Archive for the ‘influenza’ Category

Coughs, colds and flu Part 2: what's new with flu?

Thursday, January 17th, 2013

Like we always do, we got our flu shots early, this year on the day after they first became available. Several friends said they were going to wait a few months; I'm always concerned that the supply of vaccine will be gone by then and as former Air Force medical staff, we got in the habit of being told, "It's time for your flu shot." Our timing was excellent; flu struck earlier than usual (it typically peaks in February). And the New York State Department of Health agreed that the best time to get a flu shot is as soon as the vaccine is available.

This is a bad flu season with not only an early peak in case numbers, but also an unusual virus. I looked at the flu primer, updated for the 2012-2013 season, by arstechnica, a technology news and information website. The influenza virus has an outer layer of proteins around its genetic material core; the specific proteins of the coating determine what kind of cells the flu bug can attach to and therefore infect  (they also act as chemicals that our immune system can react to), while the inside core lets the virus take over the cell and make new viral particles.

flu virus with Hs and Ns sticking out; I think of them as arms and legs

The most important proteins in the outside coating are called hemagglutinin (H) and neuraminidase (N); there are a variety of each with the CDC saying there are 16 different Hs and 9 Ns. Three variants, H1N1, H1N3 and H3N2, are currently infecting humans while the highly pathogenic H5N1 avian flu was of major concern in recent years. As of January 5th, 2013, the influenza A H3N2 virus was the predominant strain causing flu in the United States.

There are three types of influenza viruses, logically enough labeled types A, B and C. Type A can affect both humans and some animals and is responsible for the largest and most widespread  outbreaks termed pandemics. Type B only occurs in people and usually is responsible for less severe reactions; it is not classified by subtypes and isn't responsible for pandemics. Type C, also only a human strain, doesn't cause epidemics, much less pandemics and doesn't lead to severe illness. The yearly vaccine protects against two type A strains (H1N1 and H3N2) and one type B virus with specific viruses chosen based on scientific estimations of what the coming year's flu will most likely be. The CDC webpage titled "Key Facts about Seasonal Flu Vaccine" mentions three different flu shot varieties and one nasal vaccine; the shots are all made from inactivated viruses (one is a high-dose form designed for those of us 65 and older). The nasal spray is made from live attenuated (weakened) viruses and can be given to anyone age 2 to 49 who is not pregnant and is otherwise healthy.

Now civilian hospitals in a number of areas have fired staff members who refused to get vaccinated for influenza. Some of those former hospital employees are threatening to sue, but my own viewpoint is the hospitals have done the right thing. The last thing I think they need is their own docs, nurses, techs and other staff infecting patients who are already ill with something that may make them more likely to have flu complications.

What about pregnant women who work for the hospital? Should they get flu shots or does that place their fetuses at risk? I wasn't sure until I saw the 1-16-2013 edition of the New England Journal of  Medicine. A Norwegian study performed during the 2009 flu pandemic had convincing figures: there were 117,347 eligible pregnancies and 54% of the women were vaccinated in their second or third trimester with substantial reduction in moms getting the flu.

Pregnant women in this study who did have influenza had an increased risk of fetal death. Vaccination did not increase fetal mortality (and may actually have reduced it).

epidemics are many more cases than usual; pandemics have widespread cases

The real problem with bad cases of flu is bacterial coinfection, often with "bugs" that colonize our nasopharynx area: staph aureus, strep pneumoniae and strep pyogenes. This highly significant flu complication was present in almost everyone who died in the great flu pandemic in 1918 and, even today, with our panoply of antibiotics, frequently occurs in influenza victims who require ICU care. A third of those needing such intensive care in the 2009 H1N1 pandemic had such a combined illness.

The CDC has a superb webpage, "What you should know for the 2012-2013 Influenza Season," and I strongly recommend using that as a source.

Here's hoping you get a yearly vaccination and don't ever get the flu.


