Expression of CD117 (c-Kit) on Circulating B Cells in Pediatric Schistosomiasis.

Few B cells express CD27, the primary marker for memory B cells, in pediatric schistosomiasis, suggesting B cell malfunction. This study further demonstrates unexpected high expression of CD117 on circulating B cells in children highly exposed to Schistosoma mansoni infectious larvae. CD117 is expressed by immature or lymphoma B cells, but not by mature, circulating cells. We therefore sought to define the significance of CD117 on blood B cells. We found that CD117-positive (CD117+) B cells increased with the intensity of schistosome infection. In addition, CD117 expression was reduced on CD23+ B cells previously shown to correlate with resistance to infection. Stimulation with a panel of cytokines demonstrated that CD117 levels were upregulated in response to a combination of interleukin 4 (IL-4) and stem cell factor (SCF), the ligand for CD117, whereas IL-2 led to a reduction. In addition, stimulation with SCF generally reduced B cell activation levels. Upon further investigation, it was established that multiple circulating cells expressed increased levels of CD117, including monocytes, neutrophils, and eosinophils, and expression levels correlated with that of B cells. Finally, we identified a population of large circulating cells with features of reticulocytes. Overall, our results suggest that hyperexposure to intravascular parasitic worms elicits immature cells from the bone marrow. Levels of SCF were shown to reduce as children began to transition through puberty. The study results pose an explanation for the inability of children to develop significant immunity to infection until after puberty.

A Persistent Hotspot of Schistosoma mansoni Infection in a Five-Year Randomized Trial of Praziquantel Preventative Chemotherapy Strategies.

Background: Persistent hotspots have been described after mass drug administration (MDA) for the control of schistosomiasis, but they have not been studied during the course of a multiyear MDA program. Methods: In data from a 5-year study of school-based and village-wide preventive chemotherapy strategies for Schistosoma mansoni, spatial scan statistics were used to find infection hotspots in 3 populations: 5- to 8-year-olds, 9- to 12-year-olds, and adults. Negative binomial regression was used to analyze changes from baseline, and receiver operating characteristic analyses were used to predict which villages would reach prevalence and intensity endpoints. Results: We identified a persistent hotspot, not associated with study arm, where S. mansoni infection prevalence and intensity did not decrease as much as in villages outside the hotspot. Significant differences from baseline were realized after 1 year of MDA: we did not identify factors that moderated this relationship. Villages meeting specified endpoints at year 5 were predicted from prior year data with moderately high sensitivity and specificity. Conclusions: The MDA strategies were less effective at reducing prevalence and intensity in the hotspot compared with other villages. Villages that reached year 5 endpoints could be detected earlier, which may provide the opportunity to amend intervention strategies.

Protocol and baseline data for a multi-year cohort study of the effects of different mass drug treatment approaches on functional morbidities from schistosomiasis in four African countries.

BACKGROUND: The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) focus is on randomized trials of different approaches to mass drug administration (MDA) in endemic countries in Africa. Because their studies provided an opportunity to evaluate the effects of mass treatment on Schistosoma-associated morbidity, nested cohort studies were developed within SCORE's intervention trials to monitor changes in a suite of schistosomiasis disease outcomes. This paper describes the process SCORE used to select markers for prospective monitoring and the baseline prevalence of these morbidities in four parallel cohort studies. METHODS: In July 2009, SCORE hosted a discussion of the potential impact of MDA on morbidities due to Schistosoma infection that might be measured in the context of multi-year control. Candidate markers were reviewed and selected for study implementation. Baseline data were then collected from cohorts of children in four country studies: two in high endemic S. mansoni sites (Kenya and Tanzania), and two in high endemic S. haematobium sites (Niger and Mozambique), these cohorts to be followed prospectively over 5 years. RESULTS: At baseline, 62% of children in the S. mansoni sites had detectable eggs in their stool, and 10% had heavy infections (≥ 400 eggs/g feces). Heavy S. mansoni infections were found to be associated with increased baseline risk of anemia, although children with moderate or heavy intensity infections had lower risk of physical wasting. Prevalence of egg-positive infection in the combined S. haematobium cohorts was 27%, with 5% of individuals having heavy infection (≥50 eggs/10 mL urine). At baseline, light intensity S. haematobium infection was associated with anemia and with lower scores in the social domain of health-related quality-of-life (HRQoL) assessed by Pediatric Quality of Life Inventory. CONCLUSIONS: Our consensus on practical markers of Schistosoma-associated morbidity indicated that height, weight, hemoglobin, exercise tolerance, HRQoL, and ultrasound abnormalities could be used as reference points for gauging treatment impact. Data collected over five years of program implementation will provide guidance for future evaluation of morbidity control in areas endemic for schistosomiasis. TRIAL REGISTRATION: These cohort studies are registered and performed in conjunction with the International Standard Randomised Controlled Trial Registry trials ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 , and ISRCTN32045736 .

