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Travel Health Information Sheets

Cholera

Introduction

Cholera is an acute diarrhoeal disease caused by the Gram negative bacillus Vibrio cholerae serogroup O1 or O139; Humans are the only known natural hosts. V. cholerae is endemic in many low-income countries, and is usually associated with poverty, poor sanitation and poor access to clean drinking water. V. cholerae is occasionally reported in non-endemic countries, most often as a result of importation [1].

Although more than 100 serogroups exist, only two cause epidemic cholera: V. cholerae O1 (of which there are two biotypes Classical and El Tor, further divided into serotypes; Inaba, Ogawa and (rarely) Hikojima.) and V. cholerae O139, which emerged in the Bay of Bengal in 1992 and remains confined to Asia.  Vibrio cholerae serogroup O1 accounts for most cases in the current, seventh pandemic [2]. In recent years, new variants of V. cholerae (El Tor) have emerged.  These strains first identified in Bangladesh and since associated with outbreaks in Africa, Asia and Hispaniola, appear to be more virulent, causing more severe disease. Antibiotic resistance is also emerging in some parts of the world [1].

It has been estimated that there are between 3 and 5 million cases of cholera each year [1, 3].  

 

Epidemiology

Global epidemiology of cholera

Cholera is a disease that occurs in low-income regions of the world where sanitation and food and water hygiene are inadequate. Imported cases occasionally occur in travellers returning from endemic areas [2]. 

In areas without clean water or sewage disposal (as may occur after natural disasters or in displaced populations in areas of conflict), cholera can spread quickly and have a case fatality rate of as high as 50% in vulnerable groups with limited medical care [2, 3] 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 [4].

Figure 1.Map of Global Epidemiology of Cholera 2011-2012 (courtesy of the World Health Organization)

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Cholera often occurs in large epidemics or pandemics. In the 19th century, pandemics frequently originated from the Ganges delta in India, and up to the mid 20th century, were largely confined to Asia (except for a large epidemic in Egypt in 1947). The current, seventh pandemic caused by V. cholerae O1 El Tor, originated in Indonesia in 1961 and spread rapidly through most of Asia [2]. In 1970, this biotype was introduced into West Africa, and is now endemic in many African countries. In 1991, it was introduced into Peru where it had been absent for nearly 100 years, and from there spread throughout many countries of Latin America. Another serogroup, V. cholerae O139, was discovered as the cause of cholera epidemics in India and Bangladesh in 1992 and has since spread to other countries in South East Asia and China [1].

Fifty eight countries reported cholera cases to WHO in 2011, compared to 48 countries reporting in 2010 [1, 4].  Of the 2011 global total of 589,854 cases reported, the majority (340,311 including 2,869 deaths) were from Haiti where the large outbreak that started in October 2010 continues. Elsewhere in the Americas, autochthonous transmission was reported in Mexico (one case) and the US (two cases) and imported cases were reported from the Bahamas (1), the Bolivarian Republic of Venezuela (49), Brazil (1), Canada (9), Chile (1) and the Dominican Republic (45) [1].

In Africa, 27 countries reported a total of 188,678 cases (including 4,183 deaths). The majority of cases were reported from four countries (Cameroon, Democratic Republic of Congo, Nigeria and Somalia) [1].

Asia reported a total of 38,298 cases in 15 countries; the greatest number of cases were reported from Afghanistan (3,733 cases including 4 deaths) and Iran (1,187 cases including 12 deaths).  Oceania reported 1,535 cases with two deaths in 2011, all in Papua New Guinea, which has been considered endemic since the outbreak of 2009 [1].

During May and June 2011, Ukraine reported 33 cases in Mariupol, Doetsk Oblast. Although Ukraine is not classified as an endemic country, cholera had previously been reported in Ukraine in 2005 (1 case) and during 1994-5 (1,370 cases and 32 deaths) [3, 5, 6].   

Globally, mortality and morbidity relating to cholera is likely to be grossly under-reported due to the limitations of surveillance and reporting systems [1]. WHO estimates the actual global burden of disease as 3 to 5 million cholera cases and 100,000 to 120,000 deaths each year [1, 3].

The large numbers of acute watery diarrhoea, estimated to number between 500,000-700,000 cases globally each year and many of which may be cholera, are not included in WHO cholera reports.

 

Cholera in travellers from England and Wales:

Cholera is rarely reported in UK travellers. Between 2004 and 2012, an average of 16 cases of cholera, caused by V. cholerae serogroups O1 and O139, were reported in England and Wales by the Public Health England Gastrointestinal Infections Reference Unit (Figure 2).

 

Figure 2. Laboratory reports of Vibrio cholerae O1 and O139: England and Wales, 2004 - 2012

 

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The Indian sub-continent is the most common region of acquisition of cholera reported in England and Wales [7].

