Limited efficacy of repeated praziquantel treatment in Schistosoma mansoni infections as revealed by highly accurate diagnostics, PCR and UCP-LF CAA (RePST trial).

BACKGROUND: Most studies assessing praziquantel (PZQ) efficacy have used relatively insensitive diagnostic methods, thereby overestimating cure rate (CR) and intensity reduction rate (IRR). To determine accurately PZQ efficacy, we employed more sensitive DNA and circulating antigen detection methods. METHODOLOGY: A sub-analysis was performed based on a previously published trial conducted in children from Côte d'Ivoire with a confirmed Schistosoma mansoni infection, who were randomly assigned to a standard (single dose of PZQ) or intense treatment group (4 repeated doses of PZQ at 2-week intervals). CR and IRR were estimated based on PCR detecting DNA in a single stool sample and the up-converting particle lateral flow (UCP-LF) test detecting circulating anodic antigen (CAA) in a single urine sample, and compared with traditional Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA). PRINCIPAL FINDINGS: Individuals positive by all diagnostic methods (i.e., KK, POC-CCA, PCR, and UCP-LF CAA) at baseline were included in the statistical analysis (n = 125). PCR showed a CR of 45% (95% confidence interval (CI) 32-59%) in the standard and 78% (95% CI 66-87%) in the intense treatment group, which is lower compared to the KK results (64%, 95% CI 52-75%) and 88%, 95% CI 78-93%). UCP-LF CAA showed a significantly lower CR in both groups, 16% (95% CI 11-24%) and 18% (95% CI 12-26%), even lower than observed by POC-CCA (31%, 95% CI 17-35% and 36%, 95% CI 26-47%). A substantial reduction in DNA and CAA-levels was observed after the first treatment, with no further decrease after additional treatment and no significant difference in IRR between treatment groups. CONCLUSION/SIGNIFICANCE: The efficacy of (repeated) PZQ treatment was overestimated when using egg-based diagnostics (i.e. KK and PCR). Quantitative worm-based diagnostics (i.e. POC-CCA and UCP-LF CAA) revealed that active Schistosoma infections are still present despite multiple treatments. These results stress the need for using accurate diagnostic tools to monitor different PZQ treatment strategies, in particular when moving toward elimination of schistosomiasis. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, NCT02868385.

Prevalence of Schistosoma mono- and co-infections with multiple common parasites and associated risk factors and morbidity profile among adults in the Taabo health and demographic surveillance system, South-Central Côte d'Ivoire.

BACKGROUND: Schistosomiasis remains an important public health problem, also among adults, and infected individuals not treated serve as a reservoir for continued transmission. Despite this fact, evidence on the epidemiology of schistosomiasis in adults in Côte d'Ivoire is scanty. This study aimed to determine the prevalence and risk factors of Schistosoma infection and co-infection with other helminth species and Plasmodium among adults in the Taabo region in the south-central part of Côte d'Ivoire. METHODS: A cross-sectional survey was carried out in April and May 2017 in the frame of the "Côte d'Ivoire Dual Burden of Disease Study" (CoDuBu). A total of 901 randomly selected individuals, aged 18-90 years, provided blood, stool and urine samples for the diagnosis of malaria and helminth infections. Stool samples were subjected to the Kato-Katz technique for detection of Schistosoma mansoni and soil-transmitted helminth eggs, while urine samples were examined for eggs of Schistosoma haematobium and circulating cathodic antigen of S. mansoni. Risk factors and morbidity profiles were assessed using health examination and questionnaires. Multinomial logistic regressions were employed to identify risk factors and morbidity patterns associated with S. mansoni mono- and co-infections. RESULTS: The prevalence of S. mansoni and S. haematobium was 23.2% and 1.0%, respectively. Most S. mansoni were mono-infections (81.3%). Independent determinants of S. mansoni infection were young age, low socioeconomic status (mono- and co-infection) and poor hygiene practices (co-infection) (P < 0.05). S. mansoni infection was independently associated with higher pain and symptom scores (mono-infection), poor self-rated health and low healthcare use (co-infection) (P < 0.05). CONCLUSIONS: This study showed that adults represent a substantial reservoir of S. mansoni. To sustain schistosomiasis control and improve people's wellbeing, it is important to expand preventive chemotherapy from school-aged children to adults, coupled with hygiene and health education.

Effectiveness of Four Different Interventions Against Schistosoma haematobium in a Seasonal Transmission Setting of Côte d'Ivoire: A Cluster Randomized Trial.

BACKGROUND: Annual mass drug administration (MDA) using praziquantel is the cornerstone of schistosomiasis morbidity control but is not sufficient to interrupt transmission. We implemented a cluster-randomized trial to compare the effectiveness of 4 different intervention packages to interrupt transmission of Schistosoma haematobium in a seasonal transmission setting of Côte d'Ivoire. METHODS: Sixty-four localities with a S. haematobium prevalence in school children aged 13-14 years above 4% were randomly assigned to 1 of 4 intervention arms over a 3-year period: (1) the current standard strategy consisting of annual MDA before peak of transmission, (2) annual MDA after peak of transmission, (3) biannual MDA, and (4) standard MDA combined with snail control. The primary outcome was prevalence and intensity of S. haematobium infection in children aged 9-12 years 1 year after the final intervention, using urine filtration performed by experienced microscopists. RESULTS: By study end, we observed the lowest S. haematobium prevalence in the biannual MDA, compared to the standard treatment arm (0.6% vs 7.5%; odds ratio [OR] = 0.07, 95% confidence interval [CI] = .02 to .24). The prevalence in arms 2 and 4 was about 3.5%, which was not statistically significantly different from the standard strategy (both ORs 0.4, 95% CI = .1 to ~1.8). New cases of infection were still observed in all arms at study end. CONCLUSIONS: Biannual MDA was the only regimen that outperformed the standard treatment. All strategies resulted in decreased prevalence of infection; however, none of them was able to interrupt transmission of S. haematobium within a 3-year period. CLINICAL TRIALS REGISTRATION: ISRCTN10926858.

Spatial variation of life-history traits in Bulinus truncatus, the intermediate host of schistosomes, in the context of field application of niclosamide in Côte d'Ivoire.

BACKGROUND: Control of intermediate host snails using molluscicides for the control and/or elimination of schistosomiasis is a strategy in line with WHO recommendations. Niclosamide is the main chemical molluscicide recommended by WHO. However, except the immediate killing of the snail, the extent of the impact of the molluscicide application on the evolution of snail life-history traits, in relation to recolonization of treated sites is not well known. This study aimed to characterize the spatial variation of life-history traits of populations of the freshwater snail Bulinus truncatus, in relation to niclosamide spraying in the field. From 2016 to 2018, we conducted a trial, using niclosamide to control the intermediate host snails for interrupting the seasonal transmission of urinary schistosomiasis in northern and central Côte d'Ivoire. Five villages (sites) were considered, including three test and two control villages. In the test villages, the molluscicide was sprayed in habitats harboring B. truncatus snails three times a year (November, February-March and June). We sampled six B. truncatus populations: two populations from the control villages without any treatment; one collected before treatment and three sampled 2-3 months after treatment of the site with niclosamide. The snail populations were monitored for several life-history traits, including survival, growth, fecundity and hatchability, under laboratory conditions, over one generation (G1). We tested the population, region (North/Centre) and treatment status (treated/untreated) effects on the variation of the measured life-history traits and correlations between pairs of traits were estimated. RESULTS: On the whole, the traits varied among populations. The risk of death was lower in northern populations compared to central ones. The age at first reproduction was reached earlier with a smaller size of snails in northern populations. Values of first reproduction features (size and fecundity) were lower in treated snail populations. The overall growth of untreated populations was higher than that of treated ones. The late fecundity and egg hatching were higher in northern than in central snails. At first reproduction, age was negatively correlated with some fecundity parameters. However, growth was positively associated with fecundity. CONCLUSIONS: Our study showed a spatial variation of life-history traits in B. truncatus snails. The mollusciciding seems to have led to the depression of some life-history traits in the snail populations. However, investigations should be carried out over several generations of snails to better clarify the impact of niclosamide on the evolution of the life-history traits.

Accuracy of Two Circulating Antigen Tests for the Diagnosis and Surveillance of Schistosoma mansoni Infection in Low-Endemicity Settings of Côte d'Ivoire.