Effect of Repeated Anthelminthic Treatment on Malaria in School Children in Kenya: A Randomized, Open-Label, Equivalence Trial.

BACKGROUND: School children living in the tropics are often concurrently infected with plasmodium and helminth parasites. It has been hypothesized that immune responses evoked by helminths may modify malaria-specific immune responses and increase the risk of malaria. METHODS: We performed a randomized, open-label, equivalence trial among 2436 school children in western Kenya. Eligible children were randomized to receive either 4 repeated doses or a single dose of albendazole and were followed up during 13 months to assess the incidence of clinical malaria. Secondary outcomes were Plasmodium prevalence and density, assessed by repeat cross-sectional surveys over 15 months. Analysis was conducted on an intention-to-treat basis with a prespecified equivalence range of 20%. RESULTS: During 13 months of follow-up, the incidence rate of malaria was 0.27 episodes/person-year in the repeated treatment group and 0.26 episodes/person-year in the annual treatment group (incidence difference, 0.01; 95% confidence interval, -.03 to .06). The prevalence and density of malaria parasitemia did not differ by treatment group at any of the cross-sectional surveys. CONCLUSIONS: Our findings suggest that repeated deworming does not alter risks of clinical malaria or malaria parasitemia among school children and that school-based deworming in Africa may have no adverse consequences for malaria. CLINICAL TRIALS REGISTRATION: NCT01658774.

Gaining and sustaining schistosomiasis control: study protocol and baseline data prior to different treatment strategies in five African countries.

BACKGROUND: The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was established in 2008 to answer strategic questions about schistosomiasis control. For programme managers, a high-priority question is: what are the most cost-effective strategies for delivering preventive chemotherapy (PCT) with praziquantel (PZQ)? This paper describes the process SCORE used to transform this question into a harmonized research protocol, the study design for answering this question, the village eligibility assessments and data resulting from the first year of the study. METHODS: Beginning in 2009, SCORE held a series of meetings to specify empirical questions and design studies related to different schedules of PCT for schistosomiasis control in communities with high (gaining control studies) and moderate (sustaining control studies) prevalence of Schistosoma infection among school-aged children. Seven studies are currently being implemented in five African countries. During the first year, villages were screened for eligibility, and data were collected on prevalence and intensity of infection prior to randomisation and the implementation of different schemes of PZQ intervention strategies. RESULTS: These studies of different treatment schedules with PZQ will provide the most comprehensive data thus far on the optimal frequency and continuity of PCT for schistosomiasis infection and morbidity control. CONCLUSIONS: We expect that the study outcomes will provide data for decision-making for country programme managers and a rich resource of information to the schistosomiasis research community. TRIAL REGISTRATION: The trials are registered at International Standard Randomised Controlled Trial registry (identifiers: ISRCTN99401114 , ISRCTN14849830 , ISRCTN16755535 , ISRCTN14117624 , ISRCTN95819193 and ISRCTN32045736 ).

Experiences and perspectives of community health workers from implementing treatment for schistosomiasis using the community directed intervention strategy in an informal settlement in Kisumu City, western Kenya.

BACKGROUND: The Community Directed Intervention (CDI) strategy has been used to conduct various health interventions in Africa, including control of Neglected Tropical Diseases (NTDs). Although the CDI approach has shown good results in the control of onchocerciasis and lymphatic filariasis with respect to treatment coverage using community drug distributors, its utility in the control of schistosomiasis among urban poor is yet to be established. Using a longitudinal qualitative study, we explored the experiences, opportunities, challenges as well as recommendations of Community Health Workers (CHWs) after participation in annual mass drug administration (MDA) activities for schistosomiasis using the CDI approach in an urban setting. METHODS: Unstructured open-ended group discussions were conducted with CHWs after completion of annual MDA activities. Narratives were obtained from CHWs using a digital audio recorder during the group discussions, transcribed verbatim and translated into English where applicable. Thematic decomposition of data was done using ATLAS.ti. software, and themes explored using the principle of interpretative phenomenological analysis (IPA). RESULTS: From the perspective of the CHWs, opportunities for implementing CDI in urban settings, included the presence of CHWs, their supervisory structures and their knowledge of intervention areas, and opportunity to integrate MDA with other health interventions. Several challenges were mentioned with regards to implementing MDA using the CDI strategy among them lack of incentives, fear of side effects, misconceptions regarding treatment and mistrust, difficulties working in unsanitary environmental conditions, insecurity, and insufficient time. A key recommendation in promoting more effective MDA using the CDI approach was allocation of more time to the exercise. CONCLUSION: Findings from this study support the feasibility of using CDI for implementing MDA for schistosomiasis in informal settlements of urban areas. Extensive community sensitization and provision of incentives may help address the aforementioned challenges associated with implementing MDA using the CDI strategy. Opportunities highlighted in this study may be of value to other programmes that may be considering the adoption of the CDI strategy for rolling out interventions in the urban setting.

Evaluation of medicine retail outlets for sale of typhoid fever vaccine among adults in two urban and rural settings in western Kenya: a proof-of-concept study.

BACKGROUND: Private sector medicine outlets are an important provider of health services across the developing world, and are an untapped means of distributing and selling vaccines outside of childhood immunization programs. The present study assessed the viability of medicine outlets (chemists and pharmacies) as potential channels for sale of vaccines. METHODS: To evaluate the viability of the medicine outlet model, we partnered with nine outlets across urban and rural communities in western Kenya to sell a nurse-administered typhoid vaccine. Purchasers were surveyed to reveal market demographic characteristics, reasons for vaccine purchase, and sources of information about the program. Key informant interviews and focus group discussions defined acceptability, demand, and additional suggestions for improving this mechanism of selling and distributing vaccines. RESULTS: There was a higher than expected demand for the vaccine that resulted in stock-outs. Previous instance of typhoid, desire to prevent disease, affordable price and convenience were cited by most participants as main reasons for purchase of vaccine at the local outlet. The most common source of information on the vaccine sale was word-of-mouth and referral from friends. Longer vaccine sale duration, adequate stocking of vaccines and extended hours of administration in the evening to allow working individuals to buy vaccines were cited by participants as ways for improved participation in the future. CONCLUSIONS: This study demonstrated a high demand for vaccines at community medicine outlets. Important insights on how to improve and sustain such a program included extension of distribution time, education of outlet keepers, and minimizing vaccine stockouts. With improved social marketing, infrastructure mapping, education and pricing schemes, medicine outlets could become a sustainable avenue for selling adult vaccines in emerging markets for both routine and pandemic vaccines.

A non-synonymous polymorphism in IL-23R Gene (rs1884444) is associated with reduced risk to schistosomiasis-associated Immune Reconstitution Inflammatory Syndrome in a Kenyan population.

