RESUMO
BACKGROUND: Since 2005, artemisinin-based combination therapy (ACT) has been recommended to treat uncomplicated falciparum malaria in Madagascar. Artesunate-amodiaquine (ASAQ) and artemether-lumefantrine (AL) are the first- and second-line treatments, respectively. A therapeutic efficacy study was conducted to assess ACT efficacy and molecular markers of anti-malarial resistance. METHODS: Children aged six months to 14 years with uncomplicated falciparum malaria and a parasitaemia of 1000-100,000 parasites/µl determined by microscopy were enrolled from May-September 2018 in a 28-day in vivo trial using the 2009 World Health Organization protocol for monitoring anti-malarial efficacy. Participants from two communes, Ankazomborona (tropical, northwest) and Matanga (equatorial, southeast), were randomly assigned to ASAQ or AL arms at their respective sites. PCR correction was achieved by genotyping seven neutral microsatellites in paired pre- and post-treatment samples. Genotyping assays for molecular markers of resistance in the pfk13, pfcrt and pfmdr1 genes were conducted. RESULTS: Of 344 patients enrolled, 167/172 (97%) receiving ASAQ and 168/172 (98%) receiving AL completed the study. For ASAQ, the day-28 cumulative PCR-uncorrected efficacy was 100% (95% CI 100-100) and 95% (95% CI 91-100) for Ankazomborona and Matanga, respectively; for AL, it was 99% (95% CI 97-100) in Ankazomborona and 83% (95% CI 76-92) in Matanga. The day-28 cumulative PCR-corrected efficacy for ASAQ was 100% (95% CI 100-100) and 98% (95% CI 95-100) for Ankazomborona and Matanga, respectively; for AL, it was 100% (95% CI 99-100) in Ankazomborona and 95% (95% CI 91-100) in Matanga. Of 83 successfully sequenced samples for pfk13, no mutation associated with artemisinin resistance was observed. A majority of successfully sequenced samples for pfmdr1 carried either the NFD or NYD haplotypes corresponding to codons 86, 184 and 1246. Of 82 successfully sequenced samples for pfcrt, all were wild type at codons 72-76. CONCLUSION: PCR-corrected analysis indicated that ASAQ and AL have therapeutic efficacies above the 90% WHO acceptable cut-off. No genetic evidence of resistance to artemisinin was observed, which is consistent with the clinical outcome data. However, the most common pfmdr1 haplotypes were NYD and NFD, previously associated with tolerance to lumefantrine.
Assuntos
Amodiaquina/uso terapêutico , Antimaláricos/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , DNA de Protozoário/genética , DNA de Protozoário/isolamento & purificação , Combinação de Medicamentos , Feminino , Humanos , Lactente , Madagáscar/epidemiologia , Malária Falciparum/epidemiologia , Masculino , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Plasmodium falciparum/genética , Reação em Cadeia da Polimerase , Polimorfismo Genético , Gravidez , Prevalência , Recidiva , ReinfecçãoRESUMO
INTRODUCTION: This study aims to assess the adherence of private health providers to the use of malaria rapid diagnostic tests (RDTs) and to the prescription of artemisinin-containing combinations (ACT) in patients with uncomplicated malaria. METHODS: We conducted an analytical, retrospective and cross-sectional study in 11 Madagascar's health districts divided into four epidemiological strata in September and in October 2015. A total of 43 health providers from 39 private health care facilities (PHF) were interviewed and visited. RESULTS: Health providers declared having read the malaria management manual in 16.3% of cases (4/43). Only one quarter (25.6%) of health providers had RDTs in their office. ACT was reported as "first-line drug" for the treatment of uncomplicated malaria by 83.7% of health providers. In practice, 55.6% of health providers had doubts about the results of the RDTs. The use of antimalarial drugs, despite having had negative RDTs results (38.2%), was more frequent among those who had raised doubts (p = 0.03). Conversely, despite having had positive RDTs results, half of the health providers did not prescribe ACT (50%). The decision to not participate in periodic reviews by the Health District (p = 0.05) negatively influenced the adherence to the policies. CONCLUSION: The low adherence of private health providers to the national guidelines for the management of uncomplicated malaria raises questions about the importance of exercising more control over health providers activities.