Characterization of the treatment trajectory and assessment of the disease weight during uncomplicated malaria in the Democratic Republic of Congo

Introduction: The emergence of Plasmodium falciparum (Pf) resistance to artemisinin (PfART-R) in Africa is a worrisome situation that would annihilate the progress made in reducing the global burden of malaria. The discovery of mutations occurring in portions of the Pf gene sequence encoding kelch 13 (PfK13) – propeller domain and inducing PfART-R, has provided unprecedented opportunities for monitoring such resistance at large scale.
Aim: This study aimed to review the PfK13 allelic polymorphism and its spatial distribution in Africa for drawing a baseline for subsequent epidemiological surveillance and containment efforts of PfART-R.
Methods: A systematic review was performed according to PRISMA guidelines through six electronic databases consulted up to December 2018. Studies assessing the PfK13 gene in any of the 54 African countries were explored and data related to individual single nucleotide polymorphisms from each report and sampling location were geo-referenced and locus-referenced to be uploaded on maps displaying spatial and molecular patterns.
Results: From 8,678 screened records, 50 reports were identified as eligible providing 22,739 Pf isolates successfully sequenced for the PfK13 and originating from 109 sites surveyed in 41 African countries. Overall 619 nonsynonymous (NS) mutants (2.7% of sequenced isolates) were reported at varied relative frequencies (0.5 to 50%) most often being K189T and A578S.Intermediate proportions (30 to 50%) of NS mutants were found in Western and Eastern Africa, moderate proportions (10 to 20%) in Middle Africa and low to very low proportions (<5%), elsewhere. NS mutations were not detected in 11 of 41 sampling countries. A total of 8 PfK13 NS mutations (F446I, C469Y, R515K, S522C, P553L, V568G, P574L, and A675V) out of 24 known as “associated molecular markers” for PfART-R were noticed at relative frequencies from 0.08 to 10.2%. One NS mutation (M476I) out of 6 established as “validated molecular markers” for PfART-R was reported at a relative frequency of 0.42%. Possible foci of NS mutations were noticed in Eastern, Western, and Middle Africa.
Conclusion: Africa has noticed rare but alarming signals of possible emergence of Pf-ART-R. Proactive surveillance strategies are needed to be established in different African regions to refrain from massive development of resistance.