Background

Cholera is an acute water-borne diarrhoeal infection caused by the enterotoxin subunit-A of Vibrio cholerae.¹ Cholera is prevalent in areas with poor sanitation and food and water hygiene and constitutes a major global public health problem.¹ Without treatment, severe infection has a mortality rate of 30-50%.² Oral cholera vaccines are safe, immunogenic and effective but must not be considered as a substitute for basic preventative measures such as clean water and sanitation.²

• Epidemiology - the disease is endemic to parts of Africa, Asia, the Middle East and South America.² Large outbreaks are common after natural disasters or in populations displaced by war, where there is inadequate sewage disposal and contaminated water.¹ Over 100,000 cases of cholera and 2,345 associated deaths were reported to the World Health Organization (WHO) in 2004, although it is estimated that figures represent only 5-10% of actual worldwide cases.²
• Epidemics and pandemics - two serotypes of V. cholerae cause epidemic cholera (serotype O1 and serotype O139). Serotype O1 is further divided into classical and El Tor biotypes. Outbreaks caused by the classical biotype are infrequent whereas V. cholerae El Tor now predominates and is responsible for the current seventh cholera pandemic.³ Serotype O139 emerged in 1992 and quickly spread through Asia. It is now responsible for almost 60% of recent cholera cases in China and the threat of pandemic remains.²
• United Kingdom - an average of only 10 cases of cholera are imported into the UK annually. The most common serotype is V. cholerae El Tor and most infections are acquired on the Indian subcontinent. The risk of cholera for most travellers to endemic areas is very low. The overall incidence of cholera in travellers is only 2-3 per million but, for those staying in areas of outbreaks, the incidence rises to 5 per thousand.¹

Indications - UK recommendations

Cholera vaccine is not licensed for use as an infection control tool in the management of cholera contacts or for prevention of travellers' diarrhoea. The vaccination must not be used as an alternative to standard hygiene precautions, which remain the most effective preventative measures for all food and water-borne diseases.^1,4

• Aid workers helping in disaster relief or refugee camps
• Backpackers travelling to remote areas where access to medical care is likely to be limited
• The vaccine may be considered for at-risk travellers with underlying gastrointestinal illness or immune suppression

Certification of vaccination against cholera is no longer a requirement for entry into any country.⁴

Efficacy

The vaccine confers specific protection against V. cholerae serotype O1. It is therefore ineffective for prevention of infection with non-O1 strains including V. cholerae serotype O139. Oral cholera vaccines are safe and offer good protection. It appears safe and effective for up to 2 years with a single dose and 3 or 4 years with a booster at 1 year.^5,6

Trials of the primary immunisation course using an early vaccine formulation showed an efficacy rate of 85% against El Tor disease at 6 months and 50% after 3 years. Due to cross-immunity to heat-labile enterotoxin, the vaccine also provides moderate, short-term protection against many strains of enterotoxic Escherichia coli, but this is an unlicensed indication.⁷

Preparations

The preparation Dukoral® is the only cholera vaccine licensed in the UK. It consists of four inactivated strains of V. cholerae serotype O1 combined with nontoxic, recombinant cholera toxin subunit-B.⁸ Oral administration stimulates an efficient, local secretory IgA antitoxin response at the intestinal epithelium. The traditional parenteral whole-cell cholera vaccine provided only maximum 50% protection for 3-6 months and was associated with significant adverse reactions. The use of parenteral vaccines is no longer recommended.⁹

Administration

Food, drink and oral medications must be avoided for one hour before and after vaccination. Effervescent sodium hydrogen carbonate granules are dissolved in water (150 ml for adults, and pour half away for children aged 2-6 years) and mixed with 3 mls of vaccine suspension.¹ The solution must be ingested within 2 hours of reconstitution.

The oral cholera vaccine can be given at the same time as other injected vaccines.

Schedule¹

Primary immunisation:

1. Adults and children over 6 years of age - two doses of oral vaccine are given with a 1-6-week interval.
2. Children aged 2-6 years - three doses of vaccine are necessary but each dose is given with a similar 1-6-week interval.
3. Should more than 6 weeks elapse between any doses, the primary immunisation course must be restarted. All individuals must complete the immunisation course at least 1 week prior to potential exposure.⁷

1. Adults and children over 6 years of age. A booster can be given 2 years after the primary course. If more than 2 years have elapsed since cholera vaccination the primary course must be repeated.
2. Children aged 2-6 years. A booster dose is given after 6 months.

Contra-indications

The oral cholera vaccine should not be administered to patients with:¹

• Confirmed anaphylactic reaction to oral cholera vaccine or any excipients
• Acute gastrointestinal illness or febrile illness at the time of vaccination

Precautions

• Pregnancy and breast-feeding - it is unlikely that vaccination of pregnant or breast-feeding women with inactivated bacteria or toxoids is associated with adverse outcomes. However, no data are available regarding the safety of oral cholera vaccine in such situations. The vaccine should be considered if the risk of cholera exposure is high.
• Immunosuppression including HIV - immunosuppressed individuals must be considered for cholera vaccination according to the recommendations above but such patients may not raise adequate immunological responses.

Adverse reactions

The oral cholera vaccine is generally well tolerated but reported side-effects include:¹

• Gastrointestinal symptoms of diarrhoea, nausea, vomiting, abdominal pain or cramps
• Arthralgia, rash, paraesthesia and flu-like syndrome which can occur occasionally

Document references

1. NaTHNac, Cholera, August 2007.
2. World Health Organization; Cholera: prevention and control.
3. World Health Organization; Factsheet No 107, Cholera, November 2008.
4. Department of Health; 'Yellow Book': Health information for overseas travel; 2001.
5. Graves P, Deeks J, Demicheli V, et al; Vaccines for preventing cholera. Cochrane Database Syst Rev. 2000;(4):CD000974. [abstract]
6. Longini IM Jr, Nizam A, Ali M, et al; Controlling endemic cholera with oral vaccines. PLoS Med. 2007 Nov 27;4(11):e336. [abstract]
7. Canada Communicable Disease Report; Statement on new oral cholera and travellers diarrhoea vaccination; 2005.
8. British National Formulary
9. National Library for Health; Primary Care Question Answering Service: What is the evidence for dukoral protecting against e.coli travellers diarhoea, and how often is a booster recommended for this indication? Nov 2005.

Internet and further reading

• World Health Organization; Cholera vaccines.

Acknowledgements