# 5969
An intriguing study from the Journal of Virology this morning that looks at an unusual route of infection - and resultant pathogenesis – of the H5N1 virus in cats (My thanks to Tetano on FluTrackers for posting this link).
The study is called:
Marked endotheliotropism of highly pathogenic avian influenza virus H5N1 following intestinal inoculation in cats.
November 2011, doi: 10.1128/JVI.06375-11
Reperant LA, van de Bildt MW, van Amerongen G, Leijten LM, Watson S, Palser A, Kellam P, Eissens AC, Frijlink HW, Osterhaus AD, Kuiken T.
Endotheliotropism is simply a 12-dollar word meaning an affinity for endothelial cells which are the cells that line the interior surface of blood vessels throughout the body.
Photo Credit – Wikipedia
From the abstract (the entire study is behind a pay wall), we learn that researchers gave cats enteric coated capsules containing H5N1 infected chicken liver in order to deliver the virus directly to the intestine.
(EXCERPT)
Intestinal inoculation of HPAIV H5N1 resulted in fatal systemic disease. The spread of HPAIV H5N1 from the lumen of the intestine to other organs took place via the blood and lymphatic vascular systems but not via neuronal transmission.
Remarkably, the systemic spread of the virus via the vascular system was associated with massive infection of endothelial and lymphendothelial cells, resulting in widespread hemorrhages.
As the abstract points out, this resulted in a disease process similar to what is seen in terrestrial poultry, and differs greatly from the pathogenesis normally seen from respiratory tract infection.
The authors conclude that:
The marked endotheliotropism of the virus following intestinal inoculation indicates that the pathogenesis of systemic influenza virus infection in mammals may differ according to the portal of entry.
The surprise here isn’t that cats (and other mammals) can acquire the H5N1 virus via a non-respiratory route (we’ve known that for some time), it is the discovery of the manner in which the virus spread systemically; via massive infection of endothelial and lymph endothelial cells.
While anything that betters our understanding of the H5N1 virus is a good thing, this discovery may eventually have practical applications as well.
Should an outbreak occur, gastrointestinal H5N1 infection (with its atypical pathogenesis) may require a different treatment regimen than is currently used with a respiratory infections.
An oral route of infection from the H5N1 virus has been suggested over the years, with several human cases being linked to the consumption of infected poultry.
One of the earliest indications that H5N1 could bind and flourish in the human gastrointestinal tract comes from this study involving the deaths of a brother and sister in Vietnam in 2004.
Fatal avian influenza A (H5N1) in a child presenting with diarrhea followed by coma.
de Jong MD, Bach VC, Phan TQ, Vo MH, Tran TT, Nguyen BH, Beld M, Le TP, Truong HK, Nguyen VV, Tran TH, Do QH, Farrar J.
In June of 2007, we got a report (see Atypical Presentations of H5N1) out of Indonesia, of a child infected with H5N1 but that presented without respiratory symptoms.
A year later, in a large review of Chinese bird flu patients (see Clinical Case Review Of 26 Chinese H5N1 Patients), we find several mentions of gastrointestinal involvement as well.
Diarrhea was present in only two H5N1 cases at admission, but developed in a quarter of cases during hospitalization. Diarrhea was a common presenting symptom among H5N1 cases in Vietnam and Thailand , but was reported infrequently among cases in Hong Kong SAR, China and Indonesia.
H5N1 virus and viral RNA have been detected in feces and intestines of human H5N1 cases. Whether the gastrointestinal tract is a primary site for H5N1 virus infection is currently unknown.
In 2010, we saw a study (see H5N1 Can Replicate In Human Gut) that provided even more evidence that the bird flu virus can thrive in the human gastrointestinal system.
We’ve also seen numerous reports over the years of cats infected with the H5N1 virus after consuming infected birds. The following comes from a World Health Organization GAR report from 2006.
H5N1 avian influenza in domestic cats
28 February 2006
(EXCERPTS)
Several published studies have demonstrated H5N1 infection in large cats kept in captivity. In December 2003, two tigers and two leopards, fed on fresh chicken carcasses, died unexpectedly at a zoo in Thailand. Subsequent investigation identified H5N1 in tissue samples.
In February 2004, the virus was detected in a clouded leopard that died at a zoo near Bangkok. A white tiger died from infection with the virus at the same zoo in March 2004.
In October 2004, captive tigers fed on fresh chicken carcasses began dying in large numbers at a zoo in Thailand. Altogether 147 tigers out of 441 died of infection or were euthanized. Subsequent investigation determined that at least some tiger-to-tiger transmission of the virus occurred.
In 2006, Dr. C.A. Nidom demonstrated that of 500 cats he tested in and around Jakarta, 20% had antibodies for the bird flu virus.
In 2007 the FAO warned that:
Avian influenza in cats should be closely monitored
So far no sustained virus transmission in cats or from cats to humans
For an overview of a number of other cases involving cats, see Apparently They Didn't Get The Memo.
And it isn’t just the H5N1 virus which as shown some propensity for gastrointestinal involvement.
Seasonal A & B Influenza viruses, along with the 2009 H1N1 virus, have been looked at for exhibiting unusual gastrointestinal symptoms, albeit nowhere near as severe as described in today’s study.
In January of 2010, in Influenza’s Gastrointestinal Connection, I wrote about a study that appeared in BMC Infectious Diseases, that looked at seasonal flu in pediatric patients.
Influenza virus infection among pediatric patients reporting diarrhea and influenza-like illness
The detection of influenza viral RNA and viable influenza virus from stool suggests that influenza virus may be localized in the gastrointestinal tract of children, may be associated with pediatric diarrhea and may serve as a potential mode of transmission during seasonal and epidemic influenza outbreaks.
And lastly, during the 2009 pandemic, the CDC’s Interim guidance on Infection Control for the pandemic H1N1 Virus, warned:
Transmission of influenza through the air over longer distances, such as from one patient room to another, is thought not to occur. All respiratory secretions and bodily fluids, including diarrheal stools, of patients with 2009 H1N1 influenza are considered to be potentially infectious.
More evidence (as if we needed it) to show that influenza is a far more complex, and fascinating, virus than most people give it credit for.
