PLoS One: Seroprevalence Of H9N2 In Poultry Workers – Pune, India

 

 

# 6337

 

While H5N1 gets the lion’s share of the media’s attention, there are other influenza viruses in the wild believed capable of sparking the next flu pandemic.  Over the past dozen years we’ve seen a number of avian flu strains that have made limited jumps to human hosts.

 

• In 2003, an outbreak of H7N7 at a poultry farm in the Netherlands went on to infect at least 89 people (mostly mildly, but 1 death), and many more may have been infected subclinically.
• In Egypt - in 2004 -  2 infants were shown to be infected by the H10N7 avian flu virus.
• In 2006 1 person in the UK was confirmed to have contracted H7N3, and the following year, 4 people tested positive for H7N2 – both following local outbreaks in poultry.

 

But in terms of greatest concern, the closest runner up to H5N1 is probably H9N2 – which is known to have infected a handful of humans, mostly in Asia.

 

To date, most of these cases have produced relatively mild illness.  

 

Nevertheless, the World Health Organization  has announced that work has begun on the creation of an H9N2 candidate vaccine (see WHO Report : Antigenic & Genetic Characteristics of H5N1 & H9N2 Viruses).

 

Last year, in PNAS: Reassortment Potential Of Avian H9N2 , researchers looked at the reassortment potential of the avian H9N2 virus and H1N1, generating four reassortant viruses, three of which showed efficient respiratory droplet transmission in the ferret model.

 

These authors had previously successfully created laboratory reassortments between seasonal H3N2 and H9N2. 

 

Experiments that are, in many ways, similar to the H5N1 experiments of Fouchier and Kawaoka that have caused such a stir these past few months, albeit on a (thus far) much-less-pathogenic flu virus.

 

These successes (and others, see PNAS: Reassortment Of H1N1 And H9N2 Avian viruses), along with the wide geographic distribution of the H9 avian virus in poultry across Asia and the Middle East, have led many researchers to call for better research and surveillance on this avian strain.

 

Which brings us to a new study, published late last week in the journal Plos One, that looks at the prevalence of antibodies to the H9N2 strain among poultry workers – and the general population – in Pune, India.

 

Avian Influenza H9N2 Seroprevalence among Poultry Workers in Pune, India, 2010

Shailesh D. Pawar, Babasaheb V. Tandale, Chandrashekhar G. Raut, Saurabh S. Parkhi, Tanaji D. Barde, Yogesh K. Gurav, Sadhana S. Kode, Akhilesh C. Mishra

PLoS ONE 7(5): e36374. doi:10.1371/journal.pone.0036374

Abstract

Avian influenza (AI) H9N2 has been reported from poultry in India. A seroepidemiological study was undertaken among poultry workers to understand the prevalence of antibodies against AI H9N2 in Pune, Maharashtra, India.

 

A total of 338 poultry workers were sampled. Serum samples were tested for presence of antibodies against AI H9N2 virus by hemagglutination inhibition (HI) and microneutralization (MN) assays.

 

A total of 249 baseline sera from general population from Pune were tested for antibodies against AI H9N2 and were negative by HI assay using ≥40 cut-off antibody titre.

 

Overall 21 subjects (21/338 = 6.2%) were positive for antibodies against AI H9N2 by either HI or MN assays using ≥40 cut-off antibody titre. A total of 4.7% and 3.8% poultry workers were positive for antibodies against AI H9N2 by HI and MN assay respectively using 40 as cut-off antibody titre.

 

This is the first report of seroprevalence of antibodies against AI H9N2 among poultry workers in India.

 

 

Although a bit of a gray area, an antibody titer level of ≥40 is generally assumed to be suggestive of a previous (possibly sub-clinical) infection by a specific virus.

 

Interestingly, none of the 249 sera samples from the general population showed elevated antibody titers to the H9N2 virus (using the ≥40 cut-off standard), but among poultry workers, 21 of the 338 sera samples (6.2%) tested positive for H9N2 antibodies.

A fairly low number given the amount of exposure,  but indicative that some transmission of the virus to humans appears to be taking place.

The authors warn that:

 

The evidence of AI (H9N2) in poultry market may provide the opportunity for human infections and the possibility of reassortment with the existing poultry AI viruses including HPAI H5N1 virus.

 

Warnings over the pandemic potential of the H9N2 virus are not new. A few notable stories from the past include:

 

• In December 2008 I ran a blog featuring an interview in which world famous Hong Kong virologist Malik Peiris cautioned that the H9N2 virus may be circulating far more commonly than we believe. Revisiting A Malik Peiris Interview On H9N2.

• In January of 2010, in H9N2: The Other Bird Flu Threat, I wrote about the World Health Organization  recommending the creation of a candidate vaccine virus for H9N2.

• And in November 2010, in Study: The Continuing Evolution Of Avian H9N2, we looked at computer modeling that suggested that the H9N2 virus moving towards becoming more `human-adapted’.

 

 

Unlike the H7 and H5 avian flu strains, poultry (and swine) infections by the H9N2 virus are not required to be reported to the OIE.  

 

Admittedly, the next influenza virus to successfully jump species could come out of left field, as we saw in 2009 with the H1N1 swine flu.

 

 

Which is why the global monitoring of influenza viruses - in humans, on the farm, and in the wild - remains crucial if we hope to detect, and prepare for, the next pandemic at the earliest possible moment.

»» Read More

South Korea Confirms H9N2 Outbreak

South Chungcheong Province – Credit Wikipedia

 

# 6221

 

 

Although considered to pose a far lower risk to humans and poultry than do the H5 and H7 strains of avian flu, H9N2 has been known to infect humans - and while generally producing mild symptoms  – is considered to have at least some degree of pandemic potential.

 

Since H9N2 circulates in many regions of the world where influenza testing is rarely done, we don’t really know how often this virus infects humans.

 

Over the past dozen years a small handful of cases have been identified – mostly in Hong Kong (see CIDRAP Avian Influenza (Bird Flu): Implications for Human Disease).

 

 

Last year Bangladesh detected a human infection and sent a virus sample to the CDC for development into a `seed strain’ for possible use in a vaccine (see  CIDRAP NEWS Bangladesh shares H9N2 virus).

 

Which brings us to a report from Xinhua News this morning on an outbreak of avian flu in Korea – first feared to be H5 – but now shown to be H9N2.

 

S. Korea confirms outbreak of low pathogenic avian influenza

English.news.cn   2012-03-13 18:32:00

 

SEOUL, March 13 (Xinhua) -- South Korea on Tuesday confirmed an outbreak of a low pathogenic avian influenza virus in chickens previously tested positive for avian flu, the government said Tuesday.

 

The Ministry for Food, Agriculture, Forestry and Fisheries said the birds at a poultry farm in South Chungcheong Province were found to have been infected with the low pathogenic H9N2 strain of the avian influenza virus that is less damaging to both birds and humans.

 

Quarantine authorities conducted thorough examinations after six of 10 chickens at the farm tested positive for avian flu. Some 100 chickens at the farm had shown symptoms of avian flu.

 

The ministry ordered the affected farm to remain under watch until restrictions on travel to and from the site will be removed.

 

 

After the widespread outbreaks of H5N1 last year in South Korea that led to the culling of millions of birds, it is no doubt a relief to officials that this turned out to be an LPAI H9 virus.

 

Unlike the H7 and H5 avian flu strains, poultry (and swine) infections by the H9N2 virus are not required to be reported to the OIE.  So we have far less data on how widespread H9N2 might be.

 

Despite causing rare human infection, H9N2 would likely need to acquire a number of genetic changes before it could pose a serious public health threat.

 

Which is why we concern ourselves with influenza’s ability to reassort with other co-circulating flu strains. Reassortment happens when two different influenza viruses co-infect the same host and swap genetic material.

 

 

 

In February of 2011, in PNAS: Reassortment Of H1N1 And H9N2 Avian viruses, we saw research from Chinese scientists that created – using reverse genetics – 128 reassorted viruses from the avian H9N2 virus and the (formerly pandemic) H1N1 virus.

 

In mouse testing, they found half of the hybrid viruses were biologically `fit’ as far as replication goes, and 8 hybrids were significantly more pathogenic than either of their parental viruses.

 

Research such as this shows the potential for the H9N2 virus to move towards a more `humanized’ pathogen. And with H1N1 and H9N2 both known to be circulating in pigs in Asia, there are ample opportunities for them to co-infect the same host.

 

While admittedly not at the top of our viral hit parade, H9N2 still commands respect. A few notable H9N2 stories from the past include:

 

• In December 2008 Revisiting A Malik Peiris Interview On H9N2

• In January of 2010, in H9N2: The Other Bird Flu Threat

• And in November of 2010 Study: The Continuing Evolution Of Avian H9N2

 

 

It is worth remembering that while everyone was watching the H5N1 virus for development, the 2009 H1N1 pandemic emerged from a completely unexpected region (North America), species (swine), and viral strain (H1).

 

All of which highlights the importance of establishing better global surveillance of humans, and farm animals, for the next emerging influenza virus.

 

Regardless of its strain.

»» Read More

Study: Subclinical H5 & H9 Infections In Humans

 

 

 

# 5994

 

 

As of November 29th, 2011 the World Health Organization has logged 571 confirmed human infections with the H5N1 virus, with 335 deaths. The case fatality rate (CFR) – based on the numbers we know – is a staggeringly high 58.6%.

 

Mash up of WHO data

 

But most observers will grant that these totals are not likely to represent the entire burden of the H5N1 virus in humans around the world. As with any other illness or disease, surveillance is imperfect, and not every case is counted.

 

Surveillance across much of Asia and the Middle East - where the virus is known to be endemic - is spotty at best, and many countries do not have the laboratory facilities, budget, or political will to adequately screen for the virus.

 

It has been suggested that the reason the CFR of this virus is perceived to be so high is because milder cases are more likely to go unrecognized or unreported.

 

 

And while that sounds reasonable, without evidence of a substantial number subclinical or mild infections, you can’t just leap to that conclusion.

 

Finding that evidence would be a good news-bad news proposition.  

 

The good news is that it would reduce the CFR of the virus, albeit perhaps not by a lot.

 

The bad news is that it could indicate the virus is slightly better adapted to human physiology than we currently believe, and that it might even be transmitting at low levels.

 

Last night CIDRAP News carried a small summary of a letter that appears in the Dec. 5th Clinical Infectious Disease Journal that reported on the detection of several villagers in and around Beijing, China who showed serological evidence of prior infection by H5 and H9 avian viruses.

 

The link to the letter follows:

 

 

Infection With Multiple Avian Influenza Viruses in a Man Without Poultry-Handling Practices Suggesting an Increased Probability of Emergent Pandemic Influenza Virus in General Population

Peng Yang, Weixian Shi, Shujuan Cui, Yi Zhang, Xiujun Liu, and Quanyi Wang

 

The CIDRAP news summary of this letter can be read at the following link:

 

Chinese scientists find evidence of avian flu infection with 2 strains

Chinese researchers identified several villagers who didn't handle poultry to be seropositive for avian flu, including a man who tested seropositive for two strains, according to their letter in Clinical Infectious Diseases yesterday.

