title: Monitoring antimalarial drug resistance in India via sentinel sites: outcomes and risk factors for treatment failure, 2009-2010.
abstract: OBJECTIVE
  To describe India's National Antimalarial Drug Resistance Monitoring System, measure the efficacy of first-line malaria treatments, and determine risk factors for treatment failure.
  
  
  METHODS
  In 2009-2010, prospective studies with 28 days of follow-up were conducted at 25 sentinel sites. Patients infected with Plasmodium falciparum were given artesunate plus sulfadoxine-pyrimethamine (AS+SP); those infected with P. vivax were given chloroquine. Polymerase chain reaction was used to distinguish post-treatment reinfection from treatment failure. Isolates of P. falciparum were checked for dhfr and dhps mutations.
  
  
  RESULTS
  Overall, 1664 patients were enrolled. Kaplan-Meier survival analysis showed an efficacy of 98.8% for AS+SP. Most patients with P. falciparum parasitaemia cleared their parasitaemias within 24 hours of treatment initiation, but six, including four with treatment failure, remained parasitaemic after 72 hours. Double mutants in dhfr were found in 68.4% of the genotyped isolates. Triple or quadruple mutants in dhfr and mutations in dhps were rare. A daily dose of artesunate of < 3 mg per kg of body weight, age of less than 5 years, and fever at enrolment were associated with an increased risk of treatment failure. Chloroquine remained 100% efficacious and generally cleared P. vivax parasitaemias within 48 hours. Vomiting (seen in 47 patients) was the most common adverse event.
  
  
  CONCLUSIONS
  India's National Antimalarial Drug Resistance Monitoring System provides wide coverage. The first-line antimalarials used in the country remain safe and efficacious. The treatment of malaria in young children and the relative benefits of age- and weight-based dosing need further exploration.
authors.affiliation: National Institute of Malaria Research, Indian Council of Medical Research, Sector 8, Dwarka, New Delhi 110 077, India.
authors.forename: Neelima
authors.initials: N
authors.lastname: Mishra
authors.forename: Jai Prakash Narayan
authors.initials: JP
authors.lastname: Singh
authors.forename: Bina
authors.initials: B
authors.lastname: Srivastava
authors.forename: Usha
authors.initials: U
authors.lastname: Arora
authors.forename: Naman K
authors.initials: NK
authors.lastname: Shah
authors.forename: S K
authors.initials: SK
authors.lastname: Ghosh
authors.forename: R M
authors.initials: RM
authors.lastname: Bhatt
authors.forename: S K
authors.initials: SK
authors.lastname: Sharma
authors.forename: M K
authors.initials: MK
authors.lastname: Das
authors.forename: Ashwani
authors.initials: A
authors.lastname: Kumar
authors.forename: Anupkumar R
authors.initials: AR
authors.lastname: Anvikar
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Kaitholia
authors.forename: Ruchi
authors.initials: R
authors.lastname: Gupta
authors.forename: G S
authors.initials: GS
authors.lastname: Sonal
authors.forename: A C
authors.initials: AC
authors.lastname: Dhariwal
authors.forename: Neena
authors.initials: N
authors.lastname: Valecha
mesh_terms: D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use; D004352:Drug Resistance, Microbial / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D016778:Malaria, Falciparum / Q000188:drug therapy*; D016780:Malaria, Vivax / Q000188:drug therapy*; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use; D012307:Risk Factors; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C578917:sulfadoxine-pyrimethamine-artesunate; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine