SARS-CoV-2 Antibody Prevalence and Population-Based Death Rates, Greater Omdurman, Sudan.

In a cross-sectional survey in Omdurman, Sudan, during March-April 2021, we estimated that 54.6% of the population had detectable severe acute respiratory syndrome coronavirus 2 antibodies. Overall population death rates among those >50 years of age increased 74% over the first coronavirus disease pandemic year.

High prevalence of urinary schistosomiasis in a desert population: results from an exploratory study around the Ounianga lakes in Chad.

BACKGROUND: Researching a water-borne disease in the middle of the Sahara desert might not seem the most relevant concern. However, nomadic Sahelian pastoralists health concerns regarding their livestock and anecdotal reports about trematode infections of Fasciola spp. and Schistosoma spp. in desert-raised animals justified an exploratory study focusing on the lakes of Ounianga in Northern Chad. The aim was to test whether trematode parasites such as Schistosoma spp. occur in human populations living around the Sahara desert lakes of Ounianga Kebir and Ounianga Serir in northern Chad. METHODS: The study was carried out in January 2019 and comprised of three components. First, a cross sectional survey based on a random sample drawn from the population to detect infections with S. haematobium and S. mansoni; second, focus group discussions exploring disease priorities, access to health and health seeking behaviour; and third, surveying water contact sites for intermediate host snails. Samples of trematode parasites and snails were confirmed on species level by molecular genetic methods. For parasitological and malacological surveys descriptive statistics were performed. Qualitative data analysis included the full review of all transcripts, followed by a descriptive and explorative thematic analysis. RESULTS: Among 258 participants, the overall S. haematobium prevalence using urine filtration was 39.2% [95% confidence interval (CI): 33.5-45.1%], with 51.5% of the infected suffering from heavy infection. The intermediate host snail of S. haematobium (Bulinus truncatus) occurred at water contact sites near both study villages, revealing the potential for local transmission. Although a positive S. mansoni point-of-care circulating cathodic antigen (POC-CCA) test result was obtained from 8.6% (95% CI 5.7-12.8%) of the samples, no intermediate host snails of S. mansoni were found, and the relevance of S. mansoni remains uncertain. Qualitative findings underline the importance of morbidity caused by urinary schistosomiasis, and the lack of access to diagnostics and treatment as a major health concern. CONCLUSIONS: This research revealed a high prevalence of urinary schistosomiasis in the population living around the lakes of Ounianga in the Sahara, a United Nations Educational, Scientific and Cultural Organization (UNESCO) world heritage site in Chad. Despite the high public health importance of the associated morbidity expressed by the population, there is no access to diagnostics and treatment. Further work is needed to develop and test a context-adapted intervention.

One mean to rule them all? The arithmetic mean based egg reduction rate can be misleading when estimating anthelminthic drug efficacy in clinical trials.

Animal and human helminth infections are highly prevalent around the world, with only few anthelminthic drugs available. The anthelminthic drug performance is expressed by the cure rate and the egg reduction rate. However, which kind of mean should be used to calculate the egg reduction rate remains a controversial issue. We visualized the distributions of egg counts of different helminth species in 7 randomized controlled trials and asked a panel of experts about their opinion on the egg burden and drug efficacy of two different treatments. Simultaneously, we calculated infection intensities and egg reduction rates using different types of means: arithmetic, geometric, trimmed, winsorized and Hölder means. Finally, we calculated the agreement between expert opinion and the different means. We generated 23 different trial arm pairs, which were judged by 49 experts. Among all investigated means, the arithmetic mean showed poorest performance with only 64% agreement with expert opinion (bootstrap confidence interval [CI]: 60-68). Highest agreement of 94% (CI: 86-96) was reached by the Hölder mean M0.2, followed by the geometric mean (91%, CI: 85-94). Winsorized and trimmed means showed a rather poor performance (e.g. winsorization with 0.1 cut-off showed 85% agreement, CI: 78-87), but they performed reasonably well after excluding treatment arms with a small number of patients. In clinical trials with moderate sample size, the currently recommended arithmetic mean does not necessarily rank anthelminthic efficacies in the same order as might be obtained from expert evaluation of the same data. Estimates based on the arithmetic mean should always be reported together with an estimate, which is more robust to outliers, e.g. the geometric mean.

Clinical evaluation for morbidity associated with soil-transmitted helminth infection in school-age children on Pemba Island, Tanzania.

BACKGROUND: More than 1.5 billion people are infected with soil-transmitted helminths (Ascaris lumbricoides, hookworm, Strongyloides stercoralis, and Trichuris trichiura), causing an estimated global burden in excess of 3 million disability-adjusted life years. However, the relationship between soil-transmitted helminth infection, adverse health consequences, and beneficial effects of deworming are not well understood. METHODOLOGY: We pursued a detailed longitudinal clinical evaluation of school-age children to evaluate morbidity associated with soil-transmitted helminth infection and responses to treatment. This exploratory study was embedded into a randomized controlled trial. Overall, 434 children, aged 7-14 years, underwent a detailed medical history, physical examination, stool microscopy for soil-transmitted helminths, and hemoglobin (Hb) measurement at baseline. Medical history and stool examination were repeated at 3 and 18 weeks posttreatment. Additionally, Hb measurement was performed at the 18-week treatment follow-up. Logistic regression was employed to assess clinical factors associated with soil-transmitted helminth infection at baseline, and longitudinal data analysis to examine change in health outcomes following treatment over time. PRINCIPAL FINDINGS: All enrolled children were infected with T. trichiura, and randomized into four different treatment interventions. None of the medical history, physical examination, and laboratory (i.e., Hb) findings were associated with A. lumbricoides, hookworm, or S. stercoralis infection at baseline. A composite of physical exam findings for anemia, including pallor of the conjunctiva, nail beds, and palmar creases predicted lower Hb values (-3.8 g/dl, 95% confidence interval (CI): -6.9, -0.6 g/dl). When examining longitudinal trends, we did not find improvements to Hb or face Wong-Baker Likert scale among children with soil-transmitted helminth infection compared to those without infection, although there was a slight trend toward improving Hb values after treating hookworm infection. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates the challenges of measuring morbidity in the context of soil-transmitted helminth infection and treatment, thus confirming the mainly subtle morbidity effects of infection.

Drug Combinations Against Soil-Transmitted Helminth Infections.

The soil-transmitted helminths (STHs), Ascaris lumbricoides, hookworm and Trichuris trichiura are common in areas with warm and moist climates with little access to adequate water, sanitation, and hygiene affecting the poorest populations. The current control strategy of the World Health Organization is preventive chemotherapy (PC), i.e., the administration of the two benzimidazoles (albendazole and mebendazole) using single, oral doses to at risk populations without prior diagnosis. The recent success of PC is threatened by anthelmintic drug resistance and the low efficacy of the drugs against hookworm (mebendazole) and T. trichiura (albendazole and mebendazole). Only a handful of alternative drugs with anthelmintic properties are available, however, none of the drugs show high efficacy against all three STHs. The combination of two drugs with different activity profiles presents an attractive alternative, which could prevent the development of drug resistance and increase the efficacy compared to monotherapy. In this review, we summarize the efficacy of current and alternative anthelmintics, coadministrations and triple drug therapies assessed by means of network meta-analysis including only randomized controlled trials. Our results highlight that coadministrations have improved efficacy over monotherapy and the necessity of adapting current STH control strategies for the successful continuation of PC programs.

Off-target effects of tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel-pamoate, and albendazole plus oxantel-pamoate on the human gut microbiota.

Soil-transmitted helminths infect 1.5 billion people worldwide. Treatment with anthelminthics is the key intervention but interactions between anthelminthic agents and the gut microbiota have not yet been studied. In this study, the effects of four anthelminthic drugs and combinations (tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel-pamoate, and albendazole plus oxantel-pamoate) on the gut microbiota were assessed. From each hookworm infected adolescent, one stool sample was collected prior to treatment, 24 h post-treatment and 3 weeks post-treatment, and a total of 144 stool samples were analyzed. The gut bacterial composition was analyzed using 16S rRNA gene sequencing. Tribendimidine given alone or together with oxantel-pamoate, and the combination of albendazole and oxantel pamoate were not associated with any major changes in the taxonomic composition of the gut microbiota in this population, at both the short-term post-treatment (24 h) and long-term post-treatment (3 weeks) periods. A high abundance of the bacterial phylum Bacteroidetes was observed following administration of tribendimidine plus ivermectin 24 h after treatment, due predominantly to difference in abundance of the families Prevotellaceae and Candidatus homeothermaceae. This effect is transient and disappears three weeks after treatment. Higher abundance of Bacteroidetes predicts an increase in metabolic pathways involved in the synthesis of B vitamins. This study highlights a strong relationship between tribendimidine and ivermectin administration and the gut microbiota and additional studies assessing the functional aspects as well as potential health-associated outcomes of these interactions are required.