 

They conducted a serologic analysis of 605 Beijing-area residents, randomly selected from 24 villages ,who did not have a history of handling poultry. The investigators found antibodies against H9 avian flu by hemagglutination inhibition assay in five of the villagers, and one of these, a 55-year-old man, also tested positive for H5 antibodies.

(Continue . . . )

 

 

Admittedly, these numbers are pretty low.

 

Less than 1% tested positive for prior exposure to H9 avian flu, and only one showed evidence of H5N1 infection.

 

But they do validate that some degree of undetected human infection by these avian influenza viruses have occurred  - and they have happened in the general population - not just in those with frequent poultry exposures.

 

While serological studies like this are rare, we have seen other research over the past couple of years suggesting that both H5N1 and H9N2 have caused silent, or unreported, infections in humans.

 

In September of this year we saw a study that reported the results of this kind of serological testing conducted in a rural village in Thailand in 2008 (see Bangladesh To Share H9N2 Bird Flu Virus). 

 

Out of 800 villagers tested, the authors found 4.7% were seropositive for the Hong Kong H9N2 avian strain, 5.6% had antibodies to A/Thailand/676/2005 H5N1 bird flu, and 3.5% were shown to be seropositive to A/Thailand/384/2006 H5N1 .

 

Last May, in EID Journal: Unraveling Pakistan’s H5N1 Outbreak, we looked at a study that suggested that the actual number of human cases in the 2007 Pakistan cluster was higher than reported.

 

From the abstract, the authors write:

 

Volume 17, Number 6–June 2011

Dispatch

Human Infection with Avian Influenza Virus, Pakistan, 2007

Mukhtiar Zaman, Saadia Ashraf, Nancy A. Dreyer, and Stephen Toovey

Abstract

Human infection with avian influenza (H5N1) virus raises concern for the possibility of a pandemic. We report 20 cases, which ranged from asymptomatic to fatal, in Pakistan in 2007.

 

These cases indicate human-to-human-to-human transmission of this virus, and the number of cases may be higher than realized.

 

In May of 2009 (see Cambodian Study Finds Rare Asymptomatic H5N1 Infections) we saw a seroprevalence study published in the Journal of Infectious Diseases  conducted on more than 600 members of a Cambodian village where 2 human H5N1 cases were detected in 2006.

 

Antibody titers showed that only 1% (7 of 674) of the villagers tested had contracted, and fought off, the H5N1 virus.   A figure much lower than many had expected.

 

Another study – presented at the Options For Influenza Control VI  Conference in Toronto in 2007, came up with similar results (see Seroprevalence Study).

 

So far, all we have are a few ragged pieces of this serological puzzle, gleaned over a period of several years from a handful of countries, and involving extremely small population samples.

 

All of which makes it impossible to draw any firm conclusions.

 

For the glass half-full crowd, these studies do suggest that mild or subclinical infections by these avian viruses – while not particularly common –  can occur. And that may moderate the CFR somewhat.

 

For the glass half-empty contingent, the number of subclinical cases may not be enough to lower the CFR as much as some have hoped, and their detection – even these at low levels – raise concerns over the eventual adaptation of these viruses to humans.

 

What is sorely needed are more detailed serological studies, both among the general population where these viruses are endemic, and among close contacts to known H5N1 and H9N2 infections.

 

But these studies are expensive, difficult to mount due to geographic, societal, political and religious reasons, and are further complicated by the existence of least 20 genetically separate clades of the H5N1 virus, with many minor variants of each clade thrown in the mix.

 

A study conducted where clade 2.3.4 of the H5N1 virus is endemic may not tell us much about subclinical human infections in areas where clade 2.3.2.1 is circulating.

 

 

Without better data, public health officials are forced to make vital decisions regarding the pandemic potential of H5N1, H9N2, and  many other novel viruses based on incomplete information.

 

Which is hardly an enviable position for a world that is unlikely to have much in the way of immunity to a future pandemic caused by one of these emerging influenza strains. 

»» Read More

H9N2: Part Of A Crowded Viral Field

 

 

 

# 5958

 

 

Although chickens often bear the brunt of the blame in the media, aquatic waterfowl are actually the natural host (and likely the principal culprits in spreading) of avian influenza.

 

Unlike poultry and some species of wild birds which tend to visibly sicken and often die from HPAI (Highly Pathogenic Avian Influenza) viruses - ducks and waterfowl can frequently carry these viruses with little or no ill effects.

 

The influenza virus in birds is primarily a gastrointestinal infection, and is spread through feces. Where ducks and chickens intermingle – a common occurrence in Asia – the virus can easily jump to poultry.

 

The focus over the past few years has been on HPAI H5N1, because of its tremendous impact on the poultry industry around the world and the horrendously high mortality rate in the small number of human infections.

 

But other avian flu viruses are in circulation, and of concern as well.

 

In 2003, an outbreak of H7N7 at a poultry farm in the Netherlands went on to infect at least 89 people (mostly mildly, but 1 death), and many more may have been infected subclinically.

In Egypt - in 2004 -  2 infants were shown to be infected by the H10N7 avian flu virus.

 

In 2006 1 person in the UK was confirmed to have contracted H7N3, and the following year, 4 people tested positive for H7N2 – both following local outbreaks in poultry.

 

But in terms of concern, the closest runner up to H5N1 virus right now is probably H9N2 – which is known to have infected a handful of humans, mostly in Asia – and has the World Health Organization concerned enough that they are working on the creation of a candidate vaccine (see WHO Report : Antigenic & Genetic Characteristics of H5N1 & H9N2 Viruses).

 

Admittedly, the next influenza virus to successfully jump species could come out of left field, as we saw in 2009 with the H1N1 swine flu.

 

 

All of which serves as prelude to a new study that has just been published in the Archives of Virology that looks at the panorama of influenza pathogens detected in Vietnamese ducks over the past couple of years. 

 

Below you’ll find excerpts from the abstract (reparagraphed for readability).

 

 

Arch Virol. 2011 Nov 9. [Epub ahead of print]

Characterization of avian influenza viruses isolated from domestic ducks in Vietnam in 2009 and 2010.

 

Nomura N, Sakoda Y, Endo M, Yoshida H, Yamamoto N, Okamatsu M, Sakurai K, Hoang NV, Nguyen LV, Chu HD, Tien TN, Kida H.

Abstract

In the surveillance of avian influenza in Vietnam, 26 H9N2, 1 H3N2, 1 H3N8, 7 H4N6, 3 H11N3, and 1 H11N9 viruses were isolated from tracheal and cloacal swab samples of 300 domestic ducks in April 2009, and 1 H9N6 virus from 300 bird samples in March 2010.

 

Out of the 27 H9 virus isolates, the hemagglutinins of 18 strains were genetically classified as belonging to the sublineage G1, and the other nine belonged to the Korean sublineage.

 

Phylogenetic analysis revealed that one of the 27 H9 viruses was a reassortant in which the PB2 gene belonged to the Korean sublineage and the other seven genes belonged to the G1 sublineage.

 

Three representative H9N2 viruses were intranasally inoculated into ducks, chickens, pigs, and mice. On the basis of experimental infection studies, it was found that each of the three viruses readily infected pigs and replicated in their upper respiratory tracts, and they infected chickens with slight replication.

 

Viruses were recovered from the lungs of mice inoculated with two of the three isolates. The present results reveal that H9 avian influenza viruses are prevailing and genetic reassortment occurs among domestic ducks in Vietnam.

 

It is recommended that careful surveillance of swine influenza with H9 viruses should be performed to prepare for pandemic influenza.

 

 

Although 7 different avian flu viruses were detected, 2/3rds were of the H9 variety.  And their `fitness’ for replication in other species, particularly swine, is concerning.

 

Today only H5 and H7 avian viruses are required to be reported to the OIE, and given that H9N2 often spreads asymptomatically in poultry, its actual prevalence is probably underestimated around the globe.

 

In 2009, in the Journal of Clinical Virology, we saw a study out of China that looked for serological signs of human infection by both H7 and H9 influenza viruses.

 

 

 

Serological reports of human infections of H7 and H9 avian influenza viruses in northern China.

Jia N, de Vlas SJ, Liu YX, Zhang JS, Zhan L, Dang RL, Ma YH, Wang XJ, Liu T, Yang GP, Wen QL, Richardus JH, Lu S, Cao WC.

(EXCERPT)

A total of 583 sera collected from farmers in Xinjiang were tested, and 10 (1.7%) were positive for H9 virus infection. Out of 200 sera collected from Liaoning, two (1.0%) were infected by H9 virus. No H7 virus infection was detected in the above serum samples. Neither H7 nor H9 virus infection was identified in 277 poultry workers of Shandong and in 407 residents of Shanxi.

CONCLUSIONS:

Although H9 virus infection was limited in farmers from Xinjiang and Liaoning, a public health alert is needed as novel pandemic influenza strains may develop unnoticed given the presence of subclinical infections, and the possibility of re-assortment with prevailing H5N1 virus in these regions.

 

In another study (see Evidence for Subclinical Avian Influenza Virus Infections Among Rural Thai Villagers), testing of 800 villagers found:

 

• 38 (4.7%) who were seropositive for the Hong Kong H9N2 flu strain
• 45 (5.6%) had antibodies to A/Thailand/676/2005 H5N1
• 28 (3.5%) were shown to be seropositive to A/Thailand/384/2006 H5N1.

 

While the absolute number of positive detections so far have been small, these studies reinforce the idea that H5N1 isn’t the only bird flu game in town.

 

A few notable H9N2 stories from the past include:

 

• In December 2008 Revisiting A Malik Peiris Interview On H9N2

• In January of 2010, in H9N2: The Other Bird Flu Threat

• And from November 2010  Study: The Continuing Evolution Of Avian H9N2

 

All of which highlights the importance of establishing better global surveillance of humans, and farm animals, for the next emerging influenza virus. 

 

Regardless of its strain.

»» Read More

WHO Report : Antigenic & Genetic Characteristics of H5N1 & H9N2 Viruses

 

 

# 5874

The World Health Organization has published a 12-page document (dated 9/29) – that summarizes recent global activity of A(H5N1) and A(H9N2) avian influenza viruses and describes the current status of candidate vaccines under development.

 

Similar reports have been issued twice each year since 2006.

 

This latest report may be read, and downloaded at:

 

Antigenic and genetic characteristics of influenza A(H5N1) and influenza A(H9N2) viruses and candidate vaccine viruses developed for potential use in human vaccines

September 2011

This summary provides a review on the influenza A(H5N1) and A(H9N2) virus activity and virus characterization, and describes the current status of the development of new A(H5N1) and A(H9N2) candidate vaccine viruses. It is meant to provide guidance for national authorities and vaccine companies on the selection of candidate viruses for use in vaccine development.

• Full Text - September 2011

As you can tell by the above chart, the H5N1 virus continues to diversify into additional clades - and there  remain substantial gaps in our knowledge of the virus – particularly among strains circulating in Indonesia.

 

The spread of the 2.3.2.1 clade of the virus – which was the subject of an FAO announcement (see FAO Warns On Bird Flu) a month ago – is particularly  pronounced in this report with detections in Bangladesh, China Hong Kong SAR, India, Japan, the Republic of Korea, Myanmar, and Vietnam.

 

This `new’ clade differs antigenically from the poultry vaccines currently being used in many Asian countries, and the concern is that a new wave of bird flu may spread through poultry this winter.

 

This document summaries this new clade by saying:

 

Clade 2.3.2.1 (previously part of clade 2.3.2) viruses were detected in wild birds in Bangladesh, Japan and  the  Republic of Korea, and  also  in poultry in  Bangladesh,  China  Hong Kong Special
Administrative Region (China Hong Kong SAR), India, Japan, Myanmar, Republic of Korea and Viet
Nam.

Although  there is some genetic  (Figure 3) and antigenic heterogeneity  among  viruses of this
clade, recently  isolated viruses reacted well with post-infection ferret antisera against either A/Hong
Kong/6841/2010  (an  A/Hubei/1/2010-like virus)  or  A/barn swallow/Hong Kong/D10-1161/2010
(Tables 2 and 3), from which candidate vaccine viruses have been developed (Table 5). 

 

While newer 2.3.2.1 clade samples reacted well against a couple of candidate vaccines already selected, the 2.3.4.2 clade out of Bangladesh does not. Therefore, the development of a new clade 2.3.4.2 candidate vaccine virus is proposed.

Similarly, after the detection of a human infection by the avian H9N2 virus in Bangladesh earlier this year, a proposal has been made to develop a candidate vaccine for that strain as well.

 

And lastly, the document addresses the detection of several SOIV (Swine Origin Influenza Virus) infections this year in Indiana, and Pennsylvania.

 

Swine-Origin Influenza A(H3N2) 

Swine influenza A(H3N2) viruses are enzootic in swine herds of North America and other parts of the
world. Characterisation of recent A(H3N2) viruses from swine in North America indicates that their HA genes have evolved from the human virus precursors that circulated in the mid-1990s. Isolation of swine-origin influenza viruses (SOIV) A(H3N2) from humans has been reported infrequently.  The United States of America reported eight infections due to A(H3N2) SOIV between January 2005 and 15 February 2011. 

A(H3N2) SOIV infections from 16 February 2011 to 19 September  2011

There have been four human infections  with A(H3N2) SOIV  in the states of Indiana (1) and Pennsylvania (3), United States of America, in this period. The HA and neuraminidase genes of these four viruses were similar to those  of swine viruses that circulate  in the United States  of America.

Sequencing data indicated that the  matrix  genes of these viruses were acquired  from an A(H1N1)pdm09 virus, unlike SOIV isolates from previous human cases.

Antigenic analysis indicated that these viruses were distinct from currently circulating human  A(H3N2)  viruses  but  similar to  swine A(H3N2) viruses from previous years as well as to A/Minnesota/11/2010 (H3N2) SOIV (Table 7), from which a candidate vaccine virus is under development.

 

 

Avian viruses, like all influenza A viruses, are constantly under pressure to change and mutate, looking for a biological advantage. Most of these mutations, thankfully, are evolutionary dead ends and fail to spread and thrive.

 

But in this viral version of king-of-the-hill, nature occasionally produces a more `fit’ and competitive virus, and it begins to dominate and spread.

 

Which is why continual monitoring of the genetic and antigenic changes in these viruses is so crucial.  As avian viruses evolve, new candidate vaccines must be developed, else we could be caught flat footed if a pandemic suddenly began.

 

Having a candidate vaccine already in hand could save weeks in the time it would take to produce and deploy an emergency vaccine. 

 

And during a severe pandemic, a few weeks delay could translate into the loss of thousands of lives.

»» Read More

Bangladesh To Share H9N2 Bird Flu Virus

 

 

# 5849

 

 

To go along with my blog earlier today (see Dr. Robert Webster’s bird flu concerns), we’ve a report from Bangladesh on an agreement to share samples of the H9N2 bird flu virus with the U.S. CDC for development of a seed vaccine.

 

As has been mentioned here before, H9N2 – while generally producing mild symptoms in humans and poultry – is considered to have pandemic potential.

 

The concern is that it could reassort (swap genes) with other influenza viruses (including H5N1), producing a more virulent and easily transmissible strain.

 

First today’s report from bdnews24.com  (h/t Treyfish on FluTrackers), and then I’ll return with more.

 

 

B'desh to help make bird flu vaccine

Sun, Sep 18th, 2011 9:24 pm BdST

 

Nurul Islam Hasib bdnews24.com Senior Correspondent

Dhaka, Sep 18 (bdnews24.com) – Bangladesh will share a new strain of bird flu virus, identified as a possible pandemic threat, with US Centres for Disease Control and Prevention (US CDC) to develop 'seed virus,' key ingredient to make a vaccine in emergency.

"We will share the vaccine for scientific use," health secretary Muhammad Humayun Kabir told bdnews24.com on Sunday as he confirmed about the sharing of the H9N2 strain of bird flu—A/Bangladesh/0994/2011 (H9N2).

(Continue . . . )

 

 

This article mentions human infections from H9N2 were detected in Bangladesh last March, although no details are provided.  FluTrackers did pick up an FAO/EMPRES report on a human case during that time period which you can read here.

 

Since H9N2 circulates in regions of the world where influenza testing is rarely done, we don’t really know how often this virus infects humans. Over the past dozen years a small handful of cases have been identified – mostly in Hong Kong (see CIDRAP Avian Influenza (Bird Flu): Implications for Human Disease).

 

Adding to the concern, just last week a study was published that looked at level of antibodies to H5N1 and H9N2 flu viruses among rural villagers in Thailand.

 

Evidence for Subclinical Avian Influenza Virus Infections Among Rural Thai Villagers

Clinical Infectious Diseases

Volume53, Issue8

Pp. e107-e116

Benjawan P. Khuntirat1, In-Kyu Yoon1, Patrick J. Blair2, Whitney S. Krueger3,4, Malinee Chittaganpitch5, Shannon D. Putnam2, Krongkaew Supawat5, Robert V. Gibbons1, Sirima Pattamadilok5, Pathom Sawanpanyalert5, Gary L. Heil3,4, John A. Friary3,4, Ana W. Capuano6, and Gregory C. Gray3,4

 

 

In testing 800 villagers they found 38 (4.7%) who were seropositive for the Hong Kong H9N2 flu strain, 45 (5.6%) had antibodies to A/Thailand/676/2005 H5N1, and 28 (3.5%) were shown to be seropositive to A/Thailand/384/2006 H5N1.

 

Interestingly, direct exposure to poultry was not found to be associated with positive serologic findings for any of these avian strains.

 

This study – while limited – suggests that mild (or possibly subclinical) infections by these avian viruses may be occurring in parts of Asia.  

 

Despite causing rare human infection, these avian viruses need to acquire genetic changes before they could spark a pandemic. Which is why we concern ourselves with their ability to reassort with other flu strains.

 

Reassortment (or Shift), happens when two different influenza viruses co-infect the same host and swap genetic material.

 

 

Influenza A viruses have 8 gene segments (PB2, PB1, PA, HA, NP, NA, M1, M2, NS1, NS2).

 

Which means that any two compatible influenza viruses could conceivably – and under the right conditions – generate 256 different combinations by swapping one or more of their 8 (potentially) interchangeable gene segments.

 

 

Last February in PNAS: Reassortment Of H1N1 And H9N2 Avian viruses we saw research from Chinese scientists that created – using reverse genetics – 128 reassorted viruses from the avian H9N2 virus and the (formerly pandemic) H1N1 virus.

 

In mouse testing, they found half of the hybrid viruses were biologically `fit’ as far as replication goes, and 8 hybrids were significantly more pathogenic than either of their parental viruses.

 

Research such as this shows the potential for the H9N2 virus to move towards a more `humanized’ pathogen. And with H1N1 and H9N2 both known to be circulating in pigs in Asia, there are ample opportunities for them to co-infect the same host.

 

A few notable H9N2 stories from the past include:

• In December 2008 Revisiting A Malik Peiris Interview On H9N2

• In January of 2010, in H9N2: The Other Bird Flu Threat

• And just this past November Study: The Continuing Evolution Of Avian H9N2

 

Unlike the H7 and H5 avian flu strains, poultry (and swine) infections by the H9N2 virus are not required to be reported to the OIE.  So we have far less data on how widespread H9N2 might be.

 

As we saw in 2009, sometimes a pandemic virus will emerge from an unexpected source, and with a surprising lineage. While the world was waiting for an H5 bird flu to emerge from Asia, we were blindsided by a H1N1 swine flu from North America.

 

All of which highlights the importance of establishing better global surveillance of humans, and farm animals, for the next emerging influenza virus. 

 

Regardless of its strain.

»» Read More

PNAS: Reassortment Potential Of Avian H9N2

 

 

 

# 5675

 

All that is required to spark a pandemic is for a novel influenza virus to emerge that mankind has little or no resistance to, for it to cause significant morbidity and mortality, and for it to adapt to human physiology so that it transmits efficiently.

 

The H5N1 virus fulfills these first two criteria, but fails on the third. 

 

For now, anyway.

 

But there are many other influenza viruses circulating in birds, pigs, and other species that have the potential to either mutate - or more likely - reassort (swap gene segments with another flu strain) and adapt to human hosts.

 

Below you’ll find a chart lifted and edited from CIDRAP’s excellent overview Avian Influenza (Bird Flu): Implications for Human Disease  showing non-H5N1 avian flu infections in humans over the past decade.

 

 

Since surveillance is – at best - haphazard (or even non-existent) in many parts of the world, how often these types of novel infections really occur is unknown.  

 

Despite rare known human infections, these viruses need to acquire genetic changes before they could spark a pandemic. Which is why we concern ourselves with their ability to reassort with other – already humanized – flu strains.

 

Reassortment (or Shift), happens when two different influenza viruses co-infect the same host and swap genetic material.

 

 

Influenza A viruses have 8 gene segments (PB2, PB1, PA, HA, NP, NA, M1, M2, NS1, NS2)

.

Which means that any two compatible influenza viruses could conceivably – and under the right conditions – generate 256 different combinations by swapping one or more of their 8 (potentially) interchangeable gene segments.

 

The key words being “under the right conditions”.

 

 

Last February in PNAS: Reassortment Of H1N1 And H9N2 Avian viruses we saw research from Chinese scientists that created – using reverse genetics – 128 reassorted viruses from the avian H9N2 virus and the (formerly pandemic) H1N1 virus.

 

In mouse testing, they found half of the hybrid viruses were biologically `fit’ as far as replication goes, and 8 hybrids were significantly more pathogenic than either of their parental viruses.

 

 

Today, again from PNAS, we have a new study that once again looks at the reassortment potential of the avian H9N2 virus and H1N1.

 

This time, research was done using ferrets, whose respiratory physiology is closer to human than are mice.

 

Compatibility of H9N2 avian influenza surface genes and 2009 pandemic H1N1 internal genes for transmission in the ferret model

J. Brian Kimble, Erin Sorrell,  Hongxia Shao,  Philip L. Martin, and Daniel Roberto Perez

Abstract

In 2009, a novel H1N1 influenza (pH1N1) virus caused the first influenza pandemic in 40 y. The virus was identified as a triple reassortant between avian, swine, and human influenza viruses, highlighting the importance of reassortment in the generation of viruses with pandemic potential.

