Monitoring for Plasmodium falciparum drug resistance to artemisinin and artesunate in Binh Phuoc Province, Vietnam: 1998-2009

Abstract

BackgroundArtemisinin 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.MethodsThe 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 artesunateResultsIn 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.ConclusionsThis 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.

Comparative Ex Vivo Activity of Novel Endoperoxides in Multidrug-Resistant Plasmodium falciparum and P. vivax

“…However, for P. vivax, the assay options remain limited, and in view of the marked stage specificity of drug action, microscopic quantification of parasite growth remains the preferred option (12a, 17, 31). Previous studies have demonstrated that IC 50 estimates de- rived from schizont maturation tend to be higher than those derived by in vitro reinvasion assays with growth quantified by 3 Hhypoxanthine incorporation (1,23,36,39).…”

No Evidence of Delayed Parasite Clearance after Oral Artesunate Treatment of Uncomplicated Falciparum Malaria in Mali

“…Thanh and others 24 recently reported stable levels of P. falciparum sensitivity to artemisinins between 1998 and 2008-2009 in Vietnam, with a mean parasite clearance time ranging from 1.8 to 2.3 days. We used three different measures of parasite clearance: time to clearance of 100%, time to clearance of 95%, and slope half-life.…”

Delayed Parasite Clearance after Treatment with Dihydroartemisinin-Piperaquine in Plasmodium falciparum Malaria Patients in Central Vietnam

“…Monitoring data on drug resistance collected from 1998 to 2009 in the southern province of Binh Phuoc in Vietnam, bordering Cambodia, showed stable sensitivity of P. falciparum to artemisinins, both in vivo and in vitro (12). However, in 2010 and 2011 in the same area, the parasite clearance time was slower than in previous years (13).…”