Cholera

What

Cholera is usually caused by ingesting contaminated food or water. Cholera is characterised by the sudden onset of diarrhoea and can result in severe dehydration. Only 2 serogroups of the bacterium Vibrio cholerae produce the enterotoxin that causes disease: O1 and O139.

Who

Cholera vaccine is recommended for children (≥2 years of age) and adult travellers who:

• have a high risk of acquiring diarrhoeal disease
• are travelling to areas where there is a high likelihood of exposure to cholera

How

Cholera vaccination is only available in Australia as an oral vaccine against serogroup O1.

Children aged 2–6 years are recommended to receive 3 doses of cholera vaccine with an interval of 1–6 weeks between each dose.

Adults and children aged ≥6 years are recommended to receive 2 doses of cholera vaccine with an interval of 1–6 weeks between each dose.

Why

Cholera causes a large burden of disease in developing countries. It can be brought back to Australia by children and adults travelling to cholera-endemic areas.

Cholera vaccine available in Australia

The Therapeutic Goods Administration website provides product information for each vaccine.

See also Vaccine information and Variations from product information for more details.

Dose and route

Dukoral is an oral vaccine.

Avoid food and drink for 1 hour before and 1 hour after receiving the inactivated cholera vaccine, because the vaccine is acid-labile

Children aged 2–6 years

Children aged 2–6 years are recommended to receive 3 doses of cholera vaccine. They need 75 mL cholera vaccine for each dose.

The interval between each dose is 1–6 weeks. If the previous dose was more than 6 weeks ago, restart the primary course.

To give the vaccine to children aged 2–6 years:

• dissolve the buffer granules in 150 mL water
• pour away half the solution
• mix the entire contents of the vaccine vial in the remaining 75 mL
• administer to the child

Reconstituted vaccine should be used within 2 hours.

If there is an ongoing risk of cholera, a single booster dose is recommended 6 months after finishing the primary course. If the interval between primary immunisation and the booster dose is more than 6 months, repeat the primary course.

Adults and children aged >6 years

Adults and children aged ≥6 years are recommended to receive 2 doses of cholera vaccine. They need 150 mL cholera vaccine for each dose.

The interval between doses is 1–6 weeks. If the 2nd dose is more than 6 weeks after the 1st dose, restart the primary course.

Adults and children aged >6 years need 150 mL cholera vaccine for each dose.

To give the vaccine to adults and children aged >6 years:

• dissolve the buffer granules in 150 mL water
• mix the entire contents of the vaccine vial in the buffer
• administer to the person

Reconstituted vaccine should be used within 2 hours.

If there is an ongoing risk of cholera, a single booster dose is recommended up to 2 years after finishing the primary course. If the interval between primary immunisation and the booster dose is more than 2 years, repeat the primary course.

Co-administration with other vaccines

Travellers can receive the inactivated oral cholera vaccine at any time before or after, or with, other travel vaccines, such as yellow fever or parenteral Vi polysaccharide typhoid vaccines.

People receiving inactivated oral cholera vaccine and oral live attenuated typhoid vaccine should have the vaccines at least 8 hours apart. See Contraindications and precautions.

Contraindications

The only absolute contraindications to cholera vaccine are:

• anaphylaxis after a previous dose of any cholera vaccine
• anaphylaxis after any component of a cholera vaccine

Precautions

Illness

People should not receive cholera vaccine if they have either:

• acute febrile illness, or
• acute gastrointestinal illness with persistent diarrhoea or vomiting

Wait until they have recovered.

Immunocompromising conditions

People who are immunocompromised can receive cholera vaccine, including people with HIV. However, there are limited data on the effectiveness of the vaccine in this population.

Women who are pregnant or breastfeeding

Cholera vaccine is not routinely recommended for pregnant or breastfeeding women.

There is limited information on using inactivated oral cholera vaccine during pregnancy and breastfeeding. ¹ Evidence suggests that, if vaccination is warranted, the high potential benefit outweighs the minimal risks. ^{1, 2}

See Table. Recommendations for vaccines that are not routinely recommended in pregnancy: inactivated bacterial vaccines in Vaccination for women who are planning pregnancy, pregnant or breastfeeding for more details.

