Cholera and Cholera Vaccination

Cholera is an acute diarrhoeal infection caused by the enterotoxin subunit-A of Vibrio cholerae. Vibrios are one of the most common organisms in surface waters of the world. Cholera is a water-borne infection caught through ingestion of faecally contaminated water or shellfish. Person-to-person spread via the faeco-oral route can also occur.

It can produce watery diarrhoea that is very profuse and this can rapidly lead to severe dehydration and death. Transmission is usually from contaminated water and direct person-to-person transmission by the faeco-oral route can occur.

Over 100 serotypes of V. cholerae exist but only two cause disease. V. cholerae O1 has two variants called classical and El Tor. The other pathogen is O139.

There are other types of species of V. cholerae which also cause infection in humans. They include V. parahaemolyticus, V. mimicus, V. damsela and V. hollisae and they also cause diarrhoea. There are also two other related families called aeromonas and plesiomonas and they cause diarrhoea, wound infections, septicaemia, ocular infections and meningitis.

Two serotypes of V. cholerae cause epidemic cholera (serotype O1 and serotype O139). Serotype O1 is further divided into classical and El Tor biotypes. The World Health Organization (WHO) reports the emergence of new, apparently more virulent strains of V. cholerae O1 which now predominate in parts of Africa and Asia, and the emergence and spread of antibiotic-resistant strains^[1].

Epidemiology

Cholera is prevalent in areas with poor sanitation and poor food and water hygiene and constitutes a major global public health problem. The disease is not endemic to the UK and is rarely imported from abroad (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 disease is endemic to parts of Africa, Asia, the Middle East and South America. Large outbreaks are common after natural disasters or in populations displaced by war, where there are inadequate sewage disposal and contaminated water.
• The cholera burden has grown strikingly during a period of four years and has spread to countries previously spared by this disease^[2].
• Most of the recent pandemics have been due to El Tor but O1 classical and O139 are endemic in India and Bangladesh.
• Non-O1 and non-O139 V. cholerae can cause mild diarrhoea but do not generate epidemics.
• There are an estimated 3-5 million cholera cases and 100,000-120,000 deaths due to cholera every year^[1].

Risks for travellers

• 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^[3].
• A high infecting dose (as many as 1,011 organisms) is necessary to cause illness in healthy individuals.
• Drinking untreated water or eating poorly cooked seafood in endemic areas carries a high risk.
• Large outbreaks are common after natural disasters or in populations displaced by war, where inadequate sewage disposal and contaminated water exist.
• Travellers living in unsanitary conditions, such as humanitarian relief workers in disaster areas, are also at risk.

Presentation

The incubation period is usually 2-5 days. However, it can sometimes be a few hours. 75% of those infected are asymptomatic^[4]. However, those who remain asymptomatic excrete the organism for 7 to 14 days.

History

A number develop a moderate form of diarrhoea that is clinically indistinguishable from other forms of gastroenteritis. No more than 10% develop the very profuse diarrhoea that is regarded as characteristic of the disease.

• Severe illness - sudden onset of profuse, watery diarrhoea with nausea and vomiting.
• The volume of fluid lost can be up to 20 litres a day.
• If not replaced, heavy fluid loss rapidly leads to serious dehydration and circulatory collapse.

Examination

The severely dehydrated patient will look very unwell with sunken eyes and possibly impaired level of consciousness. Skin will be dry and lacking turgor. Pulse will be fast but weak with a low blood pressure indicating haemodynamic instability.

Investigations

• Stool specimen to identify the organism.
• U&E, as the patient is likely to be significantly dehydrated, and to monitor IV fluid replacement. Creatinine may rise if the kidneys fail with circulatory collapse.
• FBC will often show a high Hb with haemoconcentration.
• WCC is likely to be raised but will not aid diagnosis or management.

A good way of estimating net fluid loss or gain if changes are large is to weigh the patient daily. 1 kg of weight represents 1 litre of fluid.

Management

Without treatment, severe infection has a mortality rate of 30-50%. However, cholera is an easily treatable disease. Prompt correct treatment reduces mortality to less than 1%.

Resuscitation

• The basis of treatment is the replacement of lost fluid.
• This may be done orally if not very severe or if there is no access to facilities for IV replacement but the latter is required in severe fluid loss.
• Up to 80% of people can be treated successfully through prompt administration of oral rehydration salts.

Antibiotics

• Antibiotic treatment decreases volume and duration of diarrhoea by 50% and is recommended for patients with moderate-to-severe dehydration^[5].
• Tetracycline, doxycycline or ciprofloxacin are often used.
• Mass administration of antibiotics is not recommended, as it has no effect on the spread of cholera and contributes to increasing antimicrobial resistance^[1].

Antidiarrhoeal and antisecretory drugs

• Antidiarrhoeal drugs are not recommended.
• Many antisecretory drugs have been tried as an adjunct therapy but none has been found useful.

Prevention

All travellers should take sensible precautions about food and water hygiene. An oral cholera vaccine is now available in the UK (see below) . The vaccine is not required by most travellers but may be suitable for those who are unable to take adequate precautions in highly endemic or epidemic settings. This would include aid workers assisting in disaster relief or refugee camps, and more adventurous backpackers who do not have access to medical care.

Some countries have already used oral cholera vaccines to immunise populations considered to be at high risk for cholera outbreaks^[6].

Cholera vaccination

Indications for vaccine - UK recommendations

Cholera vaccine is not licensed for use as an infection control tool in the management of cholera contacts or for prevention of traveller's diarrhoea^[7].

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.

Immunisation can be considered for the following:

• Aid workers helping in disaster relief or refugee camps.
• Backpackers travelling to remote areas where access to medical care is likely to be limited.
• Certification of vaccination against cholera is no longer a requirement for entry into any country.

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.
• The currently available oral killed whole-cell vaccines can prevent 50-60% of cholera episodes during the first two years after the primary vaccination schedule^[8].
• Injectable cholera vaccine provides unreliable protection and is no longer available in the UK^[9].

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 non-toxic, recombinant cholera toxin subunit-B^[7]. 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.

Administration

Food, drink and oral medications must be avoided for one hour before and one hour 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^[7]. The solution must be ingested within two hours of reconstitution.

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

Schedule^[7]

Primary immunisation

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

Boosters
A single booster to augment immunity is recommended:

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

Contra-indications

The oral cholera vaccine should not be administered to patients with^[3]:

• Confirmed anaphylactic reaction to oral cholera vaccine.
• Confirmed anaphylactic reaction to any of the components of the vaccine.
• Acute gastrointestinal illness - the vaccine should be delayed in those with acute gastrointestinal illness. Pre-existing gastrointestinal illnesses are not contra-indications to the vaccine.

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 may not raise adequate immunological responses.

Adverse reactions

• The oral cholera vaccine is generally well tolerated but reported side-effects include^[3]:
• Gastrointestinal symptoms of diarrhoea, nausea, vomiting, abdominal pain or cramps occurring in up to 1 in 100 cases.
• Arthralgia, rash, paraesthesia and flu-like syndrome which can occur rarely.