Detection of acute dengue virus infection, with and without concurrent malaria infection, in a cohort of febrile children in Kenya, 2014-2019, by clinicians or machine learning algorithms.

Poor access to diagnostic testing in resource limited settings restricts surveillance for emerging infections, such as dengue virus (DENV), to clinician suspicion, based on history and exam observations alone. We investigated the ability of machine learning to detect DENV based solely on data available at the clinic visit. We extracted symptom and physical exam data from 6,208 pediatric febrile illness visits to Kenyan public health clinics from 2014-2019 and created a dataset with 113 clinical features. Malaria testing was available at the clinic site. DENV testing was performed afterwards. We randomly sampled 70% of the dataset to develop DENV and malaria prediction models using boosted logistic regression, decision trees and random forests, support vector machines, naïve Bayes, and neural networks with 10-fold cross validation, tuned to maximize accuracy. 30% of the dataset was reserved to validate the models. 485 subjects (7.8%) had DENV, and 3,145 subjects (50.7%) had malaria. 220 (3.5%) subjects had co-infection with both DENV and malaria. In the validation dataset, clinician accuracy for diagnosis of malaria was high (82% accuracy, 85% sensitivity, 80% specificity). Accuracy of the models for predicting malaria diagnosis ranged from 53-69% (35-94% sensitivity, 11-80% specificity). In contrast, clinicians detected only 21 of 145 cases of DENV (80% accuracy, 14% sensitivity, 85% specificity). Of the six models, only logistic regression identified any DENV case (8 cases, 91% accuracy, 5.5% sensitivity, 98% specificity). Without diagnostic testing, interpretation of clinical findings by humans or machines cannot detect DENV at 8% prevalence. Access to point-of-care diagnostic tests must be prioritized to address global inequities in emerging infections surveillance.

Integrated survey of helminthic neglected tropical diseases and comparison of two mosquito sampling methods for lymphatic filariasis molecular xenomonitoring in the River Galana area, Kilifi County, coastal Kenya.

A lymphatic filariasis (LF) endemic focus along the River Galana/ Sabaki in Kilifi County, coastal Kenya, provided a platform to conduct an integrated survey for three helminthic neglected tropical diseases (NTDs), namely soil-transmitted helminthiasis (STH), schistosomiasis (SCH) and LF. Additionally, the study compared the performance of two mosquito trapping methods for LF molecular xenomonitoring (MX). Cross-sectional surveys measuring STH, SCH and LF prevalence were conducted in four villages. Mosquitoes were trapped using the CDC light trap (CDC-LT) and the Ifakara A tent trap (Ifakara-TT) methods and stored in pools which were tested for Wuchereria bancrofti DNA using the real-time polymerase chain reaction assay. A total of 907 people (436 adults; 471 children) participated in the parasitological testing. Among the STH infections, Trichuris trichiura and hookworms were most prevalent among the children and adult populations, respectively. The schistosome worm eggs detected belonged to the species Schistosoma haematobium and the prevalence of the infection was generally higher among the children compared with the adult population. The prevalence of LF infection among the adult population ranged from 1.8% to 7.6% across all 4 villages (P < 0.05). A total of 3,652 mosquitoes, including Anopheles, Culex, Mansonia, and Aedes species were collected. One mosquito pool consisting of Anopheles mosquitoes tested positive for filarial DNA out of 1,055 pools that were tested. The CDC-LT caught significantly more mosquitoes compared with the Ifakara-TT (P < 0.001). This study demonstrated that integrated epidemiological surveys using standard parasitological and entomological methods can provide useful information on co-endemic parasitic diseases which could help direct interventions and surveillance activities.

Differences in HIV, STI and Other Risk Factors Among Younger and Older Male Sex Workers Who Have Sex With Men in Nairobi, Kenya.

