Abstract
BACKGROUND: The success of malaria elimination in sub-Saharan Africa rests largely on the sustained efficacies of the chemointerventions used in malaria treatment and chemoprophylaxis in the highest-burden countries such as Nigeria. Data on the impact of these interventions can guide policy for sustained malaria control toward elimination. We report the complexity of infection (number of genetically distinct same-species parasite strains observed in an infection) and genetic diversity of Plasmodium falciparum in Nigeria and their antimalarial resistance profiles. METHODS: We used targeted amplicon sequencing techniques to analyze 895 P falciparum clinical isolates collected from the 6 geopolitical zones of Nigeria, mostly between 2017 and 2021. Genotypes from 101 single-nucleotide polymorphisms and 36 nonsynonymous amino acid mutations associated with antimalarial drug resistance were used to determine the complexity of infection, the haplotypes of drug resistance genetic markers, genetic diversity, and pairwise relatedness of infections, according to R packages. RESULTS: Overall, infections were highly complex, with approximately 30% of these having more than a single genetically distinct parasite clone. Furthermore, 55.1% of the parasite isolates carried wild type alleles of the chloroquine transporter gene Pfcrt at codons 74 to 76. Highly related chloroquine-sensitive infections were observed in recent infections in several sites, especially Bauchi. However, the chloroquine-resistant haplotype CVIET persisted in 40.9% of infections, 26.5% of which were monoclonal and 14.4% were mixed. Sulfadoxine-pyrimethamine resistance alleles (codons 51, 59, and 108) at Pfdhfr loci were observed in >50% of infections, while the Pfdhps A437G mutation was detected in 87.3%. Most infections were wild type at Pfkelch13, although 12 nonsynonymous propeller domain mutations were observed. CONCLUSIONS: Chloroquine sensitivity at the molecular level is now dominant in Nigeria, while antifolate resistance persists. Enhanced molecular surveillance of drug resistance-associated loci will serve as an early warning to safeguard the efficacy of chemointerventions in Nigeria.