ABSTRACT
BACKGROUND: Sympatric existence of Plasmodium falciparum and Plasmodium vivax, and the practice of malaria treatment without microscopic confirmation suggest that the accidental treatment of vivax malaria with sulfadoxine-pyrimethamine (SP) is common. METHODS: In this study, the frequency distribution of alleles associated with SP resistance were analysed among the P. vivax infections from malariometric surveys and its association with SP treatment failure in clinical studies in Indonesia. The dhfr and dhps alleles were detected using PCR-RFLP method. RESULTS: Analysis of 159 P. vivax isolates from malariometric surveys and 69 samples from in vivo SP efficacy study revealed various the existence of various alleles of the pvdhfr and pfdhps genes including 57L/I, 58R, 61M, and 117N/T. Allele 13L of the dhfr gene and 553G of the dhps gene were not detected in any isolates examined in both studies. In the dhfr gene, tandem repeat type-A was the major tandem repeat observed in any isolates analysed. In the dhps gene, only the 383G allele was observed. Isolates carrying double, triple and quadruple mutants of dhfr gene were found in Lampung, Purworejo, Sumba, and Papua. Although this study revealed a wide distribution of dhfr and dhps alleles among the P. vivax isolates across a broad geographic regions in Indonesia, impact on SP efficacy was not observed in Sumba. CONCLUSION: With proper malaria diagnosis, SP may still be used as a rational anti-malarial drug either as a single prescription or in combination with artemisinin.
Subject(s)
Antimalarials/therapeutic use , Dihydropteroate Synthase/genetics , Gene Frequency , Malaria, Vivax/drug therapy , Plasmodium vivax/enzymology , Pyrimethamine/therapeutic use , Sulfadoxine/therapeutic use , Tetrahydrofolate Dehydrogenase/genetics , Adolescent , Adult , Antimalarials/pharmacology , Child , Child, Preschool , Drug Combinations , Drug Resistance , Female , Humans , Indonesia/epidemiology , Malaria, Vivax/epidemiology , Malaria, Vivax/parasitology , Male , Middle Aged , Plasmodium vivax/genetics , Pyrimethamine/pharmacology , Sulfadoxine/pharmacology , Surveys and Questionnaires , Treatment Failure , Young AdultABSTRACT
Reports on treatment failures associated with the use of first-and second-line antimalarial drugs chloroquine and sulfadoxine-pyrimethamine have recently increased in many parts of Indonesia. The present study evaluated artemisinin-based combination therapy for treatment of persons with uncomplicated Plasmodium falciparum malaria in West Sumba District, East Nusa Tenggara Province. A total of 103 persons 1-57 years of age were enrolled, given standard artesunate-amodiaquine therapy, and followed-up for 28 days. All persons clinically recovered, but two persons were again parasitemic on day 7. This finding indicated that these two persons had recurrent parasitemias on days 21 and 28. Molecular analyses suggested both recurrences were caused by reinfections. There were no severe adverse events, but complaints of gastrointestinal upset, nausea and vomiting, and headache linked to therapy occurred among 9.7%, 5.8% and 5.8% of the persons, respectively. Artesunate-amodiaquine proved efficacious therapy for treatment of persons with uncomplicated P. falciparum malaria at one site in eastern Indonesia but it may have tolerability problems that merit further investigation.
