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.

Baseline and Impact of First-Year Intervention on Schistosoma haematobium Infection in Seasonal Transmission Foci in the Northern and Central Parts of Côte d'Ivoire.

In order to assess the impact of different control strategies against Schistosoma haematobium in seasonal transmission foci in Côte d'Ivoire, a three-year cluster randomized trial was implemented. The decrease in S. haematobium prevalence among children aged 9-12 years was the primary outcome. In the first step, an eligibility survey was conducted, subjecting 50 children aged 13-14 years to a single urine filtration. Sixty-four villages with a prevalence of S. haematobium of ≥4% were selected and randomly assigned to four intervention arms consisting of annual mass drug administration (MDA) before (arm 1) and after (arm 2) the peak transmission, biannual treatment with praziquantel before and after the peak transmission season (arm 3), and annual MDA before the peak transmission season, coupled with focal chemical snail control using molluscicides (arm 4). At baseline, we observed a prevalence of 24.8%, 10.1%, 13.9%, and 15.9% in study arms 1, 2, 3, and 4, respectively. One year after the first intervention, the prevalence decreased in all study arms by about two-thirds or more. The prevalence in arm 2 was lower than in arm 1 (3.5% vs. 8.1%), but the difference was not statistically significant (odds ratio (OR) = 0.42, 95% confidence interval (CI) = 0.10-1.80). After adjusting for baseline prevalence, arms 1 and 2 performed roughly similarly (adjusted odds ratio (aOR) = 1.03, 95% CI = 0.34-3.07). The prevalence in arms 3 and 4 (1.9% and 2.2%) were significantly lower compared to arm 1 in the unadjusted and the adjusted models (arm 3 vs. arm 1, OR = 0.22, 95% CI = 0.05-0.95, aOR = 0.19, 95% CI = 0.08-0.48; arm 4 vs. arm 1, OR = 0.26, 95% CI = 0.08-0.85, aOR = 0.23, 95% CI = 0.06-0.87). The initial intervention showed a significant impact on the prevalence of S. haematobium. It will be interesting to monitor the comparative impact of the different intervention arms and to determine whether the interruption of seasonal transmission of S. haematobium can be achieved in this epidemiological setting within three years.

Snail-Related Contributions from the Schistosomiasis Consortium for Operational Research and Evaluation Program Including Xenomonitoring, Focal Mollusciciding, Biological Control, and Modeling.

The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) was created in 2008 to answer questions of importance to program managers working to reduce the burden of schistosomiasis in Africa. In the past, intermediate host snail monitoring and control was an important part of integrated schistosomiasis control. However, in Africa, efforts to control snails have declined dramatically over the last 30 years. A resurgence of interest in the control of snails has been prompted by the realization, backed by a World Health Assembly resolution (WHA65.21), that mass drug administration alone may be insufficient to achieve schistosomiasis elimination. SCORE has supported work on snail identification and mapping and investigated how xenomonitoring techniques can aid in the identification of infected snails and thereby identify potential transmission areas. Focal mollusciciding with niclosamide was undertaken in Zanzibar and Côte d'Ivoire as a part of elimination studies. Two studies involving biological control of snails were conducted: one explored the association of freshwater riverine prawns and snail hosts in Côte d'Ivoire and the other assessed the current distribution of Procambarus clarkii, the invasive Louisiana red swamp crayfish, in Kenya and its association with snail hosts and schistosomiasis transmission. SCORE also supported modeling studies on the importance of snail control in achieving elimination and a meta-analysis of the impact of molluscicide-based snail control programs on human schistosomiasis prevalence and incidence. SCORE's snail control studies contributed to increased investment in building capacity, and specimens collected during SCORE research deposited in the Schistosomiasis Collections at the Natural History Museum (SCAN) will provide a valuable resource for the years to come.

Molecular characterization and distribution of Schistosoma cercariae collected from naturally infected bulinid snails in northern and central Côte d'Ivoire.

BACKGROUND: Accurate identification of schistosome species infecting intermediate host snails is important for understanding parasite transmission, schistosomiasis control and elimination. Cercariae emerging from infected snails cannot be precisely identified morphologically to the species level. We used molecular tools to clarify the distribution of the Schistosoma haematobium group species infecting bulinid snails in a large part of Côte d'Ivoire and confirmed the presence of interspecific hybrid schistosomes. METHODS: Between June 2016 and March 2017, Bulinus snails were sampled in 164 human-water contact sites from 22 villages of the northern and central parts of Côte d'Ivoire. Multi-locus genetic analysis (mitochondrial cox1 and nuclear ITS) was performed on individual schistosome cercariae shed from snails, in the morning and in the afternoon, for species and hybrid identification. RESULTS: Overall, 1923 Bulinus truncatus, 255 Bulinus globosus and 1424 Bulinus forskalii were obtained. Among 2417 Bulinus screened, 25 specimens (18 B. truncatus and seven B. globosus) shed schistosomes, with up to 14% infection prevalence per site and time point. Globally, infection rates per time point ranged between 0.6 and 4%. Schistosoma bovis, S. haematobium and S. bovis × S. haematobium hybrids infected 0.5%, 0.2% and 0.4% of the snails screened, respectively. Schistosoma bovis and hybrids were more prevalent in B. truncatus, whereas S. haematobium and hybrid infections were more prevalent in B. globosus. Schistosoma bovis-infected Bulinus were predominantly found in northern sites, while S. haematobium and hybrid infected snails were mainly found in central parts of Côte d'Ivoire. CONCLUSIONS: The data highlight the necessity of using molecular tools to identify and understand which schistosome species are transmitted by specific intermediate host snails. The study deepens our understanding of the epidemiology and transmission dynamics of S. haematobium and S. bovis in Côte d'Ivoire and provides the first conclusive evidence for the transmission of S. haematobium × S. bovis hybrids in this West African country. Trial registration ISRCTN, ISRCTN10926858. Registered 21 December 2016; retrospectively registered (see: http://www.isrctn.com/ISRCTN10926858 ).

Spatio-temporal population genetic structure, relative to demographic and ecological characteristics, in the freshwater snail Biomphalaria pfeifferi in Man, western Côte d'Ivoire.

Combining the analysis of spatial and temporal variation when investigating population structure enhances our capacity for unravelling the biotic and abiotic factors responsible for microevolutionary change. This work aimed at measuring the spatial and temporal genetic structure of populations of the freshwater snail Biomphalaria pfeifferi (the intermediate host of the trematode Schistosoma mansoni) in relation to the mating system (self-fertilization), demography, parasite prevalence and some ecological parameters. Snail populations were sampled four times in seven human-water contact sites in the Man region, western Côte d'Ivoire, and their variability was measured at five microsatellite loci. Limited genetic diversity and high selfing rates were observed in the populations studied. We failed to reveal an effect of demographic and ecological parameters on within-population diversity, perhaps as a result of a too small number of populations. A strong spatial genetic differentiation was detected among populations. The temporal differentiation within populations was high in most populations, though lower than the spatial differentiation. All estimates of effective population size were lower than seven suggesting a strong effect of genetic drift. However, the genetic drift was compensated by high gene flow. The genetic structure within and among populations reflected that observed in other selfing snail species, relying on high selfing rates, low effective population sizes, environmental stochasticity and high gene flow.

Interrupting seasonal transmission of Schistosoma haematobium and control of soil-transmitted helminthiasis in northern and central Côte d'Ivoire: a SCORE study protocol.

BACKGROUND: To achieve a world free of schistosomiasis, the objective is to scale up control and elimination efforts in all endemic countries. Where interruption of transmission is considered feasible, countries are encouraged to implement a comprehensive intervention package, including preventive chemotherapy, information, education and communication (IEC), water, sanitation and hygiene (WASH), and snail control. In northern and central Côte d'Ivoire, transmission of Schistosoma haematobium is seasonal and elimination might be achieved. In a cluster-randomised trial, we will assess different treatment schemes to interrupt S. haematobium transmission and control soil-transmitted helminthiasis over a 3-year period. We will compare the impact of (i) arm A: annual mass drug administration (MDA) with praziquantel and albendazole before the peak schistosomiasis transmission season; (ii) arm B: annual MDA after the peak schistosomiasis transmission season; (iii) arm C: two yearly treatments before and after peak schistosomiasis transmission; and (iv) arm D: annual MDA before peak schistosomiasis transmission, coupled with chemical snail control using niclosamide. METHODS/DESIGN: The prevalence and intensity of S. haematobium and soil-transmitted helminth infections will be assessed using urine filtration and Kato-Katz thick smears, respectively, in six administrative regions in northern and central parts of Côte d'Ivoire. Once a year, urine and stool samples will be collected and examined from 50 children aged 5-8 years, 100 children aged 9-12 years and 50 adults aged 20-55 years in each of 60 selected villages. Changes in S. haematobium and soil-transmitted helminth prevalence and intensity will be assessed between years and stratified by intervention arm. In the 15 villages randomly assigned to intervention arm D, intermediate host snails will be collected three times per year, before niclosamide is applied to the selected freshwater bodies. The snail abundance and infection rates over time will allow drawing inference on the force of transmission. DISCUSSION: This cluster-randomised intervention trial will elucidate whether in an area with seasonal transmission, the four different treatment schemes can interrupt S. haematobium transmission and control soil-transmitted helminthiasis. Lessons learned will help to guide schistosomiasis control and elimination programmes elsewhere in Africa. TRIAL REGISTRATION: ISRCTN ISRCTN10926858 . Registered 21 December 2016. Retrospectively registered.

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.

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).

Prior selfing and the selfing syndrome in animals: an experimental approach in the freshwater snail Biomphalaria pfeifferi.

Inbreeding species of hermaphroditic animals practising copulation have been characterized by few copulations, no waiting time (the time that an isolated individual waits for a partner before initiating reproduction compared with paired individuals) and limited inbreeding (self-fertilization) depression. This syndrome, which has never been fully studied before in any species, is analysed here in the highly selfing freshwater snail Biomphalaria pfeifferi. We conducted an experiment under laboratory conditions over two generations (G1 and G2) using snails sampled from two populations (100 individuals per population). G1 individuals were either isolated or paired once a week (potentially allowing for crosses), and monitored during 29 weeks for growth, fecundity and survival. Very few copulations were observed in paired snails, and there was a positive correlation in copulatory activity (e.g. number of copulations) between the male and female sexual roles. The waiting time was either null or negative, meaning that isolated individuals initiated reproduction before paired ones. G2 offspring did not differ in hatching rate and survival (to 28 days) between treatments, but offspring from paired individuals grew faster than those from isolated individuals. On the whole, the self-fertilization depression was extremely low in both populations. Another important result is that paired G1 individuals began laying (selfed) eggs several weeks prior to initiating copulation: this is the first characterization of prior selfing (selfing initiated prior to any outcrossing) in a hermaphroditic animal. A significant population effect was observed on most traits studied. Our results are discussed with regard to the maintenance of low outcrossing rates in highly inbreeding species.