Successful Treatment of Plasmodium Falciparum Malaria With a Six-Dose Regimen of Artemether-Lumefantrine Versus Quinine-Doxycycline in the Western Amazon Region of Brazil

Abstract

This randomized, open-label study compared a three-day, six-dose regimen of artemether-lumefantrine with a five-day, 19-dose regimen of quinine-doxycycline for the treatment of Plasmodium falciparum malaria in the western Amazon region of Brazil. All patients remained hospitalized during their treatment and the study assessments were scheduled daily from the start of treatment (day 0) through day 6. By day 3, the percentage of infected patients was 0% in the artemether-lumefantrine group and 48.8% in the quinine-doxycycline group. Median parasite clearance time was significantly shorter in the artemether-lumefantrine group (two days) compared with the quinine-doxycycline group (three days) (P < 0.0001). Two patients in the quinine-doxycycline group left the study early because of treatment ineffectiveness or adverse event. Adverse events were reported by 91.5% of the study participants, most of which were mild in severity and/or not considered related to study treatment. Artemether-lumefantrine was shown to be an efficacious, safe, and convenient treatment for P. falciparum malaria in a highly drug-resistant region of South America.

Analysis of polymorphisms in Plasmodium falciparum genes related to drug resistance: a survey over four decades under different treatment policies in Brazil

“…All patients were treated following Brazilian national guidelines for malaria chemotherapy or approved research therapeutic protocols (artemether or artesunate in monotherapy). Recrudescent parasitaemia after use of artemisinin derivatives in monotherapy were treated according to Brazilian guidelines [13, 45]. Monitoring of parasitaemia was carried out on days 3, 7, 14, 28 and 35 after treatment was started.…”

“…Mefloquine was incorporated in the 1990s as a new tool to treat resistant P. falciparum malaria , but the emergence of chemoresistance [11] led to the adoption of new strategies, such as artemisinin-based combination therapy (ACT), as recommended by the WHO in order to refrain the spread of resistance [12]. In Brazil, since 2006 the first-line treatment recommendation for non-complicated P. falciparum infections is the use of artemether plus lumefantrine or artesunate plus mefloquine combinations [13]. Nevertheless, decreased sensitivity has already been reported in Southeast Asia [14–16], Africa [17] and South America [18].…”

Chemoresistance of Plasmodium falciparum and Plasmodium vivax parasites in Brazil: consequences on disease morbidity and control

“…As might have been predicted, a continuous increase in QN resistance resulted in a pronounced P. falciparum morbidity intensification, and a phase II study was conducted in the Brazilian Amazon to compare treatments with artemether/lumefantrine (Coartem ® , supplied by Novartis) to QN/doxycycline (Alecrim et al 2006). In view of the promising results, the artemisinin-combination therapy (ACT) (represented by Coartem) and artesunate plus MQ (supplied by Farmanguinhos) were introduced by the Brazilian Malaria Control Program for uncomplicated falciparum malaria treatment starting in 2007 and 2008, respectively (Ladislau 2008, Carmargo API registers the number of malaria cases/1,000 inhabitants.…”

Evidence-based public health and prospects for malaria control in Brazil

“…This fixed-dose artesunate-mefloquine combination remains the first option for falciparum malaria in Acre, while in all other states in Brazil arthemeter-lumefantrine is the first-line therapy. A small, open-label clinical trial supported by Novartis, with 27 patients from two sites (Manaus in Western Amazonia and Santarém in Eastern Amazonia) in the arthemeter-lumefantrine arm, who were followed for seven days, described a faster clearance of P. falciparum parasitemia with a six-dose regimen of arthemeter-lumefantrine compared to quininedoxycycline [48,49]. No other published studies have investigated the in vivo efficacy of arthemeterlumefantrine, artesunate-mefloquine or other ACTbased regimens in Brazil, although several unpublished clinical trials have been performed in RAVREDA sentinel sites [41].…”