BACKGROUND: Human Immunodeficiency Virus (HIV) and Schistosomiasis co-infection is common among residents at the shores of Lake Victoria in Kenya. About 36% of this population initiating antiretroviral therapy (ART) experience Immune Reconstitution Inflammatory Syndrome (IRIS) that complicates recovery. Several IL-23R alleles have been associated with susceptibility to both autoimmune and inflammatory diseases through T-helper type 17 (TH17) cells. However, whether or not variants within the IL-23R increase susceptibility to IRIS in western Kenya is unknown. The objective of the current study was to determine the association between IL-23R gene polymorphisms, CD4+ cell counts and HIV RNA levels and IRIS in HIV and Schistosoma mansoni co-infected patients undergoing highly active anti-retroviral therapy (HAART). METHODS: A three-month case-control study was conducted on antiretroviral naïve schistosomiasis/HIV co-infected fishermen starting HAART in Uyoma Rarieda, Siaya County, Kenya. Seventy one patients were sampled at baseline and followed up for three months, to establish if they developed Schistosoma-related IRIS. In addition, the CD4+ cell counts and HIV RNA levels were determined in pre- and post-administration of HAART. Variations at five polymorphic sites of IL-23R (rs1884444, rs11465754, rs6682925, rs7530511 and rs7539625) based on >10% minor allele frequency in Yoruban reference population was determined using Allelic Discrimination Assay. The association between the five variants and susceptibility to IRIS was determined using logistic regression while controlling for potential confounders. In addition, the functional differences between the baseline CD4 + Cell counts and viral loads were determined using medians while across IL-23R genotypes were determined using Kruskal-Wallis tests. RESULTS: Overall, 26 (36.6%) patients developed schistosomiasis-associated IRIS at a median age of 35.5 years. Carriage of the TT genotype at the non-synonymous rs1884444 T > G relative to GG, was associated with a decreased risk of schistosomiasis-associated IRIS (OR, 0.25, 95% CI, 0.07-0.96, P = 0.043) while both baseline CD4+ cell counts and viral loads had no association with IRIS. CONCLUSION: These findings indicate that the non-synonymous variant rs1884444 T > G of IL-23R is associated with a decreased risk to schistosomiasis-associated IRIS. However, additional studies in a larger cohort and with an all inclusive polymorphic variants in the synonymous and non-synonymous regions need to be evaluated.

CD23-bound IgE augments and dominates recall responses through human naive B cells.

Human peripheral blood BCRµ(+) B cells express high levels of CD23 and circulate preloaded with IgE. The Ag specificity of CD23-bound IgE presumably differs from the BCR and likely reflects the Ag-specific mix of free serum IgE. CD23-bound IgE is thought to enhance B cell Ag presentation to T cells raising the question of how a B cell might respond when presented with a broad mix of Ags and CD23-bound IgE specificities. We recently reported that an increase in CD23(+) B cells is associated with the development of resistance to schistosomiasis, highlighting the potential importance of CD23-bound IgE in mediating immunity. We sought to determine the relationship between BCR and CD23-bound IgE-mediated B cell activation in the context of schistosomiasis. We found that crude schistosome Ags downregulate basal B cell activation levels in individuals hyperexposed to infectious worms. Schistosome-specific IgE from resistant, occupationally exposed Kenyans recovered responses of B cells to schistosome Ag. Furthermore, cross-linking of CD23 overrode intracellular signals mediated via the BCR, illustrating its critical and dominating role in B cell activation. These results suggest that CD23-bound IgE augments and dominates recall responses through naive B cells.

Knowledge, attitudes, practices and acceptability of a school preventive chemotherapy programme for schistosomiasis and soil-transmitted helminths control in Angola.

Schistosomiasis and soil-transmitted helminth (STH) control programs require target population engagement, assessed through knowledge, attitudes and practices (KAP) surveys. We report the results of a KAP survey of Angolan schoolchildren supported by a school preventive chemotherapy (PC) programme, without or with a school water, sanitation and hygiene (WASH) programme (PC+/WASH- and PC+/WASH+, respectively); and schoolchildren without a school PC or WASH program (PC-/WASH-). Schoolchildren from PC+/WASH- (N = 218), PC+/WASH+ (N = 250) and PC-/WASH- (N = 254) schools were interviewed. Descriptive statistics were used to report demographics and survey responses. Chi-square or Fisher's exact test was used to compare PC+/WASH- schoolchildren with (i) PC+/WASH+ and (ii) PC-/WASH- schoolchildren. A lower proportion of PC+/WASH- schoolchildren used latrines and a higher proportion practised open defecation at school compared with PC+/WASH+ schoolchildren. A lower proportion of PC+/WASH- schoolchildren always washed their hands after toileting and before meals at school compared with PC+/WASH+ schoolchildren. However, the PC+/WASH- schoolchildren reported better toileting and handwashing practices at school compared to PC-/WASH- schoolchildren. Over 90% of PC+ schoolchildren agreed with schistosomiasis and STH control and accepted schoolteacher PC delivery. Expanding the integration of both school PC and WASH programs will improve health behaviours relevant to reduce the risk of schistosomiasis and STHs in schoolchildren. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

