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This study evaluated potential changes in antischistosome immune responses in children from schools that received 4 rounds of annual mass drug administration (MDA) of praziquantel (PZQ). In a repeated cross-sectional study design, 210 schistosome egg-positive children were recruited at baseline from schools in western Kenya (baseline group). Another 251 children of the same age range were recruited from the same schools and diagnosed with schistosome infection by microscopy (post-MDA group). In-vitro schistosome-specific cytokines and plasma antibody levels were measured by ELISA and compared between the 2 groups of children. Schistosome soluble egg antigen (SEA) and soluble worm antigen preparation (SWAP) stimulated higher IL-5 production by egg-negative children in the post-MDA group compared to the baseline group. Similarly, anti-SEA IgE levels were higher in egg-negative children in the post-MDA group compared to the baseline group. Anti-SEA and anti-SWAP IgG4 levels were lower in egg-negative children in the post-MDA group compared to baseline. This resulted in higher anti-SEA IgE/IgG4 ratios for children in the post-MDA group compared to baseline. These post-MDA immunological changes are compatible with the current paradigm that treatment shifts immune responses to higher antischistosome IgE:IgG4 ratios in parallel with a potential increase in resistance to reinfection., (© 2018 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.)

World Health Organization recommendations for the timing and target population for mass drug administration (MDA) for schistosomiasis are based on the prevalence of infection in school children within a given community. In a large study comparing MDA approaches for Schistosoma mansoni control, we evaluated whether prevalence of infection and egg burdens in 9- to 12-year-old students reflected infection levels in young children and adults in the same community. Cross-sectional surveys of preadolescents (9-12 years old) were compared with those of first year students (5-8 years old) in 225 villages and adults (20-55 years old) in 150 villages along the Kenyan shores of Lake Victoria. Village schistosomiasis prevalence and intensity levels in preadolescents strongly correlated (P < 0.0001) with prevalence and infection intensity for other age groups in the community. Our findings suggest that S. mansoni prevalence and intensity among 9- to 12-year-olds are valid for community sampling purposes in mapping for MDAs., (© The American Society of Tropical Medicine and Hygiene.)

Background: The current reference test for the detection of S. mansoni in endemic areas is stool microscopy based on one or more Kato-Katz stool smears. However, stool microscopy has several shortcomings that greatly affect the efficacy of current schistosomiasis control programs. A highly specific multiplex real-time polymerase chain reaction (PCR) targeting the Schistosoma internal transcriber-spacer-2 sequence (ITS2) was developed by our group a few years ago, but so far this PCR has been applied mostly on urine samples. Here, we performed more in-depth evaluation of the ITS2 PCR as an alternative method to standard microscopy for the detection and quantification of Schistosoma spp. in stool samples., Methodology/principal Findings: Microscopy and PCR were performed in a Senegalese community (n = 197) in an area with high S. mansoni transmission and co-occurrence of S. haematobium, and in Kenyan schoolchildren (n = 760) from an area with comparatively low S. mansoni transmission. Despite the differences in Schistosoma endemicity the PCR performed very similarly in both areas; 13-15% more infections were detected by PCR when comparing to microscopy of a single stool sample. Even when 2-3 stool samples were used for microscopy, PCR on one stool sample detected more infections, especially in people with light-intensity infections and in children from low-risk schools. The low prevalence of soil-transmitted helminthiasis in both populations was confirmed by an additional multiplex PCR., Conclusions/significance: The ITS2-based PCR was more sensitive than standard microscopy in detecting Schistosoma spp. This would be particularly useful for S. mansoni detection in low transmission areas, and post-control settings, and as such improve schistosomiasis control programs, epidemiological research, and quality control of microscopy. Moreover, it can be complemented with other (multiplex real-time) PCRs to detect a wider range of helminths and thus enhance effectiveness of current integrated control and elimination strategies for neglected tropical diseases.

We evaluated the performance of a point-of-contact circulating cathodic antigen assay (POC-CCA) to detect schistosome infections in primary school children (N = 1,801) living in areas with low, moderate, and high Schistosoma mansoni prevalence in western Kenya. The commercially available assay (CCA-1) and a second, experimental formulation (CCA-2) were compared against Kato-Katz stool examinations and an anti-schistosome enzyme-linked immunosorbent assay (ELISA). A latent class model based on the four tests was used to establish "true infection status" in three different zones based on their distance from Lake Victoria. As a screening tool for community treatment according to World Health Organization (WHO) guidelines, the Kato-Katz examination was in closest agreement with the latent class model, followed by the experimental CCA-2, soluble adult worm antigen preparation (SWAP) ELISA, and CCA-1, which had high sensitivity compared with the other tests but was consistently the least specific. Our experience suggests that POC-CCA tests offer a field-friendly alternative to Kato-Katz, but need further interpretation for appropriate field use., (© The American Society of Tropical Medicine and Hygiene.)

Financial resources tend to be limited in schistosomiasis endemic areas, forcing program managers to balance financial and scientific considerations when selecting detection assays. Therefore, we compared the costs of using single stool Kato-Katz, triplicate stool Kato-Katz, and point-of-contact circulating cathodic antigen (POC-CCA) assays for the detection of Schistosoma mansoni infection. Economic and financial costs were estimated from the viewpoint of a schistosomiasis control program using the ingredients approach. Costs related to specimen collection, sample processing and analysis, and treatment delivery were considered. Analysis inputs and assumptions were tested using one-way and two-way sensitivity analysis. The total per-person cost of performing the single Kato-Katz, triplicate Kato-Katz, and POC-CCA was US$6.89, US$17.54, and US$7.26, respectively. Major cost drivers included labor, transportation, and supplies. In addition, we provide a costing tool to guide program managers in evaluating detection costs in specific settings, as costs may vary temporally and spatially., (© The American Society of Tropical Medicine and Hygiene.)

Recent years have witnessed an increase in the use of community based participatory research (CBPR) tools for understanding environment and health issues and facilitating social action. This paper explores the application and utility of photovoice for understanding water, sanitation, and hygiene (WASH) behaviours and catalysing community led solutions to change behaviours. Between June and August 2013, photovoice was conducted with eight (8) women in Usoma, a lakeshore community in Western Kenya with a follow-up community meeting (baraza) in May 2014 to discuss findings with the community members and government officials. In the first part of the study, photovoice one-on-one interviews were used to explore local perceptions and practices around water-health linkages and how the ecological and socio-political environment shapes these perceptions and practices. This paper, which is the second component of the study, uses photovoice group discussions to explore participants' experiences with and (re)action to the photographs and the photovoice project. The findings illustrate that photovoice was an effective CBPR methodology for understanding behaviours, creating awareness, facilitating collective action, and engaging with local government and local health officials at the water-health nexus.

Background: Schistosomiasis, a parasitic disease that affects over 200 million people, can lead to significant morbidity and mortality; distribution of single dose preventative chemotherapy significantly reduces disease burden. Implementation of control programs is dictated by disease prevalence rates, which are determined by costly and labor intensive screening of stool samples. Because ecological and human factors are known to contribute to the focal distribution of schistosomiasis, we sought to determine if specific environmental and geographic factors could be used to accurately predict Schistosoma mansoni prevalence in Nyanza Province, Kenya., Methodology/principal Findings: A spatial mixed model was fit to assess associations with S. mansoni prevalence in schools. Data on S. mansoni prevalence and GPS location of the school were obtained from 457 primary schools. Environmental and geographic data layers were obtained from publicly available sources. Spatial models were constructed using ArcGIS 10 and R 2.13.0. Lower S.mansoni prevalence was associated with further distance (km) to Lake Victoria, higher day land surface temperature (LST), and higher monthly rainfall totals. Altitude, night LST, human influence index, normalized difference vegetation index, soil pH, soil texture, soil bulk density, soil water capacity, population, and land use variables were not significantly associated with S. mansoni prevalence., Conclusions: Our model suggests that there are specific environmental and geographic factors that influence S. mansoni prevalence rates in Nyanza Province, Kenya. Validation and use of schistosomiasis prevalence maps will allow control programs to plan and prioritize efficient control campaigns to decrease schistosomiasis burden.

Background: Intestinal schistosomiasis continues to be a significant cause of morbidity among communities located around Lake Victoria and on its islands. Although epidemiological surveys have been conducted in other areas bordering the lake in western Kenya, Mbita district and its adjacent islands have never been surveyed, largely due to logistical challenges in accessing these areas. Consequently, there is a paucity of data on prevalence of schistosomiasis and soil-transmitted helminth (STH) infections that are endemic in this region., Methods: This cross-sectional study determined the prevalence, intensity of infection and geographical distribution of schistosome and STH infections among 4,065 children aged 5-19 years in 84 primary schools in Mbita and nearby islands of Lake Victoria (Mfangano, Ringiti, Rusinga and Takawiri), in western Kenya. Single stool samples were collected and examined for eggs of Schistosoma mansoni and STHs (Hookworms, Ascaris lumbricoides and Trichuris trichiura) using the Kato-Katz technique. Primary schools were mapped using geographical information system data on PDAs and prevalence maps generated using ArcView GIS software., Results: Overall, 65.6% (95% CI = 64.2-67.1%) of children were infected with one or more helminth species; 12.4% (95% CI = 11.4-13.4%) of children were infected with one or more STH species. Mean school prevalence of S. mansoni infection was 60.5% (95% CI = 59.0-62.0%), hookworms 8.4% (95% CI = 7.6-9.3%), A. lumbricoides 3.3% (95% CI = 2.7-3.8%), and T. trichiura 1.6% (95% CI = 1.2-2.0%). Interestingly, the mean S. mansoni prevalence was 2-fold higher on the islands (82%) compared to the mainland (41%) (z = 5.8755, P < 0.0001). Similarly, intensity of infection was 54% higher on the islands (217.2 ± 99.3) compared to the mainland (141.3 ± 123.7) (z = 3.9374, P < 0.0001). Schools in closest proximity to Lake Victoria had the highest S. mansoni prevalence while prevalence of STHs was more homogenously distributed., Conclusions: The very high prevalence of schistosomiasis in Mbita and the 4 islands is quite alarming, and indicates an urgent and critical need for control interventions. Findings from this survey indicate the need to implement treatment in remote areas not previously covered by mass drug administration programs.

Abstract. The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) includes communitywide treatment in areas with ≥ 25% prevalence of schistosomiasis along the shores of Lake Victoria using community health workers (CHWs). The CHWs are key drivers in community-owned mass drug administration (MDA) intervention programs. We explored their experiences and perceptions after initial MDA participation. Unstructured open-ended group discussions were conducted after completion of MDA activities. Narratives were obtained from CHWs using a digital audio recorder during the group discussion, transcribed verbatim and translated into English where applicable. Thematic decomposition of data was done using ATLAS.t.i. software. From the perspective of the CHWs, factors influencing MDA compliance included drug side effects, food supply stability, and conspiracy theories about the "real" purpose of treatment. The interest of CHWs to serve as community drug distributors stemmed from both intrinsic and extrinsic factors. Feedback from CHWs can promote more effective MDA in rural Kenyan communities.

A better understanding of the mechanism of anemia associated with Schistosoma mansoni infection might provide useful information on how treatment programs are implemented to minimize schistosomiasis-associated morbidity and maximize treatment impact. We used a cross-sectional study with serum samples from 206 Kenyan school children to determine the mechanisms in S. mansoni-associated anemia. Serum ferritin and soluble transferrin receptor levels were measured by using an enzyme-linked immunosorbent assay. Results suggest that S. mansoni-infected persons are more likely (odds ratio = 3.68, 95% confidence interval = 1.33-10.1) to have levels of serum ferritin (> 100 ng/mL) that are associated with anemia of inflammation (AI) than S. mansoni-uninfected children. Our results suggest that AI is the most common form of anemia in S. mansoni infections. In contrast, the mechanism of anemia in S. mansoni-uninfected children was iron deficiency. Moreover, the prevalence of AI in the study participants demonstrated a significant trend with S. mansoni infection intensity (P < 0.001). Our results are consistent with those observed in S. japonicum-associated anemia.

High levels of environmental contamination, often associated with improper waste and excreta management, are widespread among informal settlements within urban areas in developing countries. We determined the level of faecal contamination in domestic water sources and evaluated the potential contribution of these water sources to intestinal helminthiases in seven informal settlements of Kisumu City, western Kenya. Membrane filtration technique was used for enumeration of total and faecal (Escherichia coli) coliform bacteria in water samples collected from dams, rivers, springs and wells. Out of the 80 water sources sampled, 76 (95%) were highly contaminated with E coli. All water samples from unprotected wells (26) and 92.6% of samples from protected wells (25) were positive for E. coli. The highest and lowest E. coli densities were observed in samples from dams (3,800 ± 1,807 coliforms per 100 ml) and boreholes (419 ± 223 coliforms per 100 ml), respectively (p = 0.0321). Distance from pit latrines was negatively associated with E. coli coliform density for wells (r = -0.34, n = 53, p = 0.0142). Untreated well-water may not be suitable for human consumption, and its continued use constitutes a major health risk for the inhabitants of these informal settlements.

Background: Although schistosomiasis is generally considered a rural phenomenon, infections have been reported within urban settings. Based on observations of high prevalence of Schistosoma mansoni infection in schools within the informal settlements of Kisumu City, a follow-up malacological survey incorporating 81 sites within 6 informal settlements of the City was conducted to determine the presence of intermediate host snails and ascertain whether active transmission was occurring within these areas., Methods: Surveyed sites were mapped using a geographical information system. Cercaria shedding was determined from snails and species of snails identified based on shell morphology. Vegetation cover and presence of algal mass at the sites was recorded, and the physico-chemical characteristics of the water including pH and temperature were determined using a pH meter with a glass electrode and a temperature probe., Results: Out of 1,059 snails collected, 407 (38.4%) were putatively identified as Biomphalaria sudanica, 425 (40.1%) as Biomphalaria pfeifferi and 227 (21.5%) as Bulinus globosus. The spatial distribution of snails was clustered, with few sites accounting for most of the snails. The highest snail abundance was recorded in Nyamasaria (543 snails) followed by Nyalenda B (313 snails). As expected, the mean snail abundance was higher along the lakeshore (18 ± 12 snails) compared to inland sites (dams, rivers and springs) (11 ± 32 snails) (F(1, 79) = 38.8, P < 0.0001). Overall, 19 (1.8%) of the snails collected shed schistosome cercariae. Interestingly, the proportion of infected Biomphalaria snails was higher in the inland (2.7%) compared to the lakeshore sites (0.3%) (P = 0.0109). B. sudanica was more abundant in sites along the lakeshore whereas B. pfeifferi and B. globosus were more abundant in the inland sites. Biomphalaria and Bulinus snails were found at 16 and 11 out of the 56 inland sites, respectively., Conclusions: The high abundance of Biomphalaria and Bulinus spp. as well as observation of field-caught snails shedding cercariae confirmed that besides Lake Victoria, the local risk for schistosomiasis transmission exists within the informal settlements of Kisumu City. Prospective control interventions in these areas need to incorporate focal snail control to complement chemotherapy in reducing transmission.

Although schistosomiasis burden is greatest among school-age children (SAC) (6-15 years of age), infection among preschool-age children (PSAC) (1-5 years), may be underestimated in endemic areas. We conducted a cross-sectional study evaluating Schistosoma mansoni infection among children 1-15 years of age in a highly endemic community in Kenya. Diagnostic tests included stool exam (Kato/Katz technique), serum testing for schistosome-specific antibodies, and urine testing for circulating cathodic antigen (CCA). Overall, 268 SAC and 216 PSAC were enrolled; prevalence increased with age, with 14% of 1 year olds and more than 90% of children > 10 years of age infected. Stool exam was more sensitive among SAC than PSAC, but performance was similar after adjusting for infection intensity (based on CCA). Schistosomiasis poses a threat to PSAC in endemic areas, and stool exam may underestimate the prevalence of infection. Control programs in such areas should consider PSAC in addition to SAC.

Although accurate assessment of the prevalence of Schistosoma mansoni is important for the design and evaluation of control programs, the most widely used tools for diagnosis are limited by suboptimal sensitivity, slow turn-around-time, or inability to distinguish current from former infections. Recently, two tests that detect circulating cathodic antigen (CCA) in urine of patients with schistosomiasis became commercially available. As part of a larger study on schistosomiasis prevalence in young children, we evaluated the performance and diagnostic accuracy of these tests--the carbon test strip designed for use in the laboratory and the cassette format test intended for field use. In comparison to 6 Kato-Katz exams, the carbon and cassette CCA tests had sensitivities of 88.4% and 94.2% and specificities of 70.9% and 59.4%, respectively. However, because of the known limitations of the Kato-Katz assay, we also utilized latent class analysis (LCA) incorporating the CCA, Kato-Katz, and schistosome-specific antibody results to determine their sensitivities and specificities. The laboratory-based CCA test had a sensitivity of 91.7% and a specificity of 89.4% by LCA while the cassette test had a sensitivity of 96.3% and a specificity of 74.7%. The intensity of the reaction in both urine CCA tests reflected stool egg burden and their performance was not affected by the presence of soil transmitted helminth infections. Our results suggest that urine-based assays for CCA may be valuable in screening for S. mansoni infections.

Background: Age prevalence curves for areas in which schistosomiasis is endemic suggest that humans develop partial immunity to reinfection beginning in early adolescence. We conducted a 2-year longitudinal study to determine whether children infected with Schistosoma mansoni develop protection-related immune responses after treatment with praziquantel and whether the development of these immune responses is accelerated by frequent treatment after reinfection., Methods: Children (8-10 years old) were tested for S. mansoni every 4 months and treated with praziquantel when positive (arm A; n=68) or were tested and treated at the end of the 2-year follow-up period (arm B; n=49)., Results: Children in arm A who remained free of infection during follow-up had significantly higher baseline levels of schistosome-specific immunoglobulin E (IgE) than did children with > or =2 repeat diagnoses of S. mansoni infection. Children with > or =2 repeat diagnoses of S. mansoni infection had significantly increased levels of anti-schistosome IgE and CD23(+) B cells after receiving > or =3 praziquantel treatments over the course of follow-up. No increase in either parameter was seen in children who received only the baseline praziquantel treatment., Conclusions: B cell activation and anti-schistosome IgE are associated with resistance to S. mansoni in children, and these immunological parameters can be increased by multiple rounds of infections and praziquantel-induced cures.

Background: The immunologic findings that most consistently correlate with resistance in human schistosomiasis are high levels of IgE and low levels of IgG4. We have genotyped gene and promoter polymorphisms of cytokines associated with regulation of these isotypes in a cohort of men occupationally exposed to Schistosoma mansoni in western Kenya and evaluated their patterns with respect to resistance and susceptibility to reinfection after treatment and cure with praziquantel (PZQ)., Methodology/principal Findings: In this cohort, polymorphisms in IL-4 (-590T high IgE), IL-13 (-1055T high producer) and IFN-gamma (+874A high producer) demonstrated several correlations with resistance to reinfection. Resistance to reinfection was significantly correlated with the heterozygous IL-4 -590 genotype C/T (OR 3.5, [CI 1.2, 10.2]) compared to T/T. Among men with a homozygous IL-13 genotype CC/TT, having a T allele at the IFN-gamma +874 position increased the odds of resistance relative to individuals with the IFN-gamma +874 A/A genotype (OR = 17.5 [CI 3.0, 101.5]). Among men with homozygous A/A IFN-gamma genotype, the heterozygous IL-13 genotype C/T was associated with resistance relative to the homozygous C/C or T/T genotypes (OR = 22.5 [CI 3.5, 144.4]). No increases in odds of resistance were found in relation to the IL-13 genotype among those with a T allele in the IFN-gamma gene or in relation to the IFN-gamma genotype among those with a heterozygous IL-13 genotype. Calculation of the attributable proportion of resistance showed a significant synergistic interaction between IL-13 -1055 C/T and IL-4 -590 C/T., Conclusions: The identified polymorphisms do not by themselves confer resistance or susceptibility, but we propose that these genotypes allow the resistant phenotype to be developed and expressed upon suitable immune exposure. Based on the literature, these polymorphisms contribute to the regulation of their respective cytokines, likely leading to downstream differences in the production and interrelationships of critical defense mechanisms.

To investigate whether infection with human immunodeficiency virus 1 (HIV-1) affects fibrosis development in patients infected with Schistosoma mansoni, we evaluated schistosomiasis-induced pathology in the livers of Kenyan patients co-infected with HIV-1. Compared with persons with schistosomiasis alone (n = 58), there were no significant differences in distribution of ultrasound-detectable pathology in persons with HIV-1 co-infection (n = 23). Similarly, serum aspartate aminotransferase levels were not significantly different in HIV-1+ individuals. Hepatic fibrosis was associated with significantly decreased CD4+ T cell counts, even in the absence of HIV-1 infection. These data suggest that HIV-1 co-infection does not significantly alter the proportion of patients experiencing schistosomiasis-induced fibrosis, but pathology associated with S. mansoni infections leads to CD4+ T cell reductions and thereby may exacerbate the effects of HIV-1 in co-infected individuals.

For the past ten years, we have been exploring the relationship between schistosomiasis and human immunodeficiency virus (HIV-1) and how coinfection with both agents may affect the pathology and progression of each infection. To date, given the systems we have examined, the effects of HIV-1 on schistosomiasis have been more profound than the effects of schistosomiasis on HIV-1 progression. Additional key questions with important public health implications remain unanswered, but hopefully not unanswerable.

A survey of 1,246 children 10-12 years old in 32 primary schools in Kenya near Lake Victoria was conducted to determine prevalence and distribution of schistosome and geohelminth infections. Stool and urine samples were collected and examined for eggs of Schistosoma mansoni, S. haematobium, and intestinal helminths. A questionnaire was used to obtain demographic information and to quantify exposure to surface waters. Houses, schools, and water sources were mapped using a geographic information system. The mean school prevalence of S. mansoni infection was 16.3% (range = 0-80%). Proximity to the lake (r = 0.89, P < 0.001) and contact with lake water were associated with infection, as were specific water-related activities including swimming, fishing, and collecting water. Sixty-three percent of students were infected with one or more other geohelminths and these infections were more homogenously distributed. The separate distributions of schistosome and geohelminth infections have important implications for combined mass-treatment programs.

Objectives: The objectives of this study were to conduct a survey on the knowledge and practices relating to malaria prevention and treatment in two rural communities in Western Kenya, and to determine the acceptability of specially designed permethrin impregnated sisal strands curtains previously introduced into one of the study communities as barriers to mosquito biting., Design: A knowledge, attitudes and practices (KAP) survey was conducted by pre-trained interviewers using a pre-tested questionnaire., Setting: The study was conducted in two communities located 15 km northwest of Kisumu town, and next to the swamps bordering Lake Victoria in Kisumu District, Western Kenya., Participants: Adult individuals from 50 houses selected from the intervention, and 50 houses from the control sites were included in the study., Results: Both communities had a clear conception of malaria and its symptoms, and of the mosquito as its vector. Malaria was recognised as a potential cause of death by 44% and 72% of the participants in the intervention and control sites respectively. Sixty two per cent to 74% of the people interviewed in both sites named mosquitoes as the causative agents of malaria. Chloroquine was still the drug of choice for malaria treatment, with over 70% usage among the study population. Mention of pyrimethamine/sulfadoxine and pyrimethamine/sulfalene as alternative therapy was below five per cent. Despite a high level (86%) of awareness of bednets as effective barriers to mosquito biting, they were reported in use by less than 35% in both communities. Sisal strand curtains were considered effective and acceptable to more than 80% of the community., Conclusions: The results of this study underscore the existing need for affordable means of mosquito control, such as sisal strand curtains, for such rural communities which may be acutely aware of the problems associated with malaria, but are constrained from taking any action by lack of resources.

Praziquantel is the drug of choice for schistosomiasis chemotherapy. Although the exact mechanism of how praziquantel kills schistosomes remains poorly understood, the immune response of the host is an important factor in drug efficacy. It is thus possible that disease states of humans that lead to immunodeficiencies, such as infection with human immunodeficiency virus-1 (HIV-1), may render praziquantel less effective in treating schistosomiasis. To test this hypothesis, persons with high levels of Schistosoma mansoni infection who were or were not also infected with HIV-1 were treated with a standard regimen of praziquantel and monitored by quantitative fecal examination and plasma circulating cathodic antigen. Both groups responded to praziquantel therapy equally and individuals with low percentages (< 20%) of CD4+ T cells did not differ from individuals with higher CD4 cell percentages. These data demonstrate that persons with HIV-1 infection can be treated effectively for schistosomiasis with praziquantel.