Between 2004 and 2012, out of a total of 143 reported cases, 111 (78%)  were presumed to have acquired their infection in the Indian sub-continent [.Personal communication: Travel and Migrant Health Section, Public Health England, 30 May 2013].

 

 Risk for travellers

The overall risk of cholera for travellers is extremely low and is in the order of 0.2 cases per 100,000 travellers [8, 9]. For long-term travellers in areas of outbreaks the rate may be as high as 500 cases per 100,000 travellers [8], and when routine screening for V. cholerae is done in travellers with diarrhoea who have returned from endemic areas, the rate may approach five cases per 100,000 [10]. Activities that may predispose to infection include drinking untreated water or eating poorly cooked seafood in endemic areas. Travellers living in unsanitary conditions, for example relief workers in disaster or refugee areas, are also at risk [10].

 

Transmission

Cholera is transmitted via the faecal-oral route, most commonly by consumption of contaminated water and, to a lesser degree, food; direct person-to-person transmission is rare.

A high infecting dose is necessary to cause illness in healthy individuals.

 

Signs and symptoms

The usual incubation period is 2 to 5 days, although it can be as short as several hours.  Severe cholera is characterised by a sudden onset of profuse, watery diarrhoea accompanied by nausea and vomiting. If left untreated, this can rapidly lead to serious dehydration, electrolyte imbalance and circulatory collapse. Over 50% of the most severe cases die within a few hours; with prompt, effective treatment, mortality is less than 1%.

Cholera may be asymptomatic or mild in healthy individuals, with diarrhoea as the only symptom [11].

 

Treatment

Rapid fluid replacement with a balanced solution of sugar, electrolytes and water (oral rehydration salts) should be started urgently [12]. This may be done orally, but severely dehydrated cases may require intravenous administration. Cases may also be treated with antibiotics in order to improve symptoms and decrease the intestinal excretion of the organism [11]. Patients who are promptly treated should respond rapidly and recover.

Prevention

For the majority of travellers advice on food and water hygiene precautions is the most appropriate prevention strategy.

An oral cholera vaccine is available in the UK. Trials of this vaccine against cholera (serotype O1) indicate that it will protect up to 86% of people living in cholera endemic areas for four to six months [9]. Lower levels of protection continue for three years. Protection wanes more rapidly in young children.

The vaccine is not indicated for most travellers. It can be offered to humanitarian aid and relief workers and travellers with remote itineraries in areas of cholera outbreaks who have limited access to safe water and medical care.

It has been proposed that the vaccine can be used to protect against the syndrome of travellers’ diarrhoea. While there is partial protection against one agent of travellers’ diarrhoea, Escherichia coli that produce heat labile enterotoxin, the vaccine will not protect against the many other causes of travellers’ diarrhoea [9].

Cholera vaccine information

Availability of vaccine:

There is one cholera vaccine licensed for use in the UK, Dukoral™ (Crucell), which protects against infection caused by V. cholerae serogroup O1. It is inactivated, thiomersal-free, and does not contain live organisms, so therefore cannot cause cholera disease [13]. Each dose contains approximately 1x1011 bacteria of V. cholerae, combined with recombinant cholera toxin B [14]:

  • O1 Inaba classical biotype (heat-inactivated).
  • O1 Inaba El Tor biotype (formalin-inactivated).
  • O1 Ogawa classical biotype (heat-inactivated).
  • O1 Ogawa classical biotype (formalin-inactivated).
  • Recombinant cholera toxin B subunit (rCTB) 1 mg (produced in V. cholerae O1 Inaba, classical biotype).

Indications for use of vaccine:

The vaccine can be considered for travellers visiting areas with cholera of V. cholerae serogroup O1 strain, specifically [9, 13, 14]:

aid workers assisting in disaster relief or refugee camps.

travellers with remote itineraries in areas with cholera outbreaks and with limited access to medical care.

The vaccine may also provide some protection against diarrhoea caused by Escherichia coli producing a heat-labile enterotoxin. However, it is unlicensed in the UK for this use as there is limited data on efficacy in travellers; it is not recommended for this indication [9, 13]. For specific information on travellers’ diarrhoea see NaTHNaC’s separate information sheet.

Vaccine schedules:

Age Primary course Reinforcing doses
Adults and children older than 6 years

2 doses with an interval of at least one week between them. If more than six weeks have elapsed between doses, the primary course should be restarted. 

Single dose after two years. If more than 2 years have elapsed since initial course, the entire course should be repeated.
Age 2 to 6 years
3 doses with an interval of at least one week between. If more than six weeks have elapsed between doses, the primary course should be restarted.  
Single dose after six months. As with adults and children older than 6 years, if more than 2 years have elapsed, the whole course should be repeated.

Dukoral™ has been given to children between 1 and 2 years of age in immunogenicity and safety studies. However, the protective efficacy has not been studied in this age group. Therefore it is not recommended for children under 2 years of age [14].

