Bats, Viruses, And Their Immune Response

Common pipistrelle (Pipistrellus pipistrellus) – Credit Wikipedia

 

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For virologists and chiroptologists, an enduring mystery has been how bats are able to carry – without apparent ill effect – viruses that are normally deadly to most other mammals.

 

Long known for carrying rabies, over the past two decades we’ve discovered that bats can also harbor viruses such as Ebola, Marburg, Nipah, Hendra, and a variety of coronaviruses (including SARS). 

 

This week, in an article that appears in the Journal Science, we learn that some of the evolutionary changes that enable the bat to be the only mammal that can fly, may also help them to carry deadly viruses.

 

First a link to the Abstract (the whole paper is behind a pay wall), then excerpts from a Reuter’s news article that help flesh out the findings.

 

Published Online December 20 2012
< Science Express Index

Science DOI: 10.1126/science.1230835

• Report

Comparative Analysis of Bat Genomes Provides Insight into the Evolution of Flight and Immunity

Guojie Zhang, Christopher Cowled, Zhengli Shi, Zhiyong Huang, Kimberly A. Bishop-Lilly, Xiaodong Fang, James W. Wynne, Zhiqiang Xiong, Michelle L. Baker, Wei Zhao, Mary Tachedjian, Yabing Zhu, Peng Zhou, Xuanting Jiang, Justin Ng, Lan Yang, Lijun Wu, Jin Xiao, Yue Feng, Yuanxin Chen, Xiaoqing Sun, Yong Zhang, Glenn A. Marsh, Gary Crameri, Christopher C. Broder, Kenneth G. Frey, Lin-Fa Wang, Jun Wang

Abstract

Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world’s most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat-specific traits, we performed whole-genome sequencing and comparative analyses of two distantly related bat species, fruit bat Pteropus alecto and insectivorous Myotis davidii.

 

We discovered an unexpected concentration of positively selected genes in the DNA damage checkpoint and nuclear factor–κB pathways that may be related to the origin of flight, as well as expansion and contraction of important gene families. Comparison of bat genomes with other mammalian species has provided new insights into bat biology and evolution.

 

 

Admittedly, there is not much specificity in this abstract. 

 

Luckily, Tan Ee Lyn - Asia Health correspondent for Reuters – has an interview with the lead author -Professor Lin-Fa Wang, who reveals that some genetic changes necessary for flight may also help to moderate dangerous out-of-control immune responses known as Cytokine Storms.

Cytokines are a category of signaling molecules – proteins – that are released by immune cells that have encountered a pathogen, and are designed to alert and activate other immune cells to join in the fight against the invading pathogen.

 

Although poorly understood, the theory behind a `cytokine storm’ is this signaling process spirals out of control, resulting in an overwhelming immune response that can potentially kill the host.

 

According to Professor Lin-Fa Wang, this built-in suppression of the inflammatory (cytokine) response may be behind the bat’s unusual longevity (20 to 40 years), and their ability to `handle’ infection by normally deadly viruses.

 

 

Long-lived bats offer clues on diseases, aging

December 21, 2012 12:52 PM

HONG KONG: The bat, a reservoir for viruses like Ebola, SARS and Nipah, has for decades stumped scientists trying to figure out how it is immune to many deadly bugs but a recent study into its genes may finally shed some light, scientists said on Friday.Studying the DNA of two distant bat species,...

(Continue . . . )

 

 

In another article, this time in The Asian Scientist, the author talks about practical applications of this research, and is quoted as saying, “Our findings highlight the potential of using bats as a model system to study infection control, tumor biology, and the mechanisms of aging,”

 

 

Bats’ Immunity Against Deadly Viruses Linked To Their Ability To Fly

AsianScientist (Dec. 21, 2012) – An international team led by an infectious disease expert, Professor Lin-Fa Wang, at the Duke-NUS Graduate Medical School (Duke-NUS) in Singapore has found that the evolution of flight in bats may have contributed to the development of a highly effective immune system, allowing bats to harbor some of the world’s deadliest viruses such as Ebola and SARS.

(Continue . . . )

 

Both news articles are worth reading in their entirety.

 

For more on cytokine storms, and how they may affect pandemic influenza mortality, you may wish to revisit some of these earlier blogs.

 

Study: Calming The Cytokine Storm

Cytokine Storm Warnings

The Baskin Influenza Pathogenesis Study

Pt. 1   Pt. 2   Pt. 3

»» Read More

The Return Of H1N1v

 

(click to enlarge)

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Yesterday’s FluView report, in addition to updating the number of new H3N2v cases, announced the detection of a single H1N1v flu infection in a person living in Missouri. That patient has fully recovered.

