Malaria “hotspots” within a larger hotspot; what’s the role of behavioural factors in fine scale heterogeneity in western Kenya?

Background: Malaria remains a major public health problem in Kenya accounting for the highest morbidity and mortality especially among children. Previous reports indicate that infectious agents display heterogeneity in both space and time and malaria is no exception. Heterogeneity has been shown to reduce the effectiveness of interventions. Previous studies have implicated genetic (both human and parasite) and environmental factors as mainly responsible for variation in malaria risk. Human behaviour and its potential risk for contributing to variation in malaria risk has not been extensively explored.Objective: To determine if there were behavioural differences between the people living in hotspots (high malaria burden) and coldspots (low malaria burden) within a geographically homogeneous and high malaria transmission region.Design: A prospective closed cohort study.Setting: The study was conducted in the Health and Demographic Surveillance Site in Bungoma East sub-County.Subjects: A total of 400 people in randomly selected households in both the fever hotspots and cold spots were tested for malaria at quarterly intervals using malaria rapid diagnostic tests (RDTs).Results: Significant heterogeneity in malaria incidence and prevalence was observed between villages. Incidence of malaria was significantly higher in the hotspots (high malaria burden areas) compared to the coldspots (low malaria burden) (49 episodes per 1000 person months compared to 26/1000, ttest p < 0.001). The incidence also varied significantly among the individual villages by season (P: 0.0071). Knowledge on malaria therapy was significantly associated with whether one was in the cold spot or hotspot (P: 0.033). Behavioural practices relating to ITN use were significantly associated with region during particular seasons (P: 0.0001 and P: 0.0001 respectively).Conclusion: There is marked and significant variation in the incidence of malaria among the villages creating actual hotspots of malaria within the larger hotspot. There is a significant difference in malaria infections between the hotspots and cold spots. Knowledge on malaria therapy and behavioural factors such as ITN use may contribute to the observed differences during some seasons

Prevalence, heterogeneity of asymptomatic malaria infections and associated factors in a high transmission region

Background: Although current reports have shown a reduction in malaria cases, the disease still remains a major public health problem in Kenya. In most endemic regions, the majority of infections are asymptomatic which means those infected may not even know and yet they remain infectious to the mosquitoes. Asymptomatic infections are a major threat to malaria control programs since they act as silent reservoirs for the malaria parasites.Objective: The study sought to determine the prevalence of asymptomatic malaria infections, whether they show heterogeneity spatially, across age groups and across time as well as their determinants in a high transmission region.Study Design: This was part of a larger prospective cohort study on malaria indices in the HDSS.Study Setting: The study was conducted in the Webuye Health and Demographic Surveillance Site in Bungoma East Sub-County.Study Subjects: Quarterly parasitological surveys were conducted for a cohort of 400 participants from randomly selected households located in known fever “hotspots” and “coldspots”. Follow-up of all the participants continued for a period of one year. Generalized estimating equations were used to model risk factors associated with asymptomatic parasitemia.Results: Of the total 321 malaria infections detected during the five cross-sectional surveys conducted over the period of one year, almost half (46.3%) of these were asymptomatic. Overall, most of the asymptomatic cases (67%) were in households within known fever “hotspots”. The proportion of infections that were asymptomatic in the coldspots were 73.1%, 31.8%, 13.3%, 55.6% and 48.2% during the first, second, third, fourth and fifth visits respectively. In the known fever “hotspots”, the proportion of infections without symptoms was 47.7%, 48.5%, 35%, 41.3% and 47.5% during the first, second, third, fourth and fifth visits respectively. Factors associated with asymptomatic malaria include; the village one lives: people living in village M were twice likely to be asymptomatic (A.O.R: 2.141, C.I: 0.03 - 1.488), age: children aged between 6 to 15 years were more than twice likely to be asymptomatic (A.O.R: 2.67, C.I. 0.434 - 1.533) and the season: infections during the dry season (January) were less likely to be asymptomatic (A.O.R: 0.26, C.I: -2.289 - 0.400).Conclusion: The prevalence of asymptomatic infections in this region is still very high. The highest proportion of asymptomatic infections was registered in a fever coldpspot village which may explain why the village is a fever coldspot in the first place. There is a need for active surveillance to detect the asymptomatic cases as well as treat them in-order to reduce the reservoir. Targeting interventions to the asymptomatic individuals will further reduce the transmission within this region

QTL-seq for the identification of candidate genes for days to flowering and leaf shape in pigeonpea

To identify genomic segments associated with days to flowering (DF) and leaf shape in pigeonpea, QTL-seq approach has been used in the present study. Genome-wide SNP profiling of extreme phenotypic bulks was conducted for both the traits from the segregating population (F2) derived from the cross combination- ICP 5529 × ICP 11605. A total of 126.63 million paired-end (PE) whole-genome resequencing data were generated for five samples, including one parent ICP 5529 (obcordate leaf and late-flowering plant), early and late flowering pools (EF and LF) and obcordate and lanceolate leaf shape pools (OLF and LLS). The QTL-seq identified two significant genomic regions, one on CcLG03 (1.58 Mb region spanned from 19.22 to 20.80 Mb interval) for days to flowering (LF and EF pools) and another on CcLG08 (2.19 Mb region spanned from 6.69 to 8.88 Mb interval) for OLF and LLF pools, respectively. Analysis of genomic regions associated SNPs with days to flowering and leaf shape revealed 5 genic SNPs present in the unique regions. The identified genomic regions for days to flowering were also validated with the genotyping-by-sequencing based classical QTL mapping method. A comparative analysis of the identified seven genes associated with days to flowering on 12 Fabaceae genomes, showed synteny with 9 genomes. A total of 153 genes were identified through the synteny analysis ranging from 13 to 36. This study demonstrates the usefulness of QTL-seq approach in precise identification of candidate gene(s) for days to flowering and leaf shape which can be deployed for pigeonpea improvement

Malaria Parasitaemia among Febrile Children Infected with Human Immunodeficiency Virus in the Context of Prophylactic Cotrimoxazole as Standard of Care: A Cross- Sectional Survey in Western Kenya

Objective: To document the prevalence of malaria parasitaemia among the HIV infected febrile children in a malaria endemic area. Design: A cross-sectional study. Setting: An ambulatory paediatric HIV clinic in Western Kenya, between November 2011 and December 2012. Subjects: A total of 245 febrile HIV infected children aged less than 14 years attending the HIV clinic in the Webuye level IV hospital were included in the study. A systematic sampling method was used. Main outcomes: A blood sample was taken for malaria parasite testing. Presence or absence of malaria parasites was documented. Clinical and socio-demographic characteristics of the participants were also recorded. Results: A total of 245 participants were recruited mean age being 5.53 years. Malaria prevalence was 81.9%. Most participants (97%) were on cotrimoxazole prophylaxis. Some of the factors found to be positively associated with malaria parasitaemia were; male sex, care taker category (parent), WHO stage 3 and 4 of HIV disease, and a high absolute CD4 count. However, only the caretaker association was statistically significant. Conclusion: The frequency of malaria parasitaemia among febrile HIV infected children is still high regardless of the high cotrimoxazole prophylaxis uptake. It is also noted that there is a shift in the age group of fever among children toward the older age group. This implies that policies may need to be relooked at to include the older age group in the aggressive malaria prevention measures to avoid losing on the already made gains

Misdiagnosis and clinical significance of non-tuberculous mycobacteria in Western Kenya in the era of human immunodeficiency virus epidemic

Objectives: To determine and document the role of non-tuberculous mycobacteria (NTM) in TB-like disease morbidity and demonstrate the confusion they cause in the diagnosis of TB in western Kenya.Design: A cross-sectional study.Setting: One provincial and nine District hospitals in western Kenya.Subjects: Tuberculosis suspects.Interventions: Sputa from 872 tuberculosis suspects underwent microscopy and culture on solid and liquid media. The growth was identified using the Hain’s GenoType® Mycobacterium CM and GenoType® Mycobacterium AS kits. Consenting clients were screened for HIV infection using Trinity Biotech Uni-GoldTM test and positive cases were confirmed with the enzyme linked immunosorbent assay. A questionnaire was used to obtain demographic data.Main outcome measures: ZN smear positivity / negativity; Culture positivity or negativity; Mycobacterium species isolates (tuberculous or non-tuberculous); HIV status.                                                      Results: Sputa from 39.1% (341/872) of the participants were ZN smear positive, of these 53.1% (181/341) were culture positive. Only 3.8% (20/531) of the ZN smear negatives were culture positive. In total 41.4% (361/872) participants were infected with mycobacteria, of which 44.3% (160/361) were culture negative and 55.7% (201/361) were culture positive. The culture positives yielded 92.5% M. tuberculosis complexand 7.5% NTM. The overall prevalence of the NTM disease was 1.72% (15/872).                                                                            Conclusion: A low prevalence of NT M pulmonary disease in western Kenya is reported in this study, but some the NTM disease cases could have been misdiagnosed as TB cases

