Peter Thelma Ngwa Niba1,2,3, Akindeh M Nji1,2,3, Marie-Solange Evehe2,3, Innocent M Ali1,2,4, Palmer Masumbe Netongo2,3, Randolph Ngwafor2,5, Marcel N Moyeh1,2,6, Lesley Ngum Ngum1,2,7,8, Oliva Ebie Ndum2,9, Fon Abongwa Acho2, Cyrille Mbanwi Mbu'u2,10, Dorothy A Fosah5, Barbara Atogho-Tiedeu2,3, Olivia Achonduh-Atijegbe2, Rosine Djokam-Dadjeu2,3, Jean Paul Kengne Chedjou1,2,3, Jude D Bigoga1,2,3, Carole Else Eboumbou Moukoko11,12, Anthony Ajua6, Eric Achidi6, Esther Tallah13, Rose G F Leke1,2,13, Alexis Tourgordi14, Pascal Ringwald15, Michael Alifrangis16,17, Wilfred F Mbacham18,19,20,21. 1. MARCAD-DELTAS Programme, Laboratory for Public Health Research Biotechnologies, University of Yaoundé I, Yaoundé, Cameroon. 2. The Biotechnology Centre, University of Yaoundé I, Yaoundé, Cameroon. 3. Department of Biochemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon. 4. Department of Biochemistry, Faculty of Science, University of Dschang, Dschang, Cameroon. 5. National Malaria Control Programme, Ministry of Public Health, Yaoundé, Cameroon. 6. Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea, Cameroon. 7. Department of Biochemistry, Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon. 8. Institute of Medical Research and Medicinal Plant Studies, Ministry of Scientific Research and Innovation, Yaoundé, Cameroon. 9. Université Des Montagnes, Banganté, West Region, Cameroon. 10. Department of Microbiology, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon. 11. Faculty of Medicine and Pharmaceutical Sciences, University of Douala, Douala, Cameroon. 12. Malaria Research Service, Centre Pasteur Cameroon, Yaoundé, Cameroon. 13. Malaria Consortium-Cameroon Coalition Against Malaria, Yaoundé, Cameroon. 14. The Cameroon Office of the World Health Organization, Yaoundé, Cameroon. 15. Global Malaria Programme, World Health Organization, Geneva, Switzerland. 16. Centre for Medical Parasitology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 17. Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark. 18. MARCAD-DELTAS Programme, Laboratory for Public Health Research Biotechnologies, University of Yaoundé I, Yaoundé, Cameroon. wfmbacham@yahoo.com. 19. The Biotechnology Centre, University of Yaoundé I, Yaoundé, Cameroon. wfmbacham@yahoo.com. 20. Department of Biochemistry, Faculty of Science, University of Yaoundé I, Yaoundé, Cameroon. wfmbacham@yahoo.com. 21. Malaria Consortium-Cameroon Coalition Against Malaria, Yaoundé, Cameroon. wfmbacham@yahoo.com.
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.
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.
Authors: Alessandro Liberati; Douglas G Altman; Jennifer Tetzlaff; Cynthia Mulrow; Peter C Gøtzsche; John P A Ioannidis; Mike Clarke; P J Devereaux; Jos Kleijnen; David Moher Journal: BMJ Date: 2009-07-21
Authors: Abdoulaye A Djimdé; Ogobara K Doumbo; Ousmane Traore; Ando B Guindo; Kassoum Kayentao; Yacouba Diourte; Safiatou Niare-Doumbo; Drissa Coulibaly; Abdoulaye K Kone; Yacouba Cissoko; Mamadou Tekete; Bakary Fofana; Alassane Dicko; Dapa A Diallo; Thomas E Wellems; Dominic Kwiatkowski; Christopher V Plowe Journal: Am J Trop Med Hyg Date: 2003-11 Impact factor: 2.345
Authors: William Yavo; Babacar Faye; Thomas Kuete; Vincent Djohan; Serge A Oga; Richard R Kassi; Mariama Diatta; Moor V Ama; Roger Tine; Jean-Louis Ndiaye; Jean-Bedel Evi; Albert Same-Ekobo; Oumar Faye; Moussa Koné Journal: Malar J Date: 2011-07-20 Impact factor: 2.979