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.

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.

Association of riverine prawns and intermediate host snails and correlation with human schistosomiasis in two river systems in south-eastern Côte d'Ivoire.

The current emphasis of schistosomiasis control is placed on preventive chemotherapy using praziquantel. However, reinfection may occur rapidly in the absence of complementary interventions. Recent studies from Senegal suggest that predatory prawns might feed on intermediate host snails and thus impact on schistosomiasis transmission. We designed a study with four repeated cross-sectional surveys pertaining to prawns and snails, coupled with a single cross-sectional parasitological survey among humans. We assessed for potential associations between the presence/density of prawns and snails and correlation with Schistosoma infection in a composite sample of school-aged children and adults. The study was carried out between October 2015 and December 2016 in 24 villages located near the Agnéby and Mé coastal river systems in south-eastern Côte d'Ivoire. At each site, snails and prawns were collected, and in each village, 150 individuals were subjected to stool and urine examination for the diagnosis of Schistosoma mansoni and S. haematobium. We found peaks of relative abundance of intermediate host snails in the villages of the Agnéby River system, while predatory prawns were predominantly recorded in the Mé River system. A negative association was observed between intermediate host snail densities and riverine prawns; however, no pattern was found between this trend in the predator-prey relationship and the prevalence of human schistosomiasis.

Molecular detection of Anaplasma platys infection in free-roaming dogs and ticks from Kenya and Ivory Coast.

BACKGROUND: Anaplasma platys is a bacterium parasitic in the canine platelets, representing the causative agent of canine cyclic thrombocytopenia, with a worldwide distribution, mainly in tropical countries. The agent has zoonotic potential, being reported in several human clinical cases. The suspected vector is the tick Rhipicephalus sanguineus (sensu lato), widely distributed in animals and humans in the tropical regions of South America, Africa, Asia and Australia, but also in southern Europe. Only few scattered data concerning the epidemiology of A. platys in sub-Saharan Africa are available. The aim of our study was to evaluate the epidemiological status of A. platys in dogs and cats from rural communities in eastern and western Africa, where dogs and their ticks live in close contact with humans. METHODS: A total of 216 canine and 22 feline blood samples and ticks feeding on them were collected in 2013 and 2014 from eight localities in Ivory Coast and four localities in Kenya. PCR was performed using specific primers targeting a portion of the 16S rRNA gene, followed by sequencing. RESULTS: The main results highlight the high prevalence of A. platys infection in dogs in both Eastern and Western Africa and report it for the first time in Eastern Africa and in Rhipicephalus camicasi. CONCLUSIONS: The presence of A. platys DNA in R. camicasi feeding on negative hosts together with the relatively high prevalence of A. platys, correlated with the absence of the probable vector Rhipicephalus sanguineus (s.l.) in Kenyan Island suggest the involvement of other tick species in the transmission of A. platys.

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.

Diagnosis of neglected tropical diseases among patients with persistent digestive disorders (diarrhoea and/or abdominal pain ≥14 days): Pierrea multi-country, prospective, non-experimental case-control study.

BACKGROUND: Diarrhoea still accounts for considerable mortality and morbidity worldwide. The highest burden is concentrated in tropical areas where populations lack access to clean water, adequate sanitation and hygiene. In contrast to acute diarrhoea (<14 days), the spectrum of pathogens that may give rise to persistent diarrhoea (≥14 days) and persistent abdominal pain is poorly understood. It is conceivable that pathogens causing neglected tropical diseases play a major role, but few studies investigated this issue. Clinical management and diagnostic work-up of persistent digestive disorders in the tropics therefore remain inadequate. Hence, important aspects regarding the pathogenesis, epidemiology, clinical symptomatology and treatment options for patients presenting with persistent diarrhoea and persistent abdominal pain should be investigated in multi-centric clinical studies. METHODS/DESIGN: This multi-country, prospective, non-experimental case-control study will assess persistent diarrhoea (≥14 days; in individuals aged ≥1 year) and persistent abdominal pain (≥14 days; in children/adolescents aged 1-18 years) in up to 2000 symptomatic patients and 2000 matched controls. Subjects from Côte d'Ivoire, Indonesia, Mali and Nepal will be clinically examined and interviewed using a detailed case report form. Additionally, each participant will provide a stool sample that will be examined using a suite of diagnostic methods (i.e., microscopic techniques, rapid diagnostic tests, stool culture and polymerase chain reaction) for the presence of bacterial and parasitic pathogens. Treatment will be offered to all infected participants and the clinical treatment response will be recorded. Data obtained will be utilised to develop patient-centred clinical algorithms that will be validated in primary health care centres in the four study countries in subsequent studies. DISCUSSION: Our research will deepen the understanding of the importance of persistent diarrhoea and related digestive disorders in the tropics. A diversity of intestinal pathogens will be assessed for potential associations with persistent diarrhoea and persistent abdominal pain. Different diagnostic methods will be compared, clinical symptoms investigated and diagnosis-treatment algorithms developed for validation in selected primary health care centres. The findings from this study will improve differential diagnosis and evidence-based clinical management of digestive syndromes in the tropics. TRIAL REGISTRATION: ClinicalTrials.gov; identifier: NCT02105714 .

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).