 

H1N1v is one of the `viral contenders’ I mentioned two weeks ago in An Increasingly Complex Flu Field, and until just over a year ago, was the most commonly reported variant swine flu virus detected in humans since 2005.

 

 

This week’s announced case brings to 14 the total number of H1N1v cases reported since 2005.  The last reported case of H1N1v infection came from Wisconsin in December of 2011.

 

Of particular interest, this week’s detection is the second time that the H1N1v virus has been found to contain the M (matrix) gene from the 2009 H1N1 pandemic virus. 

 

Here is how this week’s FluView describes it:

 

Confirmatory testing at CDC identified H1N1v with the matrix (M) gene from the 2009 H1N1 influenza virus in specimens collected from this patient. Cases of H1N1v have been detected previously, and the current case marks the second report of H1N1v with the M gene from the 2009 H1N1 virus.

 

This M gene  has been showing up regularly in swine variant viruses (H1N1v, H1N2v, H3N2v) for more than a year. The CDC has previously stated that `This M gene may confer increased transmissibility to and among humans, compared to other variant influenza viruses.’

 

The $64 question is, what to make of all of this? 

 

Since the outbreak of H3N2v began in earnest in mid July, the CDC and local health departments have stepped up testing for novel or variant flu viruses.

 

And as one might expect, the harder you look, the more you are likely to find.

 

Given the limits of surveillance, testing, and reporting – we really don’t know what the normal `background rate’ of these types of infections are in humans. The smattering of reports since 2005 indicate they are fairly rare, but certainly not unheard of.

 

For now, the H3N2v virus – due to roughly 300 human infections across the Midwest - has captured the bulk of our attention.

 

But these other cases serve to remind us that nature continues to churn out and test new viral variations, and that the next public health threat could come out of left field.

 

The CDC’s assessment on the H3N2v virus reads:

 

It's possible that sporadic infections and even localized outbreaks among people with this virus will continue to occur. While there is no evidence at this time that sustained human-to-human transmission is occurring, all influenza viruses have the capacity to change and it's possible that this virus may become widespread.

So far, the severity of illnesses associated with this virus in people has been similar to the severity of illnesses associated with seasonal flu virus infections. Limited serologic studies indicate that adults may have some pre-existing immunity to this virus while children do not.

CDC is closely monitoring human infections with all novel influenza viruses, including H3N2v viruses, and will provide more information as it becomes available.

 

 

For more on all of this, Robert Roos of CIDRAP NEWS, has an excellent report from last night.

 

Latest variant flu cases include rare H1N1 strain

Robert Roos News Editor

»» Read More

Investigating A Viral Outbreak In Vancouver

 

 

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In medicine, one always looks first to the most common, or likely, cause of a patient’s chief complaint before considering something exotic.   The old adage, that `When walking in Central Park, if  you hear hoof beats, expect horses, not zebras’ is drummed into every medical student.

 

It is only when you eliminate the simplest explanation that you move to the next most-likely cause of a patient’s illness. 

 

And so, when a series of extremely elderly residents in a long-term nursing facility on Vancouver Island began to fall seriously ill from a respiratory ailment earlier this month, naturally the first thoughts were that it was influenza A or B.

 

But testing has ruled out these two most likely suspects, and doctors and epidemiologists are now looking for a different explanation.

 

Influenza viruses, of course, make up only a small percentage of known respiratory viruses (see ILI’s Aren’t Always The Flu).

 

The list of viral pathogens that can cause ILI's (`influenza-like Illnesses') is a long one, and includes adenoviruses, influenza viruses, human metapneumovirus, parainfluenza viruses, respiratory syncytial viruses, and rhinoviruses.

 

Yesterday the press – particularly in Canada – picked up this story. 

 

A hat tip to RoRo, Alert, Laidback Al, Tetano, and others on FluTrackers for starting this thread to track the progress of this investigation.

 

This report from the Canadian Press, followed by a press release from the local health authority.

 

Virus kills nine at Victoria hospital

 

Influenza-like virus has made 19 ill; H1N1 has been ruled out

Victoria, BC —  Last updated on Tuesday, Apr. 27, 2010 6:26PM EDT

Nine residents have died since April 5 at a Victoria hospital where an influenza-like illness has been detected, says the Vancouver Island Health Authority.

 

Spokeswoman Suzanne Germain said Tuesday that 19 people have become ill since the respiratory outbreak began at Glengarry Hospital, which is home to frail and elderly patients, many with multiple pre-existing conditions.

 

“While we know that nine people who died had the symptoms we don't know if that was what ultimately caused them to die,” she said of the patients, who were in their 80s and 90s.

