The molecular epidemiology of influenza in Cambodia

Abstract

Avian influenza viruses (AIVs) represent a risk to the health of humans and animals. The prevalence of AIVs in live bird markets in Cambodia is among the highest in the world, being detected in 45.5% of tested poultry in 2015. To better understand the potential risk presented by AIVs, this thesis investigated the genetic characteristics of AIVs circulating in Cambodia between 2014 to 2018; focusing on subtypes that pose the greatest risk to human and animal health (H5, H7 and H9). Highly pathogenic (HP) H5N1 clade 2.3.2.1c viruses and low pathogenic H9N2 BJ/94-like h9-4.2.5 clade viruses were the most frequently detected subtypes, and circulate endemically in Cambodia’s domestic poultry. Co-infections were detected and facilitated the production of two novel reassortant H5N1 AIVs with single genes from H9N2 viruses. Additionally, numerous intrasubtypic reassortment events were detected for H5 and H9 AIVs. This is concerning as reassortment events can rapidly produce novel viruses of public health risk. Phylogenetic analyses showed some genes of the Cambodian H5, H7 and H9 AIVs clustered with zoonotic viruses, suggesting a common origin. There are parallels between H5N1 and H9N2 AIVs detected in Cambodia and Vietnam, likely facilitated through the illegal trade of live poultry and/or the migration of wild birds. Molecular analyses showed H9 AIVs have major markers associated with adaptation to mammals; though during the study period the only human AIV cases were the result of HP H5N1. Molecular markers of resistance to adamantine antivirals was observed in 3% of H5 and 41% of H9 AIVs; however, both subtypes remain susceptible to first line antiviral treatment, neuraminidase inhibitors. The data presented in this thesis demonstrates that circulation of Cambodian AIVs represents a risk for the emergence of novel viruses. Interventions are urgently needed to mitigate the threat posed to poultry and humans.Doctor of Philosoph