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.

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.

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.

High prevalence of Schistosoma haematobium × Schistosoma bovis hybrids in schoolchildren in Côte d'Ivoire.

Schistosomiasis is a neglected tropical disease, though it is highly prevalent in many parts of sub-Saharan Africa. While Schistosoma haematobium-bovis hybrids have been reported in West Africa, no data about Schistosoma hybrids in humans are available from Côte d'Ivoire. This study aimed to identify and quantify S. haematobium-bovis hybrids among schoolchildren in four localities of Côte d'Ivoire. Urine samples were collected and examined by filtration to detect Schistosoma eggs. Eggs were hatched and 503 miracidia were individually collected and stored on Whatman® FTA cards for molecular analysis. Individual miracidia were molecularly characterized by analysis of mitochondrial cox1 and nuclear internal transcribed spacer 2 (ITS 2) DNA regions. A mitochondrial cox1-based diagnostic polymerase chain reaction was performed on 459 miracidia, with 239 (52.1%) exhibiting the typical band for S. haematobium and 220 (47.9%) the S. bovis band. The cox1 and ITS 2 amplicons were Sanger sequenced from 40 randomly selected miracidia to confirm species and hybrids status. Among the 33 cox1 sequences analysed, we identified 15 S. haematobium sequences (45.5%) belonging to seven haplotypes and 18 S. bovis sequences (54.5%) belonging to 12 haplotypes. Of 40 ITS 2 sequences analysed, 31 (77.5%) were assigned to pure S. haematobium, four (10.0%) to pure S. bovis and five (12.5%) to S. haematobium-bovis hybrids. Our findings suggest that S. haematobium-bovis hybrids are common in Côte d'Ivoire. Hence, intense prospection of domestic and wild animals is warranted to determine whether zoonotic transmission occurs.

Prevalence and distribution of livestock schistosomiasis and fascioliasis in Côte d'Ivoire: results from a cross-sectional survey.

BACKGROUND: Schistosoma and Fasciola are zoonotic parasites of public health and veterinary importance. However, while the epidemiology of schistosomiasis in humans is well studied, little is known about fascioliasis and schistosomiasis in livestock in Côte d'Ivoire. This study aimed to determine the prevalence and the distribution of livestock schistosomiasis and fascioliasis across Côte d'Ivoire. In 2018, we conducted a cross-sectional survey in abattoirs and farms in 13 departments of Côte d'Ivoire. In abattoirs, the mesenteric veins and livers of slaughtered cattle, sheep and goats were examined for adult Schistosoma and Fasciola flukes. Faeces from live cattle, goats and sheep were collected and examined for Schistosoma and Fasciola eggs using a sedimentation technique. RESULTS: A total of 386 cattle, 174 goats and 151 sheep from abattoirs and 435 cattle, 22 goats and 176 sheep from farms were sampled. The observed prevalence of schistosomiasis was higher in slaughtered animals. Fascioliasis was more prevalent in farm animals. The prevalence of schistosomiasis in slaughtered cattle varied between 5.9% (95% confidence interval (CI): 0.7-19.7%) and 53.3% (95% CI: 37.9-68.3%) with the highest prevalence observed in Ouangolodougou in the North. Cattle from farms had a relatively low prevalence of schistosomiasis, with the highest prevalence found in Ouangolodougou (2.4%, 95% CI: 0.7-6.1%). The prevalence of fascioliasis varied considerably from one department to another, ranging from nil (95% CI: 0.0-18.5%) to 50.8% (95% CI: 43.4-58.2%), with the highest prevalence found in farm cattle in Dikodougou in the North. Sheep and goats had a lower prevalence of schistosomiasis and fascioliasis than cattle. In slaughtered animals, cattle aged 4 years and older were at highest risk for schistosomiasis (odds ratio (OR): 2.4; 95% CI: 1.0-5.6) and fascioliasis (OR: 2.1; 95% CI: 1.1-3.9). In farm animals, male cattle had higher odds of being infected with Schistosoma (OR: 4.3; 95% CI: 0.7-26.9) than females. CONCLUSIONS: Our study confirms that schistosomiasis and fascioliasis are endemic in livestock across Côte d'Ivoire. A strategic control programme should be considered, especially for cattle, including providing drinking water in troughs to reduce faecal contamination of water sources by cattle.

Accuracy of the sedimentation and filtration methods for the diagnosis of schistosomiasis in cattle.

Infection with blood flukes of the genus Schistosoma causes considerable human and animal morbidity, mortality and economic loss to the livestock industry. Current diagnostic tools have limitations. In this study, we compared the sedimentation and filtration methods for the diagnosis of schistosomiasis in livestock. A total of 196 faecal samples from cattle in Côte d'Ivoire were subjected to sedimentation and filtration for the diagnosis of schistosomiasis and other intestinal parasite infections. Schistosoma eggs or miracidia were discovered in 32 samples: 15 by filtration only, seven by sedimentation only, six concurrently by both methods and four by observing miracidia swimming on the sedimentation slide. The sensitivity of sedimentation and filtration was 41% and 66%, respectively. Cases with no Schistosoma eggs identified in the sediment but miracidia swimming on the slide indicate that eggs had hatched before microscopy. More accurate diagnostic are required for livestock schistosomiasis, in order to better understand the epidemiology and inform control and elimination efforts in livestock and human populations.

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.

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.

Pregnancy-related morbidity and risk factors for fatal foetal outcomes in the Taabo health and demographic surveillance system, Côte d'Ivoire.

BACKGROUND: Reliable, population-based data on pregnancy-related morbidity and mortality, and risk factors for fatal foetal outcomes are scarce for low- and middle-income countries. Yet, such data are essential for understanding and improving maternal and neonatal health and wellbeing. METHODS: Within the 4-monthly surveillance rounds of the Taabo health and demographic surveillance system (HDSS) in south-central Côte d'Ivoire, all women of reproductive age identified to be pregnant between 2011 and 2014 were followed-up. A questionnaire pertaining to antenatal care, pregnancy-related morbidities, delivery circumstances, and birth outcome was administered to eligible women. Along with sociodemographic information retrieved from the Taabo HDSS repository, these data were subjected to penalized maximum likelihood logistic regression analysis, to determine risk factors for fatal foetal outcomes. RESULTS: A total of 2976 pregnancies were monitored of which 118 (4.0%) resulted in a fatal outcome. Risk factors identified by multivariable logistic regression analysis included sociodemographic factors of the expectant mother, such as residency in a rural area (adjusted odds ratio (aOR) = 2.87; 95% confidence interval (CI) 1.31-6.29) and poorest wealth tertile (aOR = 1.79; 95% CI 1.02-3.14), a history of miscarriage (aOR = 23.19; 95% CI 14.71-36.55), non-receipt of preventive treatment such as iron/folic acid supplementation (aOR = 3.15; 95% CI 1.71-5.80), only two doses of tetanus vaccination (aOR = 2.59; 95% CI 1.56-4.30), malaria during pregnancy (aOR = 1.94; 95% CI 1.21-3.11), preterm birth (aOR = 4.45; 95% CI 2.82-7.01), and delivery by caesarean section (aOR = 13.03; 95% CI 4.24-40.08) or by instrumental delivery (aOR = 5.05; 95% CI 1.50-16.96). Women who paid for delivery were at a significantly lower odds of a fatal foetal outcome (aOR = 0.39; 95% CI 0.25-0.74). CONCLUSIONS: We identified risk factors for fatal foetal outcomes in a mainly rural HDSS site of Côte d'Ivoire. Our findings call for public health action to improve access to, and use of, quality services of ante- and perinatal care.

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.

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.

Epidemiology of malaria in the Taabo health and demographic surveillance system, south-central Côte d'Ivoire.

BACKGROUND: A deep understanding of the local epidemiology of malaria is essential for the design and implementation of setting-specific control and elimination efforts. In Côte d'Ivoire, new initiatives are underway to reduce the burden of malaria, which requires high-quality longitudinal data. The epidemiology of malaria was studied in the Taabo health and demographic surveillance system (HDSS) in south-central Côte d'Ivoire and implications for control are discussed. METHODS: Two cross-sectional surveys were carried out in the rainy season of June/July in 2010 and 2011. Inhabitants of approximately 7% of randomly selected households in the Taabo HDSS were invited to participate. People were clinically examined, ear temperature was measured and spleen size determined. Finger-prick blood samples were collected and subjected to a rapid diagnostic test (RDT). Additionally, thick and thin blood films were prepared on microscope slides and diagnosed under a microscope for Plasmodium infection and parasitaemia. Haemoglobin (Hb) level was determined using a HemoCue device. RESULTS: A total of 1187 and 1264 people in 2010 and 2011, respectively, had complete data records. The prevalence of Plasmodium infection was 46.0% in 2010 and 56.6% in 2011, owing to a statistically significant difference (p < 0.05). Males showed a higher Plasmodium infection prevalence than females (49.6 and 62.8% versus 42.6 and 51.2%; respectively, in 2010 and 2011; both p < 0.05). The highest malaria prevalence was observed among infants and young children (aged ≤9 years). The risk of Plasmodium infection was significantly higher in villages compared to small hamlets and urban settings (p < 0.05). Fever, Hb level and splenomegaly were associated with parasitaemia. CONCLUSION: Malaria is highly endemic in the Taabo HDSS in south-central Côte d'Ivoire with considerable spatial heterogeneity of Plasmodium infection. There is a pressing need to scale-up control interventions against malaria.

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

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

Spatial and temporal variation of malaria entomological parameters at the onset of a hydro-agricultural development in central Côte d'Ivoire.

BACKGROUND: A deeper understanding of the ecology and small-scale heterogeneity of malaria transmission is essential for the design of effective prevention, control and elimination interventions. The spatial and temporal distribution of malaria vectors was investigated in five villages in close proximity to a hydro-agricultural system in Côte d'Ivoire over the course of construction and the early phase of irrigated rice farming. METHODS: The study was carried out in five villages (Raffierkro, N'Douakro, Ahougui, Kpokahankro, Koffikro) near Bouaké, central Côte d'Ivoire, between early 2007 and late 2009. In each village, mosquitoes were collected by human landing catches and identified morphologically at genus and species level, and entomological parameters were determined. Plasmodium infection was assessed by dissection and an enzyme-linked immunosorbent assay. RESULTS: A total of 19,404 mosquitoes belonging to the genus Anopheles were sampled during 328 human-night catches. Before the construction of the hydro-agricultural system, comparable densities of Anopheles gambiae were observed in all villages. In subsequent years, densities in Raffierkro and Ahougui were significantly higher than the other villages [Kruskal-Wallis (KW) test = 31.13, p < 0.001]. The density of Anopheles funestus in the five villages was comparable in the early stage of the project, while a high density was reported in Koffikro at the end (KW test = 11.91, p = 0.018). Transmission of Plasmodium falciparum is perennial in the study area. Over the course of the study, high entomological inoculation rates (EIRs) were found: 219-328 infectious bites per person per year with An. gambiae. For An. funestus considerably lower EIRs were observed (5.7-39.4). Changing patterns of An. gambiae were not correlated with malaria transmission. CONCLUSION: In this study setting, located in the bioclimatic transition zone of Côte d'Ivoire, rice cultivation was not observed to increase malaria transmission. The entomological parameters recorded until the onset of rice-growing activities in a hydro-agricultural system presented considerable heterogeneity both in space and time; a strong increase of Anopheles mosquitoes was observed in two of the five villages located in close proximity to the dam and irrigated rice fields. Malaria still is a main public health problem in all villages that require adequate control measures.

The effect of iron-fortified complementary food and intermittent preventive treatment of malaria on anaemia in 12- to 36-month-old children: a cluster-randomised controlled trial.

BACKGROUND: Iron deficiency (ID) and malaria co-exist in tropical regions and both contribute to high rates of anaemia in young children. It is unclear whether iron fortification combined with intermittent preventive treatment (IPT) of malaria would be an efficacious strategy for reducing anaemia in young children. METHODS: A 9-month cluster-randomised, single-blinded, placebo-controlled intervention trial was carried out in children aged 12-36 months in south-central Côte d'Ivoire, an area of intense and perennial malaria transmission. The study groups were: group 1: normal diet and IPT-placebo (n = 125); group 2: consumption of porridge, an iron-fortified complementary food (CF) with optimised composition providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferrous fumarate 6 days per week (CF-FeFum) and IPT-placebo (n = 126); group 3: IPT of malaria at 3-month intervals, using sulfadoxine-pyrimethamine and amodiaquine and no dietary intervention (n = 127); group 4: both CF-FeFum and IPT (n = 124); and group 5: consumption of porridge, an iron-fortified CF with the composition currently on the Ivorian market providing 2 mg iron as NaFeEDTA and 3.8 mg iron as ferric pyrophosphate 6 days per week (CF-FePP) and IPT-placebo (n = 127). The primary outcome was haemoglobin (Hb) concentration. Linear and logistic regression mixed-effect models were used for the comparison of the five study groups, and a 2 × 2 factorial analysis was used to assess treatment interactions of CF-FeFum and IPT (study groups 1-4). RESULTS: After 9 months, the Hb concentration increased in all groups to a similar extent with no statistically significant difference between groups. In the 2 × 2 factorial analysis after 9 months, no treatment interaction was found on Hb (P = 0.89). The adjusted differences in Hb were 0.24 g/dl (95 % CI -0.10 to 0.59; P = 0.16) in children receiving IPT and -0.08 g/dl (95 % CI -0.42 to 0.26; P = 0.65) in children receiving CF-FeFum. At baseline, anaemia (Hb <11.0 g/dl) was 82.1 %. After 9 months, IPT decreased the odds of anaemia (odds ratio [OR], 0.46 [95 % CI 0.23-0.91]; P = 0.023), whereas iron-fortified CF did not (OR, 0.85 [95 % CI 0.43-1.68]; P = 0.68), although ID (plasma ferritin <30 µg/l) was decreased markedly in children receiving iron fortified CF (OR, 0.19 [95 % CI 0.09-0.40]; P < 0.001). CONCLUSIONS: IPT alone only modestly decreased anaemia, but neither IPT nor iron fortified CF significantly improved Hb concentration after 9 months. Additionally, IPT did not augment the effect of the iron fortified CF. CF fortified with highly bioavailable iron improved iron status but not Hb concentration, despite three-monthly IPT of malaria. Thus, further research is necessary to develop effective combination strategies to prevent and treat anaemia in malaria endemic regions. TRIAL REGISTRATION: http://www.clinicaltrials.gov ; identifier NCT01634945; registered on July 3, 2012.

Disparities of Plasmodium falciparum infection, malaria-related morbidity and access to malaria prevention and treatment among school-aged children: a national cross-sectional survey in Côte d'Ivoire.

BACKGROUND: There is limited knowledge on the malaria burden of school-aged children in Côte d'Ivoire. The aim of this study was to assess Plasmodium falciparum infection, malaria-related morbidity, use of preventive measures and treatment against malaria, and physical access to health structures among school-aged children across Côte d'Ivoire. METHODS: A national, cross-sectional study was designed, consisting of clinical and parasitological examinations and interviews with schoolchildren. More than 5,000 children from 93 schools in Côte d'Ivoire were interviewed to determine household socioeconomic status, self-reported morbidity and means of malaria prevention and treatment. Finger-prick blood samples were collected and Plasmodium infection and parasitaemia determined using Giemsa-stained blood films and a rapid diagnostic test (RDT). Haemoglobin levels and body temperature were measured. Children were classified into wealth quintiles using household assets and principal components analysis (PCA). The concentration index was employed to determine significant trends of health variables according to wealth quintiles. Logistic and binomial negative regression analyses were done to investigate for associations between P. falciparum prevalence and parasitaemia and any health-related variable. RESULTS: The prevalence of P. falciparum was 73.9% according to combined microscopy and RDT results with a geometric mean of parasitaemia among infected children of 499 parasites/µl of blood. Infection with P. falciparum was significantly associated with sex, socioeconomic status and study setting, while parasitaemia was associated with age. The rate of bed net use was low compared to the rate of bed net ownership. Preventive measures (bed net ownership, insecticide spray and the reported use of malaria treatment) were more frequently mentioned by children from wealthier households who were at lower risk of P. falciparum infection. Self-reported morbidity (headache) and clinical morbidity (anaemia) were more often reported by children from less wealthy households. CONCLUSION: Seven out of ten school-aged children in Côte d'Ivoire are infected with P. falciparum and malaria-related morbidity is considerable. Furthermore, this study points out that bed net usage is quite low and there are important inequalities in preventive measures and treatment. These results can guide equity-oriented malaria control strategies in Côte d'Ivoire.

