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Cholera in Haiti and Beyond

By Amesh A. Adalja, MD, December 3, 2010

There have been 7 distinct cholera pandemics during the last 2 centuries, each caused by a different strain of V. cholerae. The current pandemic, caused by the El Tor biotype, has been occurring since 1961.1 With the onset of the recent cholera epidemic in Haiti, concerns have arisen about wider spread of this bacterium into the Western Hemisphere, especially given the subsequent importation of cases into the Dominican Republic and the United States (Florida). With cases now occurring in the U.S., clinicians should be aware of the clinical presentation of cholera and its treatment.

Toxin Mediated Disease

Following a 12- to 72-hour incubation period, infection with V. cholerae causes severe watery diarrhea (“rice water”) caused by the action of the cholera toxin that binds to cells lining intestinal mucosa. The toxin is present in all strains of pathogenic V. cholerae species. The action of the toxin increases concentrations of cAMP, blocking intestinal absorption of sodium and chloride and promoting the secretion of water and chloride by the crypt cells of the intestine. This produces the voluminous diarrhea of cholera.1

Relatively Simple Treatment

The primary treatment is fluid replacement. The mainstays of fluid resuscitation are oral rehydration solution (ORS) or IV lactated ringer’s solution. Antimicrobial therapy as an adjunct to fluid resuscitation has been shown to decrease the diarrhea duration and stool volume by approximately 50%. Antibiotics with activity against V. cholerae include tetracyclines, macrolides, fluoroquinolones, and trimethoprim-sulfamethaxazole. Strains resistant to tetracyclines and fluoroquinolones have been detected. Other adjuncts include oral zinc supplementation. Zinc is essential to the function of many enzymes, including those responsible for regeneration of intestinal epithelium, and is depleted in patients with severe diarrhea.

Vaccines

Several vaccines have been developed for cholera, none of which are currently FDA-approved and licensed for use in the U.S., including:1,2

  • Dukoral (Crucell): an oral, inactivated, toxin-containing vaccine for adults and children aged 2 years or older (primarily travelers). For immunity, children 6 and under require 3 doses, spaced 10 to 14 days apart; children over 6 years and adults need 2 doses spaced 10 to 14 days apart.  

  • Shanchol (Shantha Biotechnics) and mORC-Vax (VaBiotech): both are oral, inactivated, nontoxin-containing vaccines for adults and children over 1 year. To produce immunity, both vaccines must be administered in 2 doses, spaced 14 days apart.

  • A parenteral formulation with poor efficacy was approved by the FDA until 2001, but it was never endorsed by the World Health Organization (WHO). It is no longer available in the U.S.

  • CVD 103-HgR: a live, attenuated oral vaccine that is no longer available

Why Isn’t Cholera Vaccine Being Used in Haiti?

Thus far, the control of the cholera epidemic in Haiti has not employed vaccines. Several reasons have been offered for this decision:3

  • Inadequate vaccine supply and production capacity: millions of doses are needed, but current capacity supports production of only a few hundred thousand doses of vaccine.

  • Dukoral is the only vaccine that is WHO-prequalified for UN purchase, and it is likely too expensive for extensive use in an outbreak since it is targeted to travelers. And because 2 doses are required for immunity, administration in an outbreak cannot keep pace with spread.

  • Logistical challenges: there are millions of displaced persons in Haiti and infrastructure inadequate to support vaccination and the tracking required for administration of multiple doses.

Cholera Vaccine Stockpile

In their recent perspectives piece in the New England Journal of Medicine, Matthew Waldor, Peter Hotez, and John Clemens argue for the establishment of a strategic stockpile of vaccine within the U.S. that can be deployed to cholera hot-spots around the world. This stockpile would guard against the shortages that prevent vaccine use during epidemics and as a “diplomatic and humanitarian” resource.4 However, if the current vaccines were included in the stockpile, their utility would be limited by the need for 2 doses for full immunity.

References

  1. Seas C, Gutuzzo E. Vibrio cholera. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, PA: Churchill Livingstone; 2010.

  2. World Health Organization. Cholera vaccines: WHO position paper. Weekly Epidemiologic Record 2010; 85:117-128. http://www.who.int/wer/2010/wer8513.pdf. Accessed November 29, 2010.

  3. Butler D. Stopping an epidemic. Nature 2010; 468:484.

  4. Waldor MK, Hotez PJ, Clemens JD. A national cholera vaccine stockpile — a new humanitarian and diplomatic resource. N Eng J Med 2010. http://www.nejm.org/doi/full/10.1056/NEJMp1012300. Accessed November 29, 2010.