Study: Adaptation Of H6N1 From Avian To Human Receptor-Binding

Flu Virus binding to Receptor Cells – Credit CDC

 

# 10,019

 

A couple of days ago in EID Journal: Seropositivity For H6 Influenza Viruses In China, we looked at a study that found a low, but significant level of antibodies – particularly among live bird handlers – to the avian H6 virus in China.  This study was published not quite two years after the Taiwan CDC Reported the Human Infection With Avian H6N1.

 

The H6N1 virus has been around for decades in Chinese poultry - it possesses similar internal genes to H5N1 and H9N2 (cite 2002 J Virol  Molecular evolution of H6 influenza viruses from poultry in Southeastern China by Webster, Webby, Shortridge  et al.) - and it has been speculated that it may have been involved in the genesis of H5N1 in Hong Kong in 1997.

 

While viewed with some suspicion by virologists 15 years ago, once H5N1 emerged into the limelight again in 2003, H6N1 as a possible human threat receded back into the shadows.  It was still studied as an avian threat, of course (see 2007’s Establishment of influenza A virus (H6N1) in minor poultry species in southern China), as it continued to spread (and reassort) across Southeast Asia.

 

The discovery of the virus in a 20 year-old woman with pneumonia in Taiwan two years ago has, understandably, renewed interest in this viral contender, and we’ve seen a flurry of new studies as a result.

 

• Last March, in Avian Flu Antibody Survey In Poultry Workers – Taiwan 2012, we looked at a study that looked for antibodies to H5N2, H6N1, H7N3 and H7N9 among hundreds of subjects, and while they found a fairly low incidence of antibodies overall (max 2.99% for H5N2 in poultry vendors), only found one positive for H6N1.
• Also last March, in TSRI: H10N8 and H6N1 Bind Poorly To Human Receptor Cells - while ostensibly good news – researchers warned that both of these viruses bind differently than other avian viruses we’ve seen, and that our understanding of how these viruses mutate isn’t complete enough to warrant complacency.
• And in late 2013, the Taiwan CDC: Epidemiological Analysis Of Human H6N1 Infection, warned that a (emphasis mine)  “unique clade of H6N1 viruses with a G228S substitution of haemagglutinin have circulated persistently in poultry in Taiwan. These viruses continue to evolve and accumulate changes, increasing the potential risk of human-to-human transmission.”

 

While one (known) human infection pales against the hundreds of H5N1 and H7N9 infections we’ve see over the past decade – it is one more than we’ve seen from H5N8, H5N2, and H5N3 - and it hints as to what is possible down the road.  

 

To this mix we add a new study, published in the EMBO Journal, that finds recent and worrisome changes in the receptor binding characteristics of the H6N1 virus.  Changes they maintain have steadily moved the virus towards an affinity towards human receptor cells instead of avian receptor cells.

 

Note: The G228S substitution mentioned in the Taiwan CDC report above plays heavily in this study.

 

First the abstract, then I’ll return with a bit more:

 

Adaptation of avian influenza A (H6N1) virus from avian to human receptor-binding preference

Fei Wang^1,2,†, Jianxun Qi^2,3,†, Yuhai Bi^2,3, Wei Zhang^2,3, Min Wang^1,2, Baorong Zhang^4,5, Ming Wang¹, Jinhua Liu¹, Jinghua Yan^2,3, Yi Shi^2,3,4 and George F Gao^{1,2,3,4,6,7,*}

Article first published online: 4 MAY 2015

Abstract

The receptor-binding specificity of influenza A viruses is a major determinant for the host tropism of the virus, which enables interspecies transmission. In 2013, the first human case of infection with avian influenza A (H6N1) virus was reported in Taiwan. To gather evidence concerning the epidemic potential of H6 subtype viruses, we performed comprehensive analysis of receptor-binding properties of Taiwan-isolated H6 HAs from 1972 to 2013. We propose that the receptor-binding properties of Taiwan-isolated H6 HAs have undergone three major stages: initially avian receptor-binding preference, secondarily obtaining human receptor-binding capacity, and recently human receptor-binding preference, which has been confirmed by receptor-binding assessment of three representative virus isolates. Mutagenesis work revealed that E190V and G228S substitutions are important to acquire the human receptor-binding capacity, and the P186L substitution could reduce the binding to avian receptor. Further structural analysis revealed how the P186L substitution in the receptor-binding site of HA determines the receptor-binding preference change. We conclude that the human-infecting H6N1 evolved into a human receptor preference.

