Gut flora bacteria Source:

While researching yesterday’s blog, my interest was piqued by an interesting article in the journal Nature by none other than Jared Diamond and his colleagues at UCLA. It examined the origins of 15 temperate and 10 tropical diseases.


Why is it important?

This question is not only of practical importance to physicians, and to all the rest of us as potential victims, but also of intellectual interest to historians and evolutionary biologists. Historians increasingly recognize that infectious diseases have had major effects on the course of history; for example, on the European conquest of Native Americans and Pacific Islanders, the inability of Europeans to conquer the Old World tropics for many centuries, the failure of Napoleon’s invasion of Russia, and the failure of the French attempt to complete construction of a Panama Canal. Evolutionary biologists realize that infectious diseases, as a leading cause of human morbidity and mortality, have exerted important selective forces on our genomes.

But most important, it offers important clues as to what we can expect in the new world of urbanization, globalization, and climatic change. As George Santayana said, and everybody loves to misquote: “Those who cannot remember the past are condemned to repeat it,” (from Reason in Common Sense, the first volume of his Life of Reason).


5 stages of evolutionary development of a human infection

There are 5 stages through which a pathogen evolves, from exclusively infecting animals (stage 1) to one infecting exclusively humans (stage 5).

Of the 25 diseases examined, 17 impose the heaviest world burdens today. Of the 17 diseases, 8 are temperate (hepatitis B, influenza A, measles, pertussis, rotavirus A, syphilis, tetanus, and tuberculosis) and 9 are tropical (acquired immune deficiency syndrome (AIDS), Chagas’ disease, cholera, dengue haemorrhagic fever, East and West African sleeping sicknesses, falciparum and vivax malarias, and visceral leishmaniasis). The remaining eight (temperate diphtheria, mumps, plague, rubella, smallpox, typhoid and typhus, plus tropical yellow fever) imposed heavy burdens in the past, although modern medicine and public health have either eradicated them (smallpox) or reduced their burden. Except for AIDS, dengue fever, and cholera, which have spread and attained global impact in modern times, most of these 25 diseases have been important for more than two centuries.


Differences between temperate and tropical diseases

Comparisons of these temperate and tropical diseases yield the following conclusions:

  • A higher proportion of the diseases is transmitted by insect vectors in the tropics (8/10) than in the temperate zones (2/15).
  • A higher proportion of the diseases conveys long-lasting immunity (11/15) in the temperate zones than in the tropics (2/10).
  • Animal reservoirs are more frequent in the tropics (8/10) than in the temperate zones (3/15).
  • Most of the temperate diseases (12/15) are acute rather than slow, chronic, or latent: The patient either dies or recovers within one to several weeks. Fewer of the tropical diseases are acute: 3/10 last for one or two weeks, 3/10 last for weeks to months or years, and 4/10 last for many months to decades.
  • A higher proportion of the diseases belongs to Stage 5 (strictly confined to humans) in the temperate zones (10/15 or 11/15) than in the tropics (3/10). The paucity of Stage 2 and Stage 3 diseases (a total of only 5 such diseases) out of 25 major human diseases is noteworthy, because some Stage 2 and Stage 3 pathogens (such as anthrax and Ebola) are notoriously virulent.


Pathogen origins

The rise of agriculture starting 11,000 years ago played multiple roles in the evolution of animal pathogens into human pathogens. Those roles included both generation of the large human populations necessary for the evolution and persistence of human crowd diseases, and generation of large populations of domestic animals, with which farmers came into much closer and more frequent contact than hunter/gatherers had with wild animals.

It is interesting that fewer tropical than temperate pathogens originated from domestic animals. Why do temperate and tropical human diseases differ so markedly in their animal origins? Many tropical diseases (AIDS, dengue fever, vivax malaria, yellow fever) but only one temperate disease (hepatitis B) have wild non-human primate origins. This is because the vast majority of primate species is tropical rather than temperate. Conversely, few tropical but many temperate diseases arose from domestic animals, and this is because domestic animals live mainly in the temperate zones, and their concentration there before their introduction to the tropics was even more lopsided.


So what can we expect in the future?

  • As population densities grow, so will “crowd epidemics”.
  • As globalization allows more people to move rapidly across geographic zones, more tropical diseases will appear in the the temperate regions.
  • Immunization against tropical diseases will be difficult. An effective malaria vaccine has not been created despite decades of intensive efforts. HIV has frustrated the best minds in immunology and vaccinology.
  • Warming climate trends will allow the migration of animal reservoirs and insect vectors of disease from the tropics to the temperate north.
  • Most alarming: Stage 2 and 3 pathogens, like Ebola, will migrate north and will undergo rapid evolution to stages 4 and 5 through genetic mutations that will allow them to become exclusively human diseases. This has already happened: HIV/AIDS is a case in point. Unfortunately, more is to come.


Postscript: One day’s news

The ending of this posting (written yesterday, March 24th) bothered me a bit: Am I being an alarmist? So my senses were heightened when I read the newspaper today. Here are 2 items:

1. An example of a pathogen undergoing mutations that allow it to “graduate” from stage 3 to stage 4.

Indonesia: Warnings on Failure to Contain Avian Flu and on Increased Risk of Deadly Mutation

By Donald G. McNeil Jr.
Published: March 25, 2008

The avian flu situation in Indonesia is grave, and the risk of mutation into a human pandemic form will worsen if more is not done, the United Nations Food and Agriculture Organization warned last week.

2. Brazil: Dengue Fever Outbreak
By The Associated Press
Published: March 25, 2008

Brazil will send 670 health professionals to Rio de Janeiro State to help overwhelmed emergency rooms that are reporting 80 new cases of dengue fever every hour. So far, more than 32,000 cases have been confirmed around the state, and 49 people have been confirmed dead. But specialists believe that the number of victims could be three times as high as reported.

And that’s from one day of news reports that made it to a U.S. paper.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.