School-based preventive chemotherapy program for schistosomiasis and soil-transmitted helminth control in Angola: 6-year impact assessment.

BACKGROUND: A school preventive chemotherapy (PC) program for soil-transmitted helminths (STHs) and schistosomiasis has operated in Huambo, Uige and Zaire provinces, Angola, since 2013 and 2014, respectively; complemented by a school water, sanitation and hygiene (WASH) program in a subset of schools from 2016. Conducted in 2021, this is the first impact assessment of the school program for the control of schistosomiasis and STHs. METHODOLOGY/PRINCIPAL FINDINGS: A two-stage cluster design was used to select schools and schoolchildren for parasitological and WASH surveys. The rapid diagnostic tests (RDTs), point of care circulating cathodic antigen (POC-CCA) and Hemastix, were used to estimate Schistosoma mansoni and Schistosoma haematobium prevalence, respectively. Kato Katz was used to detect STHs, and quantify STH and S. mansoni infections. Urine filtration was used to quantify S. haematobium infections. Prevalence, infection intensity, relative prevalence reduction and egg reduction rates were calculated for schistosomiasis and STHs. Cohen's Kappa co-efficient was used to assess agreement between RDTs and microscopy. Chi-square or Fisher's exact test was used to compare WASH indicators in WASH-supported and WASH-unsupported schools. Overall, 17,880 schoolchildren (599 schools) and 6,461 schoolchildren (214 schools) participated in the schistosomiasis and STH surveys, respectively. Prevalence of any schistosomiasis in Huambo was 29.6%, Uige 35.4%, and Zaire 28.2%. Relative reduction in schistosomiasis prevalence from 2014 for Huambo was 18.8% (95% confidence interval (CI) 8.6, 29.0), Uige -92.3% (95%CI -162.2, -58.3), and Zaire -14.0% (95%CI -48.6, 20.6). Prevalence of any STH in Huambo was 16.3%, Uige 65.1%, and Zaire 28.2%. Relative reduction in STH prevalence for Huambo was -28.4% (95%CI -92.1, 35.2), Uige -10.7% (95%CI -30.2, 8.8), and Zaire -20.9% (95%CI -79.5, 37.8). A higher proportion of WASH-supported schools had improved water sources, and toilet and handwashing facilities compared to WASH-unsupported schools. CONCLUSIONS/SIGNIFICANCE: The limited impact this school program has had in controlling schistosomiasis and STHs identifies the need for a comprehensive understanding of individual, community, and environmental factors associated with transmission, and consideration for a community-wide control program.

Faecal contamination of public water sources in informal settlements of Kisumu City, western Kenya.

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.

Preclinical prophylactic efficacy testing of Sm-p80-based vaccine in a nonhuman primate model of Schistosoma mansoni infection and immunoglobulin G and E responses to Sm-p80 in human serum samples from an area where schistosomiasis is endemic.

