Monday, January 13, 2014

This is not your (great great great) grandfather's cholera

Cholera, caused by the bacterium Vibrio cholera via contact with contaminated water, affects millions of people each year. In contrast to diseases like smallpox and tuberculosis, the Vibrio strains causing cholera arose relatively recently from more benign relatives, with the first confirmed cholera epidemic occurring in 1817 in areas of present-day Bangladesh and north India. Starting with the 1817 outbreak, there have been 7 cholera pandemics, with the seventh dating from the late 60s and considered to still be ongoing.
In the modern era there have been two major disease causing strains, termed the classical and the El Tor strains, with slight differences in their epidemiology and their gene regulation of the disease-causing cholera toxin. The classical form is thought to have caused all of the first six epidemics, while El Tor, with slightly milder symptoms,  is implicated in the ongoing seventh epidemic and seems to be en route to becoming the more dominant form of the disease. Supporting the idea that the older epidemics were caused by the classical strain,  a study in the New England Journal of Medicine from last week has reported Vibrio sequences from a cholera victim from the second pandemic. The bacterial DNA was obtained from an unusual specimen-- a section of the intestine of a cholera victim from 1849 Philadelphia, which had been preserved in alcohol for 146 years.  The DNA sequences do show a great deal of similarity to the classical strain obtained from more recent epidemics.
Since the classical Vibrio strain had been on the scene for nearly 200 years, it remains to be seen why El Tor has suddenly come on the scene.There is some suggestion that the El Tor strain actively suppresses growth of the classical strain when the two are in co-culture.

The El Tor biotype has some variation over its shorter time on the world stage, and this may augur a continued evolution of the disease. Detailed analyses of bacterial DNA from the 7th (current) pandemic show 3 major genetic groupings from isolates collected over the past 4 decades, suggesting 3 sequential waves of emergence of this biotype from their origin in the northeast corner of the Indian subcontinent. By careful phylogenetic analysis, they provide evidence for intercontinental routes of transmission separated into three epochs, suggesting that the disease strains follow boom-and-bust behavior. Thus, disease-causing Vibrio is probably still evolving in the Bay of Bengal region and may yet give rise to more variant cholera epidemics in the near future.

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