 

Lab tests have confirmed that the illness is not H1N1 or influenza A and B, but further tests are being conducted to try and find out what kind of illness is involved, she said.

(Continue . . . )

 

 

The Vancouver Island Health Authority (VIHA) has released the following statement:

 

Respiratory Outbreak at Glengarry Hospital

 

April 27, 2010

VICTORIA – The Chandler Unit at Glengarry Hospital in Victoria is experiencing a respiratory outbreak which has affected a total of 19 residents. The Vancouver Island Health Authority (VIHA) is asking family and friends to consider not visiting the facility at this time, especially if they are sick. If they do visit, they will be asked to clean their hands on entering the facility and affected unit as well as follow other precautions as directed by staff.

 

The Chandler Unit at Glengarry has also been experiencing a Norovirus outbreak since April 6. Some patients on the unit began developing respiratory symptoms at the end of March, but these were often mild and not readily distinguished from the Norovirus symptoms in this group of elderly and often cognitively impaired residents. The respiratory outbreak was declared on April 22 after an increase in the number of cases and several deaths occurred.

 

Since April 5, nine residents with the respiratory symptoms have passed away. Each of these residents was elderly and frail with multiple medical challenges. Five of these residents were already receiving palliative care. Medical reviews are underway on all cases to determine what role the respiratory condition may have played – if any – in the deaths.

 

“We take outbreaks in residential care facilities very seriously because the frail, elderly population is more susceptible to serious complications and even death from illnesses,” said Dr. David Forrest, Associate Medical Director, Infection Prevention and Control with VIHA. “The fact that no staff have been affected by this illness would suggest it is a mild illness in most people that is affecting our frail elderly residents more.”

 

Lab tests have not yet confirmed the organism involved in the respiratory condition, but influenza A and B and H1N1 have been ruled out. Further testing is underway at the VIHA laboratory as well as at the BC Centre for Disease Control in Vancouver. Results are expected later this week.

 

“While the cause of the illness is not yet known, residential care facilities reflect the community.  There are many viruses circulating in the community this time of year, including rhino- and noro-viruses.   When they are introduced into the residential care setting they can have a significant impact on residents and staff,” said Dr. Forrest. “We would like to remind people not to visit when they are not feeling well.  In addition, since many infections such as influenza can be prevented by vaccination, immunization is important to prevent the development of such outbreaks and deaths.”

 

VIHA has notified family members of this latest outbreak. Heightened infection control measures are in place to prevent its spread.

These measures include:

• Limiting contact between residents (residents are isolated to their rooms)
• Closing all dining rooms (meals are being served to residents in their rooms)
• Limiting visitors to one family member per resident.
• Requiring visitors to wear protective equipment and to follow strict hand hygiene practices (e.g. mask, gown and gloves when visiting someone with symptoms).
• Restricting visitors to loved one’s room only; no visits in common areas.
• Cancelling special events and restricting movement for residents who smoke.
• Requiring staff to wear protective equipment and to follow strict infection control practices (e.g. mask with visor, gown, gloves).
• Restricting staff who have been working on the Chandler Unit from working in other residential care sites in back-to-back shifts.
• Adding housekeeping staff and enhancing housekeeping with additional infection control cleaning protocols (such as enhanced cleaning of frequent touch areas, changing of privacy curtains).
• Maintaining a previous closure to new admissions that was put in place April 6 due a Norovirus outbreak.

Residents who contract respiratory symptoms are being carefully monitored and treated as appropriate, depending on their care plan, their wishes, or the wishes of their family.  Where requested and appropriate, a resident may be transferred to hospital for additional care such as intravenous antibiotic care.

 

Glengarry has a total of 140 beds. Only the Chandler Unit (70 beds) is affected by the respiratory outbreak.

»» Read More

Yale Research: Stopping The Next Swine Flu

 

 

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One of the `up’ sides to the H5N1 scare and the H1N1 pandemic has been the increase in research into influenza, and other emerging infectious diseases it has generated.  

 

Wars (hot and cold), along with pandemics – it seems - often spur advances in scientific knowledge.

 

The space race of the 1950s and 1960s was a much about the cold war as it was about exploration and the advancement of scientific knowledge. 

 

And yet today nearly every facet of our lives – from medical telemetry to computer chips to the Internet – can be traced back to the manned space program. 

 

A pity mankind often needs these sorts of motivators.   We ought to do scientific research simply because it helps makes the world a better place to live in.   

 

But I digress . . . .

 

 

The fruits of this pandemic – in terms of scientific data collected – will be studied for years to come.   Over time, they may lead to new treatments, new preventatives, and a better understanding of the inner workings of a variety of pathogens.

