One Health Lens on Rabies: Human–Bat Interactions and Genomic Insights of Rabies Virus in Rural Lilongwe, Malawi

Rabies, a fatal zoonotic disease, affects humans, domestic animals, and wildlife predominantly in Africa, Asia, and Latin America. In Malawi, rabies virus (RABV) is primarily transmitted by infected dogs, impacting humans and cattle. Lyssavirus has also been documented in insectivorous bats. A community survey near bat roosts assessed knowledge, attitudes, and practices regarding bat-borne zoonoses. Bat samples were tested for lyssavirus using RT-PCR, and RABV genomes from humans and domestic animals were sequenced and analysed phylogenetically. The survey revealed that 50% of participants consumed bat meat, and 47% reported bats entering their homes. Reduced bat presence indoors significantly lowered contact risk (aOR: 0.075, <i>p</i> = 0.021). All 23 bat samples tested negative for lyssavirus. Malawian RABV genomes, 11,801 nucleotides long, belonged to the Africa 1b lineage, showing >95% similarity with GenBank sequences. Phylogenetic analysis indicated close clustering with strains from Tanzania, Zimbabwe, and South Africa. Human and cattle strains shared 99% and 92% amino acid similarity with dog strains, respectively, with conserved critical sites and unique substitutions across all five RABV genes. Frequent human-bat interactions pose zoonotic risks. While no lyssavirus was detected in bats, ongoing surveillance is crucial. This first comprehensive genome analysis of Malawian RABVs highlights their regional transmission and signifies the need for regional collaboration in rabies control, community education, and further study of genetic adaptations.