Rectal dihydroartemisinin versus intravenous quinine in the treatment of severe malaria: A randomised clinical trial

Objective: To compare the clinical efficacy and safety of rectal dihydroartemisinin (DATM- Cotecxin) and intravenous quinine in the treatment of severe malaria in children and adults.Setting: Moi Teaching and Referral Hospital, Eldoret, Kenya between July and November1998.Patients: A total of sixty seven patients aged two to sixty years with severe malaria were studied.Design: This was an open randomised comparative clinical trial.Outcome measures: These were parasite clearance time, fever clearance time, efficacy and the side effect profile of the two drugs.Results: The two groups were comparable on admission on the clinical and laboratory parameters. The parasite clearance time was shorter in the rectal DATM group than quinine group. There was no statistical difference on the fever clearance time and cure rates in thetwo groups. The adverse reaction profile was better with rectal DATM than with quinine, tinnitus observed more in the quinine group.Conclusion: Rectal DATM is faster in parasite clearance than quinine and is a safe and convenient alternative to quinine in the treatment of severe malaria

Survival of cervical cancer patients at Moi teaching and Referral Hospital, Eldoret in western Kenya

Background Cervical cancer is a major health burden and the second most common cancer after breast cancer among women in Kenya. Worldwide cervical cancer constitutes 3.1% of all cancer cases. Mortality rates are greatest among the low-income countries because of lack of awareness, screening and early-detection programs and adequate treatment facilities. The main aim was to estimate survival and determine survival predictors of women with cervical cancer and limited resources in western Kenya. Methods Retrospective charts review of women diagnosed with cervical cancer and follow-up for two years from the date of the histologic diagnosis. The outcome of interest was death or survival at two years. Kaplan Meier estimates of survival, log-rank test and Cox proportional hazards regression were used in the survival analysis. Results One hundred and sixty-two (162) participants were included in the review. The median duration was 0.8 (interquartile range (IQR) 0.3, 1.6) years. The mean age at diagnosis was 50.6 years (SD12.5). The mean parity was 5.9 (SD 2.6). Fifty percent (50%) did not have health insurance. Twenty six percent (26%) used hormonal contraceptives, 25.9% were HIV positive and 70% of them were on anti-retroviral treatment. The participants were followed up for 152.6 person years. Of the 162 women in the study, 70 (43.2%) died giving an overall incidence rate (IR) of 45.9 deaths per 100 person years of follow up. The hazard ratios were better for the patients who survived (0.44 vs 0.88, p-value \u3c 0.001), those who had medical insurance (0.70 vs 0.48, p-value = 0.007) and those with early stage at diagnosis (0.88 vs 0.39, p-value \u3c 0.001). Participants who were diagnosed at late stage of the disease according to the International Federation of Gynecology and Obstetrics staging for cervical cancer (FIGO stage 2B-4B) had more than eight times increased hazard of death compared to those who were diagnosed at early stage (1-2A): Hazard Ratio: 8.01 (95% CI 3.65, 17.57). Similarly, those who underwent surgical management had 84% reduced hazard of mortality compared to those who were referred for other modes of care: HR: 0.16 (95% CI: 0.07, 0.38). Conclusion: Majority of the participants were diagnosed late after presenting with symptoms. The 1 and 2-year survival probability after diagnosis of cervical cancer was 57% AND 45% respectively. It is imperative that women present early since surgery gives better prognosis or better still screening of all women prioritized

Genotyping cognate Plasmodium falciparum in humans and mosquitoes to estimate onward transmission of asymptomatic infections