 

Previously, we showed that a reassortant virus composed of wild-type avian H9N2 surface genes in a seasonal human H3N2 backbone could gain efficient respiratory droplet transmission in the ferret model.

 

Here we determine the ability of the H9N2 surface genes in the context of the internal genes of a pH1N1 virus to efficiently transmit via respiratory droplets in ferrets. We generated reassorted viruses carrying the HA gene alone or in combination with the NA gene of a prototypical H9N2 virus in the background of a pH1N1 virus.

 

Four reassortant viruses were generated, with three of them showing efficient respiratory droplet transmission. Differences in replication efficiency were observed for these viruses; however, the results clearly indicate that H9N2 avian influenza viruses and pH1N1 viruses, both of which have occasionally infected pigs, have the potential to reassort and generate novel viruses with respiratory transmission potential in mammals.

 

The entire study is available online, and open access. 

 

As noted in the abstract above, these authors had previously successfully created laboratory reassortments between seasonal H3N2 and H9N2.  

 

The fact that these hybrid viruses can be created in the laboratory doesn’t automatically mean they would be generated in the field by a co-infected host.

 

Only that it is possible.

 

And with 256 possible combinations, these 4 hybrids might not even represent the most `fit’ reassortments.

 

But research like this continues to show the potential for the H9N2 virus to move towards a more `humanized’ pathogen. And with H1N1 and H9N2 both known to be circulating in pigs in Asia, there are ample opportunities for them to co-infect the same host. 

 

A few notable H9N2 stories from the past include:

• In December 2008 I ran a blog featuring an interview in which world famous Hong Kong virologist Malik Peiris cautioned that the H9N2 virus may be circulating far more commonly than we believe. Revisiting A Malik Peiris Interview On H9N2

• In January of 2010, in H9N2: The Other Bird Flu Threat, I wrote about the World Health Organization  recommending the creation of a candidate vaccine virus for H9N2. According to the latest vaccine update from the WHO, work continues on that candidate vaccine virus.

• And just this past November, in Study: The Continuing Evolution Of Avian H9N2, we looked at computer modeling that suggested that the H9N2 virus moving towards becoming more `human-adapted’.

 

Unlike the H7 and H5 avian flu strains, poultry (and swine) infections by the H9N2 virus are not required to be reported to the OIE.  

 

As we saw in 2009, sometimes a pandemic virus will emerge from an unexpected source, and with a surprising lineage. While the world was waiting for an H5 bird flu to emerge from Asia, we were blindsided by a H1N1 swine flu from North America.

 

All of which highlights the importance of establishing better global surveillance of humans, and farm animals, for the next emerging influenza virus. 

 

Regardless of its strain.

»» Read More

PNAS: Reassortment Of H1N1 And H9N2 Avian viruses

 

 

# 5345

 

 

We’ve a study published today in PNAS that is shedding new light on the possibility of seeing a biologically `fit’ and virulent novel virus emerge from a reassortment between the H9N2 avian flu and the (former) pandemic H1N1 swine flu.

 

Researchers in China – using reverse genetics – created 127 hybrid viruses in the laboratory and tested them on mice for compatibility, replication ability, and virulence.

 

They found that half of the hybrid viruses were biologically `fit’ as far as replication goes, and 8 hybrids were significantly more pathogenic than either of their parental viruses.

 

A link to the study, followed by excerpt from the abstract, and then I’ll return with more.

 

High genetic compatibility and increased pathogenicity of reassortants derived from avian H9N2 and pandemic H1N1/2009 influenza viruses

Yipeng Sun,Kun Qin, Jingjing Wang, Juan Pu, Qingdong Tang, Yanxin Hu, Yuhai Bi,Xueli Zhao, Hanchun Yang, Yuelong Shu, and Jinhua Liu

Abstract

H9N2 influenza viruses have been circulating worldwide in multiple avian species and repeatedly infecting mammals, including pigs and humans, posing a significant threat to public health. The coexistence of H9N2 and pandemic influenza H1N1/2009 viruses in pigs and humans provides an opportunity for these viruses to reassort.

<SNIP>

Our results indicate that some avian H9-pandemic reassortants could emerge with a potentially higher threat for humans and also highlight the importance of monitoring the H9-pandemic reassortant viruses that may arise, especially those that possess the PA gene of H1N1/2009 origin.

 

 

When it comes to pathogenicity of flu viruses, mice are reasonably good test subjects  . . . but are not necessarily the best physiological surrogates for humans.

 

The authors of this study are quoted in the media as saying their next step is to repeat these experiments with ferrets and guinea pigs, lab animals that have more human-like respiratory systems.

 

We’ve discussed reassortment many times before, so those familiar with the concept may wish to skip ahead.

 

Shift, or reassortment, happens when two different influenza viruses co-infect the same host swap genetic material.

Influenza A viruses have 8 gene segments (PB2, PB1, PA, HA, NP, NA, M1, M2, NS1, NS2).

 

Which means that any two compatible influenza viruses could conceivably – and under the right conditions – generate more than 250 different combinations by swapping one or more of their 8 (potentially) interchangeable gene segments.

 

The key words being “under the right conditions”.

 

If it were easy, or a common occurrence, we’d be up to our hip boots in new, reassorted viruses all the time.

 

But it happens often enough that we recognize it as a real threat.   Shift is how new pandemic strains are born, and it was precisely the mechanism that created the 2009 `swine’ flu strain.

 

 

While the novel H1N1 `swine flu’ virus needs no introduction, the H9N2 avian virus is less well known. It is endemic in poultry across Asia, and while rare, we have seen a handful human infections. 

 

How often humans are really infected is unknown, since surveillance and testing among poultry farmers in China is practically non-existent.

 

 

A few notable H9N2 stories from the past include:

 

• In December 2008 I ran a blog featuring an interview in which world famous Hong Kong virologist Malik Peiris cautioned that the H9N2 virus may be circulating far more commonly than we believe. Revisiting A Malik Peiris Interview On H9N2

• A little over a year ago, in H9N2: The Other Bird Flu Threat, I wrote about the World Health Organization  recommending the creation of a candidate vaccine virus for H9N2. According to the latest vaccine update from the WHO, work continues on that candidate vaccine virus.

• And just this past November, in Study: The Continuing Evolution Of Avian H9N2, we looked at computer modeling that suggested that the H9N2 virus moving towards becoming more `human-adapted’.

 

Today’s PNAS study, like many others before it  . . .

 

EID Journal: H1N1 Reassortment Possibilities

mBio: A/H1N1 Potential For Mutation

PNAS: H3N2 And H5N1 Reassortment)

 

. . .  point out the potential for nature’s laboratory to come up with new, and potentially devastating, flu strains through genetic reassortment. Granted, less virulent hybrid flu strains are also a possibility.

 

While we may not be able to stop the next pandemic from happening - knowing which dangerous hybrids to look for, and conducting aggressive global surveillance - may help us detect the next outbreak at the earliest possible moment.

And a few extra week’s warning could make all the difference between having a vaccine in time to mitigate the pandemic’s peak, or having it arrive after the worst had passed.

»» Read More

Study: The Continuing Evolution Of Avian H9N2

 

 

 

# 5058

 

 

When it comes to avian influenzas, H5N1 gets the lion’s share of our attention, but it isn’t the only avian flu strain with the potential to jump to humans.

 

Below you’ll find a chart lifted and edited from CIDRAP’s excellent overview Avian Influenza (Bird Flu): Implications for Human Disease  showing non-H5N1 avian flu infections in humans over the past decade.

 

 

Since surveillance is – at best - haphazard (or even non-existent) in many parts of the world,  how often this really happens is unknown.  

 

Like the novel swine flu cases that caused such a stir last week, they probably happen a bit more often than we realize.

 

A couple of years ago, we saw a study in PNAS that indicated that the H7 virus might be moving more towards adapting to humans.

 

Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility

 

You can read more about this in a couple of blogs from 2008, H7's Coming Out Party and H7 Study Available Online At PNAS.

 

 

Today, in a similar vein, we have study appearing in the Virology Journal that suggests that the H9N2 virus may also be evolving more towards humans as well.

 

While most virological research studies are in vivo or in vitro, this one is in silica, or based primarily on computer analysis of existing data.

 

 

Avian influenza A (H9N2): computational molecular analysis and phylogenetic characterization of viral surface proteins isolated between 1997 and 2009 from the human population

Azeem M Butt, Samerene Siddique, Muhammad Idrees and Yigang Tong

Virology Journal 2010, 7:319 doi:10.1186/1743-422X-7-319

Published: 15 November 2010

Abstract (provisional)

Background

H9N2 avian influenza A viruses have become panzootic in Eurasia over the last decade and have caused several human infections in Asia since 1998. To study their evolution and zoonotic potential, we conducted an in silico analysis of H9N2 viruses that have infected humans between 1997 and 2009 and identified potential novel reassortments.

Results

A total of 22 hemagglutinin (HA) and neuraminidase (NA) nucleotide and deduced amino acid sequences were retrieved from the NCBI flu database.

It was identified that mature peptide sequences of HA genes isolated from humans in 2009 had glutamine at position 226 (H3) of the receptor binding site, indicating a preference to bind to the human alpha (2-6) sialic acid receptors, which is different from previously isolated viruses and studies where the presence of leucine at the same position contributes to preference for human receptors and presence of glutamine towards avian receptors.

Similarly, strains isolated in 2009 possessed new motif R-S-N-R in spite of typical R-S-S-R at the cleavage site of HA, which isn't reported before for H9N2 cases in humans. Other changes involved loss, addition, and variations in potential glycosylation sites as well as in predicted epitopes. The results of phylogenetic analysis indicated that HA and NA gene segments of H9N2 including those from current and proposed vaccine strains belong to two different Eurasian phylogenetic lineages confirming possible genetic reassortments.

Conclusions

These findings support the continuous evolution of avian H9N2 viruses towards human as host and are in favor of effective surveillance and better characterization studies to address this issue.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

 

 

 

In December 2008, after receiving the news of a baby in Hong Kong having been diagnosed with H9N2, I reran a blog featuring an interview in which world famous Hong Kong virologist Malik Peiris cautioned that the H9N2 virus may be circulating far more commonly than we believe. 

 

Revisiting A Malik Peiris Interview On H9N2

 

 

As it exists now, H9 poses a low threat to humans.

 

  

Sporadic reports of human infections – particularly when there is no evidence of ongoing transmission – are interesting, but not particularly alarming.

 

 

But H9, like a number of other avian viruses (H5’s, H7’s) have some pandemic potential, particularly if they can `drift’ or mutate sufficiently, or pick up genetic material from other viruses.  

 

This `reassortment’ could conceivably create a new, hybrid strain of influenza.

 

How likely is this to happen?

 

Well, that’s the big question.  No one really knows.

 

We just know that it is possible.

 

It obviously doesn’t happen often, otherwise we’d be hip deep in new, hybrid viruses all of the time.  But this is essentially the route that the 2009 H1N1 virus took to become a pandemic, and is likely the way the 1957 and 1968 pandemics came about.

 

And so we watch these rare human cases with great interest.  A dangerous reassortment or mutation may never occur with the H9 virus, or it could happen tomorrow.

 

Influenza viruses, as they say, are unpredictable.

»» Read More