Sammy M. Njenga

Cluster-randomised controlled trials of individual and combined water, sanitation, hygiene and nutritional interventions in rural Bangladesh and Kenya: the WASH Benefits study design and rationale.

Introduction Enteric infections are common during the first years of life in low-income countries and contribute to growth faltering with long-term impairment of health and development. Water quality, sanitation, handwashing and nutritional interventions can independently reduce enteric infections and growth faltering. There is little evidence that directly compares the effects of these individual and combined interventions on diarrhoea and growth when delivered to infants and young children. The objective of the WASH Benefits study is to help fill this knowledge gap. Methods and analysis WASH Benefits includes two cluster-randomised trials to assess improvements in water quality, sanitation, handwashing and child nutrition—alone and in combination—to rural households with pregnant women in Kenya and Bangladesh. Geographically matched clusters (groups of household compounds in Bangladesh and villages in Kenya) will be randomised to one of six intervention arms or control. Intervention arms include water quality, sanitation, handwashing, nutrition, combined water+sanitation+handwashing (WSH) and WSH+nutrition. The studies will enrol newborn children (N=5760 in Bangladesh and N=8000 in Kenya) and measure outcomes at 12 and 24 months after intervention delivery. Primary outcomes include child length-for-age Z-scores and caregiver-reported diarrhoea. Secondary outcomes include stunting prevalence, markers of environmental enteropathy and child development scores (verbal, motor and personal/social). We will estimate unadjusted and adjusted intention-to-treat effects using semiparametric estimators and permutation tests. Ethics and dissemination Study protocols have been reviewed and approved by human subjects review boards at the University of California, Berkeley, Stanford University, the International Centre for Diarrheal Disease Research, Bangladesh, the Kenya Medical Research Institute, and Innovations for Poverty Action. Independent data safety monitoring boards in each country oversee the trials. This study is funded by a grant from the Bill & Melinda Gates Foundation to the University of California, Berkeley. Registration Trial registration identifiers (http://www.clinicaltrials.gov): NCT01590095 (Bangladesh), NCT01704105 (Kenya).

Multimodal Pyrethroid Resistance in Malaria Vectors, Anopheles gambiae s.s., Anopheles arabiensis, and Anopheles funestus s.s. in Western Kenya

Anopheles gambiae s.s., Anopheles arabiensis, and Anopheles funestus s.s. are the most important species for malaria transmission. Pyrethroid resistance of these vector mosquitoes is one of the main obstacles against effective vector control. The objective of the present study was to monitor the pyrethroid susceptibility in the 3 major malaria vectors in a highly malaria endemic area in western Kenya and to elucidate the mechanisms of pyrethroid resistance in these species. Gembe East and West, Mbita Division, and 4 main western islands in the Suba district of the Nyanza province in western Kenya were used as the study area. Larval and adult collection and bioassay were conducted, as well as the detection of point mutation in the voltage-gated sodium channel (1014L) by using direct DNA sequencing. A high level of pyrethroid resistance caused by the high frequency of point mutations (L1014S) was detected in An. gambiae s.s. In contrast, P450-related pyrethroid resistance seemed to be widespread in both An. arabiensis and An. funestus s.s. Not a single L1014S mutation was detected in these 2 species. A lack of cross-resistance between DDT and permethrin was also found in An. arabiensis and An. funestus s.s., while An. gambiae s.s. was resistant to both insecticides. It is noteworthy that the above species in the same area are found to be resistant to pyrethroids by their unique resistance mechanisms. Furthermore, it is interesting that 2 different resistance mechanisms have developed in the 2 sibling species in the same area individually. The cross resistance between permethrin and DDT in An. gambiae s.s. may be attributed to the high frequency of kdr mutation, which might be selected by the frequent exposure to ITNs. Similarly, the metabolic pyrethroid resistance in An. arabiensis and An. funestus s.s. is thought to develop without strong selection by DDT.

Reconsideration of Anopheles rivulorum as a vector of Plasmodium falciparum in western Kenya: some evidence from biting time, blood preference, sporozoite positive rate, and pyrethroid resistance.

