Zika Syndrome (CZS) has a broad spectrum of clinical presentations that are still being described. This cohort study aimed to describe the orthopedic complications in children with microcephaly (MCP) related to Zika virus (ZIKV). Methods We evaluated 36 children with CZS up to 17 months of age followed at a pediatric rehabilitation center in the northeast of Brazil. Cohort enrollment occurred with children born between January 2015 and May 2016. We assessed their social profiles and orthopedic findings. Results Of the 36 cases, 25 were male. All of them lived in rural area. 25 had at least one congenital orthopedic alteration. Hip subluxation was the most common problem detected (n = 15); other lower limb abnormalities included knee subluxation (n = 7), clubfoot (n = 7); congenital vertical talus (n = 4); plano-valgus foot (n = 5). In relation to the upper limbs, 11 children presented with some shoulder and/or elbow abnormality and 16 had some alteration in the...
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Background Infant mortality in Brazil has increased for the first time in 26 years. This study aimed to define the Zika Syndrome (ZS) perinatal case fatality rate (PCF) since the 2015 Zika outbreak in a Brazilian northeast state highly... more
Background Infant mortality in Brazil has increased for the first time in 26 years. This study aimed to define the Zika Syndrome (ZS) perinatal case fatality rate (PCF) since the 2015 Zika outbreak in a Brazilian northeast state highly impacted by the virus. Methods Cross-sectional study conducted using data obtained through the State Health Department for cases of microcephaly (MCP) and congenital abnormalities (CA) in Rio Grande do Norte State (RN) from April 2015 to March 2, 2019. Perinatal period: commencing at 22 completed weeks (154 days) of gestation until 7 days after birth. PCF was defined as the number of deaths as a fraction of the number of sick persons with the specific disease (×100). Results There were 535 reported cases of MCP and others CA notified in RN during this period: 4 in 2014, 337 in 2015, 157 in 2016, 21 in 2017, 14 in 2018, and 2 in 2019. Of these, 151 were confirmed and 135 remain under investigation. The remaining 247 cases were ruled out by normal physi...
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Nomadic pastoralists are among the worlds hardest-to-reach and least-served populations. Pastoralist communities are notoriously difficult to capture in household surveys due to factors including their high degree of mobility, remote... more
Nomadic pastoralists are among the worlds hardest-to-reach and least-served populations. Pastoralist communities are notoriously difficult to capture in household surveys due to factors including their high degree of mobility, remote terrain, fluid domestic arrangements, and cultural barriers. Most surveys utilize census-based sampling frames which do not accurately capture the demographic and health parameters of nomadic populations. As a result, pastoralists are largely 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 surveyed this population in order to draw comparisons with reg...
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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... more
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 ...
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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)... more
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 cro...
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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... more
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...
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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... more
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.
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Background In sub-Saharan Africa, malaria is frequently overdiagnosed as the cause of an undifferentiated febrile illness, whereas arboviral illnesses are presumed to be underdiagnosed. Methods Sera from 385 febrile Kenyan children, who... more
Background In sub-Saharan Africa, malaria is frequently overdiagnosed as the cause of an undifferentiated febrile illness, whereas arboviral illnesses are presumed to be underdiagnosed. Methods 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. Results 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 ofte...
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Research Interests: Microbiology, Medical Microbiology, Biology, Medicine, Gene expression, and 15 moreClinical Microbiology, Biological Sciences, Female, Animals, Clinical, Male, Horses, Lung, Real Time, LOOP MEDIATED ISOTHERMAL AMPLIFICATION, Newcastle Disease Virus, Fusion Protein, Coronavirus, Biochemistry and cell biology, and Medical and Health Sciences
BACKGROUND AND OBJECTIVE: 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... more
BACKGROUND AND OBJECTIVE: 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. METHODS: 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 receiv...
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Research Interests: Medicine and Dengue fever
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Research Interests: Medicine and Chikungunya
We welcome the paper reporting seven cases of congenital Zika syndrome (CZS) with arthrogryposis.1 Mounting evidence that Zika virus infection in early gestation causes brain damage shows that Zika associated arthrogryposis may be... more
We welcome the paper reporting seven cases of congenital Zika syndrome (CZS) with arthrogryposis.1 Mounting evidence that Zika virus infection in early gestation causes brain damage shows that Zika associated arthrogryposis may be neurogenic. In agreement, the mechanisms underlying the CZS phenotype would be a tropism of the virus to neuronal cells,2 3 or vascular disorders, as in the …
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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... more
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 seven (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. Al...
