Barriers and misconceptions hindering reduction of intestinal schistosomiasis in Mbita Sub-County, Western Kenya.

BACKGROUND: Community and individual participation are crucial for the success of schistosomiasis control. The World Health Organization (WHO) has highlighted the importance of enhanced sanitation, health education, and Mass Drug Administration (MDA) in the fight against schistosomiasis. These approaches rely on the knowledge and practices of the community to be successful; however, where the community knowledge is low and inappropriate, it hinders intervention efforts. Hence, it is essential to identify barriers and misconceptions related to awareness of schistosomiasis, sources of infection, mode of transmission, symptoms, and control measures. METHODS: This was a mixed-method cross-sectional study involving 1200 pre-school children randomly selected and examined for Schistosoma mansoni infection using the Kato-Katz technique. All parents/guardians of selected children were enrolled for a pre-tested questionnaire survey, while 42 were engaged in focus group discussions (FGDs). The level of knowledge and awareness among parents/guardians about schistosomiasis was evaluated in relation to the infection status of their pre-school children. RESULTS: Among pre-school children, the prevalence of intestinal schistosomiasis was 45.1% (95% CI 41.7-48.5). A majority of parents/guardians (85.5%) had heard about schistosomiasis, and this awareness was associated with the participant's level of education (OR = 0.16, 95% CI 0.08, 0.34). In addition, a positive association was observed between higher educational attainment and knowledge of the causative agent (OR = 0.69, 95% CI 0.49, 0.96). Low education level was significantly associated with limited knowledge of transmission through lake water contact (OR = 0.71, 95% CI 0.52, 0.97) and infection from the lake (OR = 0.33, 95% CI 0.19, 0.57). Notably, parents/guardians who have heard of schistosomiasis could not recognize symptoms of S. mansoni infection, such as abdominal pain (91.8%, 815/888) and blood in the stool (85.1%, 756/888). Surprisingly, 49.8% (442/888) incorrectly identified hematuria (blood in urine), a key sign of S. haematobium, but not S. mansoni, in an endemic area for S. mansoni infection. The majority (82.6%, 734/888) of parents/guardians were unaware that dams are potential infection sites, despite 53.9% (479/888) of their pre-school-aged children testing positive for schistosome infection. CONCLUSIONS: Despite the high level of awareness of intestinal schistosomiasis in the study area, we identified a low level of knowledge regarding its causes, modes of transmission, signs and symptoms and potential sites of transmission within the community. This study emphasizes the need for targeted educational interventions to address the misconceptions and knowledge gaps surrounding intestinal schistosomiasis through tailored community-based programs.

Comparison of different trapping methods to collect malaria vectors indoors and outdoors in western Kenya.

BACKGROUND: Vector surveillance is among the World Health Organization global vector control response (2017-2030) pillars. Human landing catches are a gold standard but difficult to implement and potentially expose collectors to malaria infection. Other methods like light traps, pyrethrum spray catches and aspiration are less expensive and less risky to collectors. METHODS: Three mosquito sampling methods (UV light traps, CDC light traps and Prokopack aspiration) were evaluated against human landing catches (HLC) in two villages of Rarieda sub-county, Siaya County, Kenya. UV-LTs, CDC-LTs and HLCs were conducted hourly between 17:00 and 07:00. Aspiration was done indoors and outdoors between 07:00 and 11:00 a.m. Analyses of mosquito densities, species abundance and sporozoite infectivity were performed across all sampling methods. Species identification PCR and ELISAs were done for Anopheles gambiae and Anopheles funestus complexes and data analysis was done in R. RESULTS: Anopheles mosquitoes sampled from 608 trapping efforts were 5,370 constituting 70.3% Anopheles funestus sensu lato (s.l.), 19.7% Anopheles coustani and 7.2% An. gambiae s.l. 93.8% of An. funestus s.l. were An. funestus sensu stricto (s.s.) and 97.8% of An. gambiae s.l. were Anopheles arabiensis. Only An. funestus were sporozoite positive with 3.1% infection prevalence. Indoors, aspiration captured higher An. funestus (mean = 6.74; RR = 8.83, P < 0.001) then UV-LT (mean = 3.70; RR = 3.97, P < 0.001) and CDC-LT (mean = 1.74; RR = 1.89, P = 0.03) compared to HLC. UV-LT and CDC-LT indoors captured averagely 0.18 An. arabiensis RR = 5.75, P = 0.028 and RR = 5.87, P = 0.028 respectively. Outdoors, UV-LT collected significantly higher Anopheles mosquitoes compared to HLC (An. funestus: RR = 5.18, P < 0.001; An. arabiensis: RR = 15.64, P = 0.009; An. coustani: RR = 11.65, P < 0.001). Anopheles funestus hourly biting indoors in UV-LT and CDC-LT indicated different peaks compared to HLC. CONCLUSIONS: Anopheles funestus remains the predominant mosquito species. More mosquitoes were collected using aspiration, CDC-LTs and UV-LTs indoors and UV-LTs and CD-LTs outdoors compared to HLCs. UV-LTs collected more mosquitoes than CDC-LTs. The varied trends observed at different times of the night suggest that these methods collect mosquitoes with diverse activities and care must be taken when interpreting the results.

Trends of non-vaccination, under-vaccination and missed opportunities for vaccination (2003-2014) amongst children 0-23 months in Kenya.

