Tuesday, 11 October 2016 17:21

After Hurricane Matthew, Cholera Becomes a Concern

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Published in Microbial Sciences

Hurricane Matthew hit Haiti on October 4, 2016, and the southeast United States two days later, leaving tens of thousands without power, transportation, and in the worst cases, homes. Because of its extreme poverty, and its continuing recovery from previous natural disasters, Haiti is looking at a potential uptick in what had been a slight decline in its cholera epidemic. What is cholera and how might the aftermath of Hurricane Matthew affect the spread of its disease? Read below for a brief overview and more resources from ASM:

The Microbe

Vibrio cholerae is a gram-negative, comma-shaped bacterium decorated with pili and a flagellum at one end (see image). Its genome consists of two chromosomes, with both chromosomes containing important housekeeping genes.

V. cholerae lives in fresh, brackish, and coastal seawaters and often colonizes the chininous shell associated with shellfish and zooplankton in these waterways. V. cholerae populations often increase with algal blooms, which serve as food for host zooplankton. Not all V. cholerae strains can cause disease in humans, and the proportion of pathogenic to nonpathogenic strains can change rapidly within a given environment.

V. cholerae doesn’t tolerate stomach acidity well, and so requires a relatively high infectious dose to cause disease, but the bacterium can survive other immune barriers. The bile salts of the intestine often act as antimicrobial chemicals, since their detergent-like properties allow them to disrupt the microbial membrane, but V. cholerae uses bile salts as an environmental signal to increase expression of bile resistance genes as well as virulence-associated genes.

These virulence genes include the toxin coregulated pilus (TCP). This appendage helps the bacterium adhere to the epithelial cells of the intestinal cell lining. Exactly how the TCP, a type IV pilus, mediates adherence, including its binding ligand, is unknown and one of the aims of current research. The 15 TCP genes are encoded on a pathogenicity island on one of the two chromosomes.

Arguably the most important for pathogenesis is the cholera toxin. Cholera toxin, encoded by two genes, is found on a lysogenic phage that enters the lytic cycle during infection. Cholera toxin increases activity of the CFTR transporter, which leads the affected cells to pump out Na+, K+, Cl-, and HCO3- ions. The cells pump out water in an attempt to balance the difference in salt concentration, leading to the symptoms of cholera disease (namely, watery diarrhea).

Cholera toxin (CTX) itself is an A-B toxin, meaning that there are two gene products necessary for its action. The two products form a complex (in the case of cholera toxin, 1 A product for every 5 B products, so an AB5 toxin) and the CTX B portions interact with host cell receptors (in this case, GM1 gangliosides), which take up the AB5 toxin complex by endocytosis. The CTX A product then exits the endosome and disrupts normal GTP signaling by inhibiting the hydrolysis of GTP to GDP + Pi.  The increased concentration of host cell GTP increases adenylyl cyclase activity, and culminates in an overactive CFTR transporter. 

The Disease

The watery diarrhea associated with cholera disease can be quickly fatal if left untreated. Patients succumb to dehydration and electrolyte imbalance, often displaying symptoms within hours of bacterial ingestion.

Oral rehydration therapy (ORT) helps alleviate the morbidity but doesn’t shorten the course of disease. ORT is administration of electrolyte-laden fluids to help curb the massive loss of both water and electrolytes. The best course of action combines ORT with antibiotic therapy to lessen symptoms and eradicate the microbe.

Disease History and Epidemiology

Since 1800, there have been seven major cholera pandemic (we are currently in the seventh). The organism can survive in cold and warm climates, and the current Haitian outbreak, which started in 2011, is an example of how quickly a pathogenic strain can move and take over the local water system.

Before the devastating January 2010 earthquake, Haiti had very little to no cholera incidence. As ships arrived with relief supplies for those affected by the earthquake, they unknowingly carried the dangerous bacteria with them. Though denied at first by the United Nations, many genetic and genomic epidemiological studies eventually confirmed that the Haitian strain most closely matched a strain found in Nepal, which was released into Haitian waters by infected Nepalese peacekeepers. In 2016, the U.N. admitted its role in transporting the disease to Haiti. Nearly 10,000 Haitians have died.

The outbreak began in October 2010 and killed over 4500 people in less than six months. By 2013, over 6% of Haitians had suffered from cholera. Despite international efforts to fight the epidemic, the bacterium flourishes in a country where half the population lacks running water and hurricanes, tropical storms, and the rainy season further promote spread of the microbe.

Hurricane Matthew devastated Haiti last week, directly leading to over 1000 human deaths at last count. Its impact on cholera containment will likely affect far greater numbers. Not only may the wind and water currents spread the bacterium, but also thousands of displaced citizens will be relocated to crowded camps with poor hygiene – ideal conditions for disease spread.

Cholera in Yemen

In a likely unrelated outbreak, the Yemeni refugee population has also recently reported several cholera cases. The ongoing civil war has created a similar situation to Haiti: displaced civilians living in close quarters with decreased hygiene and poor infrastructure. The world will be watching to see if the current handful of reported cases (and no deaths) develops into a full-blown epidemic. Despite similar breeding grounds for disease, with luck, Yemen will be able to stave off a comparable cholera outbreak.

Further ASM Resources on Cholera

Genetic analysis of Haitian and Nepalese V. cholerae strains in mBio:

 

 

Additional ASM Journal Articles on Cholera

ASM Books and Book Chapters on Cholera

Last modified on Wednesday, 04 January 2017 17:47
Julie Wolf

ASM Communications Social Media Specialist Julie Wolf spent her research career focused on medical mycology and infectious disease. Broadly interested in microbiology and scientific communication, she has taught at Long Island University and the community biolab Genspace and has written for the Scientista Foundation and Scholastic’s Science World magazine. Follow her on Twitter for more ASM and Microbiology highlights at @JulieMarieWolf.

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