Wednesday, June 16, 2010

The bugs are winning

kw: book reviews, nonfiction, medicine, pandemics

This is one face of a pandemic (Image from this Wikipedia article). The colors indicate accredited cases of H1N1 influenza in 2009 by country, from 50,000 or more (black) through brick red and red to pink, in steps from 5,000, 500, 50 to 5, to the palest pink of between 1 and 4 cases.

The color pattern shows, for one, that H1N1 was spread by tourists, so those areas too poor to attract many tourists were actually largely spared. As influenza outbreaks go, this was a mediocre one, having led to "only" 12,000 excess deaths in the U.S. Compare this with more ordinary flu seasons, in which excess mortality ranges from 5,000 to nearly 70,000, averaging 36,000. On average, in the U.S. at least, influenza is on a par with auto accidents as a cause of death.

Let's put this against the backdrop of a real epidemic, one that goes on and on: Malaria, which infects about half a billion people and kills between one and three million yearly (a more accurate figure is not known). That makes the malaria parasite the most dangerous pathogen, and the mosquito the most dangerous vector, on Earth.

In 2002 Madeline Drexler published Secret Agents: The Menace of Emerging Infections. The 2003 paperback has recently been reissued with a new chapter and a new title, Emerging Epidemics: The Menace of New Infections. A blurb on the cover scratches the surface of the content, mentioning H1N1 flu, SARS, anthrax, and E. coli.

An opening chapter presents some recent history and enough bacteriology to help us understand the phrase, "A millennium in a fortnight", meaning that microbes evolve about 25,000 times as rapidly as humans. It is actually worse than that. A human generation is 20-30 years; a bacterium's generation is 20-30 minutes. There are half a million minutes in a year… This ushers in a major theme of the book, that viruses, bacteria and protozoans can quickly evolve ways to tolerate or defeat the medicines we use in our attempts to eradicate the diseases they cause. (A case in point is Penicillin, which went into widespread use in the early 1940s during World War II, and was losing effectiveness by the time I was born in 1947. By the time I was ten, I'd had my last Penicillin shot.)

The mosquito-borne disease theme is used in Chapter 2, focusing on the West Nile irruption a few years ago, to illustrate just how chancy is our public health system. It took the incredible persistence of a zoo veterinarian, who happened to be a middle-aged woman whose questions and date were ignored for months, for the CDC and other "official" medical organizations to recognize the connection between a rash of dead birds and a syndrome they at first attributed to St. Louis encephalitis. The dots are still not connected. How West Nile virus traveled to New York is still unknown.

In areas of the world that are free of malaria, the most frequent disease outbreaks are foodborne, including E. coli O157:H7, Listeria, Salmonella, Chlamydia, Campylobacter and Cyclospora. The third chapter focuses on these and on the difficulty of discerning a genuine outbreak from sporadic clusters: separating the signal from the noise. In a 1998 case of widely-scattered clusters of Shigella toxin poisoning, the trouble was finally traced to a single parsley grower in Mexico, from where fresh parsley was distributed worldwide. It made me look askance at the next parsley-garnished bowl of soup I ate at a restaurant. Nobody really eats the stuff; why use it?

The scariest chapter is the fourth, on superbugs, including MRSA and VRE (multiply resistant Staphylococcus aureus and Vancomycin resistant enterococci), plus the aforementioned E. coli strain and multiply resistant TB. The author points out that all antibiotics so far developed are members of just 16 molecular families, and every one of them is resisted by at least one organism. The thing about bacteria, they all seem to be a single, highly-variable species, because they all can have a kind of single-celled sex and exchange DNA. Certain viruses that prey on bacteria only make things worse, because they also inject DNA into the bacteria that may carry either resistance factors or "virulence factors" that make it easier for a pathogen to spread among us. I remember learning years ago that we all have plenty of Streptococcus living in and on us. It is only when the Strep is attacked by a certain virus that it makes a toxin, manufactured using the virus's DNA, and the toxin produces "strep throat". We get sick because one of our "passengers" is sick! The scary point: we are all out of weapons with which to fight certain battles.

Chapter 5 focuses not just on influenza, but on the 1918 pandemic that was so deadly, it killed more people than the bullets and bombs of World War I. It could return, or something like it. The 2009 pandemic was a weaker relative, which spread almost as fast, but wasn't nearly as deadly. By the way, H1 and N1 refer to protein factors that stud the surface of influenza virus particles. There are 15 H types and 9 N types, leading to 135 basic serotypes, each of which comes in other variations based on internal DNA variations. That is what makes it necessary to produce one or more new flu vaccines every year.

Chronic diseases were once considered to have other causes, such as "bad" cholesterol (heart and vascular disease), "autoimmune dysfunction" (arthritis and diabetes), excess stomach acid (ulcers), and random genetic damage (cancer). Evidence is accumulating that all of these, and others, are actually the result, or side effects, of infections. These days, your ulcer can be eradicated by a round of antibiotics. Maybe someday, an antimicrobial treatment will eradicate heart disease, cancer, and even juvenile diabetes. What'll kill old folks when there's no more chronic diseases? Maybe then we'll find out about "just dying from old age."

The seventh chapter treats of bioterror, going into quite a detailed history of germ warfare since the Medieval practice of throwing rotting bodies into besieged towns with catapults, and the use of "smallpox blankets" to decimate one Native American tribe 250 years ago; but focused much more on the U.S. and U.S.S.R. programs during the cold war. While "weaponized pathogen" stockpiles are reduced at present, there is still an uncomfortable tonnage of bio-weapons in existence, and it is evident that there are numbers of disaffected terrorists crazy enough to use them if they can steal some.

The last chapter tackles the information question. The public health apparatus has performed poorly in the past, and is still unready in the face of discerning a bioterror case from a restauranteur's error. There is hope that an internet tool such as ProMED will enable the right people to connect the dots sooner. It worked "sort of well" for SARS a few years ago. Newer web sites like GVFI (Global Viral Forecasting Initiative) are a big step in the right direction. I see a problem, though, that too many such initiatives will cause even more noise in the system, until they settle out to two or three really good ones.

What are the chances that a really nasty bug will come along and kill 10%, or even 50%, of the human population? Asteroid fans, take note: The chances are much, much greater than the chance of a 10-km asteroid such as the one that wiped out the dinosaurs. Our own lack of readiness is our greatest risk.

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