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 .

Effect of deworming on school-aged children's physical fitness, cognition and clinical parameters in a malaria-helminth co-endemic area of Côte d'Ivoire.

BACKGROUND: Malaria and helminth infections are thought to negatively affect children's nutritional status and to impair their physical and cognitive development. Yet, the current evidence-base is weak. The purpose of this study was to determine the effect of deworming against soil-transmitted helminthiasis and schistosomiasis on children's physical fitness, cognition and clinical parameters in a malaria-helminth co-endemic setting of Côte d'Ivoire. METHODS: We designed an intervention study with a 5-month follow-up among schoolchildren aged 5-14 years from Niablé, eastern Côte d'Ivoire. In late 2012, a baseline cross-sectional survey was conducted. Finger-prick blood, stool and urine samples were subjected to standardised, quality-controlled techniques for the diagnosis of Plasmodium spp., Schistosoma spp., soil-transmitted helminths and intestinal protozoa infections. Haemoglobin level was determined and anthropometric measurements were taken for appraisal of anaemia and nutritional status. Children underwent memory (digit span) and attention (code transmission) cognitive testing, and their physical fitness and strength were determined (20 m shuttle run, standing broad jump and grip strength test). All children were treated with albendazole (against soil-transmitted helminthiasis) and praziquantel (against schistosomiasis) after the baseline cross-sectional survey and again 2 months later. Five months after the initial deworming, the same battery of clinical, cognitive and physical fitness tests was performed on the same children. RESULTS: Lower scores in strength tests were significantly associated with children with harbouring nutritional deficiencies. Surprisingly, boys infected with Schistosoma mansoni achieved longer jumping distances than their non-infected counterparts. Light-intensity infection with S. mansoni was associated with slightly better aerobic capacity. Deworming showed no effect on haemoglobin levels and anaemia, but children with moderate- to heavy-intensity Schistosoma infection at baseline gained weight more pronouncedly than non-infected children. Interestingly, children with soil-transmitted helminth or Schistosoma infection at baseline performed significantly better in the sustained attention test than their non-infected counterparts at the 5-month follow-up. CONCLUSIONS: This study revealed conflicting results regarding clinical parameters and cognitive behaviour of children after two rounds of deworming. We speculate that potential beneficial effects of deworming are likely to be undermined in areas where malaria is co-endemic and nutritional deficiencies are widespread.

Evaluation of portable microscopic devices for the diagnosis of Schistosoma and soil-transmitted helminth infection.

The diagnosis of parasitic worm (helminth) infections requires specialized laboratory settings, but most affected individuals reside in locations without access to such facilities. We tested two portable microscopic devices for the diagnosis of helminth infections in a cross-sectional survey in rural Côte d'Ivoire. We examined 164 stool samples under a light microscope and then re-examined with a commercial portable light microscope and an experimental mobile phone microscope for the diagnosis of Schistosoma mansoni and soil-transmitted helminths. Additionally, 180 filtered urine samples were examined by standard microscopy and compared with the portable light microscope for detection of Schistosoma haematobium eggs. Conventional microscopy was considered the diagnostic reference standard. For S. mansoni, S. haematobium and Trichuris trichiura, the portable light microscope showed sensitivities of 84.8%, 78.6% and 81.5%, respectively, and specificities of 85.7%, 91.0% and 93.0%, respectively. For S. mansoni and T. trichiura, we found sensitivities for the mobile phone microscope of 68.2% and 30.8%, respectively, and specificities of 64.3% and 71.0%, respectively. We conclude that the portable light microscope has sufficient diagnostic yield for Schistosoma and T. trichiura infections, while the mobile phone microscope has only modest sensitivity in its current experimental set-up. Development of portable diagnostic technologies that can be used at point-of-sample collection will enhance diagnostic coverage in clinical and epidemiological settings.

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).