Typhoid Fever

Description

Typhoid fever is an acute, life-threatening febrile illness caused by the bacterium Salmonella enterica Typhi.

Occurrence

An estimated 22 million cases of typhoid fever and 200,000 related deaths occur worldwide each year. Approximately 400 cases of typhoid fever, mostly among travellers, are reported to the Centers for Disease Control and Prevention each year.

Risk for Travellers

Typhoid vaccination is not required for international travel, but CDC recommends it for travellers to areas where there is a recognised risk of exposure to S. Typhi. Risk is greatest for travellers to the Indian Subcontinent and other developing countries in Asia, Africa, the Caribbean, and Central and South America. Travellers who are visiting relatives or friends and who may be less likely to eat only safe foods (cooked and served hot) and beverages (carbonated beverages or those made from water that has been boiled) are at greater risk. Vaccination is particularly recommended for those who will be travelling in smaller cities, villages, and rural areas off the usual tourist itineraries, where food and beverage choices may be more limited. Travellers have acquired typhoid fever even during brief visits of <1 week to countries where the disease is endemic. While immunisation is recommended, travellers should be cautioned that none of the available typhoid vaccines is 100% effective, nor do they provide cross protection against other common causes of gastrointestinal infections. Typhoid vaccination is not a substitute for careful selection of food and drink.

Clinical Presentation

The hallmark of typhoid infection is persistent, high fevers. Other common symptoms and signs include headache, malaise, anorexia, splenomegaly, and relative bradycardia. Many mild and atypical infections occur.

Prevention

Vaccine

Two typhoid vaccines are currently available for use in the United States: an oral live, attenuated vaccine (Vivotif Berna vaccine, manufactured from the Ty21a strain of S. Typhi by the Swiss Serum and Vaccine Institute) and a Vi capsular polysaccharide vaccine (ViCPS) (Typhim Vi, manufactured by Aventis Pasteur) for intramuscular use. Both vaccines have been shown to protect 50%-80% of recipients. The intramuscular heat-phenol-inactivated vaccine (manufactured by Wyeth-Ayerst) has been discontinued. Table 4-20 provides information on vaccine dosage and administration. The time required for primary vaccination differs for the two vaccines, as do the lower age limits for use in children.

Primary vaccination with oral Ty21a vaccine consists of a total of four capsules, one taken every other day. The capsules should be kept refrigerated (not frozen), and all four doses must be taken to achieve maximum efficacy. Each capsule should be taken with cool liquid no warmer than 37°C (98.6°F), approximately 1 hour before a meal. This regimen should be completed 1 week before potential exposure. The vaccine manufacturer recommends that Ty21a not be administered to infants or children <6 years of age.

Primary vaccination with ViCPS consists of one 0.5 mL (25 µg) dose administered intramuscularly. One dose of this vaccine should be given at least 2 weeks before expected exposure. The manufacturer does not recommend the vaccine for infants <2 years of age. (See "Vaccine Recommendations for Infants and Children," "Typhoid Vaccine," for a discussion of typhoid immunisation for infants who will be travelling.) Current recommendations for revaccination with either vaccine are provided in Table 4-20.

Adverse Reactions

Information on adverse reactions is presented in Table 4-21. Information is not available on the safety of these vaccines when they are used during pregnancy; it is prudent on theoretical grounds to avoid vaccinating pregnant women. (See Chapter 9.) Live, attenuated Ty21a vaccine should not be given to immunocompromised travellers, including those infected with HIV. The intramuscular vaccine presents theoretically safer alternatives for this group. The only contraindication to vaccination with ViCPS vaccine is a history of severe local or systemic reactions after a previous dose. Neither of the available vaccines should be given to travellers with an acute febrile illness.

Table 4-20. Dosage and schedule for typhoid fever vaccination

Vaccination	Age (yrs)	Dose/mode of administration	No. of doses	Dosing interval	Boosting interval
Oral, live, attenuated TY21a vaccine
Primary series	6	1 capsule1/ oral	4	48 hours	Not applicable
Booster	6	1 capsule1/ oral	4	48 hours	Every 5 years
Vi Capsular polysaccharide vaccine
Primary series	2	0.50 mL/ intramuscular	1	Not applicable	Not applicable
Booster	2	0.50 mL/ intramuscular	1	Not applicable	Every 2 years

1Administer with cool liquid no warmer than 37°C (98.6°F).

Table 4-21. Common adverse reactions to typhoid fever vaccines

Vaccine	Reactions
Vaccine	Fever	Headache	Local reactions
Ty21a1	0%-5%	0%-5%	Not applicable
Vi Capsular polysaccharide	0%-1%	16%-20%	7% erythema or induration 1cm

1The side effects of Ty21a are rare and mainly consist of abdominal discomfort, nausea, vomiting, and rash or urticaria.

Precautions and Contraindications

Theoretical concerns have been raised about the immunogenicity of live, attenuated Ty21a vaccine in persons concurrently receiving antibiotics, immune globulin, or viral vaccines. The growth of the live Ty21a strain is inhibited in vitro by various antibacterial agents. Vaccination with Ty21a should be delayed for >24 hours after the administration of any antibacterial agent. Available data do not suggest that simultaneous administration of oral polio or yellow fever vaccine decreases the immunogenicity of Ty21a. If typhoid vaccination is warranted, it should not be delayed because of administration of viral vaccines. Simultaneous administration of Ty21a and immune globulin does not appear to pose a problem.

Other Prevention

See Risks From Food and Water.

Treatment

Specific antimicrobial therapy shortens the clinical course of typhoid fever and reduces the risk of death. Persons who are potentially exposed to S. Typhi and who develop symptoms of typhoid fever should seek appropriate medical care. Antimicrobial therapy should be guided by local data on antimicrobial sensitivity.

Bibliography

Crump JA, Luby SP, Mintz ED. The global burden of typhoid fever. Bull World Health Organ. 2004;82:346-53.
Klugman KP, Gilbertson IT, Koornhof HJ, et al. Protective activity of Vi capsular polysaccharide vaccine against typhoid fever. Lancet. 1987;2:1165-9.
Levine MM, Ferreccio C, Black RE, et al. Large-scale field trial of Ty21a live oral typhoid vaccine in enteric-coated capsule formulation. Lancet. 1987;1:1049-52.
Mermin JH, Townes JM, Gerber M, et al. Typhoid fever in the United States, 1985-1994: changing risks of international travel and increasing antimicrobial resistance. Arch Intern Med. 1998;158:633-8.
Parry CM, Hien TT, Dougan G, et al. Typhoid fever. N Engl J Med. 2002;347:1770-82.
Simanjuntak CH, Paleologo FP, Punjabi NH, et al. Oral immunisation against typhoid fever in Indonesia with Ty21a vaccine. Lancet. 1991;338:1055-9.
Steinberg EB, Bishop RB, Dempsey AF, et al. Typhoid fever in travellers: who should be targeted for prevention? Clin Infect Dis. 2004; 39:186-91.
World Health Organization. Background document: the diagnosis, treatment and prevention of typhoid fever. Geneva, Switzerland: World Health Organization; 2003.

- Steve Luby and Eric Mintz

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