Vaccines are effective and cost-effective. Non-vaccination, under-vaccination, and missed opportunities for vaccination (MOV), have contributed to incomplete vaccination coverage in Kenya. Analyzing their trends is essential for targeting interventions and improvement strategies. This study aimed to assess trends of non-vaccination, under-vaccination, and MOV among children aged 0-23 months in Kenya using data obtained from the Kenya Demographic and Health Surveys (KDHS) conducted in 2003, 2008/09, and 2014. A two-stage, multi-stage, and stratified sampling technique was used. Weighted analysis was conducted to ensure generalizability to the full population. Using the KDHS sample size estimation process, the sample size was estimated for each indicator, with varying standard error estimates, level of coverage and estimated response rates. Final sample size was 2380 (2003), 2237 (2008/09) and 7380 (2014). To determine the level of non-vaccination, under-vaccination and MOV among children aged 0-23 months, a weighted descriptive analysis was used to estimate their prevalence, with 95% confidence intervals (CI) for each year. MOV was defined using an algorithm as a binary variable. Data coding and recoding were done using Stata (version 14; College Station, TX: StataCorp LP). Trends in proportions of non-vaccination, under-vaccination and MOV were compared between 2003, 2008/09, and 2014 using the Cochrane-Armitage trend test. All results with P≤0.05 were considered statistically significant. Trends in proportion of non-vaccination among children aged 0-23 months in Kenya was 13.2%, 6.1% and 3.2% in 2003, 2008/09 and 2014, respectively (P = 0.0001). Trends in proportion of under-vaccination among children aged 0-23 months in Kenya was 54.3%, 50% and 51.3% in 2003, 2008/09 and 2014, respectively (P = 0.0109). The trends in proportion of children who experienced MOV was 22.7% in 2003, 31.9% in 2008/09 and 37.6% in 2014 (P = 0.0001). In the study duration, non-vaccination decreased by 10%, under-vaccination remained relatively stable, and MOV increased by ~15%. There is need for the Government and partners to implement initiatives that improve vaccine access and coverage, particularly in regions with low coverage rates, and to address missed opportunities for vaccination.

Factors influencing patients' adherence to malaria artemisinin-based combination therapy in Kamuli District, Uganda.

BACKGROUND: Patients' adherence to artemisinin-based combination therapy (ACT) is a malaria control strategy. Studies report varied experiences regarding patients' adherence to ACT. The study aimed at determining factors influencing patients' adherence to ACT for malaria in Kamuli, Uganda. METHODS: In a longitudinal study, 1266 participants at 8 public health facilities were enrolled. Equal numbers (422) were assigned to the three arms (no follow-up, day 2 and day 4). To establish the mean difference between groups, Student t-test was used and a chi-square test was used for proportionality. A multivariate logistic regression analysis was used to establish the influence of predictor variables on the dependent variable. Statistical significance was established at p < 0.05. RESULTS: A total of 844 patients were analysed. The median age was 20 years, majority (64.3%) were females. Overall patients' adherence was 588/844 (69.7%). At bivariate level, age (t-test = 2.258, p = 0.024), household head (χ2 = 14.484, p = 0.002), employment status (χ2 = 35.886, p < 0.0001), patients' preference of ACT to other anti-malarials (χ2 = 15.981, p < 0.0001), giving a patient/caregiver instructions on how to take the medication (χ2 = 7.134, p = 0.011), being satisfied with getting ACT at facility (χ2 = 48.261, p < 0.0001), patient/caregiver knowing the drug prescribed (χ2 = 5.483, p = 0.019), patient history of saving ACT medicines (χ2 = 39.242, p < 0.0001), and patient ever shared ACT medicines (χ2 = 30.893, p < 0.0001) were all associated with patients' adherence to ACT. Multivariate analysis demonstrated that adhering to ACT is 3.063 times higher for someone satisfied with getting ACT at the facility (OR = 3.063; p < 0.0001), 4.088 times for someone with history of saving ACT medicines (OR = 4.088; p < 0.0001), 2.134 times for someone who shared ACT (OR = 2.134; p = 0.03), and 2.817 times for someone with a household head (OR = 2.817; p = 0.008). CONCLUSION: Patients' adherence to ACT is generally good in the studied population. However, patients' tendencies to save ACT for future use and sharing among family members is a threat, amidst the benefits associated with adherence. There is a need to educate all about adherence to medicines as prescribed, and tighten government medicine supply chain to avoid stock-outs.

Seasonality of associations between production of indigenous foods and food security status of mother-child dyads in Kisumu County, Kenya.

BACKGROUND: Food insecurity is a major predicament for rural populations, especially mothers and children, whose livelihoods are often dependent on rain-fed agriculture. Indigenous foods have the potential of mitigating food insecurity as they can thrive in poor agro-ecological conditions. However, the associations between indigenous food production and food security status of mothers and children drawn from rural contexts has not been expansively assessed. Food insecurity evident by high food poverty rates remain high in Kisumu County due to over-reliance on food imports from other counties. The objective of the study was to assess seasonality in associations between production of selected indigenous foods (kidney beans, soya beans, millet, cassava, sweet potatoes, groundnuts, green grams, cow peas, amaranth leaves, spider plant leaves, black night shade leaves, mangoes, guavas, lime, and tamarind) and food security status of mothers and children during planting and harvesting seasons. METHODS: We used a longitudinal study design adopting both quantitative and qualitative data collection methods. A structured questionnaire assessed production of selected indigenous foods in the sampled households, Household Food Insecurity Access Scale for mother's food security status and Prevalence of Underweight for children's food security status. Ordinal logistic regression was used to derive odds ratio (OR), which assessed strength of associations between dependent variables (mother's and children's food security status) and independent variables (production of selected indigenous foods). Significance was determined at α ≤ 0.05. RESULTS: Results demonstrated that during planting season, production of kidney beans decreased the odds of mothers being severely food insecure by 53% (OR = 0.469, 95% CI = 0.228-0.964, p = 0.039). In the same season, sorghum production demonstrated 3.5 times increase in odds of children being severely food insecure (OR = 3.498, 95% CI = 1.454-8.418, p = 0.005). During harvesting season, production of kidney beans was associated with a 62% reduction in the odds of children being severely food insecure (OR = 0.379, 95% CI = 0.190-0.754, p = 0.006). CONCLUSIONS: Production of some of the selected indigenous foods demonstrated significant odds of predicting mother's and children's food security status across both study seasons. An intervention-based study approach that would best establish causal associations of indigenous food production and food security status is recommended.

