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Background: Artemisinin resistant Plasmodium falciparum has emerged in the countries of the Greater Mekong sub-region posing a serious threat to global malaria elimination efforts. The relationship of artemisinin resistance to treatment failure has been unclear. Methods: In annual studies conducted in three malaria endemic provinces in the south of Vietnam (Binh Phuoc, Ninh Thuan and Gia Lai) between 2011 and 2015, 489 patients with uncomplicated P. falciparum malaria were enrolled in detailed clinical, parasitological and molecular therapeutic response assessments with 42 days follow up. Patients received the national recommended first-line treatment dihydroartemisinin-piperaquine for three days. Results: Over the 5 years the proportion of patients with detectable parasitaemia on day 3 rose steadily from 38 to 57% (P < 0.001). In Binh Phuoc province, the parasite clearance half-life increased from 3.75 h in 2011 to 6.60 h in 2015 (P < 0.001), while treatment failures rose from 0% in 2012 and 2013, to 7% in 2014 and 26% in 2015 (P < 0.001). Recrudescence was associated with in vitro evidence of artemisinin and piperaquine resistance. In the treatment failures cases of 2015, all 14 parasite isolates carried the C580Y Pfkelch 13 gene, marker of artemisinin resistance and 93% (13/14) of them carried exoE415G mutations, markers of piperaquine resistance. Conclusions: In the south of Vietnam recent emergence of piperaquine resistant P. falciparum strains has accelerated the reduced response to artemisinin and has led to treatment failure rates of up to 26% to dihydroartemisinin-piperaquine, Vietnam's current first-line ACT. Alternative treatments are urgently needed. [ABSTRACT FROM AUTHOR]

Background: The importance of the submicroscopic reservoir of Plasmodium infections for malaria elimination depends on its size, which is generally considered small in low transmission settings. The precise estimation of this reservoir requires more sensitive parasite detection methods. The prevalence of asymptomatic, sub-microscopic malaria was assessed by a sensitive, high blood volume quantitative real-time polymerase chain reaction method in three countries of the Greater Mekong Sub-region. Methods: Cross-sectional surveys were conducted in three villages in western Cambodia, four villages along the Thailand-Myanmar border and four villages in southwest Vietnam. Malaria parasitaemia was assessed by Plasmodium falciparum/pan malaria rapid diagnostic tests (RDTs), microscopy and a high volume ultra-sensitive real-time polymerase chain reaction (HVUSqPCR: limit of detection 22 parasites/mL). All villagers older than 6 months were invited to participate. Results: A census before the surveys identified 7355 residents in the study villages. Parasite prevalence was 224/5008 (4 %) by RDT, 229/5111 (5 %) by microscopy, and 988/4975 (20 %) when assessed by HVUSqPCR. Of these 164 (3 %) were infected with P. falciparum, 357 (7 %) with Plasmodium vivax, 56 (1 %) with a mixed infection, and 411 (8 %) had parasite densities that were too low for species identification. A history of fever, male sex, and age of 15 years or older were independently associated with parasitaemia in a multivariate regression model stratified by site. Conclusion: Light microscopy and RDTs identified only a quarter of all parasitaemic participants. The asymptomatic Plasmodium reservoir is considerable, even in low transmission settings. Novel strategies are needed to eliminate this previously under recognized reservoir of malaria transmission. [ABSTRACT FROM AUTHOR]

Background: By 2009, there were worrying signs from western Cambodia that parasitological responses to artesunate-containing treatment regimens for uncomplicated Plasmodium falciparum malaria were slower than elsewhere which suggested the emergence of artemisinin resistance. Vietnam shares a long land border with Cambodia with a large number of migrants crossing it on a daily basis. Therefore, there is an urgent need to investigate whether there is any evidence of a change in the parasitological response to the artemisinin derivatives in Vietnam. Methods: From August 2010 to May 2011, a randomized controlled clinical trial in uncomplicated falciparum malaria was conducted to compare two doses of artesunate (AS) (2mg/kg/day versus 4 mg/kg/day for three days) followed by dihydroartemisinin-piperaquine (DHA-PPQ) and a control arm of DHA-PPQ. The goal was characterization of the current efficacy of artesunate in southern Vietnam. The primary endpoint of this study was the parasite clearance half-life; secondary endpoints included the parasite reduction ratios at 24 and 48 hours and the parasite clearance time. Results: 166 patients were recruited into the study. The median parasite clearance half-lives were 3.54 (AS 2mg/kg), 2.72 (AS 4mg/kg), and 2.98 hours (DHA-PPQ) (p=0.19). The median parasite-reduction ratio at 24 hours was 48 in the AS 2mg/kg group compared with 212 and 113 in the other two groups, respectively (p=0.02). The proportions of patients with a parasite clearance time of >72 hours for AS 2mg/kg, AS 4mg/kg and DHA-PPQ were 27%, 27%, and 22%, respectively. Early treatment failure occurred in two (4%) and late clinical failure occurred in one (2%) of the 55 patients in the AS 2mg/kg group, as compared with none in the other two study arms. The PCR-corrected adequate clinical and parasitological response (APCR) rates in the three groups were 94%, 100%, and 100% (p=0.04). Conclusions: This study demonstrated faster P. falciparum parasite clearance in southern Vietnam than in western Cambodia but slower clearance in comparison with historical data from Vietnam. Further studies to determine whether this represents the emergence of artemisinin resistance in this area are needed. Currently, the therapeutic response to DHA-PPQ remains satisfactory in southern Vietnam. Trial registration: NTC01165372. [ABSTRACT FROM AUTHOR]