Elimination of Plasmodium falciparum in an area of multi-drug resistance.
BACKGROUND
Resistance to the artemisinin derivatives in Plasmodium falciparum has emerged in Cambodia and is now spreading throughout South-East Asia. The rapid elimination of P. falciparum seems to be the only viable option to avoid a public health disaster but this is difficult because even in low transmission settings many residents have asymptomatic parasitaemias.


METHODS
In response to a large number of malaria cases reported in three remote villages on the Thai-Myanmar border where malaria is endemic and the disease is seasonal, surveys were conducted using an ultra-sensitive qPCR assay (LOD 22 parasites per mL). In one of the villages where it was feasible, mass anti-malarial drug administration was proposed to the population as a potential solution, and this was adopted.


RESULTS
In the three villages 204/356 (57.3 %), 212/385 (55.1 %) and 195/286 (68.2 %) of the resident populations were positive by qPCR (approximately one-third P. falciparum and two-thirds P. vivax). Of those positive for P. falciparum 62 % carried single point mutations in the P. falciparum kelch protein (a marker of artemisinin resistance). In one of the villages 217 of 674 inhabitants received at least one dose of dihydroartemisinin-piperaquine chemoprevention in June 2012, 155 (71.4 %) received two consecutive months, and 98 (45.2 %) received three treatment doses. The chemoprevention was generally well tolerated. The sub-microscopic reservoir of P. falciparum malaria was eliminated during the six-month follow-up period (prevalence fell from 7 to 0 %); P. vivax malaria persisted (prevalence fell from 35 to 8 %). From June to October 2012 (rainy season) the number of clinical episodes of P. falciparum was six times lower (46), than during the same period in the previous year (290).


CONCLUSIONS
Mass drug administration with dihydroartemisinin-piperaquine may be an effective strategy to eliminate P. falciparum rapidly where multi-drug resistance is present.
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand. drkhin_mg_lwin@shoklo-unit.com.
Khin Maung
KM
Lwin
Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. noi@tropmedres.ac.|Department of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. noi@tropmedres.ac.
Mallika
M
Imwong
Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. euudeye@hotmail.com.
Preyanan
P
Suangkanarat
Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. atthanee@tropmedres.ac.
Atthanee
A
Jeeyapant
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand. benchawan@shoklo-unit.com.
Benchawan
B
Vihokhern
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand. klanarong@shoklo-unit.com.
Klanarong
K
Wongsaen
Sorbonne Universités, UPMC Univ Paris 06, UPMC UMRS CR7, 75005, Paris, France. snounou@mnhn.fr.|Centre d'Immunologie et de Maladies Infectieuses (CIMI), Paris, Institut National de la Santé et de la Recherche Médicale (Inserm) U1135, Centre National de la Recherche Scientifique (CNRS) ERL 8255, 75013, Paris, France. snounou@mnhn.fr.
Georges
G
Snounou
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand. lilly@shoklo-unit.com.
Lilly
L
Keereecharoen
Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. nickw@tropmedres.ac.|Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. nickw@tropmedres.ac.
Nicholas J
NJ
White
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand. francois@tropmedres.ac.|Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK. francois@tropmedres.ac.
Francois
F
Nosten
D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000494:pharmacology; D002648:Child; D003430:Cross-Sectional Studies; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000453:epidemiology* / Q000469:parasitology / Q000517:prevention & control*; D008297:Male; D002052:Myanmar / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics; D013785:Thailand / Q000453:epidemiology
D000962:Antimalarials