Effectiveness of dihydroartemisinin-piperaquine for treating Plasmodium falciparum malaria from sub-Saharan Africa: a retrospective study

Abstract

Background: Artemisinin-based combination therapies (ACTs) are the recommended first-line treatment for uncomplicated malaria. However, growing reports of artemisinin resistance, particularly in Southeast Asia, raise concerns about the efficacy of ACTs. This study aimed to assess potential changes over time in the effectiveness of a three-day regimen of dihydroartemisinin-piperaquine (DHA-PPQ) for treating imported uncomplicated Plasmodium falciparum malaria.

Methods: A retrospective observational study was conducted. We reviewed the records of patients treated for uncomplicated P. falciparum malaria in a single centre in Italy (2013-2024). The inclusion criteria were treatment with DHA-PPQ and available data on parasitaemia at baseline and on day three. The primary objective was to determine the rate of parasitaemia clearance on day three.

Results: All 90 patients but one were infected in sub-Saharan Africa. We excluded the patient infected in Yemen to obtain a more homogenous cohort. Baseline median parasitaemia was 0.136 % (IQR 0.029-0.750). On day 3, only 6 patients (6.7 %) still had circulating parasites, though in absence of early treatment failure. Follow-up data (available for 63 patients) excluded also late parasitological failures. No significant trend in day-3 positivity was observed across the three study periods (2013-2015, 2016-2019, 2020-2023; p = 0.339).

Conclusions: This study revealed no significant reduction in the effectiveness of DHA-PPQ over time for the treatment of uncomplicated P. falciparum malaria imported from Africa. While ACT failure remains rare in sub-Saharan Africa, continued surveillance is essential, especially to monitor resistance trends and inform treatment protocols.

Keywords: Artemisinin derivatives; Artemisinin-based combination therapy; Dihydroartemisinin-piperaquine; Malaria; Plasmodium falciparum; Resistance.