Rapid and Comprehensive Screening for Urogenital and Gastrointestinal Schistosomiasis with Handheld Digital Microscopy Combined with Circulating Cathodic Antigen Testing.

Novel methods are required to aid the monitoring of schistosomiasis control and elimination initiatives through mass drug administration. Portable digital and mobile phone microscopy is a promising tool for this purpose. This cross-sectional study evaluated the diagnostic operating characteristics of a converted mobile phone microscope (the SchistoScope) for the detection of Schistosoma haematobium eggs, as determined by community-based field workers and expert microscopists, compared with a field gold standard of light microscopy. Three hundred sixty-five urine samples were evaluated by conventional light microscopy, with 49 (13.4%) positive for S. haematobium. Compared with light microscopy, the sensitivity and specificity of S. haematobium detection by field microscopists trained to use the SchistoScope were 26.5% (95% CI: 14.9-41.1%) and 98.4% (95% CI: 96.3-99.5%), respectively. The sensitivity and specificity of S. haematobium detection by expert microscopists using the SchistoScope was 74% (95% CI: 59.7-85.4%) and 98.1% (95% CI: 95.9-99.3%), respectively, compared with light microscopy. The sensitivity rose to 96.1% and 100% when evaluating for egg counts greater than five and 10 eggs per 10 mL, respectively. A point-of-care circulating cathodic anion (POC CCA) test was used to evaluate Schistosoma mansoni; however, there were too few positive samples to reliably comment on diagnostic characteristics. This study demonstrated that a "urine-only" approach to rapidly screen for schistosomiasis at the point of sample collection can be conducted with mobile phone microscopy (S. haematobium) coupled with POC CCA (S. mansoni). Such an approach may aid in streamlined schistosomiasis control and elimination initiatives.

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.

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

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

Prevalence and seasonal transmission of Schistosoma haematobium infection among school-aged children in Kaedi town, southern Mauritania.

BACKGROUND: Mauritania is at the fringe of transmission of human schistosomiasis, which mainly occurs in the southern and southeastern parts of the country. This study aimed to assess the influence of rainfall seasonality on the prevalence of Schistosoma haematobium infection among school-aged children in Kaedi, southern Mauritania. METHODS: Cross-sectional surveys (i.e. parasitological, malacological and observations on water-related human activities) were carried out in Kaedi between September 2014 and May 2015, during both the wet and dry seasons. A total of 2162 children aged 5-15 years provided a single urine sample that was subjected to S. haematobium diagnosis. Snails were sampled and checked for cercarial shedding. Water contact patterns of the local population were recorded by direct observation. RESULTS: The prevalence of S. haematobium was 4.0% (86/2162, 95% confidence interval (CI): 3.2-4.9%) with a geometric mean egg count per 10 ml of urine of 3.7 (95% CI: 2.8-4.3). Being male (adjusted odds ratio (aOR) 1.78, 95% CI: 1.13-2.80), being at primary school (aOR 1.73, 95% CI: 1.04-2.87) and dry season (aOR 0.56, 95% CI: 0.35-0.89) were significantly associated with S. haematobium. Among 284 potential intermediate host snail specimens collected over the rainy and dry seasons, three species were identified: Bulinus senegalensis (n = 13) and B. forskalii (n = 161) in the rainy season, and B. truncatus (n = 157) in the wet season. No snail was shedding cercariae. On average, seven human water contacts were recorded per hour per observer over a 28-day observation period. Twelve types of water contact activities were identified among which, swimming/bathing was predominant (n = 3788, 36.9%), followed by washing clothes (n = 2016, 19.7%) and washing dishes (n = 1322, 12.9%). Females (n = 5270, 51.4%) were slightly more in contact with water than males (n = 4983, 48.6%). The average time spent in the water per person per day was 14.2 min (95% CI: 13.8-14.6 min). The frequency and duration of water contact followed a seasonal pattern. CONCLUSION: Our findings demonstrate a low prevalence and intensity of S. haematobium among school-aged children in Kaedi. Appropriate integrated control measures, including health education among at-risk communities and snail control may help to interrupt transmission of S. haematobium in Kaedi.

Efficacy and safety of praziquantel in preschool-aged and school-aged children infected with Schistosoma mansoni: a randomised controlled, parallel-group, dose-ranging, phase 2 trial.

BACKGROUND: Praziquantel has been the drug of choice for schistosomiasis control for more than 40 years, yet surprisingly, the optimal dose for children younger than 4 years is not known. We aimed to assess the efficacy and safety of escalating praziquantel dosages in preschool-aged children (PSAC). METHODS: We did a randomised controlled, parallel-group, single-blind, dose-ranging, phase 2 trial in PSAC (2-5 years) and school-aged children (SAC; aged 6-15 years) as a comparator group in southern Côte d'Ivoire. Children were randomly assigned (1:1:1:1) to 20 mg/kg, 40 mg/kg, or 60 mg/kg praziquantel or placebo. Participants, investigators, and laboratory technicians were masked to group assignment, while the investigator providing treatment was aware of the treatment group. The primary objective was to estimate the nature of the dose-response relation in terms of cure rate using the Kato Katz technique. Dose-response curves were estimated using Emax models. Available case analysis was done including all participants with primary endpoint data. This trial is registered with International Standard Randomised Controlled Trial, number ISRCTN15280205. FINDINGS: Between Nov 11, 2014, and Feb 18, 2015, 660 PSAC and 225 SAC were assessed for eligibility; of whom 161 (24%) PSAC and 180 (80%) SAC had a detectable Schistosoma mansoni infection. 161 PSAC were randomly allocated of whom 154 received treatment: 42 were assigned to 20 mg/kg praziquantel, of whom 40 received treatment; 38 were assigned to 40 mg/kg praziquantel, of whom 38 received treatment; 41 were assigned to 60 mg/kg praziquantel, of whom 39 received treatment; and 40 were assigned to placebo, of whom 37 received placebo. 180 SAC were randomly allocated of whom 177 received treatment: 49 were assigned to 20 mg/kg praziquantel, of whom 47 received treatment; 46 were assigned to 40 mg/kg praziquantel, of whom 46 received treatment; 42 were assigned to 60 mg/kg praziquantel, of whom 42 received treatment; and 43 were assigned to placebo, of whom 43 received treatment. Follow-up (available-case) data were available for 143 PSAC and 174 SAC. In PSAC, the 20 mg/kg dose resulted in cure in 23 children (62%; 95% CI 44·8-77·5), 40 mg/kg in 26 children (72%; 54·8-85·8), 60 mg/kg in 25 children (71%; 53·7-85·4), and placebo in 13 children (37%; 21·5-55·1). In SAC, the 20 mg/kg dose resulted in cure in 14 children (30%; 95% CI 17·7-45·8), 40 mg/kg in 31 children (69%; 53·4-81·8), 60 mg/kg in 34 children (83%; 67·9-92·8), and placebo in five children (12%; 4·0-25·6). For both age groups, the number of adverse events was similar among the three praziquantel treatment groups, with fewer adverse events observed in the placebo groups. The most common adverse events in PSAC were diarrhoea (11 [9%] of 124) and stomach ache (ten [8%]) and in SAC were diarrhoea (50 [28%] of 177), stomach ache (66 [37%]), and vomiting (26 [15%]) 3 h post treatment. No serious adverse events were reported. INTERPRETATION: Praziquantel shows a flat dose-response and overall lower efficacy in PSAC compared with in SAC. In the absence of treatment alternatives, a single dose of praziquantel of 40 mg/kg, recommended by the WHO for S mansoni infections in SAC can be endorsed for PSAC in preventive chemotherapy programmes. FUNDING: European Research Council.

Bayesian risk profiling of soil-transmitted helminth infections and estimates of preventive chemotherapy for school-aged children in Côte d'Ivoire.