Research Interests: Biology, Kenya, Adolescent, Medicine, Humans, and 15 moreMadagascar, Female, Animals, Male, Risk factors, Middle Aged, Adult, Risk Factors, Rift Valley Fever, Rift Valley fever virus, Enzyme Linked Immunosorbent Assay, Epidemics, Neutralization tests, immunoglobulin M, and Medical and Health Sciences
Background: Rift Valley fever virus (RVFV) causes an acute, mosquito-borne viral disease in livestock and humans. To determine the exposure factors and range of disease symptoms associated with human RVF, we performed a household cluster... more
Background: Rift Valley fever virus (RVFV) causes an acute, mosquito-borne viral disease in livestock and humans. To determine the exposure factors and range of disease symptoms associated with human RVF, we performed a household cluster survey in six villages in Northeastern Kenya in 2011. Methods: We performed a household cluster survey in six villages in Northeastern Kenya in 2011. 1081 participants were tested via anti-RVFV IgG ELISA. Results: 1081 participants were tested via anti-RVFV IgG ELISA, yielding 16% seroprevalence (95% C.I. 0.1-0.2). No significant differences were found among villages. 31% (154/498) of adults were seropositive vs. 3% of children (≤15 years; 17/583). With each additional year of age, participants were 5% more likely to be seropositive (95% C.I. 1.0-1.1). Documentation of a 3y/o seropositive boy confirmed interepidemic transmission. Males were 2.6 times more likely to be seropositive (p<0.001; 95% C.I. 1.7-3.8); herders were 1.7 times more likely (p...
This section of Pediatrics in Review reminds clinicians of those conditions that can present in a misleading fashion and require suspicion for early diagnosis. Emphasis has been placed on conditions in which early diagnosis is important... more
This section of Pediatrics in Review reminds clinicians of those conditions that can present in a misleading fashion and require suspicion for early diagnosis. Emphasis has been placed on conditions in which early diagnosis is important and that the general pediatrician might be expected to encounter, at least once in a while. The reader is encouraged to write possible diagnoses for each case before turning to the discussion, which is on the following page. We invite readers to contribute case presentations and discussions. Case 1 Presentation The parents of a 22-month-old boy complain that he has been increasingly clumsy and cranky for the past 7 days. He initially developed a stumbling gait and now prefers to crawl; he no longer can sit on his own. The child has been afebrile but has had a cough for several weeks. He has been on antibiotics for otitis media (with a presumed labyrinthitis) for 5 days. There have been no other recent illnesses, and he has not been ill in the past. On examination, the child appears irritable and has occasional jerking movements of his extremities. His temperature is 36.3°C, pulse is 128 beats/min, and blood pressure is 84/40 mm Hg. Chaotic, irregular eye movements are present.
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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... more
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 s...
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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... more
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 empirical...
Research Interests: Kenya, Adolescent, Medicine, Animal Husbandry, Biological Sciences, and 15 moreDisease Outbreaks, Humans, Child, Female, Animals, Male, Aged, Prevalence, Middle Aged, Adult, Rift Valley Fever, Rift Valley fever virus, Cross Sectional Studies, Enzyme Linked Immunosorbent Assay, and Medical and Health Sciences
Emerging evidence suggests that children are at higher risk for West Nile virus (WNV) exposure, but may have a lower risk for infection-related morbidity and mortality. Limited data exist regarding risk determinants of childhood WNV... more
Emerging evidence suggests that children are at higher risk for West Nile virus (WNV) exposure, but may have a lower risk for infection-related morbidity and mortality. Limited data exist regarding risk determinants of childhood WNV infection. We conducted a survey to analyze the differences between pediatric and adult behavior relevant to WNV exposure. Residents of participating sampled households responded to a questionnaire that measured knowledge, attitudes, personal protective behaviors, and clinical history to evaluate the association between personal behavior and exposure to WNV. Children were more likely to have high levels of outdoor exposure compared to adults (83% vs. 70%). Children were less likely to avoid going outdoors (4% vs. 13%) and to wear long sleeves or pants compared to adults (8% vs. 19%). Both groups were highly educated about WNV. Television, not health-care provider education, was the most common source of WNV information. Participants were more concerned a...