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PLoS Med. Nov 2007; 4(11): e336.
Published online Nov 27, 2007. doi:  10.1371/journal.pmed.0040336
PMCID: PMC2082648

Controlling Endemic Cholera with Oral Vaccines

Lorenz von Seidlein, Academic Editor

Abstract

Background

Although advances in rehydration therapy have made cholera a treatable disease with low case-fatality in settings with appropriate medical care, cholera continues to impose considerable mortality in the world's most impoverished populations. Internationally licensed, killed whole-cell based oral cholera vaccines (OCVs) have been available for over a decade, but have not been used for the control of cholera. Recently, these vaccines were shown to confer significant levels of herd protection, suggesting that the protective potential of these vaccines has been underestimated and that these vaccines may be highly effective in cholera control when deployed in mass immunization programs. We used a large-scale stochastic simulation model to investigate the possibility of controlling endemic cholera with OCVs.

Methods and Findings

We construct a large-scale, stochastic cholera transmission model of Matlab, Bangladesh. We find that cholera transmission could be controlled in endemic areas with 50% coverage with OCVs. At this level of coverage, the model predicts that there would be an 89% (95% confidence interval [CI] 72%–98%) reduction in cholera cases among the unvaccinated, and a 93% (95% CI 82%–99%) reduction overall in the entire population. Even a more modest coverage of 30% would result in a 76% (95% CI 44%–95%) reduction in cholera incidence for the population area covered. For populations that have less natural immunity than the population of Matlab, 70% coverage would probably be necessary for cholera control, i.e., an annual incidence rate of ≤ 1 case per 1,000 people in the population.

Conclusions

Endemic cholera could be reduced to an annual incidence rate of ≤ 1 case per 1,000 people in endemic areas with biennial vaccination with OCVs if coverage could reach 50%–70% depending on the level of prior immunity in the population. These vaccination efforts could be targeted with careful use of ecological data.

Abstract

Editors' Summary

Background.

Throughout history, there have been devastating outbreaks of cholera—a gut infection characterized by diarrhea and severe dehydration—around the world. These days, cholera is mainly confined to developing countries where it disrupts social structures, impedes economic development, and probably causes about 100,000 deaths a year. People get cholera, which is caused by a bacterium called Vibrio cholerae, by eating food or drinking water contaminated with feces (stools) from an infected person. Most infected people have no or mild symptoms but shed the bug in their feces for up to two weeks. Other people develop severe diarrhea, producing stools that look like water with flecks of rice in it. If untreated, patients with severe cholera can die from dehydration within hours of developing symptoms. The standard treatment for cholera is replacement of the fluids and salts lost through diarrhea by drinking an oral rehydration solution or, in the worst cases, by fluid replacement directly into a vein. Without this treatment, which is not always available in the developing countries where cholera is endemic (always present), one in every two people with severe symptoms die.

Why Was This Study Done?

The best way to control cholera is to ensure that everyone has access to safe water and good sanitation, but this is not possible in some poor countries, in refugee camps, or after natural disasters such as floods. Oral cholera vaccines (preparations given by mouth that stimulate the immune system to attack V. cholerae) are available but they are not 100% effective and the protection they provide wanes over time. Consequently, vaccination has not been adopted as a control measure for endemic cholera. Recently, however, researchers have suggested that oral cholera vaccines induce “herd immunity.” With a disease that passes between people, when most of the population is immune to it, it is unlikely that an infected person will come into contact with a susceptible person and pass the disease on. In effect, both vaccinated and unvaccinated people are protected from the disease. If cholera vaccines do induce herd immunity, then mass immunization might help to control endemic cholera. In this study, the researchers have used a mathematical model to investigate this possibility.

What Did the Researchers Do and Find?

The researchers built a large-scale model of cholera transmission using information about the population of Matlab, Bangladesh (a region where cholera is endemic), together with data on the biology of cholera and data from a large oral vaccine trial done in Matlab in the 1980s. They used this model to predict whether cholera would be controlled after vaccination of different proportions of the population. They found that cholera transmission would be controlled if half the population in the region was vaccinated. This level of vaccine coverage reduced the number of cholera cases among unvaccinated people by 89% and among the entire population by 93%. With only one-third of the population vaccinated, the number of cases of cholera still fell by three-fourths. The model also predicted that in areas where there is less natural immunity to cholera (the people in Matlab are constantly exposed to V. cholerae, so they have some immunity to the bug even without vaccination), 70% of the population would probably need to be vaccinated to control cholera.

What Do These Findings Mean?

These findings suggest that, because of herd immunity, vaccinating only half the population could control cholera transmission in endemic regions where there is a high level of natural immunity. Where there is less natural immunity, more of the population would need to be immunized. Although mass immunization of even 70% of a population should be achievable, for maximal protection against V. cholerae, two doses of the oral cholera vaccine need to be given a week apart followed by a booster every two years. In developing countries this regimen might not always be logistically feasible or affordable. Furthermore, because the accuracy of the model's predictions depends on the assumptions made to construct it and on the data incorporated into it, these findings need to be checked in field trials in other endemic areas. Nevertheless, these findings suggest that public-health officials should consider including mass vaccination in their efforts to control endemic cholera.

Additional Information.

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040336.

  • The MedlinePlus encyclopedia contains a page on cholera (in English and Spanish)
  • Information is available from the World Health Organization on cholera, including a fact sheet on the disease (in English, Spanish, French, Russian, Arabic, and Chinese)
  • The US Centers for Disease Control and Prevention provide information on cholera (in English, Spanish and Portuguese).
  • The UK National Health service provides simple information on vaccines and immunization, which includes an animation that explains herd immunity

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