title: High chloroquine treatment failure rates and predominance of mutant genotypes associated with chloroquine and antifolate resistance among falciparum malaria patients from the island of Car Nicobar, India.
abstract: OBJECTIVE
  An in vivo chloroquine efficacy study was undertaken on the island of Car Nicobar because a temporal rise in the Plasmodium falciparum parasite population containing mutations in the chloroquine resistance transporter (PfCRT) protein has been reported there.
  
  
  METHODS
  A WHO protocol with a 28 day follow-up schedule was used for chloroquine efficacy studies. Finger-prick blood from P. falciparum malaria patients was used for sequencing the genes encoding PfCRT (exon 2), dihydrofolate reductase (PfDHFR) and dihydropteroate synthetase (PfDHPS).
  
  
  RESULTS
  The majority of patients showed chloroquine treatment failure (60.42%, n=48). A higher early treatment failure (ETF) rate was recorded among non-responders (23 of 29, 79.31%). Each patient, irrespective of their chloroquine response, was infected with P. falciparum that contained mutated PfCRT (predominantly genotype C72V73I74E75T76) associated with high chloroquine resistance and none with the wild-type pfcrt gene. Therefore, mutated PfCRT was also present in the P. falciparum isolates of all the chloroquine responders. The majority of individuals from both groups also contained parasites with a high number of two-locus PfDHFR-PfDHPS mutations, associated with a high level of antifolate resistance.
  
  
  CONCLUSIONS
  There is a predominance of chloroquine- and antifolate-resistant P. falciparum malaria in Car Nicobar, requiring an alternative antimalarial drug treatment policy, such as implementation of artesunate combination therapy (ACT), for this island.
authors.affiliation: National Institute of Malaria Research, F.U., T.B. Sanatorium Complex, Itki, Ranchi 835301, Jharkhand, India.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Das
authors.forename: Vanshika
authors.initials: V
authors.lastname: Lumb
authors.forename: Pooja
authors.initials: P
authors.lastname: Mittra
authors.forename: Shiv S
authors.initials: SS
authors.lastname: Singh
authors.forename: Aditya P
authors.initials: AP
authors.lastname: Dash
authors.forename: Yagya D
authors.initials: YD
authors.lastname: Sharma
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use*; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004094:Dihydropteroate Synthase / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007194:India; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D020125:Mutation, Missense; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D015800:Protozoan Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; D002738:Chloroquine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase