Molecular Surveillance of malaria in Nigeria reveals expansion of chloroquine-sensitive infections

Background The success of malaria elimination in sub-Saharan Africa rests largely on the sustained efficacies of the control and prevention chemo-interventions used in malaria treatment and chemoprophylaxis in the highest-burden countries. Data on the impact of these interventions can guide policy for sustained malaria control towards elimination. We report the complexity of infection and genetic diversity of Plasmodium falciparum in Nigeria and their antimalarial resistance profiles.

We used targeted amplicon sequencing techniques to analyse 895 Plasmodium falciparum clinical isolates collected from the six geopolitical zones of Nigeria, mostly between 2017 and 2021. Genotypes determined from 101 single nucleotide polymorphisms (SNPs) and 36 non-synonymous amino acid mutations associated with antimalarial drug resistance were used to determine the Complexity of infection (COI), drug resistance haplotypes and genetic diversity of the parasites.

Overall, there was a high complexity of infection, with 30.1 – 31.3% of the infections having more than a single genetically distinct parasite clone. 55.1% of the parasite isolates carried wildtype alleles of the chloroquine transporter gene, Pfcrt codons 74 – 76. The chloroquine-resistant haplotype CVIET was in 26.5% as mono-infections and 14.4% as mixed infections, with an overall presence of 40.9%. High frequencies of sulfadoxine-pyrimethamine (SP) resistance at Pfdhfr loci (50%) were observed and the Pfdhps A437G mutation was detected in 87.3% of infections. Wild-type haplotypes for Pfkelch13 were detected, although 12 non-synonymous mutations, were observed.

Sustained molecular surveillance for malaria in high-burden countries can support the implementation of current and new malaria strategies for malaria control and elimination. Competing Interest Statement The authors have declared no competing interest. Funding Statement This work was supported by the EDCTP senior fellowship plus to Prof Amambua-Ngwa (Ref: TMA2019SFP-2843). Additional support to the Malaria Population Biology Group at MRCG for molecular epidemiology of malaria was received from the National Institutes of Health Research (NIHR) Global Health (Award ID: 17/63/91 and NIHR134717) and the PAMGEN project, an H3Africa consortium funded by Science for Africa Foundation (H3AFull/17/008). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Nigerian Institute of Medical Research Institutional Review Board (IRB/21/019; IRB/20/081; IRB/17/038) The Joint University of Ibadan/University College Hospital Ethical Committee (UI/EC/16/0075; UI/EC/19/0114; UI/EC/16/0091; UI/IRC/06/0087) The Oyo State Ministry of Health Ethics Committee (AD 13/479/206) Kebbi State Health Research Ethics Committee (KSHREC 105: 23/2020) The Government of Cross River State Ministry of Health Research Ethics Committee (CRSMOH/RP/REC2017/809; CRS/MH/HREC/017/Vol.V1/109) The Health Research Ethics Committee of the University of Calabar Teaching Hospital (NHREC/07/10/2012; UCTH/HREC/33/489) The Gambia Government/MRCG Joint Ethics Committee (Ref: SCC 1626v1.2; SCC 1629). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors