Potential of antibody test using Schistosoma mansoni recombinant serpin and RP26 to detect light-intensity infections in endemic areas.

Schistosomiasis remains a worldwide public health problem, especially in sub-Saharan Africa. The World Health Organization targets the goal for its elimination as a public health problem in the 2030 Neglected Tropical Diseases (NTDs) Roadmap. Concerted action and agile responses to challenges will be necessary to achieve the targets. Better diagnostic tests can accelerate progress towards the elimination by monitoring disease trends and evaluating the effectiveness of interventions; however, current examinations such as Kato-Katz technique are of limited power to detect light-intensity infections. The point-of-care circulating cathodic antigen (POC-CCA) test shows a higher sensitivity compared to the reference standard, Kato-Katz technique, but it still lacks sufficient sensitivity with low infection intensity. In this study, we examined antibody reactions against recombinant protein antigens; Schistosoma mansoni serine protease-inhibitor (SmSerpin) and RP26, by enzyme-linked immunosorbent assay (ELISA) in plasma samples with light-intensity infection. The sensitivity using the cocktail antigen of recombinant SmSerpin and RP26 showed 83.7%. The sensitivity using S. mansoni soluble egg antigen (SmSEA) was 90.8%, but it showed poor specificity (29.7%), while the cocktail antigen presented improved specificity (61.4%). We conclude that antibody detection to the SmSerpin and RP26 protein antigens is effective to detect S. mansoni light-intensity infections. Our study indicates the potential of detecting antibody against recombinant protein antigens to monitor the transmission of schistosomiasis in low endemicity contexts.

A high-intensity cluster of Schistosoma mansoni infection around Mbita causeway, western Kenya: a confirmatory cross-sectional survey.

In Kenya, communities residing along the shores and islands of Lake Victoria bear a substantial burden of schistosomiasis. Although there is a school-based deworming program in place, the transmission of Schistosoma mansoni varies even at a fine scale. Given the focal nature of schistosomes' transmission, we aim to identify areas with high intensity of S. mansoni infection in Mbita, Homabay County, western Kenya, for prioritized integrated control measures. Our findings confirm a high intensity of S. mansoni infection cluster around Mbita causeway. While the current efforts to curtail morbidity due to schistosomiasis through preventive chemotherapy in schools are crucial, fine-scale mapping of risk areas is necessary for specific integrated control measures.

Modulation of immune responses by Plasmodium falciparum infection in asymptomatic children living in the endemic region of Mbita, western Kenya.

Individuals living in malaria endemic areas become clinically immune after multiple re-infections over time and remain infected without apparent symptoms. However, it is unclear why a long period is required to gain clinical immunity to malaria, and how such immunity is maintained. Although malaria infection is reported to induce inhibition of immune responses, studies on asymptomatic individuals living in endemic regions of malaria are relatively scarce. We conducted a cross-sectional study of immune responses in asymptomatic school children aged 4-16years living in an area where Plasmodium falciparum and Schistosoma mansoni infections are co-endemic in Kenya. Peripheral blood mononuclear cells were subjected to flow cytometric analysis and cultured to determine proliferative responses and cytokine production. The proportions of cellular subsets in children positive for P. falciparum infection at the level of microscopy were comparable to the negative children, except for a reduction in central memory-phenotype CD8+ T cells and natural killer cells. In functional studies, the production of cytokines by peripheral blood mononuclear cells in response to P. falciparum crude antigens exhibited strong heterogeneity among children. In addition, production of IL-2 in response to anti-CD3 and anti-CD28 monoclonal antibodies was significantly reduced in P. falciparum-positive children as compared to -negative children, suggesting a state of unresponsiveness. These data suggest that the quality of T cell immune responses is heterogeneous among asymptomatic children living in the endemic region of P. falciparum, and that the responses are generally suppressed by active infection with Plasmodium parasites.

High-density lipoprotein suppresses tumor necrosis factor alpha production by mycobacteria-infected human macrophages.

