Age-group associations of schistosomiasis prevalence from trial data, Côte d'Ivoire, Kenya and the United Republic of Tanzania.

Objective: To determine if the prevalence of schistosomiasis in children aged 9-12 years is associated with the prevalence in 5-8-year-olds and adults after preventive chemotherapy in schools or the community. Methods: We combined data from four community-randomized, preventive chemotherapy trials in treatment-naïve populations in Côte d'Ivoire, Kenya and the United Republic of Tanzania during 2010-2016 according to the number of praziquantel treatments and the delivery method. Schistosoma mansoni infection was sought on two slides prepared from each participant's first stool using the Kato-Katz technique. We assessed associations between S. mansoni prevalence in 9-12-year-olds and 5-8-year-olds and adults in the community before and after treatment using Bayesian regression models. Findings: Stool samples from 47 985 5-8-year-olds, 81 077 9-12-year-olds and 20 492 adults were analysed. We found associations between the prevalence in 9-12-year-olds and that in 5-8-year-olds and adults after preventive treatment, even when only school-age children were treated. When the prevalence in 9-12-year-olds was under 10%, the prevalence in 5-8-year-olds was consistently under 10%. When the prevalence in 9-12-year-olds was under 50%, the prevalence in adults after two or four rounds of preventive chemotherapy was 10%-15% lower than before chemotherapy. Post-chemotherapy age-group associations were consistent with pre-chemotherapy associations in this analysis and previous studies. Conclusion: The prevalence of S. mansoni infection in 9-12-year-olds was associated with the prevalence in other age groups and could be used to guide community treatment decisions.

Genetic characterization of schistosome species from cattle in Côte d'Ivoire.

BACKGROUND: Schistosomiasis is a water-based parasitic disease that affects humans, livestock and wild animals. While considerable resources are dedicated to the surveillance, disease mapping, control and elimination of human schistosomiasis, this is not the case for livestock schistosomiasis. Indeed, there are important data and knowledge gaps concerning the species present, population genetic diversity, infection prevalence, morbidity and economic impact. This study aimed to identify circulating schistosome species in cattle across Côte d'Ivoire and to investigate their population diversity and structuring. METHODS: Overall, 400 adult schistosomes were collected from slaughtered cattle at six sites across Côte d'Ivoire. Additionally, 114 miracidia were collected from live cattle at one site: Ferkessédougou, in the northern part of Côte d'Ivoire. DNA from all specimens was extracted and the cox1 and ITS1/2 regions amplified and analysed to confirm species. The genetic diversity and structuring of the schistosome populations were investigated using 12 microsatellite markers. RESULTS: All adult schistosomes and miracidia presented Schistosoma bovis mitochondrial cox1 profile. Nuclear ITS1/2 data were obtained from 101 adult schistosomes and four miracidia, all of which presented an S. bovis profile. Genetic diversity indices revealed a deficiency of heterozygotes and signals of inbreeding across all sites, while structure analyses displayed little geographic structuring and differentiation. Cattle in Côte d'Ivoire thus appear to be mono-species infected with S. bovis. Hybrids of Schistosoma haematobium × S. bovis have not been identified in this study. Cattle schistosomes appear to be panmictic across the country. CONCLUSIONS: Our results contribute to a deeper understanding of schistosome populations in Ivorian cattle and emphasize a One Health approach of joint human and animal surveillance and prevention and control programmes for schistosomiasis.

Prevalence and risk factors of schistosomiasis and hookworm infection in seasonal transmission settings in northern Côte d'Ivoire: A cross-sectional study.

BACKGROUND: Schistosomiasis and hookworm infection remain public health problems in large parts of sub-Saharan Africa. The epidemiology of schistosomiasis and hookworm was studied in seasonal transmission settings in the northern part of Côte d'Ivoire. METHODOLOGY: In August 2018, a cross-sectional study was conducted. Urine and stool samples were collected from 742 individuals aged 6-96 years in 16 localities from four departments in northern Côte d'Ivoire. Urine samples were examined by a filtration method for quantification of Schistosoma haematobium eggs. Stool samples were subjected to duplicate Kato-Katz thick smears and eggs of Schistosoma mansoni and soil-transmitted helminths (STHs) were counted. Additionally, a questionnaire was administered to determine demographic characteristics and to identify risk factors of schistosomiasis and STHs. Malacologic surveys were carried out at water points that are contacted by humans and animals. PRINCIPAL FINDINGS: The prevalence of schistosomiasis was very low. Only two cases of S. mansoni were found (0.3%, 95% confidence interval [CI]: 0.1-1.0%). The distribution of S. haematobium was focal, with cases found only in two departments; Ferkessédougou (5.4%, 95% CI: 2.5-9.9%) and Ouangolodougou (2.7%, 95% CI: 0.9-6.3%). Hookworm was the only STH species observed with a prevalence of 1.5% (95% CI: 0.8-2.8%). A higher risk of S. haematobium infection was observed in males compared to females, but the difference was not statistically significant (2.3% versus 1.3%, odds ratio [OR]: 1.5, 95% CI: 0.8-2.7). Participants aged 16-20 years showed the highest prevalence of S. haematobium. A total of 111 human- and animal-water contact points were identified at 47 water sources. Three potential intermediate host snails of schistosomes were collected; namely, Bulinus forskalii (n = 761), Bulinus truncatus (n = 205), and Biomphalaria pfeifferi (n = 1). Yet, only one specimen of Bu. truncatus was found to be shedding schistosome cercariae. CONCLUSIONS/SIGNIFICANCE: This study confirms very low transmission of schistosomiasis and hookworm in northern Côte d'Ivoire. The establishment and rigorous implementation of integrated surveillance-response systems could lead to the elimination of schistosomiasis and hookworm in this part of Côte d'Ivoire.

Efficacy, safety, and palatability of arpraziquantel (L-praziquantel) orodispersible tablets in children aged 3 months to 6 years infected with Schistosoma in Côte d'Ivoire and Kenya: an open-label, partly randomised, phase 3 trial.

BACKGROUND: WHO has underlined the need for a child-friendly treatment for schistosomiasis, a prevalent parasitic disease in low-income and middle-income countries. After successful phase 1 and 2 trials, we aimed to evaluate the efficacy, safety, palatability, and pharmacokinetics of arpraziquantel (L-praziquantel) orodispersible tablets for preschool-aged children. METHODS: This open-label, partly randomised, phase 3 study was conducted at two hospitals in Côte d'Ivoire and Kenya. Children with a minimum bodyweight of 5 kg in those aged 3 months to 2 years and 8 kg in those aged 2-6 years were eligible. In cohort 1, participants aged 4-6 years infected with Schistosoma mansoni were randomly assigned (2:1) to receive a single dose of oral arpraziquantel 50 mg/kg (cohort 1a) or oral praziquantel 40 mg/kg (cohort 1b) using a computer-generated randomisation list. Cohorts 2 (aged 2-3 years) and 3 (aged 3 months to 2 years) infected with S mansoni, and the first 30 participants in cohort 4a (aged 3 months to 6 years) infected with Schistosoma haematobium, received a single dose of oral arpraziquantel 50 mg/kg. After follow-up assessments, arpraziquantel was increased to 60 mg/kg (cohort 4b). Laboratory personnel were masked to the treatment group, screening, and baseline values. S mansoni was detected using a point-of-care circulating cathodic antigen urine cassette test and confirmed using the Kato-Katz method. The primary efficacy endpoint was clinical cure rate at 17-21 days after treatment in cohorts 1a and 1b, measured in the modified intention-to-treat population and calculated using the Clopper-Pearson method. This study is registered with ClinicalTrials.gov, NCT03845140. FINDINGS: Between Sept 2, 2019, and Aug 7, 2021, 2663 participants were prescreened and 326 were diagnosed with S mansoni or S haematobium. 288 were enrolled (n=100 in cohort 1a, n=50 in cohort 1b, n=30 in cohort 2, n=18 in cohort 3, n=30 in cohort 4a, and n=60 in cohort 4b), but eight participants received antimalarial drugs and were excluded from the efficacy analyses. The median age was 5·1 years (IQR 4·1-6·0) and 132 (47%) of 280 participants were female and 148 (53%) were male. Cure rates with arpraziquantel were similar to those with praziquantel (87·8% [95% CI 79·6-93·5] in cohort 1a vs 81·3% [67·4-91·1] in cohort 1b). No safety concerns were identified during the study. The most common drug-related treatment-emergent adverse events were abdominal pain (41 [14%] of 288 participants), diarrhoea (27 [9%]), vomiting (16 [6%]), and somnolence (21 [7%]). INTERPRETATION: Arpraziquantel, a first-line orodispersible tablet, showed high efficacy and favourable safety in preschool-aged children with schistosomiasis. FUNDING: The Global Health Innovative Technology Fund, the European and Developing Countries Clinical Trials Partnership, and the healthcare business of Merck KGaA, Darmstadt, Germany (CrossRef Funder ID: 10.13039/100009945).

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.

Population genetic structure of Schistosoma haematobium and Schistosoma haematobium × Schistosoma bovis hybrids among school-aged children in Côte d'Ivoire.

While population genetics of Schistosoma haematobium have been investigated in West Africa, only scant data are available from Côte d'Ivoire. The purpose of this study was to analyze both genetic variability and genetic structure among S. haematobium populations and to quantify the frequency of S. haematobium × S. bovis hybrids in school-aged children in different parts of Côte d'Ivoire. Urine samples were subjected to a filtration method and examined microscopically for Schistosoma eggs in four sites in the western and southern parts of Côte d'Ivoire. A total of 2692 miracidia were collected individually and stored on Whatman® FTA cards. Of these, 2561 miracidia were successfully genotyped for species and hybrid identification using rapid diagnostic multiplex mitochondrial cox1 PCR and PCR Restriction Fragment Length Polymorphism (PCR-RFLP) analysis of the nuclear ITS2 region. From 2164 miracidia, 1966 (90.9%) were successfully genotyped using at least 10 nuclear microsatellite loci to investigate genetic diversity and population structure. Significant differences were found between sites in all genetic diversity indices and genotypic differentiation was observed between the site in the West and the three sites in the East. Analysis at the infrapopulation level revealed clustering of parasite genotypes within individual children, particularly in Duekoué (West) and Sikensi (East). Of the six possible cox1-ITS2 genetic profiles obtained from miracidia, S. bovis cox1 × S. haematobium ITS2 (42.0%) was the most commonly observed in the populations. We identified only 15 miracidia (0.7%) with an S. bovis cox1 × S. bovis ITS2 genotype. Our study provides new insights into the population genetics of S. haematobium and S. haematobium × S. bovis hybrids in humans in Côte d'Ivoire and we advocate for researching hybrid schistosomes in animals such as rodents and cattle in Côte d'Ivoire.

Title: Structuration génétique des populations de Schistosoma haematobium et des hybrides Schistosoma haematobium × Schistosoma bovis chez les enfants d'âge scolaire en Côte d'Ivoire. Abstract: Alors que la génétique des populations de Schistosoma haematobium a été étudiée en Afrique de l'Ouest, seules quelques données sont disponibles pour la Côte d'Ivoire. Le but de cette étude était d'analyser à la fois la variabilité génétique et la structure génétique des populations de S. haematobium et de quantifier la fréquence des hybrides S. haematobium × S. bovis chez les enfants d'âge scolaire dans différentes régions de la Côte d'Ivoire. Des échantillons d'urine ont été soumis à une méthode de filtration et examinés au microscope pour les œufs de Schistosoma dans quatre sites de l'ouest et du sud de la Côte d'Ivoire. Au total, 2 692 miracidia ont été collectés individuellement et stockés sur des cartes Whatman® FTA. Parmi ceux-ci, 2 561 miracidia ont été génotypés avec succès pour l'identification des espèces et des hybrides à l'aide de la PCR multiplex de diagnostic rapide du cox1 mitochondrial et d'une analyse du polymorphisme de longueur des fragments de restriction de PCR (PCR-RFLP) de la région ITS2 de l'ADN nucléaire. Sur 2 164 miracidia, 1 966 (90,9 %) ont été génotypés avec succès en utilisant au moins 10 loci microsatellites nucléaires pour étudier la diversité génétique et la structure de la population. Des différences significatives ont été trouvées entre les sites dans tous les indices de diversité génétique et une différenciation génotypique a été observée entre le site de l'Ouest et les trois sites de l'Est. L'analyse au niveau de l'infrapopulation a révélé un regroupement des génotypes de parasites au sein de chaque enfant, en particulier à Duekoué (Ouest) et Sikensi (Est). Parmi les six profils génétiques cox1-ITS2 possibles obtenus à partir de miracidia, S. bovis cox1 × S. haematobium ITS2 (42,0 %) était le plus fréquemment observé dans les populations. Nous avons identifié seulement 15 miracidia (0,7 %) avec un génotype S. bovis cox1 × S. bovis ITS2. Notre étude apporte de nouvelles connaissances sur la génétique des populations de S. haematobium et des hybrides S. haematobium × S. bovis chez l'homme en Côte d'Ivoire et nous plaidons pour la recherche de schistosomes hybrides chez les animaux (rongeurs et bovins) en Côte d'Ivoire.

