Interspecies Transmission Of Canine H3N2 In The Laboratory

 

 

# 6343

 

Readers with good memories may recall that in July of 2011, in a blog called Korea: Interspecies Transmission of Canine H3N2, I wrote about a study that reported on a recently emerged canine H3N2 influenza virus that had been observed to infect and sicken domestic cats at an animal shelter in South Korea.

 

This canine H3N2 was of a different lineage than the human H3N2 we have been dealing with since the late 1960s. It first appeared in Korea in 2007 – and unlike the other canine flu (H3N8)  -which jumped from equines to dogs, this strain appears to have emerged directly from an avian source.

 

In 2008 the CDC’s EID Journal carried the following report on this newly emerging canine flu.

 

Transmission of Avian Influenza Virus (H3N2) to Dogs

Daesub Song, Bokyu Kang, Chulseung Lee, Kwonil Jung, Gunwoo Ha, Dongseok Kang, Seongjun Park, Bongkyun Park, and Jinsik Oh

Abstract

In South Korea, where avian influenza virus subtypes H3N2, H5N1, H6N1, and H9N2 circulate or have been detected, 3 genetically similar canine influenza virus (H3N2) strains of avian origin (A/canine/Korea/01/2007, A/canine/Korea/02/2007, and A/canine/Korea/03/2007) were isolated from dogs exhibiting severe respiratory disease.

 

To determine whether the novel canine influenza virus of avian origin was transmitted among dogs, we experimentally infected beagles with this influenza virus (H3N2) isolate. The beagles shed virus through nasal excretion, seroconverted, and became ill with severe necrotizing tracheobronchitis and bronchioalveolitis with accompanying clinical signs (e.g., high fever).

 

Consistent with histologic observation of lung lesions, large amounts of avian influenza virus binding receptor (SAα 2,3-gal) were identified in canine tracheal, bronchial, and bronchiolar epithelial cells, which suggests potential for direct transmission of avian influenza virus (H3N2) from poultry to dogs.

 

Our data provide evidence that dogs may play a role in interspecies transmission and spread of influenza virus.

 

Which brings us today to a new study by the same group of researchers that reported on the initial species jump to cats, that looks at laboratory transmission of the canine H3N2 virus to cats, and to ferrets.

 

Inter- and intraspecies transmission of canine influenza virus (H3N2) in dogs, cats, and ferrets

Hyekwon Kim^, Daesub Song, Hyoungjoon Moon, Minjoo Yeom, Seongjun Park, Minki Hong, Woonseong Na, Richard J. Webby, Robert G. Webster, Bongkyun Park, Jeong-Ki Kim, Bokyu Kang

Article first published online: 23 MAY 2012

DOI: 10.1111/j.1750-2659.2012.00379.x

ABSTRACT (excerpts)

Results The interspecies transmission of CIV H3N2 via airborne was only observed from dogs to cats and not from dogs to ferrets. However, direct intranasal infection of either cats or ferrets with CIV could induce influenza-like clinical signs, viral shedding, and serological responses. Additionally, naïve cats and ferrets could be infected by CIV via direct contact with infected animals of the same species.

 

Conclusion Cats appear to be another susceptible host of CIV H3N2, whereas ferrets are not likely natural hosts. The molecular-based mechanism of interspecies and intraspecies transmission of CIV H3N2 should be further studied.

(Continue . . . )

 

CIDRAP NEWS published some details not available in the abstract above in their flu news roundup last night.

 

Follow the link to read:

Study: Canine influenza H3N2 can spread to cats

In a laboratory study, the canine influenza virus (CIV) H3N2 spread from dogs to cats via respiratory droplets, suggesting that cats could be another host for the virus, according to a report published today in Influenza and Other Respiratory Viruses.

 

<SNIP details of experiment>

 

"These data suggest that cats, in addition to dogs, can be another susceptible host of CIV H3N2; ferrets may not be susceptible host but may be susceptible after viral adaptation," the researchers write. They say the transmission of the virus between dogs and cats "underscores the concern that these same viruses might also be able to infect humans who come in contact with the animals."

May 23 Influenza Other Respi Viruses

abstract

 

 

Many of the common illnesses we think of as `human’ diseases actually began in other species, and only later adapted and migrated to humans.

 

• The scourge of Tuberculosis, which now infects 1/3rd of humanity, probably jumped to humans when man began to corral and raise its traditional hosts; goats and cattle.
• Measles appears to have evolved from canine distemper and/or the Rinderpest virus of cattle.  
• Influenza, as most of you know, is native to aquatic birds – but jumped species thousands of years ago and many strains have adapted to humans, pigs, and other species.

 

 

The list of zoonotic diseases (those shared between humans and animals) is long and continually expanding, and includes: SARS, Babesiosis, Borrelia (Lyme), Nipah, Hendra, Malaria, Hantavirus, Ebola, Bartonella, Leptospirosis, Q-Fever, bird flu and many, many others.

 

So understandably, anytime we see a virus – particularly a flu virus – jump species, it gets our attention.

 

The good news is that so far, these new canine viruses haven’t shown the ability to infect humans. 

 

But as the author’s of the 2008 EID study pointed out:

 

Transmission of avian influenza A virus to a new mammalian species is of great concern, because it potentially allows the virus to adapt to a new mammalian host, cross new species barriers, and acquire pandemic potential.

 

 

And when they infect companion animals, such as dogs and cats, it becomes of even greater concern because of how closely we humans interact with them. 

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The Long And The Short Of It

 

 

# 5304

 

 

Admittedly, I can’t help but think about MRSA (and other pathogenic nasties) every time a nurse slips a well worn BP cuff around my arm, or a doctor places the bell of his trusty stethoscope against my bare chest. 

 

How long, I wonder, has it been since they’ve been sanitized for my protection?

 

Just as quickly, I decide I don’t really want to know as I surreptitiously reach for my bottle of alcohol hand sanitizer.

 

But it does explain why my B/P is always 10 points higher at the doctor’s office.

 

While I’ve long been germ-averse, my visceral reaction has grown stronger ever since I read Maryn McKenna’s vivid account of growing antimicrobial resistance in her book Superbug: The Fatal Menace of MRSA, which I reviewed last year here.  

 

 

 

Luckily, awareness of the dangers of MRSA and other pathogens has improved in the health care industry – and while serious infection control gaps remain – policies are being introduced to try to reduce the risks.

In recent years, physician’s ties, long coats, and long sleeves have all been pointed to as potential carriers of pathogens as doctors  make their rounds from one patient to the next.

 

While the science behind these suspicions has been scant, some hospitals have invoked a `no-tie’ policy, while others have barred the wearing of long sleeved coats. 

 

Today, in the Journal of Hospital Medicine, we get a study that looks at the level of bacterial contamination (including MRSA) on long sleeve coats compared with newly laundered short-sleeved uniforms worn by 100 physicians, and bacterial counts on their wrists wearing either garment.

 

The good news is, after 8 hours of wear, no difference was observed in the degree of bacterial contamination of freshly laundered short sleeve uniforms versus infrequently laundered white coats.

 

The slightly less reassuring flip side to this finding was that after 8 hours of wear, both groups were equally colonized with bacteria. 

 

Exactly how contaminated both cohorts were, unfortunately, was not revealed in the study’s abstract.

 

 

Original Research

Newly cleaned physician uniforms and infrequently washed white coats have similar rates of bacterial contamination after an 8-hour workday: A randomized controlled trial

Marisha Burden MD,Lilia Cervantes MD, Diane Weed MA, MT, Angela Keniston, Connie S. Price MD, Richard K. Albert MD

 

As this study is in a pay-to-view journal, we are lucky to have more details available from the press release.

 

 

Contact: Jennifer Beal
healthnews@wiley.com
44-012-437-70633
Wiley-Blackwell

Long- and short-sleeved physician workwear receive same amount of bacterial and MRSA contamination

Governmental agencies in the United Kingdom recently instituted guidelines banning physicians' white coats and the wearing of long-sleeved garments to decrease the transmission of bacteria within hospitals due to the belief that cuffs of long-sleeved shirts carry more bacteria. However, a new study published today in the Journal of Hospital Medicine shows that after an eight-hour day, there is no difference in contamination of long- and short-sleeved shirts, or on the skin at the wearers' wrists.

 

A group of researchers from the University of Colorado, USA, decided to assess the accuracy of the assumption that longer sleeves lead to more contamination by testing the uniforms of 100 physicians at Denver Health randomly assigned to wearing a freshly washed, short-sleeved uniform or their usual long-sleeved white coat. "We were surprised to find no statistical difference in contamination between the short- and long-sleeved workwear," said lead researcher Marisha Burden, MD. "We also found bacterial contamination of newly laundered uniforms occurs within hours of putting them on."

 

50 physicians were asked to start the day of the trial in a standard, freshly washed, short-sleeved uniform, and the 50 physicians wearing their usual long-sleeved white coats were not made aware of the trial date until shortly before the cultures were obtained, to ensure that they did not change or wash their coats. Cultures were taken from the physicians' wrists, cuffs and pockets. No significant differences were found in bacteria colony counts between each style.

 

The researchers also found that although the newly laundered uniforms were nearly sterile prior to putting them on, by three hours of wear nearly 50% of the bacteria counted at eight hours were already present.

 

"By the end of an eight-hour work day, we found no data supporting the contention that long-sleeved white coats were more heavily contaminated than short-sleeved uniforms. Our data do not support discarding white coats for uniforms that are changed on a daily basis, or for requiring health care workers to avoid long-sleeved garments," concluded Burden.

 

 

While I’m somewhat placated by these results, I doubt that I’ll be completely comfortable until I’m able to  retrofit the shower at my place to dispense 62% alcohol gel.

 

Not that I’m germ phobic, or anything.

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Ferreting Out The Transmissibility Of Aerosolized H5N1

 

 

# 4903

 

One of the (many) unanswered questions about H5N1 avian flu is why it doesn’t more easily infect humans and why is human-to-human transmission so rare?

 

We think we know part of the reason:

 

Avian adapted influenza viruses bind preferentially to Alpha 2,3 receptor cells, which are commonly found in the digestive tract of birds.  This explains why most avian flu viruses are gastrointestinal infections in birds.

 

Human adapted viruses have an affinity for the alpha 2,6 receptor cell, which populate the upper airway and lungs.  This is why influenza is a respiratory virus in humans.

 

But of course, we’ve got at least 500 exceptions to the rule.   H5N1 does, on rare occasion, find a home in a human host. 

Some scientists believe these rare human infection occur due to the presence of α2-3 receptor cells deep in the lungs and in the human gut, areas where the virus can reach, albeit with difficulty.

 

But of course, until proven, that remains a less than satisfactory answer. 

 

Adding to our list of unanswered questions, is exactly how influenza viruses are transmitted from one host to the next. The easy answer is via coughs and sneezes, but we are actually looking for something more specific than that.

 

The three commonly cited routes are large-droplets, aerosols, and  direct contact with secretions and fomites. Most scientists concede that all three probably play a role in transmission, but how much each method contributes is less certain.

 

Coughing and sneezing produces virus laden large-droplets that remain airborne for a very short period of time, and then settle to the ground (or other surfaces).

 

The `range’ of these droplets is assumed to be 6 to 10 feet, and traditionally this has been considered the primary route of transmission.

 

Photo Credit PHIL (Public Health Image Library)

 

But coughs and sneezes also produce fine aerosolized particles, that can remain airborne for extended periods.  

 

Tellier, in Review of Aerosol Transmission of Influenza A Virus, makes the case for the aerosol transmission of influenza as being an important mode of transmission.

 

Aerosolized particles, in addition to remaining airborne longer, are also more likely to be drawn deeper into a human’s respiratory system. 

