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Metagenomic analysis reveals extreme complexity of Plasmodium spp. infections in high transmission in West Africa

Tan, M. H.; Bangre, O.; Rios-Teran, C. A.; Tiedje, K. E.; Deed, S. L.; Zhan, Q.; Rasyidi, F.; Pascual, M.; Ansah, P. O.; Day, K. P.

2025-05-02 infectious diseases
10.1101/2025.04.29.25326533 medRxiv
Show abstract

Mixed-species, mixed-strain Plasmodia infections are known to occur in humans in malaria endemic areas. To date, the true extent of this complexity has not been explored in high- burden countries of sub-Saharan Africa. Here we take a metagenomic lens to infections obtained by sampling variable blood volumes from residents living in high, seasonal transmission in northern Ghana. We identified significantly higher prevalence of Plasmodium spp. and inter-/intra-species complexity in larger blood volumes. Overall, malaria infections displayed high levels of metagenomic complexity comprising single-, double-, and triple- species infections with varying levels of complexity for P. falciparum, P. malariae, P. ovale curtisi, and P. ovale wallikeri. We present evidence of individuals with greater susceptibility to highly-complex infections that cannot be explained by age or location. The implications of these findings to malaria epidemiology and control are illustrated by a geographic scaling exercise to district and region levels in Ghana.

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