Efficacy and safety of praziquantel in preschool-aged children in an area co-endemic for Schistosoma mansoni and S. haematobium

BACKGROUND: In sub-Saharan Africa the recommended strategy to control schistosomiasis is preventive chemotherapy. Emphasis is placed on school-aged children, but in high endemicity areas, preschool-aged children are also at risk, and hence might need treatment with praziquantel. Since a pediatric formulation (e.g., syrup) is not available outside of Egypt, crushed praziquantel tablets are used, but the efficacy and safety of this treatment regimen is insufficiently studied.METHODOLOGY: We assessed the efficacy and safety of crushed praziquantel tablets among preschool-aged children (>6 years) in the Azaguié district, south Côte d'Ivoire, where Schistosoma mansoni and S. haematobium coexist. Using a cross-sectional design, children provided two stool and two urine samples before and 3 weeks after treatment. Crushed praziquantel tablets, mixed with water, were administered at a dose of 40 mg/kg. Adverse events were assessed and graded 4 and 24 hours posttreatment by interviewing mothers/guardians.PRINCIPAL FINDINGS: Overall, 160 preschool-aged children had at least one stool and one urine sample examined with duplicate Kato-Katz thick smears and a point-of-care circulating cathodic antigen (POC-CCA) cassette for S. mansoni, and urine filtration for S. haematobium diagnosis before and 3 weeks after praziquantel administration. According to the Kato-Katz and urine filtration results, we found high efficacy against S. mansoni (cure rate (CR), 88.6%; egg reduction rate (ERR), 96.7%) and S. haematobium (CR, 88.9%; ERR, 98.0%). POC-CCA revealed considerably lower efficacy against S. mansoni (CR, 53.8%). Treatment was generally well tolerated, but moderately severe adverse events (i.e., body and face inflammation), were observed in four Schistosoma egg-negative children. CONCLUSIONS/SIGNIFICANCE: Crushed praziquantel administered to preschool-aged children at a dose of 40 mg/kg is efficacious against S. mansoni and S. haematobium in a co-endemic setting of Côte d'Ivoire. Further research is required with highly sensitive diagnostic tools and safety must be investigated in more depth.TRIAL REGISTRATION: Controlled-Trials.com ISRCTN53172722

Effets de la couverture des cages flottantes et de la période de distribution de l\'aliment sur la survie et la croissance des alevins du poisson-chat africain Heterobranchus longifilis Valenciennes 1840 en élevage intensif

L\'influence du recouvrement des cages flottantes par des bâches plastiques noires non transparentes et de la période (jour ou nuit) de distribution de l\'aliment sur la survie et la croissance du poisson-chat africain Heterobranchus longifilis a été évaluée. L\'expérience a consisté à observer le jour et la nuit des alevins nourris en quatre repas, dans deux types de cages flottantes : cages couvertes et cages non couvertes. Quelle que soit la période de distribution de l\'aliment, les meilleurs taux de survie ont été observés dans les cages couvertes (73,0 ± 2,6 % le jour et 75,0 ± 1,7 % la nuit contre 64,0 ± 3,5 % le jour et 67,0 ± 2,0 % la nuit). Les poids moyens finaux des poissons enregistrés dans ces cages sont de 16,9 ± 1,9 g le jour et 17,8 ± 1,9 g la nuit. Ces poids sont comparables à ceux observés dans les cages non couvertes avec distribution nocturne de l\'aliment (16,8 ± 1,1 g). Ces résultats montrent qu\'en cages couvertes, la période de distribution de l\'aliment n\'a aucune influence sur la croissance des poissons.The effects of covering the breeding floating cages with a black plastic canvas and the feeding period (day or night) on the survival and growth of the african cat-fish Heterobranchus longifilis have been investigated. Juvenile individuals of this species fed four times during daytime and nighttime were reared in two types of floating cages : covered with black plastic canvas and without any canvas. Whatever the feeding period, the best survival rates were recorded in covered cages (73,0 ± 2,6 % for daytime and 75,0 ± 1,7 % for nighttime, against 64,0 ± 3,5 % for daytime and 67,0 ± 2,0 % for nighttime). In these cages, final mean weights of fishes recorded were 16,9 ± 1,9 g for daytime and 17,8 ± 1,9 g for nighttime. These data were similar to those recorded in non covered floating cage with nighttime feeding. Results suggest that there is no effect of the feeding period on the growth of H. longifilis reared in cages with canvas. Keywords: Heterobranchus longifilis, alevinage, cage flottante, éclairement, horaires de nourrissage./Heterobranchus longifilis, fry rearing, floating cage, light, feeding time.Sciences & Nature Vol. 4 (1) 2007: pp. 85-9