In low-endemicity settings, current tools for the diagnosis and surveillance of schistosomiasis are often inaccurate in detecting true infection. We assessed the accuracy of an up-converting phosphor lateral flow circulating anodic antigen (UCP-LF CAA) test and a point-of-care circulating cathodic antigen (POC-CCA) urine cassette test for the diagnosis of Schistosoma mansoni. Our study was conducted in eight schools of western Côte d'Ivoire. Fifty children, aged 9-12 years, were enrolled per school. From each child, a single urine specimen and two stool specimens were collected over consecutive days for diagnostic work-up. Urine samples were subjected to UCP-LF CAA and POC-CCA tests. From each stool sample, triplicate Kato-Katz thick smears were examined. Overall, 378 children had complete data records. The prevalence of S. mansoni, as assessed by six Kato-Katz thick smears, was 4.0%. The UCP-LF CAA and POC-CCA tests revealed S. mansoni prevalence of 25.4% and 30.7%, respectively, when considering trace results as positive, and prevalence of 23.3% and 10.9% when considering trace results as negative. In the latter case, based on a composite "gold" standard, the sensitivity of UCP-LF CAA (80.7%) was considerably higher than that of POC-CCA (37.6%) and six Kato-Katz thick smears (13.8%). The negative predictive value of UCP-LF CAA, POC-CCA, and six Kato-Katz thick smears was 92.8%, 79.8%, and 74.1%, respectively. Our results confirm that UCP-LF CAA is more accurate than Kato-Katz and POC-CCA for the diagnosis of S. mansoni in low-endemicity settings.

Estimating true prevalence of Schistosoma mansoni from population summary measures based on the Kato-Katz diagnostic technique.

BACKGROUND: The prevalence of Schistosoma mansoni infection is usually assessed by the Kato-Katz diagnostic technique. However, Kato-Katz thick smears have low sensitivity, especially for light infections. Egg count models fitted on individual level data can adjust for the infection intensity-dependent sensitivity and estimate the 'true' prevalence in a population. However, application of these models is complex and there is a need for adjustments that can be done without modeling expertise. This study provides estimates of the 'true' S. mansoni prevalence from population summary measures of observed prevalence and infection intensity using extensive simulations parametrized with data from different settings in sub-Saharan Africa. METHODOLOGY: An individual-level egg count model was applied to Kato-Katz data to determine the S. mansoni infection intensity-dependent sensitivity for various sampling schemes. Observations in populations with varying forces of transmission were simulated, using standard assumptions about the distribution of worms and their mating behavior. Summary measures such as the geometric mean infection, arithmetic mean infection, and the observed prevalence of the simulations were calculated, and parametric statistical models fitted to the summary measures for each sampling scheme. For validation, the simulation-based estimates are compared with an observational dataset not used to inform the simulation. PRINCIPAL FINDINGS: Overall, the sensitivity of Kato-Katz in a population varies according to the mean infection intensity. Using a parametric model, which takes into account different sampling schemes varying from single Kato-Katz to triplicate slides over three days, both geometric and arithmetic mean infection intensities improve estimation of sensitivity. The relation between observed and 'true' prevalence is remarkably linear and triplicate slides per day on three consecutive days ensure close to perfect sensitivity. CONCLUSIONS/SIGNIFICANCE: Estimation of 'true' S. mansoni prevalence is improved when taking into account geometric or arithmetic mean infection intensity in a population. We supply parametric functions and corresponding estimates of their parameters to calculate the 'true' prevalence for sampling schemes up to 3 days with triplicate Kato-Katz thick smears per day that allow estimation of the 'true' prevalence.

Effectiveness of school-based preventive chemotherapy strategies for sustaining the control of schistosomiasis in Côte d'Ivoire: Results of a 5-year cluster randomized trial.

BACKGROUND: Preventive chemotherapy using praziquantel is the mainstay for schistosomiasis control. However, there is little evidence on what is supposed to be the most effective school-based treatment strategy to sustain morbidity control. The aim of this study was to compare differences in Schistosoma mansoni prevalence and infection intensity between three different schedules of school-based preventive chemotherapy in an area with moderate prevalence of S. mansoni in Côte d'Ivoire. METHODOLOGY: Seventy-five schools were randomly assigned to one of three intervention arms: (i) annual school-based preventive chemotherapy with praziquantel (40 mg/kg) over four years; (ii) praziquantel treatment only in the first two years, followed by two years whithout treatment; and (iii) praziquantel treatment in years 1 and 3 without treatment in-between. Cross-sectional parasitologic surveys were carried out prior to each round of preventive chemotherapy. The difference in S. mansoni prevalence and infection intensity was assessed by multiple Kato-Katz thick smears, among children aged 9-12 years at the time of each survey. First-grade children, aged 5-8 years who had never received praziquantel, were also tested at baseline and at the end of the study. PRINCIPAL FINDINGS: Overall, 7,410 children aged 9-12 years were examined at baseline and 7,223 at the final survey. The baseline prevalence of S. mansoni was 17.4%, 20.2%, and 25.2% in arms 1, 2, and 3, respectively. In the final year, we observed the lowest prevalence of 10.4% in arm 1, compared to 18.2% in arm 2 and 17.5% in arm 3. The comparison between arms 1 and 2 estimated an odds ratio (OR) of 0.52 but the difference was not statistically significant (95% confidence interval (CI) = 0.23-1.16). Likewise the difference between arms 1 and 3 lacked statistical significance (OR = 0.55, 95% CI = 0.23-1.29). There was no noteworthy difference observed between arms 2 and 3 (OR = 1.06, 95% CI = 0.64-1.75). The lowest S. mansoni fecal egg counts in the final year survey were observed in arm 1 (7.9 eggs per gram of stool (EPG)). However, compared with 11.5 EPG in arm 2 and 15.4 EPG in arm 3, the difference lacked statistical significance. There were 4,812 first-grade children examined at baseline and 4,513 in the final survey. The overall prevalence of S. mansoni in these children slightly decreased in arms 1 (from 4.5% to 3.6%) and 2 (from 4.7% to 4.3%), but increased in arm 3 (from 6.8% to 7.9%). However, there was no significant difference in prevalence and infection intensity observed between study arms. CONCLUSIONS/SIGNIFICANCE: The three treatment schedules investigated led to a reduction in the prevalence and intensity of S. mansoni infection among children aged 9-12 years. Comparing intervention arms at the end of the study, no statistically significant differences were observed between annual treatement and the other two treatment schedules, neither in reduction of prevalence nor intensity of infection. It is important to combine our results with those of three sister trials conducted simultaneously in other African countries, before final recommendations can be drawn.

Characteristics of persistent hotspots of Schistosoma mansoni in western Côte d'Ivoire.

BACKGROUND: Preventive chemotherapy with praziquantel is the cornerstone of schistosomiasis control. However, in some social-ecological settings, the prevalence and/or intensity of Schistosoma infection does not lower meaningfully despite multiple rounds of preventive chemotherapy, a phenomenon termed persistent hotspot (PHS). We assessed the characteristics of PHS in a Schistosoma mansoni-endemic area of Côte d'Ivoire. METHODS: In October 2016, a cross-sectional survey was conducted in 14 schools in the western part of Côte d'Ivoire, one year after multiple rounds of preventive chemotherapy. In each school, 50 children aged 9-12 years provided two stool samples and one urine sample. Stool samples were subjected to triplicate Kato-Katz thick smears for S. mansoni diagnosis. Urine samples were examined by a filtration method for S. haematobium eggs. PHS was defined as failure to achieve a reduction in the prevalence of S. mansoni infection of at least 35% and/or a reduction of infection intensity of at least 50%. Six schools underwent more detailed investigations, including a questionnaire survey for demographic characteristics and a malacological survey. RESULTS: In the six schools subjected to detailed investigations, the overall prevalence of S. mansoni and S. haematobium was 9.5% and 2.6%, respectively. Four schools were classified as PHS. The S. mansoni prevalence in the four PHS was 10.9% compared to 6.6% in the remaining two schools. The S. mansoni infection intensity, expressed as arithmetic mean eggs per gram of stool (EPG) among infected children, was 123.8 EPG in PHS and 18.7 EPG in the other two schools. Children bathing in open freshwater bodies were at higher odds of S. mansoni infection (odds ratio: 4.5, 95% confidence interval: 1.6-12.6). A total of 76 human-water contact sites (53 in PHS and 23 in the other schools) were examined and 688 snails were collected, including potential intermediate host snails of Schistosoma (Biomphalaria pfeifferi, Bulinus forskalii, Bu. globosus and Bu. truncatus). CONCLUSION: Children in PHS schools bathed more frequently in open freshwater bodies, and hence, they are more exposed to Schistosoma transmission. Our findings call for an integrated control approach, complementing preventive chemotherapy with other interventions, particularly in PHS settings.

Efficacy of single versus four repeated doses of praziquantel against Schistosoma mansoni infection in school-aged children from Côte d'Ivoire based on Kato-Katz and POC-CCA: An open-label, randomised controlled trial (RePST).

BACKGROUND: Preventive chemotherapy with praziquantel (PZQ) is the cornerstone of schistosomiasis control. However, a single dose of PZQ (40 mg/kg) does not cure all infections. Repeated doses of PZQ at short intervals might increase efficacy in terms of cure rate (CR) and intensity reduction rate (IRR). Here, we determined the efficacy of a single versus four repeated treatments with PZQ on Schistosoma mansoni infection in school-aged children from Côte d'Ivoire, using two different diagnostic tests. METHODS: An open-label, randomized controlled trial was conducted from October 2018 to January 2019. School-aged children with a confirmed S. mansoni infection based on Kato-Katz (KK) and point-of-care circulating cathodic antigen (POC-CCA) urine cassette test were randomly assigned to receive either a single or four repeated doses of PZQ, administered at two-week intervals. The primary outcome was the difference in CR between the two treatment arms, measured by triplicate KK thick smears 10 weeks after the first treatment. Secondary outcomes included CR estimated by POC-CCA, IRR by KK and POC-CCA, and safety of repeated PZQ administration. PRINCIPAL FINDINGS: During baseline screening, 1,022 children were assessed for eligibility of whom 153 (15%) had a detectable S. mansoni infection, and hence, were randomized to the standard treatment group (N = 70) and the intense treatment group (N = 83). Based on KK, the CR was 42% (95% confidence interval (CI) 31-52%) in the standard treatment group and 86% (95% CI 75-92%) in the intense treatment group. Observed IRR was 72% (95% CI 55-83%) in the standard treatment group and 95% (95% CI 85-98%) in the intense treatment group. The CR estimated by POC-CCA was 18% (95% CI 11-27%) and 36% (95% CI 26-46%) in the standard and intense treatment group, respectively. Repeated PZQ treatment did not result in a higher number of adverse events. CONCLUSION/SIGNIFICANCE: The observed CR using KK was significantly higher after four repeated treatments compared to a single treatment, without an increase in adverse events. Using POC-CCA, the observed CR was significantly lower than measured by KK, indicating that PZQ may be considerably less efficacious as concluded by KK. Our findings highlight the need for reliable and more accurate diagnostic tools, which are essential for monitoring treatment efficacy, identifying changes in transmission, and accurately quantifying the intensity of infection in distinct populations. In addition, the higher CR in the intense treatment group suggests that more focused and intense PZQ treatment can help to advance schistosomiasis control. TRIAL REGISTRATION: www.clinicaltrials.gov NCT02868385.

Translating preventive chemotherapy prevalence thresholds for Schistosoma mansoni from the Kato-Katz technique into the point-of-care circulating cathodic antigen diagnostic test.

BACKGROUND: Intervention guidelines against Schistosoma mansoni are based on the Kato-Katz technique. However, Kato-Katz thick smears show low sensitivity, especially for light-intensity infections. The point-of-care circulating cathodic antigen (POC-CCA) is a promising rapid diagnostic test detecting antigen output of living worms in urine and results are reported as trace, 1+, 2+, and 3+. The use of POC-CCA for schistosomiasis mapping, control, and surveillance requires translation of the Kato-Katz prevalence thresholds into POC-CCA relative treatment cut-offs. Furthermore, the infection status of egg-negative but antigen-positive individuals and the intensity-dependent sensitivity of POC-CCA should be estimated to determine its suitability for verification of disease elimination efforts. METHODOLOGY: We used data from settings in Africa and the Americas characterized by a wide range of S. mansoni endemicity. We estimated infection intensity-dependent sensitivity and specificity of each test at the unit of the individual, using a hierarchical Bayesian egg-count model that removes the need to define a 'gold' standard applied to data with multiple Kato-Katz thick smears and POC-CCA urine cassette tests. A simulation study was carried out based on the model estimates to assess the relation of the two diagnostic tests for different endemicity scenarios. PRINCIPAL FINDINGS: POC-CCA showed high specificity (> 95%), and high sensitivity (> 95%) for moderate and heavy infection intensities, and moderate sensitivity (> 75%) for light infection intensities, and even for egg-negative but antigen-positive infections. A 10% duplicate slide Kato-Katz thick smear prevalence corresponded to a 15-40% prevalence of ≥ trace-positive POC-CCA, and 10-20% prevalence of ≥ 1+ POC-CCA. The prevalence of ≥ 2+ POC-CCA corresponded directly to single slide Kato-Katz prevalence for all prevalence levels. CONCLUSIONS/SIGNIFICANCE: The moderate sensitivity of POC-CCA, even for very light S. mansoni infections where the sensitivity of Kato-Katz is very low, and the identified relationship between Kato-Katz and POC-CCA prevalence thresholds render the latter diagnostic tool useful for surveillance and initial estimation of elimination of S. mansoni. For prevalence below 10% based on a duplicate slide Kato-Katz thick smear, we suggest using POC-CCA including trace results to evaluate treatment needs and propose new intervention thresholds that need to be validated in different settings.

