Detection and genome characterization of Middelburg virus strains isolated from CSF and whole blood samples of humans with neurological manifestations in South Africa.

Old World alphaviruses are mainly associated with polyarthritis in humans. Global emergence of chikungunya virus raises concerns regarding disease potential of neglected African arboviruses. New World alphaviruses are associated with severe neurological disease in humans and horses in the Americas with a high mortality rate. Middelburg virus (MIDV) is an Old World alphavirus previously associated with neurological disease and fatalities in horses and wildlife in southern Africa but not yet linked to disease in humans. This study investigated MIDV in humans presenting with acute neurological symptoms in South Africa. MIDV infection was confirmed in 4/189 (2%) such cases using a generic Alphavirus real-time RT-PCR and phylogenetic analysis. MIDV full genomes were obtained from a cerebrospinal fluid sample of a 2-year-old child and a whole blood sample of a veterinary student, both presenting with neurological signs. This study suggests MIDV may be associated with unsolved neurological disease in humans in Africa.