In Vietnam, the artemisinin-based combination therapy (ACT) of dihydroartemisinin-piperaquine (DHA-PPQ) is used for first-line treatment of Plasmodium falciparum malaria. DHA-PPQ resistance is present in Binh Phuoc province in south Vietnam with failure rates of 26% in 2015. Therapeutic efficacy studies (TES) of DHA-PPQ have revealed a delayed parasite clearance in Dak Nong, Gia Lai, Khanh Hoa, Quang Nam and Ninh Thuan provinces with over 10% of patients microscopically positive on day 3 after starting treatment prompting concerns of declining efficacy of DHA-PPQ and emphasizing the importance of monitoring resistance.
In 2015-2016, in Ninh Thuan province we conducted a TES of ACTs (artesunate for 4 days followed by DHA-PPQ for 3 days versus a 3-day course of artemether-lumefantrine), which revealed the ACTs to be curative in treating P. falciparum infections. As part of the TES the in vitro susceptibility of 11 P. falciparum isolates to 9 antimalarials was characterized using the hypoxanthine incorporation assay. Of these, a sub-set of 5 P. falciparum isolates were assessed using the ring stage survival assay (RSA) and the piperaquine survival assay (PSA), recognized methods for predicting delayed parasite clearance and treatment failures with DHA-PPQ. The P. falciparum MRA1239 (DHA-sensitive) and MRA1240 (DHA-resistant) isolates, both from Cambodia, were used as references in the RSA and PSA. The in vitro findings showed that in the RSA the survival rates ranged between 0.7-1.5% (<10.88% cut-off) for the field isolates, greater than that for MRA1239 (0.16%), but markedly lower than that for MRA1240 (7.3%). In the PSA the field isolates and both MRA lines were sensitive to PPQ, with survival rates ranging 1.8 to 4.8% (<10% cut-off). These data provide additional evidence and confirmation of the clinical findings on efficacy of DHA-PPQ at the field site, but also reinforces the need for monitoring emerging resistance.