Monitoring for Plasmodium falciparum drug resistance to artemisinin and artesunate in Binh Phuoc Province, Vietnam: 1998-2009.
BACKGROUND
Artemisinin derivatives have been used for malaria treatment in Vietnam since 1989. Reported malaria cases have decreased from 1,672,000 with 4,650 deaths in 1991, to 91,635 with 43 deaths in 2006. Current national guidelines recommend artemisinin-based combination therapy (ACT), although artesunate is still available as monotherapy through the private sector. Recent reports suggest that effectiveness of ACT and artesunate monotherapy has declined in western Cambodia. This study examined Plasmodium falciparum resistance patterns over 10 years in southwest Vietnam in infected patients treated with artemisinin compounds.


METHODS
The study was conducted in two communes in Phuoc Long district, Binh Phuoc province, 100 km west of the Cambodian border. This was chosen as a likely site for emerging artemisinin resistance because of the high prevalence of P. falciparum malaria, and the length of time that artemisinin had been in use. In vivo and in vitro monitoring of P. falciparum susceptibility to anti-malarial drugs was conducted in 1998, 2001, 2004/5, and 2008/9. Patients with confirmed P. falciparum malaria received therapy with 5 or 7 days of artemisinin (1998 and 2001 respectively) or 7 days of artesunate


RESULTS
In the four surveys, 270 patients were recruited and treated. The mean parasite clearance times differed between 1998, 2001 and 2004/5 (1.8, 2.3 and 2.1 days, P < 0.01) but not between 1998 and 2008/2009. The mean parasite clearance times were correlated with parasite density at day 0 (r = 0.4; P < 0.001). Treatment failure rates after PCR adjustment were 13.8%, 2.9%, 1.2%, and 0% respectively. Susceptibility of P. falciparum to artemisinin in in vitro tests was stable during the period, except for a rise in EC90 and EC99 in 2001.


CONCLUSIONS
This study showed stable levels of P. falciparum sensitivity to artemisinin compounds in the two sites over a ten-year period. The introduction of ACT in this area in 2003 may have protected against the development of artemisinin resistance. Adherence to the latest WHO and Vietnamese guidelines, which recommend ACT as first-line therapy in all malarious areas, and continued monitoring along the Vietnam-Cambodia border will be essential to prevent the spread of artemisinin resistance in Vietnam.
Thanh
Ngo V
NV
Department of Medicine RMH/WH, The University of Melbourne, 4th Floor Clinical Sciences Building, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
Toan
Tran Q
TQ
Cowman
Alan F
AF
Casey
Gerard J
GJ
Phuc
Bui Q
BQ
Tien
Nong T
NT
Hung
Nguyen M
NM
Biggs
Beverley-Ann
BA
D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D000962:Antimalarials / Q000494:pharmacology*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D002648:Child; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D020128:Inhibitory Concentration 50; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D018512:Parasitemia / Q000188:drug therapy; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012008:Recurrence; D012680:Sensitivity and Specificity; D013997:Time Factors; D014744:Vietnam; D055815:Young Adult
D000890:Anti-Infective Agents; D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; C031327:artemisinin