Avian Flu Diary: EID Journal: Highly Pathogenic Avian Influenza A(H5N1) from Wild Birds, Poultry, and Mammals, Peru

#17,761

HPAI H5 reached the South American continent just over a year ago (see WOAH: Colombia Reports Two Outbreaks of HPAI H5N1) and was swiftly carried by migratory birds south along the west coast, making its first big impact in Peru followed quickly by Ecuador.

By the end of November 2022 Peru had reported nearly 14,000 Wild Bird Deaths and was investigating the deaths of sea lions. In late January of 2023, Peru: SERNANP Reported At Least 585 Sea Lions & 50,000 birds killed by Avian Flu.

While the losses to marine mammals and birds can only be estimated, tens of thousands of marine mammals have died, along with hundreds of thousands of birds (see EID Journal: Mass Mortality of Sea Lions Caused by HPAI A(H5N1) Virus (Peru)), as the virus worked its way down the continent.

Preprint: First Mass Mortality of Marine Mammals Caused by Highly Pathogenic Influenza Virus (H5N1) in South America

Chile: SERNSPESCA Reports > 4,300 Marine Animal Deaths

Argentina: SENASA Reports More Sea Lion Deaths From H5N1 - Issues Health Guidelines

Much as we saw in 2022's Preprint: Rapid Evolution of A(H5N1) Influenza Viruses After Intercontinental Spread to North America, the longer HPAI H5N1 has circulated in South America - the more reassortment opportunities it has had - and more genotypes it has generated.

Add in host adaptations from spillover into mammals, and inevitable antigenic drift, and you have the ingredients needed for rapid, and potentially worrisome, evolution of the virus.

We've previously seen evidence of increased host range and mammalian adaptations (see Denmark: Risk Assessment Of H5N1 Spillover Into Mammals) along with some hints of potential resistance to antivirals from around the world.

Yesterday the CDC's EID Journal published a research letter on evolutionary changes found in HPAI H5 in Peruvian birds and mammals. I've only included some excerpts, so follow the link to read the letter in its entirety.

I'll have a brief postscript after the break.

Research Letter
Highly Pathogenic Avian Influenza A(H5N1) from Wild Birds, Poultry, and Mammals, Peru

Cristopher D. Cruz, M. Eliana Icochea, Victoria Espejo, Gilda Troncos, Gina R. Castro-Sanguinetti, Megan A. Schilling, and Yeny Tinoco

Abstract

We identified highly pathogenic avian influenza A(H5N1) virus clade 2.3.4.4b in wild birds, poultry, and a lion in Peru during November 2022–February 2023 and markers associated with transmission adaptation and antiviral drug resistance. Continuous genomic surveillance is needed to inform public health measures and avoid mass animal deaths.

(SNIP)

We performed phylogenetic analysis to classify subclades by using the maximum-likelihood method. We retrieved H5 sequences from HPAI clade 2.3.4.4 and low pathogenicity avian influenza viruses published in GISAID (https://www.gisaid.orgExternal Link) and GenBank during 2014–2023 (until July 20, 2023). The phylogenetic tree of HA sequences placed H5N1 strains from North, Central, and South America into different groups within subclade 2.3.4.4b.

We identified 6 subclades comprising sequences from 1–5 countries (Venezuela, Colombia, Ecuador, Mexico/Honduras/Costa Rica/Panama/Colombia, Costa Rica/Panama/Colombia, and Ecuador/Peru/Chile) and 1 sequence from Colombia that did not cluster with other strains from South America. Our results suggest that the strains from South America were not monophyletic and represented 7 independent virus introduction events (Figure), complementing a previous report (8).

We also compared available amino acid sequences of virus proteins among strains from South America to identify differences among subclades (Appendix Table 2). We identified several amino acid changes that were shared among members of the same subclade (Appendix Table 3). Those changes were consistent with our HA phylogenetic analysis, supporting the hypothesis that independent virus introduction events occurred in South America.

We performed molecular marker analysis to identify specific amino acid mutations associated with HPAI adaptation, transmission, and antiviral drug resistance, such as those in neuraminidase (NA), matrix protein 2, and polymerase acidic protein (9). We identified 21 molecular markers involved in HPAI H5N1 pathogenicity that were present in all analyzed sequences from South America and 7 markers that were found in some sequences (Table).

However, 2 mutations in the polymerase basic 2 protein (Q591K and D701N) associated with mammal adaptation were identified only in sequences from sea lions in Peru and from 1 human case in Chile.
The T271A mutation in polymerase basic 2 protein linked to mammal adaptation and S369I and I396M mutations in NA that were observed in the mink outbreak in Spain (2) were not found in sequences from South America.
We did not find amino acid mutations related to resistance to the antiviral drugs oseltamivir, zanamivir and peramivir (in NA), amantadine and rimantadine (in matrix protein 2), or baloxavir (in PA).
We only found the H252Y mutation in NA associated with moderately reduced susceptibility to oseltamivir (10).

In conclusion, HPAI H5N1 virus clade 2.3.4.4b was identified in samples collected in Peru from wild birds, poultry, and a lion during November 2022–February 2023. According to phylogenetic analysis, the multiple cluster distribution revealed independent introductions of HPAI H5N1 clade 2.3.4.4b viruses into South America from North and Central America. Four introductions occurred in Colombia, 2 in Ecuador, and 1 in Venezuela/Peru. In addition, strains from Peru were closely related to those from Ecuador and Chile.

Finally, we describe the presence of previously reported mutations that might have public health implications because of their associations with increased virulence and virus replication and mammal host adaptation along with reduced susceptibility to oseltamivir.

Continuous genomic surveillance is needed to identify markers associated with mammal adaptation and potential human-to-human transmission, to inform public health measures, avoid mass animal deaths, and to protect human populations.

Mr. Cruz is a research investigator at the US Naval Medical Research Unit SOUTH. His primary interest focuses on molecular analysis of viruses, such as dengue, SARS-CoV-2, and influenza viruses.

While the lack of more substantial signs of antiviral resistance is encouraging, this is a snapshot from a limited geographic region, and may not represent what is happening elsewhere in the world.

Nature's unsupervised and unregulated avian flu gain of function (GOF) field experiment continues on a global scale, and while we haven't seen solid evidence that this virus is capable of sparking a pandemic, the virus shows no signs of stopping.