Introduction: Previous surveys of male sex workers (MSW) in sub-Saharan Africa have not fully documented the HIV and sexually transmitted infections (STIs) rates and vulnerabilities by age category. Methods: The bio-behavioral survey of MSW in Nairobi, Kenya, utilized respondent-driven sampling to recruit MSW. Structured interviews captured MSW's behavioral aspects, and biological tests for HIV and other STIs. Results: Analysis of the two age categories, 18-24 years (younger MSW) and 25 years and above (older MSW), shows that of all participants, a significantly higher proportion of younger MSW (59.6% crude, 69.6% RDS-adjusted) were recruited compared to older MSW (40.4% crude, 30.4% RDS-adjusted, P < 0.001). Young male sex workers were more likely to report multiple sexual partnerships in the last 12 months and had multiple receptive anal intercourses (RAI) acts in the last 30 days than older MSW: 0-2 RAI acts (20.6 vs. 8.6%, P = 0.0300), 3-5 RAI acts (26.3 vs. 11.5, P < 0.001), and >5 RAI acts (26.3 vs. 11.5%, P < 0.01). Furthermore, younger MSW were significantly more likely to have 3-5 insertive anal intercourse (IAI) with a regular male sex partner in the last 30 days than older MSW (24.3 vs. 8.0%, P < 0.01). Younger MSW were also more likely to report other STIs [28.5% (95% CI: 19.1-40.4%)] than older MSW [19.0% (95% CI: 7.7-29.2%)]. However, older MSWs were more likely to be infected with HIV than younger MSW (32.3 vs. 9.9 %, P < 0.01). Conclusions: Owing to the high risk sexual behaviors, HIV and STIs risks among younger and older MSW, intensified and targeted efforts are needed on risk reduction campaigns and expanded access to services.

Dietary Intake and Pneumococcal Vaccine Response Among Children (5-7 Years) in Msambweni Division, Kwale County, Kenya.

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.

Night Time Extension of Aedes aegypti Human Blood Seeking Activity.

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.

High Frequency of Antibiotic Prescription in Children With Undifferentiated Febrile Illness in Kenya.

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 5 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 (ie, cough, runny nose), HEENT findings on exam (ie, 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.

Factors associated with early childhood stunted growth in a 2012-2015 birth cohort monitored in the rural Msambweni area of coastal Kenya: a cross-sectional study.

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 6-37 months), 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.

Early Childhood Anemia in a Birth Cohort in Coastal Kenya: Links to Infection and Nutrition.

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 ß = -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 (ß = -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.

Nasopharyngeal Carriage of Streptococcus pneumoniae in Children in Coastal Kenya.

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.

Characteristics of Aedes aegypti adult mosquitoes in rural and urban areas of western and coastal Kenya.

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.

Cross-sectional interview study of fertility, pregnancy, and urogenital schistosomiasis in coastal Kenya: Documented treatment in childhood is associated with reduced odds of subfertility among adult women.

BACKGROUND: Previous research has documented an increased risk of subfertility in areas of sub-Saharan Africa, as well as an ecological association between urogenital schistosomiasis prevalence and decreased fertility. This pilot project examined reproductive patterns and the potential effects of childhood urogenital Schistosoma haematobium infection and individual treatment experience on adult subfertility among women who were long-term residents in an S. haematobium-endemic region of coastal Kenya. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed findings from 162 in-depth interviews with women of childbearing age in a rural, coastal community, linking them, if possible, to their individual treatment records from previous multi-year longitudinal studies of parasitic infections. Reproductive histories indicated a much local higher local rate of subfertility (44%) than worldwide averages (8-12%). Although, due to the very high regional prevalence of schistosomiasis, a clear relationship could not be demonstrated between a history of S. haematobium infection and adult subfertility, among a convenience sub-sample of 61 women who had received documented treatment during previous interventional trials, a significant association was found between age at first anti-schistosomal treatment and later fertility in adulthood, with those women treated before age 21 significantly less likely to have subfertility (P = 0.001). CONCLUSIONS/SIGNIFICANCE: The high subfertility rate documented in this pilot study suggests the importance of programs to prevent and treat pelvic infections in their early stages to preclude reproductive tract damage. The available documented treatment data also suggest that early anti-schistosomal treatment may prevent the fertility-damaging effects of urogenital schistosomiasis, and lend support for programs that provide universal treatment of children in S. haematobium-endemic regions.

Principles, practices and knowledge of clinicians when assessing febrile children: a qualitative study in Kenya.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Malaria and Chikungunya Detected Using Molecular Diagnostics Among Febrile Kenyan Children.