Co-administration with oral live attenuated typhoid vaccine

People receiving inactivated oral cholera vaccine and oral live attenuated typhoid vaccine should have the vaccines at least 8 hours apart. This is because the buffer in the cholera vaccine may affect how the capsules of oral typhoid vaccine move through the gastrointestinal tract.

Inactivated oral cholera vaccine has a good safety profile. Mild abdominal pain, discomfort and diarrhoea were reported from post-marketing surveillance at a frequency of 0.1–1%.³ Similar rates of adverse events were reported among vaccine and placebo clinical trial participants.^1,4,5

Pathogenesis and transmission

Cholera is caused by Vibrio cholerae, a motile, curved gram-negative bacterium. Transmission mainly occurs when people ingest faecally contaminated food or water. Seafood caught from contaminated water has also caused outbreaks.⁶

There are more than 150 serogroups of V. cholerae, distinguished by differences in the O antigens. Only 2 serogroups produce the enterotoxin that causes cholera disease: O1 and O139.

Persistence in the environment

Vibrio cholerae can persist in water, depending on the temperature, pH, salinity and nutrient availability.

It can survive under unfavourable conditions in a viable dormant state.⁶

Symptoms of cholera

Cholera is an acute bacterial infection that is characterised by the sudden onset of diarrhoea that is:

• painless
• profuse
• watery

Cases vary from mild to severe. Subclinical infection can also occur.⁶

Death from cholera is rare, but, when cases are severe, cholera is one of the most rapidly fatal diseases in humans.⁶ Cholera can be fatal within 6–12 hours of symptom onset. Case-fatality rates can range from 2% to 10% without appropriate medical care.⁷

The cholera toxin does not cause intestinal inflammation. It causes increased amounts of electrolytes to be secreted into the intestinal lumen. This results in mild to severe dehydration, and sometimes metabolic acidosis.

Cholera in Australia

About 2–6 cases of cholera occur in Australia each year.

Since the National Notifiable Diseases Surveillance System started in 1991, nearly all reported cholera cases have been acquired outside Australia. The exceptions include 1 case of laboratory-acquired cholera in 1996 and 3 cases in 2006 that were associated with eating raw imported whitebait.^8,9 These 3 people with food-acquired cholera had no history of recent travel to known cholera-endemic areas.⁹

In 1977, a locally acquired case led to the discovery of Vibrio cholerae in some rivers along the Queensland coast.¹⁰ Because of this, health workers should be aware that sporadic cases of cholera may occur after contact with estuarine waters. However, this is rare.

Cholera in other countries

Cholera is a large health burden in developing countries. It is endemic in:¹

• Haiti
• South and Southeast Asia
• sub-Saharan Africa

Cholera epidemics are common in situations in which food and water supplies can be contaminated, such as after natural disasters and civil unrest.¹¹ The overall risk of cholera is low for travellers who have access to a safe water source and hygienic food preparation, even in endemic countries.

The risk of infection is estimated to be 0.2 cases per 100,000 travellers from western countries. The risk of severe disease is considerably lower.¹² However, cholera in travellers is likely to be underdetected and under-reported.^11-13

Vaccine efficacy

Efficacy trials of the oral cholera vaccine have mainly been done in Bangladesh and Peru. These trials used vaccines containing inactivated whole-cell Vibrio cholerae serogroup O1 combined with recombinant cholera toxin B subunit (rCTB).^4,14-19

The large randomised controlled trial in Bangladesh found that age appeared to affect vaccine efficacy. Efficacy was lower and waned more rapidly in children aged 2–5 years.¹⁷ In this age group, efficacy was 100% during the first 4–6 months after vaccination but decreased rapidly after that. Overall efficacy was 38% after 1 year and similar after 2 years. 

In contrast, for people aged >5 years, the efficacy estimates were 78% after 1 year and 63% after 2 years.^15-17 When the cholera cases in all age groups were aggregated, the protective efficacy was 62% after 1 year and 57% after 2 years.

Long-term follow-up to 5 years showed no significant protective efficacy beyond 2 years.^16,17

The protective efficacy of the vaccine over a 3-year follow-up period was not significantly different between those who received 2 doses and those who received 3 doses (including all ages).^15,16 

The randomised controlled trial in Peru among military recruits 16–45 years of age found a vaccine efficacy of 86% against symptomatic cholera after 2 vaccine doses.¹⁹

Another Peruvian household study in people 2–65 years of age showed that a booster dose 10 months after a 2-dose primary series had an overall efficacy of 61%.⁴

Vaccine effectiveness

A case–control study was done in Mozambique during a mass oral cholera vaccination program. People in the study were aged ≥2 years and lived in an endemic area. The inactivated oral cholera vaccine was 78% protective 1–6 months after the 1st dose and 84% protective 0.5–4.5 months after the 2nd dose. ²⁰

Vaccine against serogroup O139

The vaccine marketed in Australia does not protect against infection with Vibrio cholerae serogroup O139.

Transport according to National Vaccine Storage Guidelines: Strive for 5.²¹ Store at +2°C to +8°C. Do not freeze. Protect from light.

The person to be vaccinated is responsible for the vaccine after they buy it. Carefully explain:

• how to transport the vaccine from pharmacy to home
• how to store it at home in the refrigerator

Cholera is a notifiable disease in all states and territories in Australia. People with cholera must also be quarantined.

State and territory public health authorities can provide advice about the public health management of cholera, including management of cases and contacts.

The production information for Dukoral states that a booster dose is recommended for adults 2 years after completing the primary vaccine course if there is an ongoing risk of cholera or in circumstances of repeated travel.

The Australian Technical Advisory Group on Immunisation recommends a booster dose for people >6 years of age 2 years after completing the primary vaccine course if there is an ongoing risk of cholera.

1. World Health Organization (WHO). Cholera vaccines: WHO position paper – August 2017. Weekly Epidemiological Record 2017;92:477-98.
2. Hashim R, Khatib AM, Enwere G, et al. Safety of the recombinant cholera toxin B subunit, killed whole-cell (rBS-WC) oral cholera vaccine in pregnancy. PLoS Neglected Tropical Diseases 2012;6:e1743.
3. Cholera. In: Ramsay M, ed. Immunisation against infectious disease: the green book. London: Public Health England; 2013. 
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5. Peltola H, Siitonen A, Kyrönseppä H, et al. Prevention of travellers' diarrhoea by oral B-subunit/whole-cell cholera vaccine. The Lancet 1991;338:1285-9.
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12. Jelinek T, Kollaritsch H. Vaccination with Dukoral® against travelers' diarrhea (ETEC) and cholera. Expert Review of Vaccines 2008;7:561-7.
13. Weinke T, Liebold I, Burchard GD, et al. Prophylactic immunisation against traveller's diarrhoea caused by enterotoxin-forming strains of Escherichia coli and against cholera: does it make sense and for whom? Travel Medicine and Infectious Disease 2008;6:362-7.
14. Clemens JD, Sack DA, Harris JR, et al. Field trial of oral cholera vaccines in Bangladesh. The Lancet 1986;2:124-7.
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16. Clemens JD, Sack DA, Harris JR, et al. Field trial of oral cholera vaccines in Bangladesh: results from three-year follow-up. The Lancet 1990;335:270-3.
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18. Clemens JD, Stanton BF, Chakraborty J, et al. B subunit-whole cell and whole cell-only oral vaccines against cholera: studies on reactogenicity and immunogenicity. Journal of Infectious Diseases 1987;155:79-85.
19. Sanchez JL, Vasquez B, Begue RE, et al. Protective efficacy of oral whole-cell/recombinant-B-subunit cholera vaccine in Peruvian military recruits. The Lancet 1994;344:1273-6.
20. Lucas ME, Deen JL, von Seidlein L, et al. Effectiveness of mass oral cholera vaccination in Beira, Mozambique. New England Journal of Medicine 2005;352:757-67.
21. National Vaccine Storage Guidelines: Strive for 5. 3rd ed. Canberra: Australian Government Department of Health and Ageing; 2019. https://www.health.gov.au/resources/publications/national-vaccine-storage-guidelines-strive-for-5