Synopsis

Historical analysis of influenza H6N1 isolates from 1972 until 2013, when the first human infection occurred, reveals amino acid changes that change receptor binding preference from birds to humans and therefore virus ability to cross the species barrier.

• Human-infecting avian influenza H6N1 has gained human receptor binding preference.
• H6N1 HA has changed binding preference in at least two steps.
• First, E190V and G228S substitutions provide human receptor binding ability.
• Subsequently, P186L substitution reduces avian receptor binding, and provides human receptor binding preference.

 

For an influenza virus to infect a host, the virus must bind (attach) itself to the surface of a cell.  To do that influenza viruses have an RBS - Receptor Binding Site (the area of its genetic sequence that allows it to attach to, and infect, host cells) that – like a key slipping into a padlock -`fit’ the host’s receptor cells.

 

Avian adapted flu viruses, like the H5N1 virus, bind preferentially to the alpha 2,3 receptor cells found in the gastrointestinal tract of birds.  While there are some alpha 2,3 cells deep in the lungs of humans, for an influenza to be successful in a human host, most researchers believe it needs to a able to bind to the α2-6 receptor cell found in the upper airway (trachea).

 

Although a preferential binding to human receptor cells is considered perhaps the biggest obstacle for an avian virus to successfully jump species – it isn’t the only one.

 

Another major requirement is the ability to replicate efficiently at the lower temperatures found in the upper respiratory system of humans, as opposed to the hotter gastrointestinal system of birds.  There are other factors – some we know about, others we don’t – that must come together properly to allow an avian virus to jump species successfully.

 

All of which means that even with an improved receptor binding ability, the H6N1 virus may be far from being ready for prime time.

 

But it does mean that H6N1 is legitimately a virus worth watching, both for further evolutionary changes, and for how it behaves in poultry and in humans.

EID Journal: Seropositivity For H6 Influenza Viruses In China

Flu Virus binding to Receptor Cells – Credit CDC

 

# 10,011

 

 

In the summer of 2013 Taiwan reported the first known human infection with an avian H6N1 virus, in a a 20-year-old female who was hospitalized with mild pneumonia on the May 8th, treated with oseltamivir (Tamiflu ®), and released from the hospital on the 11th.

 

Were it not for the enhanced surveillance for H7N9, which had only recently broken out in Mainland China, there is a pretty good chance this novel flu infection would have gone unnoticed.

 

And that’s why we really don’t have a good handle on just how often these novel flu viruses jump to humans. Often, these infections present just like any other flu or respiratory infection, and only rarely are the right tests done to determine the cause.

Over the years we’ve seen heated debates and scientific `guesstimates’ that have attempted to quantify the number of people who have been infected with novel H5N1 (see The Great CFR Divide), H3N2v (see CID Journal: Estimates Of Human Infection From H3N2v (Jul 2011-Apr 2012), and H7N9 (see Lancet: Clinical Severity Of Human H7N9 Infection) with varying results.

 

Although difficult to mount, expensive, and subject to some limitations – serological testing of a large cohort of individuals is undoubtedly the best way to determine what the level of exposure to a particular virus a community has experienced.  Infections – even mild or asymptomatic ones – generally leave behind strain-specific antibodies which may be detectable months or even years later.

Assuming your test is sensitive enough to detect the right antibodies, and specific enough not to produce false positives, you can get a pretty good idea how many people in a community have had a previous exposure.  

 

Categorize your test subjects by age, gender, location, and occupation – and you can not only get an idea how common infection with this novel virus is across a population, you can begin to tease out some interesting information about relative exposure risks.

 

Which is exactly what researchers in China have done, looking for evidence of previous H6 influenza exposure among a cross section of people from both Northern and Southern China.  Yesterday, the EID Journal published the following letter, which describes a small, but significant number of people in their serological study who tested positive for H6 influenza antibodies (indicating previous exposure).

 

While the overall number of positives was low (298 by HI, 63 by MN) out of 15,689 samples, not unexpectedly, people with frequent exposure to poultry and/or live birds were more likely to test positive. 

