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.