A clinical and molecular study of artesunate + sulphadoxine-pyrimethamine in three districts of central and eastern India

Malaria Journal

Research

Manoj K Das¹  Neelima Mishra²  Surya K Sharma²  Neena Valecha²  Naman K Shah²  Anupkumar R Anvikar²  Prakriti Srivastava²  Bina Srivastava²  Jagnyeswar Ratha³ 

[1] National Institute of Malaria Research, Ranchi Field Unit, Ranchi, Jharkhand, India;National Institute of Malaria Research, Sector 8, 110077, Dwarka, New Delhi, India;School of life Sciences, Sambalpur University, 768019, Odisha, India;

关键词: Artesunate + sulphadoxine-pyrimethamine;    Plasmodium falciparum;    Dihydrofolate reductase;    Dihydropteroate synthetase;    Falciparum malaria;   

DOI  :  10.1186/1475-2875-12-247

 received in 2013-03-15, accepted in 2013-07-07,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundArtesunate + sulphadoxine-pyrimethamine (AS + SP) is recommended throughout India as the first-line treatment for uncomplicated falciparum malaria. Due to the presence of several eco-epidemiological zones of malaria and variable drug pressure, it is necessary to evaluate the efficacy of this combination in different regions of India. The objective of this study was to use clinical and molecular methods to monitor the efficacy of AS + SP in three diverse sites.MethodsThe study was undertaken in three high endemic sites of central and eastern India. Patients with uncomplicated falciparum malaria were enrolled and followed for 28 days. Molecular genotyping was conducted for merozoite surface protein (msp1 and msp2) to differentiate between re-infection and recrudescence and for the dhfr and dhps genes to monitor antifolate drug resistance.ResultsIn all, 149 patients were enrolled at the three sites. The crude cure rates were 95.9%, 100%, and 100% in Ranchi, Keonjhar, and West Garo Hills respectively. PCR-corrected cure rates were 100% at all sites. In dhfr, 27% of isolates had triple mutations, while 46% isolates were double-mutants. The most prevalent mutation was S108N followed by C59R. 164 L mutation was observed in 43/126 (34%) isolates. In dhps, most (76%) of the isolates were wild-type. Only 2.5% (2/80) isolates showed double mutation. dhfr-dhps two locus mutation were observed in 16% (13/80) isolates. Parasite clearance time was not related with antifolate mutations.ConclusionsAS + SP combination therapy remained effective against falciparum malaria despite common mutations promoting resistance to antifolate drugs. Although the prevalence of double and triple mutations in dhfr was high, the prevalence of dhfr-dhps two locus mutations were low. Even isolates with dhfr triple and dhfr-dhps two locus mutations achieved adequate clinical and parasitological response.

【 授权许可】

CC BY   
© Srivastava et al.; licensee BioMed Central Ltd. 2013