BACKGROUND: In sub-Saharan Africa, malaria is frequently overdiagnosed as the cause of an undifferentiated febrile illness, whereas arboviral illnesses are presumed to be underdiagnosed. METHODS: Sera from 385 febrile Kenyan children, who presented to 1 of 4 clinical sites, were tested using microscopy and real-time molecular assays for dengue virus (DENV), chikungunya virus (CHIKV), malaria, and Leptospira. RESULTS: Malaria was the primary clinical diagnosis for 254 patients, and an arboviral infection (DENV or CHIKV) was the primary diagnosis for 93 patients. In total, 158 patients (41.0%) had malaria and 32 patients (8.3%) had CHIKV infections. Compared with real-time polymerase chain reaction, microscopy demonstrated a percent positive agreement of 49.7%. The percentage of malaria cases detected by microscopy varied significantly between clinical sites. Arboviral infections were the clinical diagnosis for patients on the Indian Ocean coast (91 of 238, 38.2%) significantly more 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). CONCLUSIONS: 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.

Development of a Real-Time Reverse Transcription Polymerase Chain Reaction for O'nyong-nyong Virus and Evaluation with Clinical and Mosquito Specimens from Kenya.

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

Characterization and productivity profiles of Aedes aegypti (L.) breeding habitats across rural and urban landscapes in western and coastal Kenya.

BACKGROUND: 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. METHODS: Twenty sentinel houses in each of four study sites (in western and coastal Kenya) were assessed for immature mosquito infestation once a month for a period of 24 months (June 2014 to May 2016). All water-holding containers in and around the households were inspected for Ae. aegypti larvae and pupae. RESULTS: 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. CONCLUSIONS: 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.

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

BACKGROUND AND OBJECTIVE: Streptococcus pneumoniae is a leading cause of mortality before age 5, but few studies examine details of childhood response to pneumococcal vaccine in less-developed settings. Although malnutrition, HIV, and concurrent infections can impair response, evidence suggests that chronic parasitic infections can also contribute to poor vaccination results. The objective of this study was to determine whether response to pneumococcal vaccine varied among children either exposed to parasitic infections in utero, previously infected in infancy, or infected at the time of immunization. METHODS: Children from a 2006 to 2010 maternal-infant cohort were eligible for the current study. Children were screened for malaria, schistosomiasis, filariasis, intestinal helminths, and protozoa. Data on in utero exposure and early life infections were linked, and baseline antipneumococcal immunoglobulin G levels and nasopharyngeal carrier status were determined. Participants received decavalent pneumococcal vaccine, and 4 weeks later, serology was repeated to assess vaccine response. RESULTS: 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. CONCLUSIONS: 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.

Monitoring the impact of a national school based deworming programme on soil-transmitted helminths in Kenya: the first three years, 2012 - 2014.

BACKGROUND: In 2012, the Kenyan Ministries of Health and of Education began a programme to deworm all school-age children living in areas at high risk of soil-transmitted helminths (STH) and schistosome infections. The impact of this school-based mass drug administration (MDA) programme in Kenya is monitored by the Kenya Medical Research Institute (KEMRI) as part of a five-year (2012-2017) study. This article focuses on the impact of MDA on STH infections and presents the overall achieved reductions from baseline to mid-term, as well as yearly patterns of reductions and subsequent re-infections per school community. METHODS: The study involved a series of pre- and post-intervention, repeat cross-sectional surveys in a representative, stratified, two-stage sample of schools across Kenya. The programme contained two tiers of monitoring; a national baseline and mid-term survey including 200 schools, and surveys conducted among 60 schools pre- and post-intervention. Stool samples were collected from randomly selected school children and tested for helminth infections using Kato-Katz technique. The prevalence and mean intensity of each helminth species were calculated at the school and county levels and 95 % confidence intervals (CIs) were obtained by binomial and negative binomial regression, respectively, taking into account clustering by schools. RESULTS: The overall prevalence of STH infection at baseline was 32.3 % (hookworms: 15.4 %; Ascaris lumbricoides: 18.1 %; and Trichuris trichiura: 6.7 %). After two rounds of MDA, the overall prevalence of STH had reduced to 16.4 % (hookworms: 2.3 %; A. lumbricoides: 11.9 %; and T. trichiura: 4.5 %). The relative reductions of moderate to heavy intensity of infections were 33.7 % (STH combined), 77.3 % (hookworms) and 33.9 % (A. lumbricoides). For T. trichiura, however, moderate to heavy intensity of infections increased non-significantly by 18.0 % from baseline to mid-term survey. CONCLUSION: The school-based deworming programme has substantially reduced STH infections, but because of ongoing transmission additional strategies may be required to achieve a sustained interruption of transmission.

