Predictors of treatment failures of plasmodium falciparum malaria in Vietnam: a 4-year single‐centre retrospective study

Abstract

Background Drug-resistant falciparum malaria is an increasing public health burden. This study examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam. Methods Medical records of all 443 patients with malaria infection admitted to the Hospital for Tropical Diseases between January 2015 and December 2018 were used to extract information on demographics, risk factors, symptoms, laboratory tests, treatment, and outcome. Results More than half (59.8%, 265/443, CI 55.1–64.4%) of patients acquired Plasmodium falciparum infection of whom 21.9% (58/265, CI 17.1–27.4%) had severe malaria, while 7.2% (19/265, CI 4.6–10.9%) and 19.2% (51/265, CI 14.7–24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. Among 58 patients with severe malaria, 14 (24.1%) acquired infection in regions where artemisinin resistance has been documented including Binh Phuoc (11 patients), Dak Nong (2 patients) and Gia Lai (1 patient). Under treatment with intravenous artesunate, the median (IQR) parasite half-life of 11 patients coming from Binh Phuoc was 3 h (2.3 to 8.3 h), two patients coming from Dak Nong was 2.8 and 5.7 h, and a patient coming from Gia Lai was 6.5 h. Most patients (98.5%, 261/265) recovered completely. Four patients with severe malaria died. Severe malaria was statistically associated with receiving treatment at previous hospitals (P < 0.001), hepatomegaly (P < 0.001) and number of inpatient days (P < 0.001). Having severe malaria was a predictor of ETF (AOR 6.96, CI 2.55–19.02, P < 0.001). No predictor of LTF was identified. Conclusions Plasmodium falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. To reduce the risk for ETF, studies are needed to examine the effectiveness of combination therapy including parenteral artesunate and a parenteral partner drug for severe malaria. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam, which are known as non-endemic areas of anti-malarial drug resistance. A more comprehensive study using molecular technique in these regions is required to completely understand the magnitude of drug-resistant malaria and to design appropriate control strategies.

Exploring the feasibility of introducing triple artemisinin-based combination therapy in the malaria treatment policy in Vietnam

“…Respondents confirmed their awareness of the emergence and spread of artemisinin resistance in Vietnam, but the situation was considered somewhat more positive than in other countries in the region. The treatment failure rate with DHA-PPQ reached up to 60%, which was also confirmed by recent therapeutic efficacy studies [ 28 , 29 ]. Artesunate–mefloquine is currently not widely used in the NMP.…”

Exploring the feasibility of introducing triple artemisinin-based combination therapies in the malaria treatment policy in Vietnam

“…The treatment failure rate with DHA-PPQ reached up to 60%, which was also con rmed by recent therapeutic e cacy studies (27,28). Artesunate-me oquine is currently not widely used in the NMP.…”

Defining the next generation of severe malaria treatment: a target product profile

“…Modelling studies suggest that delayed parasite killing associated with artemisinin partial resistance may affect clinical outcomes for some patients with severe malaria [ 35 ]. However, reports of intravenous artesunate failures from the GMS where artemisinin partial resistance is established, but where severe malaria is uncommon, are limited [ 36 , 37 ]. Nevertheless, WHO guidelines suggest a combination of parenteral artesunate and quinine for severe malaria in regions with artemisinin partial resistance [ 11 ], though clinical data are sparse on the feasibility, safety and efficacy of this combination [ 38 ].…”