Angelle LaBeaud, MD

Abstract

Neonates are vulnerable to vector-borne diseases given the potential for mother-to-child congenital transmission. To determine factors associated with chikungunya virus (CHIKV) infection among pregnant women in Grenada, West Indies, a retrospective cohort study enrolled women who were pregnant during the 2014 CHIKV epidemic. In all, 520/688 women (75.5%) were CHIKV IgG positive. Low incomes, use of pit latrines, lack of home window screens, and subjective reporting of frequent mosquito bites were associated with increased risk of CHIKV infection in bivariate analyses. In the multivariate modified Poisson regression model, low income (adjusted relative risk [aRR]: 1.05 [95% CI: 1.01-1.10]) and frequent mosquito bites (aRR: 1.05 [95% CI: 1.01-1.10]) were linked to increased infection risk. In Grenada, markers of low socioeconomic status are associated with CHIKV infection among pregnant women. Given that Grenada will continue to face vector-borne outbreaks, interventions dedicated to improving living conditions of the most disadvantaged will help reduce the incidence of arboviral infections.

View details for DOI 10.4269/ajtmh.23-0157

View details for PubMedID 37253436

View details for DOI 10.1038/s41572-023-00442-5

View details for PubMedID 37208376

Abstract

BACKGROUND: Late relapsing hepatitis after yellow fever (LHep-YF) during the convalescent phase of the disease has been described during recent yellow fever (YF) outbreaks in Brazil. LHep-YF is marked by the rebound in liver enzymes and non-specific clinical manifestations around 30-60 days after YF symptom onset.METHODS: Here we have characterized the clinical course and risk factors for LHep-YF using data from a representative cohort of patients who survived YF in Brazil, 2017-2018. A total of 221 YF-positive patients were discharged from the infectious disease reference hospital in Minas Gerais, and were followed-up at 30-, 45- and 60- days post symptom onset (dps).RESULTS: From 46 up to 60 dps, 16% of YF patients (n=36/221) exhibited a rebound of transaminases (AST or ALT >500 IU/L), alkaline phosphatase, and total bilirubin levels. Other etiologies of liver inflammation such as infectious hepatitis, autoimmune hepatitis, and metabolic liver disease were ruled out. Jaundice, fatigue, headache, and low platelet levels were associated with LHep-YF. Demographic factors, clinical manifestations, laboratory tests, ultrasound findings, and viral load during the acute phase of YF were not associated with the occurrence of LHep-YF.CONCLUSIONS: These findings provide new data on the clinical course of late relapsing hepatitis during the convalescent phase of YF and highlight the need for extended patient follow-up after acute YF.

View details for DOI 10.1093/cid/ciad249

View details for PubMedID 37099356

Abstract

Chikungunya virus is widespread throughout the tropics, where it causes recurrent outbreaks of chikungunya fever. In recent years, outbreaks have afflicted populations in East and Central Africa, South America and Southeast Asia. The virus is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Chikungunya fever is characterized by severe arthralgia and myalgia that can persist for years and have considerable detrimental effects on health, quality of life and economic productivity. The effects of climate change as well as increased globalization of commerce and travel have led to growth of the habitat of Aedes mosquitoes. As a result, increasing numbers of people will be at risk of chikungunya fever in the coming years. In the absence of specific antiviral treatments and with vaccines still in development, surveillance and vector control are essential to suppress re-emergence and epidemics.

View details for DOI 10.1038/s41572-023-00429-2

View details for PubMedID 37024497

View details for PubMedCentralID 9860750

Abstract

This study described a soluble mediator storm in acute Yellow Fever/YF infection along the kinetic timeline towards convalescent disease. The analyses of the YF Viral RNAnemia, chemokines, cytokines, and growth factors were performed in YF patients at acute/(D1-15) and convalescent/(D16-315) phases. Patients with acute YF infection displayed a trimodal viremia profile spreading along D3, D6, and D8-14. A massive storm of mediators was observed in acute YF. Higher levels of mediators were observed in YF with higher morbidity scores, patients under intensive care, and those progressing to death than in YF patients who progress to late-relapsing hepatitis/L-Hep. A unimodal peak of biomarkers around D4-6 with a progressive decrease towards D181-315 was observed in non-L-Hep patients, while a bimodal pattern with a second peak around D61-90 was associated with L-Hep. This study provided a comprehensive landscape of evidence that distinct immune responses drive pathogenesis, disease progression, and L-Hep in YF patients.

View details for DOI 10.1016/j.clim.2023.109321

View details for PubMedID 37019421

Abstract

Malaria, chikungunya virus (CHIKV), and dengue virus (DENV) are endemic causes of fever among children in Kenya. The risks of infection are multifactorial and may be influenced by built and social environments. The high resolution overlapping of these diseases and factors affecting their spatial heterogeneity has not been investigated in Kenya. From 2014-2018, we prospectively followed a cohort of children from four communities in both coastal and western Kenya. Overall, 9.8% were CHIKV seropositive, 5.5% were DENV seropositive, and 39.1% were malaria positive (3521 children tested). The spatial analysis identified hot-spots for all three diseases in each site and in multiple years. The results of the model showed that the risk of exposure was linked to demographics with common factors for the three diseases including the presence of litter, crowded households, and higher wealth in these communities. These insights are of high importance to improve surveillance and targeted control of mosquito-borne diseases in Kenya.

View details for DOI 10.1186/s12879-023-08157-4

View details for PubMedID 36991340

View details for PubMedCentralID 6881070

Abstract

Aedes aegypti is an important vector of several arboviruses including dengue and chikungunya viruses. Accurate identification of larval habitats of Ae. aegypti is considered an essential step in targeted control. This study determined Ae. aegypti productivity in selected larval habitats in Msambweni, Kwale County, Kenya. Three sequential larval habitat surveys were conducted. The first survey was habitat census (baseline) through which 83 representative larval habitats were identified and selected. The second and third surveys involved estimating daily productivity of the 83 selected larval habitats for 30 consecutive days during a wet and a dry season, respectively. Of 664 larval habitats examined at baseline, 144 larval habitats (21.7%) were found to be infested with Ae. aegypti larvae. At baseline, majority (71%) of the pupae were collected from two (2/6) larval habitat types, tires and pots. Multivariate analysis identified habitat type and the habitat being movable as the predictors for pupal abundance. During the 30-day daily pupal production surveys, only a few of the habitats harbored pupae persistently. Pupae were found in 28% and 12% of the larval habitats during the wet and dry seasons, respectively. In the wet season, drums, tires, and pots were identified as the key habitat types accounting for 85% of all pupae sampled. Three habitats (all drums) accounted for 80% of all the pupae collected in the dry season. Predictors for pupal productivity in the wet season were habitat type, place (whether the habitat is located at the back or front of the house), habitat purpose (use of the water in the habitat), and source of water. Although the multivariate model for habitat type did not converge, habitat type and habitat size were the only significant predictors during the dry season. Drums, pots, and tires were sources of more than 85% of Ae. aegypti pupae, reinforcing the "key container concept." Targeting these three types of habitats makes epidemiological sense, especially during the dry season.

View details for DOI 10.1007/s00436-022-07777-0

View details for PubMedID 36683088

Abstract

Rift Valley fever virus (RVFV) is a zoonotic arbovirus that has profound impact on domestic ruminants and can also be transmitted to humans via infected animal secretions. Urban areas in endemic regions across Africa have susceptible animal and human hosts, dense vector distributions, and source livestock (often from high risk locations to meet the demand for animal protein). Yet, there has never been a documented urban outbreak of RVF. To understand the likely risk of RVFV introduction to urban communities from their perspective and guide future initiatives, we conducted focus group discussions with slaughterhouse workers, slaughterhouse animal product traders, and livestock owners in Kisumu City and Ukunda Town in Kenya. For added perspective and data triangulation, in-depth interviews were conducted one-on-one with meat inspector veterinarians from selected slaughterhouses. A theoretical framework relevant to introduction, transmission, and potential persistence of RVF in urban areas is presented here. Urban livestock were primarily mentioned as business opportunities, but also had personal sentiment. In addition to slaughtering risks, perceived risk factors including consumption of fresh milk. High risk groups' knowledge and experience with RVFV and other zoonotic diseases impacted their consideration personal risk, with consensus towards lower risk in the urban setting compared to rural areas as determination of health risk was said to primarily rely on hygiene practices rather than the slaughtering process. Groups relied heavily on veterinarians to confirm animal health and meat safety, yet veterinarians reported difficulty in accessing RVFV diagnostics. We also identified vulnerable public health regulations including corruption in meat certification outside of the slaughterhouse system, and blood collected during slaughter being used for food and medicine, which could provide a means for direct RVFV community transmission. These factors, when compounded by diverse urban vector breeding habitats and dense human and animal populations, could create suitable conditions for RVFV to arrive an urban center via a viremic imported animal, transmit to locally owned animals and humans, and potentially adapt to secondary vectors and persist in the urban setting. This explorative qualitative study proposes risk pathways and provides initial insight towards determining how urban areas could adapt control measures and plan future initiatives to better understand urban RVF potential.

View details for DOI 10.1371/journal.pntd.0010460

View details for PubMedID 36634153

Abstract

Rift Valley fever virus (RVFV) is an economically devastating, zoonotic arbovirus endemic across Africa with potential to cause severe disease in livestock and humans. Viral spread is primarily driven by movement of domestic ruminants and there is a high potential for transboundary spread. Despite influx of livestock to urban areas in response to the high demand for meat and animal products, RVFV has not been detected in any urban center. The objectives of this study were to determine the feasibility of assessing risk of RVFV introduction to urban Kisumu, Kenya, by testing slaughtered livestock for RVFV exposure and mapping livestock origins. Blood was collected from cattle, sheep, and goats directly after slaughter and tested for anti-RVFV IgG antibodies. Slaughterhouse businessmen responded to a questionnaire on their individual animals' origin, marketplace, and transport means. Thereafter, we mapped livestock flow from origin to slaughterhouse using participatory methods in focus group discussions with stakeholders. Qualitative data on route choice and deviations were spatially integrated into the map. A total of 304 blood samples were collected from slaughtered livestock in October and November 2021. Most (99%) of animals were purchased from 28 different markets across eight counties in Western Kenya. The overall RVFV seroprevalence was 9% (19% cattle, 3% in sheep, and 7% in goats). Migori County bordering Tanzania had the highest county-level seroprevalence (34%) and 80% of all seropositive cattle were purchased at the Suba Kuria market in Migori County. Road quality and animal health influenced stakeholders' decisions for choice of transport means. Overall, this proof-of-concept study offers a sampling framework for RVFV that can be locally implemented and rapidly deployed in response to regional risk. This system can be used in conjunction with participatory maps to improve active livestock surveillance and monitoring of RVFV in Western Kenya, and these methods could be extrapolated to other urban centers or livestock diseases.

View details for DOI 10.1016/j.onehlt.2022.100457

View details for Web of Science ID 000890330700002

View details for PubMedID 36532672

View details for PubMedCentralID PMC9754961

Abstract

Microplastics are plastic particles <5mm in diameter. Since the 1950s, there has been an exponential increase in the production of plastics. As of 2015, it is estimated that approximately 6300 million metric tons of plastic waste had been generated of which 79% has accumulated in landfills or the natural environment. Further, it is estimated that if current trends continue, roughly 12,000 million metric tons of plastic waste will accumulate by 2050. Plastics and microplastics are now found ubiquitously-in the air, water, and soil. Microplastics are small enough to enter the tissues of plants and animals and have been detected in human lungs, stools, placentas, and blood. Their presence in human tissues and the food chain is a cause for concern. While direct clinical evidence or epidemiological studies on the adverse effects of microplastic on human health are lacking, in vitro cellular and tissue studies and in vivo animal studies suggest potential adverse effects. With the ever-increasing presence of plastic waste in our environment, it is critical to understand their effects on our environment and on human health. The use of plastic additives, many of which have known toxic effects are also of concern. This review provides a brief overview of microplastics and the extent of the microplastic problem. There have been a few inroads in regulating plastics but currently these are insufficient to adequately mitigate plastic pollution. We also review recent advances in microplastic testing methodologies, which should support management and regulation of plastic wastes. Significant efforts to reduce, reuse, and recycle plastics are needed at the individual, community, national, and international levels to meet the challenge. In particular, significant reductions in plastic production must occur to curb the impacts of plastic on human and worldwide health, given the fact that plastic is not truly recyclable.

View details for DOI 10.1016/j.envpol.2022.120442

View details for PubMedID 36272609

Abstract

Disposal of health care waste is one of the biggest threats to global sustainable health care. Current practices of dumping domestic and international health care waste into the earth's terra firma and oceans also undermine global health equity by adversely affecting the health of vulnerable communities. While the United Kingdom works toward circular health care economy streams that produce minimal waste, the United States continues to amplify downstream environmental and health effects of health care organizational waste management decisions. This article suggests how to reframe social and ethical responsibility for health care waste production and management by assigning strict accountability to health care organizational leaders, incentivizing circular supply chain implementation and maintenance, and encouraging strong collaborations across medical, plastic, and waste industries.

View details for DOI 10.1001/amajethics.2022.986

View details for PubMedID 36215191

Abstract

Prior studies have demonstrated prolonged presence of yellow fever virus (YFV) RNA in saliva and urine as an alternative to serum. To investigate the presence of YFV RNA in urine, we used RT-PCR for YFV screening in 60 urine samples collected from a large cohort of naturally infected yellow fever (YF) patients during acute and convalescent phases of YF infection from recent YF outbreaks in Brazil (2017 to 2018). Fifteen urine samples from acute phase infection (up to 15days post-symptom onset) and four urine samples from convalescent phase infection (up to 69days post-symptom onset), were YFV PCR-positive. We genotyped YFV detected in seven urine samples (five collected during the acute phase and two collected during the YF convalescent phase). Genotyping indicated the presence of YFV South American I genotype in these samples. To our knowledge, this is the first report of wild-type YFV RNA detection in the urine this far out from symptom onset (up to 69 DPS), including YFV RNA detection during the convalescent phase of YF infection. The detection of YFV RNA in urine is an indicative of YFV infection; however, the results of RT-PCR using urine as sample should be interpreted with care, since a negative result does not exclude the possibility of YFV infection. With a possible prolonged period of detection beyond the viremic phase, the use of urine samples coupled with serological tests, epidemiologic inquiry, and clinical assessment could provide a longer diagnostic window for laboratory YF diagnosis.

View details for DOI 10.1128/jcm.00254-22

View details for PubMedID 35916519

Abstract

The impacts of climate change on global health and populations are far-reaching, yet they disproportionately affect vulnerable groups, thereby exacerbating disparities. As humanity reckons with the emergency of climate change, our global health community needs to contend with our own contributions to greenhouse gas emissions. We know that transformation is possible and that climate action is the antidote to the existential challenge. As a global health community, we have an immense opportunity, responsibility, and commitment to lead, support, inspire, and empower climate action, research, and innovation that align deeply with our mission and core values.

View details for DOI 10.4269/ajtmh.22-0189

View details for PubMedID 35895350

Abstract

The Rift Valley fever virus (RVFV) is a zoonotic arbovirus that can also transmit directly to humans from livestock. Previous studies have shown consumption of sick animal products are risk factors for RVFV infection, but it is difficult to disentangle those risk factors from other livestock rearing activities. Urban areas have an increased demand for animal source foods, different vector distributions, and various arboviruses are understood to establish localized urban transmission cycles. Thus far, RVFV is an unevaluated public health risk in urban areas within endemic regions. We tested participants in our ongoing urban cohort study on dengue (DENV) and chikungunya (CHIKV) virus for RVFV exposure and found 1.6% (57/3,560) of individuals in two urban areas of Kenya had anti-RVFV IgG antibodies. 88% (50/57) of RVFV exposed participants also had antibodies to DENV, CHIKV, or both. Although livestock ownership was very low in urban study sites, RVFV exposure was overall significantly associated with seeing goats around the homestead (OR = 2.34 (CI 95%: 1.18-4.69, p = 0.02) and in Kisumu, RVFV exposure was associated with consumption of raw milk (OR = 6.28 (CI 95%: 0.94-25.21, p = 0.02). In addition, lack of piped water and use of small jugs (15-20 liters) for water was associated with a higher risk of RVFV exposure (OR = 5.36 (CI 95%: 1.23-16.44, p = 0.01) and this may contribute to interepidemic vector-borne maintenance of RVFV. We also investigated perception towards human vaccination for RVFV and identified high acceptance (91% (97/105) at our study sites. This study provides baseline evidence to guide future studies investigating the urban potential of RVFV and highlights the unexplored role of animal products in continued spread of RVFV.

View details for DOI 10.1371/journal.pgph.0000505

View details for PubMedID 36962424

View details for PubMedCentralID PMC10021321

Abstract

Arboviruses are important public health threats in many regions of the world. Nigeria has experienced outbreaks of arboviruses over the past decades, leading to concerns of widespread endemicity, which are frequently misdiagnosed. This study aimed to determine the seroprevalence of dengue virus (DENV) (a flavivirus) and chikungunya virus (CHIKV) (an alphavirus) infections in three major population centers of Nigeria. A convenience sample of 701 sera was collected from both healthy and febrile participants between August 2010 and March 2018. Sera were tested for prior exposure to CHIKV virus and DENV using indirect IgG ELISA. Results showed that 54.1% (379/701) of participants were seropositive for anti-DENV antibodies, 41.3% (290/701) were seropositive for anti-CHIKV antibodies, and 20.1% (141/701) had previous exposure to both. The seropositivity for prior CHIKV exposure and prior exposure to DENV and CHIKV was significantly associated with age (CHIKV: OR = 2.7 (95% CI: 1.7-4.3); DENV and CHIKV: OR = 2.2 (95% CI: 1.2-4.0) for adults compared to participants under 18 years old). Overall, the high seropositivity across all age groups suggests that arboviral infections are prevalent in Nigeria and indicates that surveillance and further epidemiological studies are required to determine the true burden of these infections and the spectrum of diseases associated with these exposures.

View details for DOI 10.3390/pathogens11070762

View details for PubMedID 35890007

Abstract

This study examined whether Aedes aegypti extends its human blood seeking activity into night hours. Human landing catches (HLC) were conducted hourly from early morning (04:30) to late evening (21:30) in urban and rural sites in Kisumu County in western Kenya, and in Kwale County at the coast. Out of 842 female Ae. aegypti mosquitoes, 71 (8.5%) were collected at night (nocturnal), 151 (17.9%) at twilight (crepuscular), and 620 (73.6%) during the day (diurnal). Three-fold and significantly more Ae. aegypti female mosquitoes were collected during the twilight (crepuscular) hours than night (nocturnal) hours. Significantly more Ae. aegypti female mosquitoes were collected during daytime (diurnal) than night time (nocturnal). In general, the number of mosquitoes collected reduced as darkness increased. Extended time into the night to seek for blood meals enhances chances for Ae. aegypti to contact humans and transmit arboviruses diseases.

View details for DOI 10.4269/ajtmh.21-0309

View details for PubMedID 35640647

Abstract

Since March 2020, SARS-CoV-2 has plagued the world with COVID-19 and individuals of all ages have experienced varying symptoms of disease. Older adults were experiencing more severe disease compared to children and were prioritized by vaccination efforts. While biologic therapies and vaccinations were implemented, there were changes in public health restrictions with subsequent surges resulting in more infected children. During these surges there was a rise of different SARS-CoV-2 variants with the dominant variant initially alpha (B.1.1.7 and other Pango lineages) and epsilon (B.1.427/B.1.429) in early 2021 and a dramatic shift to delta (B.1.617.2 and other Pango lineages) by mid-summer 2021. In this study we aimed to characterize the clinical severity and host factors associated with disease by SARS-CoV-2 variant and evaluate if there are differences in disease severity by circulating variant. We retrospectively included all individuals 0-25 years of age who presented to our center and had a positive SARS-CoV-2 RT-PCR, SARS-CoV-2 variant mutation testing, and documented clinical notes from 1 January 2021 through 31 December 2021. We identified 745 individuals who met inclusion criteria and found the delta variant was associated with severe/critical disease compared to the other variants studied. The results of the model showed that underlying respiratory disease and diabetes were risk factors for progression to severe disease. These insights are important when evaluating public health measures and treatment options for children as more variants arise.

View details for DOI 10.3389/fmed.2022.896352

View details for Web of Science ID 000807127000001

View details for PubMedID 35677819

View details for PubMedCentralID PMC9168367

Abstract

From 1975-2009, the WHO guidelines classified symptomatic dengue virus infections as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. In 2009 the case definition was changed to a clinical classification after concern the original criteria was challenging to apply in resource-limited settings and not inclusive of a substantial proportion of severe dengue cases. Our goal was to examine how well the current WHO definition identified new dengue cases at our febrile surveillance sites in Kenya. Between 2014 and 2019 as part of a child cohort study of febrile illness in our four clinical study sites (Ukunda, Kisumu, Msambweni, Chulaimbo) we identified 369 dengue PCR positive symptomatic cases and characterized whether they met the 2009 revised WHO diagnostic criteria for dengue with and without warning signs and severe dengue. We found 62% of our PCR-confirmed dengue cases did not meet criteria per the guidelines. Our findings also correlate with our experience that dengue disease in children in Kenya is less severe as reported in other parts of the world. Although the 2009 clinical classification has recently been criticized for being overly inclusive and non-specific, our findings suggest the 2009 WHO dengue case definition may miss more than 50% of symptomatic infections in Kenya and may require further modification to include the African experience.

View details for DOI 10.1371/journal.pgph.0000175

View details for PubMedID 36962138

Abstract

BACKGROUND: Since Aedes aegypti mosquitoes preferentially breed in domestic containers, control efforts focus on larval source reduction. Our objectives were to design and test the effectiveness of a source reduction intervention to improve caregiver knowledge and behaviors in coastal Kenya.METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cluster-randomized controlled trial with 261 households from 5 control villages and 259 households from 5 intervention villages. From each household, one child (10-16 years old) and his or her primary caregiver participated in the intervention. We assessed caregiver knowledge and behavior at baseline, as well as 3 and 12 months after the intervention. We assessed household entomological indices at baseline and 12 months after the intervention to avoid seasonal interference. We conducted qualitative interviews with 34 caregivers to understand barriers and facilitators to change. We counted and weighed containers collected by children and parents during a community container clean-up and recycling event. After 12 months, caregiver knowledge about and self-reported behavior related to at least one source reduction technique was more than 50 percentage points higher in the intervention compared to control arm (adjusted risk differences for knowledge: 0.69, 95% CI [0.56 to 0.82], and behavior: 0.58 [0.43 to 0.73]). Respondents stated that other family members' actions were the primary barriers to proper container management. The number of containers at households did not differ significantly across arms even though children and parents collected 17,200 containers (1 ton of plastics) which were used to planted 4,000 native trees as part of the community event.CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that source reduction interventions can be effective if designed with an understanding of the social and entomological context. Further, source reduction is not an individual issue, but rather a social/communal issue, requiring the participation of other household and community members to be sustained.

View details for DOI 10.1371/journal.pntd.0010199

View details for PubMedID 35363780

Abstract

Dengue is a re-emerging neglected disease of major public health importance. This review highlights important considerations for dengue disease in Africa, including epidemiology and underestimation of disease burden in African countries, issues with malaria misdiagnosis and co-infections, and potential evidence of genetic protection from severe dengue disease in populations of African descent. The findings indicate that dengue virus prevalence in African countries and populations may be more widespread than reported data suggests, and that the Aedes mosquito vectors appear to be increasing in dissemination and number. Changes in climate, population, and plastic pollution are expected to worsen the dengue situation in Africa. Dengue misdiagnosis is also a problem in Africa, especially due to the typical non-specific clinical presentation of dengue leading to misdiagnosis as malaria. Finally, research suggests that a protective genetic component against severe dengue exists in African descent populations, but further studies should be conducted to strengthen this association in various populations, taking into consideration socioeconomic factors that may contribute to these findings. The main takeaway is that Africa should not be overlooked when it comes to dengue, and more attention and resources should be devoted to this disease in Africa.

View details for DOI 10.3390/v14020233

View details for PubMedID 35215827

Abstract

There is increasing understanding, globally, that climate change and increased pollution will have a profound and mostly harmful effect on human health. This review brings together international experts to describe both the direct (such as heat waves) and indirect (such as vector-borne disease incidence) health impacts of climate change. These impacts vary depending on vulnerability (i.e., existing diseases) and the international, economic, political and environmental context. This unique review also expands on these issues to address a third category of potential longer-term impacts on global health: famine, population dislocation, and environmental justice and education. This scholarly resource explores these issues fully, linking them to global health in urban and rural settings in developed and developing countries. The review finishes with a practical discussion of action that health professionals around the world in our field can yet take.

View details for DOI 10.1111/all.15229

View details for PubMedID 35073410

Abstract

BACKGROUND: Rift 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 FINDINGS: The 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 surveillance methods were also tabulated. In meta-analysis of risks, summary odds ratios were computed using random-effects modeling. 1104 unique human or animal RVFV transmission events were reported in 39 countries during 1999-2021. Outbreaks among humans or animals occurred at rates of 5.8/year and 12.4/year, respectively, with Mauritania, Madagascar, Kenya, South Africa, and Sudan having the most human outbreak years. Men had greater odds of RVFV infection than women, and animal contact, butchering, milking, and handling aborted material were significantly associated with greater odds of exposure. Animal infection risk was linked to location, proximity to water, and exposure to other herds or wildlife. RVFV was detected in a variety of mosquito vectors during interepidemic periods, confirming ongoing transmission.CONCLUSIONS/SIGNIFICANCE: With broad variability in surveillance, case finding, survey design, and RVFV case confirmation, combined with uncertainty about populations-at-risk, there were inconsistent results from location to location. However, it was evident that RVFV transmission is expanding its range and frequency. Gaps assessment indicated the need to harmonize human and animal surveillance and improve diagnostics and genotyping. Given the frequency of RVFV outbreaks, human vaccination has strong potential to mitigate the impact of this now widely endemic disease.

View details for DOI 10.1371/journal.pntd.0009852

View details for PubMedID 35073355

Abstract

Background: Vaccine and sufficient food availability are key factors for reducing pneumonia outbreaks in sub-Saharan Africa.Methods: In this study, the 10-valent pneumococcal conjugate vaccine (Synflorix or PCV10) was administered to a child cohort (5-7 years old, n = 237) in Msambweni, Kenya, to determine relationships between dietary intake, nutritional/socioeconomic status of mothers/caregivers, and vaccine response. 7-day food frequency questionnaire (FFQ), dietary diversity score (DDS) and single 24-h dietary recall were used to address participants' dietary assessment and nutritional status. Individual food varieties were recorded and divided into 9 food groups as recommended by Food and Agriculture Organization. Anthropometric measurements, nasopharyngeal swabs and vaccine administration were performed at the initial visit. Participants were followed 4-8 weeks with a blood draw for pneumococcal IgG titers assessed by Luminex assay.Findings: Chronic malnutrition was prevalent in the cohort (15% stunting, 16% underweight). Unbalanced dietary intake was observed, with mean energy intake 14% below Recommended Dietary Allowances (1,822 Kcal) for 5-7 years age range. 72% of the daily energy was derived from carbohydrates, 18% from fats and only 10% from proteins. Poor anthropometric status (stunting/underweight) was associated with low socioeconomic/educational status and younger mother/caregiver age (p < 0.002). Limited intake of essential micronutrients (vitamins A, E, K) and minerals (calcium, potassium) associated with low consumption of fresh fruits, vegetables, and animal source foods (dairy, meat) was observed and correlated with poor vaccine response (p < 0.001). In contrast, children who consumed higher amounts of dietary fiber, vitamin B1, zinc, iron, and magnesium had adequate vaccine response (p < 0.05). Correlation between higher dietary diversity score (DDS), higher Vitamin E, K, Zinc intake and adequate vaccine response was also observed (p < 0.03).Interpretation: Overall, this study highlights ongoing food scarcity and malnutrition in Kenya and demonstrates the links between adequate socioeconomic conditions, adequate nutrient intake, and vaccine efficacy.

View details for DOI 10.3389/fnut.2022.830294

View details for PubMedID 35677545

View details for Web of Science ID 000778105603117

View details for Web of Science ID 000778105603098

View details for Web of Science ID 000778105601139

View details for Web of Science ID 000778105601094

View details for Web of Science ID 000778105602270

View details for Web of Science ID 000778105601206

View details for Web of Science ID 000778105601180

View details for Web of Science ID 000778105601143

View details for Web of Science ID 000778105603435

View details for Web of Science ID 000778105602535

View details for Web of Science ID 000778105602276

View details for Web of Science ID 000778105603092

View details for Web of Science ID 000778105603119

Abstract

OBJECTIVE: Zika virus (ZIKV) targets neural stem cells in the developing brain. However, the majority of ZIKV-exposed children are born without apparent neurological manifestations. It remains unclear if these children were protected from ZIKV neurotropism or if they harbour subtle pathology that is disruptive to brain development. We assess this by comparing neurodevelopmental outcomes in normocephalic ZIKV-exposed children relative to a parallel control group of unexposed controls.DESIGN: Cohort study.SETTING: Public health centres in Grenada, West Indies.PATIENTS: 384 mother-child pairs were enrolled during a period of active ZIKV transmission (April 2016-March 2017) and prospectively followed up to 30 months. Child exposure status was based on laboratory assessment of prenatal and postnatal maternal serum.MAIN OUTCOME MEASURES: The INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) package and Cardiff Vision Tests, administered and scored by research staff masked to child's exposure status.RESULTS: A total of 131 normocephalic ZIKV exposed (n=68) and unexposed (n=63) children were assessed between 22 and 30 months of age. Approximately half of these children completed vision testing. There were no group differences in sociodemographics. Deficits in visual acuity (31%) and contrast sensitivity (23%) were apparent in the ZIKV-exposed infants in the absence of cognitive, motor, language or behavioural delays.CONCLUSIONS: Overall neurodevelopment is likely to be unaffected in ZIKV-exposed children with normal head circumference at birth and normal head growth in the first 2 years of life. However, the visual system may be selectively vulnerable, which indicates the need for vision testing by 3 years of age.

View details for DOI 10.1136/archdischild-2020-321031

View details for PubMedID 34479857

Abstract

Rift Valley fever virus (RVFV), an emerging arboviral and zoonotic bunyavirus, causes severe disease in livestock and humans. Here, we report the isolation of a panel of monoclonal antibodies (mAbs) from the B cells of immune individuals following natural infection in Kenya or immunization with MP-12 vaccine. The B cell responses of individuals who were vaccinated or naturally infected recognized similar epitopes on both Gc and Gn proteins. The Gn-specific mAbs and two mAbs that do not recognize either monomeric Gc or Gn alone but recognized the hetero-oligomer glycoprotein complex (Gc+Gn) when Gc and Gn were coexpressed exhibited potent neutralizing activities in vitro, while Gc-specific mAbs exhibited relatively lower neutralizing capacity. The two Gc+Gn-specific mAbs and the Gn domain A-specific mAbs inhibited RVFV fusion to cells, suggesting that mAbs can inhibit the exposure of the fusion loop in Gc, a class II fusion protein, and thus prevent fusion by an indirect mechanism without direct fusion loop contact. Competition-binding analysis with coexpressed Gc/Gn and mutagenesis library screening indicated that these mAbs recognize four major antigenic sites, with two sites of vulnerability for neutralization on Gn. In experimental models of infection in mice, representative mAbs recognizing three of the antigenic sites reduced morbidity and mortality when used at a low dose in both prophylactic and therapeutic settings. This study identifies multiple candidate mAbs that may be suitable for use in humans against RVFV infection and highlights fusion inhibition against bunyaviruses as a potential contributor to potent antibody-mediated neutralization.

View details for DOI 10.1073/pnas.2025642118

View details for PubMedID 33782133

Abstract

As we pass the nearly 9 month mark of the coronavirus virus disease 2019 (COVID-19) pandemic in the United States, we sought to compile a brief multi-disciplinary compendium of COVID-19 information learned to date. COVID-19 is an active viral pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that confers high morbidity and mortality. COVID-19 has been associated with: pulmonary compromise and acute respiratory distress syndrome, thrombotic events, inflammation and cytokine, and post-infectious syndromes. Mitigation of these complications and expeditious therapy are a global urgency; this is brief summary of current data and management approaches synthesized from publications, experience, cross-disciplinary expertise (Figure 1).

View details for DOI 10.1016/j.jtct.2021.02.036

View details for PubMedID 33686384

Abstract

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 from long-term means (1983-2019 for rainfall, 2000-2019 for LST) across four study locations in Kenya. We classified extreme climate events as the upper and lower 10% of these calculated LST or rainfall deviations. Monthly Ae. aegypti abundance was recorded in Kenya using four trapping methods. Blood samples were also collected from children with febrile illness presenting to four field sites and tested for dengue virus using an IgG enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). We found that mosquito eggs and adults were significantly more abundant one month following an abnormally wet month. The relationship between mosquito abundance and dengue risk follows a non-linear association. Our findings suggest that early warnings and targeted interventions during periods of abnormal rainfall and temperature, especially flooding, can potentially contribute to reductions in risk of viral transmission.

View details for DOI 10.1371/journal.pntd.0009182

View details for PubMedID 33735293

Abstract

O'nyong-nyong virus (ONNV) is a little-known arbovirus causing intermittent, yet explosive, outbreaks in Africa. It is closely related to chikungunya virus, an emerging infectious disease. O'nyong-nyong virus causes a self-limited illness characterized by bilateral polyarthritis, rash, low-grade fever, and lymphadenopathy. In 1959, an extensive outbreak of ONNV occurred in East Africa, and decades later, another large outbreak was documented in Uganda in 1996. Limited evidence for interepidemic transmission is available, although serologic studies indicate a high prevalence of exposure; 1,045 febrile child participants in western and coastal Kenya were tested for the presence of ONNV using a multiplexed real-time reverse transcriptase-PCR assay. More than half of the participants had malaria parasitemia, and there was no evidence of active ONNV viremia in these participants. Further work is required to better understand the interepidemic circulation of ONNV and to reconcile evidence of high serologic exposure to ONNV among individuals in East Africa.

View details for DOI 10.4269/ajtmh.20-0580

View details for PubMedID 33617476

Abstract

Throughout the last decade, chikungunya virus (CHIKV) and Zika virus (ZIKV) infections have spread globally, causing a spectrum of disease that ranges from self-limited febrile illness to permanent severe disability, congenital anomalies, and early death. Nevertheless, estimates of their aggregate health impact are absent from the literature and are currently omitted from the Global Burden of Disease (GBD) reports. We systematically reviewed published literature and surveillance records to evaluate the global burden caused by CHIKV and ZIKV between 2010 and 2019, to calculate estimates of their disability-adjusted life year (DALY) impact. Extracted data on acute, chronic, and perinatal outcomes were used to create annualized DALY estimates, following techniques outlined in the GBD framework. This study is registered with PROSPERO (CRD42020192502). Of 7,877 studies identified, 916 were screened in detail, and 21 were selected for inclusion. Available data indicate that CHIKV and ZIKV caused the average yearly loss of over 106,000 and 44,000 DALYs, respectively, between 2010 and 2019. Both viruses caused substantially more burden in the Americas than in any other World Health Organization (WHO) region. This unequal distribution is likely due to a combination of limited active surveillance reporting in other regions and the lack of immunity that left the previously unexposed populations of the Americas susceptible to severe outbreaks during the last decade. Long-term rheumatic sequelae provided the largest DALY component for CHIKV, whereas congenital Zika syndrome (CZS) contributed most significantly for ZIKV. Acute symptoms and early mortality accounted for relatively less of the overall burden. Suboptimal reporting and inconsistent diagnostics limit precision when determining arbovirus incidence and frequency of complications. Despite these limitations, it is clear from our assessment that CHIKV and ZIKV represent a significant cause of morbidity that is not included in current disease burden reports. These results suggest that transmission-blocking strategies, including vector control and vaccine development, remain crucial priorities in reducing global disease burden through prevention of potentially devastating arboviral outbreaks.

View details for DOI 10.1371/journal.pntd.0009055

View details for PubMedID 33661908

View details for DOI 10.4269/ajtmh.21-0968

View details for PubMedID 34749307

Abstract

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 robustly capture climate-virus relationships can help guide intervention efforts and climate change disease projections.

View details for DOI 10.1038/s41467-021-21496-7

View details for PubMedID 33623008

Abstract

This commentary describes the creation of the Zika Virus Individual Participant Data Consortium, a global collaboration to address outstanding questions in Zika virus (ZIKV) epidemiology through conducting an individual participant data meta-analysis (IPD-MA). The aims of the IPD-MA are to (1) estimate the absolute and relative risks of miscarriage, fetal loss, and short- and long-term sequelae of fetal exposure; (2) identify and quantify the relative importance of different sources of heterogeneity (e.g., immune profiles, concurrent flavivirus infection) for the risk of adverse fetal, infant, and child outcomes among infants exposed to ZIKV in utero; and (3) develop and validate a prognostic model for the early identification of high-risk pregnancies and inform communication between health care providers and their patients and public health interventions (e.g., vector control strategies, antenatal care, and family planning programs). By leveraging data from a diversity of populations across the world, the IPD-MA will provide a more precise estimate of the risk of adverse ZIKV-related outcomes within clinically relevant subgroups and a quantitative assessment of the generalizability of these estimates across populations and settings. The ZIKV IPD Consortium effort is indicative of the growing recognition that data sharing is a central component of global health security and outbreak response.

View details for DOI 10.3390/tropicalmed5040152

View details for Web of Science ID 000602276200001

View details for PubMedID 33007828

View details for PubMedCentralID PMC7709585

View details for DOI 10.1016/j.ijid.2020.09.921

View details for Web of Science ID 000612135101122

View details for DOI 10.1016/j.ijid.2020.11.065

View details for Web of Science ID 000612135100533

Abstract

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 and video electroencephalography (vEEG). vEEG was collected using a multi-channel microEEG system for a minimum of 20 minutes along with video recording of participant behavior time-locked to the EEG. vEEGs were interpreted independently by two pediatric epileptologists, who were blinded to ZIKV status, via telemedicine platform. Positive screening cases were referred to a local pediatrician for an epilepsy diagnostic evaluation. Epilepsy screens were positive in 2/71 EC (IR: 0.028; 95% CI: 0.003-0.098) and 0/71 UC. In both epilepsy-positive cases, questionnaire responses and interictal vEEGs were consistent with focal, rather than generalized, seizures. Both children met criteria for a clinical diagnosis of epilepsy and good seizure control was achieved with carbamazepine. Our results indicate that epilepsy rates are modestly elevated in EC. Given our small sample size, results should be considered preliminary. They support the use of epilepsy screening procedures in larger epidemiological studies of children with congenital ZIKV exposure, even in the absence of microcephaly, and provide guidance for conducting epilepsy surveillance in resource limited settings.

View details for DOI 10.1371/journal.pntd.0008874

View details for PubMedID 33253174

Abstract

Human health is increasingly threatened by rapid and widespread changes in the environment and climate, including rising temperatures, air and water pollution, disease vector migration, floods, and droughts. In the United States, many medical schools, the American Medical Association, and the National Academy of Sciences have published calls for physicians and physicians-in-training to develop a basic knowledge of the science of climate change and an awareness of the associated health risks. The authors--all medical students and educators--argue for the expeditious redesign of medical school curricula to teach students to recognize, diagnose, and treat the many health conditions exacerbated by climate change as well as understanding public health issues. In this Invited Commentary, the authors briefly review the health impacts of climate change, examine current climate change course offerings and proposals, and describe the rationale for promptly and comprehensively including climate science education in medical school curricula. Efforts in training physicians now will benefit those physicians' communities, whose health will be impacted by a period of remarkable climate change. The bottom line is that the health effects of climate reality cannot be ignored, and people everywhere must adapt as quickly as possible.

View details for DOI 10.1097/ACM.0000000000003861

View details for PubMedID 33239537

Abstract

Little is known about the extent and serotypes of dengue viruses circulating in Africa. We evaluated the presence of dengue viremia during 4 years of surveillance (2014-2017) among children with febrile illness in Kenya. Acutely ill febrile children were recruited from 4 clinical sites in western and coastal Kenya, and 1,022 participant samples were tested by using a highly sensitive real-time reverse transcription PCR. A complete case analysis with genomic sequencing and phylogenetic analyses was conducted to characterize the presence of dengue viremia among participants during 2014-2017. Dengue viremia was detected in 41.9% (361/862) of outpatient children who had undifferentiated febrile illness in Kenya. Of children with confirmed dengue viremia, 51.5% (150/291) had malaria parasitemia. All 4 dengue virus serotypes were detected, and phylogenetic analyses showed several viruses from novel lineages. Our results suggests high levels of dengue virus infection among children with undifferentiated febrile illness in Kenya.

View details for DOI 10.3201/eid2611.200960

View details for Web of Science ID 000596803200012

View details for PubMedID 33079035

View details for PubMedCentralID PMC7588514

Abstract

Yellow fever (YF) is a re-emerging viral zoonosis caused by the Yellow Fever virus (YFV), affecting humans and non-human primates (NHP). YF is endemic in South America and Africa, being considered a burden for public health worldwide despite the availability of an effective vaccine. Acute infectious disease can progress to severe hemorrhagic conditions and has high rates of morbidity and mortality in endemic countries. In 2016, Brazil started experiencing one of the most significant YF epidemics in its history, with lots of deaths being reported in regions that were previously considered free of the disease. Here, we reviewed the historical aspects of YF in Brazil, the epidemiology of the disease, the challenges that remain in Brazil's public health context, the main lessons learned from the recent outbreaks, and our perspective for facing future YF epidemics.

View details for DOI 10.3390/v12111233

View details for Web of Science ID 000594354900001

View details for PubMedID 33143114

View details for PubMedCentralID PMC7692154

Abstract

BACKGROUND: Aedes aegypti is an efficient vector of several arboviruses of public health importance, including Zika and dengue. Currently vector management is the only available avenue for disease control. Development of efficient vector control strategies requires a thorough understanding of vector ecology. In this study, we identified households that are consistently productive for Ae. aegypti pupae and determined the ecological and socio-demographic factors associated with the persistence and abundance of pupae in households in rural and urban Kenya.METHODS: We collected socio-demographic, environmental and entomological data monthly from July 2014 to June 2018 from 80 households across four sites in Kenya. Pupae count data were collected via entomological surveillance of households and paired with socio-demographic and environmental data. We calculated pupal persistence within a household as the number of months of pupal presence within a year. We used spatially explicit generalized additive mixed models (GAMMs) to identify the risk factors for pupal abundance, and a logistic regression to identify the risk factors for pupal persistence in households.RESULTS: The median number of months of pupal presence observed in households was 4 and ranged from 0 to 35 months. We identified pupal persistence in 85 house-years. The strongest risk factors for high pupal abundance were the presence of bushes or tall grass in the peri-domicile area (OR: 1.60, 95% CI: 1.13-2.28), open eaves (OR: 2.57, 95% CI: 1.33-4.95) and high habitat counts (OR: 1.42, 95% CI: 1.21-1.66). The main risk factors for pupal persistence were the presence of bushes or tall grass in the peri-domicile (OR: 4.20, 95% CI: 1.42-12.46) and high number of breeding sites (OR: 2.17, 95% CI: 1.03-4.58).CONCLUSIONS: We observed Ae. aegypti pupal persistence at the household level in urban and rural and in coastal and inland Kenya. High counts of potential breeding containers, vegetation in the peri-domicile area and the presence of eaves were strongly associated with increased risk of pupal persistence and abundance. Targeting households that exhibit pupal persistence alongside the risk factors for pupal abundance in vector control interventions may result in more efficient use of limited resources.

View details for DOI 10.1186/s13071-020-04378-7

View details for PubMedID 33004074

Abstract

Yellow Fever (YF) is an acute febrile illness caused by yellow fever virus (YFV), a mosquito-borne flavivirus transmitted to humans and non-human primates. In Brazil, YF is a public health threat and may cause recurrent epidemics, even with the availability of a vaccine. We evaluated the sero-status for YFV in 581 individuals living in a risk area for YF in Brazil. The area presents history of cases and is located in the southeast region of country where outbreaks of YF have been reported since 2016. Through, a PRNT assay, we found 25.8% of individuals lacking YF-neutralizing antibodies. Furthermore, neutralizing antibodies were not detected in 10 individuals with proven vaccination. Our findings reinforce the importance of surveillance systems and the need of an urgent intensification of immunization programs in regions with YFV circulation. Monitoring susceptible individuals that could act as potential disseminators for YFV in risk areas should also be considered.

View details for DOI 10.1016/j.vaccine.2020.07.077

View details for Web of Science ID 000573425200015

View details for PubMedID 32788140

Abstract

BACKGROUND: In low-resource, malaria-endemic settings, accurate diagnosis of febrile illness in children is challenging. The World Health Organization (WHO) currently recommends laboratory-confirmed diagnosis of malaria prior to starting treatment in stable children. Factors guiding management of children with undifferentiated febrile illness outside of malaria are not well understood.METHODS: This study examined clinical presentation and management of a cohort of febrile Kenyan children at five hospital/clinic sites from January 2014 to December 2017. Chi-squared and multivariate regression analyses were used to compare frequencies and correlate demographic, environmental, and clinical factors with patient diagnosis and prescription of antibiotics.RESULTS: Of 5735 total participants, 68% were prescribed antibiotic treatment (n = 3902), despite only 28% given a diagnosis of bacterial illness (n = 1589). Factors associated with prescription of antibiotic therapy included: negative malaria testing, reporting head, ears, eyes, nose and throat (HEENT) symptoms (i.e., cough, runny nose), HEENT findings on exam (i.e., nasal discharge, red throat), and having a flush toilet in the home (likely a surrogate for higher socioeconomic status).CONCLUSION: In a cohort of acutely ill Kenyan children, prescription of antimalarial therapy and malaria test results were well correlated, whereas antibiotic treatment was prescribed empirically to most of those who tested malaria negative. Clinical management of febrile children in these settings is difficult given the lack of diagnostic testing. Providers may benefit from improved clinical education and implementation of enhanced guidelines in this era of malaria testing, as their management strategies must rely primarily on critical thinking and decision-making skills.

View details for DOI 10.1093/cid/ciaa1305

View details for PubMedID 32882032

View details for Web of Science ID 000569270300013

Abstract

In November 2019, The World Health Organization (WHO) issued a draft set of Target Product Profiles (TPPs) describing optimal and minimally acceptable targets for vaccines against Rift Valley fever (RVF), a Phlebovirus with a three segmented genome, in both humans and ruminants. The TPPs contained rigid requirements to protect against genomic reassortment of live, attenuated vaccines (LAVs) with wild-type RVF virus (RVFV), which place undue constraints on development and regulatory approval of LAVs. We review the current LAVs in use and in development, and conclude that there is no evidence that reassortment between LAVs and wild-type RVFV has occurred during field use, that such a reassortment event if it occurred would have no untoward consequence, and that the TPPs should be revised to provide a more balanced assessment of the benefits versus the theoretical risks of reassortment.

View details for DOI 10.1016/j.jvacx.2020.100060

View details for Web of Science ID 000608620000001

View details for PubMedID 32337506

View details for PubMedCentralID PMC7176985

Abstract

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. Furthermore, publications on dengue prevalence are temporally and geographically fragmented, perhaps due to limited resources. However, this gap in data and knowledge highlights the urgent need for a country-wide surveillance system and continued study of dengue burden in Sudan to accurately estimate the disease prevalence and determine the associated risk factors.

View details for DOI 10.3390/tropicalmed5030120

View details for PubMedID 32708492

Abstract

Rift Valley fever virus (RVFV) is a zoonotic phlebovirus of the Phenuiviridae family with great opportunity for emergence in previously unaffected regions, despite its current geographical limits. Outbreaks of RVFV often infect humans or domesticated animals, such as livestock, concurrently and occur sporadically, ranging from localized outbreaks in villages to multi-country events that spread rapidly. The true burden of Rift Valley fever (RVF) is not well defined due to underreporting, misdiagnosis caused by the broad spectrum of disease presentation, and minimal access for rapid and accurate laboratory confirmation. Severe symptoms may include hemorrhagic fever, loss of vision, psychological impairment or disturbances, and organ failure. Those living in endemic areas and travelers should be aware of the potential for exposure to ongoing outbreaks or interepidemic transmission, and engage in behaviors to minimize exposure risks, as vaccinations in humans are currently unavailable and animal vaccinations are not used routinely or ubiquitously. The lack of vaccines approved for use in humans is concerning, as RVFV has proven to be highly pathogenic in naive populations, causing severe disease in a large percent of confirmed cases, which could have considerable impact on human health.

View details for DOI 10.3390/tropicalmed5020089

View details for PubMedID 32498264

Abstract

BACKGROUND: Prevention and treatment of malaria during pregnancy is crucial in dealing with maternal mortality and adverse fetal outcomes. The World Health Organization recommendation to treat all pregnant women with sulfadoxine-pyrimethamine (SP) through antenatal care structures was implemented in Kenya in the year 1998, but concerns about its effectiveness in preventing malaria in pregnancy has arisen due to the spread of SP resistant parasites. This study aimed to determine the prevalence of SP resistance markers in Plasmodium falciparum parasites isolated from pregnant women seeking antenatal care at Msambweni County Referral Hospital, located in coastal Kenya, between the year 2013 and 2015.METHODS: This hospital-based study included 106 malaria positive whole blood samples for analysis of SP resistance markers within the Pfdhfr gene (codons 51, 59 and 108) and Pfdhps gene (codons 437 and 540). The venous blood collected from all pregnant women was tested for malaria via light microscopy, then the malaria positive samples were separated into plasma and red cells and stored in a -86 freezer for further studies. Archived red blood cells were processed for molecular characterization of SP resistance markers within the Pfdhfr and Pfdhps genes using real time PCR platform and Sanger sequencing.RESULTS: All samples had at least one mutation in the genes associated with drug resistance; polymorphism prevalence of Pfdhfr51I, 59R and 108N was at 88.7%, 78.3% and 93.4%, respectively, while Pfdhps polymorphism accounted for 94.3% and 91.5% at 437G and 540E, respectively. Quintuple mutations (at all the five codons) conferring total SP resistance had the highest prevalence of 85.8%. Quadruple mutations were observed at a frequency of 10.4%, and 24.5% had a mixed outcome of both wildtype and mutant genotypes in the genes of interest.CONCLUSION: The data suggest a high prevalence of P. falciparum genetic variations conferring resistance to SP among pregnant women, which may explain reduced efficacy of IPTp treatment in Kenya. There is need for extensive SP resistance profiling in Kenya to inform IPTp drug choices for successful malaria prevention during pregnancy.

View details for DOI 10.1186/s12936-020-03263-z

View details for PubMedID 32448228

Abstract

BACKGROUND: Chronic malnutrition, often measured as stunted growth, is an understudied global health problem. Though poor nutritional intake has been linked to stunted growth, there is evidence suggesting environmental exposures may have a significant role in its occurrence. Here, we characterize the non-nutritional prenatal and postnatal factors that contribute to early childhood stunted growth in rural coastal Kenya.METHODS: Overall, 232 women and 244 children from a 2012-2015 maternal-child cohort in Msambweni, Kenya were included. Women were tested for parasitic infections during the prenatal period and at the time of delivery. Children were tested for parasitic infections and assessed for stunted growth using height-for-age Z-scores (HAZ) at 6-month intervals after birth. Socioeconomic status (SES) was evaluated using both a simplified water, asset, maternal education, and income (WAMI) index and a principal component analysis (PCA) asset score. Multivariate logistic regression analysis was used to determine the relative influence of prenatal and postnatal factors on the occurrence of stunted growth.RESULTS: Of the 244 children (ages 6-37months), 60 (25%) were stunted at the study endpoint. 179 mothers (77%) had at least one parasitic infection during pregnancy and 94 children (38%) had at least one parasitic infection during the study period. There was no significant association between maternal parasitic infection and child stunted growth (p=1.00). SES as determined using the WAMI index was not associated with HAZ in linear regression analysis (p=0.307), however, the PCA asset score was (p=0.048). Multivariate logistic regression analysis identified low birth weight (AOR: 3.24, 95% CI: [1.38, 7.57]) and child parasitic infectious disease burden (AOR: 1.41, 95% CI: [1.05, 1.95]) as independent predictors of stunted growth, though no significant association was identified with PCA asset score (AOR: 0.98, 95% CI: [0.88, 1.10]).CONCLUSIONS: Stunted growth remains highly prevalent in rural Kenya, with low birth weight and child parasitic infectious disease burden demonstrated to be significantly associated with this indicator of chronic malnutrition. These results emphasize the multifaceted nature of stunted growth and the need to address both the prenatal and postnatal environmental factors that contribute to this problem.

View details for DOI 10.1186/s12887-020-02110-z

View details for PubMedID 32398049

View details for DOI 10.1002/oa.2862

View details for Web of Science ID 000512278200001

Abstract

The GloPID-R (Global Research Collaboration for Infectious Disease Preparedness) chikungunya (CHIKV), o'nyong-nyong (ONNV) and Mayaro virus (MAYV) Working Group has been established to investigate natural history, epidemiology and clinical aspects of infection by these viruses. Here, we present a report dedicated to entomological aspects of CHIKV, ONNV and MAYV. Recent global expansion of chikungunya virus has been possible because CHIKV established a transmission cycle in urban settings using anthropophilic vectors such as Aedes albopictus and Aedes aegypti. MAYV and ONNV have a more limited geographic distribution, being confined to Africa (ONNV) and central-southern America (MAYV). ONNV is probably maintained through an enzootic cycle that has not been characterized yet, with Anopheles species as main vectors and humans as amplification hosts during epidemics. MAYV is transmitted by Haemagogus species in an enzootic cycle using non-human primates as the main amplification and maintenance hosts, and humans becoming sporadically infected when venturing in or nearby forest habitats. Here, we focused on the transmission cycle and natural vectors that sustain circulation of these viruses in their respective locations. The knowledge of the natural ecology of transmission and the capacity of different vectors to transmit these viruses is crucial to understand CHIKV emergence, and to assess the risk that MAYV and ONNV will expand on wide scale using anthropophilic mosquito species not normally considered primary vectors. Finally, the experts identified knowledge gaps and provided adapted recommendations, in order to address future entomological investigations in the right direction.

View details for DOI 10.1016/j.antiviral.2019.104670

View details for Web of Science ID 000523596900024

View details for PubMedID 31812638

Abstract

The risk of emergence and/or re-emergence of arthropod-borne viral (arboviral) infections is rapidly growing worldwide, particularly in Africa. The burden of arboviral infections and diseases is not well scrutinized because of the inefficient surveillance systems in endemic countries. Furthermore, the health systems are fully occupied by the burden of other co-existing febrile illnesses, especially malaria. In this review we summarize the epidemiology and risk factors associated with the major human arboviral diseases and highlight the gap in knowledge, research, and control in Sudan. Published data in English up to March 2019 were reviewed and are discussed to identify the risks and challenges for the control of arboviruses in the country. In addition, the lack of suitable diagnostic tools such as viral genome sequencing, and the urgent need for establishing a genomic database of the circulating viruses and potential sources of entry are discussed. Moreover, the research and healthcare gaps and global health threats are analyzed, and suggestions for developing strategic health policy for the prevention and control of arboviruses with focus on building the local diagnostic and research capacity and establishing an early warning surveillance system for the early detection and containment of arboviral epidemics are offered.

View details for DOI 10.3390/v12010081

View details for PubMedID 31936607

Abstract

Yellow fever (YF) is an acute viral disease, affecting humans and non-human primates (NHP), caused by the yellow fever virus (YFV). Despite the existence of a safe vaccine, YF continues to cause morbidity and mortality in thousands of people in Africa and South America. Since 2016, massive YF outbreaks have taken place in Brazil, reaching YF-free zones, causing thousands of deaths of humans and NHP. Here we reviewed the main epidemiological aspects, new clinical findings in humans, and issues regarding YFV infection in vectors and NHP in Brazil. The 2016-2019 YF epidemics have been considered the most significant outbreaks of the last 70years in the country, and the number of human cases was 2.8 times higher than total cases in the previous 36years. A new YFV lineage was associated with the recent outbreaks, with persistent circulation in Southeast Brazil until 2019. Due to the high number of infected patients, it was possible to evaluate severity and death predictors and new clinical features of YF. Haemagogus janthinomys and Haemagogus leucocelaenus were considered the primary vectors during the outbreaks, and no human case suggested the occurrence of the urban transmission cycle. YFV was detected in a variety of NHP specimens presenting viscerotropic disease, similar to that described experimentally. Further studies regarding NHP sensitivity to YFV, YF pathogenesis, and the duration of the immune response in NHP could contribute to YF surveillance, control, and future strategies for NHP conservation.

View details for DOI 10.1186/s12985-019-1277-7

View details for PubMedID 31973727

Abstract

Background: Iron deficiency may impair adaptive immunity and is common among African infants at time of vaccination. Whether iron deficiency impairs vaccine response and whether iron supplementation improves humoral vaccine response is uncertain. Methods: We performed two studies in southern coastal Kenya. In a birth cohort study, we followed infants to age 18 mo and assessed whether anemia or iron deficiency at time of vaccination predicted vaccine response to three-valent oral polio, diphtheria-tetanus-whole cell pertussis-Haemophilus influenzae type b vaccine, ten-valent pneumococcal-conjugate vaccine and measles vaccine. Primary outcomes were anti-vaccine-IgG and seroconversion at age 24 wk and 18 mo. In a randomized trial cohort follow-up, children received a micronutrient powder (MNP) with 5 mg iron daily or a MNP without iron for 4 mo starting at age 7.5 mo and received measles vaccine at 9 and 18 mo; primary outcomes were anti-measles IgG, seroconversion and avidity at age 11.5 mo and 4.5 y. Findings: In the birth cohort study, 573 infants were enrolled and 303 completed the study. Controlling for sex, birthweight, anthropometric indices and maternal antibodies, hemoglobin at time of vaccination was the strongest positive predictor of: (A) anti-diphtheria and anti-pertussis-IgG at 24 wk (p = 0.0071, p = 0.0339) and 18 mo (p = 0.0182, p = 0.0360); (B) anti-pertussis filamentous hemagglutinin-IgG at 24 wk (p = 0.0423); and (C) anti-pneumococcus 19 IgG at 18 mo (p = 0.0129). Anemia and serum transferrin receptor at time of vaccination were the strongest predictors of seroconversion against diphtheria (p = 0.0484, p = 0.0439) and pneumococcus 19 at 18 mo (p = 0.0199, p = 0.0327). In the randomized trial, 155 infants were recruited, 127 and 88 were assessed at age 11.5 mo and 4.5 y. Compared to infants that did not receive iron, those who received iron at time of vaccination had higher anti-measles-IgG (p = 0.0415), seroconversion (p = 0.0531) and IgG avidity (p = 0.0425) at 11.5 mo. Interpretation: In Kenyan infants, anemia and iron deficiency at time of vaccination predict decreased response to diphtheria, pertussis and pneumococcal vaccines. Primary response to measles vaccine may be increased by iron supplementation at time of vaccination. These findings argue that correction of iron deficiency during early infancy may improve vaccine response.

View details for DOI 10.3389/fimmu.2020.01313

View details for PubMedID 32754150

Abstract

Understanding mosquito breeding behavior as well as human perspectives and practices are crucial for designing interventions to control Aedes aegypti mosquito-borne diseases as these mosquitoes primarily breed in water-holding containers around people's homes. The objectives of this study were to identify productive mosquito breeding habitats in coastal Kenya and to understand household mosquito management behaviors and their behavioral determinants. The field team conducted entomological surveys in 444 households and semi-structured interviews with 35 female caregivers and 37 children in Kwale County, coastal Kenya, between May and December 2016. All potential mosquito habitats with or without water were located, abundances of mosquito immatures measured and their characteristics recorded. Interviews explored household mosquito management behaviors and their behavioral determinants. 2,452 container mosquito habitats were counted containing 1,077 larvae and 390 pupae, predominantly Aedes species. More than one-third of the positive containers were found outside houses in 1 of the 10 villages. Containers holding water with no intended purpose contained 55.2% of all immature mosquitoes. Containers filled with rainwater held 95.8% of all immature mosquitoes. Interviews indicated that households prioritize sleeping under bednets as a primary protection against mosquito-borne disease because of concern about night-time biting, malaria-transmitting Anopheles mosquitoes. Respondents had limited knowledge about the mosquito life cycle, especially with respect to day-time biting, container-breeding Aedes mosquitoes. Therefore, respondents did not prioritize source reduction. Most mosquitoes breed in containers that have no direct or immediate purpose ("no-purpose containers"). These containers may be left unattended for several days allowing rainwater to collect, and creating ideal conditions for mosquito breeding. An intervention that requires little effort and targets only the most productive containers could effectively reduce mosquito indices and, relatedly, mosquito-borne disease risk.

View details for DOI 10.1371/journal.pntd.0008239

View details for PubMedID 32392226

Abstract

Malaria is a long-standing public health problem in sub-Saharan Africa, whereas arthropod-borne viruses (arboviruses) such as dengue and chikungunya cause an under-recognised burden of disease. Many human and environmental drivers affect the dynamics of vector-borne diseases. In this Personal View, we argue that the direct effects of warming temperatures are likely to promote greater environmental suitability for dengue and other arbovirus transmission by Aedes aegypti and reduce suitability for malaria transmission by Anopheles gambiae. Environmentally driven changes in disease dynamics will be complex and multifaceted, but given that current public efforts are targeted to malaria control, we highlight Ae aegypti and dengue, chikungunya, and other arboviruses as potential emerging public health threats in sub-Saharan Africa.