Accuracy of a rapid diagnosis test, microscopy and loop-mediated isothermal amplification in the detection of asymptomatic Plasmodium infections in Korhogo, Northern Côte d'Ivoire.

BACKGROUND: Highly sensitive and accurate malaria diagnostic tools are essential to identify asymptomatic low parasitaemia infections. This study evaluated the performance of histidine-rich protein 2 (HRP-2) based rapid diagnostic tests (RDTs), microscopy and loop-mediated isothermal amplification (LAMP) for the detection of asymptomatic Plasmodium spp. infections in Northern Côte d'Ivoire, using nested polymerase chain reaction (nPCR) as reference. METHODS: A household-based survey was carried out in July 2016, in the health district of Korhogo, involving 1011 adults without malaria symptom nor history of fever during the week before recruitment. The fresh capillary blood samples were collected to detect Plasmodium infections using on HRP-2-based RDTs, microscopy and LAMP and stored as dried blood spots (DBS). A subset of the DBS (247/1011, 24.4%) was randomly selected for nPCR analyses. Additionally, venous blood samples, according to LAMP result (45 LAMP positive and 65 LAMP negative) were collected among the included participants to perform the nested PCR used as the reference. RESULTS: The prevalence of asymptomatic Plasmodium spp. infections determined by RDT, microscopy, and LAMP were 4% (95% confidence interval (CI) 2.8-5.3), 5.2% (95% CI 3.9-6.6) and 18.8% (95% CI 16.4-21.2), respectively. Considering PCR on venous blood as reference, performed on 110 samples, the sensibility and specificity were, respectively, 17.8% (95% CI 6.1-29.4) and 100% for RDT, 20.0% (95% CI 7.8-32) and 100% for microscopy, and 93.3% (95% CI 85.7-100) and 95.4% (95% CI 92.2-100) for LAMP. CONCLUSION: In Northern Côte d'Ivoire, asymptomatic Plasmodium infection was found to be widely distributed as approximately one out of five study participants was found to be Plasmodium infected. LAMP appears currently to be the only available diagnostic method that can identify in the field this reservoir of infections and should be the method to consider for potential future active case detection interventions targeting elimination of these infections.

Impact of newly constructed primary healthcare centres on antenatal care attendance, facility delivery and all-cause mortality: quasi-experimental evidence from Taabo health and demographic surveillance system, Côte d'Ivoire.

OBJECTIVES: Access to quality care remains limited, particularly in low-income and middle-income countries. Although better health outcomes for families living in close proximity to healthcare facilities have been documented in cross-sectional studies, evidence on the extent to which additional health facilities can contribute to improved population health remains scanty. We aimed to estimate the causal impact of newly constructed primary healthcare facilities within a health and demographic surveillance (HDSS) site in Côte d'Ivoire. DESIGN: We conducted a quasi-experimental study. Logistic and Cox proportional hazards regression models were used to estimate the impact of new healthcare facilities on healthcare-seeking behaviour and all-cause mortality. SETTING: Data were collected prospectively through the Taabo HDSS located in south-central Côte d'Ivoire between 2010 and 2018. PARTICIPANTS: We analysed 2957 deaths across 440 973 person-year observations as well as 14 132 live births. PRIMARY OUTCOME MEASURES: The primary outcomes were antenatal care (ANC) attendance, facility delivery and mortality. Logistic and Cox proportional hazards models were employed to estimate the impact of the new health facilities on ANC attendance, facility delivery and child as well as adult mortality. RESULTS: Average distance to the nearest healthcare facility declined from 5.5 km before to 2.8 km after opening of four new healthcare facilities in targeted villages. No improvement was observed for ANC attendance, institutional deliveries and adult mortality. New facilities reduced the risk of post-neonatal infant mortality by 46% (HR 0.54, 95% CI 0.31 to 0.94, p<0.05), suggesting a mortality gradient of 2 deaths per 1000 for each additional km (Coef=0.002, 95% CI 0.000 to 0.004, p<0.05). CONCLUSIONS: Our results suggest that new facilities do not necessarily improve healthcare utilisation and health outcomes. Further research is needed to identify the best ways to ensure access to quality care in resource-constrained settings.

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.

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.

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.

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.

Distribution of bovine Fasciola gigantica (Cobbold, 1885) in the district des Savanes, northern Côte d'Ivoire.

Fascioliasis, caused by an infection with liver flukes of the genus Fasciola, is an important disease of livestock in most parts of the world. However, little is known about the distribution of fascioliasis in sub-Saharan Africa. We report results of a cross-sectional study conducted in 2014 in the district des Savanes in the northern part of Côte d'Ivoire. We obtained 275 livers from bovine suspected with fascioliasis and 51 unsuspected livers from 24 slaughterhouses. Livers were dissected using a standard operating procedure and all Fasciola gigantica flukes were removed from the tissues of the liver and the biliary ducts. We found F. gigantica in 125 livers from bovines suspected with fascioliasis (45.5%) in 10 departments of the district des Savanes. Among the unsuspected livers, five were positive for F. gigantica (9.8%). The distribution of fascioliasis showed considerable spatial heterogeneity, both at regional (ranging from 18.0% to 52.3%) and departmental level (ranging from 14.3% to 64.0%). Poro region was the most affected (52.3%) with a relatively homogeneous distribution. The departments most affected by fascioliasis were M'Bengué (64.0%), Sinématiali (62.1%) and Ferkessédougou (52.9%). Our study confirms that fascioliasis is an important veterinary disease in the northern part of Côte d'Ivoire, and hence, high-risk areas need to be targeted for prevention and control measures.

Efficacy of triclabendazole and albendazole against Fasciola spp. infection in cattle in Côte d'Ivoire: a randomised blinded trial.

Triclabendazole is the anthelminthic of choice for the treatment of fascioliasis, however, it is only registered in a few countries. We investigated the efficacy of a single-dose of triclabendazole (12 mg/kg) or albendazole (15 mg/kg) against Fasciola spp. infection in cattle on farms in the northern part of Côte d'Ivoire in a randomized clinical trial. Faecal samples were obtained from 196 cattle, of which 155 (79.1%) were found positive for Fasciola spp. by the sedimentation technique. Cattle infected with Fasciola spp. were randomly allocated (3:3:1) to receive triclabendazole (n = 66), albendazole (n = 67) or left untreated to serve as control (n = 22). Follow-up faecal samples were collected on days 21, 28, 90 and 188 post-treatment. No adverse events were observed as reported by farmers in any of the treatment groups. The proportion of non-egg shedding cattle, assessed at day 21 (primary outcome), was significantly higher in cattle treated with triclabendazole (95.4%) compared to those receiving albendazole (70.3%; odds ratio [OR] 8.73, 95% confidence interval [CI] 2.43-31.28, p <0.001). The egg reduction rate (ERR) expressed as number of eggs per gram of faeces, a secondary endpoint assessed at day 21 post-treatment, was significantly higher in the triclabendazole arm (arithmetic mean (AM) ERR = 99.8%) than in the albendazole arm (AM ERR = 92.2%), with a difference of 7.6%-points (95% CI: 0.9-14.5%-points, p=0.026). This is the first report of efficacy of triclabendazole against Fasciola spp. in naturally infected cattle in Côte d'Ivoire. Our results confirm that triclabendazole is the most effective treatment of fascioliasis and therefore, should be considered for the control of livestock fascioliasis; if resources allow in combination with intermediate host snail control and raising farmers awareness of pasture and livestock management to avoid reinfection.

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.

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.

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.

Determinants of Modern Paediatric Healthcare Seeking in Rural Côte d'Ivoire.

Objectives: To determine factors that influence healthcare seeking among children with fatal and non-fatal health problems. Methods: Last disease episodes of surviving children and fatal outcomes of children under 5 years of age were investigated by means of an adapted social autopsy questionnaire administered to main caregivers. Descriptive analysis and logistic models were employed to identify key determinants of modern healthcare use. Results: Overall, 736 non-fatal and 82 fatal cases were assessed. Modern healthcare was sought for 63.9% of non-fatal and 76.8% of fatal cases, respectively. In non-fatal cases, young age, caregiver being a parent, secondary or higher education, living <5 km from a health facility, and certain clinical signs (i.e., fever, severe vomiting, inability to drink, convulsion, and inability to play) were positively associated with modern healthcare seeking. In fatal cases, only signs of lower respiratory disease were positively associated with modern healthcare seeking. A lack of awareness regarding clinical danger signs was identified in both groups. Conclusion: Interventions promoting prompt healthcare seeking and the recognition of danger signs may help improve treatment seeking in rural settings of Côte d'Ivoire and can potentially help further reduce under-five mortality.