Abstract
BACKGROUND Malaria caused by Plasmodium malariae is geographically widespread and sometimes associated with prolonged infection, yet little is known about its genomic epidemiology.METHODS We performed hybrid capture and whole-genome sequencing of 77 isolates collected from Cameroon (n = 7), the Democratic Republic of the Congo (n = 16), Nigeria (n = 4), and Tanzania (n = 50) between 2015 and 2021, analyzing parasite genetic population structure and demography.RESULTS There is no evidence of geographic population structure. Nucleotide diversity was significantly lower than in colocalized P. falciparum isolates, while linkage disequilibrium was significantly higher. Genome-wide selection scans identified no erythrocyte invasion ligands or antimalarial resistance orthologs as top hits; however, targeted analyses of these loci revealed evidence of selective sweeps around 4 erythrocyte invasion ligands and 6 antimalarial resistance orthologs. Demographic inference modeling suggests that African P. malariae is recovering from a bottleneck.CONCLUSION P. malariae is genomically atypical among human Plasmodium spp. and lacks strong population structure in Africa. The low diversity has potential impacts on understanding persistent versus new infection through genomic epidemiology.FUNDING Bill & Melinda Gates Foundation (grant 002202), USAID/PMI through Jhpiego and CDC, NIH (T32AI007151, T32AI070114, R01AI107949, R01AI129812, R21 AI148579, R01AI137395, R21AI152260, R01AI132547, and K24AI134990), and the DELTAS Africa initiative (DELGEME grant 107740/Z/15/Z).
Authors
Zachary R. Popkin-Hall, Kelly Carey-Ewend, Farhang Aghakhanian, Eniyou C. Oriero, Misago D. Seth, Melchior M. Kashamuka, Billy Ngasala, Innocent M. Ali, Eric Sompwe Mukomena, Celine I. Mandara, Oksana Kharabora, Rachel Sendor, Alfred Simkin, Alfred Amambua-Ngwa, Antoinette Tshefu, Abebe A. Fola, Deus S. Ishengoma, Jeffrey A. Bailey, Jonathan B. Parr, Jessica T. Lin, Jonathan J. Juliano
Figure 1
Complexity of infection.