Preventive Chemotherapy in the Fight against Soil-Transmitted Helminthiasis: Achievements and Limitations.

Soil-transmitted helminths (STHs) are endemic in more than half of the world's countries. The World Health Organization has advocated targeted preventive chemotherapy (PC) to control STH infections by distributing albendazole or mebendazole to at-risk populations. While the overall impact and sustainability of this strategy is disputed, a decrease in moderate and heavy STH infections can be largely attributed to a scale-up of drug distribution. Two factors might jeopardise the success of PC programs. First, the benzimidazoles possess unsatisfactory efficacy against Trichuris trichiura infections. Second, increased drug distributions might trigger anthelmintic resistance. This review presents an overview of the burden of STH infections, the evolution of PC along with its success and challenges, recent estimates of the efficacy of recommended drugs, and alternative treatment options.

Diagnostic comparison between FECPAKG2 and the Kato-Katz method for analyzing soil-transmitted helminth eggs in stool.

BACKGROUND: Over one billion people are infected with soil-transmitted helminths (STH), i.e. Ascaris lumbricoides, hookworm and Trichuris trichiura. For estimating drug efficacy and monitoring anthelminthic drug resistance, accurate diagnostic methods are critical. FECPAKG2 is a new remote-diagnostic tool used in veterinary medicine, which produces an image of the stool sample that can be stored on an internet cloud. We compared for the first time FECPAKG2 with the recommended Kato-Katz method. METHODOLOGY/PRINCIPAL FINDINGS: Two stool samples were collected from adolescent participants (age 15-18 years) at baseline and 14 to 21 days after treatment in the framework of a randomized clinical trial on Pemba Island, Tanzania. Stool samples were analyzed with different diagnostic efforts: i) one or ii) two Kato-Katz thick smears from the first sample, iii) two Kato-Katz thick smears from two samples and iv) FECPAKG2 from the first sample. Parameters were calculated based on a hierarchical Bayesian egg count model. Complete data for all diagnostic efforts were available from 615 participants at baseline and 231 hookworm-positive participants at follow-up. At baseline FECPAKG2 revealed a sensitivity of 75.6% (72.0-77.7) for detecting A. lumbricoides, 71.5% (67.4-95.3) for hookworm and 65.8% (64.9-66.2) for T. trichiura, which was significantly lower (all p<0.05) than any of the Kato-Katz methods and highly dependent on infection intensity. Despite that the egg counts based on FECPAKG2 were relatively lower compared to Kato-Katz by a ratio of 0.38 (0.32-0.43) for A. lumbricoides, 0.36 (0.33-0.40) for hookworm and 0.08 (0.07-0.09) for T. trichiura, the egg reduction rates (ERR) were correctly estimated with FECPAKG2. CONCLUSIONS/SIGNIFICANCE: The sensitivity to identify any STH infection was considerably lower for FECPAKG2 compared to Kato-Katz. Following rigorous development, FECPAKG2 might be an interesting tool with unique features for epidemiological and clinical studies.

Efficacy and tolerability of triple drug therapy with albendazole, pyrantel pamoate, and oxantel pamoate compared with albendazole plus oxantel pamoate, pyrantel pamoate plus oxantel pamoate, and mebendazole plus pyrantel pamoate and oxantel pamoate against hookworm infections in school-aged children in Laos: a randomised, single-blind trial.