Protocol for the PATHOME study: a cohort study on urban societal development and the ecology of enteric disease transmission among infants, domestic animals and the environment.

INTRODUCTION: Global morbidity from enteric infections and diarrhoea remains high in children in low-income and middle-income countries, despite significant investment over recent decades in health systems and water and sanitation infrastructure. Other types of societal development may be required to reduce disease burden. Ecological research on the influence of household and neighbourhood societal development on pathogen transmission dynamics between humans, animals and the environment could identify more effective strategies for preventing enteric infections. METHODS AND ANALYSIS: The 'enteric pathome'-that is, the communities of viral, bacterial and parasitic pathogens transmitted from human and animal faeces through the environment is taxonomically complex in high burden settings. This integrated cohort-exposure assessment study leverages natural socioeconomic spectrums of development to study how pathome complexity is influenced by household and neighbourhood infrastructure and hygiene conditions. We are enrolling under 12-month-old children in low-income and middle-income neighbourhoods of two Kenyan cities (Nairobi and Kisumu) into a 'short-cohort' study involving repeat testing of child faeces for enteric pathogens. A mid-study exposure assessment documenting infrastructural, behavioural, spatial, climate, environmental and zoonotic factors characterises pathogen exposure pathways in household and neighbourhood settings. These data will be used to inform and validate statistical and agent-based models (ABM) that identify individual or combined intervention strategies for reducing multipathogen transmission between humans, animals and environment in urban Kenya. ETHICS AND DISSEMINATION: The protocols for human subjects' research were approved by Institutional Review Boards at the University of Iowa (ID-202004606) and AMREF Health Africa (ID-ESRC P887/2020), and a national permit was obtained from the Kenya National Commission for Science Technology and Innovation (ID# P/21/8441). The study was registered on Clinicaltrials.gov (Identifier: NCT05322655) and is in pre-results stage. Protocols for research on animals were approved by the University of Iowa Animal Care and Use Committee (ID 0042302).

Human NCR3 gene variants rs2736191 and rs11575837 alter longitudinal risk for development of pediatric malaria episodes and severe malarial anemia.

BACKGROUND: Plasmodium falciparum malaria is a leading cause of pediatric morbidity and mortality in holoendemic transmission areas. Severe malarial anemia [SMA, hemoglobin (Hb) < 5.0 g/dL in children] is the most common clinical manifestation of severe malaria in such regions. Although innate immune response genes are known to influence the development of SMA, the role of natural killer (NK) cells in malaria pathogenesis remains largely undefined. As such, we examined the impact of genetic variation in the gene encoding a primary NK cell receptor, natural cytotoxicity-triggering receptor 3 (NCR3), on the occurrence of malaria and SMA episodes over time. METHODS: Susceptibility to malaria, SMA, and all-cause mortality was determined in carriers of NCR3 genetic variants (i.e., rs2736191:C > G and rs11575837:C > T) and their haplotypes. The prospective observational study was conducted over a 36 mos. follow-up period in a cohort of children (n = 1,515, aged 1.9-40 mos.) residing in a holoendemic P. falciparum transmission region, Siaya, Kenya. RESULTS: Poisson regression modeling, controlling for anemia-promoting covariates, revealed a significantly increased risk of malaria in carriers of the homozygous mutant allele genotype (TT) for rs11575837 after multiple test correction [Incidence rate ratio (IRR) = 1.540, 95% CI = 1.114-2.129, P = 0.009]. Increased risk of SMA was observed for rs2736191 in children who inherited the CG genotype (IRR = 1.269, 95% CI = 1.009-1.597, P = 0.041) and in the additive model (presence of 1 or 2 copies) (IRR = 1.198, 95% CI = 1.030-1.393, P = 0.019), but was not significant after multiple test correction. Modeling of the haplotypes revealed that the CC haplotype had a significant additive effect for protection against SMA (i.e., reduced risk for development of SMA) after multiple test correction (IRR = 0.823, 95% CI = 0.711-0.952, P = 0.009). Although increased susceptibility to SMA was present in carriers of the GC haplotype (IRR = 1.276, 95% CI = 1.030-1.581, P = 0.026) with an additive effect (IRR = 1.182, 95% CI = 1.018-1.372, P = 0.029), the results did not remain significant after multiple test correction. None of the NCR3 genotypes or haplotypes were associated with all-cause mortality. CONCLUSIONS: Variation in NCR3 alters susceptibility to malaria and SMA during the acquisition of naturally-acquired malarial immunity. These results highlight the importance of NK cells in the innate immune response to malaria.

Nasal Carriage of Methicillin-Resistant Staphylococcus Sciuri Group by Residents of an Urban Informal Settlement in Kenya.

Background: The Staphylococcus sciuri group constitutes animal-associated bacteria but can comprise up to 4% of coagulase-negative staphylococci isolated from human clinical samples. They are reservoirs of resistance genes that are transferable to Staphylococcus aureus but their distribution in communities in sub-Saharan Africa is unknown despite the clinical importance of methicillin-resistant S. aureus. Objectives: We characterised methicillin-resistant S. sciuri group isolates from nasal swabs of presumably healthy people living in an informal settlement in Nairobi to identify their resistance patterns, and carriage of two methicillin resistance genes. Method: Presumptive methicillin-resistant S. sciuri group were isolated from HardyCHROM™ methicillin-resistant S. aureus media. Isolate identification and antibiotic susceptibility testing were done using the VITEK®2 Compact. DNA was extracted using the ISOLATE II genomic kit and polymerase chain reaction used to detect mecA and mecC genes. Results: Of 37 presumptive isolates, 43% (16/37) were methicillin-resistant including - S. sciuri (50%; 8/16), S. lentus (31%; 5/16) and S. vitulinus (19%; 3/16). All isolates were susceptible to ciprofloxacin, gentamycin, levofloxacin, moxifloxacin, nitrofurantoin and tigecycline. Resistance was observed to clindamycin (63%), tetracycline (56%), erythromycin (56%), sulfamethoxazole/trimethoprim (25%), daptomycin (19%), rifampicin (13%), doxycycline, linezolid, and vancomycin (each 6%). Most isolates (88%; 14/16) were resistant to at least 2 antibiotic combinations, including methicillin. The mecA and mecC genes were identified in 75% and 50% of isolates, respectively. Conclusion: Colonizing S. sciuri group bacteria can carry resistance to methicillin and other therapeutic antibiotics. This highlights their potential to facilitate antimicrobial resistance transmission in community and hospital settings. Surveillance for emerging multidrug resistant strains should be considered in high transmission settings where human-animal interactions are prevalent. Our study scope precluded identifying other molecular determinants for all the observed resistance phenotypes. Larger studies that address the prevalence and risk factors for colonization with S. sciuri group and adopt a one health approach can complement the surveillance efforts.

Entire Expressed Peripheral Blood Transcriptome in Pediatric Severe Malarial Anemia.

This study on severe malarial anemia (SMA: Hb < 6.0 g/dL), a leading global cause of childhood morbidity and mortality, analyzed the entire expressed transcriptome in whole blood from children with non-SMA (Hb ≥ 6.0 g/dL, n = 41) and SMA (n = 25). Analyses revealed 3,420 up-regulated and 3,442 down-regulated transcripts, signifying impairments in host inflammasome activation, cell death, innate immune responses, and cellular stress responses in SMA. Immune cell profiling showed a decreased antigenic and immune priming response in children with SMA, favoring polarization toward cellular proliferation and repair. Enrichment analysis further identified altered neutrophil and autophagy-related processes, consistent with neutrophil degranulation and altered ubiquitination and proteasome degradation. Pathway analyses highlighted SMA-related alterations in cellular homeostasis, signaling, response to environmental cues, and cellular and immune stress responses. Validation with a qRT-PCR array showed strong concordance with the sequencing data. These findings identify key molecular themes in SMA pathogenesis, providing potential targets for new malaria therapies.

Hemoglobinopathies, merozoite surface protein-2 gene polymorphisms, and acquisition of Epstein Barr virus among infants in Western Kenya.

BACKGROUND: Epstein Barr virus (EBV)-associated endemic Burkitt's Lymphoma pediatric cancer is associated with morbidity and mortality among children resident in holoendemic Plasmodium falciparum regions in western Kenya. P. falciparum exerts strong selection pressure on sickle cell trait (SCT), alpha thalassemia (-α3.7/αα), glucose-6-phosphate dehydrogenase (G6PD), and merozoite surface protein 2 (MSP-2) variants (FC27, 3D7) that confer reduced malarial disease severity. The current study tested the hypothesis that SCT, (-α3.7/αα), G6PD mutation and (MSP-2) variants (FC27, 3D7) are associated with an early age of EBV acquisition. METHODS: Data on infant EBV infection status (< 6 and ≥ 6-12 months of age) was abstracted from a previous longitudinal study. Archived infant DNA (n = 81) and mothers DNA (n = 70) samples were used for genotyping hemoglobinopathies and MSP-2. The presence of MSP-2 genotypes in maternal DNA samples was used to indicate infant in-utero malarial exposure. Genetic variants were determined by TaqMan assays or standard PCR. Group differences were determined by Chi-square or Fisher's analysis. Bivariate regression modeling was used to determine the relationship between the carriage of genetic variants and EBV acquisition. RESULTS: EBV acquisition for infants < 6 months was not associated with -α3.7/αα (OR = 1.824, P = 0.354), SCT (OR = 0.897, P = 0.881), or G6PD [Viangchan (871G > A)/Chinese (1024 C > T) (OR = 2.614, P = 0.212)] and [Union (1360 C > T)/Kaiping (1388G > A) (OR = 0.321, P = 0.295)]. There was no relationship between EBV acquisition and in-utero exposure to either FC27 (OR = 0.922, P = 0.914) or 3D7 (OR = 0.933, P = 0.921). In addition, EBV acquisition in infants ≥ 6-12 months also showed no association with -α3.7/αα (OR = 0.681, P = 0.442), SCT (OR = 0.513, P = 0.305), G6PD [(Viangchan (871G > A)/Chinese (1024 C > T) (OR = 0.640, P = 0.677)], [Mahidol (487G > A)/Coimbra (592 C > T) (OR = 0.948, P = 0.940)], [(Union (1360 C > T)/Kaiping (1388G > A) (OR = 1.221, P = 0.768)], African A (OR = 0.278, P = 0.257)], or in utero exposure to either FC27 (OR = 0.780, P = 0.662) or 3D7 (OR = 0.549, P = 0.241). CONCLUSION: Although hemoglobinopathies (-α3.7/αα, SCT, and G6PD mutations) and in-utero exposure to MSP-2 were not associated with EBV acquisition in infants 0-12 months, novel G6PD variants were discovered in the population from western Kenya. To establish that the known and novel hemoglobinopathies, and in utero MSP-2 exposure do not confer susceptibility to EBV, future studies with larger sample sizes from multiple sites adopting genome-wide analysis are required.

Clinical malaria incidence and health seeking pattern in geographically heterogeneous landscape of western Kenya.

BACKGROUND: Malaria remains a public health problem in Kenya despite sustained interventions deployed by the government. One of the major impediments to effective malaria control is a lack of accurate diagnosis and effective treatment. This study was conducted to assess clinical malaria incidence and treatment seeking profiles of febrile cases in western Kenya. METHODS: Active case detection of malaria was carried out in three eco-epidemiologically distinct zones topologically characterized as lakeshore, hillside, and highland plateau in Kisumu County, western Kenya, from March 2020 to March 2021. Community Health Volunteers (CHVs) conducted biweekly visits to residents in their households to interview and examine for febrile illness. A febrile case was defined as an individual having fever (axillary temperature ≥ 37.5 °C) during examination or complaints of fever and other nonspecific malaria related symptoms 1-2 days before examination. Prior to the biweekly malaria testing by the CHVs, the participants' treatment seeking methods were based on their behaviors in response to febrile illness. In suspected malaria cases, finger-prick blood samples were taken and tested for malaria parasites with ultra-sensitive Alere® malaria rapid diagnostic tests (RDT) and subjected to real-time polymerase chain reaction (RT-PCR) for quality control examination. RESULTS: Of the total 5838 residents interviewed, 2205 residents had high temperature or reported febrile illness in the previous two days before the visit. Clinical malaria incidence (cases/1000people/month) was highest in the lakeshore zone (24.3), followed by the hillside (18.7) and the highland plateau zone (10.3). Clinical malaria incidence showed significant difference across gender (χ2 = 7.57; df = 2, p = 0.0227) and age group (χ2 = 58.34; df = 4, p < 0.0001). Treatment seeking patterns of malaria febrile cases showed significant difference with doing nothing (48.7%) and purchasing antimalarials from drug shops (38.1%) being the most common health-seeking pattern among the 2205 febrile residents (χ2 = 21.875; df = 4, p < 0.0001). Caregivers of 802 school-aged children aged 5-14 years with fever primarily sought treatment from drug shops (28.9%) and public hospitals (14.0%), with significant lower proportions of children receiving treatment from traditional medication (2.9%) and private hospital (4.4%) (p < 0.0001). There was no significant difference in care givers' treatment seeking patterns for feverish children under the age of five (p = 0.086). Residents with clinical malaria cases in the lakeshore and hillside zones sought treatment primarily from public hospitals (61.9%, 60/97) traditional medication (51.1%, 23/45) respectively (p < 0.0001). However, there was no significant difference in the treatment seeking patterns of highland plateau residents with clinical malaria (p = 0.431).The main factors associated with the decision to seek treatment were the travel distance to the health facility, the severity of the disease, confidence in the treatment, and affordability. CONCLUSION: Clinical malaria incidence remains highest in the Lakeshore (24.3cases/1000 people/month) despite high LLINs coverage (90%). The travel distance to the health facility, severity of disease and affordability were mainly associated with 80% of residents either self-medicating or doing nothing to alleviate their illness. The findings of this study suggest that the Ministry of Health should strengthen community case management of malaria by providing supportive supervision of community health volunteers to advocate for community awareness, early diagnosis, and treatment of malaria.

Nonsynonymous amino acid changes in the α-chain of complement component 5 influence longitudinal susceptibility to Plasmodium falciparum infections and severe malarial anemia in kenyan children.

Background: Severe malarial anemia (SMA; Hb < 5.0 g/dl) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission regions such as western Kenya. Methods: We investigated the relationship between two novel complement component 5 (C5) missense mutations [rs17216529:C>T, p(Val145Ile) and rs17610:C>T, p(Ser1310Asn)] and longitudinal outcomes of malaria in a cohort of Kenyan children (under 60 mos, n = 1,546). Molecular modeling was used to investigate the impact of the amino acid transitions on the C5 protein structure. Results: Prediction of the wild-type and mutant C5 protein structures did not reveal major changes to the overall structure. However, based on the position of the variants, subtle differences could impact on the stability of C5b. The influence of the C5 genotypes/haplotypes on the number of malaria and SMA episodes over 36 months was determined by Poisson regression modeling. Genotypic analyses revealed that inheritance of the homozygous mutant (TT) for rs17216529:C>T enhanced the risk for both malaria (incidence rate ratio, IRR = 1.144, 95%CI: 1.059-1.236, p = 0.001) and SMA (IRR = 1.627, 95%CI: 1.201-2.204, p = 0.002). In the haplotypic model, carriers of TC had increased risk of malaria (IRR = 1.068, 95%CI: 1.017-1.122, p = 0.009), while carriers of both wild-type alleles (CC) were protected against SMA (IRR = 0.679, 95%CI: 0.542-0.850, p = 0.001). Conclusion: Collectively, these findings show that the selected C5 missense mutations influence the longitudinal risk of malaria and SMA in immune-naïve children exposed to holoendemic P. falciparum transmission through a mechanism that remains to be defined.

Influence of landscape heterogeneity on entomological and parasitological indices of malaria in Kisumu, Western Kenya.

BACKGROUND: Identification and characterization of larval habitats, documentation of Anopheles spp. composition and abundance, and Plasmodium spp. infection burden are critical components of integrated vector management. The present study aimed to investigate the effect of landscape heterogeneity on entomological and parasitological indices of malaria in western Kenya. METHODS: A cross-sectional entomological and parasitological survey was conducted along an altitudinal transect in three eco-epidemiological zones: lakeshore along the lakeside, hillside, and highland plateau during the wet and dry seasons in 2020 in Kisumu County, Kenya. Larval habitats for Anopheles mosquitoes were identified and characterized. Adult mosquitoes were sampled using pyrethrum spray catches (PSC). Finger prick blood samples were taken from residents and examined for malaria parasites by real-time PCR (RT-PCR). RESULTS: Increased risk of Plasmodium falciparum infection was associated with residency in the lakeshore zone, school-age children, rainy season, and no ITNs (χ2 = 41.201, df = 9, P < 0.0001). Similarly, lakeshore zone and the rainy season significantly increased Anopheles spp. abundance. However, house structures such as wall type and whether the eave spaces were closed or open, as well as the use of ITNs, did not affect Anopheles spp. densities in the homes (χ2 = 38.695, df = 7, P < 0.0001). Anopheles funestus (41.8%) and An. arabiensis (29.1%) were the most abundant vectors in all zones. Sporozoite prevalence was 5.6% and 3.2% in the two species respectively. The lakeshore zone had the highest sporozoite prevalence (4.4%, 7/160) and inoculation rates (135.2 infective bites/person/year). High larval densities were significantly associated with lakeshore zone and hillside zones, animal hoof prints and tire truck larval habitats, wetland and pasture land, and the wet season. The larval habitat types differed significantly across the landscape zones and seasonality (χ2 = 1453.044, df = 298, P < 0.0001). CONCLUSION: The empirical evidence on the impact of landscape heterogeneity and seasonality on vector densities, parasite transmission, and Plasmodium infections in humans emphasizes the importance of tailoring specific adaptive environmental management interventions to specific landscape attributes to have a significant impact on transmission reduction.

Effectiveness of targeted antenatal family planning information provision on early postpartum family planning uptake in Kisumu County: Protocol for a simple randomized control trial (I DECIDE Study).

Overlooking the contraceptive needs of postpartum women constitutes missed opportunities in health system. Inter-birth interval of at least three years can prevent poor maternal, perinatal and neonatal outcomes and afford women socio-economic benefits of family planning (FP). The unmet need for FP in the postpartum period remains unacceptably high and far exceeds the FP unmet need of other women. The Kenya Demographic and Health Survey (KDHS) estimate the unmet need for postpartum FP to be 74%. Maternal and Child Health (MCH) continuum provides a great opportunity for postpartum FP (PPFP) interventions integration especially antenatal targeted FP information giving and gauging of fertility intentions. However, there is no protocol for structured, targeted antenatal FP information giving and behavioural contracting to influence postpartum fertility intentions of mothers before delivery. Knowledge gap regarding fertility intentions and best antenatal strategies for postpartum FP still exists. The available evidence differs across settings and demography. Equally, there has been inadequate exploration of operationally-feasible ways to integrate FP counselling into existing ANC services with limited number of methodologically rigorous trials. The current protocol will therefore examine the effectiveness of targeted antenatal family planning information provision on early postpartum FP uptake using a randomized control trial in Kisumu County, Kenya. The protocol will assess socio-cultural beliefs towards PPFP and perceived individual control of PPFP choice, analyze knowledge and intention for PPFP, and finally compare and examine the determinants of PPFP uptake between study groups. Through simple sampling, a group of 246 antenatal mothers will be randomly assigned to control, community and facility intervention groups as per eligibility criteria in the study facilities. After at least 3 months of intervention and postpartum follow-up, clinical superiority will be used to gauge which intervention was effective and the model superiority. Questionnaire and Case Report Forms will be the main source of data. The participant will form the unit of analysis which will be by intention to treat. Bivariate analysis will be applied as the selection criteria for inclusion of predictors of intention and uptake in the final logistic regression model. Odds Ratios and 95% confidence interval (CI) will be used to demonstrate significance and the strength of association between selected variables. Dissemination will be through conference presentations and peer reviewed journals. The trial has been registered with the Pan African Clinical Trials Registry PACTR202109586388973 on the 28th September 2021.

Evidence of co-exposure with Brucella spp, Coxiella burnetii, and Rift Valley fever virus among various species of wildlife in Kenya.

BACKGROUND: Co-infection, especially with pathogens of dissimilar genetic makeup, may result in a more devastating impact on the host. Investigations on co-infection with neglected zoonotic pathogens in wildlife are necessary to inform appropriate prevention and control strategies to reduce disease burden in wildlife and the potential transmission of these pathogens between wildlife, livestock and humans. This study assessed co-exposure of various Kenyan wildflife species with Brucella spp, Coxiella burnetii and Rift Valley fever virus (RVFV). METHODOLOGY: A total of 363 sera from 16 different wildlife species, most of them (92.6%) herbivores, were analysed by Enzyme-linked immunosorbent assay (ELISA) for IgG antibodies against Brucella spp, C. burnetii and RVFV. Further, 280 of these were tested by PCR to identify Brucella species. RESULTS: Of the 16 wildlife species tested, 15 (93.8%) were seropositive for at least one of the pathogens. Mean seropositivities were 18.9% (95% CI: 15.0-23.3) for RVFV, 13.7% (95% CI: 10.3-17.7) for Brucella spp and 9.1% (95% CI: 6.3-12.5) for C. burnetii. Buffaloes (n = 269) had higher seropositivity for Brucella spp. (17.1%, 95% CI: 13.0-21.7%) and RVFV (23.4%, 95% CI: 18.6-28.6%), while giraffes (n = 36) had the highest seropositivity for C. burnetii (44.4%, 95% CI: 27.9-61.9%). Importantly, 23 of the 93 (24.7%) animals positive for at least one pathogen were co-exposed, with 25.4% (18/71) of the positive buffaloes positive for brucellosis and RVFV. On molecular analysis, Brucella DNA was detected in 46 (19.5%, CI: 14.9-24.7) samples, with 4 (8.6%, 95% CI: 2.2-15.8) being identified as B. melitensis. The Fisher's Exact test indicated that seropositivity varied significantly within the different animal families, with Brucella (p = 0.013), C. burnetii (p = <0.001) and RVFV (p = 0.007). Location was also significantly associated (p = <0.001) with Brucella spp. and C. burnetii seropositivities. CONCLUSION: Of ~20% of Kenyan wildlife that are seropositive for Brucella spp, C. burnetii and RVFV, almost 25% indicate co-infections with the three pathogens, particularly with Brucella spp and RVFV.

Impact of integrated water, sanitation, hygiene, health and nutritional interventions on diarrhoea disease epidemiology and microbial quality of water in a resource-constrained setting in Kenya: A controlled intervention study.

OBJECTIVES: We assessed the impact of water, hygiene and sanitation (WASH), maternal, new-born and child health (MNCH), nutrition and early childhood development (ECD) on diarrhoea and microbial quality of water in a resource-constrained rural setting in Kenya. METHODS: Through a controlled intervention study, we tested faecal and water samples collected from both the intervention and control sites before and after the interventions using microbiological, immunological and molecular assays to determine the prevalence of diarrhoeagenic agents and microbial quality of water. Data from the hospital registers were used to estimate all-cause diarrhoea prevalence. RESULTS: After the interventions, we observed a 58.2% (95% CI: 39.4-75.3) decline in all-cause diarrhoea in the intervention site versus a 22.2% (95% CI: 5.9-49.4) reduction of the same in the control site. Besides rotavirus and pathogenic Escherichia coli, the rate of isolation of other diarrhoea-causing bacteria declined substantially in the intervention site. The microbial quality of community and household water improved considerably in both the intervention (81.9%; 95% CI: 74.5%-87.8%) and control (72.5%; 95% CI: 64.2%-80.5%) sites with the relative improvements in the intervention site being slightly larger. CONCLUSIONS: The integrated WASH, MNCH, nutrition and ECD interventions resulted in notable decline in all-cause diarrhoea and improvements in water quality in the rural resource-limited population in Kenya. This indicates a direct public health impact of the interventions and provides early evidence for public health policy makers to support the sustained implementation of these interventions.

Genetic variation in CSF2 (5q31.1) is associated with longitudinal susceptibility to pediatric malaria, severe malarial anemia, and all-cause mortality in a high-burden malaria and HIV region of Kenya.

Plasmodium falciparum infections remain among the leading causes of morbidity and mortality in holoendemic transmission areas. Located within region 5q31.1, the colony-stimulating factor 2 gene (CSF2) encodes granulocyte-macrophage colony-stimulating factor (GM-CSF), a hematopoietic growth factor that mediates host immune responses. Since the effect of CSF2 variation on malaria pathogenesis remains unreported, we investigated the impact of two genetic variants in the 5q31.1 gene region flanking CSF2:g-7032 G > A (rs168681:G > A) and CSF2:g.64544T > C (rs246835:T > C) on the rate and timing of malaria and severe malarial anemia (SMA, Hb < 5.0 g/dL) episodes over 36 months of follow-up. Children (n = 1654, aged 2-70 months) were recruited from a holoendemic P. falciparum transmission area of western Kenya. Decreased incidence rate ratio (IRR) for malaria was conferred by inheritance of the CSF2:g.64544 TC genotype (P = 0.0277) and CSF2 AC/GC diplotype (P = 0.0015). Increased IRR for malaria was observed in carriers of the CSF2 AT/GC diplotype (P = 0.0237), while the inheritance of the CSF2 AT haplotype increased the IRR for SMA (P = 0.0166). A model estimating the longitudinal risk of malaria showed decreased hazard rates among CSF2 AC haplotype carriers (P = 0.0045). Investigation of all-cause mortality revealed that inheritance of the GA genotype at CSF2:g-7032 increased the risk of mortality (P = 0.0315). Higher risk of SMA and all-cause mortality were observed in younger children (P < 0.0001 and P = 0.0015), HIV-1(+) individuals (P < 0.0001 and P < 0.0001), and carriers of HbSS (P = 0.0342 and P = 0.0019). Results from this holoendemic P. falciparum area show that variation in gene region 5q31.1 influences susceptibility to malaria, SMA, and mortality, as does age, HIV-1 status, and inheritance of HbSS.

Genetic differentiation in East African ethnicities and its relationship with endurance running success.

Since the 1960s, East African athletes, mainly from Kenya and Ethiopia, have dominated long-distance running events in both the male and female categories. Further demographic studies have shown that two ethnic groups are overrepresented among elite endurance runners in each of these countries: the Kalenjin, from Kenya, and the Oromo, from Ethiopia, raising the possibility that this dominance results from genetic or/and cultural factors. However, looking at the life history of these athletes or at loci previously associated with endurance athletic performance, no compelling explanation has emerged. Here, we used a population approach to identify peaks of genetic differentiation for these two ethnicities and compared the list of genes close to these regions with a list, manually curated by us, of genes that have been associated with traits possibly relevant to endurance running in GWAS studies, and found a significant enrichment in both populations (Kalenjin, P = 0.048, and Oromo, P = 1.6x10-5). Those traits are mainly related to anthropometry, circulatory and respiratory systems, energy metabolism, and calcium homeostasis. Our results reinforce the notion that endurance running is a systemic activity with a complex genetic architecture, and indicate new candidate genes for future studies. Finally, we argue that a deterministic relationship between genetics and sports must be avoided, as it is both scientifically incorrect and prone to reinforcing population (racial) stereotyping.

Risk associations of submicroscopic malaria infection in lakeshore, plateau and highland areas of Kisumu County in western Kenya.

