Cholera

Cholera is characterised by rapid onset of watery diarrhoea, resulting in dehydration. It can be fatal within 24 hours.

The symptoms are caused by cholera toxin excreted by Vibrio cholera serotypes O1 Inaba, O1 Ogawa and O139 Bengal. These Vibrio species are associated with widespread cholera outbreaks which occur intermittently over decades and have established cholera as a global disease with a presence in south-east Asia, Latin America and most recently Haiti.

Worldwide, cholera accounts for about 120 000 deaths each year. Westerners can develop it after travelling to endemic areas.

The World Health Organisation (WHO) recommends using oral cholera vaccine to control and prevent the disease. An oral vaccine containing recombinant cholera toxin B subunit and killed whole cells is licensed. 

Standardisation

NIBSC holds three World Health Organisation (WHO) International Standards (IS) in stock – 2 for whole cell cholera vaccines Inaba and Ogawa and one for IgG directed against cholera toxin. NIBSC staff drafted monograph 2327 of the European Pharmacopoeia ‘cholera vaccine (inactivated, oral)’.

NIBSC and the International Vaccine Institute, with support of The Bill and Melinda Gates Foundation, are developing International Standards to ensure the quality of the LPS inhibition ELISA. This assay determines the potency of oral inactivated cholera vaccines, which is important because this vaccine is currently used widely and also forms the WHO stockpile used in emergencies. The project includes International Standards for a reference inactivated cholera vaccine vaccine and monoclonal antibodies against O1 and O139 LPS. 

Control

The enteric vaccine group is responsible for the batch release of oral inactivated cholera vaccine, which contains killed V. cholerae O1 cells and recombinant cholera toxin B subunit. This involves review of batch manufacturing records to ascertain the batch meets the specification of the vaccine product licence.

In addition, each batch is subjected to visual inspection, agglutination using Inaba and Ogawa antisera, electrophoresis to ascertain purity of the cholera toxin B subunit and immuno assays to determine the quantity of lipopolysaccharide serotype O1 (Inaba and Ogawa) and the cholera toxin B subunit.  

Research and development

There is currently no active R&D programme. In the past we have developed molecular assays for genotyping of V cholera O1 variants and to measure ADP-ribosylation activity of the cholera toxin A subunit using a fluorescent peptide substrate to confirm absence of the A subunit in oral cholera vaccine.