Abstract
Melioidosis is increasingly recognised in tropical and subtropical regions worldwide as a serious and potentially fatal bacterial infection affecting humans and animals, acquired from the environment. Until now, human cases of melioidosis had not been reported in Southern Africa. Over a four-year period, we identified three human and two animal cases of melioidosis in South Africa and Namibia. Burkholderia pseudomallei isolates were investigated by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and whole-genome sequencing (WGS). Phylogenetic analysis demonstrated substantial diversity, suggesting long-term cryptic persistence of the bacterium in the Southern African region. Limited awareness of the disease and inadequate diagnostic capacity likely contribute to its apparent rarity in the region. These findings underscore the urgent need for increased surveillance, improved diagnostics, and greater awareness of melioidosis in Southern Africa to better understand its true epidemiological burden and prevent future cases.