The 1918 flu virus and its descendants: Part 2 Rediscovering the culprit

Sunday, May 13th, 2012

many other major pandemics were associated with rodents, but not the 1918 flu

I re-read my last post a day after writing it and amended the first line, since I found it misleading. It was the worst flu pandemic ever, but I knew that smallpox, the Black Plague, AIDS, malaria and perhaps even typhus each have caused nearly as many or even more deaths over a period of years. I eventually found a rather strange, non-medical website with the "7 Worst Killer Plagues in history," and confirmed my belief that no other bacteria or virus had wreaked as much havoc in brief span of time as the 1918-1919 H1N1 influenza virus.

I wanted to find out what happened to that highly pathogenic organism and, after searching the web, realized the PBS article on the "Spanish flu" was a good place to start. It mentions that the influenza virus was not identified until 1933 and that the actual genetic identity of the particular strain involved in that pandemic (as opposed to the basic type...H1N1) was not identified for many years. The influenza virus responsible for the 1918-1919 pandemic has had many descendants, none as deadly as their ancestor.

In 1950, Johan V Hultin, a graduate student starting his doctoral studies in microbiology, got a clue from a visiting professor who suggested hunting for the virus in bodies buried 32 years prior in the permafrost of the Arctic. Hultin and his faculty advisor traveled to Alaska where flu among the Inuits had been especially deadly with 50 to 100% death rates in five villages.

early days in the Far North

Gold miners, under contract with the Territorial government, had served as grave diggers in 1918-1919 and tissue samples were recovered from four bodies exhumed in 1951. Pathology slides fit with viral lung damage and, in some cases, secondary bacterial pneumonia. But tissue cultures from the samples did not cause disease in ferrets and no influenza virus was recovered.

It wasn't until 1995 that science had advanced enough to for researchers to start the work necessary to identify the virus's unique features. Jeffrey Taubenberger, a molecular pathologist then working at the Armed Forces Institute of Pathology (AFIP), began a ten-plus-year-long project starting with autopsy tissues from the time of the pandemic that had been preserved in the National Tissue Repository. His project was stimulated by a paper published in the journal Science in February, 1995, in which preserved tissue samples from the famous British scientist John Dalton (often called the father of modern atomic theory) were examined. Dalton was color-blind and had donated his eyes at his death in 1844 to determine the cause of the defect; his DNA was studied 150 years later and the resultant publication gave Taubenberger the impetus to do the same with the flu virus.

Hultin read the first paper from Taubenberger's group, wrote to him and eventually went back to Alaska to exhume more flu victims. One was an obese woman whose lungs had the findings of acute viral infection. Samples of these permafrost-preserved tissue had RNA incredibly similar to those obtained from the AFIP National Tissue repository.

And so began an amazing chapter in the history of virology.

The 1918 flu and its descendants: part 1

Friday, May 11th, 2012

In some years this sign should be in red

The worst flu pandemic of all time began near the end of World War I, in the fall of 1918. It killed, in the next year, somewhere between 20 and 50 million people across the globe.  The comparison to WW I deaths, eight and a half million from all countries involved, is striking.

There had been major influenza pandemics before and since, some severe and some relatively mild. The term itself conventionally refers to a worldwide outbreak of an infectious disease with some adults in every continent (except Antarctica) involved, but doesn't imply how lethal the illness is.  For example the H1N1 "swine flu" pandemic in 2009-2010 involved 74 countries, but the death rate was relatively low.

Stanford University has a superb description of the so-called Spanish flu online. Usually flu kills the very young and the very old more than young adults; this time was different with far more deaths between the ages of 20 and 40 (some say 20-50 and others 15 to 34) than in the typical flu season. The influenza-related death rate, normally about 0.1%, has been estimated at 2.5 to 3% and may have been even higher. A fifth to a third of everyone alive at the time caught the virus, so half a billion victims may have been inflicted.

For Americans, including soldiers, the end of the war was near, but over 40,000 servicemen and nearly two-thirds of a million back home would die of this modern plague.

The precise origin of the disease is unclear; swine were affected in a nearly simultaneous fashion, but have not been blamed for the human ailment. The war itself and its resultant transportation of large numbers of troops, could have facilitated its spread globally. A first wave of the infection struck American army encampments in the United States, but was comparatively mild, at least when contrasted to the second and third outbreaks later in 1918 and then in 1919.

He was at risk as well

Public health measures were widely instituted, but the actual effectiveness of quarantine, gauze face masks, limited school closures and banning of public events is unknown.

In the midst of what for many was a typical flu infection, some developed a highly virulent form of the disease, with a strikingly abrupt onset, fever, exhaustion and rapid progression to pulmonary complications and death.

Many cases developed secondary bacterial infections and one species of bacteria was initially blamed for the disease. Then two French scientists reported a filter-passing virus in the British Medical Journal in November 1918. They used filtration to remove bacteria from the sputum coughed up by a flu patient and then injected the remaining fluid into the the eyes and noses of two monkeys. After their primate subjects were noted to have fevers, a human volunteer was given a subcutaneous injection of the same filtrate. He was the only person in their laboratory to develop the flu.

The extraordinary mortality rate of the 1918 influenza is shown on a graph plotting deaths in America from a variety of common infectious diseases over the years from 1900 to 1970. Another way to gauge the impact of the pandemic is to note that average life expectancy in the United States fell by ten years for that period.

And yet the incidence of influenza ebbed and since 1920 we've returned to the normal cycle of seasonal flu, intermittent epidemics and occasional pandemics, none as severe and deadly as the Great Flu of 1918-1919.


Influenza H5N1 HPAI research: lots of viewpoints

Friday, March 16th, 2012

When experts disagree, who should we believe?

Shortly after I wrote my post on the dangers of H5N1 HPAI, my weekly copy of JAMA, AKA the Journal of the American Medical Association, arrived containing a commentary titled "International Debate Erupts over Research on Potentially Dangerous Flu Strains." The pros and cons of release of the two groups' research were discussed and the rationale for publishing the methods and details was explained.

One expert in the field had a balanced view. He felt release of the details of the recent research on H5N1 HPAI might be extremely useful to  those who evaluate which strains of influenza are about to pose a real threat to humans and could potentially cause epidemics. Doing so might provide lead time for other scientists who work on vaccines to prevent wider spread of the particular strain of flu.

But in a January, 2012 online discussion of the controversy the head of a university Center for Biosecurity felt the lives of hundreds of millions of people could be at risk if such an engineered virus strain were to be released, even accidentally. He feels that continued research would require the level of biosecurity utilized with other dire agents such as smallpox.

The first infectious disease specialist countered with the concept that H5N1 HPAI wasn't an especially likely pick for those interested in bioterroism. It's certainly not a selective weapon and its use would require considerable expertise.

The second expert noted there had been no data that such a strain of flu would ever develop naturally, outside the lab, and we had to return to the concept of weighing potential harm versus good.

Now the original researchers have stated that the new viral subtype isn't as deadly as feared; it hasn't killed the ferrets being used as laboratory substitutes for humans and has proven to be controllable with vaccines and antiviral medications. Because of ethical limitations it hasn't been tried on human subjects and they don't know whether it even could be spread among humans.

And which of these is the worst?

I think we're treading very close to the edge here. I don't look forward to widespread beneficial effects of complete publication of the ongoing lab research results. And I do fear the possibility of groups who don't care if they kill off a third of everyone, including their own followers. Accidental release of a lab-engineered organism into the human population could also happen, even if unlikely.

Another online article said the work on the mutant form of H5N1 had been performed in BS-3 labs, used for studying agents that can cause serious or lethal disease, but do not ordinarily spread among humans and have existing preventives or treatments.

A GAO 2009 report counted 400 accidents at BS-3 labs in the previous decade. Scientists argued that the H5N1 HPAI studies must be moved to BS-4 labs with one professor stating, "An escape would still produce the worst pandemic in history." Yet between 1978 and 1999, over 1,200 people acquired deadly microbes from BS-4 laboratories, the biosafety-4 level facilities that normally deal with infectious agents that have no known preventive measures or treatment.