 

Administration:

Dukoral™ is an oral vaccine. The preparation consists of a 3 ml suspension of vaccine and a separate packet of effervescent granules. For adults, the granules are first dissolved into approximately 150ml of water, and then the vaccine is added. The solution is stirred well and should be drunk within two hours of preparation [13].

For children aged 2 to 6 years, half the solution containing the effervescent granules is poured away and the vaccine suspension is added to the remaining 75mls.

Interrupted courses:

The Summary of Product Characteristics (SPC) advises that if more than six weeks have elapsed between doses during the primary vaccination course, the course should be begun again.

The SPC also suggests that if more than two years have elapsed between the completion of the primary course and administration of a reinforcing dose, the primary course should be repeated [14].

Contraindications:

  • Hypersensitivity to active substances or ingredients of the vaccine.
  • Current acute gastrointestinal illness or febrile illness.

 

Adverse events:

 

In clinical trials, adverse events were uncommon; those most frequently reported were gastrointestinal. These included abdominal pain, diarrhoea, abdominal cramps and general discomfort [13, 14].

References

1. World Health Organization. Cholera 2011. Wkly Epidemiol Rec. 87:289-304. [Accessed 5 June, 2013]. Available at: http://www.who.int/wer/2012/wer8731_32.pdf

2. Lam C, Octavia S, Reeves P, et al. Evolution of seventh cholera pandemic and origin of 1991 epidemic, Latin America. Emerg Infect Dis. 2010 16:1130-2, 2010. [Accessed  5 June, 2013]. Available at: http://www.cdc.gov/EID/content/16/7/1130.htm.

 3. Ali M, Lopez AL, You YA et al.  The global burden of cholera. Bull World Health Organ. 2012 Mar 1; 90(3):209-218A. doi: 10.2471/BLT.11.093427. Epub 2012 Jan 24. [Accessed 5 June, 2013]. Available at: http://www.who.int/bulletin/volumes/90/3/11-093427/en/

4. World Health Organization. Cholera vaccines: WHO position paper. Wkly Epidemiol Rec. 85:117-28, 2010. [Accessed 5 June 28 May, 2013]. Available at: http://www.who.int/wer/2011/wer8631.pdf

5. World Health Organization. Europe Region. 6 June 2011. Ukraine reports 14 cholera cases. [Accessed 5 June 28 May, 2013]. Available at: http://goo.gl/b2y5q

6. Clark CG, Kravetz AN, Alekseenko VV. Microbiological and epidemiological investigation of cholera epidemic in Ukraine during 1994 and 1995.  Epidemiol Infect. 1998 Aug; 121(1):1-13.

7. Public Health England. Cholera. [Accessed 5 June, 2013]. Available at: http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/

TravelHealth/EpidemiologicalData/GastrointestinalInfections/

travCholera/

8. Wittlinger F, Steffen R, Watanabe H, Handszuh H. Risk of cholera among Western and Japanese travellers. J Travel Med 2:154-8, 1995.

9. Hill DR, Ford L and Lalloo, DG. Oral cholera vaccines: use in clinical practice. Lancet Infect Dis. 6:361-73, 2006.

Morger H, Steffen R, Schär M. Epidemiology of cholera in travellers, and conclusions for vaccination recommendations. BMJ. 286:184-6, 1983.

10. Field VF, Ford L, Hill DR (eds). Health Information for Overseas Travel. National Travel Health Network and Centre, London, UK. 2010

11. World Health Organization. Cholera fact Sheet No.107. July 2012.. [Accessed 5 June, 2013]. Available at:  http://www.who.int/mediacentre/factsheets/fs107/en/index.html

12. Cholera. Ch 14 In: Salisbury D, Ramsay M, Noakes K., eds. Immunisation against infectious disease. Department of Health. 3rd ed, London:TSO. 99-108, 2006. [Accessed 5 June, 2013]. Available at:  https://www.gov.uk/government/publications/cholera-the-green-book-chapter-14

13. Jansen-Cilag Ltd.. Dukoral Oral Cholera Vaccine – Summary of Product Characteristics. Crucell. Bradford. 20 May 2010. [Accessed 5 June, 2013]. Available at: http://www.medicines.org.uk/emc/medicine/26272/SPC/

Dukoral+Oral+Cholera+Vaccine/

Reading List

Field VF, Ford L, Hill DR, eds. Health Information for Overseas Travel. National Travel Health Network and Centre, London, UK, 2010.

Centers for Disease Control and Prevention. Chapter 5: Other Infectious Diseases Related to Travel – Cholera. Health Information for International Travel 2010. Atlanta. Elsevier. 2012. Ch 3. Available at: http://wwwnc.cdc.gov/travel/yellowbook/2010/chapter-5/cholera.aspx

World Health Organization. International Travel and Health. 2012.

Updated June 2013