Cholera is an acute diarrheal illness caused by the bacterium Vibrio cholerae. It is one of the oldest infectious diseases known to mankind. In the eighteenth century the disease spread from its original reservoir, the Ganges Delta in India, causing epidemics and pandemics resulting in the death of massive numbers of people across the globe.

Cholera is an intestinal infection with toxigenic strains of V. cholerae serogroups O1 and O139. V. cholerae O1 serogroup is further classified into two serotypes—Ogawa and Inaba—and two biotypes—classical and El Tor. The mode of transmission is through ingestion of contaminated food and water [ 1 ]. The disease occurs in children and adults especially in the lower socioeconomic groups. The short incubation period of 2 h to 5 days is responsible for exponential wave of this disease. Following consumption of infected food, the bacterium uses its virulence factors—toxin- coregulated pilus (TCP) [ 2 ], hemagglutinin [ 3 ], and single flagellum to colonize the small intestine and secretes cholera enterotoxin (CT). The “-B-” subunit of CT binds to the GM1 ganglioside receptor, facilitating entry into the intestinal mucosal cells and “-A-” subunit activates adenyl cyclase leading to excess fluid and salt secretion. Clinical symptoms include acute diarrhea and vomiting rapidly leading to electrolyte imbalances, hypovolemic shock, multiorgan failure, and death. Cholera can be fatal if there is a delay in replacement of fluid and electrolytes. Diagnosis is made clinically and by identifying the bacterium in stool cultures. Serologic tests are available but are nonspecific.

The global annual incidence of cholera is uncertain but the approximate cases may be 3–5 million causing 100,000–120,000 deaths. More than half the cases occur in Africa and remainder in Asia. There have been sporadic cases along the US Gulf Coast associated with undercooked or contaminated seafood. The majority of other cases in the developed countries are secondary to travel to endemic areas.

The preparation of the earliest vaccine against cholera began in the late eighteenth century. Initial studies were made with a parenteral killed whole-cell cholera vaccine in the 1880s which had limited use owing to short-term efficacy. The currently licensed cholera vaccines contain either genetically attenuated strains, killed organisms, or antigens. Three oral vaccines—two killed and one live—have been developed and licensed in several countries. The whole-cell killed vaccine plus CTB (WC-rCTB/Dukoral) contains killed strains of V. cholerae O1 (classical, El Tor, Ogawa, and Inaba) with B subunit of cholera toxin. The vaccine is given as two oral doses combined with a liquid oral buffer, 7–14 days apart in adults and in three doses in children 2–6 years of age with need for further booster doses. The vaccine is WHO prequalified but remains experimental in the USA. The reformulated bivalent killed whole- cell- only vaccine (WC-only/Shancol in India/mORCVAX in Vietnam) contains killed whole cells of V. cholerae O1 and O139. It is given as two doses 2 weeks apart with further boosters at 3-year intervals. Since the vaccine does not contain the gastric acid-labile cholera toxin subunit, it does not have to be coadministered with a buffer. The only live oral cholera vaccine is CVD103- HgR (Orochol or Mutachol). The vaccine is a live attenuated Inaba strain, which is genetically engineered to express CTB subunit and not the active CTA subunit. The vaccine is administered as a single oral dose with a buffer and does not require booster doses. The live vaccine has not been prequalified by WHO.

The WHO recommends the use of the two killed oral vaccines in cholera endemic areas and areas at risk for outbreaks [ 4 ]. The cholera vaccine is unavailable in the USA and CDC does not recommend cholera vaccines to most travelers owing to short-term and incomplete protection. These vaccines however cannot replace the pivotal role played by hygiene and proper sanitation in the control of cholera outbreaks.

References

-------------

[1] Blake PA, Allegra DT, Snyder JD et al (1980) Cholera: a possible endemic focus in the United States. N Engl J Med 302:305–309

[2] Tacket CO, Taylor RK, Losonsky G et al (1998) Investigation of the role of toxin coregulated pili and mannose- sensitive hem agglutinin pili in the pathogenesis of Vibrio cholerae 0139 infection. Infect Immun 66: 692–695

 [3] Silva A, Leitch G, Camilli A et al (2006) Contribution of hemagglutination/protease and motility to pathogenesis of El Tor biotype cholera. Infect Immun 74:2072–2079

[4] www.who.int/cholera/vaccines