BACKGROUND: Albendazole and mebendazole are commonly used to control hookworm, but have shortcomings in their efficacy profiles. We assessed whether triple drug therapy (TDT) with albendazole, pyrantel pamoate, and oxantel pamoate was more effective than the co-administration of two drugs for the treatment of hookworm infections. METHODS: A randomised, single-blind trial was done from Sept 27 until Nov 17, 2017, in Laos. Children (6-15 years) from six schools were invited to participate. Hookworm-positive children were randomly assigned (2:2:1:1) by a computer stratified list (block sizes of six and 12) to TDT with albendazole (400 mg), pyrantel pamoate (20 mg/kg), and oxantel pamoate (20 mg/kg); albendazole plus oxantel pamoate; pyrantel pamoate plus oxantel pamoate; or mebendazole (500 mg) combined with both pyrantel pamoate and oxantel pamoate (used as proof of concept to compare the two TDTs). Two stool samples were collected at baseline and follow-up (17-30 days after treatment) and analysed with the Kato-Katz method. The primary outcome was the proportion of hookworm egg-negative children at follow-up in all Kato-Katz slides (cure rate [CR]) in the TDT with albendazole, pyrantel pamoate, and oxantel pamoate group compared with the albendazole plus oxantel pamoate and pyrantel pamoate plus oxantel pamoate groups. Secondary outcomes were tolerability 3 h and 24 h after treatment, egg reduction rates (ERRs) against hookworm, and efficacy against concomitant soil-transmitted helminth infections. Participating children and field and laboratory technicians were masked to treatment allocation. All children with follow-up data were included in the primary analysis. This trial is registered with ClinicalTrials.gov, number NCT03278431. FINDINGS: 1529 children were assessed for eligibility, of whom 533 provided complete baseline data and 414 provided complete outcome data. The CR was higher for the TDT albendazole, pyrantel pamoate, and oxantel pamoate (116 [84%] of 138) than with albendazole plus oxantel pamoate (73 [53%] of 138; odds ratio 4·7, 95% CI 2·7-8·3; p<0·0001) and pyrantel pamoate plus oxantel pamoate (36 [52%] of 69; 4·8, 2·5-9·3; p<0·0001). The geometric ERR of the TDT albendazole, pyrantel pamoate, and oxantel pamoate (99·9%) was higher than that for albendazole plus oxantel pamoate (99·0%; difference in ERR 0·9 percentage points, 95% CI 0·5-1·4), and pyrantel pamoate plus oxantel pamoate (99·2%; 0·7 percentage points, 0·3-1·3). Adverse events were reported by six (1%) children 3 h and none 24 h after treatment, without any difference across treatment groups. INTERPRETATION: TDT with albendazole, pyrantel pamoate, and oxantel pamoate could make a difference, in particular in the context of soil-transmitted helminth elimination. Pyrantel pamoate might be a useful alternative to prevent benzimidazole resistance; however, larger trials are needed to confirm this finding. FUNDING: Swiss National Science Foundation.

Efficacy and safety of tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel pamoate, and albendazole plus oxantel pamoate against hookworm and concomitant soil-transmitted helminth infections in Tanzania and Côte d'Ivoire: a randomised, controlled, single-blinded, non-inferiority trial.

BACKGROUND: Preventive chemotherapy is the current strategy to control soil-transmitted helminth infections (caused by Ascaris lumbricoides, hookworm, and Trichuris trichiura). But, to improve efficacy and avoid emerging resistance, new drugs are warranted. Tribendimidine has shown good anthelmintic efficacy and is therefore a frontrunner for monotherapy and combination chemotherapy. METHODS: We did a randomised, controlled, single-blinded, non-inferiority trial on Pemba Island, Tanzania, and in Côte d'Ivoire. We recruited adolescents aged 15-18 years from four primary schools on Pemba, and school attendees and non-schoolers from two districts in Côte d'Ivoire. Only hookworm-positive participants were randomly assigned (1:1:1:1) to single, oral doses of tribendimidine 400 mg plus placebo (tribendimidine monotherapy), tribendimidine 400 mg plus ivermectin 200 µg/kg, tribendimidine 400 mg plus oxantel pamoate 25 mg/kg, or albendazole 400 mg plus oxantel pamoate 25 mg/kg. Randomisation was done via a computer-generated list in block sizes of four or eight. Participants were asked to provide two stool samples on 2 consecutive days at baseline and again 14-21 days at follow-up. The primary outcome was the difference in egg-reduction rates (ERRs; ie, the geometric mean reduction) in hookworm egg counts between treatment groups, measured by the Kato-Katz technique. Differences in coadministrated treatment groups were assessed for non-inferiority with a margin of -3% to albendazole plus oxantel pamoate based on the available-case population, analysed by intention to treat. Safety was assessed 3 h and 24 h after treatment. This study is registered with ISRCTN (number 14373201). FINDINGS: Between July 26, and Dec 23, 2016, we treated 636 hookworm-positive participants, and outcome data were available for 601 participants (151 assigned to tribendimidine monotherapy, 154 to tribendimidine plus ivermectin, 148 to tribendimidine plus oxantel pamoate, and 148 to albendazole plus oxantel pamoate). Tribendimidine plus ivermectin was non-inferior to albendazole plus oxantel pamoate (ERRs 99·5% [95% CI 99·2-99·7] vs 96·0% [93·9-97·4]; difference 3·52 percentage points [2·05-5·65]). Likewise, tribendimidine plus oxantel pamoate was non-inferior to albendazole plus oxantel pamoate (ERRs 96·5% [95% CI 94·9 to 97·6] vs 96·0% [93·9 to 97·4]; difference 0·48 percentage points [-1·61 to 2·88]). 3 h after treatment, headache (n=50 [8%]) and vertigo (n=37 [6%]) were the most widely reported symptoms; 24 h after treatment, 50 (8%) patients reported vertigo and 41 (7%) reported headache. Mainly mild adverse events were reported with peak numbers (n=111 [18%]) at 24 h after treatment. Three participants had moderate adverse events 3 h after treatment: two (<1%) had vertigo and one (<1%) had headache, and two had moderate adverse events 24 h after treatment: one (<1%) had vomiting and one (<1%) had vomiting plus diarrhoea. INTERPRETATION: Tribendimidine in combination with either ivermectin or oxantel pamoate had a similar, non-inferior efficacy profile as albendazole plus oxantel pamoate, hence tribendimidine will be a useful addition to the depleted anthelmintic drug armamentarium. FUNDING: Swiss National Science Foundation.

Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta-analysis.

Objective To evaluate efficacies of anthelmintic drugs against soil transmitted helminths in terms of cure rates and egg reduction rates.Design Systematic review and network meta-analysis.Data Sources PubMed, ISI Web of Science, Embase, ScienceDirect, the Cochrane Central Register of Clinical Trials, and the World Health Organization library database from 1960 until 31 December 2016.Study selection Randomised controlled trials evaluating the efficacy of a single dose regimen of albendazole, mebendazole, levamisole, and pyrantel pamoate against Ascaris lumbricoides, hookworm (Necator americanus and Ancylostoma duodenale) and Trichuris trichiura. The primary outcomes included cure rates analysed by network meta-analysis with mixed logistic regression models and egg reduction rates with mixed linear models.Results 55 and 46 randomised controlled trials were included in the analysis of cure rates and egg reduction rates, respectively. All drugs were highly efficacious against A lumbricoides Albendazole showed the highest efficacy against hookworm infections with a cure rate of 79.5% (95% confidence interval 71.5% to 85.6%) and an egg reduction rate of 89.6% (81.9% to 97.3%). All drugs had low efficacy against T trichiura, with mebendazole showing the highest cure rate of 42.1% (25.9% to 60.2%) and egg reduction rate of 66.0% (54.6% to 77.3%). Estimates for the years 1995 and 2015 showed significant reductions in efficacy of albendazole against T trichiura: by 2015 the egg reduction rates fell from 72.6% (53.7% to 91.5%) to 43.4% (23.5% to 63.3%; P=0.049) and the cure rates fell from 38.6% (26.2% to 52.7%) to 16.4 (7.7% to 31.3%; P=0.027).Conclusions All four currently recommended drugs show limitations in their efficacy profile. While only albendazole showed good efficacy against hookworm infection, all drugs had low efficacy against T trichiura The decrease in efficacy of albendazole against T trichiura over the past two decades is of concern. The findings indicate the need for strengthening efforts to develop new drug treatments, with a particular focus on drugs against T trichiura.

Unexpected low soil-transmitted helminth prevalence in the Butha-Buthe district in Lesotho, results from a cross-sectional survey.

BACKGROUND: Soil-transmitted helminth (STH) infections with Ascaris lumbricoides, hookworm and Trichuris trichiura affect large parts of the world's population. For the implementation of national STH control programs, e.g. preventive chemotherapy (treatment with albendazole and mebendazole), the spatial distribution and prevalence of STH infections must be known. However, for Lesotho only little data were available and the STH distribution remains largely unknown. METHODS: In early 2016, a cross-sectional parasitological STH survey was conducted including six different primary schools in the Butha-Buthe district of Lesotho. In each school stool samples were collected from 50 children (age 8-14 years) and analysed with a duplicate Kato-Katz thick smear for the presence of A. lumbricoides, hookworm and T. trichiura. RESULTS: A total of 301 children provided a stool sample. All children were negative for A. lumbricoides and T. trichiura. Only two children from one primary school showed a light hookworm infection. CONCLUSION: Our data indicate a low prevalence of STH infections in the Butha-Buthe district of Lesotho. Additional parasitological surveys on the prevalence and the spatial distributions of STH infections across the entire country of Lesotho are needed.

Efficacy and reinfection with soil-transmitted helminths 18-weeks post-treatment with albendazole-ivermectin, albendazole-mebendazole, albendazole-oxantel pamoate and mebendazole.

BACKGROUND: Preventive chemotherapy with albendazole or mebendazole is the current strategy to control soil-transmitted helminth (STH) infections (i.e. Ascaris lumbricoides, hookworm and Trichuris trichiura). STH reinfections, in particular A. lumbricoides and T. trichiura occur rapidly after treatment with the standard drugs. However, their low efficacy against T. trichiura, made an accurate assessment of reinfection patterns impossible. METHODS: In 2013 a randomised controlled trial was conducted on Pemba Island, Tanzania. School-aged children diagnosed positive for T. trichiura, were randomly allocated to (i) albendazole-ivermectin; (ii) albendazole-mebendazole; (iii) albendazole-oxantel pamoate; or (iv) mebendazole. Here we report the efficacy [cure rates (CR) and egg-reduction rates (ERR)], reinfection rates and new infections determined 18 weeks post-treatment. RESULTS: For a total of 405 children complete baseline and follow-up data were available. Similar to the efficacy determined after 3 weeks, 18 weeks after treatment albendazole-oxantel pamoate showed a significantly higher efficacy against T. trichiura (CR: 54.0 %, 95 % CI: 43.7-64.0; ERR: 98.6 %, 95 % CI: 97.8-99.2) compared to the other treatment arms. Children treated with albendazole-oxantel pamoate or albendazole-ivermectin had fewer moderate infections compared to children treated with albendazole. The reinfection rates 18 weeks post-treatment among all treatment arms were 37.2 % for T. trichiura (95 % CI: 28.3-46.8), 34.6 % for A. lumbricoides (95 % CI: 27.3-42.3) and 25.0 % for hookworms (95 % CI: 15.5-36.6). CONCLUSION: The moderate reinfection rates with STHs 18 weeks post-treatment support the concept of regular anthelminthic treatment in highly endemic settings. Combination chemotherapy might achieve decreased morbidity in children since in the albendazole plus oxantel pamoate and albendazole plus ivermectin treatment arms only few moderate T. trichiura infections remained. Further trials should investigate the long term efficacy of albendazole-oxantel pamoate (i.e. 6 and 12 month post-treatment) and after several rounds of treatment in order to develop recommendations for appropriate control approaches for STH infections. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80245406.

Efficacy and safety of oxantel pamoate in school-aged children infected with Trichuris trichiura on Pemba Island, Tanzania: a parallel, randomised, controlled, dose-ranging study.

