Abstract
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.
Highlights
Malaria is a major cause of morbidity and mortality in pediatrics in malaria endemic areas
The study characteristics are indicated in Additional file 1
By the type of malaria infection, all selected studies were conducted on P. falciparum
Summary
Malaria is a major cause of morbidity and mortality in pediatrics in malaria endemic areas. Despite being home for malaria, the WHO African region accounted for 88% of the 172,000 fewer global death reports in 2017 as compared to 2010 [1]. One of the key strategies devised in the advent of malaria management was emphasizing on the importance of early diagnosis and treatment [2]. This was progressively disadvantaged by emergence of resistance of malaria parasites to the existing treatment options. A global resistance of P. falciparum to chloroquine and the sulphadoxine-pyrimethamine prompted the 2001 WHO expert panel to suggest use of artemisininbased combination therapy (ACT) for uncomplicated P. falciparum malaria management [3]. WHO recommends ACTs as the first-line and second-line treatments for uncomplicated P. falciparum malaria as well as for P. vivax malaria resistant to chloroquine
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