 

Seroprevalence was noticeably higher in the southern provinces than in the north.  Interestingly, this same study found a far lower seropositivity for H5N1 (only 2 positive results), but a much greater seropositivity for H9N2 (3.4% positive).

 

Follow the link below to read this letter, and view its data, in its entirety:

 

Volume 21, Number 7—July 2015

Letter

Seropositivity for Avian Influenza H6 Virus among Humans, China

Li Xin, Tian Bai, Jian Fang Zhou, Yong Kun Chen, Xiao Dan Li, Wen Fei Zhu, Yan Li, Jing Tang, Tao Chen, Kun Qin, Jing Hong Shi, Rong Bao Gao, Da Yan Wang, Ji Ming Chen, and Yue Long Shu

To the Editor: Influenza virus subtype H6 was first isolated from a turkey in 1965 in the United States (1) and was subsequently found in other parts of the world (2). Over the past several decades, the prevalence of H6 virus has dramatically increased in wild and domestic birds (2–4). In China, highly pathogenic influenza A(H5N1), low pathogenicity influenza (H9N2), and H6 are the most prevalent avian influenza viruses among poultry (5). Although only 1 case of H6 virus infection in a human has been reported worldwide (6), several biological characteristics of H6 viruses indicate that they are highly infectious to mammals. Approximately 34% of H6 viruses circulating in China have enhanced affinity to human-like receptors (ɑ-2,6 NeuAcGal) (2). H6 viruses can also infect mice without prior adaptation (2,7), and some H6 viruses can be transmitted efficiently among guinea pigs (2). To evaluate the potential threat of H6 viruses to human health, we conducted a systematic serologic study in populations occupationally exposed to H6 viruses.

During 2009–2011, a total of 15,689 serum samples were collected from live poultry market workers, backyard poultry farmers, large-scale poultry farmers, poultry-slaughter factory workers, and wild bird habitat workers in 22 provinces in mainland China. A/chicken/Y94/Guangdong/2011 (H6N2), a representative isolate of predominant H6 viruses in mainland China, was used for the serologic testing (Technical Appendix[PDF - 155 KB - 4 pages] Table 1). Hemagglutination inhibition (HI) assay was performed for all serum samples, and samples with an HI titer ≥20 were verified by a microneutralization (MN) assay, as indicated by World Health Organization guidelines (8). An MN result of ≥20 was considered positive.

The HI result was ≥20 for H6N2 virus in 298 of the 15,689 specimens, and the MN result was positive in 63 of the 298 specimens (overall seropositivity range 20–320, mean 32.7, 0.4%) (Technical Appendix[PDF - 155 KB - 4 pages] Table 2). The proportion of group members who were seropositive differed significantly according to occupational exposure (p = 0.0125). Seropositivity was highest among workers in live poultry markets, backyard poultry farmers, and workers in wild bird habitats (s0.66%, 0.42%, and 0.51%, respectively) (Table). According to χ² test results, seropositivity among workers in live poultry markets was significantly higher than that among large-scale poultry farmers (p = 0.0015, adjusted ɑ = 0.005. Analysis by unconditional logistic regression model showed that exposure to live poultry markets was a risk factor for human infection with avian influenza H6 virus (odds ratio 2.1, 95% CI 1.27–3.47).

Seropositivity did not differ significantly among male and female persons tested (p = 0.08) (Table). No children were positive for the H6N2 virus. For other age groups, seropositivity ranged from 0.25% to 0.45%, but differences were not significant (p>0.05) (Table).

Of the 22 provinces from which serum specimens were collected, 11 were northern provinces and 11 were southern provinces. Positive specimens were detected in all southern provinces. In northern China, no seropositive results were detected in Henan, Liaoning, or Jilin Provinces. According to χ² test results, seropositivity in southern China was significantly higher than seropositivity in northern China (p = 0.0375) (Table).

Human infection with influenza H6 virus in mainland China has not been reported, but 63 serum specimens tested in our study were positive for the H6 virus. This level of seropositivity is much higher than that for highly pathogenic avian influenza A(H5N1) virus, for which only 2 of the serum specimens we tested were positive (data not shown), but much lower than the seropositivity level for low pathogenicity avian influenza A(H9N2) virus; 3.4% of the samples tested were positive for A/Chicken/Hong Kong/G9/1997(H9N2)–like virus (data not shown). A previous US study has reported H6N2-positive antibodies in veterinarians (9). Our results and the veterinarian study indicate that the H6N2 virus could infect humans.

