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

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..

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 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

Rabies immunoglobulin: brief history and recent experiences in Côte D'Ivoire

Rabies is a fatal viral zoonosis mainly transmitted via dog bites. The estimated 59'000 annual deaths caused by the disease are preventable through correct and timely administration of post-exposure prophylaxis (PEP). PEP should be initiated as soon as possible after an exposure to a rabies suspected animal and consists of a course of active vaccinations and administration of rabies immunoglobulin (RIG) in case of severe exposure. However, RIG is not accessible in most rabies endemic countries and its impact on survival in combination with modern vaccines and its cost-effectiveness is unclear. We examined the effect of equine RIG (eRIG) in a field-trial in Côte d'Ivoire, a developing country with low but chronic rabies burden and persistent lack of RIG, similar to a majority of rabies endemic countries attempting elimination of the disease.; Data from 3367 patients attending anti-rabies centers (Centres Anti-Rabiques, CARs) of the National Institute for Public Hygiene (Institut National d'Hygiène Publique, INHP) in the departments of Bouaké and San Pédro in Côte d'Ivoire was prospectively collected between April 2016 and March 2018. We identified 1594 patients at risk of rabies infection as eligible for RIG administration. Depending on local availability of eRIG and vaccination protocol applied, PEP consisted of active immunization only (non-eRIG group, n = 1145) or active and passive immunization (eRIG group, n = 449). Patients were followed-up by phone interviews at least 15 months after their exposure to assess for rabies suspected deaths.; Follow-up data was available for 641 patients in the non-eRIG group (56%) and 242 in the eRIG group (54%). Three suspected or possible rabies deaths occurred in each of the two groups, corresponding to a possible rabies mortality of 1.2% (95% CI 0.3-3.6%) in the eRIG group and 0.5% (95% CI 0.1-1.4%) in the non-eRIG group. The difference in proportions was small and not statistically significant (0.7%, p = 0.21). Deaths in both groups were associated with treatment delay after exposure and non-compliance to PEP protocol. No death occurred after correct and timely active immunization independent of eRIG administration.; The provision of eRIG did not lead to a measurable reduction of rabies burden in our study population. This underlines that improved access to active vaccines will be effective in reducing rabies deaths even if access to eRIG remains difficult in developing countries. A possible benefit of eRIG administration for severely exposed patients cannot be excluded based on these results

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

The influence of human interaction on guinea pigs: behavioral and thermographic changes during animal-assisted therapy

Guinea pigs are often involved in animal-assisted therapy (AAT) but there is little knowledge about the effects of human contact on guinea pigs involved in AAT. The aim of this study was to investigate effects of availability of a retreat, presence of conspecifics, prior experience with AAT, and human interaction on indicators of welfare in guinea pigs involved in AAT. Guinea pigs of both sexes and different ages (n=20) were assigned to a randomized, controlled within-subject trial with repeated measurements. Each guinea pig was tested in four settings: (I) therapy with retreat possibility with conspecifics, (II) therapy with retreat possibility without conspecifics, (III) therapy without retreat possibility, and (IV) setting without human interaction. We measured changes in eye temperature, as a proxy to infer stress levels, at 5-s intervals with a thermographic camera. All sessions were video recorded and the guinea pigs' behavior was coded using continuous recording and focal animal sampling. For the statistical analysis we used generalized linear mixed models, with therapy setting as a fixed effect and individual guinea pig as a random effect. We observed a temperature increase relative to baseline in settings (I) therapy with retreat with conspecifics present and (III) therapy without retreat. The percentage of time a guinea pig was petted was positively correlated with a rise in the eye temperature independent of the setting. Time spent eating was reduced in all therapy settings (I-III) compared to the setting without HAI (human animal interaction) (IV). In the setting with retreat (I), guinea pigs showed more active behaviors such as locomotive behavior or startling compared to the setting without retreat (III) and the setting without HAI (IV). When no retreat was available (III), they showed more passive behaviors, such as standing still or freezing compared to therapy with retreat (I). Based on our results we identified the behaviors "reduced eating", "increased startle" and "increased freezing" as indicators of an increased stress level. Petting the guinea pigs was correlated with a rise in the eye temperature and might be a factor which can cause stress. Our results support the suggestion that guinea pigs involved in AAT should have a retreat possibility, should have access to conspecifics, and should be given time to adapt to a new setting. In this way, stress might be reduced

Risk factors for Entamoeba histolytica infection in an agricultural community in Hanam province, Vietnam

BACKGROUND: Entamoeba histolytica is an important protozoan intestinal infection in resource-poor settings, including Vietnam. The study objective was to assess risk factors of E. histolytica infection in a community in Vietnam, where wastewater and human excreta are used in agriculture. A case-control study was conducted among residents of Hanam province, Northern Vietnam. Cases (n=46) infected with E. histolytica and non-infected controls (n=138) were identified in a cross-sectional survey among 794 randomly selected individuals and matched for age, sex and place of residence. Potential risk factors including exposure to human and animal excreta and household wastewater were assessed with a questionnaire. RESULTS: People from households with an average socio-economic status had a 4.3 times higher risk of E. histolytica infection (95% confidence interval [CI] 1.3-14.0) compared with those from households with a good socioeconomic status. Those individuals who never or rarely used soap for hand washing had a 3.4 times higher risk for infection (95% CI 1.1-10.0), compared to those who used always soap. In contrast, none of the factors related to use of human or animal excreta was statistically significant associated with E. histolytica infection. People having close contact with domestic animals presented a greater risk of E. histolytica infection (odds ratio [OR]=5.9, 95% CI 1.8-19.0) than those without animal contact. E. histolytica infection was not associated with direct contact with Nhue river water, pond water and household's sanitary conditions, type of latrine or water source used. CONCLUSIONS: Our study suggests that in settings where human and animal excreta and Nhue River water are intensively used in agriculture, socio-economic and personal hygiene factors determine infection with E. histolytica, rather than exposure to human and animal excreta in agricultural activitie

Chapitre 11 - Modèles de transmission animaux-humains

Introduction Plus de 60 % des maladies infectieuses humaines sont imputables à des agents pathogènes communs avec les animaux (Karesh et al., 2012). Bien qu’un vaste corpus de connaissances existe sur la transmission intraspécifique des maladies infectieuses, nous en savons étonnamment peu sur la dynamique de transmission d’agents pathogènes zoonotiques entre espèces (Lloyd-Smith et al., 2009). Toutefois, pour comprendre..