Monday, November 17, 2008

Hiding In Plain Sight?

 

# 2472

 

 

 

For reasons not well understood we continue to get reports that the H5N1 virus appears to be capable of residing asymptomatically in a variety of birds and mammals. 

 

 

Today we look at an interesting study from St. Judes Research Hospital that may provide some answers.

 

 

By definition, a highly pathogenic virus should produce excess mortality and morbidity in its host.   We do know, however, that some waterfowl - the natural reservoir of influenza viruses - appear to tolerate H5N1 infection. At least for awhile.

 

Most birds, however, succumb quickly to the highly pathogenic H5N1 virus.

 

Asymptomatic infections are problematic because they would allow the virus to spread more efficiently, over larger geographic areas, and often without human notice.    Infected birds can mix with healthy birds, spreading the disease.

 

 

How prevalent this phenomenon might be in the wild is unknown, but over the past few months I've reported on a variety of asymptomatic cases and laboratory experiments, including:

 

 

Reservoir Dogs (Cats, Foxes, and Raccoons)

This study demonstrates that red foxes fed bird carcasses infected with HPAI virus (H5N1) can excrete virus while remaining free of severe disease, thereby potentially playing a role in virus dispersal

 

 

Infection Of Cattle By H5N1

Experimental Infection of Cattle with Highly Pathogenic Avian Influenza Virus (H5N1)

Abstract

Four calves were experimentally inoculated with highly pathogenic avian influenza virus A/cat/Germany/R606/2006 (H5N1) isolated from a cat in 2006.

 

All calves remained healthy, but several animals shed low amounts of virus, detected by inoculation of nasal swab fluid into embryonated chicken eggs and onto MDCK cells. All calves seroconverted.

 

 

Hong Kong: Bird Flu Discovered In 4 Markets - Mass Culling To Begin

 

Of particular concern is that these infected birds were discovered by routine testing, that no unusual bird die offs had been reported, raising the specter that these birds are asymptomatic carriers of the virus.

 

The Secret Woid Is `Asymptomatic'

 

On Monday we learned that 2% of the birds sampled in Siberia showed antibodies to the H5N1 virus.  These birds, alive and healthy, were exposed at some point in their lives to the virus and either recovered or were never sickened to begin with.

 

We've seen repeated reports (here, here, here, and here)  over the past year from Vietnam, Indonesia, and other parts of the world of asymptomatic birds spreading the disease without showing signs of illness themselves. 

 

 

 

While at first it may seem a good sign that the H5N1 virus is becoming less deadly, there is no reason at this time to believe that this attenuation of its effects extends to humans.

 

And in fact, it may well be the host adapting to the virus - rather than a change in the virus itself - that is responsible for this phenomenon.

 

The concern is, that without the alerting signal of sick or dying birds, the virus can spread silently, beneath the radar screen.   Routine testing of `healthy birds' is rarely done in hot zone countries (Hong Kong being an exception).

 

 

The question arises, what possible mechanism would allow some birds and mammals to remain asymptomatic when infected with the H5N1 virus when most sicken and die?

 

 

Well, we have at least one potential clue today in this paper by Khalenkov A, Perk S, Panshin A, Golender N, Webster RG,  epublished early ahead of print in Virology.

 

 

Researchers at St. Judes Children's Hospital have determined that when birds are first infected with the mild H9N2 avian virus they became largely immune to the ill effects of the H5N1 virus.   

 

Despite suffering no ill effects, they did shed the H5N1 virus.

 

While likely not the only explanation for asymptomatic spread of the H5N1 virus (it may not even be a significant one), this does show one plausible avenue for the silent spread of the disease.

 

 

A Hat tip to Ironorehopper on Flutrackers for posting this link.

 

 

Modulation of the severity of highly pathogenic H5N1 influenza in chickens previously inoculated with Israeli H9N2 influenza viruses.



Khalenkov A, Perk S, Panshin A, Golender N, Webster RG. - Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA.

 


The continued evolution of H9N2 and H5N1 viruses and their spread and re-emergence across Eurasia raise concern that prior H9N2 virus infection may limit the detection of subsequent H5N1 infection in gallinaceous poultry by attenuating the severity of disease.

 


We show that H9N2 viruses isolated from Israeli turkeys during 2000-2004 were antigenically and genetically distinguishable.

 


These three H9N2 viruses caused no overt signs of disease in chickens.

 

The 2004 isolate replicated and spread most efficiently, and chickens previously inoculated with this H9N2 virus showed 90%-100% survival after inoculation 1 to 35 days later with lethal H5N1 virus.

 


Chickens that survived did not show signs of disease but did shed lethal H5N1 virus from the cloaca.

 


The modulation of survivability was time-dependent; the effect was maximal 5 days after H9N2 inoculation.

 


These findings suggest that co-circulation of H9N2 viruses can contribute to the spread of lethal H5N1 viruses.


PMID: 18992907 [PubMed - as supplied by publisher