Dihydroartemisinin‐piperaquine versus artesunate‐amodiaquine for treatment of malaria infection in pregnancy in Ghana: an open‐label, randomised, non‐inferiority trial

Abstract

Abstractobjective To determine whether dihydroartemisinin-piperaquine (DHA-PPQ) is non-inferior to artesunate-amodiaquine (ASAQ) for treating uncomplicated malaria infection in pregnancy.methods A total of 417 second/ third trimester pregnant women with confirmed asymptomatic Plasmodium falciparum parasitaemia were randomised to receive DHA-PPQ or ASAQ over 3 days. Women were followed up on days 1, 2, 3, 7, 14, 28 and 42 after treatment start and at delivery for parasitological, haematological, birth outcomes and at 6-week post-partum to ascertain the health status of the babies. Parasitological efficacy (PE) by days 28 and 42 were co-primary outcomes. Analysis was per-protocol (PP) and modified intention-to-treat (ITT). Non-inferiority was declared if the two-sided 95% confidence interval for PE at the endpoints excluded 5% lower efficacy for DHA-PPQ. Secondary outcomes were assessed for superiority.results In PP analysis, PE was 91.6% for DHA-PPQ and 89.3% for ASAQ by day 28 and 89.0% and 86.5%, respectively, by day 42. DHA-PPQ was non-inferior to ASAQ with respect to uncorrected PE [adjusted difference by day 28 (DHA-PPQ-ASAQ); 3.5% (95%CI: À1.5, 8.5); and day 42: 3.9% (95%CI: À2.7, 10.4)]. ITT analysis gave similar results. PCR to distinguish recrudescence and reinfection was unsuccessful. DHA-PPQ recipients had fewer adverse events of vomiting, dizziness, and general weakness compared to ASAQ. Both drugs were well-tolerated, and there was no excess of adverse birth outcomes.conclusion DHA-PPQ was non-inferior to ASAQ for treatment of malaria infection during pregnancy. No safety concerns were identified. Our findings contribute to growing evidence that DHA-PPQ is useful for control of malaria in pregnancy.

Systematic literature review and meta-analysis of the efficacy of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: methodological challenges

“…In seven studies, assessors and laboratory staff (n = 2) [ 45 , 48 ] or only laboratory staff (e.g. microscopists) (n = 5) [ 44 , 46 , 50 , 52 , 57 ] were blinded.…”

“…non-fixed dose combination ASMQ) [ 39 – 42 , 48 ]. Ten RCTs compared different combinations of ABT [ 38 , 45 , 49 , 50 , 52 – 57 ] (see Additional file 6 ). Two RCTs compared different regimens of QBT [ 17 , 43 ], two compared quinine versus non-ABT [ 36 , 37 ] and three compared ABT versus non-ABT (e.g.…”

“…Asymptomatic patients were included in 55% (12/22) of RCTs and 50% (13/26) of non-RCTs. Two of them included only asymptomatic women [ 52 , 60 ]. Fifteen studies (31%, 15/48) intentionally included patients who failed previous treatment, but only three of them were RCTs [ 38 , 43 , 45 ].…”

Molecular Markers of Plasmodium falciparum Drug Resistance in Parasitemic Pregnant Women in the Middle Forest Belt of Ghana

“…We assessed the prevalence of SNPs/haplotypes in the Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps genes in a cross-sectional study of asymptomatic pregnant women of all gravidity enrolled in a drug trial from antenatal clinics at St. Michael's and Bekwai Government hospitals in the Bosomtwe and Bekwai districts, respectively, in Ghana. 13 The geometric mean parasite density was 224/μL (95% confidence interval; 193, 289). 13 Some women were likely exposed to IPTp-SP in previous pregnancies whereas ACT use cannot be ruled out given that second and third trimester women were enrolled.…”

“…13 The geometric mean parasite density was 224/μL (95% confidence interval; 193, 289). 13 Some women were likely exposed to IPTp-SP in previous pregnancies whereas ACT use cannot be ruled out given that second and third trimester women were enrolled.…”