Infection Connection

Are you under the influence? I hope not, but if so, get to bed and get some rest, drink lots of fluids, and next year, you might want to consider getting the flu shot.

That's right, I'm not talking about your over-indulgence in certain alcoholic libations, you party animals, I'm talking about everyone's least favorite winter-time scourge, influenza. Influenza is the Italian word for influence, and it is believed to have gotten its name, long before the causative virus was discovered in 1933, because illness was once thought to be influenced by the stars.

Influenza has been around for thousands of years, but pandemics began to take place with the development of large cities in the 18th and 19th centuries. Human influenza developed as a result of close proximity to animals such as pigs, horses, and chickens, and that is still the case. In general, pandemic flu occurs every 25-30 years. (By the way, the difference between an epidemic and a pandemic is that an epidemic is more confined, e.g., to a daycare center or nursing home; a pandemic occurs over a large geographic area and affects the population at large.) It is widely accepted that there were three influenza pandemics in the 20th century, and the mother of them all was what is known as the Spanish Lady of 1918-19, and that is what I'll focus on here.

The 1918 outbreak is now realized to be one of the most widespread and lethal pandemics in world history in terms of deaths. In the United States, some 550,000 people died...more than the military deaths in both World Wars, Korea, and Vietnam. Combined. In beleaguered cities, social services ground to a halt as police officers, firefighters, telephone operators, and garbage collectors fell ill. Schools were closed and businesses were shuttered as public health officials tried in vain to halt the spread of the disease. Cities had to resort to mass graves, as the number of dead grew too large to accommodate individual graves. When both parents died from the flu, orphan children wandered the streets.

By the time the pandemic ended in 1919, it was originally thought that 40-50 million people had died worldwide. Current estimates are 50-100 million. At that time, influenza was not a reportable disease, and not tracked by public health agencies, so records are spotty. But based on descriptions of various illnesses at that time, and the widespread infection rate (up to 20%), it's certain that tens of millions died.

So what made this strain such a killer? Take a look at this chart of deaths by age group. See the U-shaped curve with the dotted line? That's how influenza normally behaves. It kills more children and the elderly. The 1918 strain affected those groups as well, but also seemed to target the young and healthy, as shown on the graph by the solid line. The virus spread like wildfire through military bases, killing many young men in the prime of their life. After the pandemic ended, the strain of virus seemed to vanish into oblivion, with the same symptoms never occurring again. For many years, the virulence of that particular strain was a mystery. All influenza viruses have the usual virulence factors, such as Hemagglutinin, a protein that causes the viruses to stick to the host cell, and Neuraminidase, an enzyme that aids in allowing a virus to enter the host cell; it also aids in the release of replicated viruses produced in infected cells. If you see the notation H5N1, for example, that is how avian influenza is characterized. But there had to be more there in the 1918 strain than the typical virulence factors.

In the late 1990's, a team of scientists found the body of an Inuit woman, a 1918 influenza victim, buried in a mass grave in Alaska. They found well-preserved viral material in her lungs, and they recovered enough viral RNA that they were able uncover the complete gene sequence of the strain that for decades they thought was gone from history (it is characterized as an H1N1 strain). Using this "reanimated" virus, another team of scientists was able to conduct tests (in BioSafety Level 4 conditions--suits and air hoses--of course) that resulted in the discovery of at least one virulence mechanism: in the host, this strain triggers an immune response that is often called a cytokine storm. Massive amounts of chemicals and disease-fighting cells pour into the lungs, resulting in such an accumulation of cellular material and fluids that the victim literally drowns. A similar mechanism has been found with avian influenza, which fortunately is not easily passed from human to human. For now. There is still much to be discovered about the 1918 strain, but what an amazing start, and a possible clue to how to respond more effectively to current strains.

This is one of the reasons I get a flu shot every year! Now, if such a killer strain emerges again (and in my humble opinion, I believe it will), it will be an unexpected strain that has mutated via antigenic shift. The flu vaccine will not fully protect against such a different strain. But there may be enough protection to keep you from the worst case scenario. (That would be death.) That's one of the reasons influenza is such a nasty and unpredictable bug--it's the mother of multiple mutations. If you get a particular strain of influenza, your body puts up a good fight and triggers an immune response...hey presto, you've got antibodies to that strain and won't get it again. But the virus changes from year to year via antigenic drift. These are subtle changes in the virus's RNA makeup, but they are enough that your body is unable to recognize it as a strain it's encountered before, and thus the antibodies from the previous strain aren't released. Still with me? There is no such thing as a natural immunity to influenza. To a particular strain, yes, but that particular strain isn't going to exist next year...it's going to change its makeup just enough so that your immune response won't be full and immediate.

The flu vaccine isn't 100%, and the production depends upon the trends of the previous year. Scientists and doctors do their best to track various strains and figure out what will be the prevalent strains the following year, and include those in the vaccine. This doesn't always work, and last year, we saw a strain that wasn't included in the vaccine. Some of my work pals got it and were laid low for quite a while. But a flu shot can help protect you, your loved ones, and the community in general. Call your doctor, or your county health department, for more information. The county health department should have low-cost or no-cost options for you.

Stay healthy this year, and may all your influences be good ones!

Sources:

University of Wisconsin-Madison (2007, January 17). Lethal Secret Of 1918 Influenza Virus Uncovered. ScienceDaily. Retrieved November 13, 2008, from http://www.sciencedaily.com­ /releases/2007/01/070117134419.htm

NIH/National Institute of Allergy and Infectious Diseases (2007, July 4). Scientists Describe How 1918 Influenza Virus Sample Was Exhumed In Alaska. ScienceDaily. Retrieved November 13, 2008, from http://www.sciencedaily.com­ /releases/2007/07/070702145610.htm

Nikiforuk, Andrew. The Fourth Horseman. London: Phoenix; 1993

Kolata, Gina. Flu: The Story of the Great Influenza Pandemic of 1918 and the Search for the Virus that Caused It. New York: Farrar, Straus and Giroux; 1999