Drug resistance markers within an evolving efficacy of anti-malarial drugs in Cameroon: A systematic review and meta-analysis (1998–2020)

Authors: Peter Thelma Ngwa Niba, Akindeh M. Nji, Marie‑Solange Evehe, Innocent M. Ali, Palmer Masumbe Netongo, Randolph Ngwafor, Marcel N. Moyeh, Lesley Ngum Ngum, Oliva Ebie Ndum, Fon Abongwa Acho, Cyrille Mbanwi Mbu’u, Dorothy A. Fosah, Barbara Atogho‑Tiedeu, Olivia Achonduh‑Atijegbe, Rosine Djokam‑Dadjeu, Jean Paul Kengne Chedjou, Jude D. Bigoga, Carole Else Eboumbou Moukoko, Anthony Ajua, Eric Achidi, Esther Tallah, Rose G. F. Leke, Alexis Tourgordi, Pascal Ringwald, Michael Alifrangis, Wilfred F. Mbacham

This review determines the prevalence and distribution of Plasmodium falciparum medicine resistance markers within an evolving efficacy of anti-malarial medicines.

Background

Malaria remains highly endemic in Cameroon. The rapid emergence and spread of drug resistance was responsible for the change from monotherapies to artemisinin-based combinations. This systematic review and meta-analysis aimed to determine the prevalence and distribution of Plasmodium falciparum drug resistance markers within an evolving efcacy of anti-malarial drugs in Cameroon from January 1998 to August 2020.

Methods

The PRISMA-P and PRISMA statements were adopted in the inclusion of studies on single nucleotide poly‑morphisms (SNPs) of P. falciparum anti-malarial drug resistance genes (Pfcrt, Pfmdr1, Pfdhfr, Pfdhps, Pfatp6, Pfcytb and Pfk13). The heterogeneity of the included studies was evaluated using the Cochran’s Q and I statistics. The random effects model was used as standard in the determination of heterogeneity between studies.

Results

Out of the 902 records screened, 48 studies were included in this aggregated meta-analysis of molecular data. A total of 18,706 SNPs of the anti-malarial drug resistance genes were genotyped from 47,382 samples which yielded a pooled prevalence of 35.4 percent (95 percent CI 29.1–42.3 percent). Between 1998 and 2020, there was signifcant decline 
(P<0.0001 for all) in key mutants including Pfcrt 76 T (79.9 percent – 43.0 percent), Pfmdr1 86Y (82.7 percent – 30.5 percent), Pfdhfr 51I (72.2 percent – 66.9 percent), Pfdhfr 59R (76.5 percent – 67.8 percent), Pfdhfr 108 N (80.8 percent –67.6 percent). The only exception was Pfdhps 437G which increased over time (30.4 percent – 46.9 percent, P<0.0001) and Pfdhps 540E that remained largely unchanged (0.0 percent – 0.4 percent, P=0.201). Exploring mutant haplotypes, the study observed a signifcant increase in the prevalence of Pfcrt CVIET mixed quintuple haplotype from 57.1 percent in 1998 to 57.9 percent in 2020 (P<0.0001). In addition, within the same study period, there was no signifcant change in the triple Pfdhfr IRN mutant haplotype (66.2 percent – 67.3 percent, P=0.427). The Pfk13 amino acid poly‑morphisms associated with artemisinin resistance were not detected.

Published in Malaria Journal