 

This would – theoretically, at least – give an avian virus with an affinity for the  α2-3 receptor cells found deep in the lungs a better shot at binding and taking hold.

 

The third mode of transmission, is the transfer of virus particles or secretions from fomites (inanimate objects) or an infected host to a new host’s oral, conjunctival and nasal mucus membranes.

 

All of which is prelude to a study, published today in the Virology Journal titled:

 

Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1)

John A Lednicky , Sara B Hamilton , Richard S Tuttle , William A Sosna , Deirdre E Daniels  and David E Swayne

Virology Journal 2010, 7:231doi:10.1186/1743-422X-7-231

Background

There is limited knowledge about the potential routes for H5N1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized H5N1 virus particles. Ferrets are often used as a animal model for humans in influenza pathogenicity and transmissibility studies.

In this manuscript, a nose-only bioaerosol inhalation exposure system that was recently developed and validated was used in an inhalation exposure study of aerosolized A/Vietnam/1203/2004 (H5N1) virus in ferrets. The clinical spectrum of influenza resulting from exposure to A/Vietnam/1203/2004 (H5N1) through intranasal verses inhalation routes was analyzed.

Results

Ferrets were successfully infected through intranasal instillation or through inhalation of small particle aerosols with four different doses of Influenza virus A/Vietnam/1203/2004 (H5N1).

The animals developed severe influenza encephalomyelitis following intranasal or inhalation exposure to 10E1, 10E2, 10E3, or 10E4 infectious virus particles per ferret.

Conclusions

Aerosolized Influenza virus A/Vietnam/1203/2004 (H5N1) is highly infectious and lethal in ferrets. Clinical signs appeared earlier in animals infected through inhalation of aerosolized virus compared to those infected through intranasal instillation.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

 

 

Of course, this doesn’t really answer the question as to why H5N1 doesn’t more readily infect humans.  In fact, it raises questions, since ferrets appear to be quite susceptible to aerosolized H5N1.

 

That aside, there are some very interesting findings in this study.

 

The researchers first simulated large-droplet infection of test ferrets with direct intranasal inoculation of three different H5N1 viruses (A/Mongolia/244/2005, A/Iraq/207-NAMRU3/2006, and A/Vietnam/1203/2004).

 

Although all three strains induced influenza infection in the ferrets, one; A/Vietnam/1203/2004 (VN/04) caused neurological symptoms and was seen as particularly virulent.

 

This strain was selected for aerosol testing using a nose-only bioaerosol inhalation exposure system (NBIES). 

 

While they caution that the number of test subjects was small, and large conclusions shouldn’t be drawn, the authors note that infection through inhalation of aerosols resulted in more abrupt clinical signs and a greater probability of developing neurological disease than through intranasal inoculation.

They write:

 

Some general conclusions inferred from our histology/ immunohistochemistry and virology work are that:

(a) histologic changes may not be present even with high virus titer in particular tissues, and

(b) that brain lesions are possible without lung lesions in H5N1 infections suggesting direct extension of the virus from posterior nasal cavity through olfactory nerves into the brain, in agreement with a previous report

 

They also write:

 

Furthermore, sneezing, which primarily results in the formation of droplets, was rarely observed in the infected animals. Thus, droplet transmission may be lower than that encountered with seasonal influenza viruses. It remains unclear why ferret to ferret transmission is inefficient with this virus; perhaps the virus is not present in significant quantities in aerosols that might accompany sneezes or coughs.

 

After reviewing some of the theories regarding why H5N1 has yet to transmit efficiently in humans, the authors write:

 

Taken together, tropism for cells of the LRT tract, and the rarity of sneezing/coughing in ferrets, result in poor transmissibility of the virus. This study predicts that person-to-person transmission will readily occur if H5N1 acquires the ability to replicate in the URT and is readily aerosolized or expelled in droplets.

 

 

Something, we obviously hope, will never happen.

 

The entire article is open access, interesting, and worth reading in its entirety.  I’ve only provided a brief overview in order to hopefully whet your appetite. 

»» Read More

Fluing The Friendly Skies (Revisited)

 

 

# 4230

 

 

Six weeks before last Spring’s outbreak of novel H1N1 in Mexico and California, I wrote a blog entitled:

 

 

Sunday, March 08, 2009

How The Next Pandemic Will Arrive

# 2876

There is a lot we don't currently know about the next pandemic.  We don't know when it will arrive.  We don't know what virus will cause it.  And we don't know how bad it will be.

 

But there is one thing almost certain.

 

It will arrive in most countries by airplane.

 

 

The video above, which as been making the rounds for several months, was made by ZHAW (Zürcher Hochschule für Angewandte Wissenschaften) or The Zurich University of Applied Sciences.

(Continue . . .)

 

 

Granted, this essay was mostly inspired by finding the youtube video above . . . But timing is everything . . .

 

And as it turned out, college students returning from Spring Break in Mexico were credited – in large part - for the rapid world-wide spread of the H1N1 virus last spring. 

 

This is the price we pay for global commerce and travel.  A greater vulnerability to rapidly spreading pathogens.   

What has been less clear is how much transmission of an influenza virus takes place during an airline flight. 

 

We’ve heard airline reassurances about HEPA filtering, and the number of air exchanges per hour in the passenger cabin, but instinctively most of us suspect that jamming a couple of hundred people into a plane like sardines must entail some infection risks.

 

Today, researchers at UCLA have quantified that risk.  And as one might expect, the denser the seating arrangement (economy class), the better chance of viral transmission. 

 

This from the UCLA Newsroom.

 

 

Study finds H1N1 virus spreads easily by plane

Your best bet? Avoid economy and fly first class, UCLA researchers say

 

By Mark Wheeler January 06, 2010 Category: Health Sciences, Research

 

Viruses love plane travel. They get to fly around the world inside a closed container while their infected carrier breathes and coughs, spreading pathogens to other passengers, either by direct contact or through the air. And once people deplane, the virus can spread to other geographical areas.

 

Scientists already know that smallpox, measles, tuberculosis, seasonal influenza and severe acute respiratory syndrome (SARS) can be transmitted during commercial flights. Now, in the first study to predict the number of H1N1 flu infections that could occur during a flight, UCLA researchers found that transmission during transatlantic travel could be fairly high.

 

Reporting in the current online edition of the journal BMC Medicine, Sally Blower, director of the Center for Biomedical Modeling at the Semel Institute for Neuroscience and Human Behavior at UCLA, along with Bradley Wagner and Brian Coburn, postdoctoral fellows in Blower's research group, used novel mathematical modeling techniques to predict in-flight transmission of the H1N1 virus.

 

They found that transmission could be rather significant, particularly during long flights, if the infected individual travels in economy class. Specifically, two to five infections could occur during a five-hour flight, five to 10 during an 11-hour flight, and seven to 17 during a 17-hour flight.

 

"Clearly, it was air travel, by transporting infectious individuals from the epicenter in Mexico to other geographic locations, that significantly affected the spread of H1N1 during the outbreak last spring," Coburn said. "However, until our study, it hadn't been determined how important in-flight transmission could be. Therefore, we decided to make a mathematical model and predict what could be expected to occur during a flight."

 

(Continue. . . )

 

 

There is obviously very little you can do to protect yourself from influenza during a prolonged flight if the person seated next to you is infected with the virus.

Very little, except of course, getting the flu vaccine every year.

 

There’s always that.

»» Read More

NEJM: Household Transmission Of The H1N1 Virus

 

 

# 4203

 

A study today from the NEJM which suggests the novel H1N1 virus isn’t as easily transmissible as other novel pandemic viruses of the past. 

 

In a study of 216 households where an index case of H1N1 infection was identified, only about 13% of household contacts (about 1 in 8) came down with the infection.

 

Looked at another way, in roughly 72% of the households where a case was identified, no one else came down with the virus.   In 21% of the households, only one additional member acquired the infection.  And in only 6% of households did more than one other family member fall ill.

 

Children and teens under the age of 18 were twice as likely to catch the virus than those aged 19 to 50.  Those over the age of 50 were even less likely to fall ill.

 

For reasons that are less than clear, the rate of viral transmission in households with just two members was much higher than in households with four or more members.  

 

Excerpts from the abstract are below, but follow the link to read the entire study.

 

 

Household Transmission of 2009 Pandemic Influenza A (H1N1) Virus in the United States

Simon Cauchemez, Ph.D., Christl A. Donnelly, Sc.D., Carrie Reed, D.Sc., Azra C. Ghani, Ph.D., Christophe Fraser, Ph.D., Charlotte K. Kent, Ph.D., Lyn Finelli, Dr.P.H., and Neil M. Ferguson, D.Phil.

ABSTRACT

 
Background As of June 11, 2009, a total of 17,855 probable or confirmed cases of 2009 pandemic influenza A (H1N1) had been reported in the United States. Risk factors for transmission remain largely uncharacterized. We characterize the risk factors and describe the transmission of the virus within households.

 
Methods Probable and confirmed cases of infection with the 2009 H1N1 virus in the United States were reported to the Centers for Disease Control and Prevention with the use of a standardized case form. We investigated transmission of infection in 216 households — including 216 index patients and their 600 household contacts — in which the index patient was the first case patient and complete information on symptoms and age was available for all household members.

 

Results An acute respiratory illness developed in 78 of 600 household contacts (13%). In 156 households (72% of the 216 households), an acute respiratory illness developed in none of the household contacts; in 46 households (21%), illness developed in one contact; and in 14 households (6%), illness developed in more than one contact.

The proportion of household contacts in whom acute respiratory illness developed decreased with the size of the household, from 28% in two-member households to 9% in six-member households. Household contacts 18 years of age or younger were twice as susceptible as those 19 to 50 years of age (relative susceptibility, 1.96; Bayesian 95% credible interval, 1.05 to 3.78; P=0.005), and household contacts older than 50 years of age were less susceptible than those who were 19 to 50 years of age (relative susceptibility, 0.17; 95% credible interval, 0.02 to 0.92; P=0.03).

Infectivity did not vary with age. The mean time between the onset of symptoms in a case patient and the onset of symptoms in the household contacts infected by that patient was 2.6 days (95% credible interval, 2.2 to 3.5).

 

Conclusions The transmissibility of the 2009 H1N1 influenza virus in households is lower than that seen in past pandemics. Most transmissions occur soon before or after the onset of symptoms in a case patient.

 

 

A few caveats to this study are in order.

 

First, this study took place very early in the outbreak, essentially during the first 3 weeks of May.  

 

While it may not have appreciably changed, this is a snapshot of the transmissibility of the virus at that time.

 

Second, the data was collected by interviewing (telephone or face-to-face) family members within 7 days of an index case having been identified in their household. 

 

Illnesses that fell outside of that 7 day follow up period were not directly identified.

 

Third, reports of ILI (influenza-like illness) among family members or contacts within 7 days were assumed to have been due to exposure to the index case.

 

Testing for H1N1 wasn’t always done, and the actual chain of infection may have been other than from the index case.

 

None of which is mentioned to negate the findings of this study, but simply stated to illustrate that these sorts of studies have limitations, and those must be considered when you view the data.

 

This study does seem to suggest that compared to teenagers and children, those over the age of 18 may have some limited immunity to the virus. And that immunity appears to increase with age, becoming more prevalent in those over the age of 50.

 

The authors put it this way :

 

. . .  our findings are consistent with serologic analyses of the 2009 H1N1 virus suggesting that there are some preexisting pandemic H1N1 immune responses in the elderly; these are present to a lesser extent in younger adults but are rarely present in children.

 

Just as I was about to post this entry, I noticed that Maryn McKenna, writing for CIDRAP, has posted her summary of the report.   You’ll find it at the link below.

 

Study: H1N1 not highly contagious in households

»» Read More