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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.

SUBMITTER: Banek K

PROVIDER: S-EPMC3893456 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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

Banek Kristin K Lalani Mirza M Staedke Sarah G SG Chandramohan Daniel D

Malaria journal 20140106

<h4>Background</h4>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.<h4>Methods</h4>A systematic search of the published literature was undertake ...[more]

PMID: 24386988

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Project description:BACKGROUND:The World Health Organization recommends the use of artemisinin-based combination therapy (ACT) to treat uncomplicated malaria for the control of malaria across the world. There are several types of ACT used across malaria-endemic countries, yet there is little information about preferences and adherence practices regarding different types of ACT. The objective of this study was to evaluate levels of adherence to two types of ACT, artemether-lumefantrine (AL) and artesunate?+?amodiaquine (ASAQ), for the treatment of uncomplicated malaria among prescribers and patients in Guinea in 2016. METHODS:The study included a review of records of malaria patients and three health-facility, cross-sectional surveys. Patients diagnosed with uncomplicated malaria and prescribed ACT (n?=?1830) were recruited and visited in their home after receiving the medication and administered a questionnaire regarding ACT adherence. Prescribers (n?=?115) and drug dispensers (n?=?43) were recruited at the same public health facilities and administered questionnaires regarding prescribing practices and opinions regarding the national treatment policies and protocols. RESULTS:According to the registry review, 35.8% of all-cause consultations were recorded as malaria. Of these, 26.6% were diagnosed clinically without documentation of laboratory confirmation. The diagnosis of uncomplicated malaria represented 64.1% of malaria cases among children under 5 years and 74.9% of those 5 years of age and older. An ACT was prescribed for 83.5% of cases of uncomplicated malaria. Among participants in the study, ACT adherence was 95.4% (95% CI 94.4, 96.3). Overall, about one in four patients (23.4%; 95% CI 21.5, 25.3) reported experiencing adverse events. While patients prescribed ASAQ were significantly more likely to report experiencing adverse effects than patients on AL (p?<?0.001), given the overall high adherence, there was no evidence of a statistically significant difference in adherence between AL and ASAQ. Patients 5 years or older who reported experiencing adverse events were more likely to be non-adherent. CONCLUSION:Although there were more reported adverse events associated with ASAQ when compared with AL, both prescribers and patients were found to be mostly adherent to ACT for the treatment of malaria, regardless of ACT type.

Project description:BACKGROUND:Artemisinin combination therapy (ACT) is recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria, whereas chloroquine is still commonly used for the treatment of non-falciparum species (Plasmodium vivax, Plasmodium ovale and Plasmodium malariae). A more simplified, more uniform treatment approach across all malaria species is worthwhile to be considered both in endemic areas and for malaria as an imported condition alike. METHODS:A PROSPERO-registered systematic review to determine the efficacy and safety of ACT for the treatment of non-falciparum malaria was conducted, following PRISMA guidelines. Without language restrictions, Medline/PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, Biosis Previews and the African Index Medicus were searched for studies published up to November 2014. RESULTS:The literature search identified 986 reports; 40 publications were found eligible for inclusion, all of them on non-falciparum malaria in endemic areas. Most evidence was available for P. vivax (n?=?35). Five clinical trials in total were identified evaluating ACT for P. ovale, P. malariae and Plasmodium knowlesi. Most ACT presentations have high efficacy against P. vivax parasites; artemisinin-based combinations have shorter parasite and fever clearance times compared to chloroquine. ACT is as effective as chloroquine in preventing recurrent parasitaemia before day 28. Artemisinin-based combinations with long half-lives show significantly fewer recurrent parasitaemia up to day 63. The limited evidence available supports both the use of chloroquine and an ACT for P. ovale and P. malariae. ACT seems to be preferable for optimal treatment of P. knowlesi. CONCLUSION:ACT is at least equivalent to chloroquine in effectively treating non-falciparum malaria. These findings may facilitate development of simplified protocols for treating all forms of malaria with ACT, including returning travellers. Obtaining comprehensive efficacy and safety data on ACT use for non-falciparum species particularly for P. ovale, P. malariae and P. knowlesi should be a research priority. TRIAL REGISTRATION:CRD42014009103.

Project description:BACKGROUND:Malaria is a major public health problem in endemic countries including Sudan, where about 75% of populations are at risk. Due to widespread of chloroquine-resistant strains of Plasmodium falciparum, artemisinin-based combination therapy (ACT) is currently treatment of choice for malaria in the vast majority of malaria-endemic countries. This systematic review and meta-analysis is performed to obtain an overall stronger evidence of the outcomes of ACT in the treatment of uncomplicated falciparum malaria from the existing literature in Sudan. METHODS:The preferred reporting items for systematic review and meta-analysis statement were used to select studies to be included in this review. A computerized systematic strategy was adopted to search articles from PubMed, Google Scholar and Science Direct databases. Unpublished materials were also included. Open Meta-Analyst software was used to perform the meta-analysis. Random effects model was used to combine the included studies and the heterogeneity of studies was assessed using Cochrane Q and I2 (χ2 = 73.05, df (19), P < 0.001 and I2 = 73.99). RESULTS:Twenty studies fulfilled the inclusion criteria (ACT in the treatment of uncomplicated falciparum malaria) and were included in the final analysis with a total number of 4070 participants. Malaria treatment outcome was assessed using World Health Organization guidelines. Adequate clinical and parasitological response was used to assess treatment success at the 28th day. Treatment success of all combined studies was 98% [(95% CI 97.2-98.8%), P < 0.001]. Treatment success was higher in malaria patients treated with artemether + lumefantrine (AL) than patients treated with artesunate + sulfadoxine-pyrimethamine (AS + SP) (98.9% (95% CI 98.4-99.4%) vs 97.1% (95% CI 95.5-98.6%), P < 0.001). Eleven studies reported adverse drug reactions (ADRs) to ACT (184 participants out of 3957 (4.65%). The ADRs were mild and resolved spontaneously. There was no severe ADRs or deaths. CONCLUSION:Based on this review, the overall malaria treatment success was high (98%). AL regimen showed higher efficacy compared to AS + SP. The overall regimens were associated with mild low rates ADRs.

Project description:BackgroundFollowing the development of resistance to anti-malarial mono-therapies, malaria endemic countries in Africa now use artemisinin-based combination therapy (ACT) as recommended first-line treatment for uncomplicated malaria. Patients' adherence to ACT is an important factor to ensure treatment efficacy, as well as to reduce the likelihood of parasite resistance to these drugs. This study reports adherence to a specific ACT, artemether-lumefantrine (AL), under conditions of routine clinical practice in Kenya.MethodThe study was undertaken in Garissa and Bunyala districts among outpatients of five government health facilities. Patients treated with AL were visited at home four days after having been prescribed the drug. Respondents (patients ≥ 15 years and caregivers of patients < 15 years) were interviewed using a standardized questionnaire, AL blister packs were physically inspected and the adherence status of patients was then recorded. Multivariate logistic regression modelling was used to determine predictors of adherence.ResultsOf the 918 patients included in the study, 588 (64.1%) were 'probably adherent', 291 (31.7%) were 'definitely non-adherent' and 39 (4.2%) were 'probably non-adherent'. Six factors were found to be significant predictors of adherence: patient knowledge of the ACT dosing regimen (odds ratio (OR) = 1.76; 95% CI = 1.32-2.35), patient age (OR = 1.65; 95% CI = 1.02-1.85), respondent age (OR = 1.37; 95% CI = 1.10-2.48), whether a respondent had seen AL before (OR = 1.46; 95% CI = 1.08-1.98), whether a patient had reported dislikes to AL (OR = 0.62 95% CI = 0.47-0.82) and whether a respondent had waited more than 24 hours to seek treatment (OR = 0.73; 95% CI = 0.54-0.99).ConclusionOverall, adherence to AL was found to be low in both Garissa and Bunyala districts, with patient knowledge of the AL dosing regimen found to be the strongest predictor of adherence. Interventions aimed at increasing community awareness of the AL dosing regimen, use of child friendly formulations and improving health workers' prescribing practices are likely to ensure higher adherence to AL and eventual treatment success.

Project description:BackgroundMalaria is a major cause of morbidity and mortality in pediatrics in malaria endemic areas. Artemisinin-based combination therapies (ACTs) are the drugs of choice for malaria management particularly across malaria-endemic countries. This systematic review and meta-analysis was performed to assess efficacy and safety of ACTs for uncomplicated malaria in pediatric populations.MethodsA body of evidence was searched for published ACT trials until March 06, 2020. The search was focused on efficacy and safety studies of ACTs for uncomplicated malaria in pediatrics. PubMed library was searched using best adapted search terms after multiple trials. References were exported to the endnote library and then to Covidence for screening. Data was extracted using the Covidence platform. The per-protocol analysis report for the efficacy and the intention-to-treat analysis for the safety were synthesized. Met-analysis was carried using Open Meta-Analyst software. Random effects model was applied and the heterogeneity of studies was evaluated using I2 statistic.ResultsNineteen studies were included in the final analysis. Overall, crude, PCR-corrected P. falciparum malaria treatment success rate was 96.3 and 93.9% for day 28 and 42, respectively. In the subgroup analysis, PCR-corrected adequate clinical and parasitological response (ACPR) of dihydroartemisinin-piperaquine (DP) was 99.6% (95% CI: 99.1 to 100%, I2 = 0%; 4 studies) at day 28 and 99.6% (95% CI of 99 to 100%, I2 = 0%; 3 studies) at day 42. Nine studies reported ACT related adverse drug reactions (ADR) (8.3%, 356/4304). The reported drug related adverse reactions ranged from 1.8% in DP (two studies) to 23.3% in artesunate-pyronaridine (AP). Gastrointestinal symptoms were the most common ACT related adverse effects, and all ADRs were reported to resolve spontaneously.ConclusionACTs demonstrated a high crude efficacy and tolerability against P. falciparum. The high treatment success and tolerability with low heterogeneity conferred by DP has implication for policy makers who plan the use of ACTs for uncomplicated falciparum malaria treatment in pediatrics.

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

Publications

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

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