In our study, positive samples were detected in 19 of 22 provinces and in all tested worker populations, suggesting that the H6 virus has been broadly circulating in birds in China. Live poultry market exposure is the major risk factor for human infection with avian influenza H6 virus. The limitation of this study is that antigen selection may not accurately detect neutralization antibodies for different subtypes of H6 viruses. Surveillance of the H6 virus in birds and occupationally exposed populations should be strengthened for pandemic preparedness.

(Continue . . . )

 

TSRI: H10N8 and H6N1 Bind Poorly To Human Receptor Cells

Flu Virus binding to Receptor Cells – Credit CDC

 

# 9818

 

Considering the recent spate of worrisome H5 and H7N9 bird flu news, I’m happy to report that at least two recently emerged avian viruses haven’t yet acquired one of the main traits that would allow them to become serious pandemic threats; the ability to bind preferentially to human receptor cells.

While our gaze has been focused primarily on H5N1 and H7N9, in the summer of 2013 Taiwan reported the first known human infection with an avian H6N1 virus, and a few months later mainland China reported the first three cases of H10N8 (two fatal). 

 

While only four cases were recorded, they – along with H5N6, and the globe-trotting H5N8 avian virus and its descendents – have shown just how quickly new subtypes can emerge.

 

Luckily, turning up in a small handful of cases is a far cry from being ready for prime time.

Human adapted influenza viruses have an RBS - Receptor Binding Site (the area of its genetic sequence that allows it to attach to, and infect, host cells) that – like a key slipping into a padlock -`fit’ the receptor cells commonly found in the human upper respiratory tract; the alpha 2,6 receptor cell.

 

While avian adapted flu viruses, like the H5N1 virus, bind preferentially to the alpha 2,3 receptor cells found in the gastrointestinal tract of birds.

Although there are some alpha 2,3 cells deep in the lungs of humans, for an influenza to be successful in a human host, most researchers believe it needs to able to bind to the a 2,6 receptor cell.  

 

There are other requirements – some we know about, others we don’t – that determine how well a virus can infect, replicate, and transmit in humans.  The ability to replicate at the lower temperatures found in the upper respiratory system is one of them. 

 

But first, and foremost, the virus must be able to bind to human receptor cells.

 

And here, the news on these two viruses remains encouraging.  

 

The journal Cell, Host & Microbe carries a pair of studies this week that look at the binding properties of these viruses, and both find they fall short.  While behind a pay wall,  we do have a press release from the The Scripps Research Institute (TSRI)  which provides some welcome details.

Links to the studies, and excerpts from the press release, follow:

 

Structure and Receptor Binding of the Hemagglutinin from a Human H6N1 Influenza Virus

Netanel Tzarum, Robert P. de Vries, Xueyong Zhu, Wenli Yu, Ryan McBride, James C. Paulson, Ian A. Wilson

Highlights

• The human H6N1 HA receptor binding site is distinct from other avian and human HAs
• The HA of a human H6N1 influenza virus retains avian receptor specificity
• The interactions of H6 HA with avian receptor analogs differ from other HAs
• Additional mutations are required to switch H6 HA to human receptor specificity

(Continue . . .)

 

A Human-Infecting H10N8 Influenza Virus Retains a Strong Preference for Avian-type Receptors

Heng Zhang, Robert P. de Vries, Netanel Tzarum, Xueyong Zhu, Wenli Yu, Ryan McBride, James C. Paulson, Ian A. Wilson

Highlights

• Human influenza H10N8 HA has negligible binding to human-like receptors
• Human influenza H10N8 HA retains strong binding to avian-like receptors
• The human receptor orientation in H10 HA differs from most human HA complexes
• Mutations that switch specificity in pandemic viruses do not alter H10 specificity

          (Continue . . .)

 

While ostensibly good news, the press release from Scripps warns that both of these viruses bind differently than other avian viruses we’ve seen, and that our understanding of how these viruses mutate isn’t complete enough to warrant complacency.

 

Scripps Research Institute Study Shows Two New Flu Strains Do Not Yet Easily Infect Humans

But Great Versatility of Viruses Suggests Continued Caution

LA JOLLA, CA—March 11, 2015—Scientists at The Scripps Research Institute (TSRI) have analyzed a key protein from two influenza strains that recently began causing sporadic infections among people in China and Taiwan.

The analyses suggest that the flu viruses, variants of subtypes H10N8 and H6N1, have not acquired changes that would allow them to infect people easily and cause a much-feared pandemic.

Yet the studies also highlight the versatility that bird flu viruses apparently have in attaching to host cells.

“These bird flu viruses seem able to bind to receptors on host cells in different ways and thus can probably mutate in different ways to jump to humans—so we shouldn’t be complacent about our ability to predict the viral changes required to get a pandemic,” said Ian A. Wilson, Hansen Professor of Structural Biology and chair of TSRI’s Department of Integrative Structural and Computational Biology.

<SNIP>

Difficult to Predict

How did such bird viruses end up causing infections of people? “We suspect that sporadic cases of human infection by a bird flu virus can occur, even without a change in the receptor specificity, if the dose of the viral exposure is high enough and/or it gets deep into the lungs, where there are some flu-virus receptors like those found in birds,” said Tzarum, a research associate in the Wilson laboratory who was first author of the H6N1 paper.

Flu viruses with these HAs thus remain essentially bird viruses, with limited ability to infect humans. Yet further mutations that would enable a switch in preference to human receptors—and a potential global pandemic—are still possible.

The new TSRI analyses also show that, at the atomic scale, these new bird flu HAs bind to host-cell receptors in ways not observed in studies of other bird flu viruses—implying that the mutations required for the switch to human receptors may be different for different strains and inherently hard to know in advance.

“There appear to be no general rules for this switch among bird flu viruses,” said Tzarum.

Determining whether a bird flu strain has truly jumped the species barrier will therefore continue to require detailed receptor-binding and structural studies like these, Wilson said.

(Continue . . . )

Taiwan CDC: Epidemiological Analysis Of Human H6N1 Infection

 

# 7975

 

Early in June of this year (see Taiwan CDC Reports Human Infection With Avian H6N1) we learned of the first known human infection with the avian H6N1 strain of influenza.  The patient was a 20-year-old female, diagnosed in May of this year, no doubt  picked up because of the heightened surveillance for H7N9 in Taiwan. 

Today, Taiwan’s CDC published an epidemiological analysis of that case in The Lancet Respiratory Medicine, which highlights the need to be prepared for known novel influenza threats (like H5N1, H7N9, H3N2v), but also for something emerging from out of left field (which is exactly what happened with the swine-origin H1N1 pandemic virus of 2009).

First a link and a short except from the Abstract, followed by the press release from Taiwan’s CDC.

 

Human infection with avian influenza A H6N1 virus: an epidemiological analysis

Sung-Hsi Wei*, Ji-Rong Yang*, Ho-Sheng Wu*, Ming-Chuan Chang*, Jen-Shiou Lin, Chi-Yung Lin, Yu-Lun Liu, Yi-Chun Lo, Chin-Hui Yang, Jen-Hsiang Chuang, Min-Cheng Lin, Wen-Chen Chung, Chia-Hung Liao, Min-Shiuh Lee, Wan-Ting Huang, Pei-Jung Chen, Ming-Tsan Liu, Feng-Yee Chang

Summary

(Excerpts)

Interpretation This is the first report of human infection with a wild avian influenza A H6N1 virus. A unique clade of H6N1 viruses with a G228S substitution of haemagglutinin have circulated persistently in poultry in Taiwan. These viruses continue to evolve and accumulate changes, increasing the potential risk of human-to-human transmission. Our report highlights the continuous need for preparedness for a pandemic of unpredictable and complex avian influenza

(Continue . . . )

Press Releases

Article describing world’s first case of human infection with avian influenza A(H6N1) virus confirmed in Taiwan to be published in international medical journal ( 2013-11-14 )

 

The Taiwan Centers for Disease Control (Taiwan CDC) announced an article describing the world’s first case of human infection with avian influenza A (H6N1) virus confirmed in Taiwan in June, 2013 had been submitted to The Lancet Respiratory Medicine by scientists working at Taiwan CDC. At the time of writing, this article has been accepted and will be published in the journal on November 14, 2013.

A genetic analysis of the avian influenza A (H6N1) virus isolated from this case shows that the virus is closest to that from poultry in Taiwan, suggesting that this virus originates from poultry in Taiwan. Notably, the virus had a G228S substitution in the haemagglutinin (HA) protein that might increase its ability to infect human cells. In addition, based on the sequences of the NA protein, the virus is susceptible to neuraminidase (NA) –inhibitors such as Oseltamivir and Relenza.

Taiwan CDC further explained that the case’s condition improved after administering antivirals and the case fully recovered after appropriate medical treatment.  Among the 36 close contacts of the case, none has been found to be infected with avian influenza A (H6N1) virus. Moreover, Taiwan CDC conducted enhanced influenza surveillance in patients that visit the 3 hospitals and 7 clinics located within the 8-km radius of the case’s residence for three months. A cumulative total of 178 influenza-like illness (ILI) specimens have been tested through this surveillance and none has been tested positive for avian influenza A (H6N1) virus. On the other hand, thus far in 2013, the contracted virology laboratories in the nation have tested a cumulative total of 6,985 respiratory specimens collected from the community and none has been tested positive for avian influenza A (H6N1) virus. Based on the results of the epidemiological investigation, the case presenting mild pneumonia is a sporadic case and testing of the close contacts of the case has not yielded any evidence of human-to-human transmission of this virus in the community. Both the health and agricultural authorities will continue to reinforce avian influenza surveillance in humans, poultry and the environment.

Taiwan CDC points out that avian influenza A (H6N1) virus is commonly found in poultry. No avian influenza A (H6N1) virus had been detected in humans till the world’s first case was confirmed in Taiwan.  To prevent avian-to-human transmission of avian influenza infections, Taiwan CDC advises poultry vendors to take relevant personal precautions and the general public to avoid unnecessary direct contact with poultry and birds or their droppings.  In addition, the public is also advised to practice good personal hygiene such as washing hands frequently and consuming only thoroughly cooked poultry and eggs to reduce the risk of infection.  If influenza-like illness symptoms or conjunctivitis develop, please put on a surgical mask, seek immediate medical attention and inform your doctor of your exposure history to birds/poultry, job contents and travel history. 

(Continue . . .)

Taiwan CDC Reports Human Infection With Avian H6N1

 

 

# 7416

 

 

An unusual story this morning out of Taiwan, where we learn of a 20-year-old female who was diagnosed with an avian H6N1 strain of influenza in May. She was hospitalized with mild pneumonia on the 8th, treated with oseltamivir (Tamiflu ®), and released from the hospital on May 11th.

 

No doubt, this case was picked up due to enhanced surveillance for the H7N9 virus after the outbreak in China, and the subsequent importation of a case to Taiwan in April.

 

First some extended excerpts from the Taiwan CDC press release, and then I’ll return with a bit more about `oddball’ human infection with avian flu strains.

 

 

Laboratory-confirmed case of human infection with avian influenza A(H6N1) virus in Taiwan recovered; Taiwan CDC urges public to take precautions to stay healthy( 2013-06-21 )

On May 20, 2013, the Taiwan Centers for Disease Control (Taiwan CDC) received a report from a hospital concerning a case of human infection with unsubtypable influenza A virus in a 20-year-old female presenting mild pneumonia who resides in central Taiwan. The virus isolated from the respiratory specimen from the case was then submitted to Taiwan CDC for further identification.

After conducting whole genome sequencing, the National Influenza Center (NIC) at Taiwan CDC identified the virus to be a novel avian-origin influenza A (H6N1) virus. A total of 36 close contacts of the case have been traced for follow-up.  4 of them experienced influenza-like illness symptoms, but none of them has been found to be infected with influenza A (H6N1) virus.

 

Taiwan CDC continues to closely monitor the influenza activity and advises the public to seek immediate medical attention when experiencing any influenza-like illness with respiratory distress.

 

According to the epidemiological investigation, the case works at a breakfast shop. She has not traveled out of the country and has not been exposed to any poultry or bird.  On May 5, she developed symptoms, including fever, cough, headache and muscle ache.  On May 8, when her fever persisted and she developed shortness of breath, she sought medical attention at a hospital and was hospitalized for treatment. Her chest X-ray showed mild pneumonia.  After administering Oseltamivir, her symptoms improved next day.  On May 11, she was discharged from the hospital.

 

As of now, she has fully recovered.  Influenza A (H6N1) virus was isolated from the respiratory specimen collected from the case on May 7. The case was found to have an antibody titer of 1:20 in the serum specimen collected on May 24.  Another serum specimen was collected from the case on June 8 and the antibody titer in this specimen was found to be 1:40.   Besides testing the respiratory specimen collected from the case for influenza viruses, the NIC also tested the specimen for 23 other common respiratory viruses such as adenovirus, respiratory syncytial virus, coronavirus, enterovirus and rhinovirus and the specimen tested negative for all these viruses.

 

The agricultural authority has collected specimens from the poultry from the two poultry farms located within the 1-km perimeter of the case’s residence.  No avian influenza A (H6N1) virus has been detected in any of the specimens.

(Continue . . . )

  

Avian flu infections in humans are rare, and most have been due to H5N1, H7N7, and H7N9 strains. Even less common, we’ve seen a few human infections with H9N2, H7N2, and H7N3 over the past decade.

 

But surveillance and testing for `oddball’ flu strains – even in developed countries – while improving, is spotty at best.

 

It is likely that occasional `one-off’ human infection with unusual avian strains happens with some regularity, and no one is ever the wiser.

 

Last year, in EID Journal: Human Infection With H10N7 Avian Influenza, we saw a report of two Australian abattoir workers infected with H10N7 (7 workers were symptomatic).  All the cases were mild, and the abattoir has instituted new policies requiring PPEs (personal protective equipment) for employees who have direct exposure to birds and carcasses.

 

While rare, human infection with H10N7 isn’t completely unheard of. In Egypt - in 2004 -  2 infants were shown to be infected by the H10N7 avian flu virus, as well. 

 

A fascinating bit of research, published in 2006 in the CDC’s EID Journal , looked for avian influenza antibodies in duck hunters and wildlife professionals.

 

Avian Influenza among Waterfowl Hunters and Wildlife Professionals

James S. Gill,* Richard Webby,† Mary J.R. Gilchrist,* and Gregory C. Gray‡
*University of Iowa Hygienic Laboratory, Iowa City, Iowa, USA; †St Jude Children's Research Hospital, Memphis, Tennessee, USA; and ‡University of Iowa College of Public Health, Iowa City, Iowa, USA

ABSTRACT

We report serologic evidence of avian influenza infection in 1 duck hunter and 2 wildlife professionals with extensive histories of wild waterfowl and game bird exposure. Two laboratory methods showed evidence of past infection with influenza A/H11N9, a less common virus strain in wild ducks, in these 3 persons.

 

While antibodies to the relatively rare H11N9 virus were detected in these 3 individuals, antibodies for the far more common H4 and H6 avian viruses (known to circulate in American ducks) were not.

 

Which begs the question, why not?

 

One theory is that humans are less likely to develop long-lasting antibodies when exposed to avian-type influenza viruses. In 1991, Beare and Webster published a study where 40 volunteers were inoculated with three avian influenza strains (H4N8, H6N1, and H10N7).  

 

While 11 subjects had mild clinical symptoms, none developed a detectable antibody response.

 

Replication of avian influenza viruses in humans.

Beare AS, Webster RG.

Clinical Research Centre, Harvard Hospital, Salisbury, Wiltshire, U.K.

Abstract

Volunteers inoculated with avian influenza viruses belonging to subtypes currently circulating in humans (H1N1 and H3N2) were largely refractory to infection. However 11 out of 40 volunteers inoculated with the avian subtypes, H4N8, H6N1, and H10N7, shed virus and had mild clinical symptoms: they did not produce a detectable antibody response.

 

 

Returning to the 2006 EID study, the authors in their conclusion state:

 

The relative lack of antibody response in our study population, who had substantial exposures to waterfowl with influenza A infections, and in inoculated volunteers from Beare and Webster (12) suggests that avian influenza infections in humans exposed to wild waterfowl may occur more commonly than we are able to detect with current methods.

 

 

With testing methods improving every year, and greatly ramped up surveillance due to H7N9 avian flu and MERS-CoV, I wouldn’t be at all surprised to see more of these `incidental’ avian (or swine) flu detections in the months to come.

 

As these viruses tend to produce mild symptoms, and only rarely transmit onward in humans, most will pose no substantial public health threat.