Malaria control may be enhanced by targeting reservoirs of Plasmodium falciparum transmission. One putative reservoir is asymptomatic malaria infections and the scale of their contribution to transmission in natural settings is not known. We assess the contribution of asymptomatic malaria to onward transmission using a 14-month longitudinal cohort of 239 participants in a high transmission site in Western Kenya. We identify P. falciparum in asymptomatically- and symptomatically-infected participants and naturally-fed mosquitoes from their households, genotype all parasites using deep sequencing of the parasite genes pfama1 and pfcsp, and use haplotypes to infer participant-to-mosquito transmission through a probabilistic model. In 1,242 infections (1,039 in people and 203 in mosquitoes), we observe 229 (pfcsp) and 348 (pfama1) unique parasite haplotypes. Using these to link human and mosquito infections, compared with symptomatic infections, asymptomatic infections more than double the odds of transmission to a mosquito among people with both infection types (Odds Ratio: 2.56; 95% Confidence Interval (CI): 1.36–4.81) and among all participants (OR 2.66; 95% CI: 2.05–3.47). Overall, 94.6% (95% CI: 93.1–95.8%) of mosquito infections likely resulted from asymptomatic infections. In high transmission areas, asymptomatic infections are the major contributor to mosquito infections and may be targeted as a component of transmission reduction

Characterization and mapping of Dt1 locus which co-segregates with CcTFL1 for growth habit in pigeonpea

Pigeonpea (Cajanus cajan) is one of the most important legume crops grown in arid and semi-arid regions of the world. It is characterized with few unique features compared with other legume species, such as Lotus, Medicago, and Glycine. One of them is growth habit, an important agronomic trait. In the present study, identification of mutations affecting growth habit accompanied by a precise analysis of phenotype has been done which will shed more light upon developmental regulation in pigeonpea. A genetic study was conducted to examine the inheritance of growth habit and a genotyping by sequencing (GBS)-based genetic map constructed using F2 mapping population derived from crossing parents ICP 5529 and ICP 11605. Inheritance studies clearly demonstrated the dominance of indeterminate (IDT) growth habit over determinate (DT) growth habit in F2 and F2:3 progenies. A total of 787 SNP markers were mapped in the genetic map of 1454 cM map length. Growth habit locus (Dt1) was mapped on the CcLG03 contributing more than 61% of total phenotypic variations. Subsequently, QTL analysis highlighted one gene, CcTFL1, as a candidate for determinacy in pigeonpea, since an Indel marker derived from this gene co-segregated with the Dt1 locus. Ability of this Indel-derived marker to differentiate DT/IDT lines was also validated on 262 pigeonpea lines. This study clearly demonstrated that CcTFL1 is a candidate gene for growth habit in pigeonpea and a user-friendly marker was developed in the present study which will allow low-cost genotyping without need of automation

Genetic variation and relationships of total seed protein content with some agronomic traits in pigeonpea (Cajanus cajan (L.) Millsp.)

Seed protein content (SPC) is an important grain quality trait, which impacts the nutritional importance of pigeonpea seed in the diet of over a billion people globally. The present study was carried out to determine variation in SPC and its relationships with some agronomic traits among 23 parental lines of different types of pigeonpea mapping populations. The parental lines were evaluated under field conditions during 2014-2015 growing season. A randomised complete block design in two replications was used. Data were recorded on SPC, days to first flower (DTF), plant height at maturity (PltH), number of pods per plant (NPP), number of seeds per pod (NSP), hundred-seed weight (SW) and seed yield per plant (SY). There were significant differences among genotypes for all traits. Broad-sense heritability was 0.693 for SPC but ranged from 0.519 (NPP) to 0.999 (DTF) while genetic advance was 2.4% for SPC but ranged from 1.2 % (NSP) to 141.2 % (SY), and genetic gain ranged from 11.0 % (SPC) to 230.0 % (SY). Simple correlation showed that SPC is only significantly but negatively correlated with SW (r = -0.30, P < 0.05), while path analyses revealed that SPC is negatively associated SW and NPP but positively with DTF, PltH, NSP and SY. It is concluded that genetic variation for SPC and agronomic traits exist among pigeonpea genotypes studied. The variation is accompanied by both favourable and unfavourable relationships of SPC with the agronomic traits