Testing public Bt maize events for control of stem borers in the first confined field trials in Kenya

Transgenic maize (Zea mays L), developed using modified genes from the bacterium Bacillus thuringiensis (Bt), controls stem borers without observable negative effects to humans, livestock or the environment, and is now sown on 134 million hectares globally. Bt maize could contribute to increasing maize production in Kenya. Nine public Bt maize events of cry1Ab and cry1Ba genes were tested in confined field trials site (CFTs) to assess the control of four major Kenyan stem borer species. Leaf damage rating, number of exit holes and tunnel length were scored in the field evaluations. Leaf area consumed and mortality rates among stem borers were scored in the leaf bioassays in a Biosafety Level II laboratory, located at the Kenya Agricultural Research Institute (KARI), National Agricultural Research Laboratories (NARL). Field evaluations showed that Bt maize controlled Chilo partellus with mean damage scores of 1.2 against 2.7 for the non-Bt CML216 control. Laboratory bioassays showed high control for Eldana saccharina and Sesamia calamistis, with mean larval mortality of 64 and 92%, respectively. However, substantial control was not observed for Busseola fusca. These results showed that Bt maize could control three of the four major stem borers in Kenya with mortality records of 52.7% for B. fusca, 62.3% for E. saccharina and 85.8% for S. calamistis. Additional Bt genes need to be sought and tested for effective stem borer control in all maize growing ecologies in Kenya

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 costeffective 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: NCT0239777

Effects, equity, and cost of school-based and community-wide treatment strategies for soil-transmitted helminths in Kenya: a cluster-randomised controlled trial

Background School-based deworming programmes can reduce morbidity attributable to soil-transmitted helminths in children but do not interrupt transmission in the wider community. We assessed the effects of alternative mass treatment strategies on community soil-transmitted helminth infection. Methods In this cluster-randomised controlled trial, 120 community units (clusters) serving 150 000 households in Kenya were randomly assigned (1:1:1) to receive albendazole through annual school-based treatment targeting 2–14 year olds or annual or biannual community-wide treatment targeting all ages. The primary outcome was community hookworm prevalence, assessed at 12 and 24 months through repeat cross-sectional surveys. Secondary outcomes were Ascaris lumbricoides and Trichuris trichiura prevalence, infection intensity of each soil-transmitted helminth species, and treatment coverage and costs. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02397772. Findings After 24 months, prevalence of hookworm changed from 18·6% (95% CI 13·9–23·2) to 13·8% (10·5–17·0) in the annual school-based treatment group, 17·9% (13·7–22·1) to 8·0% (6·0–10·1) in the annual community-wide treatment group, and 20·6% (15·8–25·5) to 6·2% (4·9–7·5) in the biannual community-wide treatment group. Relative to annual school-based treatment, the risk ratio for annual community-wide treatment was 0·59 (95% CI 0·42–0·83; p<0·001) and for biannual community-wide treatment was 0·46 (0·33–0·63; p<0·001). More modest reductions in risk were observed after 12 months. Risk ratios were similar across demographic and socioeconomic subgroups after 24 months. No adverse events related to albendazole were reported. Interpretation Community-wide treatment was more effective in reducing hookworm prevalence and intensity than school-based treatment, with little additional benefit of treating every 6 months, and was shown to be remarkably equitable in coverage and effects. Funding Bill & Melinda Gates Foundation, the Joint Global Health Trials Scheme of the Medical Research Council, the UK Department for International Development, the Wellcome Trust, and the Children’s Investment Fund Foundation

Consuming cassava as a staple food places children 2-5 years old at risk for inadequate protein intake, an observational study in Kenya and Nigeria

<p>Abstract</p> <p>Background</p> <p>Inadequate protein intake is known to be deleterious in animals. Using WHO consensus documents for human nutrient requirements, the protein:energy ratio (P:E) of an adequate diet is > 5%. Cassava has a very low protein content. This study tested the hypothesis that Nigerian and Kenyan children consuming cassava as their staple food are at greater risk for inadequate dietary protein intake than those children who consume less cassava.</p> <p>Methods</p> <p>A 24 hour dietary recall was used to determine the food and nutrient intake of 656 Nigerian and 449 Kenyan children aged 2-5 years residing in areas where cassava is a staple food. Anthropometric measurements were conducted. Diets were scored for diversity using a 12 point score. Pearson's Correlation Coefficients were calculated to relate the fraction of dietary energy obtained from cassava with protein intake, P:E, and dietary diversity.</p> <p>Results</p> <p>The fraction of dietary energy obtained from cassava was > 25% in 35% of Nigerian children and 89% of Kenyan children. The mean dietary diversity score was 4.0 in Nigerian children and 4.5 in Kenyan children, although the mean number of different foods consumed on the survey day in Nigeria was greater than Kenya, 7.0 compared to 4.6. 13% of Nigerian and 53% of Kenyan children surveyed had inadequate protein intake. The fraction of dietary energy derived from cassava was negatively correlated with protein intake, P:E, and dietary diversity. Height-for age z score was directly associated with protein intake and negatively associated with cassava consumption using regression modeling that controlled for energy and zinc intake.</p> <p>Conclusions</p> <p>Inadequate protein intake was found in the diets of Nigerian and Kenyan children consuming cassava as a staple food. Inadequate dietary protein intake is associated with stunting in this population. Interventions to increase protein intake in this vulnerable population should be the focus of future work.</p