Efficacy and safety of albendazole in hookworm-infected preschool-aged children, school-aged children and adults in Côte d'Ivoire: a phase II randomized controlled dose-finding trial

BACKGROUND: Infections with hookworms affect about half a billion people worldwide. Recommended therapy includes 400 mg of albendazole, which is moderately efficacious. Higher doses have been rarely assessed. METHODS: A randomized controlled dose-finding trial was conducted in a low transmission setting in Cote d'Ivoire aiming to recruit 120 preschool-aged children (PSAC), 200 school-aged children (SAC) and 200 adults. Eligible PSAC were randomized 1:1:1 to 200 mg, 400 mg, or 600 mg of albendazole, the other age groups 1:1:1:1:1 to placebo or 200 mg, 400 mg, 600 mg, or 800 mg. The primary outcome was cure rates (CRs) assessed 14-21 days post-treatment by quadruplicate Kato-Katz thick smears. Hyperbolic Emax models were used to determine dose-response. RESULTS: 38 PSAC, 133 SAC, and 196 adults were enrolled. In adults, predicted CRs increased with ascending doses of albendazole with a CR of 74.9% (95% Confidence Interval: 55.6%-87.7%) in the 800 mg arm. Observed CRs increased with ascending doses of albendazole and reached a maximum of 94.1% (95% CI: 80.3%-99.3%). In SAC, the predicted dose-response curve increased marginally with CRs ranging from 64.0% in the 200 mg to 76.0% in the 800 mg arm. Sample size in PSAC was considered too small to derive meaningful conclusions. Only 10.7% and 5.1% of participants reported any adverse event at 3 hours and 24 hours post-treatment, respectively. CONCLUSIONS: A single 800 mg albendazole dose provides higher efficacy against hookworm and is well tolerated in adults and should be considered for community-based strategies targeting adults. For PSAC/SAC, current recommendations suffice

PALUDISME ET PHARMACIENS D’OFFICINE DE BAMAKO, MALI : CONNAISSANCE, ATTITUDES ET PRATIQUES

Objectif : L’objectif de notre étude était d’évaluer l’évolution des connaissances et attitudes pratiques des pharmaciens d’officine dans la lutte contre le paludisme en vue d’une implication des pharmaciens d’officines dans la lutte contre le paludisme. Méthodes : Il s’agissait d’une étude transversale descriptive qui s’est déroulée en deux phases dans les officines privées du district de Bamako, Mali. La première phase de l’étude (enquête initiale) s’est déroulée du mois d’avril à mai 2014, elle a porté sur 55 pharmaciens de la commune III et VI de Bamako. La seconde phase (monitorage) s’est déroulée de novembre 2014 à novembre 2015, après une formation de l’ensemble des pharmaciens d’officine du district de Bamako conformément aux directives du PNLP, qui avait concerné tous les pharmaciens du district de Bamako. Résultats : Cette étude a révélé que certains indicateurs se sont améliorés de manière significative: possession d’un document de la politique nationale ; connaissance des médicaments recommandés pour le paludisme simple ; pratique et vente des tests de diagnostic rapide du paludisme. D’autres indicateurs ont connu une progression: disponibilité des CTA; vente de moustiquaires imprégnées d’insecticide; comportement devant une suspicion de paludisme simple ; comportement devant une suspicion de paludisme grave. Conclusion : Ainsi, une implication des pharmaciens d’officines dans la surveillance épidémiologique palustre pourra diminuer de façon considérable le taux de morbidité et de mortalité liés au paludisme. Nous recommandons aux pharmaciens d’officine la dispensation des antipaludiques conformément aux recommandations du programme national de lutte contre le paludisme

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 four different intervention packages to interrupt transmission of Schistosoma haematobium in a seasonal transmission setting of Cote d'Ivoire. METHODS: Sixty-four localities with a S. haematobium prevalence in school children aged 13-14 years above 4% were randomly assigned to one of four 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] = 0.02 to 0.24). 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 = 0.1 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

Optimizing implementation of preventive chemotherapy against soil-transmitted helminthiasis and intestinal schistosomiasis using high-resolution data: Field-based experiences from Côte d'Ivoire

BACKGROUND: Despite efforts to control neglected tropical diseases (NTDs) using preventive chemotherapy (PC), soil-transmitted helminthiases and schistosomiasis remain widely prevalent in sub-Saharan Africa. The current PC regimen in endemic settings is defined based on health district-level prevalence. This work aims to highlight the need for high-resolution data when elimination, rather than morbidity control, is the targeted goal. METHODOLOGY: Cross-sectional parasitological surveys were conducted from July to August 2019 and from September to October 2019, respectively, across the entire Dabou and Jacqueville health districts in southern Cote d'Ivoire. From every village, 60 school-aged children (6-15 years) were randomly selected and invited to provide one fresh stool sample, whereof duplicate Kato-Katz thick smears were prepared and read by two independent technicians. PRINCIPAL FINDINGS: 4338 school-aged children from 77 villages were screened from the Dabou (n = 2174; 50.12%, 39 villages) and Jacqueville (n = 2164; 49.88%, 38 villages) health districts. The prevalence of any soil-transmitted helminth (STH) infection was 12.47% and 11.09% in the Dabou and Jacqueville health districts, respectively. Species-specific district-level prevalence remained below 10%, varying between 0.51% (hookworm in Jacqueville) and 9.06% (Trichuris trichiura in Dabou). However, when considering sub-districts or villages only, several STH infection hotspots (five sub-districts with >/=20% and four villages with more than 50% infected) were observed. Schistosoma mansoni infection was found in less than 1% of the examined children in each health district. CONCLUSIONS/SIGNIFICANCE: We conclude that keeping health district-level prevalence as a reference for PC implementation leaves many high-risk sub-districts or villages requiring PC (>/=20% prevalence) untreated. To avoid maintaining those high-risk villages as STH reservoirs by skipping control interventions and jeopardizing the successes already achieved in STH control through PC during the past two decades, precision mapping is required. Further investigation is needed to assess cost-efficient approaches to implement small-scale disease surveillance

Efficacy and safety of co-administered ivermectin and albendazole in school-aged children and adults infected with; Trichuris trichiura; in Côte d'Ivoire, Laos, and Pemba Island, Tanzania: a double-blind, parallel-group, phase 3, randomised controlled trial

