In their Perspectives piece published in the journal Science, Weifeng Shi and George Gao, both of whom are affiliated with multiple institutions in China, suggest that the makeup and history of the H5N8 strain of avian influenza virus threaten the possibility of another pandemic.
As Shi and Gao note, the new strain of influenza virus was first discovered in a duck in China back in 2010. By 2014, outbreaks had been seen in Japan and South Korea in both domestic and wild birds.
Shi and Gao note that this history indicates that the virus is able to spread very rapidly. Even more concerning was a report of crossover infections in seven Russian farm workers this past December. The authors note that the infected workers did not have any symptoms (they were tested for safety reasons) and there was no indication that the virus was transmissible from one person to the next.
But they point out, that once a crossover has been made, it generally does not take a virus long to adapt to spread to other victims – they note how quickly the virus mutated to jump from duck to duck and then to other bird species.
On a more optimistic note, Shi and Gao note that it is not too late to take preventive measures that could prevent a pandemic. They suggest that vigilant surveillance of farms, live markets and wild birds, along with the implementation of standard infection control measures, could slow the spread of the virus, giving pharmaceutical companies time to develop a vaccine for it.
Influenza A viruses are enveloped viruses of the Alphainfluenzavirus genus in the Orthomyxoviridae family. Their negative-stranded RNA genome consists of 8 segments encoding a total of 10–14 proteins. Avian influenza viruses (AIVs) are classified on the basis of antigenic differences in their surface glycoproteins, hemagglutinin (H1–H16) and neuraminidase (N1–N9) (1). H5 and H7 subtypes can become highly pathogenic avian influenza (HPAI) viruses after the evolution of multiple basic amino acids in the cleavage site of hemagglutinin protein (2,3).
This mutation enables the virus to replicate efficiently in all organs, causing a severe and often fatal systemic disease. In contrast, the cleavage site of hemagglutinin in low pathogenicity AIVs lacks these multiple amino acids, restricting viral replication to the respiratory and digestive tracts.
Low pathogenicity AIVs cause subclinical or mild disease that can be aggravated by secondary infections (4,5). Because H5 and H7 AIVs can evolve to be highly pathogenic, the diseases caused by these subtypes are notifiable to national and international bodies (6).
Since 1996, highly pathogenic H5 viruses of the A/goose/Guangdong/1/96 (Gs/GD/96) lineage have caused recurrent outbreaks with high death rates in birds. These HPAIs are categorized into 10 distinct clades (0–9) on the basis of hemagglutinin sequences (7). These clades are found in Asia; a few have spread to Africa, Europe, and North America (8–10).
Europe experienced major introductions of H5N1 of clade 2.2 during 2005–2007 and H5N8 of clade 220.127.116.11 during 2014–2020 (11–14). Many reassortments were observed on Gs/Gd/1/96–like viruses, especially within clade 18.104.22.168. The reassortments generated several subtypes including H5N1, H5N2, H5N5, H5N6, and H5N8 (11,15–17).
During winter 2016–17, twenty-nine countries in Europe reported 1,576 cases of Gs/Gd/1/96–like H5N8 infections in wild birds and 1,134 in poultry, especially domestic ducks (18).
During this outbreak, researchers identified 6 HPAI A(H5N8) genotypes in Europe; 2 of these genotypes were identified using 6 sequences from infected birds in France (19). France had 539 cases of HPAI A(H5N8) infections, 51 in wild birds and 488 in poultry flocks, most of which occurred at duck farms producing foie gras (18).
A previous study used spatiotemporal analysis of clinical cases comprising 2 distinct epizootic periods in southwestern France (20). The first period spanned November 28, 2016–February 2, 2017 and comprised 4 spatiotemporal clusters (20). The second period spanned February 3–March 23, 2017 and comprised a single spatiotemporal cluster (20).
During the first period, the disease spread mainly among local farms; during the second period, after local farm-to-farm spread, the average distance between affected farms increased (20). To limit viral spread among poultry farms, the French Ministry of Agriculture and Food established protection zones (3 km radius) and surveillance zones (1 km radius) around outbreak sites according to European Union regulations (21).
Additional control measures included preventive culling of poultry inside surveillance zones and of outdoor palmipeds inside protection zones (21). We sequenced 212 whole genomes of HPAI A(H5N8) viruses infecting wild and domestic birds during the outbreak in France. We used these molecular data to identify the geographic distribution and track the spread of H5N8 genotypes.