Scandia National Laboratory's International Biological Threat Reduction program directed by Ren Salerno has a worldwide ongoing effort to prevent laboratory accidents, but there are varying standards for biosafety and at least 18 BS-4 labs outside of the US as of 2011.

So I'm still worried.


The "sex life" of a virus

Saturday, March 10th, 2012

The double helix

Most of us who are adults (and many who are not) have personal knowledge of human sexual reproduction, the process by which a man and a woman each contribute genetic material that contains DNA (deoxyribonucleic acid), the chemical basis of new life. DNA is an incredibly long twisted molecule. Its structure is a double helix with two strands composed of a sugar-phosphate backbone linked by four specific chemicals: adenine (A), thymine (T), cytosine (C) and guanine (G). These are called bases and match up in specific pairs, A always with T and G with C.

DNA has an amazing ability to replicate itself; the strands separate and each becomes the pattern for a duplicate to be constructed. Occasional mistakes are made, but we have a cleanup chemical, DNA polymerase, a kind of automatic spellchecker, that makes corrections.

Our human DNA has about 3 billion pairs of these bases; yours and mine and Cousin Flo's will be 99% identical. The remaining 1% is what makes the difference between an Einstein, a sports hero, a jazz musician and you and me. Our DNA is 98% the same as a chimpanzees and 85% the same as a mouse, but these comparisons clearly understate the importance a single base pair difference can make.

Viral "reproduction" is quite different. Influenza viruses don't have DNA; instead they contain RNA and have to replicate in living cells. Once they are inside one, the process results in many viral "offspring." These eventually leave to infect other cells in the organism and in doing so kill the one they replicated in. RNA (ribonucleic acid) is somewhat like DNA, but has one different base and a slightly different sugar in its "backbone." It's usually found as single strands shorter than those of DNA or, in the case of the flu virus, in seven or eight pieces. It lacks a proofreading enzyme so most of the new influenza virus copies are actually mutants.

Most of these changes, called antigenic drift, are minor. So the flu shot I get every year, which is an educated best guess as to what this years flu virus will be, offers considerable, but not total protection.

flu shots make sense

Sometimes the mutations are more significant; the process is called antigenic shift. That may occur when a host is infected with two different influenza viruses at the same time. The swine flu, for example, contained genes from pigs, humans and birds. When this happens, pandemics may occur.

Influenza is spread in several different ways: an infected person coughs or sneezes and you inhale the aerosolized virus; humans may come into direct contact with bird droppings or nasal secretions; various surfaces may become contaminated (viral particles in mucous may survive several weeks on banknotes).

Modern techniques for producing new flu vaccines rapidly may prevent millions of deaths and steps toward a "universal flu vaccine" are being researched. In the meantime logical precautions and yearly flu shots can save lives.



Viral Diseases: Influenza, Part 2

Thursday, March 8th, 2012

Homo Habilis, the first member of the genus Homo

I realized, as I wrote my last post, that I was using medical jargon that might make no sense to most readers. So I want to examine how the influenza virus is described by doctors, specialists in epidemics (AKA epidemiologists) and other scientifically-trained groups.

First of all let's briefly talk about how we classify everything that is alive. There's a complex system called taxonomy which is conventionally used to group separate different  groups of dissimilar and similar organisms. It has seven major layers, or taxa. Humans, for example,  belong to the kingdom Animalia, the phylum Chordata, the class Mammalia, the order Primata, the family Hominidae, the genus Homo and the species Homo sapiens. 

Flu viruses fall into three genuses, and those logically enough are called A, B and C.  The A type has only one species, lives in nature in wild aquatic birds (but can infect other animals), and causes the most severe diseases in humans. Subtypes of flu A can be identified by a variety of laboratory tests that determine which kind of two glycoproteins (complex chemicals that contain both carbohydrate and protein constituents) are found on the surface of the virus.

One of those is called hemagglutinin (H for short) and the other neauraminidase (N). There are 16 H types and 9 Ns; Hs bind the virus to a cell and help it insert its genetic information into that cell. Ns get involved later in the infection and help the virus release its "offspring" from the cells they were produced in.

Laboratory tests can show which H and N are present.  Both are antigens, substances that can cause an immune reaction if taken into your body by one route or another (e.g., breathing them in) and cause your body to produce antibodies, chemicals that are produced to combine with and counter the effects of the antigen. Some important influenza viruses are H1N1 which caused the 1918 Spanish Flu and the 2009 Swine flu, H2N2 (Asian flu of 1957), H3N2 (Hong Kong Flu 1968) and H5N1 (Bird Flu in 2004).

The CDC's short article on types of influenza viruses mentions there are seasonal epidemics nearly every winter in the United States; those are caused by type A or B, not by type C. All of the terrible flu pandemics have been caused by type A flu viruses. The B virus types are normally found only in humans (seals and ferrets are the only other animals that can be infected by flu B).

We get ours every year

Why is type A the killer? It mutates much more rapidly than B, usually by minor changes in the H and N  surface proteins, occasionally by sudden major changes. The first kind of change may alter the antigens you can be exposed to so the antibodies you've developed to fight off a flu infection don't work. That's also why the vaccine you get, which contains two A subtypes and one B strain, may not fully protect you. That's not a reason to skip your flu shot.

The other kind of mutation is more serious and I'll write about it next.


Viral diseases old and new: Let's just begin with the flu

Sunday, March 4th, 2012

A cause for alarm and action

Two days ago I began a post on zoonoses, diseases that spread from animals to humans. As usual, my interest led me from one fairly-limited topic to more-generalized subjects and I eventually decide to write a multi-post discussion of viral diseases that either have caused massive, widespread epidemics (AKA pandemics) or could potentially lead to them.

The number of deaths they have resulted in is staggering. HIV/AIDS has killed over 25 million of us in the past 30 years; the Black Plague over a 330-year period killed 75 million and smallpox is estimated to have caused over 300 million deaths over the centuries.

But let's start with influenza, the virus that we read about year after year as a worldwide threat. In the fall my wife and I get flu shots; we got used to doing so when we were both on active duty as Air Force medical staff personnel. It was routine; I didn't pay a lot of attention to what this year's shot contained and only vaguely kept up with anything written about the flu itself.

Then so-called "bird flu" came along and  the world geared up for a terrible pandemic.Usually the kind of influenza virus found in birds doesn't infect humans. But one unusual strain, called H5N1 (I'll explain what that means later) killed a six-year-old boy in Thailand in 2003. Of the people who caught this virus, 60 % died.

Most of us have heard about the Spanish flu, a major pandemic that infected a third of everyone living in 1918-1919 and caused 20 to 40 million deaths worldwide. Yet only 3% of those whom the virus infected died from it.

The so-called Asian flu pandemic in 1956-1958 causes 2 million deaths; the Hong Kong flu in 1968-1969 killed 1 million and the yearly seasonal flu results in anywhere from 5 to 15% of us getting ill; 250,000 to 500,000 die as a result. But these flu strains actually only resulted in a death ratio of less than 0.1%.

As it turned out, there was very little person to person spread of the avian flu. If there had been the results could have been catastrophic.

But the pigs had nothing to worry about; we did!

One of the outcomes of the avian H5N1 outbreak was fortuitous. When the "Swine flu" pandemic occurred in 2009-2010, the public health establishment and the medical community were considerably better prepared. The CDC summary is worth reading as it documents the steps taken to contain the virus; actually this was a flu strain that was transmitted from person to person and wasn't present in US pig herds.

The virus itself had genes from four different influenza virus sources, two from pigs, one from birds and one from a human flu virus. The CDC widely distributed kits to labs enabling them to identify the new viral strain. They and the World Health Organization (WHO) kept tabs on the numbers of cases of the new disease and WHO announced a global pandemic in June, 2009 .

A vaccine was developed with unusual speed and a preliminary target group of higher-risk individuals was identified; this consisted of 159 million people in the US. Vaccine safety was tested in various groups and the vaccine itself was administered starting in early October; by late December 2009 enough had been produced to allow vaccination of anyone wishing it.

The final results were impressive; less than two-thirds of a million people caught the virus and the death rate was 0.03%