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

Abstract

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 efficacy 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 polymorphisms (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 I2 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% (95% CI 29.1–42.3%). Between 1998 and 2020, there was significant decline (P < 0.0001 for all) in key mutants including Pfcrt 76 T (79.9%-43.0%), Pfmdr1 86Y (82.7%-30.5%), Pfdhfr 51I (72.2%-66.9%), Pfdhfr 59R (76.5%-67.8%), Pfdhfr 108 N (80.8%-67.6%). The only exception was Pfdhps 437G which increased over time (30.4%-46.9%, P < 0.0001) and Pfdhps 540E that remained largely unchanged (0.0%-0.4%, P = 0.201). Exploring mutant haplotypes, the study observed a significant increase in the prevalence of Pfcrt CVIET mixed quintuple haplotype from 57.1% in 1998 to 57.9% in 2020 (P < 0.0001). In addition, within the same study period, there was no significant change in the triple Pfdhfr IRN mutant haplotype (66.2% to 67.3%, P = 0.427). The Pfk13 amino acid polymorphisms associated with artemisinin resistance were not detected. Conclusions This review reported an overall decline in the prevalence of P. falciparum gene mutations conferring resistance to 4-aminoquinolines and amino alcohols for a period over two decades. Resistance to artemisinins measured by the presence of SNPs in the Pfk13 gene does not seem to be a problem in Cameroon. Systematic review registration PROSPERO CRD42020162620

Antimalarial drug resistance in the Central and Adamawa regions of Cameroon: Prevalence of mutations in P. falciparum crt, Pfmdr1, Pfdhfr and Pfdhps genes

“…This study assessed the prevalence of antimalarial drug resistance mutations in P . falciparum genes, Pfcrt , Pfmdr1 , Pfdhfr and Pfdhps , in two different regions of Cameroon (Central and Adamawa Regions) more than 15 years after the malaria drug policy have changed from the use of CQ through AQ and SP to ACTs in 2004 [ 8 , 53 ].…”

“…Even though high prevalences of Pfdhfr resistance alleles among P . falciparum in Cameroon was were reported as early as 2000 [ 53 ], it is surprising to find high proportions nowadays despite the adoption of ACTs for treatment of uncomplicated malaria. It is possible that the SP combination is still widely used outside the official sector for treatment of uncomplicated malaria by people who prefer to revert to SP instead of the three days daily doses of ACTs [ 10 ].…”

“…Earlier studies carried out in Cameroon have reported the presence of almost all mutations described above [ 13 , 52 , 53 ]. However, unlike in other African countries, relatively few studies have been carried out on the evolution of drug resistance following the introduction of ACTs and chemoprevention interventions [ 4 , 9 , 10 , 15 , 54 ].…”

“…However, unlike in other African countries, relatively few studies have been carried out on the evolution of drug resistance following the introduction of ACTs and chemoprevention interventions [ 4 , 9 , 10 , 15 , 54 ]. Moreover, almost all the data available are limited to forest zones (Central, South-East and North-East Regions) in Cameroon [ 53 ]. Thus, the profile of malaria resistance in savannah areas, such as in Tibati, is still unclear.…”

Adaptive Drug Resistance in Malaria Parasite: A Threat to Malaria Elimination Agenda?

“…Common among causes of resistance is exposure to non-lethal doses of anti-malaria drugs [15]. Malaria parasites have unique ability to evolving mechanisms for evading the immune response in humans [43] and they are actively evolving resistance to anti-plasmodia drugs [44]. But there is a dearth of information are to the effect of plasmodia resistance to drug, especially adaptive resistance, which though is temporal, could influence the development of novel plasmodium stains not targeted by currently available anti-malaria drug.…”