Atovaquone-proguanil in the treatment of imported uncomplicated Plasmodium falciparum malaria: a prospective observational study of 553 cases

Abstract

BackgroundEach year, thousands of cases of uncomplicated malaria are imported into Europe by travellers. Atovaquone-proguanil (AP) has been one of the first-line regimens used in France for uncomplicated malaria for almost ten years. While AP’s efficacy and tolerance were evaluated in several trials, its use in “real life” conditions has never been described. This study aimed to describe outcome and tolerance after AP treatment in a large cohort of travellers returning from endemic areas.MethodsBetween September 2002 and January 2007, uncomplicated malaria treated in nine French travel clinics with AP were followed for 30 days after AP initiation. Clinical and biological data were collected at admission and during the follow-up.ResultsA total of 553 patients were included. Eighty-eight percent of them were born in Africa, and 61.8% were infected in West Africa, whereas 0.5% were infected in Asia. Migrants visiting friends and relatives (VFR) constituted 77.9% of the patients, the remainder (32.1%) were backpackers. Three-hundred and sixty-four patients (66%) fulfilled follow-up at day 7 and 265 (48%) completed the study at day 30. Three patients had treatment failure. One-hundred and seventy-seven adverse drug reactions (ADR) were reported during the follow-up; 115 (77%) of them were digestive ADR. Backpackers were more likely to experiment digestive ADR compared to VFR (OR = 3.8; CI 95% [1.8-8.2]). Twenty patients had to be switched to another regimen due to ADR.ConclusionThis study seems to be the largest in terms of number of imported uncomplicated malaria cases treated by AP. The high rate of reported digestive ADR is striking and should be taken into account in the follow-up of patients since it could affect their adherence to the treatment. Beside AP, artemisinin combination therapy (ACT) is now recommended as first-line regimen. A comparison of AP and ACT, in terms of efficacy and tolerance, would be useful.

Plasmodium falciparum Clearance Is Pitting-Dependent With Artemisinin-Based Drugs but Pitting-Independent With Atovaquone-Proguanil or Mefloquine

“…Treatment with AP results in longer parasite clearance, which raised concerns for higher risk of treatment failure. However, the high cure rate in travelers [10] suggests that the delayed parasite clearance post-AP may be due to lack of pitting in the spleen rather than defective parasite killing. Pitting is absent in splenectomized patients treated for malaria by artemisinins, but the prolonged circulation of red cells containing dead parasite remnants ("hearse RBCs") in these patients does not correlate with an obvious increase in treatment failure.…”

UK malaria treatment guidelines 2016

“…Atovaquoneeproguanil (Malarone Ò ) has been used extensively in some Western settings with high levels of efficacy, although parasite clearance is relatively slow (66% at three days). 47,49 Almost a quarter of patients experienced gastro-intestinal side-effects and patients should be warned about these to ensure full adherence.…”

Targeted deep amplicon sequencing of kelch 13 and cytochrome b in Plasmodium falciparum isolates from an endemic African country using the Malaria Resistance Surveillance (MaRS) protocol

“…Both the EU and the USA, recommend the use of atovaquone/proguanil (AP) for chemoprophylaxis [5][6][7]. In the USA, AP is used as a primary treatment choice for imported uncomplicated P. falciparum cases, while in the EU, two ACTs, artemether-lumefantrine (AL) and dihydroartemisinin/piperaquine (DHA/PPQ) are licensed as treatment options for uncomplicated P. falciparum malaria [8][9][10]; AP can be used if an ACT is not available [10].…”