Efficacy and safety of artemisinin-based combination therapies for the treatment of uncomplicated malaria in pediatrics: a systematic review and meta-analysis

Abstract

Background Malaria 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. Methods A 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. Results Nineteen 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. Conclusion ACTs 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.

Host-directed therapy, an untapped opportunity for antimalarial intervention

“… 96 The much lower mortality rate for malaria (in 2019, there was an estimated 409,000 deaths for 229 million cases, or a >0.2% mortality rate) makes any risk associated with antimalarial drugs deployed for mass treatment essentially unacceptable, even more so if one considers liver stage-targeting prophylactics. Severe malaria complications, such as cerebral malaria (which has a mortality rate of ∼20% and can have very serious sequelae in survivors 97 ), may arguably justify the use of drugs with higher toxicity; however, here again, tolerability should be very high, as exemplified by the current treatment with artesunate 98 ; furthermore, these drugs would need to act very quickly, as death can occur very rapidly after the onset of severe malaria symptoms.…”

Parasite Viability as a Measure of In Vivo Drug Activity in Preclinical and Early Clinical Antimalarial Drug Assessment

“…Of additional concern, parasite resistance to artemisinin-based combination therapies, the most effective antimalarial regimens, is on the rise ( 2 , 3 ). Hence, there has been a large international effort both to monitor the efficacy of existing antimalarials ( 4 – 6 ) and to develop new drugs ( 7 – 16 ).…”

Establishment and evaluation of glucose-modified nanocomposite liposomes for the treatment of cerebral malaria

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