Cholera is an intestinal disease that is caused by infection by the bacterium Vibrio cholerae. Primary symptoms include watery diarrhea and vomiting, which depending on the degree of illness may result in severe dehydration and electrolyte imbalance. The WHO reports an estimated 3-5 million cases a year, predominantly occurring in Asia and Africa with recent outbreaks in Haiti. Diarrheal diseases including cholera are the second leading cause of mortality in children under the age of 5 (Harris et al. 2012).
http://remf.dartmouth.edu/images/bacteriaSEM/source/1.html
The first reported cases of cholera occurred in India where the disease has existed for centuries. Since 1817, however, the disease has spread beyond the Indian subcontinent and six world-wide pandemics have occurred between 1817 and 1923. The seventh pandemic began in 1961 in Indonesia and is currently ongoing (Harris et al. 2012). The bacteria is commonly present in coastal waters and estuaries around the world where they exist as individual organisms or in association with zooplankton and transmission mainly occurs from either contaminated food or water (Banerjee et al. 2014).
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3153193/bin/toxins-02-00310-g001.jpg
The bacterial component that results in the onset of symptoms is cholera toxin (CT), which is a protein complex that infects cells and elevates intracellular levels of cAMP, thus resulting in chloride secretion and diarrhea (Wernick et al. 2010). The accompanying dehydration and electrolyte imbalance can be managed by oral or intravenous rehydration methods. Effective antibiotic therapy can also shorten the duration of diarrhea and reduce the volume of stool loss by 50%. Dukoral, Shanchol, and mORCVAX constitute the oral vaccines that are currently available and provide 60–85% protective efficacy for 2–3 years. Other preventative measures include the provision of water and adequate sanitation (Harris et al. 2012).
I think this is a great overview of the disease and provides the reader with enough initial information about the disease. The only thing I would really like clarification on is how the increased chloride secretion affects the cells and how it manifests in dehydration and diarrhea.
Also, I am curious about how the antibiotic therapy mitigates the symptoms. What exactly does it do to the cell? Or does it kill the bacteria? And along these lines, how do the drugs mentioned confer protective measures and why only for 2 -3 years? Is this the way the current outbreak being handled? If not, how so?
Thanks for the comment, Kat. To answer your question about the mechanisms leading up to chloride secretion, once inside the cell, the A1 domain of the cholera toxin A subunit becomes cleaved and goes on to enter the cytosol, where it activates the G protein Gsa. Upon activation, the G protein stays stuck in its GTP-bound form, thus continually activated adenylate cyclase and stimulating production of cAMP. The elevated levels of cAMP in turn activate the cystic fibrosis transmembrane conductance regulator (CFTR), a Cl-channel, and the increased levels of Cl-. The efflux of ions creates an osmotic gradient, thus resulting in increased water secretion and causing diarrhea.
And yes, the antibiotics are bactericidal in function. Also, I wasn’t able to find an exact answer as to why the vaccines only last for a couple of years, but I’m assuming that it’s because microorganisms are constantly evolving and the same immunity may not be effective towards new strains.
Lastly, according to a recent WHO paper, these are the current measures being taken to mitigate outbreak.
Good title page, very clear. What’s the target of cholera toxin? In other words, what is it activating/deactivating in order to elevate extracellular cAMP? Also, how does cAMP levels tie into chloride release?
Also, do you know any statistics of how many children under 5 die from cholera and other diarrheal diseases each year?
Thanks for your comment, Hudson! Please refer to my reply to Kat’s comment below for the mechanism of cholera toxin. But to reiterate, cAMP targets cystic fibrosis transmembrane conductance regulator (CFTR), which is a Cl-channel.
And the WHO’s website says that 760,000 children under 5 die every year from diarrheal disease.
Good overview of the disease and its history! How do individuals go about being tested for cholera disease? Have there been any reported cases in the United States? Also, could you further clarify on how cholera toxin leads to diarrhea? Thanks!
It was simple, clear, and really easy to read. I was interested in how the bacteria started specifically in India and the reasons behind that?
A solid overview of the disease’s origins and it’s effects on humans. The topics discussed flow in a natural way that is easy to understand. Overall, an informative summary.
Good and short and to the point! However, I would have liked to read more about how treatment for the bacteria works, and maybe more specifics about the pathway it messes up. Of course, cAMP does everything, so I was curious if a specific type of cell is affected. It seems like if systemic cAMP was altered it would kill you a lot faster.
You very thoroughly explained the origins, effects, and treatment of the disease in a clear and concise manner which was easy to understand and follow. Overall, very informative.
This intro is simple and clear. Gives some good information on what the disease is and the locations where it can be found. Would be interested to know behaviors that should be followed if you are traveling to regions where this is prevalent? Are the deaths in children a result in the inability to get adequate or proper medication(or could lives be saved if medication was available)?
Nice clarity! It could be interesting to explore how the structure of CT allows for its pathogenesis, going through a biochemical mechanism of its activity. Is there any attempt to create a specific inhibitor of CT as a quick method of stopping the toxic effects of cholera?
First of all, I would like to thank everyone for taking the time to read my title page. Your comments are greatly appreciated!