Assessing drivers of the IgG4 antibody reactivity to recombinant antigen Bm14 in Wuchereria bancrofti endemic populations in East Africa.

A high proportion of the human population in lymphatic filariasis (LF) endemic areas is positive for filarial specific IgG4 antibodies, including many individuals without microfilariae (mf; circulating larvae in the human blood) or circulating filarial antigens (CFA; marker of adult worm infection). The antibodies are commonly regarded as markers of infection and/or exposure to filarial larvae, but a direct association between the antibodies and these indices has not been well documented. The present study assessed the role and relative effect of potential drivers of the human IgG4 antibody reactivity to the recombinant filarial antigen Bm14 in Wuchereria bancrofti endemic populations in East Africa. Sera collected during previous studies from 395 well characterized individuals with regard to age, sex, mf, CFA, household vector biting and household exposure to infective filarial larvae were tested for IgG4 antibodies to Bm14, and associations between antibody reactivity and the different variables were statistically analyzed. IgG4 reactivity to Bm14 was highly positively associated with CFA, and to a lesser extent with age. However, an expected association with household exposure to infective filarial larvae was not found. Bm14 antibody reactivity thus appeared mainly to reflect actual infection of individuals with adult filarial worms rather than ongoing exposure to transmission. The analyses moreover suggested that many of the CFA negative but Bm14 positive individuals had early or low level infections where antibodies had been induced but where CFA was not (yet?) measurable. Although the study indicated that IgG4 reactivity to Bm14 is a marker of filarial infection, assessment of this reactivity, especially in children, will still be useful for indirect monitoring of changes in transmission intensity, including break of transmission and post-elimination surveillance, in LF control.

Schistosoma haematobium and soil-transmitted Helminths in Tana Delta District of Kenya: infection and morbidity patterns in primary schoolchildren from two isolated villages.

BACKGROUND: Schistosomes and soil-transmitted helminths (STH) (hookworm, Trichuris trichiura and Ascaris lumbricoides) are widely distributed in developing countries where they infect over 230 million and 1.5 billion people, respectively. The parasites are frequently co-endemic and many individuals are co-infected with two or more of the species, but information on how the parasites interact in co-infected individuals is scarce. The present study assessed Schistosoma haematobium and STH infection and morbidity patterns among school children in a hyper-endemic focus in the Tana River delta of coastal Kenya. METHODS: Two hundred and sixty-two children aged 5-12 years from two primary schools were enrolled in the study. For each child, urine was examined for S. haematobium eggs and haematuria, stool was examined for STH eggs, peripheral blood was examined for eosinophilia and haemoglobin level, the urinary tract was ultrasound-examined for S. haematobium-related pathology, and the height and weight was measured and used to calculate the body mass index (BMI). RESULTS: Prevalences of S. haematobium, hookworm, T. trichiura and A. lumbricoides infection were 94, 81, 88 and 46 %, respectively. There was no significant association between S. haematobium and STH infection but intensity of hookworm infection significantly increased with that of T. trichiura. Lower BMI scores were associated with high intensity of S. haematobium (difference =-0.48, p > 0.05) and A. lumbricoides (difference =-0.67, p < 0.05). Haematuria (both macro and micro) was common and associated with S. haematobium infection, while anaemia was associated with high intensity of S. haematobium (OR = 2.08, p < 0.05) and high hookworm infections OR = 4.75; p < 0.001). The majority of children had eosinophilia, which was significantly associated with high intensity of hookworm infection (OR = 5.34, p < 0.05). Overall 38 % of the children had ultrasound-detectable urinary tract morbidity, which was associated with high intensity of S. haematobium infection (OR = 3.13, p < 0.05). CONCLUSION: Prevalences of S. haematobium and STH infections among the primary school children were high and the parasites were responsible for significant morbidity. A clear synergistic interaction was observed between hookworm and T. trichiura infections. Increased coverage in administration of praziquantel and albendazole in the area is recommended to control morbidity due to these infections.

Use of prospective hospital surveillance data to define spatiotemporal heterogeneity of malaria risk in coastal Kenya.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.