A multicentre randomized controlled trial of the efficacy and safety of single-dose praziquantel at 40 mg/kg vs. 60 mg/kg for treating intestinal schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil

Autor: Mamadou Diaw, Godfrey M. Kaatano, Tereza Cristina Favre, Olivier Lapujade, Mohamed Ouldabdallahi, Otávio Sarmento Pieri, Nicholas J.S. Lwambo, Piero Olliaro, AnaLucia C. Domingues, Fabiana Alves, Michel Vaillant, Vincente Belizario, Lester Chitsulo, Maria Lourdes E. Amarillo
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Male
Intestinal schistosomiasis
Philippines
Treatment outcome
Tanzania
Gastroenterology
Praziquantel
law.invention
Randomized controlled trial
law
Secondary Prevention
Schistosomiasis
Child
Anthelmintics
biology
Incidence
lcsh:Public aspects of medicine
Mauritania
Treatment Outcome
Infectious Diseases
Medicine
Female
Public Health
Brazil
Research Article
Neglected Tropical Diseases
medicine.drug
medicine.medical_specialty
lcsh:Arctic medicine. Tropical medicine
Adolescent
Clinical Research Design
lcsh:RC955-962
Young Adult
Internal medicine
parasitic diseases
Parasitic Diseases
medicine
Humans
Clinical Trials
Parasite Egg Count
business.industry
Public Health
Environmental and Occupational Health
lcsh:RA1-1270
Drug Policy
biology.organism_classification
medicine.disease
Schistosomiasis mansoni
Abdominal Pain
Surgery
Meta-Analyses
business
Zdroj: PLoS Neglected Tropical Diseases, Vol 5, Iss 6, p e1165 (2011)
PLoS Neglected Tropical Diseases
ISSN: 1935-2735
1935-2727
Popis: Background Praziquantel at 40 mg/kg in a single dose is the WHO recommended treatment for all forms of schistosomiasis, but 60 mg/kg is also deployed nationally. Methodology/Principal Findings Four trial sites in the Philippines, Mauritania, Tanzania and Brazil enrolled 856 patients using a common protocol, who were randomised to receive praziquantel 40 mg/kg (n = 428) or 60 mg/kg (n = 428). While the sites differed for transmission and infection intensities (highest in Tanzania and lowest in Mauritania), no bias or heterogeneity across sites was detected for the main efficacy outcomes. The primary efficacy analysis was the comparison of cure rates on Day 21 in the intent-to-treat population for the pooled data using a logistic model to calculate Odd Ratios allowing for baseline characteristics and study site. Both doses were highly effective: the Day 21 cure rates were 91.7% (86.6%–98% at individual sites) with 40 mg/kg and 92.8% (88%–97%) with 60 mg/kg. Secondary parameters were eggs reduction rates (ERR), change in intensity of infection and reinfection rates at 6 and 12 months. On Day 21 the pooled estimate of the ERR was 91% in both arms. The Hazard Ratio for reinfections was only significant in Brazil, and in favour of 60 mg/kg on the pooled estimate (40 mg/kg: 34.3%, 60 mg/kg: 23.9%, HR = 0.78, 95%CI = [0.63;0.96]). Analysis of safety could not distinguish between disease- and drug-related events. 666 patients (78%) reported 1327 adverse events (AE) 4 h post-dosing. The risk of having at least one AE was higher in the 60 than in the 40 mg/kg group (83% vs. 73%, p
Author Summary Control of urinary and intestinal schistosomiasis is based on mass administration of praziquantel at the World Health Organization (WHO) recommended dose of 40 mg/kg, though some countries use 60 mg/kg. This multi-country randomized clinical trial compared the efficacy (cure and egg reduction rates three weeks post-treatment) and safety of these two doses for treating intestinal schistosomiasis in 856 patients in Brazil, Mauritania and Tanzania (Schistosoma mansoni), and The Philippines (S. japonicum). Transmission and infection intensities varied across the sites, but there was no bias or heterogeneity in efficacy outcomes. The two doses are equally effective in curing intestinal schistosomiasis; the higher dose may be less well tolerated, though effects are generally mild and transient. In endemic areas people can be re-infected; one year post-treatment patients on 60 mg/kg had fewer re-infections but this finding is difficult to explain. This study was conducted to respond to the demand for evidence about the dose of praziquantel when deployed in endemic countries. The results, along with those of systematic reviews, support the current WHO recommendation for using praziquantel at 40 mg/kg and should inform policy decisions in countries. The Philippines has already changed from 60 to 40 mg/kg after this study.
Databáze: OpenAIRE
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