Efficacy of artemether-lumefantrine therapy for the treatment of uncomplicated Plasmodium falciparum malaria in Southwestern Ethiopia

Abstract

Background: The development and spread of chloroquine-resistant Plasmodium falciparum threatens the health of millions of people and poses a major challenge to the control of malaria. Monitoring drug efficacy in 2-year intervals is an important tool for establishing rational anti-malarial drug policies. This study addresses the therapeutic efficacy of artemether-lumefantrine (AL) for the treatment of Plasmodium falciparum in southwestern Ethiopia.

Methods: A 28-day in vivo therapeutic efficacy study was conducted from September to December, 2011, in southwestern Ethiopia. Participants were selected for the study if they were older than 6 months, weighed more than 5 kg, symptomatic, and had microscopically confirmed, uncomplicated P. falciparum. All 93 eligible patients were treated with AL and followed for 28 days. For each patient, recurrence of parasitaemia, the clinical condition, and the presence of gametoytes were assessed on each visit during the follow-up period. PCR was conducted to differentiate re-infection from recrudescence.

Results: Seventy-four (83.1 %) of the study subjects cleared fever by day 1, but five (5.6 %) had fever at day 2. All study subjects cleared fever by day 3. Seventy-nine (88.8 %) of the study subjects cleared the parasite by day 1, seven (7.9 %) were blood-smear positive by day 1, and three (3.4 %) were positive by day 2. In five patients (5.6 %), parasitaemia reappeared during the 28-day follow-up period. From these five, one (1.1 %) was a late clinical failure, and four (4.5 %) were a late parasitological failure. On the day of recurrent parasitaemia, the level of chloroquine/desethylchloroquine (CQ-DCQ) was above the minimum effective concentration (>100 ng/ml) in one patient. There were 84 (94.4 %) adequate clinical and parasitological responses. The 28-day, PCR-uncorrected (unadjusted by genotyping) cure rate was 84 (94.4 %), whereas the 28-day, PCR-corrected cure rate was 87 (97.8 %). Of the three re-infections, two (2.2 %) were due to P. falciparum and one (1.1 %) was due to P. vivax. From 89 study subjects, 12 (13.5 %) carried P. falciparum gametocytes at day 0, whereas the 28-day gametocyte carriage rate was 2 (2.2 %).

Conclusions: Years after the introduction of AL in Ethiopia, the finding of this study is that AL has been highly effective in the treatment of uncomplicated P. falciparum malaria and reducing gametocyte carriage in southwestern Ethiopia.

Fig. 1

Study subjects participated on AL efficacy study and treatment outcome. From a total of 125 P. falciparum cases, 93 fulfilled the inclusion criteria and gave written and informed consent and assent to participate in the therapeutic efficacy of AL for the treatment of P. falciparum, while 32 study subjects did not meet the inclusion criteria and were excluded from the study. From 32 excluded from the study, 11 excluded to provide consent and assent, 12 had a low parasite count from the thick blood film, 2 had sever disease (Tb positive) and 7 were less than 6 months. Among the 93 study participants, one blood film reading was discrepant between the two microscopic readers and decision was made based on the third senior laboratory personnel reading. On the first day of the study, two study subjects vomited the drug twice and excluded from the study and analysis. On day 14 and 21, two patients did not return on the follow-up day. We could not find one of the patients, and we were informed that the other patient had moved from the area, so both were considered lost to follow-up.