Lead optimization of a pyrazole sulfonamide series of trypanosoma brucei N -myristoyltransferase inhibitors:Identification and evaluation of CNS penetrant compounds as potential treatments for stage 2 human african trypanosomiasis

[Image: see text] Trypanosoma bruceiN-myristoyltransferase (TbNMT) is an attractive therapeutic target for the treatment of human African trypanosomiasis (HAT). From previous studies, we identified pyrazole sulfonamide, DDD85646 (1), a potent inhibitor of TbNMT. Although this compound represents an excellent lead, poor central nervous system (CNS) exposure restricts its use to the hemolymphatic form (stage 1) of the disease. With a clear clinical need for new drug treatments for HAT that address both the hemolymphatic and CNS stages of the disease, a chemistry campaign was initiated to address the shortfalls of this series. This paper describes modifications to the pyrazole sulfonamides which markedly improved blood–brain barrier permeability, achieved by reducing polar surface area and capping the sulfonamide. Moreover, replacing the core aromatic with a flexible linker significantly improved selectivity. This led to the discovery of DDD100097 (40) which demonstrated partial efficacy in a stage 2 (CNS) mouse model of HAT

The Childhood Acute Illness and Nutrition (CHAIN) network nested case-cohort study protocol: a multi-omics approach to understanding mortality among children in sub-Saharan Africa and South Asia

Introduction: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network ( www.chainnnetwork.org) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach. Methods and analysis; The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and 270/1140 well community children of similar age and household location) from nine sites in six countries across sub-Saharan Africa and South Asia. Systemic proteome, metabolome, lipidome, lipopolysaccharides, haemoglobin variants, toxins, pathogens, intestinal microbiome and biomarkers of enteropathy will be determined. Computational systems biology analysis will include machine learning and multivariate predictive modelling with stacked generalization approaches accounting for the different characteristics of each biological modality. This systems approach is anticipated to yield mechanistic insights, show interactions and behaviours of the components of biological entities, and help develop interventions to reduce mortality among acutely ill children. Ethics and dissemination. The CHAIN Network cohort and CNCC was approved by institutional review boards of all partner sites. Results will be published in open access, peer reviewed scientific journals and presented to academic and policy stakeholders. Data will be made publicly available, including uploading to recognised omics databases. Trial registration NCT03208725

Performance of selected sweetpotato varieties in Kenya

The major constraints to sweetpotato production in Kenya are use of low yielding albeit well adapted varieties and poor agronomic practices. Utilisation of higher yielding varieties could therefore increase yields. This study was conducted to evaluate introduced germplasm and identify clones with desirable traits. Twenty five clones selected on the basis of high root yield and high dry matter content were evaluated during the 1998 and 1999 long rains seasons. From these, 12 clones were selected for further evaluation in the 2000 long rains. Significant (P = 0.01) genotypic effects were observed for all traits, while genotype x season interactions were significant (P = 0.05) for large and total root yields. Twenty two of the clones had significantly lower foliage yields, compared to the check variety Mafuta. Clones 282-H-12 and WAGA-L-4 consistently recorded dry matter content of over 30%, which is above the critical value of 27%. Mean total root yields were highest in 1999 (14.6 tons ha-1) followed by 1998 (12.0 tons ha-1). The best performing clones were TZ-H-7, 120-H-11, 282-H-12 and TZ-H-10, all producing over 20 tons ha-1 with TZ-H-7 yielding significantly higher than the check variety Naveto. TZ-H-7 also recorded the second highest yield of 13.3 tons ha-1 during 2000. The consistently high number of clones outyielding the check varieties suggests a gain from introduction of new germplasm into the breeding programme in Kenya. Key Words: Dry matter, foliage production, germplasm, sweetpotato breeding (African Crop Science Journal 2001 9(1): 49-58

Participatory on-farm selection of sweetpotato varieties in western Kenya

Sweet potato production in western Kenya is constrained by widespread use of low yielding and late maturing traditional varieties. Studies conducted at several sites in Kenya between 1994 and 1996 identified some potential varieties for production in different sweet potato growing agro-ecologies in western Kenya. The objective of this study was to assess the performance of the selected varieties under farmer management conditions. Four sweet potato varieties Mugande, SPK013, SPK004 and Kemb 10 were evaluated by farmers at four clusters of trial sites between 1997 and 1999. Information on yield, taste and farmer acceptance was obtained at each trial site. Varieties Mugande, SPK013 and Kemb 10 performed better than the local check 'Mar Ooko' at all sites. Mugande and Kemb 10 had a wide adaptation while SPK013 yielded well in the Upper Midland high potential areas of western Kenya. Key Words: Adaptability, farmer acceptance, Ipomea batatas, western Kenya (African Crop Science Journal 2001 9(1): 41-49