Throughout history the waterborne and highly infectious bacterium Vibrio cholerae has caused devastating outbreaks in most parts of the world, resulting in millions of cases and hundreds of thousands of deaths. Humans are the only known natural host for V. cholerae.
The disease is spread by faecal contamination of water and food, with endemicity and epidemicity closely linked to poor sanitation often accompanying natural disasters and situations that crowd people together under poor sanitary conditions that interrupt access to clean water. V. cholerae colonizes the lining epithelium of the gut, resulting in an acute, profuse watery diarrhea with children and the elderly particularly vulnerable. In its extreme manifestation, a previously healthy person may become hypotensive within 3-4 hours after infection and may die within 6-8 hours. An increasing number of geographical areas are becoming endemic for cholera, reflecting a failure of socio-economic infrastructure and difficulties in implementation of control measures.
Protective immunity in cholera is mediated mainly, if not exclusively, by antibodies produced locally in the intestinal mucosa and secreted onto the gut mucosal surface. These antibodies bind to bacterial components and inhibit bacterial colonization and multiplication and block the action of the toxin released by V. cholerae responsible for inducing diarrhea.
For many years killed whole-cell cholera vaccine was the only vaccine available which was administered by injection. However, this vaccine offers at best only limited protection of short duration, it does not prevent transmission of the infective agent, and it produces unpleasant side-effects in many patients. In view of these limitations, the vaccine has not been considered satisfactory for general public health use, and in 1973 the World Health Assembly abolished the requirement established by the International Health Regulations for a certificate of vaccination against cholera. Because the inactivated vaccine is no longer recommended for general public health use (although it is still produced in some countries), the Expert Committee for Biological Standardization discontinued the requirements relating to the parenteral whole-cell vaccine in 1999.
Considerable progress has been made in the development of a new generation of oral vaccines against cholera. Two distinct types of oral cholera vaccine have been developed; those based on a live attenuated bacteria (the genetically manipulated strain CVD 103-HgR) and those based on killed (inactivated) bacterial cells combined with a recombinant B-subunit of cholera toxin (WC/rBS). The latter must be given with a bicarbonate buffer to protect the toxin B subunit from being destroyed by gastric acid.
Both vaccines provide more substantial and longer lasting protection than the previous parenteral vaccine and are in use for traveller's vaccination. However, neither vaccine provides effective protection of children less than two years of age, limiting their utility in national infant immunization programmes.
Cholera Vaccine Standardization
WHO guidelines for inactivated oral cholera vaccines were which were adopted by the Expert Committee on Biological Standardization in 2001 describe the characteristics, production and control of inactivated oral cholera vaccines. This document was prepared to facilitate progress towards the international licensure and use of the new generation of oral vaccines against cholera.
Guidelines for the production and control of inactivated oral cholera vaccine, Annex 3, Technical Report Series 924, 2004
WHO reference reagents for the Inaba and Ogawa cholera vaccine antigens are available to qualified applicants: