title: A clinical and molecular study of artesunate + sulphadoxine-pyrimethamine in three districts of central and eastern India.
abstract: BACKGROUND
  Artesunate + 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  AS + 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.
authors.forename: Prakriti
authors.initials: P
authors.lastname: Srivastava
authors.forename: Jagnyeswar
authors.initials: J
authors.lastname: Ratha
authors.forename: Naman K
authors.initials: NK
authors.lastname: Shah
authors.forename: Neelima
authors.initials: N
authors.lastname: Mishra
authors.forename: Anupkumar R
authors.initials: AR
authors.lastname: Anvikar
authors.forename: Surya K
authors.initials: SK
authors.lastname: Sharma
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Das
authors.forename: Bina
authors.initials: B
authors.lastname: Srivastava
authors.forename: Neena
authors.initials: N
authors.lastname: Valecha
mesh_terms: D000293:Adolescent; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics; D019353:Endemic Diseases; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D017354:Point Mutation; D015995:Prevalence; D011446:Prospective Studies; D015800:Protozoan Proteins / Q000235:genetics; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D015800:Protozoan Proteins; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine