Widely Distributed Pigeon Paramyxovirus Sub‐Genotypes Pose a Risk to Immunocompromised Humans

Introduction Pigeon paramyxovirus type 1 (PPMV‐1) is an antigenic variant of Avian Orthoavulavirus 1 (AOAV‐1) (Newcastle disease virus) with a global distribution that causes lethal infections in pigeon and dove species. AOAV‐1's infecting humans normally cause mild, self‐limiting conjunctivitis, but since 2003, PPMV‐1 has been associated with an increased number of severe and lethal respiratory and neurological infections in immunocompromised persons in the Netherlands, the USA, France, China and Australia. Methods PPMV‐1's isolated from free‐living pigeons and doves across South Africa from 2012 to 2024 were sequenced using conventional or next generation technologies. Maximum likelihood and time‐scaled phylogenetic analyses were conducted. Cases of human infections with AOAV‐1 were reviewed, and where the genotypes were not previously assigned, the sequence data were re‐analysed for classification purposes. Results PPMV‐1 sub‐genotype VI.2.1.1.2.1, present in South Africa since at least 2005, continued to circulate in 2021. Sub‐genotype VI.2.1.1.2.2, that is widely distributed across Europe, Asia and Australia, was identified in South Africa for the first time, with introduction estimated around September 2017 (95% HPD January 2016–June 2019). Previously unclassified viruses causing lethal human infections in the Netherlands (2003), the USA (2007) and France (2021) were identified as sub‐genotypes VI.2.1.1.2.2, VI.2.1.1.1 and XXI.1.1, respectively. Conclusions Five recorded AOAV‐1‐associated human fatalities since 1953 were all caused by PPMV‐1. Three out of the five human fatalities, plus one seriously ill survivor, were associated with sub‐genotype VI.2.1.1.2.2 viruses, and sub‐genotypes VI.2.1.1.1 and XXI.1.1 each caused one human death. PPMV‐1's, found widely in pigeons and doves, pose a serious health risk to immunocompromised persons.