Failure of dihydroartemisinin plus piperaquine treatment of falciparum malaria by under-dosing in an overweight patient

Pham

Nguyen

et al. 2021

Malar J

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.

Section: Discussionmentioning

confidence: 99%

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

Pham

Nguyen

et al. 2021

Malar J

“…In Vietnam, before 2015 DHA-PPQ treatment dose depended on patient's age (46). However, many studies have showed that PPQ underdosing (<48mg/kg) is an important factor for recrudescent parasitemia (44,47). In order to optimize the effectiveness of DHA-PPQ, the WHO recommends treatment with 3 days of ATCs to cover at least two asexual life circles of P. falciparum and DHA-PPQ weight-based dosing (7).…”

Section: Discussionmentioning

confidence: 99%

Spread of multidrug-resistant Plasmodium falciparum malaria and predictors of treatment failures in Vietnam

Pham²,

Nguyen³

et al. 2019

Preprint

Background Drug-resistant falciparum malaria is an increasing public health burden. We 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. ResultsMore than half (59.8%, 95%CI 55.1%-64.4%) of patient acquired P. falciparum infection of whom 21.9% (95%CI 17.1%-27.4%) had severe malaria, while 10.2% (95%CI 6.8%-14.5%) and 19.2% (95%CI 14.7%-24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. ETF was 6.8% among patients referred from Binh Phuoc province and Central Highland, 11.3% from other areas in Vietnam, and 6.9% from Africa. LTF was 16.2% among patients from Binh Phuoc province and Central Highland, 22.6% from other areas in Vietnam, and 27.6% from Africa.Most patients (98.5%) recovered completely. Having severe malaria was a predictor of ETF (AOR 4.42, 95%CI 1.85-10.61, P = 0.001). No predictor of LTF was identified.Conclusion P. falciparum remains the prevalent malaria parasite. Despite low mortality rate, severe malaria is not rare and is a significant predictor of ETF. Parenteral artesunate and an oral partner drug should be concurrently used for severe malaria to reduce the risk for ETF. The study alerts the possibility of drug-resistant malaria in Africa and other areas in Vietnam which are known as nonendemic areas of antimalarial 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.

“…In Vietnam, before 2016, DHA-PPQ treatment dose depended on patient's age (54). However, many studies have showed that PPQ under-dosing (< 48 mg/kg) is an important factor for recrudescent parasitemia (52,55). It is documented that the underdose of DHA-PPQ increases recrudescent parasitemia and sequentially increases treatment failure (52).…”

Section: Demographic Characteristics Of Study Participantsmentioning

confidence: 99%

Predictors of treatment failures of Plasmodium falciparum malaria in Vietnam: a 4-year single-center retrospective study

Pham²,

Nguyen³

et al. 2020

Preprint

BackgroundDrug-resistant falciparum malaria is an increasing public health burden. We examined the magnitude of Plasmodium falciparum infection and the patterns and predictors of treatment failure in Vietnam. MethodsMedical 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 outcomes. ResultsMore than half (59.8%, CI 55.1%-64.4%) of patient acquired P. falciparum infection of whom 21.9% (CI 17.1%-27.4%) had severe malaria, while 7.2% (CI 4.6%-10.9%) and 19.2% (CI 14.7%-24.5%) developed early treatment failure (ETF) and late treatment failure (LTF) respectively. ETF was 4.7% among patients referred from Binh Phuoc province and Central Highland, 12.9% from other areas in Vietnam, and 6.9% from Africa. LTF was 16.2% among patients from Binh Phuoc province and Central Highland, 22.6% from other areas in Vietnam, and 27.6% from Africa. Most patients (98.5%) recovered completely. 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.ConclusionP. 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 nonendemic areas of antimalarial 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.