Sensitivity of the Point-of-Care Circulating Cathodic Antigen Urine Cassette Test for Diagnosis of Schistosoma mansoni in Low-Endemicity Settings in Côte d'Ivoire.

The sensitivity of a point-of-care circulating cathodic antigen (POC-CCA) urine cassette test for diagnosis of Schistosoma mansoni in low-endemicity settings is poorly understood. We conducted a cross-sectional survey in 14 villages in western Côte d'Ivoire and diagnosed children aged 9-12 years for schistosomiasis. Two stool samples were subjected to triplicate Kato-Katz thick smears each for diagnosis of S. mansoni, whereas a single urine sample was examined by POC-CCA for S. mansoni, filtration for Schistosoma haematobium, and reagent strip for microhematuria. According to the Kato-Katz technique, we found 45 out of 681 children positive for S. mansoni (6.6%) with a mean intensity among infected children of 72.2 eggs per gram of stool. Point-of-care circulating cathodic antigen revealed a prevalence of S. mansoni of 33.0% when trace results were considered positive and 12.5% when trace results were considered negative. Eggs of S. haematobium were found in eight participants (1.2%), whereas the prevalence of microhematuria was 13.5%. A single POC-CCA urine cassette test revealed a several-fold higher prevalence of S. mansoni than multiple Kato-Katz thick smears in this low-endemicity area. Our findings have important ramifications for choosing an appropriate diagnostic tool in low-endemic areas that might be targeted for elimination.

Are schoolchildren less infected if they have good knowledge about parasitic worms? A case study from rural Côte d'Ivoire.

BACKGROUND: Parasitic worms (helminths) are common infections in low- and middle-income countries. For most helminth species, school-aged children are at highest risk of infection and morbidity, such as impaired cognitive and physical development. Preventive chemotherapy is the current mainstay for helminthiases control. Sanitation improvement and hygiene-related education are important complementary strategies, which act by altering children's behaviour. However, little is known about the effect of improved knowledge on the risk of helminth infection. The aim of this study was to assess the potential influence of knowledge that children acquired at home or in school, without any specific health education intervention, on helminth infections. METHODS: In May 2014, we conducted a cross-sectional survey in western Côte d'Ivoire. A total of 2498 children, aged 9-12 years, were subjected to three consecutive stool examinations using duplicate Kato-Katz thick smears to determine infections with soil-transmitted helminths and Schistosoma mansoni. Additionally, children were interviewed to assess their knowledge about helminth infections. Four knowledge scores were constructed by factor analysis; one, reflecting general knowledge about helminths and three manifesting helminth species-specific knowledge. The effect of general and specific knowledge on children's helminth infection status was determined using meta-analysis. RESULTS: Children who scored high in the hookworm-specific knowledge were less likely to be infected with hookworm but no association was found for the other helminth species. Moreover, greater general knowledge was not associated with lower odds of being infected with any helminth species. Most of the children interviewed believed that the effect of preventive chemotherapy is permanent, and hence, re-treatment is not necessary. CONCLUSIONS: Specific knowledge about different types of helminths might not suffice to induce behavioural change which in turn reduces infection and reinfection with helminths. Health education interventions should strive to strengthen the perception of risk and to clarify the true benefit of preventive chemotherapy.

Sustaining Control of Schistosomiasis Mansoni in Western Côte d'Ivoire: Results from a SCORE Study, One Year after Initial Praziquantel Administration.

