Therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Chewaka District, Ethiopia

Abstract

Background The efficacy of artemether-lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria in south-western Ethiopia is poorly documented. Regular monitoring of drug efficacy is an important tool for supporting national treatment policies and practice. This study investigated the therapeutic efficacy of AL for the treatment of P. falciparum malaria in Ethiopia. Methods The study was a one-arm, prospective, evaluation of the clinical and parasitological, responses to directly observed treatment with AL among participants 6 months and older with uncomplicated P. falciparum malaria. Real-time polymerase chain reaction (PCR) and nested PCR reaction methods were used to quantify and genotype P. falciparum . A modified protocol based on the World Health Organization 2009 recommendations for the surveillance of anti-malarial drug efficacy was used for the study with primary outcomes, clinical and parasitological cure rates at day-28. Secondary outcomes assessed included patterns of fever and parasite clearance. Cure rate on day-28 was assessed by intention to treat (ITT) and per protocol (PP) analysis. Parasite genotyping was also performed at baseline and at the time of recurrence of parasitaemia to differentiate between recrudescence and new infection. Results Of the 80 study participants enrolled, 75 completed the follow-up at day-28 with ACPR. For per protocol (PP) analysis, PCR-uncorrected and-corrected cure rate of AL among the study participants was 94.7% (95% CI 87.1–98.5) and 96% (95% CI 88.8–99.2), respectively. For intention to treat (ITT) analysis, the cure rate was 90% (95% CI 88.8–99.2). Based on Kaplan–Meier survival estimate, the cumulative incidence of failure rate of AL was 3.8% (95% CI 1.3–11.4). Only three participants 3.8% (95% CI 0.8–10.6) of the 80 enrolled participants were found to be positive on day-3. The day three-positive participants were followed up to day 28 and did not correspond to treatment failures observed during follow-up. Only 7.5% (6/80) of the participants were gametocyte-positive on enrollment and gametocytaemia was absent on day-2 following treatment with AL. Conclusions The therapeutic efficacy of AL is considerably high (above 90%). AL remained highly efficacious in the treatment of uncomplicated malaria in the study area resulted in rapid fever and parasite clearance as well as low gametocyte carriage rates despite the use of this combination for more than 15 years.

Efficacy and Safety of Artemether-Lumefantrine for Treatment of Uncomplicated P. Falciparum malaria in Ethiopia: A Systematic Review and Meta-Analysis

“…An adverse event was de ned as any undesirable medical occurrence (symptoms, signs or laboratory ndings) in a patient once they were enrolled to the studies regardless of whether it was related to the treatment. Adverse events were judged according to their causal association with AL (unlikely, possible and probable) and severity (mild, moderate or severe) [7].In this review, mild adverse events (a headache, cough, fever, diarrhoea, vomiting, perioral ulcer, anorexia, abdominal pain, dizziness and nausea, weakness/fatigue and others) were reported and almost all were resolved soon after completion of the treatment except cough [48,53,54]. Similar mild adverse events have been associated with AL, the most common being headache, fever, vomiting followed by gastrointestinal disturbances [65,69].The observed rate of 36.1%, (550/1523)ADRs was comparable with the rate reported in the previous review in Ethiopia where 269 of 633 patients had ADRs, with a pooled event rate of 41.2% [68].…”

“…The summary characteristics of the included studies are shown in Table 1.Fifteen studies satis ed the inclusion criteria and were included in this systematic review and meta-analysis with a total sample size of 1523 participants that ranged from 60 patients [46] to 315 patients [47]. Seven of the studies were interventional [47,48,49,50,51,52,53], and the other eight studies were observational study [46,54,55,56,57,58,59,60].These studies were conducted in different malarious parts of the Country with varied transmission intensity (Fig. 2).…”

“…2). From the analyses of 15 studies included, only seven studies used PCR-corrected cure rates of AL [47,48,49,50,51,52,53] while PCR-uncorrected AL cure rates were used for the remaining studies. Overall, a signi cant high malaria treatment success of 98.4% (95% CI 97.6-99.1)(Fig.…”

“…The PCR-corrected cure rates of AL ranged from 95.0 to 99.4% in per-protocol analysis and 88.8 to 97.4% in intention-to-treat analysis.The percentage of ACPR and the 95% CI are presented in Table 2.The highest cure rate 99.4 %( 95% CI 97.4-100.0) was reported by study conducted in Jimma Zone, Southwest Ethiopia in 2012 [47], and97.4%(95% CI: 93.9-100) reported by study conducted in Bishoftu Malaria Clinic and Bulbula Health Center, Oromia Regional State, Ethiopia 2011 [49]. .Some authors did not measure fever clearance on subsequent days post drug administration and only choose day-3 for this clinical measurement [53,57].Among the fteen studies that reported parasite clearance, ve studies showed day-3 parasitaemic cases of 5.7%,5.1%, 5%, 3.9 and 3.8% [48,51,57,58,59].Table 3shows the overall progress of fever and parasite clearance in the rst three days of AL treatment.…”

“…Seven interventional studies [47,48,49,50,51,52,53] were assessed using the modi ed Jadad scale [38] with high qualities with a value score of 4 (Additional le 4: Table S4) and while the remaining eight observational studies [46,54,55,56,57,58,59,60] were assessed with the STROBE statement [39]with high qualities a range of 81.8 % to 91 % (Additional le 4: Table S4. ).…”