BACKGROUND: Commonly used drugs for preventive chemotherapy against soil-transmitted helminths (ie, albendazole and mebendazole) show low efficacy against Trichuris trichiura. Recent studies with oxantel pamoate revealed good cure rates and high egg-reduction rates against T trichiura. We aimed to assess the nature of the dose-response relation to determine the optimum dose. METHODS: We did a parallel, randomised, placebo-controlled, single-blind trial with oxantel pamoate in school-aged children (aged 6-14 years) infected with T trichiura on Pemba Island, Tanzania. Children were asked to provide two stool samples and children positive for T trichiura were eligible to participate in the trial. Children were excluded if they suffered from any systematic illness. Children were randomly assigned to six different oxantel pamoate doses (5-30 mg/kg) or a placebo. Randomisation was stratified by baseline infection intensity using random block sizes of seven and 14. The primary endpoints were cure rates and egg-reduction rates against T trichiura, both analysed by available case. Drug safety was assessed 2 h and 24 h after treatment. The trial is registered at www.isrctn.com, number ISRCTN86603231. FINDINGS: Between Oct 14, and Nov 28, 2014, we enrolled 480 participants and randomly assigned 350 children to the different oxantel pamoate doses or the placebo. 5 mg/kg oxantel pamoate was the minimum effective dose (10 of 46 children cured [cure rate 22%, 95% CI 11-36]; egg-reduction rate 85·0%, 64·5-92·9). An increased probability of being cured and reduced egg counts with escalating doses was recorded. At 25 mg/kg oxantel pamoate 27 of 45 children were cured (cure rate 60%, 95% CI 44-65) with an egg-reduction rate of 97·5% (94·4-98·9), and at 30 mg/kg 27 of 46 children were cured (59%, 43-73) with an egg-reduction rate of 98·8% (96·8-99·6). Oxantel pamoate was well tolerated across all treatment groups; only mild adverse events were reported by the participants 2 h (27 [10%]) and 24 h (12 [4%]) after treatment. INTERPRETATION: Our dose-finding study revealed an excellent tolerability profile of oxantel pamoate in children infected with T trichiura. An optimum therapeutic dose range of 15-30 mg/kg oxantel pamoate was defined. With a weight independent dose of 500 mg oxantel pamoate 95% of children aged 7-14 years in sub-Saharan Africa would receive doses of 11·7-32·0 mg/kg. Future research should include studies with oxantel pamoate in younger children and on different continents with the ultimate goal to be able to add oxantel pamoate to soil-transmitted helminth control programmes. FUNDING: Swiss National Science Foundation.

The spatial and seasonal distribution of Bulinus truncatus, Bulinus forskalii and Biomphalaria pfeifferi, the intermediate host snails of schistosomiasis, in N'Djamena, Chad.

There is a paucity of epidemiological and malacological data pertaining to schistosomiasis in Chad. In view of a recently articulated elimination agenda, a deeper understanding of the spatio-temporal distribution of schistosomiasis intermediate host snails is pivotal. We conducted cross-sectional malacological surveys during the dry season (April/May 2013) and after the short rainy season (October 2013) in N'Djamena, the capital of Chad. Snails were identified at the genus and species level using morphological keys and molecular DNA barcoding approaches. Those belonging to Bulinus and Biomphalaria were examined for cercarial shedding. Snail habitats were characterised and their predictive potential for the presence of schistosomiasis intermediate host snails explored. Seasonal patterns were studied using geographical information system and kriging in order to interpolate snail abundance data to make predictions at non-sampled locations across N'Djamena. Overall, 413 Bulinus truncatus, 369 Bulinus forskalii and 108 Biomphalaria pfeifferi snails were collected and subjected to cercarial shedding. During the dry season, one Bu. truncatus of 119 snails collected shed Schistosoma spp. cercariae (0.84%), while S. mansoni was shed by one of 108 Bi. pfeifferi snails (0.93%). None of the snails collected after the rainy season shed Schistosoma spp. cercariae. The abundance of Bu. truncatus and Bu. forskalii showed an inverse U-shape relationship with the square term of conductivity, i.e. low abundance at the lowest and highest levels of conductivity and high abundance at intermediate levels. Bi. pfeifferi showed a negative, linear association with pH in the dry seasons. It is planned to link these intermediate host snail data to infection data in human populations with the goal to draw a predictive risk map that can be utilised for control and elimination of schistosomiasis in N'Djamena.