BACKGROUND: Preventive chemotherapy with albendazole or mebendazole remains one of the cornerstones of soil-transmitted helminth control. However, these drugs are less effective against Trichuris trichiura. Combined ivermectin-albendazole is a promising treatment alternative, yet robust evidence is lacking. We aimed to demonstrate superiority of co-administered ivermectin-albendazole over albendazole monotherapy in three distinct epidemiological settings. METHODS: We conducted a double-blind, parallel-group, phase 3, randomised controlled trial in community members aged 6-60 years infected with T trichiura in Cote d'Ivoire, Laos, and Pemba Island, Tanzania, between Sept 26, 2018, and June 29, 2020. Participants with at least 100 T trichiura eggs per g of stool at baseline were randomly assigned (1:1) using computer-generated randomisation sequences in varying blocks of four, six, and eight, stratified by baseline T trichiura infection intensity, to orally receive either a single dose of ivermectin (200 mug/kg) plus albendazole (400 mg) or albendazole (400 mg) plus placebo. Patients, field staff, and outcome assessors were masked to treatment assignment. The primary outcome was cure rate against T trichiura, defined as the proportion of participants with no eggs in their faeces 14-21 days after treatment, assessed by Kato-Katz thick smears, and analysed in the available-case population according to intention-to-treat principles. Safety was a secondary outcome and was assessed 3 h and 24 h after drug administration. The trial is registered at ClinicalTrials.gov, NCT03527732. FINDINGS: Between Sept 13 and Dec 18, 2019, Jan 12 and April 5, 2019, and Sept 26 and Nov 5, 2018, 3737, 3694, and 1435 community members were screened for trial eligibility in Cote d'Ivoire, Laos, and Pemba Island, respectively. In Cote d'Ivoire, Laos, and Pemba Island, 256, 274, and 305 participants, respectively, were randomly assigned to the albendazole group, and 255, 275, and 308, respectively, to the ivermectin-albendazole group. Primary outcome data were available for 722 participants treated with albendazole and 733 treated with ivermectin-albendazole. Ivermectin-albendazole showed significantly higher cure rates against T trichiura than albendazole in Laos (66% [140 of 213]vs 8% [16 of 194]; difference 58 percentage points, 95% CI 50 to 65, p<0.0001) and Pemba Island (49% [140 of 288]vs 6% [18 of 293], 43 percentage points, 36 to 49, p<0.0001) but had similar efficacy in Cote d'Ivoire (14% [32 of 232]vs 10% [24 of 235], 4 percentage points, -2 to 10, p=0.24). No serious adverse events were reported; observed events were mostly classified as mild (95% [266 of 279] in the albendazole group and 91% [288 of 317] in the ivermectin-albendazole group), and all were transient in nature. INTERPRETATION: Treatment with ivermectin-albendazole resulted in higher efficacy against trichuriasis than albendazole alone in Laos and Pemba Island but not in Cote d'Ivoire. We recommend implementation of this combination therapy for soil-transmitted helminth control in countries with high T trichiura prevalence and proven enhanced efficacy of this treatment, particularly where ivermectin is beneficial against other endemic helminthiases. FUNDING: Bill & Melinda Gates Foundation

Assessment of fecal calprotectin and fecal occult blood as point-of-care markers for soil-transmitted helminth attributable intestinal morbidity in a case-control substudy conducted in Côte d'Ivoire, Lao PDR and Pemba Island, Tanzania

Background: Infections with soil-transmitted helminths (STHs) may result in chronic inflammatory disorders affecting the human host. The objective of this study was to evaluate Fecal Calprotectin (FC) and Fecal Occult Blood (FOB) in individuals infected and non-infected with STHs to identify potential intestinal morbidity markers. Methods: Stool from participants diagnosed positive for Trichuris trichiura and concomitant STH infections from three countries was used to perform FC and FOB point-of-care assays. Simultaneously, identified STH negative participants underwent FC and FOB testing as controls. Potential associations between test results and determinants were analyzed using multivariable logistic regression. Findings: In total, 1034 T. trichiura infected cases (mostly light infections) and 157 STH negative controls were tested for FC and FOB. Among all participants tested, 18.5% had >/= 50 microg/g FC concentration, while 14 (1.2%) were positive for FOB. No statistically significant association was found between T. trichiura infection or Ascaris lumbricoides co-infection and FC concentration, while an inverse association (odds ratio (OR): 0.45, 95% credible intervals (CrI): 0.26, 0.75) was found between hookworm co-infection and FC concentration. In Lao PDR, the proportion of participants in the >/= 50 microg/g FC category was significantly higher in the oldest age category compared to the 5-11 years group (OR: 3.31, 95% CrI: 1.62, 7.24). Too few participants were found positive for FOB to derive any conclusions. Interpretation: Studies are needed to better understand the relationship between intestinal morbidity and STH infections. Suitable, standardized, low-cost markers of STH attributable morbidity to better monitor the impact of STH control interventions are necessary. Funding: BMGF (OPP1153928)