Cholera and Other Vibrio Infections

Definition

Cholera is a dreaded epidemic diarrheal disease caused by Vibrio cholerae serogroup O1 and, since 1992, by the new serogroup O139. The disease is characterized by acute, large-volume watery diarrhea. In its more severe form, a person may be severely dehydrated and in hypovolemic shock; the patient may die in a matter of a few hours after contracting the infection if treatment is not provided.

Epidemiology

Cholera has both a predisposition to cause epidemics with pandemic potential and an ability to remain endemic in all affected areas.

Cholera is endemic today in Africa, Asia, and Latin America. Seven pandemics have been registered in history since 1817; the most recent has lasted more than five decades since its recognition in Indonesia in 1961. In Africa, cholera causes an estimated million or more cases annually, far more than the 70,000 or so reported cases, and nearly 40,000 annual deaths. Although cholera mostly affects developing countries, several developed countries, such as the United States, Canada, and Australia, have reported indigenous and imported cases. The most recent epidemics occurred in Haiti in 2022 to 2023 and Yemen in 2016 and 2017. Fig. 278-1 shows the distribution of cholera in the world from 1989 to 2019.

People of all ages are at risk to contract the infection in epidemic settings, whereas children older than 2 years are mainly affected in endemic areas. V. cholerae lives in riverine, brackish, and estuarine ecosystems, where both O1 and non-O1 strains coexist, with non-O1 and nontoxigenic O1 strains predominating over toxigenic O1 strains. In its natural environment, V. cholerae lives attached to algae or to crustacean shells and copepods, with which it coexists in a symbiotic manner. Several conditions, such as temperature, salinity, and availability of nutrients, determine the survival of V. cholerae ; when these conditions are adverse, vibrios survive in a viable but nonculturable state. Cholera phages modulate the abundance of V. cholerae in the environment and determine the beginning and end of epidemics. Phages may also play a role in the emergence of new V. cholerae serogroups by transferring genetic material to nontoxigenic strains.

From its aquatic environment, V. cholerae is introduced to humans through contamination of water sources and food. Once humans are infected, very high attack rates may take place, particularly in previously naïve populations. The disease can be acquired by drinking contaminated water from rivers, ponds, lakes, and even tube well sources. Drinking unboiled water, introducing hands into containers used to store drinking water, drinking beverages from street vendors, drinking beverages with contaminated ice, and drinking water outside the home are risk factors. Drinking boiled water, acidic beverages, and carbonated water and using narrow-necked vessels for storing water are protective measures. Epidemics of cholera can be associated with the ingestion of leftover rice, raw fish, cooked crabs, seafood, raw oysters, and fresh vegetables and fruits.

Person-to-person transmission is less likely to occur because a large inoculum is necessary to transmit disease. Nevertheless, high transmission rates (approximately 50%) are reported among household contacts of patients with cholera in endemic areas.

Epidemics of cholera tend to occur during the hot season. Factors affecting climate change and climate variability have an impact on the incidence of cholera. The El Niño–Southern Oscillation, which is a periodic phenomenon representative of global climate variability, causes the warming of normally cool waters in the Pacific coastline of Peru, thereby promoting phytoplankton bloom, zooplankton bloom, and the proliferation of V. cholerae .

Some host factors are important in the transmission of cholera. The chronic gastritis associated with Helicobacter pylori ( Chapter 125 ) predisposes to cholera by inducing hypochlorhydria, which reduces the ability of the stomach to contain the infection. Use of proton pump inhibitors or histamine-2 blockers and other conditions that cause achlorhydria also increase the risk. An unexplained predisposition to severe disease due to El Tor biotype in persons with the O blood group has been observed in Asia and more recently in Latin America. Innate predisposition has also been reported in endemic areas. Thus, complex associations among climatic, seasonal, bacterial, and human factors affect the transmission of cholera.

Pathobiology

V. cholerae O1 and O139 cause clinical disease by secreting an enterotoxin that promotes the secretion of fluids and electrolytes by the small intestine. The infectious dose of bacteria varies with the vehicle. When water is the vehicle, more bacteria are needed to cause disease (10 ³ to 10 ⁸ ), but when the vehicle is food, lower amounts are needed (10 ² to 10 ⁴ ).

The genetic material of El Tor V. cholerae O1 is included in two circular chromosomes, the larger containing 3 megabases and the smaller containing 1.07 megabases. The main virulence genes are ctxA and ctxB , which encode cholera toxin subunits A and B, respectively, and tcpA , which codes for toxin coregulated pilus. Genes unique to El Niño–Southern Oscillation V. cholerae may encode specific features that allow this biotype to survive better in the environment as well as to be more infectious to humans.

Cholera toxin has two subunits, a pentamer B subunit and a monomer A subunit. The B subunit allows binding of the toxin to a specific receptor, which is a ganglioside (GM ₁ ) located on the surface of cells lining the mucosa along the intestine of humans and certain suckling mammals. The active, or A, subunit has two components, A1 and A2, linked by a disulfide bond. Activation of adenylate cyclase by the A1 component increases cyclic adenosine monophosphate in intestinal epithelial cells, thereby blocking the absorption of sodium and chloride by microvilli and promoting the secretion of chloride and water by crypt cells. These events lead to the production of watery diarrhea with electrolyte concentrations similar to those of plasma ( Table 278-1 ). Other toxins also have been isolated from pathogenic V. cholerae , but their roles in genesis of the disease are less clear.