BackgroundAnopheles gambiae, An. arabiensis, and An. funestus are widespread malaria vectors in Africa. Anopheles rivulorum is the next most widespread species in the An. funestus group. The role of An. rivulorum as a malaria vector has not been fully studied, although it has been found to be a minor or opportunistic transmitter of Plasmodium falciparum.MethodsMosquitoes were collected indoors over a 12-hour period using a light source attached to a rotating bottle collector in order to determine peak activity times and to provide DNA for meal source identification. Gravid female mosquitoes were collected indoors via an aspirator to generate F1 progeny for testing insecticidal susceptibility. Blood meal sources were identified using a multiplexed PCR assay for human and bovine cytochrome-B, and by matching sequences generated with primers targeting vertebrate and mammalian cytochrome-B segments to the Genbank database.ResultsAnopheles rivulorum fed on human blood in the early evening between 18:00 and 20:00, when insecticide-treated bed nets are not in use, and the presence of Plasmodium falciparum sporozoites in 0.70% of the An. rivulorum individuals tested was demonstrated. Susceptibility to permethrin, deltamethrin, and DDT is higher in An. rivulorum (84.8%, 91.4%, and 100%, respectively) than in An. funestus s.s. (36.8%, 36.4%, and 70%, respectively), whereas mortality rates for propoxur and fenitrothion were 100% for both species. Resistance to pyrethroids was very high in An. funestus s.s. and the potential of the development of high resistance was suspected in An. rivulorum.ConclusionGiven the tendency for An. rivulorum to be active early in the evening, the presence of P. falciparum in the species, and the potential for the development of pyrethroid resistance, we strongly advocate reconsideration of the latent ability of this species as an epidemiologically important malaria vector.

Malaria Vectors in Lake Victoria and Adjacent Habitats in Western Kenya

The prevalence of malaria among the residents of the Lake Victoria basin remains high. The environment associated with the lake may maintain a high number of malaria vectors. Lake habitats including water hyacinths have been suspected to be the source of vectors. This study investigated whether malaria vectors breed in the lake habitats and adjacent backwater pools. Anopheline larvae were collected within the littoral zone of the lake and adjacent pools located along approximately 24.3 km of the lakeshore in western Kenya, and their breeding sites characterized. Three primary vector species, Anopheles arabiensis, Anopheles gambiae s.s. and Anopheles funestus s.s., and three potential vectors, were found in the lake habitats. Unexpectedly, An. arabiensis was the most dominant vector species in the lake sampling sites. Its habitats were uncovered or covered with short grass. A potential secondary malaria vector, Anopheles rivulorum, dominated the water hyacinths in the lake. Most breeding sites in the lake were limited to areas that were surrounded by tall emergent plants, including trees, and those not exposed to waves. Nearly half of adjacent habitats were lagoons that were separated from the lake by sand bars. Lagoons contained a variety of microhabitats. Anopheles arabiensis dominated open habitats, whereas An. funestus s.s. was found mainly in vegetated habitats in lagoons. The current study confirmed that several breeding sites are associated with Lake Victoria. Given that Lake Victoria is the second largest lake in the world, the lake related habitats must be extensive; therefore, making targeted vector control difficult. Further exploration is necessary to estimate the effects of lake associated habitats on malaria transmission so as to inform a rational decision-making process for vector control.

Sustained reduction in prevalence of lymphatic filariasis infection in spite of missed rounds of mass drug administration in an area under mosquito nets for malaria control.

BackgroundThe Global Programme to Eliminate Lymphatic Filariasis (GPELF) was established by the World Health Organisation (WHO) in 2000 with the goal of eliminating lymphatic filariasis (LF) as a public health problem globally by 2020. Mass drug administration (MDA) of antifilarial drugs is the principal strategy recommended for global elimination. Kenya launched a National Programme for Elimination of Lymphatic Filariasis (NPELF) in Coast Region in 2002. During the same year a longitudinal research project to monitor trends of LF infection during MDA started in a highly endemic area in Malindi District. High coverage of insecticide treated nets (ITNs) in the coastal region has been associated with dramatic decline in hospital admissions due to malaria; high usage of ITNs is also expected to have an impact on LF infection, also transmitted by mosquitoes.ResultsFour rounds of MDA with diethylcarbamazine citrate (DEC) and albendazole were given to 8 study villages over an 8-year period. Although annual MDA was not administered for several years the overall prevalence of microfilariae declined significantly from 20.9% in 2002 to 0.9% in 2009. Similarly, the prevalence of filarial antigenaemia declined from 34.6% in 2002 to 10.8% in 2009. All the examined children born since the start of the programme were negative for filarial antigen in 2009.ConclusionsDespite the fact that the study villages missed MDA in some of the years, significant reductions in infection prevalence and intensity were observed at each survey. More importantly, there were no rebounds in infection prevalence between treatment rounds. However, because of confounding variables such as insecticide-treated bed nets (ITNs), it is difficult to attribute the reduction to MDA alone as ITNs can lead to a significant reduction in exposure to filariasis vectors. The results indicate that national LF elimination programmes should be encouraged to continue provision of MDA albeit constraints that may lead to missing of MDA in some years.

