Description

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

Occurrence

An estimated 22 million cases of typhoid fever and 200,000 related deaths occur worldwide each year (1). Approximately 400 cases of typhoid fever among persons with onset of illness in the United States, most of whom are recent travelers, are reported to CDC each year.

Risk for Travelers

Risk is greatest for travelers to South Asia and developing countries in Asia, Africa, the Caribbean, and Central and South America. Travelers to South Asia are at highest risk for infections that are nalidixic acid-resistant or multidrug-resistant (i.e., resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole) (2). Travelers 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. Travelers have acquired typhoid fever even during brief visits of less than 1 week to countries where the disease is endemic (3).

Clinical Presentation

The hallmark of typhoid infection is persistent, high fever as high as 103° to 104° F (39° to 40° C). Other common symptoms and signs include headache, malaise, anorexia, splenomegaly, a rash of flat, rose-colored spots, and relative bradycardia (4). Many mild and atypical infections occur.

Prevention

Typhoid vaccination is not required for international travel, but CDC recommends it for travelers to areas where there is a recognized risk of exposure to S. Typhi. Vaccination is particularly recommended for those who will be traveling in smaller cities, villages, and rural areas off the usual tourist itineraries, where food and beverage choices may be more limited. While immunization is recommended, travelers 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 (see Chapter 2).

VACCINE

Two typhoid vaccines are currently available 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 sanofi pasteur) for intramuscular use. Both vaccines protect 50%-80% of recipients (5,6). The intramuscular heat-phenol-inactivated vaccine (manufactured by Wyeth-Ayerst) was discontinued in 2000. Combined hepatitis A/typhoid fever vaccines are not licensed in the United States, but may be available in other countries (7). Table 4-21 provides information on vaccine dosage, administration, and revaccination. The time required for primary vaccination differs for the two vaccines, as do the lower age limits.

Primary vaccination with oral Ty21a vaccine consists 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 younger than 6 years of age.

Primary vaccination with ViCPS consists of one 0.5-mL (25-µg) dose administered intramuscularly. One dose of this vac-cine should be given at least 2 weeks before expected exposure. The manufacturer does not recommend the vaccine for infants and children younger than 2 years of age. (See Chapter 8 for a discussion of typhoid immunization for infants who will be traveling.)

Adverse Reactions

Information on adverse reactions is presented in Table 4-22. Information is not available on the safety of these vaccines in 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 travelers, including those infected with HIV. The intramuscular vaccine presents a theoretically safer alternative 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 persons with an acute febrile illness.

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 (9). 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 drink in Chapter 2.

Treatment

Specific antimicrobial therapy shortens the clinical course of typhoid fever and reduces the risk of death. Persons who may have been exposed to Salmonella enterica serotype Typhi and who develop symptoms of typhoid fever should seek medical care. Antimicrobial therapy should be guided by data on antimicrobial sensitivity, particularly for travelers to South Asia. Patients should be monitored to ensure that fever wanes within a few days of starting treatment. If fever does not subside, alternative antimicrobial agents or other foci of infection should be considered.

References

1. Crump JA, Luby SP, Mintz ED. The global burden of typhoid fever. Bull World Health Organ. 2004;82(5):346-53.
2. Ackers ML, Puhr ND, Tauxe RV, Mintz ED. Laboratory-based surveillance of Salmonella serotype Typhi infections in the United States: antimicrobial resistance on the rise. JAMA. 2000;283(20):2668-73.
3. Steinberg EB, Bishop R, Haber P, Dempsey AF, Hoekstra RM, Nelson JM, et al. Typhoid fever in travelers: who should be targeted for prevention? Clin Infect Dis. 2004;39:186-91.
4. Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ. Typhoid fever. N Engl J Med. 2002;347:1770-82.
5. Klugman KP, Gilbertson IT, Koornhof HJ, Robbins JB, Schneerson R, Schulz D, et al. Protective activity of Vi capsular polysaccharide vaccine against typhoid fever. Lancet. 1987;2:1165-9.
6. Simanjuntak CH, Paleologo FP, Punjabi NH, Darmowigoto R, Soeprawoto, Totosudirjo H, et al. Oral immunisation against typhoid fever in Indonesia with Ty21a vaccine. Lancet. 1991;338:1055-9.
7. Beeching NJ, Clarke PD, Kitchin NR, Pirmohamed J, Veitch K, Weber F. Comparison of two combined vaccines against typhoid fever and hepatitis A in healthy adults. Vaccine. 2004;23:29-35.
8. CDC. Typhoid immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morbid Mortal Wkly Rep. 1994;43(RR-14):1-7.
9. Kollaritsch H, Que JU, Kunz C, Wiedermann G, Herzog C, Cryz SJ Jr. Safety and immunogenicity of live oral cholera and typhoid vaccines administered alone or in combination with antimalarial drugs, oral polio vaccine, or yellow fever vaccine. J Infect Dis. 1997;175:871-5.

SHARON GREENE, ERIC MINTZ

TABLE 4-21. Dosage and schedule for typhoid fever vaccination

TABLE 4-22. Common adverse reactions to typhoid fever vaccines