Including PrEP for key populations in combination HIV prevention: a mathematical modelling analysis of Nairobi as a case-study

Background: The role of PrEP in combination HIV prevention remains uncertain. We aimed to identify an optimal portfolio of interventions to reduce HIV incidence for a given budget, and to identify the circumstances in which PrEP could be used in Nairobi, Kenya. Methods: A mathematical model was developed to represent HIV transmission among specific key populations (female sex workers (FSW), male sex workers (MSW), and men who have sex with men (MSM)) and among the wider population of Nairobi. The scale-up of existing interventions (condom promotion, anti-retroviral therapy (ART) and male circumcision) for key populations and the wider population as have occurred in Nairobi is represented. The model includes a detailed representation of a Pre-Exposure Prophylaxis (PrEP) intervention and is calibrated to prevalence and incidence estimates specific to key populations and the wider population. Findings: In the context of a declining epidemic overall but with a large sub-epidemic among MSM and MSW, an optimal prevention portfolio for Nairobi should focus on condom promotion for MSW and MSM in particular, followed by improved ART retention, earlier ART, and male circumcision as the budget allows. PrEP for MSW could enter an optimal portfolio at similar levels of spending to when earlier ART is included, however PrEP for MSM and FSW would be included only at much higher budgets. If PrEP for MSW cost as much $500, average annual spending on the interventions modelled would need to be less than$3·27 million for PrEP for MSW to be excluded from an optimal portfolio. Estimated costs per infection averted when providing PrEP to all FSW regardless of their risk of infection, and to high risk FSW only, are $65,160 (95$43,520 - $90,250) and$10,920 (95% credible interval: $4,700 -$51,560) respectively. Interpretation: PrEP could be a useful contribution to combination prevention, especially for underserved key populations in Nairobi. An ongoing demonstration project will provide important information regarding practical aspects of implementing PrEP for key populations in this setting

Introgression of drought tolerance traits into adapted Kenyan chickpea varieties using marker assisted backcrossing (MABC)

Drought is the major constraint causing considerable yield reduction in chickpea. Roots play a critical role in enhancing drought tolerance. The main objective of the study was to introgress drought tolerant root traits into Kenyan chickpea varieties through marker assisted breeding (MABC). Eight simple sequence repeat (SSR) markers, linked to quantitative trait loci (QTL) for root and yield traits, were used to screen the parents at ICRISAT, India. In addition, 1144 single nucleotide polymorphic markers (SNPs) were also used in genotyping these parents at Legume Genomics Center, United Kingdom. Crosses were made between two selected varieties, ICCV 92944 (Chania Desi II) and ICCV 00108 (LDT 068) and ‘QTL-hotspot’ donor parent ICC 4958 that has extensive rooting system. Polymor- In the face of increasing water scarcity, breeding for higher transpiration efficiency (TE), that is, the biomass produced per unit of water transpired, has become crucial. This could be achieved by reducing plant transpiration through a better closure of the stomatal pores at the leaf surface. However, this strategy generally also lowers growth, as stomatal opening is necessary for the capture of atmospheric CO2 that feeds daytime photosynthesis. Here, we considered the reduction in transpiration rate at night (En), when photosynthesis is inactive, as a possible strategy to limit water use without altering growth. We carried out a genetic analysis for En and TE in grapevine, a major crop in drought-prone areas. A 3 year experiment was conducted on the F1 progeny from a cross between Syrah and Grenache cultiphic SSR and SNP markers were used to select progenies with root QTL at F1, BC1F1 and BC2F1 that were later advanced to BC2F3. The BC2F3 populations were evaluated for root traits at Egerton University in randomized complete block design with two replications in pot experiment. The BC2F3 families were significantly different for root dry weight (RDW), shoot dry weight (SDW), total plant dry weight (PDW) and root to shoot dry weight (R/S) ratio (R/S) for Chania Desi II x ICC 4958 and R/S for LDT 068 x ICC 4958. These lineshad significantly improved root traits compared the recurrent parents. MABC is aneffective and efficient method of introgressing complex drought tolerant traits which leads to improvement in yield especially under drought conditions