Monitoring and evaluating the impact of national school-based deworming in Kenya : study design and baseline results

BackgroundAn increasing number of countries in Africa and elsewhere are developing national plans for the control of neglected tropical diseases. A key component of such plans is school-based deworming (SBD) for the control of soil-transmitted helminths (STHs) and schistosomiasis. Monitoring and evaluation (M&E) of national programmes is essential to ensure they are achieving their stated aims and to evaluate when to reduce the frequency of treatment or when to halt it altogether. The article describes the M&E design of the Kenya national SBD programme and presents results from the baseline survey conducted in early 2012.MethodsThe M&E design involves a stratified series of pre- and post-intervention, repeat cross-sectional surveys in a representative sample of 200 schools (over 20,000 children) across Kenya. Schools were sampled based on previous knowledge of STH endemicity and were proportional to population size. Stool (and where relevant urine) samples were obtained for microscopic examination and in a subset of schools; finger-prick blood samples were collected to estimate haemoglobin concentration. Descriptive and spatial analyses were conducted. The evaluation measured both prevalence and intensity of infection.ResultsOverall, 32.4% of children were infected with at least one STH species, with Ascaris lumbricoides as the most common species detected. The overall prevalence of Schistosoma mansoni was 2.1%, while in the Coast Province the prevalence of S. haematobium was 14.8%. There was marked geographical variation in the prevalence of species infection at school, district and province levels. The prevalence of hookworm infection was highest in Western Province (25.1%), while A. lumbricoides and T. trichiura prevalence was highest in the Rift Valley (27.1% and 11.9%). The lowest prevalence was observed in the Rift Valley for hookworm (3.5%), in the Coast for A. lumbricoides (1.0%), and in Nyanza for T. trichiura (3.6%). The prevalence of S. mansoni was most common in Western Province (4.1%).ConclusionsThe current findings are consistent with the known spatial ecology of STH and schistosome infections and provide an important empirical basis on which to evaluate the impact of regular mass treatment through the school system in Kenya.

Adult population as potential reservoir of NTD infections in rural villages of Kwale district, Coastal Kenya: implications for preventive chemotherapy interventions policy

BackgroundNeglected tropical diseases (NTDs) are major public health problems in developing countries where they contribute to suffering of populations living in poor settings. As part of a research project started in September 2009 in Kwale district, Coast Region, Kenya, a baseline cross-sectional survey was conducted in 5 rural villages to provide information on the status of NTDs, including urinary schistosomiasis, soil-transmitted helminthiasis (STH), and lymphatic filariasis. This paper presents the results of a parasitological investigation among adults in the study villages.MethodsA total of 599 adults in the 5 study villages were tested for NTD infections in urine, stool and blood. The presence of Schistosoma haematobium infection was determined by the urine filtration method. The presence of STH in stool was determined by Kato-Katz method while filarial antigenaemia was determined using immunochromatographic (ICT) test.ResultsThe study revealed high prevalence of hookworm (41.7%) and schistosomiasis (18.2%) infections among adults in the study villages. Of the 599 individuals examined, 50.1% had one or more helminthic infections. There was low level of polyparasitism with helminthic NTDs in the study population with 9.5% and 1.7% of the participants having two and three infections, respectively.ConclusionsIn the current study, hookworm and schistosomiasis infections were identified as important infections among adults living in areas of high endemicity for these infections. Thus, if this section of the population is left untreated it may remain an important potential reservoir and a source of re-infection for school-age children treated in school deworming programmes. Therefore, there is a need to design novel strategies for preventive chemotherapy interventions that could allow inclusion of adults in an effort to reduce force of infection in high endemic communities.

