Geographical emergence of sulfadoxine-pyrimethamine drug resistance-associated P. falciparum and P. malariae alleles in co-existing Anopheles mosquito and asymptomatic human populations across Cameroon

Nkemngo, Francis N., Raissa, Lymen W., Nguete, Daniel N., Ndo, Cyrille, Fru-Cho, Jerome, Njiokou, Flobert, Wanji, Samuel and Wondji, Charles ORCID: https://orcid.org/0000-0003-0791-3673 (2023) 'Geographical emergence of sulfadoxine-pyrimethamine drug resistance-associated P. falciparum and P. malariae alleles in co-existing Anopheles mosquito and asymptomatic human populations across Cameroon'. Antimicrobial agents and chemotherapy, Vol 67, Issue 12, e0058823.

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Abstract

Malaria molecular surveillance remains critical in detecting and tracking emerging parasite resistance to anti-malarial drugs. The current study employed molecular techniques to determine Plasmodium species prevalence and characterize the genetic diversity of Plasmodium falciparum and Plasmodium malariae molecular markers of sulfadoxine-pyrimethamine resistance in humans and wild Anopheles mosquito populations in Cameroon. Anopheles mosquito collections and parasitological survey were conducted in villages to determine Plasmodium species infection, and genomic phenotyping of anti-folate resistance was accomplished by sequencing the dihydrofolate-reductase ( dhfr ) and dihydropteroate-synthase ( dhps ) genes of naturally circulating P. falciparum and P. malariae isolates. The malaria prevalence in Elende was 73.5% with the 5–15 years age group harboring significant P. falciparum (27%) and P. falciparum + P. malariae (19%) infections. The polymorphism breadth of the pyrimethamine-associated Pfdhfr marker revealed a near fixation (94%) of the triple-mutant -A 16 I 51 R 59 N 108 I 164 . The Pfdhps backbone mediating sulfadoxine resistance reveals a high frequency of the V 431 A 436 G 437 K 540 A 581 A 613 alleles (20.8%). Similarly, the Pmdhfr N 50 K 55 L 57 R 58 S 59 S 114 F 168 I 170 haplotype (78.4%) was predominantly detected in the asexual blood stage. In contrast, the Pmdhps – S 436 A 437 occured at 37.2% frequency. The combined quadruple N 50 K 55 L 57 R 58 S 59 S 114 F 168 I 170 _ S 436 G 437 K 540 A 581 A 613 (31.9%) was the major circulating haplotype with similar frequency in humans and mosquitoes. This study highlights the increasing frequency of the P. malariae parasite mostly common in asymptomatic individuals with apparent P. falciparum infection. Interventions directed at reducing malaria transmission such as the scaling-up of SP are favoring the emergence and spread of multiple drug-resistant alleles between the human and mosquito host systems.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > QW 45 Microbial drug resistance. General or not elsewhere classified. QX Parasitology > Insects. Other Parasites > QX 510 Mosquitoes
Faculty: Department:	Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI):	https://doi.org/10.1128/aac.00588-23
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	20 Nov 2023 14:11
Last Modified:	16 Jan 2024 14:50
URI:	https://archive.lstmed.ac.uk/id/eprint/23504

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