Monday, November 04, 2019

Inf Dis. Clinics N.A.: Novel Avian Influenza A Virus Infections of Humans

Flu Virus - Credit NIAID


In the (nearly) 14 years since this blog began, we've looked at thousands of studies and reports on novel flu that have incrementally changed our appreciation and understanding of these zoonotic threats.
In 2006, the only novel influenza virus of real consequence was HPAI H5N1.  But since then we've seen the emergence of a number of other avian (H7N9, H5N6, H10N8, etc.) and swine (EA-H1N1, H3N2v, etc.) viruses that could pose legitimate pandemic threats. 
In 2009 - while we were watching avian flu -  a novel `swine-origin'  H1N1 did something few thought possible; sparking a pandemic even though a seasonal H1N1 virus had been circulating for decades.

Just a few of the things we've come to appreciate over the past few years are that LPAI (Low Pathogenic Avian Influenza) viruses can be just as deadly as HPAI (highly pathogenic) viruses in humans, that live bird markets contribute greatly to rapid reassortment and spread of avian flu viruses, and that migratory birds are much better at distributing HPAI viruses than originally believed. 
In fact, our knowledge base on novel flu changes so quickly, that even those of us who try to stay current, can find ourselves mired with outdated information and ideas.
Which is why it is nice that every once in awhile we get a comprehensive review of what we know (or at least, think we know) about novel flu.  While these reviews don't usually break any new ground, they can provide us with a valuable, and up-to-date reference tool. 
And when we get one authored by two of the best-known names in influenza research - Timothy Uyeki and Malik Peiris - you can be pretty sure that it is going to be well worth your time to read.
The December issue of Infectious Disease Clinics of North America has published just such a review, and it is open-access. While quite detailed, this particular review only covers novel avian flu.

A few excerpts below, but follow the link to download the full PDF.

Novel Avian Influenza A Virus Infections of Humans
Timothy M.Uyeki MD, MPH, MPP  

Malik Peiris MBBS, DPhil, FRCPathba

Available online 25 October 2019.


Avian influenza, H5N1, H5N6, H7N9

Key points

  • Signs, symptoms, complications of human infection with avian influenza A viruses are nonspecific; suspicion is based on a recent history of poultry exposure or close exposure to a symptomatic person.
  • Respiratory specimens for testing depend on the specific virus, time from illness onset, and the patient’s symptoms and disease severity.
  • Influenza tests available in clinical settings do not distinguish influenza A viruses of animal origin from seasonal influenza A viruses.
  • Clinical specimens must be sent to a public health laboratory for specific testing for seasonal and avian influenza A viruses.
  • Clinical management is based on prompt implementation of recommended infection prevention and control measures, antiviral treatment, and supportive care of complications.


Influenza A viruses are RNA viruses with a segmented genome and are subtyped on the basis of the 2 virus surface glycoproteins, hemagglutinin (H) and neuraminidase (N), into 16 H and 9 N subtypes. 

More recently, additional virus subtypes have been discovered in bats, but these subtypes are of uncertain significance for humans. Influenza A viruses naturally circulate in a range of avian and mammalian species, including in humans. The greatest diversity of virus subtypes are found in aquatic waterfowl, which are regarded as the natural reservoir of influenza A viruses.

Influenza A viruses of 3 subtypes—H1N1, H2N2, and H3N2—have been endemic in humans. Influenza A H1N1 caused the 1918 pandemic and circulated in humans until 1957 when a new pandemic H2N2 virus replaced it; which was in turn replaced by an H3N2 virus in 1968. The most recent pandemic was in 2009, caused by a ‘swine-origin’ H1N1 virus. 

Currently, influenza A subtypes H1N1 and H3N2 co-circulate in humans as seasonal influenza A viruses. Pandemics arise when novel influenza A viruses containing virus hemagglutinins from swine or birds emerge and spread efficiently and in a sustained manner among an immunologically na├»ve human population. In addition, avian and animal influenza A viruses may cause sporadic zoonotic human infections and disease without acquiring the ability for sustained human-to-human transmission. 

However, such infections cause global public health concern because they may cause significant morbidity and mortality; but the even greater concern is that they pose potential pandemic threats. Swine-origin H1 and H3 viruses have also caused zoonotic infections, but are not discussed in this article.



A high index of suspicion and early diagnosis of avian influenza A virus infection is essential to initiating interventions (antiviral treatment; infection prevention and control measures) as soon as possible to reduce transmission risk from symptomatic persons to close contacts, including health care personnel. Clinical suspicion relies on eliciting a history of recent exposure to poultry or to sick persons with suspected or confirmed avian influenza A virus infection. Diagnosis requires the collection of appropriate respiratory specimens, ideally from the lower respiratory tract when available, for specific testing for seasonal and avian influenza A virus subtypes at specialized public health laboratories. 

Patients with suspected infection should be isolated immediately and patients with lower respiratory tract disease should be placed on airborne precautions if possible, and NAI antiviral treatment should be started as soon as possible even before specific testing results are available. Corticosteroids and salicylates should be avoided and clinical management is focused on supportive care of complications, including nosocomial bacterial or fungal infections.

 Sporadic human infections with avian influenza A viruses resulting in mild to severe illness are expected to continue to occur in persons with close exposures to infected poultry and other birds. Options to decrease human exposure to enzootic avian influenza include interventions in live poultry markets, which serve as a major source of zoonotic infection and virus amplification.219 

Because zoonotic avian influenza A viruses pose potential pandemic threats, it is important to risk assess these viruses to prioritize countermeasure development such as vaccines.220
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