Traveller vaccination typhoid fever

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]

## Disease cause

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The typhoid bacillus Salmonella Typhi, which infects humans only. Paratyphoid and enteric fevers are caused by other species of Salmonella, which infect domestic animals as well as humans.

## Transmission

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The typhoid bacillus is transmitted by consumption of contaminated food or water. Occasionally, direct faecal-oral transmission may occur. Shellfish taken from sewage-polluted areas are an important source of infection; transmission also occurs through eating raw fruit and vegetables fertilized with human excreta and through ingestion of contaminated milk and milk products. Flies may cause human infection through transfer of the infectious agents to foods. Pollution of water sources may produce epidemics of typhoid fever when large numbers of people use the same source of drinking water.

## Nature of the disease

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Typhoid fever is a systemic disease of varying severity. Severe cases are characterized by gradual onset of fever, headache, malaise, anorexia and insomnia. Constipation is more common than diarrhea in adults and older children. Without treatment, some patients develop sustained fever, bradycardia, hepatosplenomegaly, abdominal symptoms and, occasionally, pneumonia. In whiteskinned patients, pink spots, which fade on pressure, appear on the skin of the trunk in up to 20% of cases. In the third week, untreated cases may develop gastrointestinal and cerebral complications, which may prove fatal in up to 10% to 20% of cases. The highest case fatality rates are reported in children <4 years of age. Around 2% to 5% of infected people become chronic carriers, as bacteria persist in the biliary tract after symptoms have resolved.

## Geographical distribution

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There is a higher risk of typhoid fever in countries or areas with low standards of hygiene and water supply.

## Risk for travellers

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All travellers to endemic areas are at potential risk of typhoid fever, although the risk is generally low in tourist and business centres where standards of accommodation, sanitation and food hygiene are high. Areas of high endemicity include parts of northern and western Africa, southern Asia, parts of Indonesia and Peru. Elsewhere, travellers are usually at risk only when exposed to low standards of hygiene. Even vaccinated travellers should take care to avoid consumption of potentially contaminated food and water as the vaccine does not confer 100% protection. There have been reports of increasing antibiotic resistance among S. Typhi isolates from highly endemic countries.

## Vaccine

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Typhoid fever vaccination may be offered to travellers to destinations where the risk of typhoid fever is high, especially to those staying in endemic areas for >1 month and/or in locations where antibiotic-resistant strains of S. Typhi are prevalent. For previously vaccinated tourists travelling from non-endemic to endemic areas, a booster dose is recommended after 1–7 years, depending on national recommendations. Currently, two typhoid vaccines of demonstrated safety and efficacy are available on the international market:

* The oral vaccine based on the live, attenuated mutant strain of S. Typhi Ty21a (Ty21a vaccine). This vaccine is supplied in enteric-coated capsules. To date, Ty21a has been used primarily to protect travellers and not to control endemic typhoid fever in developing countries. In Australia and Europe, three tablets are given on days 1, 3 and 5; this series is repeated every year for individuals travelling from nonendemic to endemic countries, and every three years for individuals living in countries or areas at risk. In North America, four tablets are given on days 1, 3, 5 and 7 and revaccination is recommended only after seven years (Canada) or five years (United States of America) for all, regardless of typhoid fever risk in the country or area of residence. The duration of protection following Ty21a immunization is not well defined and may vary with vaccine dose and possibly with subsequent exposures to S. Typhi (natural booster).
* The injectable Vi capsular polysaccharide (ViCPS) vaccine is given intramuscularly in a single dose. Protection is achieved about 7 days after the injection. In endemic countries, the protective efficacy 1.5 years after vaccination is about 72%, and after 3 years about 50%. The vaccine is licensed for individuals aged >2 years. To maintain protection, revaccination is recommended every 3 years. The Vi polysaccharide vaccine can be co-administered with other vaccines relevant for international travellers, such as yellow fever and hepatitis A, and with vaccines of the routine childhood immunization programmes.

A combined typhoid/hepatitis A vaccine is also available in some countries.

Contraindications and precautions:

Both typhoid vaccines are safe and there are no contraindications to their use other than previous severe hypersensitivity reactions to vaccine components. Proguanil, mefloquine and antibiotics should be stopped from 3 days before until 3 days after the administration of Ty21a. These vaccines are not recommended for use in infant immunization programmes because of insufficient information on their efficacy in children under 2 years of age.

## Summary of vaccine data

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| Considerations for travellers for Typhoid fever vaccination

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Type of vaccine  |

* The oral vaccine based on the live, attenuated mutant strain of Salmonella Typhi Ty21a (Ty21a vaccine). This vaccine is supplied in enteric-coated capsules. Depending on national recommendations, primary vaccination consists of three or four capsules, one capsule every other day. Revaccination is recommended after 1-7 years. To date, Ty21a has been used primarily to protect travellers;

* The injectable Vi capsular polysaccharide (ViCPS) vaccine is given intramuscularly in a single dose to individuals aged 2 years or more. To maintain protection, revaccination is recommended every three years. A combined typhoid/hepatitis A vaccine is also available in some countries

Contraindications  |

* Serious allergy to any of the vaccine components.

Adverse reactions  |

* Both vaccines are safe and well tolerated

Before departure  |

* In general, immunity develops about 7-10 days after primary vaccination.

Indication  |

* Long-term (>1 month) visitors to highly endemic areas, in particular where antibiotic-resistant strains of S. Typhi are prevalent.

Special precautions  |

* Proguanil, mefloquine and antibiotics should be avoided from 3 days before until 3 days after the administration of Ty21a.