Archive for the ‘viral diseases’ Category

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.


Don't vacillate, vaccinate instead!

Wednesday, March 21st, 2012

Could she have measles?

The Wall Street Journal this morning had an article titled, "Where Could The Next Outbreak Of Measles Be?" A secondary heading on a later page said, "Low Vaccination Rates Trigger Fears," and there was a US map showing problem areas. Boulder, Colorado was one of those hot spots.

The article led me back to the concept of "herd immunity," very well illustrated on a webpage from the National Institute of Allergy and Infectious Diseases. Basically it says we need a relatively high percentage of a given population to be vaccinated (AKA immunized) against a given disease in order to prevent epidemics.

The particular viral disease I'm writing about is measles, sometimes called "red measles" or, technically, rubeola. The National Library of Medicine has an excellent, brief description of this ailment and notes that before widespread vaccination became common, most people had a case of measles before age 20.

Then the MMR vaccine was developed by a Merck scientist in the 1960s. Measles incidence went from being, as a 1954 quote termed it, "as inevitable as death and taxes," to an uncommon to rare disease in developed countries. In the US for the twenty years after the vaccine was licensed, an estimated 52 million overall cases, 17,400 leading to mental retardation and 5,200 deaths were prevented.

In 2000 the WHO estimated that there were still ~45 million cases of measles worldwide yearly causing 800,000 deaths. While mortality in developed countries was ~1/1000, in sub-Saharan Africa, mortality was 10%. In cases with complications, the rate could rise to 20–30%. On average, ~450 children died every day from measles. By 2007 immunizations had cut the yearly global death rate by 75%.

But in 1998 an article in The Lancet had caused a stir that has continued to this day. A British gastroenterologist reported a series of 12 young patients who were referred to his practice with bowel complaints. Their average age was six and 8 of them developed symptoms of autism within a month after they got their MMR injection.

Should I believe what I just read?

Many parents hearing about this report stopped their children's immunizations. This was in spite of numerous much larger studies showing no connection between MMR and autism. In 2005 a Japanese group showed an increase in autism diagnoses in children who got their childhood immunizations after the country's particular MMR vaccine was withdrawn from use because of a suspected side effect of the mumps component. In 2009 a review of multiple large studies was published examining three linkages that had been proposed: MMR and autism, thiomerosal (a mercury-based preservative chemical used in some vaccines, but not in MMR) and autism, multiple vaccinations and autism.

The accumulated data from these large groups in a number of countries showed no association between any of these factors and autism. Finally in 2010 The Lancet published a rather wishy-washy retraction of the Wakefield article.  His license had been revoked by the UK General Medical Council and the British Medical Journal's editorial staff published a much stronger condemnation of Wakefield's work in 2011, calling it fraudulent.

And yet today's WSJ article note parts of the US, especially in the northwest, have relatively poor compliance rates with vaccination guidelines. Parents can opt out because of medical, religious or even philosophical concerns. Low-income kids can receive free immunizations under a federally-funded programs, but one physician interviewed said the parents in his practice who don't want their kids vaccinated are wealthy and well-educated.

We've seen some minor outbreaks in the past few years. If we don't overcome parental misinformation and fears, we may have a major epidemic.


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%