Estimating the burden of iron deficiency among African children

Background Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions. However, ID may be incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Through the current study, we have assessed different approaches to the prediction of iron status and estimated the burden of ID in African children. Methods We assayed iron and inflammatory biomarkers in 4853 children aged 0–8 years from Kenya, Uganda, Burkina Faso, South Africa, and The Gambia. We described iron status and its relationship with age, sex, inflammation, and malaria parasitemia. We defined ID using the WHO guideline (ferritin < 12 μg/L or < 30 μg/L in the presence of inflammation in children < 5 years old or < 15 μg/L in children ≥ 5 years old). We compared this with a recently proposed gold standard, which uses regression-correction for ferritin levels based on the relationship between ferritin levels, inflammatory markers, and malaria. We further investigated the utility of other iron biomarkers in predicting ID using the inflammation and malaria regression-corrected estimate as a gold standard. Results The prevalence of ID was highest at 1 year of age and in male infants. Inflammation and malaria parasitemia were associated with all iron biomarkers, although transferrin saturation was least affected. Overall prevalence of WHO-defined ID was 34% compared to 52% using the inflammation and malaria regression-corrected estimate. This unidentified burden of ID increased with age and was highest in countries with high prevalence of inflammation and malaria, where up to a quarter of iron-deficient children were misclassified as iron replete. Transferrin saturation < 11% most closely predicted the prevalence of ID according to the regression-correction gold standard. Conclusions The prevalence of ID is underestimated in African children when defined using the WHO guidelines, especially in malaria-endemic populations, and the use of transferrin saturation may provide a more accurate approach. Further research is needed to identify the most accurate measures for determining the prevalence of ID in sub-Saharan Africa

Malaria is a cause of iron deficiency in African children

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334), a genetic variant that confers specific protection against malaria2, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%

HIV-1 subtype and viral tropism determination for evaluating antiretroviral therapy options: an analysis of archived Kenyan blood samples

<p>Abstract</p> <p>Background</p> <p>Infection with HIV-1 is characterized by genetic diversity such that specific viral subtypes are predominant in specific geographical areas. The genetic variation in HIV-1 <it>pol </it>and <it>env </it>genes is responsible for rapid development of resistance to current drugs. This variation has influenced disease progression among the infected and necessitated the search for alternative drugs with novel targets. Though successfully used in developed countries, these novel drugs are still limited in resource-poor countries. The aim of this study was to determine HIV-1 subtypes, recombination, dual infections and viral tropism of HIV-1 among Kenyan patients prior to widespread use of antiretroviral drugs.</p> <p>Methods</p> <p>Remnant blood samples from consenting sexually transmitted infection (STI) patients in Nairobi were collected between February and May 2001 and stored. Polymerase chain reaction and cloning of portions of HIV-1 <it>gag</it>, <it>pol </it>and <it>env </it>genes was carried out followed by automated DNA sequencing.</p> <p>Results</p> <p>Twenty HIV-1 positive samples (from 11 females and 9 males) were analyzed. The average age of males (32.5 years) and females (26.5 years) was significantly different (p value < 0.0001). Phylogenetic analysis revealed that 90% (18/20) were concordant HIV-1 subtypes: 12 were subtype A1; 2, A2; 3, D and 1, C. Two samples (10%) were discordant showing different subtypes in the three regions. Of 19 samples checked for co-receptor usage, 14 (73.7%) were chemokine co-receptor 5 (CCR5) variants while three (15.8%) were CXCR4 variants. Two had dual/mixed co-receptor use with X4 variants being minor population.</p> <p>Conclusion</p> <p>HIV-1 subtype A accounted for majority of the infections. Though perceived to be a high risk population, the prevalence of recombination in this sample was low with no dual infections detected. Genotypic co-receptor analysis showed that most patients harbored viruses that are predicted to use CCR5.</p

Cross-species inference of long non-coding RNAs greatly expands the ruminant transcriptome

Additional file 3. This file contains all supplementary tables relating to lncRNA identification via the conservation of synteny. Table S3. lncRNAs inferred in one species by the genomic alignment of a transcript assembled with the RNA-seq libraries from a related spdecies. Table S12. Presence of intergenic lncRNAs both in sheep and cattle, in regions of conserved synteny. Table S13. Presence of intergenic lncRNAs both in sheep and goat, in regions of conserved synteny. Table S14. Presence of intergenic lncRNAs both in cattle and goat, in regions of conserved synteny. Table S15. Presence of intergenic lncRNAs both in sheep and humans, in regions of conserved synteny. Table S16. Presence of intergenic lncRNAs both in goat and humans, in regions of conserved synteny. Table S17. Presence of intergenic lncRNAs both in cattle and humans, in regions of conserved synteny. Table S18. High-confidence lncRNA pairs, those conserved across species both sequentially and positionally

Characterization of the fine specificity of bovine CD8 T-cell responses to defined antigens from the protozoan parasite Theileria parva

Immunity against the bovine intracellular protozoan parasite Theileria parva has been shown to be mediated by CD8 T cells. Six antigens targeted by CD8 T cells from T. parva-immune cattle of different major histocompatibility complex (MHC) genotypes have been identified, raising the prospect of developing a subunit vaccine. To facilitate further dissection of the specificity of protective CD8 T-cell responses and to assist in the assessment of responses to vaccination, we set out to identify the epitopes recognized in these T. parva antigens and their MHC restriction elements. Nine epitopes in six T. parva antigens, together with their respective MHC restriction elements, were successfully identified. Five of the cytotoxic-T-lymphocyte epitopes were found to be restricted by products of previously described alleles, and four were restricted by four novel restriction elements. Analyses of CD8 T-cell responses to five of the epitopes in groups of cattle carrying the defined restriction elements and immunized with live parasites demonstrated that, with one exception, the epitopes were consistently recognized by animals of the respective genotypes. The analysis of responses was extended to animals immunized with multiple antigens delivered in separate vaccine constructs. Specific CD8 T-cell responses were detected in 19 of 24 immunized cattle. All responder cattle mounted responses specific for antigens for which they carried an identified restriction element. By contrast, only 8 of 19 responder cattle displayed a response to antigens for which they did not carry an identified restriction element. These data demonstrate that the identified antigens are inherently dominant in animals with the corresponding MHC genotypes

Growth, Yield and Quality of Onion (Allium cepa L.) as Influenced by Nitrogen and Time of Topdressing

Onion (Allium cepa L.) is an important commercial vegetable crop grown by small-holder farmers in Kenya for both local and export markets. The national average production is low and quality is highly compromised due to use of low yielding varieties and poor agronomic practices. Field experiments on the influence of nitrogen and time of application on growth, yield, and quality of onion bulbs were conducted in 2014 and 2015 at the National Agricultural Research Laboratories. The experiments were laid out in a Randomized Complete Block Design (RCBD) with a split-split arrangement and replicated three times. Nitrogen (N) was applied as Calcium Ammonium Nitrate at five levels including, 0 (control), 26, 52, 78 and 104 kg N ha-1. These were applied at four different times of applications at three, six, nine and twelve weeks after transplanting. Two onion varieties popularly grown in Kenya were used, the Red Creole and Red Tropicana F1 hybrid. Nitrogen and time of application showed significant differences in all parameters studied except bolting. Nitrogen at 104 kg N ha-1 applied at 6 weeks gave the best results with regard to plant height, number of leaves, bulb ratios, bulb diameter, average bulb weight, yield and marketable yield. Six weeks after transplanting was the best application time with regard to most parameters and maturity of the crop. Yields increased linearly with increased N rates but declined by over 23% with late application at 12 weeks. High rates resulted to thick necks and increased split bulbs especially with late application at 9 and 12 weeks. Red Tropicana F1 hybrid was the best performing variety with regard to most parameters especially total and marketable yield. Nitrogen applied at the right time improves growth, increases yield and improves quality. Since the yield response was linear in both seasons, higher rates should be evaluated to get the optimal rate

The use of sociological methods to assess land-use change: A case study of Lambwe valley, Kenya

Land-use history, not readily available for most places, remains the weakest link in nearly all studies of historic vegetation change, in Africa as well as other places in the world. Notwithstanding, communities hold a great wealth of knowledge on the processes and events influencing change on the land they occupy. The Lambwe Valley, southwestern Kenya, has a multi-ethnic population of settlers from the early 1950s. These people have seen the transformation of an initially forested area with diverse challenges to their survival, to present-day scramble for the remaining high potential land. A large part of the forces driving human settlement and consequent changes in land-use and cover is attributed to the control of tsetse and trypanosomosis. The application of a socio-economic method of mapping land-use change with the participation of the community in this study depicted trends and the underlying causes. The control of tsetse fly and therefore trypanosomosis infection was significant in driving the changes in the valley. Agricultural intensification is suggested as a means to support the resultant higher populations of people and livestoc