The prophylactic efficacy of a schistosome antigen (Sm-p80) was tested in a nonhuman primate model, the baboon. Using a total of 28 baboons, different vaccination strategies were used including recombinant Sm-p80 protein formulated in Toll-like receptor 7 and Toll-like receptor 9 agonists, and DNA priming followed by boosting with protein plus adjuvants. Recombinant protein approaches provided levels of prophylactic efficacy of 52%-58%, whereas prime-boost approaches conferred 38%-47% protection in baboons. An appropriately balanced pro-inflammatory (T-helper 17 [Th17] and Th1) and anti-inflammatory (Th2) type of response was generated; the Th1 and Th17 types of immune responses appear to be indicative of increased prophylactic efficacy. Production and expression of several cytokines (interleukin 2 [IL-2], interferon γ, IL-12α, IL-1ß, IL-6, and IL-22) were up-regulated in vaccinated animals. Human correlate studies revealed Sm-p80 reactivity with immunoglobulin G in human serum samples from schistosome-infected individuals. In addition, a complete lack of prevailing Sm-p80-specific immunoglobulin E in a high-risk or infected population was observed, thus minimizing the risk of hypersensitivity reaction following vaccination with Sm-p80 in humans. This study provided the proof of concept to move Sm-p80 forward into further preclinical development leading to human clinical trials.

Potential Utility of Systemic Plasma Biomarkers for Evaluation of Pediatric Schistosomiasis in Western Kenya.

Introduction: Current diagnostic tools for schistosomiasis are limited, and new tests are necessary to enhance disease diagnosis and surveillance. Identification of novel disease-specific biomarkers may facilitate the development of such tests. We evaluated a panel of biomarkers used in sepsis and parasitic diseases for their potential suitability in the diagnosis of schistosomiasis. Objective: The study evaluated the levels of systemic plasma biomarkers in relation to Schistosoma mansoni infection and parasite burden. Methods: Six biomarkers were measured in the plasma of children from schistosomiasis-endemic regions using ELISA. The concentration of soluble CD23 (sCD23) and lipopolysaccharide (LPS) was tested in 199 and 124 plasma samples, respectively, while interleukin-6 (IL-6), soluble triggering receptor expressed on myeloid (sTREM) cells, eotaxin-1, and fatty acid-binding protein (FABP) concentrations were tested in 30 plasma samples. Results: The concentration of IL-6, eotaxin-1, FABP, and LPS was similar between schistosome-infected and uninfected children. The schistosome-infected children had higher median levels of sTREM and sCD23 as compared to uninfected children, 119.0 (29.9-208.9) versus 10.7 (0.0-73.4) (p = 0.046) and 2,549.0 (1,899.0-3,356.0) vs. 2,035.0 (1,448.0-2,939.0) (p = 0.05), respectively. In addition, sTREM was positively correlated with egg density (p = 0.017). Conclusion: Our data show that active schistosomiasis per se is associated with elevated levels of sTREM and sCD23. sTREM has potential diagnostic and prognostic values. However, these biomarkers did not distinguish between children with low egg burden and uninfected children.

Absence of lower genital tract lesions among women of reproductive age infected with Schistosoma mansoni: A cross-sectional study using a colposcope in Western Kenya.

BACKGROUND: Female genital schistosomiasis (FGS) constitutes four different lesions known to be caused by Schistosoma haematobium ova deposited in the genital tract. Schistosoma mansoni ova may also be found in the genital tract. However, it is not known if S. mansoni causes lower genital tract lesions characteristic of FGS. METHODOLOGY: This study was conducted in 8 villages along the shores of Lake Victoria, western Kenya. Stool and urine samples, collected from women of reproductive age on three consecutive days, were analysed for S. mansoni and S. haematobium infection. S. mansoni positive and S. haematobium negative willing participants, aged 18-50 years were invited to answer a questionnaire (demographics, symptoms), undergo a gynaecological examination and cytology specimen collection by an FGS expert. PRINCIPAL FINDINGS: Gynaecologic investigations were conducted in 147 S. mansoni-positive women who had a mean infection intensity of 253.3 epg (95% CI: 194.8-311.9 epg). Nearly 90% of them used Lake Victoria as their main water source. None were found to have cervicovaginal grainy sandy patches or rubbery papules. Homogenous yellow patches were found in 12/147 (8.2%) women. Women with homogenous yellow patches were significantly older (47 years) than the rest (34 years, p = 0.001). No association was found between intensity of S. mansoni infection and homogenous yellow patches (p = 0.70) or abnormal blood vessels (p = 0.14). S. mansoni infection intensity was not associated with genital itch, bloody or malodorous vaginal discharge. CONCLUSION: S. mansoni infection was neither associated with lower genital tract lesions nor symptoms typically found in women with FGS.