BACKGROUND: Soil-transmitted helminthiasis affects more than a billion people in the world and accounts for a global burden of 5.1 million disability-adjusted life years. The objectives of this study were (i) to map and predict the risk of soil-transmitted helminth infections among school-aged children in Côte d'Ivoire; (ii) to estimate school-aged children population-adjusted risk; and (iii) to estimate annual needs for preventive chemotherapy. METHODS: In late 2011/early 2012, a cross-sectional survey was carried out among school-aged children in 92 localities of Côte d'Ivoire. Children provided a single stool sample that was subjected to duplicate Kato-Katz thick smears for the diagnosis of soil-transmitted helminths. A Bayesian geostatistical variable selection approach was employed to identify environmental and socioeconomic risk factors for soil-transmitted helminth infections. Bayesian kriging was used to predict soil-transmitted helminth infections on a grid of 1 × 1 km spatial resolution. The number of school-aged children infected with soil-transmitted helminths and the amount of doses needed for preventive chemotherapy according to World Health Organization guidelines were estimated. RESULTS: Parasitological data were available from 5246 children aged 5-16 years. Helminth infections with hookworm were predominant (17.2 %). Ascaris lumbricoides and Trichuris trichiura were rarely found; overall prevalences were 1.9 % and 1.2 %, respectively. Bayesian geostatistical variable selection identified rural setting for hookworm, soil acidity and soil moisture for A. lumbricoides, and rainfall coefficient of variation for T. trichiura as main predictors of infection. The estimated school-aged children population-adjusted risk of soil-transmitted helminth infection in Côte d'Ivoire is 15.5 % (95 % confidence interval: 14.2-17.0 %). We estimate that approximately 1.3 million doses of albendazole or mebendazole are required for school-based preventive chemotherapy, and we provide school-aged children-adjusted risk aggregated at health district level. CONCLUSION: We provide the first soil-transmitted helminthiasis risk profile for entire Côte d'Ivoire, based on a robust Bayesian geostatistical framework. Our model-based estimates of treatment needs and risk maps on health district level may guide the national control program in spatial targeting of annual interventions.

Bayesian risk mapping and model-based estimation of Schistosoma haematobium-Schistosoma mansoni co-distribution in Côte d'Ivoire.

BACKGROUND: Schistosoma haematobium and Schistosoma mansoni are blood flukes that cause urogenital and intestinal schistosomiasis, respectively. In Côte d'Ivoire, both species are endemic and control efforts are being scaled up. Accurate knowledge of the geographical distribution, including delineation of high-risk areas, is a central feature for spatial targeting of interventions. Thus far, model-based predictive risk mapping of schistosomiasis has relied on historical data of separate parasite species. METHODOLOGY: We analyzed data pertaining to Schistosoma infection among school-aged children obtained from a national, cross-sectional survey conducted between November 2011 and February 2012. More than 5,000 children in 92 schools across Côte d'Ivoire participated. Bayesian geostatistical multinomial models were developed to assess infection risk, including S. haematobium-S. mansoni co-infection. The predicted risk of schistosomiasis was utilized to estimate the number of children that need preventive chemotherapy with praziquantel according to World Health Organization guidelines. PRINCIPAL FINDINGS: We estimated that 8.9% of school-aged children in Côte d'Ivoire are affected by schistosomiasis; 5.3% with S. haematobium and 3.8% with S. mansoni. Approximately 2 million annualized praziquantel treatments would be required for preventive chemotherapy at health districts level. The distinct spatial patterns of S. haematobium and S. mansoni imply that co-infection is of little importance across the country. CONCLUSIONS/SIGNIFICANCE: We provide a comprehensive analysis of the spatial distribution of schistosomiasis risk among school-aged children in Côte d'Ivoire and a strong empirical basis for a rational targeting of control interventions.

Praziquantel, mefloquine-praziquantel, and mefloquine-artesunate-praziquantel against Schistosoma haematobium: a randomized, exploratory, open-label trial.