 

Scientific research can open unexpected doors.   You never know where a new discovery, or a better understanding of our universe, will lead.

 

From the Yale Daily News we get some early details of one example of this sort of research.    Not specifically about influenza, but hopefully applicable to future pandemic viruses.

 

Will this research stop the next swine flu? 

 

Maybe, maybe not. 

 

But anything that advances our knowledge of how viruses work has got to help in that regard.

 

 

Stopping the next swine flu

By Carol Hsin

Staff Reporter

Published Wednesday, January 13, 2010

The evolutionary path of a virus can help scientists predict whether it may be the next swine flu virus, Yale researchers have found.

 

Post-doctoral fellow Nadya Morales, who works in Ecology and Evolutionary Biology professor Paul Turner’s lab, has shown that viruses that have evolved to infect multiple hosts are more likely to shift hosts. Her research findings, currently in review, may be used to prepare for epidemics like swine flu and avian flu by creating vaccines before the virus infects humans, Morales said.

 

“From this experiment, we have direct evidence for what scientists have suspected about the success of emerging pathogens,” Turner said.

 

Previously, scientists had little evidence to prove that viruses that can infect multiple hosts would be more able to infect new hosts, Turner said. Since swine flu and avian flu were caused by RNA viruses, which are known for high mutation rates, Morales used laboratory-created strains of a certain RNA virus carried by insects as a model to test this theory. When introduced to new host cells, specialized strains that were grown on either only human cancer cells or only dog cells grew less than a generalized strain that grew alternately on both species.

 

“The experiment supports the idea that generalists would do better in a new environment,” Morales said.

 

(Continue . . .  )

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Study: Global Warming And Viral Mutation

 

 

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Although the press release came out on December 22nd, the news media is just now taking notice of a study that will look at the effect of rising global temperatures on viral mutation.

 

Utilizing a $911,000 grant from the NIH, a group of scientists will conduct a study to see if viruses can become more likely to mutate as temperatures rise. 

 

Science Daily has a summary of the project, entitled:

 

Will Higher Global Temperatures Make It Easier for Viruses to Jump Species?

 

You’ll find excerpts from the University of Iowa’s press release below.

 

 

It’s Not the Heat, It’s the Mutivity

Tuesday, December 22 2009

Written by Ken Kingery

MOSCOW, Idaho – An interdisciplinary team of researchers at the University of Idaho soon will begin investigating whether viruses that have adapted to higher temperatures – similar to increases due to global warming – can jump species more easily.

 

Thanks to a $911,000 grant from the National Institutes of Health, a group that includes a computational biophysicist, an evolutionary biologist and a mathematician will conduct the study. Their results could shed light on the characteristics of host-switching viruses – such as the avian flu or H1N1 – in a world of increasing temperatures.

“It’s a pretty simple experiment, but it’s a wild ass idea,” said Holly Wichman, professor of biology and the evolutionary biologist of the group.

 

“But, if it turns out that our idea is right, it could have enormous implications,” added Marty Ytreberg, professor of physics and the computational biophysicist of the group.

 

The virus being studied is known as bacteriophage fX174. It was the first genome ever sequenced and often is used by scientists who study evolution because it has a small genome and multiplies quickly. This allows mutations and evolution to occur rapidly.

 

Through previous experiments together, the team observed mutations that allow the virus to survive in higher temperatures might also increase the stability of the capsid – the protein shell that encloses the genetic material of a virus. If true, this increased stability may make the virus more mutable, more likely to mutate and thus have an increased ability to jump hosts.

 

To test the theory, the virus will be subjected to mutations that are known to enable it to survive at higher temperatures. Then, the team will investigate if this ability results in more stabilizing mutations than the original strain that lives at lower temperatures. The team also will investigate whether or not the stabilizing mutations allow the virus to switch hosts more easily.

 

(Continue . . .)

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Ambiguous Mutations

 

 

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If you follow the various flu forums, blogs, and websites you are probably aware that there has been a fair amount of discussion in recent days revolving around the `Norwegian’ and `Ukrainian’  mutations, and increased reports of Tamiflu resistant H1N1 viruses.

 

Don McNeil Jr. of the New York Times has an article about the WHO (World Health Organization’s) attempts to dampen fears over these reports, in a piece called Experts Say Swine Flu Mutations Do Not Warrant New Alarm.

 

The tone of the message from the World Health Organization is one of reassurance, although they admit there are things they do not yet understand about these mutations.  

 

I’ll grant that the first inclination of most governments or health agencies - when faced with disturbing news - is to ratchet down public concerns.

 

It is almost an autonomic reflex, and not always a bad thing. Particularly when there is a good deal of ambiguity about the threat.

 

My take is simply that mutations happen, and that we shouldn’t be terribly surprised to see them when they do.  As virologists like to say,  `Shift Happens’   (more accurately `drift’ in this case).

 

But I’m not quick to jump on any viral bandwagon. 

 

Which is why I tend not to become too alarmed over these reports.  At least not until we can get some credible data and analysis.

 

Only time will tell if any of these mutations is `fit’ enough to compete with the existing virus strains and become a `contender’.  Most mutations fail to thrive, and are destined to die out.

 

The isolation of a single mutation, or even a handful of them around the world, doesn’t automatically make for a public health threat, regardless of what the tabloid papers are saying. 

 

But of course, every once in awhile . . .  well, let’s face it.  Every viral change started out small somewhere. 

 

Are the `Norwegian Mutations’ (which actually have been seen in  many places around the world) a big deal?  Or the Tamiflu resistant strains?

 

We don’t know yet.    Maybe.  Stay tuned.

 

Good science takes time.   You have to collect the data and then analyze it.  And sometimes, the data can be confusing or misleading.

 

Hopefully we’ll have a better handle on all of this a week or two from now.  But definitive answers could be months away.  

 

Influenza is constantly fooling us, and the `rules‘ are rarely writ in stone. If any of these mutations end up being less benign than currently advertised, I figure that will become apparent over time. 

 

For now, I regard these viral changes as worthy of our attention, but not our alarm. 

 

This from the New York Times.

 

 

 

Experts Say Swine Flu Mutations Do Not Warrant New Alarm

by DONALD G. McNEIL Jr.

Published: November 27, 2009

The World Health Organization tried this week to dampen fears about mutations seen in the swine flu virus in several countries, noting that both mutations had been found in very few people.

 

A change that created Tamiflu resistance has been found in about 75 people around the world, said Dr. Keiji Fukuda, chief flu adviser to the W.H.O.’s director general. Two clusters, in cancer units at Duke University Medical Center in North Carolina and a hospital in Wales, were both among patients whose immune systems had been severely suppressed by cancer treatment; some had had their bone marrow, which produces infection-fighting white blood cells, wiped out so that replacement blood stem cells could be injected.

 

Such patients are more likely to develop resistant viruses when on Tamiflu because they can not clear a virus on their own. But the mutant strain appears not to spread easily in people with normal immunity, like hospital workers.

 

“We don’t know the full answer, but it is more likely that we are not seeing a major shift,” Dr. Fukuda said.

 

Widespread Tamiflu resistance is a serious problem in the seasonal H1N1 virus, but it has not crossed over into the swine H1N1.

 

(Continue . . . )

»» Read More

H1N1 Mutation Found In Hong Kong

 

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In an announcement today Hong Kong authorities tell of a year-old boy hospitalized for 3 days last July who tested positive for the same mutation in the H1N1 virus as made headlines last week.

 

The amino acid change in the HA1 gene at position 222 (225 in influenza H3 numbering) from aspartic acid (D) to glycine (G) had been found in three cases of severe pandemic Influenza  in Norway.

 

The assumption by some has been that this mutation must increase the virulence of the virus because it was found in several severe cases in Norway, some with fatal outcomes.  

 

While it may indeed prove to be a factor in the virulence of H1N1, what we don’t have a good handle on is how many mild cases have occurred with this mutation? 

 

Without knowing that, it is very difficult to assess the relative dangers of this single amino acid substitution.

 

The case announced today would appear only to have been of moderate severity, as the child was only hospitalized for 3 days and has fully recovered.

 

The other key point here is that of 123 samples tested in Hong Kong, only one showed the mutation. 

 

Which would suggest it isn’t widespread in that community, and may simply be a spontaneous mutation.  

 

Also, the boy’s family did not fall ill, and the virus remained sensitive to antivirals. 

 

The significance of this mutation is not yet clear.  But each day brings us more data which will hopefully give us a better idea in the weeks and months to come. 

 

Two reports:

 

H1N1 flu virus mutation detected in HK

www.chinaview.cn 2009-11-24 07:33:52

HONG KONG, Nov. 23 (Xinhua) -- Hong Kong's Department of Health announced Monday that it had found the same mutation in a H1N1 flu virus sample as the one detected in Norway recently.

 

The department said that it had examined the genetic sequence of H1N1 flu viruses in its monitoring system. Out of the 123 sequences studied, one sample showed the same mutation as the Norway strain.

 

The virus was taken from a year-old boy who developed flu-like symptoms July 22. He was admitted to Prince of Wales Hospital July25 and discharged three days later. He has recovered.

 

Mutations are frequently encountered in influenza viruses. According to the World Health Organization, the same mutation of the virus has been found on the Chinese mainland and in other countries, including Brazil, Japan, Mexico, Ukraine and the United States.

 

The virus with this mutation remained sensitive to antiviral drugs, Tamiflu and Relenza. No evidence suggests these mutations are leading to an unusual increase in the number of H1N1 flu infections or a greater number of severe or fatal cases.

 

And an excerpt from the Hong Kong Standard

 

 

Mutated swine flu found in tot
Mary Ann Benitez
Tuesday, November 24, 2009

EXCERPT

The Department of Health announced last night that it found the same mutation in the boy, who developed symptoms on July 22 and tested positive for the virus on July 25 when he was admitted to Prince of Wales Hospital.

 

He was discharged on July 28 and recovered completely. His family members did not fall ill.

 

A department spokesman said: "The virus with this mutation remained sensitive to antiviral drugs oseltamivir [Tamiflu] and zanamivir [Relenza]."

 

The spokesman said there is no evidence that these mutations are leading to an unusual increase in the number of swine flu infections or a greater number of severe or fatal cases.

<SNIP>

 

Stene-Larsen added: "Based on what we know so far, it seems that the mutated virus does not circulate in the population, but might be a result of spontaneous changes."

»» Read More

Referral: EM on The common cold and influenza

 

 

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Revere at Effect Measure today looks at some recent reports that suggest that when the common cold (Rhinovirus) is circulating it might reduce the spread of the influenza virus. 

The idea made headlines a couple of days ago, and was covered in The New Scientist by Debora MacKenzie.

 

Common cold may hold off swine flu

• 12 November 2009 by Debora MacKenzie

A VIRUS that causes the common cold may be saving people from swine flu. If this intriguing idea turns out to be true, it would explain why swine flu's autumn wave has been slow to take off in some countries and point to new ways to fight flu.

 

"It is really surprising that there has not been more pandemic flu activity in many European countries," says Arnold Monto, an epidemiologist at the University of Michigan, Ann Arbor.

 

It is really surprising that there has not been more pandemic flu activity in many European countries.

 

In France, flu cases rose in early September, then stayed at about 160 per 100,000 people until late October, when numbers started rising again. The delayed rise was puzzling, says Jean-Sebastien Casalegno of the French national flu lab at the University of Lyon.

(Continue . . . )

 

Read Revere’s take in:

The common cold and influenza

»» Read More

Alan Sipress: Playing chicken with a nightmare flu

 

 

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From the Washington Post today, an outlook & Opinion column by Alan Sipress, WaPo’s economics editor and the author of the book "The Fatal Strain: On the Trail of Avian Flu and the Coming Pandemic."

 

Sipress has spent years on the trail of avian flu, traveling across much of Asia as he filed reports.   He gives us some deep background into the concerns held by many scientists that the H5N1 avian flu virus could meet up with, and swap genetic material, with the pandemic H1N1 virus.

 

The result could be a new, highly virulent, and easily transmissible pandemic virus.

 

While we know such reassortments are possible, we don’t know how likely it is to happen with these two viruses.  The mere possibility, however, is enough to keep some scientists up at night.

 

While speculative, this WaPo feature is well worth reading in its entirety.  When you return, a referral to a review by Crof of Sipress’s book, which he calls `the best pandemic book yet’.

 

Playing chicken with a nightmare flu

By Alan Sipress

Sunday, November 15, 2009

When swine flu erupted this spring in the southwestern United States and Mexico, it had been 40 years since the last flu pandemic. The outbreak has dispelled any illusion that pandemic influenza belonged to a bygone era, like smallpox, polio or scarlet fever. But we haven't seen how bad things might yet get.

 

What's the worst-case scenario? It could be a continuing vaccine shortage. It might be a mutation in the swine flu virus that suddenly makes the strain resistant to Tamiflu, as some seasonal flu strains already are. Or it could be that hospital ICUs become so overwhelmed that people who could have been saved die.

 

These are all unnerving possibilities. Yet many flu specialists say their real nightmare is that swine flu could meet up and swap genetic material -- or reassort, as these scientists say -- with another, deadlier flu strain, breeding a new virus that is as contagious as H1N1 but far more savage.

(Continue . . . )

 

 

Crawford Kilian, when he isn’t writing Crofsblog is a frequent contributor to The Tyee, where earlier this week he published a review of Alan Sipress's book The Fatal Strain: On the Trail of Avian Flu and The Coming Pandemic.

 

A brief snippet and a link to follow to read it in its entirety.

