Adherence to artemisinin-based combination therapy for the treatment of malaria: a systematic review of the evidence

Abstract

Background: Increasing access to and targeting of artemisinin-based combination therapy (ACT) is a key component of malaria control programmes. To maximize efficacy of ACT and ensure adequate treatment outcomes, patient and caregiver adherence to treatment guidelines is essential. This review summarizes the current evidence base on ACT adherence, including definitions, measurement methods, and associated factors.

Methods: A systematic search of the published literature was undertaken in November 2012 and updated in April 2013. Bibliographies of manuscripts were also searched and additional references identified. Studies were included if they involved at least one form of ACT and reported an adherence measurement.

Results: The search yielded 1,412 records, 37 of which were found to measure adherence to ACT. Methods to measure adherence focused on self-report, pill counts and bioassays with varying definitions for adherence. Most studies only reported whether medication regimens were completed, but did not assess how the treatment was taken by the patient (i.e. timing, frequency and dose). Adherence data were available for four different ACT formulations: artemether-lumefantrine (AL) (range 39-100%), amodiaquine plus artesunate (AQ + AS) (range 48-94%), artesunate plus sulphadoxine-pyrimethamine (AS + SP) (range 39-75%) and artesunate plus mefloquine (AS + MQ) (range 77-95%). Association between demographic factors, such as age, gender, education and socio-economic status and adherence to ACT regimens was not consistent. Some evidence of positive association between adherence and patient age, caregiver education levels, drug preferences, health worker instructions, patient/caregiver knowledge and drug packaging were also observed.

Conclusions: This review highlights the weak evidence base on ACT adherence. Results suggest that ACT adherence levels varied substantially between study populations, but comparison between studies was challenging due to differences in study design, definitions, and methods used to measure adherence. Standardising methodologies for both self-report and bioassays used for evaluating adherence of different formulations across diverse contexts would improve the evidence base on ACT adherence and effectiveness; namely, specific and measurable definitions for adherence are needed for both methodologies. Additionally, further studies of the individual factors and barriers associated with non-adherence to ACT are needed in order to make informed policy choices and to improve the delivery of effective malaria treatment.

Figure 1

Treatment effectiveness pathway. This figure depicts each step along the pathway to malaria treatment effectiveness. At the top of the pathway are the health system factors such as choosing efficacious treatments such as ACT, improving access to those treatments and targeting treatments to those that need it most. The second half of the pathway depicts individual factors that can enhance or disrupt the effectiveness pathway such as provider compliance to treatment guidelines and patient/caregiver adherence to treatment regimens. Source: Original figure courtesy of Marcel Tanner, personal communication 2012 and manuscript published by, The malERA Consultative Group on Health Systems and Operational Research, A Research Agenda for Malaria Eradication: Health Systems and Operational Research. PLoS Med, 2011. 8(1): p. E1000397.

Figure 2

Systematic review process. Flow diagram (adapted from PRISMA) describing the systematic review of the literature on ACT adherence.