BACKGROUND: Persons with submicroscopic malaria infection are a major reservoir of gametocytes that sustain malaria transmission in sub-Saharan Africa. Despite recent decreases in the national malaria burden in Kenya due to vector control interventions, malaria transmission continues to be high in western regions of the country bordering Lake Victoria. The objective of this study was to advance knowledge of the topographical, demographic and behavioral risk factors associated with submicroscopic malaria infection in the Lake Victoria basin in Kisumu County. METHODS: Cross-sectional community surveys for malaria infection were undertaken in three eco-epidemiologically distinct zones in Nyakach sub-County, Kisumu. Adjacent regions were topologically characterized as lakeshore, hillside and highland plateau. Surveys were conducted during the 2019 and 2020 wet and dry seasons. Finger prick blood smears and dry blood spots (DBS) on filter paper were collected from 1,777 healthy volunteers for microscopic inspection and real time-PCR (RT-PCR) diagnosis of Plasmodium infection. Persons who were PCR positive but blood smear negative were considered to harbor submicroscopic infections. Topographical, demographic and behavioral risk factors were correlated with community prevalence of submicroscopic infections. RESULTS: Out of a total of 1,777 blood samples collected, 14.2% (253/1,777) were diagnosed as submicroscopic infections. Blood smear microscopy and RT-PCR, respectively, detected 3.7% (66/1,777) and 18% (319/1,777) infections. Blood smears results were exclusively positive for P. falciparum, whereas RT-PCR also detected P. malariae and P. ovale mono- and co-infections. Submicroscopic infection prevalence was associated with topographical variation (χ2 = 39.344, df = 2, p<0.0001). The highest prevalence was observed in the lakeshore zone (20.6%, n = 622) followed by the hillside (13.6%, n = 595) and highland plateau zones (7.9%, n = 560). Infection prevalence varied significantly according to season (χ2 = 17.374, df = 3, p<0.0001). The highest prevalence was observed in residents of the lakeshore zone in the 2019 dry season (29.9%, n = 167) and 2020 and 2019 rainy seasons (21.5%, n = 144 and 18.1%, n = 155, respectively). In both the rainy and dry seasons the likelihood of submicroscopic infection was higher in the lakeshore (AOR: 2.71, 95% CI = 1.85-3.95; p<0.0001) and hillside (AOR: 1.74, 95% CI = 1.17-2.61, p = 0.007) than in the highland plateau zones. Residence in the lakeshore zone (p<0.0001), male sex (p = 0.025), school age (p = 0.002), and living in mud houses (p = 0.044) increased the risk of submicroscopic malaria infection. Bed net use (p = 0.112) and occupation (p = 0.116) were not associated with submicroscopic infection prevalence. CONCLUSION: Topographic features of the local landscape and seasonality are major correlates of submicroscopic malaria infection in the Lake Victoria area of western Kenya. Diagnostic tests more sensitive than blood smear microscopy will allow for monitoring and targeting geographic sites where additional vector interventions are needed to reduce malaria transmission.

Health care provider practices in diagnosis and treatment of malaria in rural communities in Kisumu County, Kenya.

BACKGROUND: Accurate malaria diagnosis and appropriate treatment at local health facilities are critical to reducing morbidity and human reservoir of infectious gametocytes. The current study assessed the accuracy of malaria diagnosis and treatment practices in three health care facilities in rural western Kenya. METHODS: The accuracy of malaria detection and treatment recommended compliance was monitored in two public and one private hospital from November 2019 through March 2020. Blood smears from febrile patients were examined by hospital laboratory technicians and re-examined by an expert microscopists thereafter subjected to real-time polymerase chain reaction (RT-PCR) for quality assurance. In addition, blood smears from patients diagnosed with malaria rapid diagnostic tests (RDT) and presumptively treated with anti-malarial were re-examined by an expert microscopist. RESULTS: A total of 1131 febrile outpatients were assessed for slide positivity (936), RDT (126) and presumptive diagnosis (69). The overall positivity rate for Plasmodium falciparum was 28% (257/936). The odds of slide positivity was higher in public hospitals, 30% (186/624, OR:1.44, 95% CI = 1.05-1.98, p < 0.05) than the private hospital 23% (71/312, OR:0.69, 95% CI = 0.51-0.95, p < 0.05). Anti-malarial treatment was dispensed more at public hospitals (95.2%, 177/186) than the private hospital (78.9%, 56/71, p < 0.0001). Inappropriate anti-malarial treatment, i.e. artemether-lumefantrine given to blood smear negative patients was higher at public hospitals (14.6%, 64/438) than the private hospital (7.1%, 17/241) (p = 0.004). RDT was the most sensitive (73.8%, 95% CI = 39.5-57.4) and specific (89.2%, 95% CI = 78.5-95.2) followed by hospital microscopy (sensitivity 47.6%, 95% CI = 38.2-57.1) and specificity (86.7%, 95% CI = 80.8-91.0). Presumptive diagnosis had the lowest sensitivity (25.7%, 95% CI = 13.1-43.6) and specificity (75.0%, 95% CI = 50.6-90.4). RDT had the highest non-treatment of negatives [98.3% (57/58)] while hospital microscopy had the lowest [77.3% (116/150)]. Health facilities misdiagnosis was at 27.9% (77/276). PCR confirmed 5.2% (4/23) of the 77 misdiagnosed cases as false positive and 68.5% (37/54) as false negative. CONCLUSIONS: The disparity in malaria diagnosis at health facilities with many slide positives reported as negatives and high presumptive treatment of slide negative cases, necessitates augmenting microscopic with RDTs and calls for Ministry of Health strengthening supportive infrastructure to be in compliance with treatment guidelines of Test, Treat, and Track to improve malaria case management.