Another highly pathogenic avian influenza (HPAI) virus is marching across Western Asia, Europe, and North Africa, killing domestic flocks and a number of wild birds, from India in the east to the Atlantic Ocean in the west.

This is the 4th wave of HPAI to sweep across large swathes of the globe in the past 11 years. The culprit this time around, an H5N8 virus, appeared in India in October and the Mediterranean basin in November 2016, leading so far to the deaths of hundreds of thousands of domestic birds and dozens of wild birds from over 30 species.

A potential silver lining to this unfolding story is that this particular H5N8 virus was first detected 4 months earlier, from a lake on the Mongolian-Russian Federation border. Prompt reporting of the find led to warnings by experts of a high likelihood of spread to exactly those regions affected so far.

Was the early warning a lucky break, or have we learned enough about HPAI epidemiology to make such predictions routine? The answer is a bit of both.

The Four Waves

The first long-distance wave of HPAI began in 2005, when an H5N1 virus circulating in southeast China swept across Asia all the way to Western Europe and West Africa, killing millions of domestic poultry but also an unprecedented number of wild birds. Most disturbing were the few, but often deadly, human cases of H5N1. The fear that this or similar HPAI viruses would adapt to transmission between people led to intense surveillance programs and stamping out measures (culling of infected and exposed animals).

The second, smaller wave moved across China to Central Asia, then on to the Black Sea, Iran, and Nepal in 2009-10.

The third intercontinental HPAI wave began in 2014 when an outbreak in South Korea made its way as far west as the United Kingdom. Unlike previous waves, however, the 2014 virus also moved eastwards, leading to the deaths (through disease and culling) of 50 million domestic poultry in the United States by the time it ended in June 2015. This was the first HPAI virus of Eurasian origin known to spread to North America.

The More Things Change…

We have seen in a previous post that viruses such as avian influenza that store their genetic material as RNA (rather than DNA) mutate quickly. This ensures that no two outbreaks are exactly alike, and this is evident in the differing mortality and morbidity rates of each of the four waves, their geographic spread, and species affected, to name a few.

The first 2005 HPAI wave was originally detected in a massive die-off of water birds at Lake Qinghai in west central China (see map), followed by more deaths as the virus moved westwards. Domestic chickens and turkeys died in even greater numbers.

As with the first wave (but not the other two), the current 2016 HPAI outbreak has been largely tracked by the dead wild birds left in its wake. Most have been ducks, particularly dabbling ducks, and other avian species associated with wetlands (though nowhere near the numbers found in 2005). Chickens and turkeys are also dying. And while previous waves more or less spared domestic ducks and geese, the current wave does not.

Only the first wave of H5N1 virus has infected people so far, and only rarely.

Patterns

Despite their differences, some familiar patterns have arisen from the various HPAI waves:

The viruses involved in all four intercontinental HPAI waves appear to have their origins in the backyard poultry and swine farms of densely populated eastern China. In fact, all of the implicated viruses appear to share a common ancestor: an avian influenza virus first isolated from a goose in China’s Guangdong province in 1996.

Following the long-distance spread of H5N1 beginning in 2005, researchers categorized the evolving viruses of this first wave according to changes in the gene controlling the hemagglutinin protein on the virus surface (represented by the “H” in H5N1).

These distinct genetic lineages (called clades) formed mainly due to mutations in the nucleotide bases making up the gene. Another pathway to genetic change in these viruses – exchanging genes with other avian influenza viruses in a process called reassortment – does not appear to have been an important factor initially.

But things changed in 2009. Suddenly the hemagglutinin gene making up the original H5N1 virus was being found with genes from other avian influenza viruses circulating in domestic ducks and geese in Asia. Two of these reassorted HPAI viruses eventually spread to Europe and North America in the third HPAI wave of 2014-15.

There is growing evidence that waterfowl migrations play a significant role in long-distance movement of HPAI. Wild bird deaths from at least two of these viruses have been found in wetlands relatively remote from domestic poultry premises, strongly suggestive that birds are flying while infected with the virus – and almost certainly transmitting it to other birds.

Most important to our story is a trend in which the intercontinental spread of an HPAI virus is preceded by detection of that virus in Central Asian wetlands in the spring, several months prior to its expansion outside of Asia.

Regular surveillance by Russian biologists at Lake Uvsu-Nur on the Mongolian- Russian Federation border has on five occasions detected highly pathogenic H5 avian influenza viruses. Four of these occasions were soon followed by long-distance spread of the detected viruses, including the current wave.

Lake Qinghai, south of Mongolia in China, has also foretold of coming outbreaks. Some 4000 wild birds found dead at the lake in spring 2005 kicked off the first intercontinental HPAI wave. Smaller numbers of dead birds at the lake in spring and summer 2009 and 2010 preceded the second HPAI wave shortly afterwards.

Dumb Luck or Crystal Ball?

Because of the evolving patterns described above, the UN’s Food & Agriculture Organization felt confident enough to issue a warning following detection of highly pathogenic H5N8 virus and dead birds around Lake Uvsu-Nur in June 2016. Countries bordering the Caspian and Black Seas in particular, as well as south Asia, the Middle East, western Europe, and Africa, were put on high alert for the virus’s potential arrival beginning in the fall, based on the behavior of previous HPAI waves.

Right on cue, in October this H5N8 virus began showing up to the south, in India, and the next month in Europe to the west, and Israel, Egypt, and Tunisia along the Mediterranean Sea.

The successful predictions stemming from Lake Uvsu-Nur surveillance this summer are encouraging. But much remains to understand about avian influenza viruses. While the smoking gun of HPAI detections and bird mortalities on Central Asian wetlands is important, we cannot expect to have such a warning every time.

And undoubtedly there will be false alarms too, with HPAI detections not followed by widespread outbreaks. It may be that these viruses become so common that they will be found every year in wild birds on Central Asian wetlands, neutralizing their predictive value.

But careful surveillance of these areas nonetheless promises to be a useful tool in our preparedness for HPAI. Early warning prompts countries to boost biosecurity and HPAI surveillance, allowing earlier detection and response measures that can limit spread of the virus. This will lessen impacts on domestic birds and reduce the mixing of these pathogens that can eventually lead to viruses better adapted to people.

Select References

The Global Consortium for H5N8 and Related Influenza Viruses. Role for migratory wild birds in the global spread of avian influenza H5N8. Science, 2016 Oct; 354(6309): 213-217.

Sims L, Khomenko S. et al. H5N8 highly pathogenic avian influenza (HPAI) of clade 2.3.4.4 detected through surveillance of wild migratory birds in the Tyva Republic, the Russian Federation – potential for international spread. Empress Watch, 2016 Sep; 35.

Verhagen JH, Herfst S. and Fouchier RAM. How a Virus Travels the World. Science, 2015 Feb; 347(6222): 616-617.