Effect of preventive chemotherapy with praziquantel on schistosomiasis among school-aged children in sub-Saharan Africa: a spatiotemporal modelling study.

BACKGROUND: Over the past 20 years, schistosomiasis control has been scaled up. Preventive chemotherapy with praziquantel is the main intervention. We aimed to assess the effect of preventive chemotherapy on schistosomiasis prevalence in sub-Saharan Africa, comparing 2000-10 with 2011-14 and 2015-19. METHODS: In this spatiotemporal modelling study, we analysed survey data from school-aged children (aged 5-14 years) in 44 countries across sub-Saharan Africa. The data were extracted from the Global Neglected Tropical Diseases database and augmented by 2018 and 2019 survey data obtained from disease control programmes. Bayesian geostatistical models were fitted to Schistosoma haematobium and Schistosoma mansoni survey data. The models included data on climatic predictors obtained from satellites and other open-source environmental databases and socioeconomic predictors obtained from various household surveys. Temporal changes in Schistosoma species prevalence were estimated by a categorical variable with values corresponding to the three time periods (2000-10, 2011-14, and 2015-19) during which preventive chemotherapy interventions were scaled up. FINDINGS: We identified 781 references with relevant geolocated schistosomiasis survey data for 2000-19. There were 19 166 unique survey locations for S haematobium and 23 861 for S mansoni, of which 77% (14 757 locations for S haematobium and 18 372 locations for S mansoni) corresponded to 2011-19. Schistosomiasis prevalence among school-aged children in sub-Saharan Africa decreased from 23·0% (95% Bayesian credible interval 22·1-24·1) in 2000-10 to 9·6% (9·1-10·2) in 2015-19, an overall reduction of 58·3%. The reduction of S haematobium was 67·9% (64·6-71·1) and that of S mansoni 53·6% (45·2-58·3) when comparing 2000-10 with 2015-19. INTERPRETATION: Our model-based estimates suggest that schistosomiasis prevalence in sub-Saharan Africa has decreased considerably, most likely explained by the scale-up of preventive chemotherapy. There is a need to consolidate gains in the control of schistosomiasis by means of preventive chemotherapy, coupled with other interventions to interrupt disease transmission. FUNDING: European Research Council and WHO.

Identification of cytokeratin 18 as a biomarker of mouse and human hepatosplenic schistosomiasis.

Previously, we demonstrated unique protein expression patterns in 20-week-Schistosoma mansoni-infected CBA/J mice with moderate splenomegaly syndrome (MSS) or hypersplemomegaly syndrome (HSS). To better understand the development of severe pathology, we compared the two-dimensional differential in-gel electrophoresis (2D-DIGE) proteomic signatures of livers from uninfected mice and mice infected for 6, 8, 12, or 20 weeks and found significant changes in collagen isoforms, interleukin-2 (IL-2), cytokeratin 18, hydroxyproline, S. mansoni phosphoenolpyruvate carboxykinase, major urinary protein isoforms, and peroxiredoxin 6. Cytokeratin 18, hydroxyproline, and connective tissue growth factor (CTGF) were chosen for analysis in mouse and human sera using targeted biochemical assays. Consistent with the liver analysis, cytokeratin 18, CTGF, and hydroxyproline were significantly elevated in sera from mice with HSS compared to those from uninfected mice or mice with MSS. Moreover, cytokeratin 18 and CTGF were found to be markers for subjects with hepatosplenic and intestinal schistosomiasis, respectively, while serum hydroxyproline was a strong indicator of fibrosis for severe HS. These findings indicate that schistosome-associated changes to the liver can be detected in the serum and reveal the potential for cytokeratin 18 to be used as a diagnostic marker for early detection of hepatosplenic schistosomiasis.

Geographical distribution of schistosomiasis and soil-transmitted helminths among school children in informal settlements in Kisumu City, Western Kenya.

