title: Monitoring the efficacy of antimalarial medicines in India via sentinel sites: Outcomes and risk factors for treatment failure.
abstract: OBJECTIVE
  To combat the problem of antimalarial drug resistance, monitoring the changes in drug efficacy over time through periodic surveillance is essential. Since 2009, systematic and continuous monitoring is being done through nationwide sentinel site system. Potential early warning signs like partner drug resistance markers were also monitored in the clinical samples from the study areas.
  
  
  METHODS
  A total of 1864 patients with acute uncomplicated malaria were enrolled in therapeutic efficacy studies of artesunate plus sulphadoxine-pyrimethamine (AS+SP) for Plasmodium falciparum; those infected with P. vivax were given chloroquine (CQ). Polymerase chain reaction (PCR) was used to distinguish post-treatment reinfection from treatment failures. Isolates of P. falciparum were also analysed for dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) gene mutations.
  
  
  RESULTS
  Overall, 1687 (91.7%) patients completed the follow-up. In most of the falciparum patients the parasitaemia was cleared within 24 h of treatment, except 12 patients who remained parasite positive after 72 h. Presence of dhfr and dhps quintuple mutation was observed predominantly in treatment failure samples. A daily dose of artesunate of < 3 mg/kg of body weight, age of <5 yr, and fever at enrolment were associated with an increased risk of treatment failure. The AS+SP in P. falciparum was effective in > 95% cases in all the sentinel sites except in Northeastern region (NE). Chloroquine remained 100% efficacious in case of P. vivax infections.
  
  
  CONCLUSIONS
  Till 2012, India's national antimalarial drug resistance monitoring system proved highly efficacious and safe towards first-line antimalarials used in the country, except in Northeastern region where a decline in efficacy of AS+SP has been observed. This led to change in first-line treatment for P. falciparum to artemether-lumefantrine in Northeastern region.
authors.affiliation: ECR Division, National Institute of Malaria Research, New Delhi, India.
authors.forename: Neelima
authors.initials: N
authors.lastname: Mishra
authors.affiliation: ECR Division, National Institute of Malaria Research, New Delhi, India.
authors.forename: Bina
authors.initials: B
authors.lastname: Srivastava
authors.affiliation: ECR Division, National Institute of Malaria Research, New Delhi, India.
authors.forename: Ram Suresh
authors.initials: RS
authors.lastname: Bharti
authors.affiliation: ECR Division, National Institute of Malaria Research, New Delhi, India.
authors.forename: Roma
authors.initials: R
authors.lastname: Rana
authors.affiliation: ECR Division, National Institute of Malaria Research, New Delhi, India.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Kaitholia
authors.affiliation: ECR Division, National Institute of Malaria Research, New Delhi, India.
authors.forename: Anupkumar R
authors.initials: AR
authors.lastname: Anvikar
authors.affiliation: National Institute of Malaria Research (Field Unit), Ranchi, Jharkhand, India.
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Das
authors.affiliation: National Institute of Malaria Research (Field Unit), Bengaluru, Karnataka, India.
authors.forename: Susanta K
authors.initials: SK
authors.lastname: Ghosh
authors.affiliation: National Institute of Malaria Research (Field Unit), Raipur, Chhattisgarh, India.
authors.forename: Rajendra M
authors.initials: RM
authors.lastname: Bhatt
authors.affiliation: National Institute of Malaria Research (Field Unit), Rourkela, Odisha, India.
authors.forename: Prajesh K
authors.initials: PK
authors.lastname: Tyagi
authors.affiliation: National Institute of Malaria Research (Field Unit), Guwahati, Assam, India.
authors.forename: Vas
authors.initials: V
authors.lastname: Dev
authors.affiliation: National Institute of Malaria Research (Field Unit), Guwahati, Assam, India.
authors.forename: Sobhan
authors.initials: S
authors.lastname: Phookan
authors.affiliation: National Vector Borne Disease Control Programme, Delhi, India.
authors.forename: Suman Lata
authors.initials: SL
authors.lastname: Wattal
authors.affiliation: National Vector Borne Disease Control Programme, Delhi, India.
authors.forename: Gagan Singh
authors.initials: GS
authors.lastname: Sonal
authors.affiliation: National Vector Borne Disease Control Programme, Delhi, India.
authors.forename: Akshay Chand
authors.initials: AC
authors.lastname: Dhariwal
authors.affiliation: ECR Division, National Institute of Malaria Research, New Delhi, India.
authors.forename: Neena
authors.initials: N
authors.lastname: Valecha
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D002738:Chloroquine / Q000494:pharmacology / Q000627:therapeutic use; D004094:Dihydropteroate Synthase / Q000235:genetics; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007194:India; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010963:Plasmodium falciparum / Q000187:drug effects*; D010966:Plasmodium vivax / Q000187:drug effects*; D011446:Prospective Studies; D011739:Pyrimethamine / Q000494:pharmacology / Q000627:therapeutic use; D012307:Risk Factors; D018571:Sentinel Surveillance; D013413:Sulfadoxine / Q000494:pharmacology / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D002738:Chloroquine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine