Residual antimalarial drug concentrations before treatment in malaria patients in Asia and Africa: A systematic review and meta-analysis depicting its implication for drug pressure

Resistance to antimalarial drugs has been a major hindrance towards malaria control and elimination. Extensive drug use may result in increased pressure on parasites, which may propagate the emergence and spread of resistance, particularly when the drug levels are below minimum inhibitory concentrations. Therefore, this review aimed at assessing the magnitude of pre-treatment antimalarial use among patients attending health facilities. Studies reporting residual drug levels among Plasmodium falciparum malaria patients were searched through the Medline, Cochrane Central Register of Controlled Trials (CENTRAL), LILACS, and EMBASE online databases. The protocol for the review was registered at PROSPERO (Reference number: CRD42024581540). Two independent reviewers extracted data. Potential publication bias was assessed using a funnel plot. Pooled proportion estimates were calculated using a random-effects model, and heterogeneity was assessed using I 2 statistics. Fifteen studies involving 3522 malaria patients were included in the analysis. The heterogeneity among the studies included in the meta-analysis was high (I 2 > 95% and p < 0.01). The overall estimated pooled proportions of malaria patients with pre-treatment drug levels using the random effects model were 24.0% (95% CI 16.0%- 34.0%), with the pooled proportion estimates being higher in Africa (31.0%, 95% CI 19.0%- 44.0%) than in Asia (11.0%, 95% CI 5.0%- 18.0%). Subgroup analysis (per drug type) showed that the pooled proportion estimates of malaria patients with pre-treatment drug levels were higher for Chloroquine and Lumefantrine (55.0%, 95% CI 26.0%–82.0% & 34.0%, 95% CI 10.0%–63.0%, respectively) contributed by most studies from Africa. With regard to mefloquine the proportion estimates were 10.0%, 95% CI 01.0%–26.0% contributed by most studies from Asia. The substantial pooled proportions of malaria patients with pre-treatment drug levels imply the existence of drug pressure which is potential for development of antimalarial drug resistance.