BACKGROUND: The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) has launched several large-scale trials to determine the best strategies for gaining and sustaining control of schistosomiasis and transitioning toward elimination. In Côte d'Ivoire, a 5-year cluster-randomized trial is being implemented in 75 schools to sustain the control of schistosomiasis mansoni. We report Schistosoma mansoni infection levels in children one year after the initial school-based treatment (SBT) with praziquantel and compare with baseline results to determine the effect of the intervention. METHODOLOGY: The baseline cross-sectional survey was conducted in late 2011/early 2012 and the first follow-up in May 2013. Three consecutive stool samples were collected from 9- to 12-year-old children in 75 schools at baseline and 50 schools at follow-up. Stool samples were subjected to duplicate Kato-Katz thick smears. Directly observed treatment (DOT) coverage of the SBT was assessed and the prevalence and intensity of S. mansoni infection compared between baseline and follow-up. PRINCIPAL FINDINGS: The S. mansoni prevalence in the 75 schools surveyed at baseline was 22.1% (95% confidence interval (CI): 19.5-24.4%). The DOT coverage was 84.2%. In the 50 schools surveyed at baseline and one year after treatment, the overall prevalence of S. mansoni infection decreased significantly from 19.7% (95% CI: 18.5-20.8%) to 12.8% (95% CI: 11.9-13.8%), while the arithmetic mean S. mansoni eggs per gram of stool (EPG) among infected children slightly increased from 92.2 EPG (95% CI: 79.2-105.3 EPG) to 109.3 EPG (95% CI: 82.7-135.9 EPG). In two of the 50 schools, the prevalence increased significantly, despite a DOT coverage of >75%. CONCLUSIONS/SIGNIFICANCE: One year after the initial SBT, the S. mansoni prevalence had decreased. Despite this positive trend, an increase was observed in some schools. Moreover, the infection intensity among S. mansoni-infected children was slightly higher at the 1-year follow-up compared to the baseline situation. Our results emphasize the heterogeneity of transmission dynamics and provide a benchmark for the future yearly follow-up surveys of this multi-year SCORE intervention study.

Sustaining the Control of Schistosoma mansoni in Western Côte d'Ivoire: Baseline Findings Before the Implementation of a Randomized Trial.

We report baseline findings before the implementation of a 4-year intervention trial designed to assess the impact of three different school-based treatment schedules with praziquantel to sustain the control of intestinal schistosomiasis. The baseline survey was conducted in 75 schools of western Côte d'Ivoire previously identified with moderate Schistosoma mansoni endemicity (prevalence: 10-24% in children aged 13-14 years). Three stool samples collected over consecutive days were subjected to duplicate Kato-Katz thick smears each. A questionnaire was administered to collect village-specific information that is relevant for schistosomiasis transmission. Overall, 4,953 first graders (aged 5-8 years) and 7,011 school children (aged 9-12 years) had complete parasitologic data. The overall prevalence of S. mansoni was 5.4% among first graders and 22.1% in 9- to 12-year-old children. Open defecation was practiced in all villages. The current baseline findings will be important to better understand the dynamics of S. mansoni prevalence and intensity over the course of this trial that might be governed by village characteristics and specific treatment interventions.

The spatial distribution of Schistosoma mansoni infection in four regions of western Côte d'Ivoire.

Schistosomiasis poses a considerable public health burden in sub- Saharan Africa and a sound understanding of the spatial distribution facilitates to better target control interventions. The objectives of this study were i) to assess the prevalence of Schistosoma mansoni among school-aged children in four regions of western Côte d'Ivoire; ii) to determine demographic, climatic and environmental factors that influence the distribution of S. mansoni; and iii) to map and predict the distribution of S. mansoni in non-sampled locations. Parasitological surveys were carried out in 264 schools from June to December 2011. In each school, we aimed to examine 50 children for S. mansoni infection using duplicate Kato-Katz thick smears. Schools were georeferenced using a hand-held global positioning system receiver. Demographic data were obtained from readily available school lists, while climatic and environmental data were extracted from open-access remote sensing databases. Multivariable, binary non-spatial models and a Bayesian geostatistical logistic regression model were used to identify demographic, climatic and environmental risk factors for S. mansoni infection. Risk maps were developed based on observed S. mansoni prevalences and using Bayesian geostatistical models to predict prevalences at non-sampled locations. Overall, 12,462 children provided a sufficiently large stool sample to perform at least one Kato-Katz thick smear. The observed overall prevalence of S. mansoni infection was 39.9%, ranging from 0 to 100% at the unit of the school. Bayesian geostatistical analysis revealed that age, sex, altitude and difference between land surface temperature at day and night were significantly associated with S. mansoni infection. The S. mansoni risk map presented here is being been used by the national schistosomiasis control programme for spatial targeting of praziquantel and other interventions.

Spatial distribution of schistosomiasis and treatment needs in sub-Saharan Africa: a systematic review and geostatistical analysis.

BACKGROUND: Schistosomiasis affects more than 200 million individuals, mostly in sub-Saharan Africa, but empirical estimates of the disease burden in this region are unavailable. We used geostatistical modelling to produce high-resolution risk estimates of infection with Schistosoma spp and of the number of doses of praziquantel treatment needed to prevent morbidity at different administrative levels in 44 countries. METHODS: We did a systematic review to identify surveys including schistosomiasis prevalence data in sub-Saharan Africa via PubMed, ISI Web of Science, and African Journals Online, from inception to May 2, 2014, with no restriction of language, survey date, or study design. We used Bayesian geostatistical meta-analysis and rigorous variable selection to predict infection risk over a grid of 1 155 818 pixels at 5 × 5 km, on the basis of environmental and socioeconomic predictors and to calculate the number of doses of praziquantel needed for prevention of morbidity. FINDINGS: The literature search identified Schistosoma haematobium and Schistosoma mansoni surveys done in, respectively, 9318 and 9140 unique locations. Infection risk decreased from 2000 onwards, yet estimates suggest that 163 million (95% Bayesian credible interval [CrI] 155 million to 172 million; 18·5%, 17·6-19·5) of the sub-Saharan African population was infected in 2012. Mozambique had the highest prevalence of schistosomiasis in school-aged children (52·8%, 95% CrI 48·7-57·8). Low-risk countries (prevalence among school-aged children lower than 10%) included Burundi, Equatorial Guinea, Eritrea, and Rwanda. The numbers of doses of praziquantel needed per year were estimated to be 123 million (95% CrI 121 million to 125 million) for school-aged children and 247 million (239 million to 256 million) for the entire population. INTERPRETATION: Our results will inform policy makers about the number of treatments needed at different levels and will guide the spatial targeting of schistosomiasis control interventions. FUNDING: European Research Council, China Scholarship Council, UBS Optimus Foundation, and Swiss National Science Foundation.

Sustaining control of schistosomiasis mansoni in moderate endemicity areas in western Côte d'Ivoire: a SCORE study protocol.

BACKGROUND: Schistosomiasis is a parasitic disease that occurs in the tropics and subtropics. The mainstay of control is preventive chemotherapy with praziquantel. In Africa, an estimated 230 million people require preventive chemotherapy. In western Côte d'Ivoire, infections with Schistosoma mansoni are widespread. To provide an evidence-base for programme decisions about preventive chemotherapy to sustain control of schistosomiasis, a 5-year multi-country study with different treatment arms has been designed by the Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) and is currently being implemented in various African settings, including Côte d'Ivoire. METHODS/DESIGN: We report the study protocol, including ethics statement and insight from a large-scale eligibility survey carried out in four provinces in western Côte d'Ivoire. The study protocol has been approved by the ethics committees of Basel and Côte d'Ivoire. A total of 12,110 children, aged 13-14 years, from 264 villages were screened for S. mansoni using duplicate Kato-Katz thick smears from single stool samples. Among the schools with a S. mansoni prevalence of 10-24%, 75 schools were selected and randomly assigned to one of three treatment arms. In each school, three stool samples are being collected from 100 children aged 9-12 years annually and one stool sample from 100 first-year students at baseline and in the final year and subjected to duplicate Kato-Katz thick smears. Cost and coverage data for the different intervention arms, along with environmental, political and other characteristics that might impact on the infection prevalence and intensity will be recorded in each study year, using a pretested village inventory form. DISCUSSION: The study will document changes in S. mansoni infection prevalence and intensity according to different treatment schemes. Moreover, factors that determine the effectiveness of preventive chemotherapy will be identified. These factors will help to develop reasonable measures of force of transmission that can be used to make decisions about the most cost-effective means of lowering prevalence, intensity and transmission in a given setting. The gathered information and results will inform how to effectively sustain control of schistosomiasis at a low level in different social-ecological contexts. TRIAL REGISTRATION: ISRCTN99401114 (date assigned: 12 November 2014).