Impact of two rounds of mass treatment with diethylcarbamazine plus albendazole on Wuchereria bancrofti infection and the sensitivity of immunochromatographic test in Malindi, Kenya

Annual single-dose mass treatment of endemic populations with a combination of either diethylcarbamazine (DEC) or ivermectin plus albendazole is recommended as the mainstay of lymphatic filariasis elimination programmes. We evaluated the impact of two rounds of annual mass drug administration (MDA) of DEC and albendazole on bancroftian filariasis in a pilot elimination programme in an endemic area of Kenya. Overall prevalence of microfilaraemia decreased by 65.4%, whereas community microfilarial load decreased by 84% after the two MDAs. The prevalence of parasite antigenaemia determined by immunochromatographic test (ICT) declined significantly by 43.5% after the two MDAs. We also studied the effect of mass treatment on the sensitivity of the ICT. Although the sensitivity of the test before treatment was high (89.9%; kappa=0.909) sensitivity was lower after two MDAs (59.3%; kappa=0.644). The finding raises concern about the reliability of the ICT in long-term monitoring of infection and for establishing programmatic endpoints. The results of the present study indicate a relatively high effectiveness of MDA using a DEC/albendazole combination against Wuchereria bancrofti infection and, therefore, it may be a useful strategy to eliminate lymphatic filariasis in onchocerciasis-free areas.

Soil-Transmitted Helminth Infection and Nutritional Status Among Urban Slum Children in Kenya

To evaluate the nutritional impact of soil-transmitted helminth (STH) infection, we conducted a cross-sectional survey of 205 pre-school (PSC) and 487 school-aged children (SAC) randomly selected from the surveillance registry of the Centers for Disease Control and Prevention of the Kibera slum in Kenya. Hemoglobin, iron deficiency (ID), vitamin A deficiency (VAD), inflammation, malaria, anthropometry, and STH ova were measured. Poisson regression models evaluated associations between STH and malnutrition outcomes and controlled for confounders. Approximately 40% of PSC and SAC had STH infection, primarily Ascaris and Trichuris; 2.9% of PSC and 1.1% of SAC had high-intensity infection. Malnutrition prevalence among PSC and SAC was anemia (38.3% and 14.0%, respectively), ID (23.0% and 5.0%, respectively), VAD (16.9% and 4.5%, respectively), and stunting (29.7% and 16.9%, respectively). In multivariate analysis, STH in PSC was associated with VAD (prevalence ratio [PR] = 2.2, 95% confidence interval = 1.1-4.6) and ID (PR = 3.3, 95% confidence interval = 1.6-6.6) but not anemia or stunting. No associations were significant in SAC. Integrated deworming and micronutrient supplementation strategies should be evaluated in this population.

Interrupting transmission of soil-transmitted helminths: a study protocol for cluster randomised trials evaluating alternative treatment strategies and delivery systems in Kenya.

Introduction In recent years, an unprecedented emphasis has been given to the control of neglected tropical diseases, including soil-transmitted helminths (STHs). The mainstay of STH control is school-based deworming (SBD), but mathematical modelling has shown that in all but very low transmission settings, SBD is unlikely to interrupt transmission, and that new treatment strategies are required. This study seeks to answer the question: is it possible to interrupt the transmission of STH, and, if so, what is the most cost-effective treatment strategy and delivery system to achieve this goal? Methods and analysis Two cluster randomised trials are being implemented in contrasting settings in Kenya. The interventions are annual mass anthelmintic treatment delivered to preschool- and school-aged children, as part of a national SBD programme, or to entire communities, delivered by community health workers. Allocation to study group is by cluster, using predefined units used in public health provision—termed community units (CUs). CUs are randomised to one of three groups: receiving either (1) annual SBD; (2) annual community-based deworming (CBD); or (3) biannual CBD. The primary outcome measure is the prevalence of hookworm infection, assessed by four cross-sectional surveys. Secondary outcomes are prevalence of Ascaris lumbricoides and Trichuris trichiura, intensity of species infections and treatment coverage. Costs and cost-effectiveness will be evaluated. Among a random subsample of participants, worm burden and proportion of unfertilised eggs will be assessed longitudinally. A nested process evaluation, using semistructured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system. Ethics and dissemination Study protocols have been reviewed and approved by the ethics committees of the Kenya Medical Research Institute and National Ethics Review Committee, and London School of Hygiene and Tropical Medicine. The study has a dedicated web site. Trial registration number NCT02397772.