Distribution of Biomphalaria Snails in Associated Vegetations and Schistosome Infection Prevalence Along the Shores of Lake Victoria in Mbita, Kenya: A Cross-Sectional Study

Background: Schistosomiasis due to Schistosoma mansoni remains a major public health problem and cause of morbidity and mortality in sub-Saharan Africa despite the implementation of control programmes. More than 6 million Kenyans are at risk of infection. Regarding control measures, Biomphalaria snail species, which are the obligatory intermediate hosts for transmission of S. mansoni, have been neglected. Mbita subcounty in Homa Bay County, western Kenya, along Lake Victoria basin, has a high prevalence of S. mansoni infection despite mass drug administration. This study aimed to determine the abundance of Biomphalaria, with their associated vegetation and schistosome infection rates, along Mbita shoreline.   Methods: Sixteen purposively selected sites along the Mbita shoreline were sampled for Biomphalaria snails using a 30-minute scooping technique. Global positioning system technology was used to map selected sites. The associated vegetation at sampling sites were collected and identified. Schistosome infection status among the snails was determined via the detection of cercaria shedding.   Results: A total of 3,135 Biomphalaria sudanica snails were collected. The number of snails collected differed significantly between the 16 sites (F=11.735; degrees of freedom [df]=15.836; P<.001). Significant mean differences (MD) were also observed in terms of the number of snails collected per vegetation type (F=7.899; df=5.846; P<.001). The mean number of snails collected from Cyprus gracilis was significantly higher than that from Enydra fluactuants (MD= 2.03; P<.001), Eichhornia crassipes (MD=4.15; P<.010), and E. fluactuants mixed with E. crassipes (MD=2.516; P<.010). A total of 21 (0.67%) snails shed human cercariae, while 27 (0.86%) snails shed nonhuman cercariae, despite 14 sites having human faeces contamination.   Conclusion: Although the schistosome infection prevalence among the snails was low, these sites may still be important exposure sites. C. gracilis is the main vegetation type associated with a high abundance of Biomphalaria snails. Molecular techniques are necessary for verification of schistosome positivity among the snails

Haplotype of non-synonymous mutations within IL-23R is associated with susceptibility to severe malaria anemia in a P. falciparum holoendemic transmission area of Kenya

Abstract Background Improved understanding of the molecular mechanisms involved in pediatric severe malarial anemia (SMA) pathogenesis is a crucial step in the design of novel therapeutics. Identification of host genetic susceptibility factors in immune regulatory genes offers an important tool for deciphering malaria pathogenesis. The IL-23/IL-17 immune pathway is important for both immunity and erythropoiesis via its effects through IL-23 receptors (IL-23R). However, the impact of IL-23R variants on SMA has not been fully elucidated. Methods Since variation within the coding region of IL-23R may influence the pathogenesis of SMA, the association between IL-23R rs1884444 (G/T), rs7530511 (C/T), and SMA (Hb < 6.0 g/dL) was examined in children (n = 369, aged 6–36 months) with P. falciparum malaria in a holoendemic P. falciparum transmission area. Results Logistic regression analysis, controlling for confounding factor of anemia, revealed that individual genotypes of IL-23R rs1884444 (G/T) [GT; OR = 1.34, 95% CI = 0.78–2.31, P = 0.304 and TT; OR = 2.02, 95% CI = 0.53–7.74, P = 0.286] and IL-23R rs7530511 (C/T) [CT; OR = 2.6, 95% CI = 0.59–11.86, P = 0.202 and TT; OR = 1.66, 95% CI = 0.84–3.27, P = 0.142] were not associated with susceptibility to SMA. However, carriage of IL-23R rs1884444T/rs7530511T (TT) haplotype, consisting of both mutant alleles, was associated with increased susceptibility to SMA (OR = 1.12, 95% CI = 1.07–4.19, P = 0.030). Conclusion Results presented here demonstrate that a haplotype of non-synonymous IL-23R variants increase susceptibility to SMA in children of a holoendemic P. falciparum transmission area

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

Abstract Background Plasmodium falciparum malaria is a leading cause of pediatric morbidity and mortality in holoendemic transmission areas. Severe malarial anemia [SMA, hemoglobin (Hb)  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

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

Abstract 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 ( 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