More Details On The trH3N2 Story

 

 

 

# 5974

 

 

The announcement yesterday out of Iowa that 3 more children have contracted a rare emerging swine flu strain (see Iowa DPH Reports 3 Novel trH3N2 Cases) has produced a number of headlines over the past 18 hours.

 

The most significant piece of new information since then is that all three children had contact with one another, and that it appears that one child transmitted the virus to the other two.

 

No additional transmission has thus far been detected, and the the mystery of how and where the first child acquired the virus remains.

 

As might be expected, Helen Branswell of the Canadian Press has some of the best and most complete coverage of this story.  

 

A link to her story (which I encourage you to read in its entirety), then I’ll be back with a little more.

 

U.S. sees 3 new infections with new flu virus

The Canadian Press

Date: Tuesday Nov. 22, 2011 8:59 PM ET

U.S. health officials have spotted three more children infected with a new swine-origin flu virus, this time in Iowa.

 

And while earlier cases of infection with this virus are believed to have been cause by exposure to pigs, this time the evidence points to person-to-person spread.

(Continue . . . )

 

 

Occasionally we’ll see a novel swine influenza virus (usually an H1N1 or H3N2 variant) jump to humans. Although the 2009 swine flu pandemic was an exception, most of the time this turns out to be a one-off dead-end transmission, and goes no further.

 

The key phrase being `most of the time’. 

 

While it is a rare event, as we saw in 2009 it is possible for one of these viruses to adapt well enough to human physiology to spark an extended outbreak, or even a pandemic.

 

Since only a tiny fraction of influenza flu viruses are ever sequenced, we really don’t know how often these types of novel infections occur.

 

It’s probably more often than we think.

 

But surveillance systems must be incredibly lucky, or wait until a novel virus has infected a sufficient percentage of the population, before they are likely to start picking up cases.

 

In these ten most recently reported cases, the virus has been a swine H3N2 virus with the M segment gene borrowed from the 2009 H1N1 virus. Essentially a hybrid – a new reassortant virus - that until this summer had not been seen before.

 

Reassorted viruses can result when two different flu strains inhabit the same host (human or otherwise) at the same time. Under the right conditions, they can swap one or more gene segments and produce a hybrid virus.

 

 

Where this virus goes from here is anyone’s guess.

 

Its appearance across four states, and in some humans without direct animal contact, certainly suggests low-level human transmission.

 

But the ability to transmit from one human to another isn’t enough to ensure its survival. In order to thrive, it must have an R₀ number (basic reproductive number) sufficient to sustain an outbreak.

 

The R₀  number signifies the average number of secondary infections caused by one infectious person entering a totally susceptible population. 

 

If less than 1.0, outbreaks are likely to sputter and die out.  If greater than 1.0, the outbreak is more capable of spreading. 

 

 

And as we’ve seen with roughly two dozen other reported novel swine infections since 2005, and with a significant number of H5, H7, and H9 avian flu infections, it is possible to have limited outbreaks of a novel flu virus without it sparking an epidemic.

 

For now, this virus doesn’t appear to be sufficiently well adapted to human physiology to spread in an efficient and sustained manner.

 

This virus may simply simmer at low levels in the human population for a spell, then die out. Or it may further adapt to humans, and produce a larger public health threat down the road.

 

We’ll simply have to keep our eyes on this story, to see where it goes.

 

In the meantime, maintaining good flu hygiene this winter, and getting your flu shot, remain the best strategies to avoid getting sick during this flu season.

Gastrointestinal Bird Flu Infection In Cats

 

 

 

# 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.

Egypt: Two New Bird Flu Cases

 

 

# 5197

 

 

Kudos to newshound Treyfish who just found, and posted on FluTrackers, a news report from Youm7 announcing two new H5N1 cases in Egypt.

 

The first case involves a 25 year-old woman who died on December 29th, from the Qena Governate, and the second regards a 27 year-old man from Ismailia who is in stable condition.

 

Assuming these cases are confirmed by the World Health Organization, and that no new cases from last year emerge, Egypt will have recorded 28 new H5N1 infections in 2010 and 12 new fatalities (42% fatality rate).

 

This represents a decrease in the total number of officially recognized cases (compared to 39 in 2009), but a significant increase in fatalities (there were just 4 in 2009).

 

 

"Health" announces the death of a new case of bird flu in Qena

Saturday, January 1, 2011 - 17:47

 

Dr. Abdel Rahman Shahin

Written by Amira Abdel-Salam

Dr. Abdel Rahman Shahin, official spokesman of the Ministry of Health, that the team monitoring the epidemic, Ministry of Health discovered two cases of bird flu, the first old lady (25 years), from Qena Governorate, and died on 29 December last year, the second man from age (27 years), from Ismailia, which is under treatment at a hospital in Ismailia and stable condition.

 

This brings the number of cases to 118 cases and 39 cases the number of deaths since the onset of the disease in 2006 until now.

 

 

Since the beginning of 2009 Sharon Sanders of FluTrackers keeps an excellent listing of human H5N1 cases officially announced by the Egyptian MOH. 

 

You can view the latest version here.

H3N2 Swine Flu

 

 

 

# 4260

 

 

Helen Branswell of the Canadian Press brings us details overnight of the detection of a single human infection by H3N2 swine influenza this fall in Iowa.   

 

While not believed to be terribly common, human infection by various (non pandemic) swine - and even avian - Influenza viruses probably happens more often than we think.

 

Improved surveillance and testing over the past couple of years will no doubt turn of more of these types of infections.

 

Farmers, hunters, and those who work closely with birds or swine are the most commonly affected.   Since most of these infections are mild, they often go unnoticed, or at least untested.

 

This story does have some unusual aspects to it.

 

First, the victim had no known contact with swine. This suggests a longer chain of infection, although there have been no signs of further human-to-human transmission.    Exactly how this person contracted the virus remains a mystery.

 

Second, this is a swine H3N2.   Up until a dozen years ago, only H1N1 was found in North American swine herds.

 

In 1998, a new triple reassortant H3N2 virus (with human, swine, and avian genes) was isolated, and has now become endemic in US herds. (see j virol. 2000 Sep, Evolution of swine H3N2 influenza viruses in the United States  and j virol. 2007, Interspecies and intraspecies transmission of triple reassortant H3N2 influenza A viruses ).

 

In 2006 and early 2007, an apparently reassorted H2N3 subtype was detected in pigs on two different Missouri farms, which was the first known appearance of an H2 virus in the wild since it was supplanted by the H3N2 virus in 1968.  

 

That discovery, along with the recent emergence of the novel H1N1 `swine’ flu last spring, gives further credence to the `pigs serving as influenza mixing vessels’ theory.

 

 

 

All of which points out the importance of surveillance and testing of livestock in this country.

 

Helen Branswell bring us more details on this story.  Follow the link to read her story in its entirety.

 

 

 

U.S. CDC reports finding single case of a new swine flu; no sustained spread

By Helen Branswell Medical Reporter (CP)

TORONTO — Another new swine flu virus has made the leap to humans, though U.S. officials say it seems almost certain the virus hit a dead end.

 

The Centers for Disease Control reported Friday that a child from Iowa became infected with a new swine flu virus in September, though the case didn't come to light until November.

 

The unnamed boy didn't need to be hospitalized and recovered fully from the illness.

 

Testing later showed he'd been infected with a swine influenza virus of the H3N2 subtype, different both from the pandemic H1N1 virus and from the seasonal H3N2 viruses that have been circulating in people for decades.

 

Human cases of infection with swine influenza viruses happen from time to time. Often, though not always, these infections are seen in people who work on pig farms or in proximity to swine herds.

(Continue . . . )