 

What Bird Flu Can Teach Us about Swine Flu

Secrecy and cultural bias are enemies. Information insures more survivors.

By Crawford Kilian, 12 Nov 2009, TheTyee.ca

• The Fatal Strain: On the Trail of Avian Flu and The Coming Pandemic
• Alan Sipress
• Viking (2009)

This book looks like a victim of bad timing: Washington Post reporter Alan Sipress covered bird flu in the hot-zone countries, wrote this account, and got blindsided by swine flu's eruption last spring.

 

No matter. This is the essential prehistory of the present pandemic, and of the next one -- which could well be bird flu after all. It also raises issues about the interaction (or lack thereof) between new and old media.

(Continue . .. )

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The Mutating Story

 

 

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Several times over the past few months we’ve seen press accounts that suggest  that the novel H1N1 `swine’ flu has `mutated’ into a more virulent strain.  

 

While some minor variations have been detected, so far, we’ve not seen any scientific evidence of any `serious’ mutations in the virus. 

 

Despite these newspaper accounts.

 

`Serious’ meaning changes that would make the vaccine less effective, or that would render antivirals ineffective, or increase the transmissibility or virulence of the virus.

 

There have been a few dozen reports of Tamiflu resistant viruses, but little to suggest that they are spreading widely at this time. 

 

Could it happen?    Sure.

 

And some scientists are surprised we haven’t seen more variation in the virus than we have to date.   Based on the (admittedly limited) genetic sequencing that’s been done around the world, the virus appears to remain remarkably stable.

 

First, an excellent background story on one of the labs in the United States, at the University of California San Francisco, that is doing "deep sequencing” of swine flu virus samples, looking for dangerous mutations.   

 

Then we’ll talk a bit about how mutations occur. Go ahead and read the whole thing.  I’ll wait.

 

 

UCSF scientists track swine flu virus for tiny changes that would cause big problems

By Lisa M. Krieger

lkrieger@mercurynews.com

Posted: 10/31/2009 08:55:00 PM PDT

 

SAN FRANCISCO — As the H1N1 flu virus spreads at breakneck speed, a team of local scientists are close behind. They are watching its evolution through a cutting-edge technology in hopes of answering the question: Where did it come from — and where is it going?

 

Their lab at the University of California-San Francisco holds a growing international collection of viral samples, including some from San Jose swabbed from the noses of sick people, since the first days of the swine flu epidemic. Genetic analysis of each sample will alert researchers to any tiny change that would create a giant problem.

 

So far, the swine flu virus seems to be evolving slowly. But a small mutation could create resistance to drugs.

 

The scientific sleuths are most worried about a big genetic leap — such as in 1918, when a mild virus turned deadly, killing 20 million to 40 million people. If such a leap does happen, the lab hopes to detect it early, triggering more aggressive treatment, quarantining and prevention measures.

 

(Continue . . . )

 

Viruses, and particularly influenza viruses, are infamous for their ability to mutate or change in relatively short periods of time.  Of course, it isn’t enough for a mutation to occur.  

 

The mutated virus must also be `biologically fit’ enough to replicate (preferably as - or more - efficiently than it's predecessor), and able to transmit efficiently to other hosts.  

 

Otherwise, it becomes an evolutionary dead-end.

 

The two most common ways for a flu virus to mutate are by making `replication errors’ in it’s genetic sequence, or by combining or reassorting with another virus.   

 

A little science.  Don’t worry, I’ll try keep to this at the junior high school level, as that’s about all I am capable of.

 

Real scientists, for their own sanity, should avert their eyes from this intentionally simplified explanation.

 

Let’s look first at how a replication error might occur.

 

The genetic sequence of the flu virus can be represented by the letters of the amino acids that make up the viral genome. These are long chains comprised of hundreds of amino acid molecules.

 

A tiny sub-section of that chain might have a sequence something like:

   NPECESLSTASSWSYI

As the virus inhabits a cell, and begins to replicate, it makes thousands of copies of itself which then burst out of the cell after a few hours and go on to infect other cells.

 

Those cells, in turn, make copies that go forth to infect more cells.

 

But being a single-strand RNA virus, the influenza virus tends to be sloppy in making copies of itself. Errors sometimes creep in. If in the process of replicating it mixes up just a single amino acid, we can end up with a mutated virus.

 

NPECESLSTASSWSYI
NPECKSLSTASSWSYI           < – A mutation!
NPECKSLSTASSWSYI            
NPECKSLSTASSWSYI                
NPECKSLSTASSWSYI               

 

Above, I’ve swapped out the amino acid Glutamic acid (E) at position 5 for Lysine (K). Assuming the result is a `biologically fit’ and competitive virus (most aren’t), then it may go on to infect other cells, and conceivably, other hosts.

 

Of course, that doesn’t mean it will make the virus more dangerous.  A mutation can make the virus less virulent or less transmissible.  Or it may simply have no effect at all.

 

These small changes in the virus are called antigenic drift, and over time changes in the virus can accumulate to the point that last year’s vaccine is no longer effective.  They can also bring about antiviral resistance, or even increase the virulence or transmissibility of the virus.

 

Big jumps, or mutations in the virus generally come about through a process called reassortment.  And that happens when two different flu strains inhabit the same host (human or otherwise) at the same time.

That isn’t as rare as you might think.

In a study entitled:

Aetiology of influenza-like illness in adults includes parainfluenzavirus type 4
J Med Microbiol 58 (2009), 408-413; DOI: 10.1099/jmm.0.006098-0

. . .   more than 10% of those tested had two or more concurrent viral (but not necessarily influenza) infections.

 

It is possible for two compatible flu viruses to swap genetic material and produce a hybrid virus. This is called reassortment, or antigenic shift. The result can be a new – or novel – virus to which humans have little or no immunity.

 

This is how pandemics occur.

 

 

Once again, most reassortments and mutations are evolutionary dead-ends. But every once in great while, we get a new, `fit’ virus that takes off. Which is exactly how the current H1N1 swine flu virus came to be.

 

It is the end result of multiple reassortments of swine, human, and avian viruses in pigs over the years.

 

While the odds of a mutation or a reassortment occurring in any one person (or animal host) is extremely low, when you spread a virus across millions (or tens of millions) of hosts, you increase the odds dramatically.

 

Which is why scientists are watching so carefully for any change to the virus.

 

But the first indication of a change may not come from a laboratory. It will probably come from an observed change in the way the virus behaves, or presents in patients; a change in patient age profiles, a change in severity or mortality, or a resistance to antivirals.

 

So we keep an eye on reports, like the ones we are seeing out of the Ukraine and India this week, for hints that something may be changing with this virus.

 

So far, we’ve been lucky. Similar reports in Argentina and Mexico have not led to the discovery of a more virulent strain.

 

Hopefully our luck continues to hold.

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IDSA: Kids Shed Virus Longer Than Adults

 

# 3913

 

 

More evidence, presented at the IDSA (the Infectious Diseases Society of America) in Philadelphia this week, indicating that children shed the influenza virus longer than adults.  

 

This isn’t the first time we’ve heard this sort of data (see Swine Flu: The Gift That Keeps On Giving).

 

The guidance from the CDC for staying home, and not going to work or school, has been scaled back from at least 7 days or 24 hours after symptoms disappear – to 24 hours after fever is gone (without using fever reducing drugs).  

 

Which means that some people may be returning to work or school following an illness while still shedding the virus.

 

Whether this really makes much of a difference is debatable. 

 

Shedding enough virus to be detectable by today’s modern RT-PCR testing or culture, and being contagious and able to spread the virus, may be two entirely different propositions.  

 

It it is believed that people can shed the flu virus for to 24 hours before ever showing symptoms – and that some may carry the virus asymptomatically, and spread the virus to others - without ever falling ill themselves (see They Walk Among Us ).

 

All of which makes it virtually impossible to keep the virus out of the schools and workplace.  Since you can’t tell who is shedding the virus and who isn’t, the only real defense is to get vaccinated, and to practice good flu hygiene. 

 

This report from Medpage Today.

 

 

IDSA: Kids Shed H1N1 Flu Longer than Adults

By Michael Smith, North American Correspondent, MedPage Today
Published: October 30, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine.

 

PHILADELPHIA -- Children appear to shed particles of the H1N1 pandemic flu virus longer than adults do, which may have implications for how long they stay out of school, a researcher said here.

 

The finding comes from an analysis of an outbreak in a Pennsylvania elementary school in May and June, according to Achuyt Bhattarai, MD, of the CDC.

 

Analysis of a series of specimens from affected children and their household contacts also showed that younger children tended to shed the virus longer than older kids, Bhattarai told attendees at the annual meeting of the Infectious Diseases Society of America.

(Continue . . .)

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Quiz: When Viruses Attack

 

 

# 3726

 

 

Newsweek has an interesting quiz on their website, which asks about a dozen multiple choice questions about viruses and emerging infectious diseases. 

 

The questions start off easy enough, but get a bit harder towards the end.

 

 

 

I’m a bit chagrined to admit that I missed one of the questions (#12), but I came up with a respectable 92%. 

 

Take the test, and see if you can beat my score.

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