This cross-sectional study determined the prevalence and distribution of schistosome and soil-transmitted helminth (STH) infections among 1,308 children aged 10-18 years in 34 primary schools in 8 informal urban settlements in Kisumu City, western Kenya. Stool samples were collected and examined for eggs of Schistosoma mansoni and STH (Hookworms, Ascaris lumbricoides and Trichuris trichiura) using the Kato-Katz technique. Haematuria was used as a proxy indicator of urinary schistosomiasis. Schools and water bodies were mapped using a geographical information system. Overall, 34% of children were infected with one or more helminth species whereas 16·2% of children were infected with one or more STH species. Schools in closest proximity to Lake Victoria and River Nyamasaria had the highest S. mansoni prevalence while schools with STH were more homogenously distributed. Mean school prevalence of S. mansoni infection was 21% (range=0-69·7%), S. haematobium 3·6% (range=0-12%), hookworms 6·1% (range=0-20%), A. lumbricoides 4·9% (range=0-18·4%), and T. trichiura 7·7% (range=0-18·6%). Helminth-related morbidities were not associated with infection. Our study demonstrates that schistosomiasis and STH are important health priorities among schools in informal settlements of Kisumu City, and highlights the need for routine deworming in similar settings.

Increases in levels of schistosome-specific immunoglobulin E and CD23(+) B cells in a cohort of Kenyan children undergoing repeated treatment and reinfection with Schistosoma mansoni.

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.

Socioeconomic determinants of Schistosoma mansoni infection using multiple correspondence analysis among rural western Kenyan communities: Evidence from a household-based study.

BACKGROUND: Socioeconomic inequality including wealth distribution is a barrier to implementation of health policies. Wealth distribution can be measured effectively using household data on durable assets. Compared to other methods of analysing Socio-economic Status (SES) using durable assets, Multiple Correspondence Analysis (MCA) can create more reliable wealth quintiles. We therefore evaluated socioeconomic determinants of Schistosoma mansoni using MCA on household data among adult population in western Kenya. The hypothesis of this study was that MCA would be a useful predictor of S. mansoni prevalence and/or intensity. METHODOLOGY: Twelve villages, 6 villages that had showed the greatest decrease in S. mansoni prevalence (Responder villages) and 6 villages that showed relatively lower decrease (Hotspot villages) between the year 2011 and 2015 were randomly selected for this study. This was according to a previous Schistosomiasis Consortium for Operational Research and Elimination (SCORE) report from western Kenya. From each village, convenience sampling was used to identify 50 adults from 50 households for inclusion in this study. An interview with a questionnaire based upon MCA indicators was conducted. One stool sample from each of the 600 adults was examined based on four slides for S. mansoni eggs using Kato Katz technique. Mean Eggs per gram(EPG) was calculated by taking the average of the readings from the four slides. A log binomial regression model was used to identify the influence of the various age-groups(<30 years, 30-60 years and >60 years), household size, wealth class, occupation, education status, main water supply, sex and sub-county of residence on S. mansoni infection. EPG was then compared across variables that were significant based on multivariate log binomial model analysis using a mixed model. PRINCIPAL FINDINGS: Overall prevalence of S. mansoni was 41.3%. Significantly higher prevalence of S. mansoni were associated with males, those aged below 30 years, those who use unsafe water sources (unprotected wells, lakes and rivers), residents of Rachuonyo North, Hotspot villages and those earning livelihood from fishing. Only sex and household size were significant predictors in the multivariate model. Males were associated with significantly higher prevalence compared to the females (aPR = 1.37; 95% CI = 1.14-1.66). In addition, households with at least four persons had higher prevalence compared to those with less than four (aPR = 1.29; 95% CI = 1.03-1.61). However, there was no difference in prevalence between the wealth classes(broadly divided into poor and less poor categories). Intensity of infection (Mean EPG)was also significantly higher among males, younger age group, Rachuonyo North residents and Hotspot Villages. CONCLUSION: Socioeconomic status based on an MCA model was not a contributing factor to S. mansoni prevalence and/or intensity possibly because the study populations were not sufficiently dissimilar. The use of convenience sampling to identify participants could also have contributed to the lack of significant findings.