Immune responses to parasitic pathogens are affected by the host physiological condition. High-density lipoprotein (HDL) and low-density lipoprotein (LDL) are transporters of lipids between the liver and peripheral tissues, and modulate pro-inflammatory immune responses. Pathogenic mycobacteria are parasitic intracellular bacteria that can survive within macrophages for a long period. Macrophage function is thus key for host defense against mycobacteria. These basic facts suggest possible effects of HDL and LDL on mycobacterial diseases, which have not been elucidated so far. In this study, we found that HDL and not LDL enhanced mycobacterial infections in human macrophages. Nevertheless, we observed that HDL remarkably suppressed production of tumor necrosis factor alpha (TNF-α) upon mycobacterial infections. TNF-α is a critical host-protective cytokine against mycobacterial diseases. We proved that toll-like receptor (TLR)-2 is responsible for TNF-α production by human macrophages infected with mycobacteria. Subsequent analysis showed that HDL downregulates TLR2 expression and suppresses its intracellular signaling pathways. This report demonstrates for the first time the substantial action of HDL in mycobacterial infections to human macrophages.

Spatial distribution and risk factors of Schistosoma haematobium and hookworm infections among schoolchildren in Kwale, Kenya.

BACKGROUND: Large-scale schistosomiasis control programs are implemented in regions with diverse social and economic environments. A key epidemiological feature of schistosomiasis is its small-scale heterogeneity. Locally profiling disease dynamics including risk factors associated with its transmission is essential for designing appropriate control programs. To determine spatial distribution of schistosomiasis and its drivers, we examined schoolchildren in Kwale, Kenya. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional study of 368 schoolchildren from six primary schools. Soil-transmitted helminths and Schistosoma mansoni eggs in stool were evaluated by the Kato-Katz method. We measured the intensity of Schistosoma haematobium infection by urine filtration. The geometrical mean intensity of S. haematobium was 3.1 eggs/10 ml urine (school range, 1.4-9.2). The hookworm geometric mean intensity was 3.2 eggs/g feces (school range, 0-17.4). Heterogeneity in the intensity of S. haematobium and hookworm infections was evident in the study area. To identify factors associated with the intensity of helminth infections, we utilized negative binomial generalized linear mixed models. The intensity of S. haematobium infection was associated with religion and socioeconomic status (SES), while that of hookworm infection was related to SES, sex, distance to river and history of anthelmintic treatment. CONCLUSIONS/SIGNIFICANCE: Both S. haematobium and hookworm infections showed micro-geographical heterogeneities in this Kwale community. To confirm and explain our observation of high S. haematobium risk among Muslims, further extensive investigations are necessary. The observed small scale clustering of the S. haematobium and hookworm infections might imply less uniform strategies even at finer scale for efficient utilization of limited resources.

Introduction of a community water supply in rural western Kenya: impact on community wellbeing and child health.

BACKGROUND: This study aimed to examine water availability and community health before and after tube wells were introduced in a rural western Kenyan community. Differences in impact among income quintile groups were quantified, and users' perceptions of their water supply measured. METHODS: We conducted a two-part pre- (2009) and post-intervention (2011), cross-sectional study using structured questionnaires for mothers. RESULTS: In total, 1391 (576 in 2009 and 815 in 2011) mothers participated. Well introduction changed the households' drinking-water source from river to ground water. The median distance to the water source was reduced by 40% (500 to 300 metres) and median collection time was reduced by 50% (30 to 15 minutes). Water consumption per household increased by approximately 20% (from 82.6 to 99.0 L) and drinking of untreated water decreased by approximately 10%. Regression analyses revealed mothers with higher monthly incomes had the highest satisfaction levels (ß=0.167, p<0.001). Positive impacts were strongest among wealthier groups. CONCLUSIONS: The small-scale community water supply dramatically affected user hygiene behaviours and daily life. Water supply access improved from 'no access' to 'basic access'. Household connections to a water supply and hygiene education are important steps to enhance community health.