Genomic surveillance of Plasmodium falciparum drug resistance and Vaccine target markers

Abstract The growing risk of resistance in antimalarial drug and vaccine evasion potentials in Plasmodium falciparum jeopardizes progress in malaria control, particularly across sub-Saharan Africa (SSA). In this study, we employed a high-throughput workflow combining multiplex PCR with Oxford Nanopore sequencing to simultaneously analyze six key P. falciparum genes in clinical isolates from northern Nigeria, including conflict-affected regions. We detected high frequencies of dhfr-IRNI (90%) and dhps-SGKAA (45%) haplotypes, indicating persistent of markers for resistance to sulfadoxine-pyrimethamine (SP), while the absence of SP-IPTp resistance markers suggests continued efficacy of preventive treatment in pregnancy. The chloroquine resistance marker Pfcrt-76T was found in 25% of samples, indicating a partial re-emergence of drug sensitivity. Although no WHO-validated Pfk13 mutations associated with artemisinin resistance were identified, novel polymorphisms were observed, warranting further surveillance. Notably, mutations in immunogenic regions of the csp gene targeted by the R21 malaria vaccine were predicted to destabilize protein structure, with potential implications for vaccine effectiveness. Regional analyses revealed genetic diversity and resistance clustering in Kano and Yobe, underscoring the influence of localized selection pressures. These findings highlight the critical need to integrate genomic surveillance into malaria control programs to support precision public health responses, adaptive treatment and vaccine strategies to mitigate the spread of resistant P. falciparum lineages across SSA.