Monday, December 01, 2014

An Avian Flu Primer

image

 

# 9392

 

Two years ago, there was essentially just one HPAI (highly pathogenic avian influenza) virus we were really watching – H5N1.  True, there were some lesser avian viruses out there – including H9N2, H5N2, and  H7N7 – but none of these were viewed as posing a major public health threat.

 

Fast forward 24 months, and the avian flu scene has changed dramatically, with the addition of multiple clades of H7N9, H10N8, H5N6, H5N8, and H5N3.   And at the rate new hybrids are emerging, this list could well expand over the next year or two.

 

With so many new avian viruses in the news, it is getting hard to keep track.  So today, a brief overview of the major avian flu `players’ – at least as things stand on this first day of December 2014.

 

But first, a word about clades.

 

While we talk about subtypes as if they represent a single strain, influenza viruses are constantly evolving, and over time each subtype can split into multiple clades; similar, but genetically distinct branches off the family tree. 

 

And within each of these clades, there can be sub-clades, and within those, minor variants.  Each clade, or variant within a clade, has the potential to behave differently.  Some clades may be more virulent than others, while others may develop resistance to antivirals or evade current poultry vaccines (see Differences In Virulence Between Closely Related H5N1 Strains).

 

As a result, the H5N1 virus circulating in Egypt is not the same H5N1 virus circulating in Cambodia.  H5N1 alone has produced more than 20 clades over the years (not all continue to circulate).

image

Diversity of circulating H5N1 Clades – Credit WHO

 

The bottom line is that what we can say about any of these avian flu subtypes today may not hold true tomorrow, as they are constantly evolving.  But we have to start somewhere . . . .

 

H5N1

The granddaddy of avian flu viruses, it first appeared (as an HPAI) in Guangdong Province in 1996, and sparked a mini-epidemic in Hong Kong in 1997 (18 infected, 6 killed).   A massive poultry cull dampened the threat until 2003, when it resurfaced in both Vietnam and China.  


Within three years the virus had spread throughout much of Asia and into Europe, and has become endemic in Indonesia, Vietnam, China, Cambodia, Bangladesh, and Egypt.  Although surveillance and testing is lacking, we know of more than 640 human infections, of which about 60% have died.


The past few years the virus has taken a backseat to some of the newer HPAI’s, but over the past couple of weeks has flared again in Egypt, infecting 7 people.   It is the most geographically widespread, and genetically diverse subtypes of HPAI, and therefore still commands respect for its potential as a public health threat.


For now, it is mainly a threat to poultry operations (it has a high mortality rate in chickens), and to those who have close contact with live (infected) birds.  Like all of the other avian flu threats, for now, it does not transmit well from human-to-human.

 

H7N9

An avian flu virus with a twist – it isn’t highly pathogenic in birds – only (it seems) in humans.  And so instead of being tipped off that the virus is circulating by sick or dead poultry, often our first indication of its presence is when humans begin to fall ill.


Not as deadly as H5N1 is to humans, it still manages to kill about 30% of those sick enough to be hospitalized with the virus. 


H7N9 first appeared nearly 2 years ago (Feb 2013) in Eastern China, where it sparked a brief epidemic that infected 130+ people.   The following year, another epidemic emerged in mid-winter, producing another 300 cases.  Although it is early in the `bird flu season’, we are beginning to see an uptick in H7N9 cases in China once again this fall.

image

Two Waves of H7N9  - Credit Hong Kong’s CHP


Because of its rapid spread to humans (despite a lack of human-to-human transmission), and because it continues to pick up `mammalian adaptations’, H7N9 is viewed as a bigger pandemic threat than H5N1, although no one knows when, or if, either of these viruses will adapt to humans.

 

In June, in Eurosurveillance: Genetic Tuning Of Avian H7N9 During Interspecies Transmission, we saw evidence of the genetic diversity, and continual evolution, of the H7N9 virus in Mainland China.  Researchers found that at least 26 separate genotypes had emerged, mostly during the first wave, through a process they called `genetic tuning’.

 

As this process appears to be ongoing, with unpredictable results, the authors warned:

Overall, due to the genetic tuning procedure, the potential pandemic risk posed by the novel avian influenza A(H7N9) viruses is greater than that of any other known avian influenza viruses.

 

While we can’t afford to turn our backs on any of the emerging avian viruses, H7N9 is considered the one to watch.

 

H5N8

 

One of the newer viruses on the block, H5N8 emerged in Korea last January both in wild & migratory birds, and in commercial poultry operations, and in short ordered spread across the peninsula.   Dozens of farms were affected, and millions of birds were culled.

image

South Korean H5N8 outbreaks – Credit Japan’s MAFF 

 

The virus also showed up briefly in Japan last April, but was quickly stamped out.  This fall H5N8 has shown up in Korea, China, Japan, and Europe – carried it appears by migratory birds – and infecting farms in Germany, the UK, and the Netherlands.


So far, while highly pathogenic in poultry, this virus has not been shown to infect humans.  However, last spring we did see  Korea Finds More Dogs With H5N8 Antibodies

 

As the virus spreads, however, it continues to evolve (see EID Journal: Describing 3 Distinct H5N8 Reassortants In Korea), giving rise to concerns that it could someday pose a greater human health threat.


H5N6

Another recent arrival – H5N6 – appeared on our radar screen last April in Southern China, where it infected local poultry and killed one person (see Sichuan China: 1st Known Human Infection With H5N6 Avian Flu).  While one human infection does not a pandemic threat make, the appearance of H5N6 six months ago was concerning enough that in September we saw the FAO Warn On H5N6.

 

After a quiet summer, in August reports of the virus began to turn up as far south as Central Vietnam and as far north as China's Heilongjiang Province -  more than 2000 miles apart. The latest FAO report (see China: H5 AI Rising) showed 24 detections of H5N6 over the past 6 weeks across thousands of miles of China.

image

Our knowledge of H5N6 remains limited right now, but its rapid spread across China and into Vietnam suggests that it too has `legs’, and could turn up elsewhere in the months and years ahead.

 

H10N8

 

Avian H10 viruses haven’t garnered a lot of attention until relatively recently, as they rarely produce symptoms in poultry, and human infections have been both rare, and mild.  All of that changed last winter when China reported three H10N8 infections (2 fatal)  (see Jiangxi Province Reports 3rd H10N8 Case) in quick succession.

 

LPAI (Low Path Avian Influenza) H10N8 had been previously reported in a duck sampled back in 2012 from Guangdong province, but was otherwise not well described. 

 

Human infections with a close cousin – H10N7 – had previously been reported in two children in Egypt in 2004 (see Avian Influenza Virus A (H10N7) Circulating among Humans in Egypt) and among abattoir workers in Australia in 2012 (see EID Journal: Human Infection With H10N7 Avian Influenza).  

 

In both cases illness was described as mild, and of short duration.

 

In any event, H10N8 is probably the wild card this winter.  We know very little about it, and no one really knows whether it reappear, or simply fade away.

 

H9N2


While only rarely found to infect humans, H9N2 appears to play a central role in the evolution of HPAI viruses.

 

The three novel avian flu strains that currently worry scientists the most – H5N1, H7N9, and the recently observed H10N8 – all share several important features,  which we’ve discussed previously.

  1. They all first appear to emanate from Mainland China
  2. They all appear to have come about through viral reassortment in poultry
  3. And most telling of all, while their HA and NA genes differ - they all carry the internal genes from the avian H9N2 virus

The avian H9N2 virus – unlike the H5 and H7 avian viruses – is not considered a `reportable’ disease by the OIE since it is viewed as a relatively stable LPAI (Low Pathogenic Avian Influenza), not prone to evolving into a more dangerous HPAI form.  It is, however:

  1. Believed ubiquitous across much of Asia’s poultry population
  2. Has occasionally infected humans (see Hong Kong: Isolation & Treatment Of An H9N2 Patient)
  3. And is viewed as having at least some `pandemic potential’ (see H9N2: The Other Bird Flu Threat)


H7N7


Until recently, H7N7 and other H7 viruses had been viewed as posing only a small threat to human health. While they have sparked a small handful of outbreaks – including the largest known H7N7 cluster (89 confirmed, 1 fatality) in the Netherlands more than a decade ago – nearly all of the reported cases have been  very mild (often just conjunctivitis).

 

The impact on the poultry industry has been major. With more than 30 million birds on more than 1,000 farms culled to control the 2003 outbreak in the Netherlands. 

 

More recently, in Mexico we saw two mild human cases in 2012 (see see MMWR: Mild H7N3 Infections In Two Poultry Workers - Jalisco, Mexico), and 3 mild cases in Italy in 2013 (see ECDC Update & Assessment: Human Infection By Avian H7N7 In Italy).

 

While H7s have been regarded as less of a human threat than H5s, in 2008 we saw a study in  PNAS that suggested the H7 virus might just be inching towards adapting to humans (see H7's Coming Out Party). The emergence of an uncharacteristically highly pathogenic (in humans) H7N9 in China in 2013 has only served to increase these concerns

 

There are others out there – H5N3,  H5N2, H6N1 . . . .   - and in truth, six months from now we may be looking at a new crop of reassorted viruses.  The continued use of only partially effective vaccines in China, and elsewhere, is viewed by many as a major driver of new viral reassortments (see EID Journal: Subclinical HPAI In Vaccinated Poultry – China).


While we can’t know when – or even if – any of these viruses will gain enough human adaptations to pose a pandemic threat, the more viral `building blocks’ that are available for nature’s laboratory, the more variations on an avian flu theme that may emerge.


All of which makes any hopes of avian flu’s demise as a pandemic threat premature.

No comments: