Adherence to treatment with artemether–lumefantrine or amodiaquine–artesunate for uncomplicated malaria in children in Sierra Leone: a randomized trial

Abstract

BackgroundPrompt, effective treatment of confirmed malaria cases with artemisinin-based combination therapy (ACT) is a cornerstone of malaria control. Maximizing adherence to ACT medicines is key to ensuring treatment effectiveness.MethodsThis open-label, randomized trial evaluated caregiver adherence to co-formulated artemether–lumefantrine (AL) and fixed-dose amodiaquine–artesunate (AQAS) in Sierra Leone. Children aged 6–59 months diagnosed with malaria were recruited from two public clinics, randomized to receive AL or AQAS, and visited at home the day after completing treatment. Analyses were stratified by site, due to differences in participant characteristics and outcomes.ResultsOf the 784 randomized children, 680 (85.6%) were included in the final per-protocol analysis (340 AL, 340 AQAS). Definite adherence (self-reported adherence plus empty package) was higher for AL than AQAS at both sites (Site 1: 79.4% AL vs 63.4% AQAS, odds ratio [OR] 2.16, compared to probable adherence plus probable or definite non-adherence, 95% confidence interval [CI] 1.34–3.49; p = 0.001; Site 2: 52.1% AL vs 37.5% AQAS, OR 1.53, 95% CI 1.00–2.33, p = 0.049). However, self-reported adherence (ignoring drug package inspection) was higher for both regimens at both sites and there was no strong evidence of variation by treatment (Site 1: 96.6% AL vs 95.9% AQAS, OR 1.19, 95% CI 0.39–3.63, p = 0.753; Site 2: 91.5% AL vs 96.4% AQAS, OR 0.40, 95% CI 0.15–1.07, p = 0.067). In Site 2, correct treatment (correct dose + timing + duration) was lower for AL than AQAS (75.8% vs 88.1%, OR 0.42, 95% CI 0.23–0.76, p = 0.004). In both sites, more caregivers in the AQAS arm reported adverse events (Site 1: 3.4% AL vs 15.7% AQAS, p < 0.001; Site 2: 15.2% AL vs 24.4% AQAS, p = 0.039).ConclusionsSelf-reported adherence was high for both AL and AQAS, but varied by site. These results suggest that each regimen has potential disadvantages that might affect adherence; AL was less likely to be taken correctly at one site, but was better tolerated than AQAS at both sites. Measuring adherence to anti-malarials remains challenging, but important. Future research should focus on comparative studies of new drug regimens, and improving the methodology of measuring adherence.Trial registration: Clinicaltrials.gov, NCT01967472. Retrospectively registered 18 October 2013, https://clinicaltrials.gov/ct2/show/NCT01967472Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2370-x) contains supplementary material, which is available to authorized users.

Coverage of community case management for malaria through CHWs: a quantitative assessment using primary household surveys of high-burden areas in Chhattisgarh state of India

“…The current study found that CHWs played an important role in ensuring completion of treatment for malaria. The method of measuring complete-treatment in this study satisfies the conditions of being called 'definite adherence' [28,29]. This is another aspect where CHWs offered a big advantage over other providers.…”

Coverage of Community Case Management for Malaria through CHWs: A Quantitative Assessment using Primary Household Surveys of High-burden Areas in Chhattisgarh state of India

“…The current study found that CHWs played an important role in ensuring completion of treatment for malaria. The method of measuring complete-treatment in this study satis es the conditions of being called 'de nite adherence' [28,29]. This is another aspect where CHWs offered a big advantage over other providers.…”

Overview of artemisinin effectiveness during outset years of its implementation in the western Brazilian Amazon

“…The “day-4” parasitaemia measure was considered a surveillance tool for artemisinin tolerance, guaranteeing the current WHO-recommended cut-off value (72 hours). 3 , 17 …”

“…2 In this fight there is a vast and efficient therapeutic arsenal, however, despite the proven efficacy treatment failures are frequent and may be the result of drug resistance or inadequate exposure to drugs, whether due to failure in prescription and dispensing, incorrect dosage and even if the patient does not adhere to the treatment. 2 , 3 Moreover, resistance to antimalarial chemotherapy has been one of the major obstacle in the fight against this disease. The monitoring of the effectiveness of antimalarial drugs is a crucial component in the disease’s control, as the parasite develops mechanisms to avoid the action of antimalarial compounds.…”