View details for DOI 10.1016/S2542-5196(20)30178-9

View details for PubMedID 32918887

Abstract

Zika virus (ZIKV) is a mosquito-borne, single-stranded DNA flavivirus that is teratogenic and neurotropic. Similar to the teratogenic effects of other TORCH infections, ZIKV infection during pregnancy can have an adverse impact on fetal and neonatal development. Epilepsy is detected in 48-96% of children with Congenital Zika Syndrome (CZS) and microcephaly. Early epilepsy surveillance is needed in children with prenatal ZIKV exposure; yet, most ZIKV-endemic regions do not have specialist epilepsy care. Here, we describe the demographic, clinical, imaging, and EEG characteristics of a 2-year-old child with CZS and microcephaly who presented with focal epileptiform activity, suboptimal growth, and severe neurodevelopmental delays. Administration of a brief seizure questionnaire by allied health professionals to the patient's caregiver helped to characterize the child's seizure semiology and differentiate focal from generalized seizure features. A telemedicine EEG interpretation platform provided valuable diagnostic information for the patient's local pediatrician to integrate into her treatment plan. This case illustrates that CZS can present with focal epilepsy features and that a telemedicine approach can be used to bridge the gap between epilepsy specialists and local care providers in resource limited ZIKV-endemic regions to achieve better seizure control in children with CZS.

View details for DOI 10.1016/j.ebr.2020.100411

View details for Web of Science ID 000610548000003

View details for PubMedID 33313503

View details for PubMedCentralID PMC7720018

Abstract

To evaluate pregnancy and neonatal outcomes, disease severity, and mother-to-child transmission of pregnant women with Chikungunya infection (CHIKV).Retrospective observational study.Grenada.Women who gave birth during a Chikungunya outbreak between January 2014 to September 2015 were eligible.This descriptive study investigated 731 mother-infant pairs who gave birth during a CHIKV outbreak. Women and infants underwent serologic testing for CHIKV by ELISA.Primary outcomes: composite pregnancy complication (abruption, vaginal bleeding, preterm labor/cervical incompetence, cesarean delivery for fetal distress/abruption/placental abnormality or delivery for fetal distress) and composite neonatal morbidity.Of 416 mother-infant pairs, 150 (36%) had CHIKV during pregnancy, 135 (33%) had never had CHIKV, and 131 (31%) had CHIKV outside of pregnancy. Mean duration of joint pain was shorter among women infected during pregnancy ( = 898 days, = 277 days) compared to infections outside of pregnancy ( = 1,064 days, = 244 days) (P<0.0001). Rates of pregnancy complications (RR = 0.76, p = 0.599), intrapartum complications (RR = 1.50, p = 0.633), and neonatal outcomes were otherwise similar. Possible mother-to-child transmission occurred in two (1.3%) mother-infant pairs and two of eight intrapartum infections (25%).CHIKV infection during pregnancy may be protective against long-term joint pain sequelae that is often associated with acute CHIKV infection. Infection during pregnancy did not appear to pose a risk for pregnancy complications nor neonatal health, but maternal infection just prior to delivery might have increased risk of mother-to-child transmission of CHIKV.

View details for DOI 10.1111/1471-0528.16562

View details for PubMedID 33040457

Abstract

The 2005-06 chikungunya virus (CHIKV) outbreak in La Runion suggested that mothers could transmit CHIKV to their neonates while viremic during the intrapartum period, and more than half of the infected neonates showed impaired neurodevelopment at two years of age. However, data sparsity precluded an overview of the developmental impact of vertical infection within the whole prenatal period.The current study assessed two-year old children born to mothers who were infected during the 2014 CHIKV outbreak in Grenada to determine the neurodevelopmental impact of perinatal CHIKV infection throughout gestation. Mother and child infection status were confirmed by serologic testing (IgG and IgM) for CHIKV. Cognitive, fine motor, gross motor, language and behavioral outcomes were assessed at two years of age on the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA).No differences in neurodevelopmental outcomes were observed between two-year-old children born to mothers infected with CHIKV during gestation (n = 149) and those born to mothers not infected with CHIKV (n = 161). No differences were found in INTER-NDA scores between children infected with CHIKV (n = 47) and children not infected with CHIKV (n = 592). Likewise, there were no differences between children infected with CHIKV post-partum (n = 19) versus children not infected with CHIKV (n = 592).Our findings suggest that children exposed and/or infected with CHIKV outside of the intrapartum period experience no significant neurodevelopmental delay at two years of age, as measured by the INTER-NDA, compared to their unexposed and/or uninfected peers. These results complement those of previous studies which showed a neurodevelopmental risk only for children infected during the intrapartum period, while the mother was highly viremic. These results might be reassuring for women of childbearing age and public health officials in CHIKV-endemic regions.

View details for DOI 10.1371/journal.pntd.0008546

View details for PubMedID 33017393

Abstract

Arboviruses are among the most important emerging pathogens due to their increasing public health impact. In Kenya, continued population growth and associated urbanization are conducive to vector spread in both urban and rural environments, yet mechanisms of viral amplification in vector populations is often overlooked when assessing risks for outbreaks. Thus, the characterization of local arbovirus circulation in mosquito populations is imperative to better inform risk assessments and vector control practices. Aedes species mosquitoes were captured at varying stages of their life cycle during different seasons between January 2014 and May 2016 at four distinct sites in Kenya, and tested for chikungunya (CHIKV), dengue (DENV) and Zika (ZIKV) viruses by RT-PCR. CHIKV was detected in 45 (5.9%) and DENV in 3 (0.4%) mosquito pools. No ZIKV was detected. Significant regional variation in prevalence was observed, with greater frequency of CHIKV on the coast. DENV was detected exclusively on the coast. Both viruses were detected in immature mosquitoes of both sexes, providing evidence of transovarial transmission of these arboviruses in local mosquitoes. This phenomenon may be driving underlying viral maintenance that may largely contribute to periodic re-emergence among humans in Kenya.

View details for DOI 10.1371/journal.pntd.0008362

View details for PubMedID 32559197

View details for DOI 10.1016/j.antiviral.2019.104611

View details for PubMedID 31545982

View details for DOI 10.1016/j.antiviral.2019.104610

View details for PubMedID 31545981

View details for DOI 10.1093/sysbio/syy087

View details for Web of Science ID 000489700900011

Abstract

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

View details for DOI 10.4269/ajtmh.18-1009

View details for PubMedID 31436151

Abstract

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

View details for DOI 10.1136/bmjopen-2018-026092

View details for PubMedID 31217315

View details for DOI 10.1016/j.antiviral.2019.03.009

View details for Web of Science ID 000469522900007

View details for DOI 10.1371/journal.pntd.0007008

View details for Web of Science ID 000470188100003

Abstract

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

View details for PubMedID 30893298

View details for DOI 10.1371/journal.pntd.0007258

View details for Web of Science ID 000463799300050

Abstract

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

View details for PubMedID 30818339

View details for DOI 10.1371/journal.pntd.0007172

View details for Web of Science ID 000459970700056

Abstract

Background: Infectious disease epidemiology and planetary health literature often cite solid waste and plastic pollution as risk factors for vector-borne diseases and urban zoonoses; however, no rigorous reviews of the risks to human health have been published since 1994. This paper aims to identify research gaps and outline potential solutions to interrupt the vicious cycle of solid wastes; disease vectors and reservoirs; infection and disease; and poverty. Methods: We searched peer-reviewed publications from PubMed, Google Scholar, and Stanford Searchworks, and references from relevant articles using the search terms ("disease" OR "epidemiology") AND ("plastic pollution," "garbage," and "trash," "rubbish," "refuse," OR "solid waste"). Abstracts and reports from meetings were included only when they related directly to previously published work. Only articles published in English, Spanish, or Portuguese through 2018 were included, with a focus on post-1994, after the last comprehensive review was published. Cancer, diabetes, and food chain-specific articles were outside the scope and excluded. After completing the literature review, we further limited the literature to "urban zoonotic and biological vector-borne diseases" or to "zoonotic and biological vector-borne diseases of the urban environment." Results: Urban biological vector-borne diseases, especially Aedes-borne diseases, are associated with solid waste accumulation but vector preferences vary over season and region. Urban zoonosis, especially rodent and canine disease reservoirs, are associated with solid waste in urban settings, especially when garbage accumulates over time, creating burrowing sites and food for reservoirs. Although evidence suggests the link between plastic pollution/solid waste and human disease, measurements are not standardized, confounders are not rigorously controlled, and the quality of evidence varies. Here we propose a framework for solutions-based research in three areas: innovation, education, and policy. Conclusions: Disease epidemics are increasing in scope and scale with urban populations growing, climate change providing newly suitable vector climates, and immunologically naive populations becoming newly exposed. Sustainable solid waste management is crucial to prevention, specifically in urban environments that favor urban vectors such as Aedes species. We propose that next steps should include more robust epidemiological measurements and propose a framework for solutions-based research.

View details for DOI 10.3389/fpubh.2019.00405

View details for PubMedID 32010659

View details for DOI 10.4269/ajtmh.17-0688

View details for Web of Science ID 000476680300039

View details for DOI 10.4269/ajtmh.18-0297

View details for Web of Science ID 000455207700036

Abstract

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

View details for PubMedID 31074407

View details for PubMedID 31071087

Abstract

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

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

View details for PubMedID 31171037

View details for Web of Science ID 000507364503150

View details for Web of Science ID 000507364502223

View details for Web of Science ID 000507364501005

View details for Web of Science ID 000507364503148

View details for Web of Science ID 000507364502167

View details for Web of Science ID 000507364504159

View details for Web of Science ID 000507364502100

Abstract

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

View details for PubMedID 30597118

View details for DOI 10.3390/ijerph15102144

View details for Web of Science ID 000448818100086

Abstract

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

View details for PubMedID 30274270

Abstract

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

View details for PubMedID 29897898

View details for DOI 10.1371/journal.pntd.0006510

View details for Web of Science ID 000437442000019

Abstract

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

View details for DOI 10.1093/infdis/jiy047

View details for Web of Science ID 000430729300014

View details for PubMedID 29390149

View details for PubMedCentralID PMC5894090

View details for Web of Science ID 000453090804009

View details for Web of Science ID 000453090801286

View details for Web of Science ID 000453090801282

View details for PubMedID 29526344

Abstract

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

View details for PubMedID 29488456

Abstract

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

View details for PubMedID 29308412

Abstract

The literature on sero-epidemiological studies of flaviviral infections in the African continent is quite scarce. Much of the viral epidemiology studies have been focussing on diseases such as HIV/AIDS because of their sheer magnitude and impact on the lives of people in the various affected countries. Increasingly disease outbreaks caused by arboviruses such as the recent cases of chikungunya virus, dengue virus and yellow fever virus have prompted renewed interest in studying these viruses. International agencies from the US, several EU nations and China are starting to build collaborations to build capacity in many African countries together with established institutions to conduct these studies. The Tofo Advanced Study Week (TASW) was established to bring the best scientists from the world to the tiny seaside town of Praia do Tofo to rub shoulders with African virologists and discuss cutting-edge science and listen to the work of researchers in the field. In 2015 the 1st TASW focussed on Ebola virus. The collections of abstracts from participants at the 2nd TASW which focused on Dengue and Zika virus as well as presentations on other arboviruses are collated in this chapter.

View details for PubMedID 29845545

View details for Web of Science ID 000461386605149

View details for Web of Science ID 000461386602182

View details for Web of Science ID 000461386602163

View details for Web of Science ID 000461386604049

View details for Web of Science ID 000461386602365

View details for Web of Science ID 000461386603233

View details for Web of Science ID 000461386604460

View details for Web of Science ID 000461386602164

View details for Web of Science ID 000461386602657

View details for Web of Science ID 000461386602140

View details for Web of Science ID 000461386602194

View details for Web of Science ID 000461386602203

View details for Web of Science ID 000461386604303

View details for Web of Science ID 000461386602240

View details for Web of Science ID 000461386602158

View details for Web of Science ID 000461386602521

View details for Web of Science ID 000461386604305

View details for Web of Science ID 000461386604097

View details for DOI 10.4269/ajtmh.16-0813

View details for Web of Science ID 000430958200014

View details for Web of Science ID 000461386603295

View details for Web of Science ID 000461386603228

Abstract

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

View details for PubMedID 29692303

Abstract

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

View details for PubMedID 29623138

Abstract

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

View details for PubMedID 29261766

View details for Web of Science ID 000412851501363

View details for Web of Science ID 000412851502228

View details for Web of Science ID 000412851502105

View details for Web of Science ID 000412851502229

View details for Web of Science ID 000412851503427

View details for Web of Science ID 000412851502230

View details for Web of Science ID 000412851501095

View details for Web of Science ID 000412851501177

View details for Web of Science ID 000412851502947

View details for Web of Science ID 000412851502864

Abstract

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

View details for DOI 10.3201/eid2311.170807

View details for Web of Science ID 000413109500030

View details for PubMedID 29048283

View details for PubMedCentralID PMC5652413

View details for Web of Science ID 000412851502888

View details for Web of Science ID 000412851502583

View details for Web of Science ID 000412851502231

View details for Web of Science ID 000412851501084

View details for Web of Science ID 000412851501092

Abstract

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

View details for PubMedID 29040262

Abstract

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

View details for PubMedID 28931399

Abstract

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

View details for DOI 10.3390/vaccines5030029

View details for PubMedID 28925970

View details for PubMedCentralID PMC5620560

View details for DOI 10.3390/vaccines5030029

View details for Web of Science ID 000411994000014

Abstract

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

View details for PubMedID 28701194

Abstract

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

View details for PubMedID 28686589

Abstract

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

View details for DOI 10.1098/rstb.2016.0128

View details for PubMedID 28438917

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

Abstract

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

View details for DOI 10.1016/j.cll.2017.01.008

View details for PubMedID 28457355

Abstract

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

View details for PubMedID 28702473

View details for Web of Science ID 000577381505323

Abstract

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

View details for DOI 10.1542/peds.2016-2781

View details for Web of Science ID 000398602400023

View details for PubMedID 28302673

View details for Web of Science ID 000406739900006

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-Barr 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

Abstract

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

View details for DOI 10.4269/ajtmh.16-0562

View details for Web of Science ID 000397822900025

View details for Web of Science ID 000423215204504

View details for Web of Science ID 000423215202343

View details for Web of Science ID 000423215203063

View details for Web of Science ID 000423215202179

View details for Web of Science ID 000423215202115

View details for Web of Science ID 000423215204097

View details for Web of Science ID 000423215202001

Abstract

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

View details for DOI 10.4269/ajtmh.17-0104

View details for Web of Science ID 000409523900020

View details for PubMedID 28719329

View details for PubMedCentralID PMC5508922

View details for Web of Science ID 000423215204491

View details for Web of Science ID 000423215203041

View details for Web of Science ID 000423215202203

View details for Web of Science ID 000423215204390

View details for Web of Science ID 000423215204210

View details for Web of Science ID 000423215202229

Abstract

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

View details for PubMedID 28719301

View details for Web of Science ID 000423215203070

View details for Web of Science ID 000423215203401

View details for DOI 10.4269/ajtmh.16-0562

View details for Web of Science ID 000401757800025

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

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, = 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

View details for DOI 10.1136/bmj.i4850

View details for PubMedID 27629599

Abstract

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

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

View details for PubMedID 26625721

Abstract

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

View details for DOI 10.4269/ajtmh.15-0383

View details for Web of Science ID 000366540800040

View details for PubMedID 26458775

View details for PubMedCentralID PMC4674260

View details for Web of Science ID 000412844103052

View details for Web of Science ID 000412844102482

View details for Web of Science ID 000412844103118

View details for Web of Science ID 000412844101124

View details for Web of Science ID 000412844101005

View details for Web of Science ID 000412844103119

View details for Web of Science ID 000412844103237

View details for Web of Science ID 000412844103504

View details for Web of Science ID 000412844101151

View details for Web of Science ID 000412844102392

View details for Web of Science ID 000412844101156

Abstract

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

View details for DOI 10.1371/journal.pntd.0003721

View details for Web of Science ID 000355303600014

View details for PubMedID 25996157

View details for PubMedCentralID PMC4440755

Abstract

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

View details for DOI 10.1371/journal.pntd.0003584

View details for PubMedID 25756647

Abstract

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

View details for DOI 10.1371/journal.pntd.0003548

View details for PubMedID 25764399

Abstract

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

View details for DOI 10.4269/ajtmh.14-0440

View details for Web of Science ID 000349065400036

View details for PubMedID 25535309

View details for PubMedCentralID PMC4347346

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

Abstract

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

View details for DOI 10.1371/journal.pntd.0003466

View details for Web of Science ID 000349318100051

View details for PubMedID 25590337

View details for PubMedCentralID PMC4295886

Abstract

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

View details for DOI 10.1371/journal.pntd.0003163

View details for Web of Science ID 000342796600044

View details for PubMedID 25211133

View details for PubMedCentralID PMC4161329

View details for DOI 10.1371/journal.pntd.0002351

View details for Web of Science ID 000323941500018

View details for PubMedID 24009785

View details for PubMedCentralID PMC3757073

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

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

View details for DOI 10.1093/cid/cir1007

View details for Web of Science ID 000304049300019

View details for PubMedID 22527963

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 (PRNT) 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 > 140 for more than 3 years. In concordance with previous studies, residents of the more rural village were more likely to be seropositive and RVFV seropositivity was associated with poor visual acuity. Raw milk consumption was strongly associated with RVFV exposure, which may represent an important new focus for public health education during future RVF outbreaks.

View details for DOI 10.1371/journal.pntd.0001265

View details for Web of Science ID 000294479800020

View details for PubMedID 21858236

View details for PubMedCentralID PMC3156691

Abstract

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

View details for DOI 10.4269/ajtmh.2011.10-0203

View details for PubMedID 21734142

View details for PubMedCentralID PMC3122361

Abstract

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

View details for DOI 10.4269/ajtmh.2011.10-0187

View details for Web of Science ID 000289023600024

View details for PubMedID 21460024

View details for PubMedCentralID PMC3062463

Abstract

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

View details for DOI 10.3201/eid1702.091666

View details for Web of Science ID 000287436400011

View details for PubMedID 21291594

View details for PubMedCentralID PMC3204744

Abstract

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

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

View details for Web of Science ID 000300215200001

View details for PubMedID 21219615

View details for PubMedCentralID PMC3024945

Abstract

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

View details for Web of Science ID 000284089600004

View details for PubMedID 21080319

View details for PubMedCentralID PMC3140430

View details for DOI 10.1371/journal.pntd.0000847

View details for Web of Science ID 000283559600001

View details for PubMedID 21049011

View details for PubMedCentralID PMC2964300

Abstract

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

View details for DOI 10.1097/QCO.0b013e32833c3da6

View details for Web of Science ID 000281653400001

View details for PubMedID 20613512

View details for PubMedCentralID PMC3126654

View details for DOI 10.4269/ajtmh.2010.09-0800

View details for PubMedID 20207854

View details for PubMedCentralID PMC2829890

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

Abstract

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

View details for DOI 10.1097/INF.0b013e3181a909d3

View details for Web of Science ID 000271253800018

View details for PubMedID 19820428

View details for PubMedCentralID PMC3133951

Abstract

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

View details for DOI 10.1016/j.jpeds.2009.03.009

View details for Web of Science ID 000270497800031

View details for PubMedID 19773005

View details for PubMedCentralID PMC3104726

Abstract

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

View details for DOI 10.1371/journal.pntd.0000442

View details for Web of Science ID 000267268000014

View details for PubMedID 19478847

View details for PubMedCentralID PMC2682196

Abstract

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

View details for DOI 10.3201/eid1408.080082

View details for Web of Science ID 000258216900008

View details for PubMedID 18680647

View details for PubMedCentralID PMC2600406

View details for DOI 10.1371/journal.pntd.0000247

View details for Web of Science ID 000261807000001

View details for PubMedID 18575597

View details for PubMedCentralID PMC2427179

Abstract

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

View details for Web of Science ID 000258662200008

View details for PubMedID 18686270

View details for PubMedCentralID PMC3140769

Abstract

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

View details for Web of Science ID 000246326300003

View details for PubMedID 17488893

View details for PubMedCentralID PMC2367216

View details for Web of Science ID 000242176700005

View details for PubMedID 17012490