title: Malaria burden and artemisinin resistance in the mobile and migrant population on the Thai-Myanmar border, 1999-2011: an observational study.
abstract: BACKGROUND
  The Shoklo Malaria Research Unit has been working on the Thai-Myanmar border for 25 y providing early diagnosis and treatment (EDT) of malaria. Transmission of Plasmodium falciparum has declined, but resistance to artesunate has emerged. We expanded malaria activities through EDT and evaluated the impact over a 12-y period.
  
  
  RESULTS
  Between 1 October 1999 and 30 September 2011, the Shoklo Malaria Research Unit increased the number of cross-border (Myanmar side) health facilities from two to 11 and recorded the number of malaria consultations. Changes in malaria incidence were estimated from a cohort of pregnant women, and prevalence from cross-sectional surveys. In vivo and in vitro antimalarial drug efficacy were monitored. Over this period, the number of malaria cases detected increased initially, but then declined rapidly. In children under 5 y, the percentage of consultations due to malaria declined from 78% (95% CI 76-80) (1,048/1,344 consultations) to 7% (95% CI 6.2-7.1) (767/11,542 consultations), p<0.001. The ratio of P. falciparum/P. vivax declined from 1.4 (95% CI 1.3-1.4) to 0.7 (95% CI 0.7-0.8). The case fatality rate was low (39/75,126; 0.05% [95% CI 0.04-0.07]). The incidence of malaria declined from 1.1 to 0.1 episodes per pregnant women-year. The cumulative proportion of P. falciparum decreased significantly from 24.3% (95% CI 21.0-28.0) (143/588 pregnant women) to 3.4% (95% CI 2.8-4.3) (76/2,207 pregnant women), p<0.001. The in vivo efficacy of mefloquine-artesunate declined steadily, with a sharp drop in 2011 (day-42 PCR-adjusted cure rate 42% [95% CI 20-62]). The proportion of patients still slide positive for malaria at day 3 rose from 0% in 2000 to reach 28% (95% CI 13-45) (8/29 patients) in 2011.
  
  
  CONCLUSIONS
  Despite the emergence of resistance to artesunate in P. falciparum, the strategy of EDT with artemisinin-based combination treatments has been associated with a reduction in malaria in the migrant population living on the Thai-Myanmar border. Although limited by its observational nature, this study provides useful data on malaria burden in a strategically crucial geographical area. Alternative fixed combination treatments are needed urgently to replace the failing first-line regimen of mefloquine and artesunate. Please see later in the article for the Editors' Summary.
authors.affiliation: Shoklo Malaria Research Unit, Mae Sot, Thailand ; Mahidol Oxford University Research Unit, Bangkok, Thailand.
authors.forename: Verena I
authors.initials: VI
authors.lastname: Carrara
authors.forename: Khin Maung
authors.initials: KM
authors.lastname: Lwin
authors.forename: Aung Pyae
authors.initials: AP
authors.lastname: Phyo
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ashley
authors.forename: Jacher
authors.initials: J
authors.lastname: Wiladphaingern
authors.forename: Kanlaya
authors.initials: K
authors.lastname: Sriprawat
authors.forename: Marcus
authors.initials: M
authors.lastname: Rijken
authors.forename: Machteld
authors.initials: M
authors.lastname: Boel
authors.forename: Rose
authors.initials: R
authors.lastname: McGready
authors.forename: Stephane
authors.initials: S
authors.lastname: Proux
authors.forename: Cindy
authors.initials: C
authors.lastname: Chu
authors.forename: Pratap
authors.initials: P
authors.lastname: Singhasivanon
authors.forename: Nicholas
authors.initials: N
authors.lastname: White
authors.forename: François
authors.initials: F
authors.lastname: Nosten
mesh_terms: D000962:Antimalarials / Q000494:pharmacology / Q000627:therapeutic use*; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use*; D000077332:Artesunate; D002980:Climate; D003150:Community Health Workers / Q000706:statistics & numerical data; D003430:Cross-Sectional Studies; D004351:Drug Resistance / Q000187:drug effects; D005260:Female; D005843:Geography; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008288:Malaria / Q000188:drug therapy* / Q000453:epidemiology* / Q000401:mortality / Q000469:parasitology; D015767:Mefloquine / Q000494:pharmacology / Q000627:therapeutic use; D002052:Myanmar / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000302:isolation & purification; D010966:Plasmodium vivax / Q000187:drug effects; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000453:epidemiology; D015995:Prevalence; D011891:Rain; D015203:Reproducibility of Results; D013696:Temperature; D013785:Thailand / Q000453:epidemiology; D014171:Transients and Migrants / Q000706:statistics & numerical data*
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; C031327:artemisinin; D015767:Mefloquine