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Friday, 26 August 2011

Cholera, DNA fingerprints and history

DNA fingerprinting is a key part of forensic science, it is also widely used in microbiology. If you want to control a disease, you must know how it spreads. Cholera provided the seminal example of early epidemiology (study of disease characteristics and causes) in the famous experiment of John Snow and the Broad Street pump ( http://www.wellcomecollection.org/explore/time--place/topics/london/video.aspx?view=mike-jay-on-john-snow-and-the) Cholera now also provides a solid example of the most modern technology being used in DNA fingerprinting, whole genome sequencing.

John Snow, image from the Wellcome Library Collection

If you have 2 people with the same disease, caused by the same germ, you want to know if it's likely they have the same germ, acquired from each other, or a common source. Sometimes, as in some food poisoning outbreaks and the cruise ship vomiting virus, the epidemiological link between the cases is so strong that is it reasonable to conclude they have the same germ from the same source. Often, this is less obvious, particularly with diseases with longer incubation periods (time from acquiring the germ to getting ill with it), such as TB.
Deciding whether 2 germs from different people are "indistinguishable"  (microbial epidemiologists generally avoid the word "same") or different can be done in a number of ways. But since the advent of genetics, some sort of DNA typing has become usual. In the past, typing depended on looking at the pattern of length fragments (fingerprint) when the germ's DNA was chopped up by a standard method; later methods relied on sequencing small sections of a limited number of genes to assign a type. With the advent of rapid whole genome sequencing (deep or high throughput), differences can now be looked for on a whole genome level. This allows much better discrimination (ability to tell the difference between strains) and also insight into the evolution of germs.
This technique was used in investigating the German E. coli outbreak earlier this year and is the subject of intensive study and development worlwide (see for instance a major UK research collaboration:  (http://www.nature.com/nm/journal/v16/n10/full/nm1010-1054a.html; http://www.modmedmicro.ac.uk/)

John Snow may have found it fitting that cholera is the target of a seminal epidemiological study once more
(http://www.sanger.ac.uk/about/press/2011/110824.html). This report, in the journal Nature, shows that the current cholera pandemic arose in the Bay of Bengal and has spread out in waves, likely to represent sequential human transmission events. It also provides insight into the mechanism of acquisition and spread of antibiotic resistance in cholera, a key factor in disease control. It is also, as a specialist from the London School of Hygiene and Tropical Medicine, Dr Valerie Curtis, puts it "a scandal"  (quoted on BBC news: http://www.bbc.co.uk/news/health-14664450) that despite the advances in epidemiology, microbiology and medicine since the days of John Snow, it is estimated that up to 3 million people worlwide, overwhelmingly the poorest, are still affected by cholera each year.

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