BACKGROUND: Treatment and morbidity control of schistosomiasis relies on a single drug, praziquantel. Hence, there is a pressing need to develop additional therapeutics against schistosomiasis. The antimalarial drug mefloquine shows antischistosomal activity in animal models and clinical trials, which calls for further investigations. METHODOLOGY: We comparatively assessed the efficacy and tolerability of the following treatments against Schistosoma haematobium in school-aged children in Côte d'Ivoire: (i) praziquantel (40 mg/kg; standard treatment); (ii) mefloquine (25 mg/kg) combined with praziquantel (40 mg/kg); and (iii) mefloquine-artesunate (3× (100 mg artesunate +250 mg mefloquine)) combined with praziquantel (40 mg/kg) (treatments administered on subsequent days). Two urine samples were collected before, and on days 21-22 and 78-79 after the first dosing. PRINCIPAL FINDINGS: Sixty-one children were present on all examination time points and had complete datasets. No difference in efficacy was observed between the three treatment groups on either follow-up. On the 21-22 day posttreatment follow-up, based on available case analysis, cure rates of 33% (95% confidence interval (CI) 11-55%), 29% (95% CI 8-50%), and 26% (95% CI 5-48%) were observed for praziquantel, mefloquine-artesunate-praziquantel, and mefloquine-praziquantel, respectively. The corresponding egg reduction rates were 94% and above. On the second follow-up, observed cure rates ranged from 19% (praziquantel) to 33% (mefloquine-artesunate-praziquantel), and egg reduction rates were above 90%. Praziquantel monotherapy was the best tolerated treatment. In the mefloquine-artesunate-praziquantel group, adverse events were reported by 91% of the participants, and in the mefloquine-praziquantel group, 95% experienced adverse events. With the exception of abdominal pain at moderate severity, adverse events were mild. CONCLUSIONS/SIGNIFICANCE: The addition of mefloquine or mefloquine-artesunate does not increase the efficacy of praziquantel against chronic S. haematobium infection. Additional studies are necessary to elucidate the effect of the combinations against acute schistosomiasis.

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.

The epidemiology of polyparasitism and implications for morbidity in two rural communities of Côte d'Ivoire.

BACKGROUND: Polyparasitism is still widespread in rural communities of the developing world. However, the epidemiology of polyparasitism and implications for morbidity are poorly understood. We studied patterns of multiple species parasite infection in two rural communities of Côte d'Ivoire, including associations and interactions between infection, clinical indicators and self-reported morbidity. METHODS: Between August and September 2011, two purposely selected rural communities in southern Côte d'Ivoire were screened for helminth, intestinal protozoa and Plasmodium infection, using a suite of quality-controlled diagnostic methods. Additionally, participants were examined clinically and we measured haemoglobin level, height, weight and mid-upper arm circumference to determine nutritional status. An anamnestic questionnaire was administered to assess people's recent history of diseases and symptoms, while a household questionnaire was administered to heads of household to collect socioeconomic data. Multivariate logistic regression models were applied for assessment of possible associations between parasitic (co-)infections and morbidity outcomes. RESULTS: 912/1,095 (83.3%) study participants had complete parasitological data and 852 individuals were considered for in-depth analysis. The rate of polyparasitism was high, with Plasmodium falciparum diagnosed as the predominant species, followed by Schistosoma haematobium, Schistosoma mansoni and hookworm. There were considerable differences in polyparasitic infection profiles among the two settings. Clinical morbidity such as anaemia, splenomegaly and malnutrition was mainly found in young age groups, while in adults, self-reported morbidity dominated. High parasitaemia of P. falciparum was significantly associated with several clinical manifestations such as anaemia, splenomegaly and fever, while light-intensity helminth infections seemed to have beneficial effects, particularly for co-infected individuals. CONCLUSIONS: Clinical morbidity is disturbingly high in young age groups in rural communities of Côte d'Ivoire and mainly related to very high P. falciparum endemicity. Interactions between helminth infections and P. falciparum burden (parasitaemia and clinical morbidity) are evident and must be taken into account to design future interventions.

