Geospatial Tracking of a Rabies Outbreak in the Eastern Cape Province, South Africa, Using Molecular Data

Rabies is a zoonotic disease known to humankind for millennia. Despite being preventable, rabies is still neglected and causes human fatalities, predominantly in resource‐limited areas in Africa and Asia. In South Africa, rabies is maintained in both domestic and wildlife reservoir hosts, with frequent cross‐species transmission. This study utilized retrospective epidemiological data from the Eastern Cape (EC) province of South Africa from November 2020 until December 2024, which included a prominent dog rabies outbreak. The majority of the rabies cases were reported in the Nelson Mandela Bay Municipality (NMBM). Subsequently, the study aimed to establish the origin of the outbreak and track its spread within the NMBM and the EC province, using descriptive summaries on epidemiological data gathered from 2596 cases, as well as partial glycoprotein gene sequence analyses generated from a panel of rabies viruses (RABVs), originating from rabies‐infected dog brain tissues ( n  = 102), human samples ( n  = 4), domestic cats ( n  = 3), and livestock ( n  = 5). Throughout the outbreak in the EC, dogs ( n  = 705) were the most commonly infected host species, highlighting the central role this domestic carnivore plays in rabies epizootiology in this country. The RABVs analyzed from this outbreak shared significant sequence homology of 99% mean sequence identity, suggesting a common progenitor and supporting the historical introduction of rabies into South Africa. Based on the sequence data, the RABVs from this outbreak were delineated into three distinct clusters, with the majority of the samples grouping within the recently described DD‐I and DD‐II clusters and a single sample cluster with wildlife samples in cluster BEF‐II. Cumulatively, our data suggest at least three independent introductions of the RABV infection into the dog populations of the NMBM between 2021 and 2024, with DD‐II subgroup C being the most dominant. The introduction of rabies into the study area may suggest a more complicated explanation linked to lapsed dog vaccinations during the outbreak period.