A Randomized Comparison of Dihydroartemisinin-Piperaquine and Artesunate-Amodiaquine Combined With Primaquine for Radical Treatment of Vivax Malaria in Sumatera, Indonesia

Abstract

Background. A high prevalence of chloroquine-resistant Plasmodium vivax in Indonesia has shifted first-line treatment to artemisinin-based combination therapies, combined with primaquine (PQ) for radical cure. Which combination is most effective and safe remains to be established.Methods. We conducted a prospective open-label randomized comparison of 14 days of PQ (0.25 mg base/kg) plus either artesunate-amodiaquine (AAQ + PQ) or dihydroartemisinin-piperaquine (DHP + PQ) for the treatment of uncomplicated monoinfection P. vivax malaria in North Sumatera, Indonesia. Patients were randomized and treatments were given without prior testing for G6PD status. The primary outcome was parasitological failure at day 42. Patients were followed up to 1 year.Results. Between December 2010 and April 2012, 331 patients were included. After treatment with AAQ + PQ, recurrent infection occurred in 0 of 167 patients within 42 days and in 15 of 130 (11.5%; 95% confidence interval [CI], 6.6%–18.3%) within a year. With DHP + PQ, this was 1 of 164 (0.6%; 95% CI, 0.01%–3.4%) and 13 of 143 (9.1%; 95% CI, 4.9%–15.0%), respectively (P > .2). Intravascular hemolysis occurred in 5 patients, of which 3 males were hemizygous for the G6PD-Mahidol mutation. Minor adverse events were more frequent with AAQ + PQ.Conclusions. In North Sumatera, Indonesia, AAQ and DHP, both combined with PQ, were effective for blood-stage parasite clearance of uncomplicated P. vivax malaria. Both treatments were safe, but DHP + PQ was better tolerated.Clinical Trials Registration. NCT01288820.

Therapeutic Efficacy and Safety of Dihydroartemisinin-Piperaquine (DP) for the Treatment of Uncomplicated Plasmodium Vivax Malaria: A Single Center Study

“…It was well tolerated with no adverse side effect on 42 days follow up. Results are similar to other trials such as comparative trial of Chloroquine and DAP in Afghanistan 16 and Open-label, randomized controlled study showing that DAP is more effective than CQ+SP, AST+SP & AL in treating uncomplicated P.Vivax malaria 16 Gametocytes were seen in 89 (86.4%) cases on enrolment, but cleared in 83(93.3%) on day 1 with 89 (100%) clearances by day 7. [Table1], similar effect of DAP was seen on gametocyte clearance in another study 17 .…”

Fixed-Dose Artesunate–Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial

“…Its influence is illustrated by 2 trials that compared the ASAQ loose-dose combination to dihydroartemisinin–piperaquine, an ACT with a longer half-life. Lower efficacy against late recurrences of ASAQ [43] was not confirmed when PQ was coadministered [44]. This rationale is supported by the higher efficacy of CQ in preventing late recurrences compared with drugs with shorter half-lives (arthemeter–lumefantrine) in areas of low prevalence of CQR [47].…”

Mechanism of dihydroartemisinin-induced apoptosis in prostate cancer PC3 cells: An iTRAQ-based proteomic analysis

“…There is therefore an urgent need for novel therapeutic strategies for CRPC. Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin isolated from the Chinese medicinal plant Artemisia annua L., has been widely used as an effective antimalarial drug [15][16][17][18][19]. Recently, many studies have shown that DHA is the most potent anticancer agent among artemisinin and its derivatives [20], and has in vitro and in vivo anticancer activity in different types of human cancer cells, such as hepatocellular carcinoma, prostate cancer, gastric cancer, osteosarcoma, breast cancer, esophageal cancer, pancreatic cancer, lung cancer, and ovarian cancer [21][22][23][24][25][26][27][28][29][30][31].…”