Accuracy of urine circulating cathodic antigen test for the diagnosis of Schistosoma mansoni in preschool-aged children before and after treatment.

BACKGROUND: The Kato-Katz technique is widely used for the diagnosis of Schistosoma mansoni, but shows low sensitivity in light-intensity infections. We assessed the accuracy of a commercially available point-of-care circulating cathodic antigen (POC-CCA) cassette test for the diagnosis of S. mansoni in preschool-aged children before and after praziquantel administration. METHODOLOGY: A 3-week longitudinal survey with a treatment intervention was conducted in Azaguié, south Côte d'Ivoire. Overall, 242 preschoolers (age range: 2 months to 5.5 years) submitted two stool and two urine samples before praziquantel administration, and 86 individuals were followed-up posttreatment. Stool samples were examined with duplicate Kato-Katz thick smears for S. mansoni. Urine samples were subjected to POC-CCA cassette test for S. mansoni, and a filtration method for S. haematobium diagnosis. PRINCIPAL FINDINGS: Before treatment, the prevalence of S. mansoni, as determined by quadruplicate Kato-Katz, single CCA considering 'trace' as negative (t-), and single CCA with 'trace' as positive (t+), was 23.1%, 34.3% and 64.5%, respectively. Using the combined results (i.e., four Kato-Katz and duplicate CCA(t-)) as diagnostic 'gold' standard, the sensitivity of a single Kato-Katz, a single CCA(t-) or CCA(t+) was 28.3%, 69.7% and 89.1%, respectively. Three weeks posttreatment, the sensitivity of a single Kato-Katz, single CCA(t-) and CCA(t+) was 4.0%, 80.0% and 84.0%, respectively. The intensity of the POC-CCA test band reaction was correlated with S. mansoni egg burden (odds ratio = 1.2, p = 0.04). CONCLUSIONS/SIGNIFICANCE: A single POC-CCA cassette test appears to be more sensitive than multiple Kato-Katz thick smears for the diagnosis of S. mansoni in preschool-aged children before and after praziquantel administration. The POC-CCA cassette test can be recommended for the rapid identification of S. mansoni infections before treatment. Additional studies are warranted to determine the usefulness of POC-CCA for assessing drug efficacy and monitoring the impact of control interventions.

Comparing diagnostic accuracy of Kato-Katz, Koga agar plate, ether-concentration, and FLOTAC for Schistosoma mansoni and soil-transmitted helminths.

BACKGROUND: Infections with schistosomes and soil-transmitted helminths exert a considerable yet underappreciated economic and public health burden on afflicted populations. Accurate diagnosis is crucial for patient management, drug efficacy evaluations, and monitoring of large-scale community-based control programs. METHODS/PRINCIPAL FINDINGS: The diagnostic accuracy of four copromicroscopic techniques (i.e., Kato-Katz, Koga agar plate, ether-concentration, and FLOTAC) for the detection of Schistosoma mansoni and soil-transmitted helminth eggs was compared using stool samples from 112 school children in Côte d'Ivoire. Combined results of all four methods served as a diagnostic 'gold' standard and revealed prevalences of S. mansoni, hookworm, Trichuris trichiura, Strongyloides stercoralis and Ascaris lumbricoides of 83.0%, 55.4%, 40.2%, 33.9% and 28.6%, respectively. A single FLOTAC from stool samples preserved in sodium acetate-acetic acid-formalin for 30 or 83 days showed a higher sensitivity for S. mansoni diagnosis (91.4%) than the ether-concentration method on stool samples preserved for 40 days (85.0%) or triplicate Kato-Katz using fresh stool samples (77.4%). Moreover, a single FLOTAC detected hookworm, A. lumbricoides and T. trichiura infections with a higher sensitivity than any of the other methods used, but resulted in lower egg counts. The Koga agar plate method was the most accurate diagnostic assay for S. stercoralis. CONCLUSION/SIGNIFICANCE: We have shown that the FLOTAC method holds promise for the diagnosis of S. mansoni. Moreover, our study confirms that FLOTAC is a sensitive technique for detection of common soil-transmitted helminths. For the diagnosis of S. stercoralis, the Koga agar plate method remains the method of choice.

Efficacy and safety of mefloquine, artesunate, mefloquine-artesunate, and praziquantel against Schistosoma haematobium: randomized, exploratory open-label trial.

BACKGROUND: Morbidity control of schistosomiasis relies on a single drug, praziquantel. The antimalarial drug mefloquine possesses interesting antischistosomal properties, yet no clinical studies have been performed. METHODS: We conducted a randomized, exploratory open-label trial to assess the efficacy and safety of mefloquine (25 mg/kg), artesunate (3 doses of 4 mg/kg), mefloquine-artesunate (3 doses of 100 mg artesunate plus 250 mg mefloquine), and praziquantel (40 mg/kg) against Schistosoma haematobium. The effects on Schistosoma mansoni, malaria parasitemia, soil-transmitted helminths, and intestinal protozoa were also determined. RESULTS: A total of 83 S. haematobium-infected schoolchildren were included in the study. Cure rates of mefloquine, artesunate, mefloquine-artesunate, and praziquantel against S. haematobium at day 26 after treatment were 21%, 25%, 61%, and 88%, respectively. Both mefloquine-artesunate and praziquantel resulted in egg reduction rates >95%. Significantly lower egg reduction rates were seen in the artesunate (85%) and mefloquine groups (74%). In children coinfected with S. mansoni, praziquantel and mefloquine-artesunate, but not mefloquine and artesunate alone, resulted in high cure rates and egg reduction rates. Mefloquine, artesunate, and mefloquine-artesunate completely cured infections due to Plasmodium falciparum. No effects were found against soil-transmitted helminths and intestinal protozoa. Abdominal pain was the most frequent adverse event, with a higher incidence among children treated with mefloquine (89%), mefloquine-artesunate (83%), and artesunate (60%) than among children treated with praziquantel (46%). CONCLUSIONS: The high efficacy of mefloquine-artesunate against S. haematobium warrants further investigation. Individuals coinfected with Plasmodium and Schistosoma who were treated with a mefloquine-artesunate combination against malaria might have a dual benefit: clearance of malaria parasitemia and reduction of schistosomiasis-related morbidity. CLINICAL TRIALS REGISTRATION: Current Controlled Trials identifier: ISRCTN06498763.

Multiple parasite infections and their relationship to self-reported morbidity in a community of rural Côte d'Ivoire.

BACKGROUND: Concomitant parasitic infections are common in the developing world, yet most studies focus on a single parasite in a narrow age group. We investigated the extent of polyparasitism and parasite associations, and related these findings to self-reported morbidity. METHODS: Inhabitants of 75 randomly selected households from a single village in western Côte d'Ivoire provided multiple faecal specimens and a single finger prick blood sample. The Kato-Katz technique and a formol-ether concentration method were employed to screen faecal samples for Schistosoma mansoni, soil-transmitted helminths and intestinal protozoa. Giemsa-stained blood smears were analysed for malaria parasites. A questionnaire was administered for collection of demographic information and self-reported morbidity indicators. RESULTS: Complete parasitological data were obtained for 500/561 (89.1%) participants, similarly distributed among sex, with an age range from 5 days to 91 years. The prevalences of Plasmodium falciparum, hookworms, Entamoeba histolytica/E. dispar, and S. mansoni were 76.4%, 45.0%, 42.2%, and 39.8%, respectively. Three-quarters of the population harboured three or more parasites concurrently. Multivariate analysis revealed significant associations between several pairs of parasites. Some parasitic infections and the total number of parasites were significantly associated with self-reported morbidity indicators. CONCLUSIONS: Our data confirm that polyparasitism is very common in rural Côte d'Ivoire and that people have clear perceptions about the morbidity caused by some of these parasitic infections. Our findings can be used for the design and implementation of sound intervention strategies to mitigate morbidity and co-morbidity.