Efficacy and safety of moxidectin, synriam, synriam-praziquantel versus praziquantel against schistosoma haematobium and S. mansoni infections: a randomized, exploratory phase 2 trial

Schistosomiasis affects millions of people, yet treatment options are limited. The antimalarial Synriam (piperaquine 150 mg/arterolane 750 mg) and the anthelminthic moxidectin revealed promising antischistosomal properties in preclinical or clinical studies.; We conducted two single-blind, randomized exploratory Phase 2 trials in Schistosoma mansoni and S. haematobium-infected adolescents in northern and central Côte d'Ivoire. Our primary endpoints were cure rates (CRs) and egg reduction rates (ERRs) based on geometric mean and safety. Each subject was asked to provide two stool samples (S. mansoni trial) for Kato-Katz analysis or three urine samples (S. haematobium trial) for urine filtration and one finger prick for malaria screening at baseline and follow-up. Participants were randomly assigned to either moxidectin, Synriam, Synriam plus praziquantel or praziquantel.; 128 adolescents (age: 12-17 years) were included in each study. Against S. haematobium moxidectin and Synriam revealed low efficacy. On the other hand, Synriam plus praziquantel and praziquantel yielded CRs of 60.0% and 38.5% and ERRs of 96.0% and 93.5%, respectively. CRs observed in the treatment of S. mansoni were 13.0%, 6.7%, 27.0%, and 27.6% for moxidectin, Synriam, Synriam plus praziquantel and praziquantel, respectively. ERRs ranged from 64.9% (Synriam) to 87.5% (praziquantel).; Synriam and moxidectin show low efficacy against S. haematobium, hence an ancillary benefit is not expected when these drugs are used for treating onchocerciasis and malaria in co-endemic settings. Further studies are needed to corroborate our findings that moxidectin and Synriam show moderate ERRs against S. mansoni

Herbivore Impact Versus Host Size Preference: Endophagous Insects on Heracleum mantegazzianum in Its Native Range

Classical biological control is a practice to control alien invasive weeds, but many introduced biological control agents exhibit only a weak negative impact on their targets. One reason is that prerelease impact studies in the natural environment are often difficult to carry out. Heracleum mantegazzianum Sommier and Levier (Apiaceae), which is native to the Caucasus, is a perennial noxious weed introduced into Europe and North America. We examined the impact and host size preference of different endophagous insect guilds in the weed's native range. Instead of the commonly used insect exclosure approach, we estimated plant vigor before and after herbivore attack under natural conditions. Endophagous herbivores were dominated by the weevil species Lixus iridis Olivier, Nastus fausti Reitter, and Otiorhynchus tatarchani Reitter (Coleoptera: Curculionidae), the fly Melanagromyza heracleana Zlobin (Diptera: Agromyzidae), and an unidentified root-boring agromyzid fly species. Most observed insect species exhibited a strong preference for either big or small plants, but none of them caused serious damage within the study period. Occurrence of root-feeding weevils was associated with weak plants, but because of their long larval development, it was not possible to assign this relationship clearly to either feeding damage or host size preference. A comparison with other studies indicated that mature H. mantegazzianum plants are quite tolerant to herbivory. Insects belonging to the feeding guilds studied here will probably not guarantee successful biological control. Further research should focus on earlier stages in the weed's life cycl

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

Molecular epidemiology of Mycobacterium africanum in Ghana

BACKGROUND: Mycobacterium africanum comprises two phylogenetic lineages within the M. tuberculosis complex (MTBC) and is an important cause of human tuberculosis (TB) in West Africa. The reasons for this geographic restriction of M. africanum remain unclear. Here, we performed a prospective study to explore associations between the characteristics of TB patients and the MTBC lineages circulating in Ghana. METHOD: We genotyped 1,211 MTBC isolates recovered from pulmonary TB patients recruited between 2012 and 2014 using single nucleotide polymorphism typing and spoligotyping. Associations between patient and pathogen variables were assessed using univariate and multivariate logistic regression. RESULTS: Of the 1,211 MTBC isolates analysed, 71.9 % (871) belonged to Lineage 4; 12.6 % (152) to Lineage 5 (also known as M. africanum West-Africa 1), 9.2 % (112) to Lineage 6 (also known as M. africanum West-Africa 2) and 0.6 % (7) to Mycobacterium bovis. Univariate analysis revealed that Lineage 6 strains were less likely to be isoniazid resistant compared to other strains (odds ratio = 0.25, 95 % confidence interval (CI): 0.05-0.77, P < 0.01). Multivariate analysis showed that Lineage 5 was significantly more common in patients from the Ewe ethnic group (adjusted odds ratio (adjOR): 2.79; 95 % CI: 1.47-5.29, P < 0.001) and Lineage 6 more likely to be found among HIV-co-infected TB patients (adjOR = 2.2; 95 % confidence interval (CI: 1.32-3.7, P < 0.001). CONCLUSION: Our findings confirm the importance of M. africanum in Ghana and highlight the need to differentiate between Lineage 5 and Lineage 6, as these lineages differ in associated patient variables

Albendazole and Mebendazole Administered Alone or in Combination with Ivermectin against Trichuris trichiura: A Randomized Controlled Trial

Background. Single-dose albendazole and mebendazole show limited efficacy in the treatment of trichuriasis. The combination of albendazole with ivermectin improves efficacy, but a mebendazole-ivermectin combination has not been previously investigated. Methods. We performed a randomized controlled trial in 2 schools in Zanzibar, Tanzania, to assess the efficacy and safety of albendazole (400 mg) plus placebo, albendazole plus ivermectin (200 µg/kg), mebendazole (500 mg) plus placebo, and mebendazole plus ivermectin in children with a parasitologically confirmed Trichuris trichiura infection. Cure rate (CR) and egg reduction rate were assessed by intent-to-treat analysis. Adverse events were monitored within 48 h after treatment. Results. Complete data records were available for 548 children. The highest CR against T. trichiura was achieved with a mebendazole-ivermectin combination (55%). Low CRs were observed with albendazole-ivermectin (38%), mebendazole (19%), and albendazole (10%). Compared with placebo, the use of ivermectin statistically significantly increased the CRs from 14% to 47% (odds ratio, 0.19; 95% confidence interval [CI], 0.12-0.28). The highest egg reduction rate (97%; 95% CI, 95%-98%) was observed using the mebendazole-ivermectin combination, followed by albendazole-ivermectin (91%; 95% CI, 87%-94%), mebendazole (67%; 95% CI, 52%-77%), and albendazole (40%; 95% CI, 22%-56%). The adverse events, reported by 136 children, were generally mild, with no significant difference between the treatment arms. Conclusions. Addition of ivermectin improves the therapeutic outcomes of both albendazole and mebendazole against T. trichiura and may be considered for use in soil-transmitted helminth control programs and individual patient management. Trial registration. isrctn.org Identifier: ISRCTN0833660

Albendazole and Mebendazole Administered Alone or in Combination with Ivermectin against Trichuris trichiura: A Randomized Controlled Trial

Background. Single-dose albendazole and mebendazole show limited efficacy in the treatment of trichuriasis. The combination of albendazole with ivermectin improves efficacy, but a mebendazole-ivermectin combination has not been previously investigated. Methods. We performed a randomized controlled trial in 2 schools in Zanzibar, Tanzania, to assess the efficacy and safety of albendazole (400 mg) plus placebo, albendazole plus ivermectin (200 µg/kg), mebendazole (500 mg) plus placebo, and mebendazole plus ivermectin in children with a parasitologically confirmed Trichuris trichiura infection. Cure rate (CR) and egg reduction rate were assessed by intent-to-treat analysis. Adverse events were monitored within 48 h after treatment. Results. Complete data records were available for 548 children. The highest CR against T. trichiura was achieved with a mebendazole-ivermectin combination (55%). Low CRs were observed with albendazole-ivermectin (38%), mebendazole (19%), and albendazole (10%). Compared with placebo, the use of ivermectin statistically significantly increased the CRs from 14% to 47% (odds ratio, 0.19; 95% confidence interval [CI], 0.12-0.28). The highest egg reduction rate (97%; 95% CI, 95%-98%) was observed using the mebendazole-ivermectin combination, followed by albendazole-ivermectin (91%; 95% CI, 87%-94%), mebendazole (67%; 95% CI, 52%-77%), and albendazole (40%; 95% CI, 22%-56%). The adverse events, reported by 136 children, were generally mild, with no significant difference between the treatment arms. Conclusions. Addition of ivermectin improves the therapeutic outcomes of both albendazole and mebendazole against T. trichiura and may be considered for use in soil-transmitted helminth control programs and individual patient management. Trial registration. isrctn.org Identifier: ISRCTN0833660

Prevalence of bovine tuberculosis and risk factor assessment in cattle in rural livestock areas of Govuro District in the Southeast of Mozambique

BACKGROUND: Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is an infectious disease of cattle that also affects other domestic animals, free-ranging and farmed wildlife, and also humans. In Mozambique, scattered surveys have reported a wide variation of bTB prevalence rates in cattle from different regions. Due to direct economic repercussions on livestock and indirect consequences for human health and wildlife, knowing the prevalence rates of the disease is essential to define an effective control strategy. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study was conducted in Govuro district to determine bTB prevalence in cattle and identify associated risk factors. A representative sample of the cattle population was defined, stratified by livestock areas (n = 14). A total of 1136 cattle from 289 farmers were tested using the single comparative intradermal tuberculin test. The overall apparent prevalence was estimated at 39.6% (95% CI 36.8-42.5) using a diagnostic threshold cut-off according to the World Organization for Animal Health. bTB reactors were found in 13 livestock areas, with prevalence rates ranging from 8.1 to 65.8%. Age was the main risk factor; animals older than 4 years were more likely to be positive reactors (OR = 3.2, 95% CI: 2.2-4.7). Landim local breed showed a lower prevalence than crossbred animals (Landim × Brahman) (OR = 0.6, 95% CI: 0.4-0.8). CONCLUSIONS/SIGNIFICANCE: The findings reveal an urgent need for intervention with effective, area-based, control measures in order to reduce bTB prevalence and prevent its spread to the human population. In addition to the high prevalence, population habits in Govuro, particularly the consumption of raw milk, clearly may potentiate the transmission to humans. Thus, further studies on human tuberculosis and the molecular characterization of the predominant strain lineages that cause bTB in cattle and humans are urgently required to evaluate the impact on human health in the region.The research leading to these results has received funding from the European Union's Seventh Framework Program (FP7/2007-2013) under grant agreement no 221948, ICONZ (Integrated Control of Neglected Zoonoses). The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Chapitre 10 - Conception d’études One Health

Qu’est-ce qu’une étude One Health ? Les études épidémiologiques sur la santé humaine et animale utilisent des enquêtes sur le terrain ou des analyses de données secondaires. La collecte et l’interprétation des données se font traditionnellement dans les secteurs de la santé animale et humaine et à des périodes différentes, mais aussi lorsque le même sujet de santé est abordé, ce qui entraîne une duplication inutile des études su..

Efficacy and safety of ascending dosages of albendazole against Trichuris trichiura in preschool-aged children, school-aged children and adults: a multi-cohort randomized controlled trial

The efficacy of the widely used albendazole against the soil-transmitted helminth; Trichuris trichiura; is limited; yet optimal doses, which may provide increased efficacy, have not been thoroughly investigated to date.; A randomized-controlled trial was conducted in Côte d'Ivoire with preschool-aged children (PSAC), school-aged children (SAC), and adults infected with; T. trichiura; . Participants were randomly assigned (1:1:1:1) using computer-generated randomization. PSAC were randomized to 200 mg, 400 mg, 600 mg of albendazole or placebo. SAC and adults were randomized to 400 mg, 600 mg, 800 mg of albendazole or placebo. The primary outcome was cure rates (CRs) against trichuriasis. Secondary outcomes were; T. trichiura; egg reduction rates (ERRs), safety, CRs and ERRs against other soil-transmitted helminths. Outcome assessors and the trial statistician were blinded. Trial registration at ClinicalTrial.gov: NCT03527745.; 111 PSAC, 180 SAC, and 42 adults were randomized and 86, 172, and 35 provided follow-up stool samples, respectively. The highest observed CR among PSAC was 27·8% (95% CI: 9·7%-53·5%) in the 600 mg albendazole treatment arm. The most efficacious arm for SAC was 600 mg of albendazole showing a CR of 25·6% (95% CI: 13·5%-41·2%), and for adults it was 400 mg of albendazole with a CR of 55·6% (95% CI: 21·2%-86·3%). CRs and ERRs did not differ significantly among treatment arms and flat dose-responses were observed. 17·9% and 0·4% of participants reported any adverse event at 3 and 24 h follow-up, respectively.; Albendazole shows low efficacy against; T. trichiura; in all populations and doses studied, though findings for PSAC and adults should be carefully interpreted as recruitment targets were not met. New drugs, treatment regimens, and combinations are needed in the management of; T. trichiura; infections.; Bill and Melinda Gates Foundation