Cholera Outbreak in Haiti — November 2010

Abstract & Commentary

By Mary-Louise Scully, MD

Dr. Scully is Director, Travel and Tropical Medicine Center, Sansum Clinic, Santa Barbara, CA.

Dr. Scully reports no financial relationships relevant to this field of study.

Synopsis: Cholera continues to claim lives in Haiti, where relief efforts focus on treatment of cholera cases, interventions to provide clean water and improve sanitation, and education of affected communities on safe water and hygiene.

Source: Pan American Health Organization (PAHO/WHO) — Health Cluster Bulletin Cholera Outbreak in Haiti. http://new.paho.org/hq/index.php. Centers for Disease Control (CDC) Cholera Outbreak — Haiti, October 2010. MMWR 2010;59(43):1393-1432.

An outbreak of cholera is ongoing in Haiti. As of Nov. 10, 2010, the Ministère de la Santé Publique et de la Population (MSPP) of Haiti reported 12,303 hospital admissions and 796 deaths in six geographic departments. The causative agent has been identified as toxigenic Vibrio cholerae 01, serotype Ogawa, biotype El Tor by the National Laboratory of Public Health of the MSPP of Haiti and confirmed by the Centers for Disease Control and Prevention (CDC). Antibiotic susceptibility testing shows resistance to trimethoprim-sulfamethoxazole, furazolidone, naldixic acid, sulfisoxazole and streptomycin and susceptibility to tetracycline, ciprofloxacin, and kanamycin.

The outbreak began in the Artibonite department, a rural but densely populated area north of Port-au-Prince. Fears of spread to Haiti's capital have now been confirmed, with an estimated 278 hospital admissions and 10 deaths reported in Port-au-Prince as of Nov. 9, 2010. The first case near the capital was reported in a 3-year-old boy from Cité Soleil, a slum north of the city where many people live in cramped, unhygienic conditions without adequate sanitation.

In January 2010, Port-au-Prince and other nearby towns were devastated by a 7.0 magnitude earthquake, which is estimated to have killed more than 250,000 people and left another million displaced and homeless, many of whom are now living in temporary tented camps around the capital. The next assault was Hurricane Tomas, which killed another 21 people and left 6,610 people homeless in early November. The hurricane passed by without destroying these tented camps, but the heavy rains caused significant flooding, which likely will facilitate the spread of cholera.

The government and its partners are in the process of setting up 10 new cholera treatment centers, each with a capacity of 100-400 beds in addition to the eight centers already in operation in Port-au-Prince and the surrounding areas. In addition, many non-profit organizations from around the world are on the ground helping in Haiti to supply educational information, oral rehydration salts (ORS), chlorine and other disinfection tablets, Ringers Lactate solution, and antibiotics in an effort to curb the outbreak.

Commentary

Cholera is transmitted through fecal contamination of water and food. Infections are often asymptomatic or cause a mild gastroenteritis, but about 5% of infected persons develop a severe, dehydrating, acute watery diarrhea. The classic description is that of "rice water stools." Blood type O is associated with increased vulnerability to severe cholera (cholera gravis). The mainstay of treatment is rehydration, either with oral rehydration salts and, when needed, intravenous fluids and electrolytes, such as Ringers Lactate solution. Antimicrobial treatment is recommended for severe cases but does not play a role, nor should it be used, for chemoprophylaxis to prevent cholera on a mass scale.

Two types of oral cholera vaccines are available globally: 1.) Dukoral; and 2.) Shanchol and mORCVAX. The once-licensed oral, live, attenuated single-dose vaccine (CVD 103-HgR) is no longer produced. An injectable vaccine prepared from phenol-inactivated strains of V. cholerae is still made in several countries but is not endorsed by the WHO because of its short duration of protection and limited efficacy.

Dukoral consists of killed whole-cell V. cholerae 01 with purified recombinant B subunit of cholera toxoid (WC-rBS) and is available in more than 60 countries, but not the United States. To protect the toxin subunit from being destroyed by gastric acid, the vaccine must be given with a bicarbonate buffer. Primary immunization consists of 2 oral doses given 7 or more days apart for adults and children older than 6 years, with a booster dose after 2 years. Children 2-5 years of age should receive 3 doses 7 or more days apart, and Dukoral is not approved for children younger than 2 years.

Field trials in Peru and Bangladesh have shown that Dukoral oral cholera vaccine confers 85-90% protection for 4-6 months among all age groups. Protection declined rapidly in young children after 6 months, but remained at about 60% after 2 years for older children and adults.1 Dukoral contains the recombinant B subunit, which is structurally similar to the heat-labile toxin of ETEC and in several studies has been shown to protect against this agent. In studies of travelers to cholera-endemic countries, 52% of travelers had short-term protection against diarrhea caused by ETEC, and the protective efficacy against a combination of ETEC and any other pathogen was 71%.2,3

Shanchol and mORCVAX are two closely related bivalent oral cholera vaccines that resulted from a technology transfer of the WC/rBS vaccine from Sweden to India and Vietnam. Shanchol will be produced for Indian markets and international use, and mORVAX is intended for domestic use in Vietnam. Both vaccines are based on serogroups 01 and 0139 and do not contain the recombinant B subunit (so they do not require a buffer); however, they do not confer protection against ETEC. Vaccine is administered in 2 liquid doses 14 days apart for persons older than 1 year of age with a booster after two years. Efficacy trials are ongoing, but an interim analysis of a large Shanchol study in Kolkata, India, showed a protective efficacy at two years of 67% among those who received 2 doses.4 Since the recombinant subunit B is not in these vaccines, production costs are much lower, and Shanchol is estimated at $1 per dose.

With these effective oral vaccines, one might ask why cholera vaccine is not being shipped to Haiti to help with the outbreak. One big problem is the supply of oral cholera vaccine. There may be only 200,000 or so doses of Dukoral, which is the only oral vaccine prequalified by the WHO. The second problem is that unlike the ring vaccination strategy that was effective in smallpox (during which everyone infected with smallpox has symptoms), once a cholera outbreak is in progress, up to 80% of people may already be asymptomatic carriers. Also, at least two doses of vaccine separated by 7-14 days are needed, with several more weeks before immunity is established. The WHO and Pan American Health Organization (PAHO) quote the logistical aspects of delivering and monitoring cholera vaccination in the midst of a cholera outbreak as reasons why they focus on traditional cholera public health measures. That said, the possibility and feasibility of vaccinating some populations beyond the current outbreak zones in Haiti (pre-emptive vaccination) is under consideration. Of note, PAHO does not recommend vaccination of health care workers nor of its own staff or visiting expert consultants traveling to Haiti since person-to-person transmission is extremely rare.

The mainstay of cholera outbreak control, therefore, goes back to proven public health measures such as providing appropriate treatment to people with cholera, implementing interventions to improve water and sanitation, and mobilizing communities by educating people about hand washing and providing the basics of safe water, soap, and oral rehydration salts. Yet despite the efforts to provide safe water and improved sanitation globally, the number of cholera cases reported to the WHO in 2009 increased by 16%. Africa suffered the worst toll, with 217,333 of the 221,226 total cases and 4883 of the 4926 total deaths. Zimbabwe, Ethiopia, and the Democratic Republic of Congo had the most cases. Important steps toward global cholera control likely will need to include broadening the implementation of the existing oral cholera vaccines as well as continued research and development of newer cholera vaccines with longer-lasting immunity.

References

  1. World Health Organization (2010) Cholera, 2009. Wkly Epidemiol Rec 2010;85:293-306.
  2. Peltola H, et al. Prevention of travelers diarrhea by oral B-subunit/whole-cell cholera vaccine. Lancet1991;338:1285-1289.
  3. Hill DR, et al. Oral cholera vaccines: Use in clinical practice. Lancet Infectious Dis 2007;7:361-373.
  4. World Health Organization (2010) Cholera vaccines: WHO Position Paper. Wkly Epidemiol Rec 2010;85:117-128.