Sunday, October 24, 2010

Quorum Sensing: Cholera

24 Oct 2010 22:38:55 GMT
Source: Reuters
A multinational medical response has slowed deaths in a Haitian cholera epidemic that has killed more than 250 people so far, but the outbreak is likely to widen, a senior U.N. official said on Sunday.

"We must gear up for a serious epidemic, even though we hope it won't happen," Nigel Fisher, the United Nations humanitarian coordinator in Haiti, told Reuters.

More than 3,000 cholera cases have been reported so far in the poor, earthquake-hit Caribbean nation, which is experiencing its second humanitarian crisis since a catastrophic earthquake on Jan. 12.

Bonnie Bassler of Princeton in her lecture:
Vibrio cholerae, like many other bacteria, uses quorum sensing to synchronize gene expression on a population-wide level. Upon infection of its human host, V. cholerae immediately initiates expression of virulence genes and causes an acute infection. This immediate use of quorum sensing stands in stark contrast to bacterial pathogens that cause persistent infections and only initiate virulence factor expression after reaching high-cell-density in the host.

I first covered Quorum Sensing in:
“Virulent bacteria do not want to begin secreting toxins too soon, or the host's immune system will quickly eliminate the nascent infection. Instead, Bassler explained, using quorum sensing, the bacteria count themselves and when they reach a sufficiently high number, they all launch their attack simultaneously. This way, the bacteria are more likely to overpower the immune system….

Then I covered Cholera in:
“Few afflictions have attracted as much attention and impacted on as many societal and biomedical areas as cholera…….The finding that cholera was due to the ingestion of contaminated water lent to the demise of the prevalent ‘miasmatic theory of contagion, set the platform for the ‘germ theory of disease,’ and promoted the growth of public health concerns for water purification and sanitation. More recent attention to this disease led to the notion of ‘secretory diarrhea’ and the translation of basic principles to the development of oral rehydration therapy and its ‘spin-offs’ (Gatorade and Pedilyte).
Stanley G. Schultz University of Texas Medical School
Cholera is caused by the organism Vibrio cholerae. Alert readers will note that Vibrio has caused much excitement because of the phenomenon of Quorum Sensing.

I well remember Hong Kong’s cholera epidemic in 1961 and the major cause of death was the rapid loss of fluid due to a specific secretive action of the cholera germ. Patients could die in a matter of hours. The medical profession has long been of the strong belief that Intravenous Fluid (IV Fluid) is the only answer. In that situation, the patient is in shock and to find a vein means a cut-down: literally cutting through the skin to find one. It is a messy business as the patient is violently pumping out fluid in the most horrendous fashion.

Johns Hopkins established a centre in Calcutta in the 1960s to study precisely a better way to replenish the fluid. IV fluids were expensive to manufacture and required medical personnel to administer. Their Clinicians sought help from basic physiology and carried out the first carefully controlled study which showed that intestinal perfusion of cholera patients with saline solutions containing glucose strikingly reduced fluid loss. Put simply, the patients could just drink a glucose and salt solution and the glucose would allow the salt to be piggy backed and absorbed, thus sparing the need to use IV fluids.

“……These compelling findings, however, did not convince the medical establishment, who remained skeptical that such a simple therapy could substitute for traditional intravenous fluid replacement in severely stricken patients under epidemic conditions in the field.”
The World had to wait for a war, this time in Pakistan, when Bangladesh fought for its independence in 1971 and 9 millionrefugees poured into India and with them cholera. When IV saline treatment was exhausted, Dr Mahalanabis, who had worked at the Johns Hopkins Centre in Calcutta, took the gamble and decided to prescribe a simple solution of glucose and salt in the right proportion for the friends and relatives of the cholera patients, thus saving at least 3.5 million people. Since that time it was estimated that such a simple and cheap remedy saved at least 40 million more lives.
No wonder The Lancet hailed the development of oral re-hydration therapy (ORT) as "the most important medical discovery of the 20th century".
The scientists at Johns Hopkins and Dr Mahalanabis received the Pollin Prize of $100,000 in 2002.


Cockroaches & Superbugs


No comments: