RESUMO
The World Health Organization (WHO) recommends periodic assessment of the therapeutic efficacy of praziquantel (PZQ) to detect reduced efficacy that may arise from drug resistance in schistosomes. In this multi-country study (2014), we assessed the therapeutic efficacy of a single oral dose of PZQ (40 mg/kg) against Schistosoma mansoni (Brazil, Cameroon, Ethiopia, Mali, Madagascar and Tanzania), S. haematobium (Cameroon, Ethiopia, Mali, Tanzania and Zanzibar) and S. japonicum (the Philippines) infections in school-aged children, across a total of 12 different trials. Each trial was performed according to the standardized methodology for evaluating PZQ efficacy as described by the WHO. Overall, therapeutic efficacy, measured as the reduction in arithmetic mean of schistosome egg counts following drug administration (egg reduction rate; ERR), was high for all three schistosome species (S. mansoni: 93.4% (95%CI: 88.8-96.8); S. haematobium: 97.7% (95%CI: 96.5-98.7) and S. japonicum: 90.0% (95%CI: 68.4-99.3). At the trial level, therapeutic efficacy was satisfactory (point estimate ERR ≥90%) for all three Schistosoma species with the exception of S. mansoni in Cameroon where the ERR was 88.5% (95%CI: 79.0-95.1). Furthermore, we observed that in some trials individual drug response could vary significantly (wide 95%CI) and that few non-responsive individuals could significantly impact ERR point estimates. In conclusion, these results do not suggest any established reduced efficacy of the standard PZQ treatment to any of the three schistosome species within these countries. Nevertheless, the substantial degree of variation in individual responses to treatment in some countries underpins the need for future monitoring. The reported ERR values serve as reference values to compare with outcomes of future PZQ efficacy studies to ensure early detection of reduced efficacies that could occur as drug pressure continues increase. Finally, this study highlights that 95%CI should be considered in WHO guidelines to classify the therapeutic efficacy of PZQ.
Assuntos
Anti-Helmínticos , Praziquantel/uso terapêutico , Esquistossomose mansoni/tratamento farmacológico , Animais , Anti-Helmínticos/uso terapêutico , Brasil , Criança , Etiópia , Humanos , Schistosoma mansoni , TanzâniaRESUMO
Schistosoma mansoni egg counts by faecal examination vary considerably and are not very sensitive, so prevalences are underestimated. The distribution of egg counts can adequately be described by a stochastic model which distinguishes variation in counts between persons and variation in repeated counts within a person. Based on this model a pocket chart has been developed which predicts the proportion of individuals harbouring at least 1 S. mansoni worm pair-the 'true prevalence'-from a simple single survey prevalence and geometric mean egg count (using common duplicate 25 mg Kato-Katz smears). The current paper describes the validation of this chart by comparing predicted true prevalences with prevalences observed after 5-7 repeated Kato-Katz faecal examinations (Burundi), by examination of a large quantity of stool using the Visser filter (Brazil) or a selective sedimentation-filtration method (Surinam). Because 5-7 repeated examinations do not suffice to measure all infections, predictions have been made of the cumulative proportion positives over 5-7 surveys-the 'approximate true prevalence'-as well. After dividing the data into age groups, 12 different subsets were considered for validation. In all 12 cases, predicted true prevalences (or approximate true prevalences for the Burundi data) agree well with those observed. The overall agreement depends only slightly on the assumed relationship between worm numbers and mean egg counts, with a good fit for a productivity between 0.8 and 4.4 eggs per gramme faeces (EPG) per worm pair (WP). This interval includes the most plausible value from the literature, i.e. 1.0 EPG/WP, which has been applied in the initial pocket chart. These findings support the validity of the chart to predict true prevalences for a wide range of productivity assumptions, and reinforces the applicability of its underlying stochastic model to describe egg count variation. However, as predictions appear to vary importantly when using only part of the data, it is also concluded that the pocket chart never compensates for limited validity of initial single survey prevalences and geometric means in consequence of small sample sizes.
Assuntos
Fezes/parasitologia , Contagem de Ovos de Parasitas , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/diagnóstico , Esquistossomose mansoni/epidemiologia , Adolescente , Adulto , Fatores Etários , Animais , Brasil/epidemiologia , Burundi/epidemiologia , Criança , Pré-Escolar , Métodos Epidemiológicos , Humanos , Prevalência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Processos Estocásticos , Suriname/epidemiologiaRESUMO
Experiences with population-based chemotherapy and other methods for the control of schistosomiasis mansoni in two subsaharan foci are described. In the forest area of Maniema (Zaire), intense transmission of Schistosoma mansoni, high prevalences and intensities of infection, and important morbidity have been documented. Taking into account the limited financial means and the poor logistic conditions, the control strategy has been based mainly on targeted chemotherapy of heavily infected people (> 600 epg). After ten years of intervention, prevalences and intensities have hardly been affected, but the initial severe hepatosplenic morbidity has almost disappeared. In Burundi, a national research and control programme has been initiated in 1982. Prevalences, intensities and morbidity were moderate, transmission was focal and erratic in time and space. A more structural control strategy was developed, based on screening and selective therapy, health education, sanitation and domestic water supply. Prevalences and intensities have been considerably reduced, though the results show focal and unpredictable variations. Transmission and reinfection were not significantly affected by chemotherapy alone, and the eventual outcome of repeated selective treatment appears to be limited by the sensitivity of the screening method. Intestinal morbidity was strongly reduced by community-based selective treatment, but hepatosplenic enlargement was hardly affected; this is possibly due to the confounding impact of increasing malaria morbidity. The experiences show the importance of local structures and conditions for the development of an adapted control strategy. It is further concluded that population-based chemotherapy is a highly valid tool for the rapid control of morbidity, but should in most operational conditions not be considered as a tool for transmission control.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Esquistossomose mansoni/prevenção & controle , Adulto , Animais , Biomphalaria/parasitologia , Burundi/epidemiologia , Criança , República Democrática do Congo/epidemiologia , Reservatórios de Doenças , Vetores de Doenças , Feminino , Educação em Saúde , Humanos , Masculino , Programas de Rastreamento , Moluscocidas , Programas Nacionais de Saúde/economia , Programas Nacionais de Saúde/organização & administração , Praziquantel/economia , Praziquantel/uso terapêutico , Prevalência , Avaliação de Programas e Projetos de Saúde , Recidiva , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/transmissão , Poluição da Água/prevenção & controleRESUMO
Experiences with population-based chemotherapy and other methods for the control of schistosomiasis mansoni in two subsaharan foci are described. In the forest area of Maniema (Zaire), intense transmission of Schistosoma mansoni, high prevalences and intensities of infection, and important morbidity have been documental. Taking into account the limited financial means and the poor logistic conditions, the control strategy has been based mainly on targeted chemotherapy of heavily infected people (>600 epg). After ten years of intervention, prevalences and intensities have hardly been affected, but the initial severe hepatosplenic morbidity has almost disappeared. In Burundi, a national research and control programme has been initiated in 1982. Prevalences, intensities and morbidity were moderate, transmission was focal and erratic in time and space. A more structural control strategy was developed, based on screening and selective therapy, health education, sanitation and domestic water supply. Prevalences and intensities have been considerably reduced, though the results show focal and unpredicatable variations. Transmission and reinfection were not signifcantly affected by chemotherapy alone, and eventual outcome of repeated selective treatment appears to be limited by the sensitivity of the screening method. Intestinal morbidity was strongly reduced by community-based selective treatment, but hepatosplenic enlargement was hardly affected; this is possibly due to the confounding impact of increasing malaria morbidity. The experiences show the importance of local structures and conditions for the development of an adapted control strategy. It is further concluded that population-based chemotherapy is a highly valid tool for the rapid control of morbidity, but should in most operational conditions not be considered as a tool for transmission control. Integration of planning, execution and surveillance in regular health services are essential, and sanition, provision of domestic water supply, and health education remain the cornerstones of long-term control