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Typhus (Anne Frank died in March 1945 of typhus, hunger, and maltreatment at the Bergen-Belsen concentration camp - as did countless others. "If God lets me live . . . I shall not remain insignificant. I shall work in the world and for mankind." A.F.)

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Primary Distribution: Numerous areas of the world, with variants and locations noted below under vectors and agents.

Agent and Vector: The typhus group of illnesses are caused by rickettsiae, gram-negative obligate intracellular bacteria transmitted by bites of infected arthropods or exposure to their feces. The typhus group of illnesses are one of several rickettsioses or febrile exanthematous illnesses that include (in addition to the typhus group of illnesses), the spotted fever group of illnesses (Rocky Mountain spotted fever, Boutonneuse fever, North Asian tick typhus, and rickettsial pox), Q fever, trench fever, and erlichiosis. The typhus group includes:

• Epidemic louse-borne typhus is caused by Rickettsia prowazekii and infection is favored by crowded, unsanitary living conditions such as in concentration or the more primitive refugee camps - especially those in cold areas. Epidemic louse-borne typhus is currently most prevalent in mountainous areas of Africa, Asia, and Latin America.
• Scrub typhus is transmitted by the bite of mites or chiggers infected with Orientia tsutsugamushi (of the family Rickettsiaceae) and is found in most areas of Asia.
• Endemic (murine) typhus is transmitted by the bite of fleas infected with Rickettsia typhi. Endemic typhus is found worldwide.

Incubation: Variable according to species: Seven days in epidemic louse-borne typhus, 6-21 days for scrub typhus, and 8-16 days endemic typhus.

Clinical Findings and Treatment

Signs and Symptoms: All the illnesses in the typhoid group are characterized by fever and exanthems. Distinguishing characteristics are as follows:

• Epidemic louse-borne typhus is characterized by a prodrome of headache and constitutional symptoms, then the abrupt onset of high fever, chills, and prostration. By the fifth day, a macular rash appears on the trunk and spreads, sparring only the face, palms, and soles. The rash progresses to maculopapular and petechial, and may become hemorrhagic and necrotic. Other common manifestations are delirium, conjunctival injection, photophobia, eye pain, flushed facies, hearing loss, hypotension, pulmonary involvement, renal insufficiency, and splenomegaly. Recovery may be spontaneous; or complications, including pneumonia, circulatory collapse, myocarditis, and uremia may lead to death. A recrudescent mild form of epidemic typhus (Brill-Zinsser disease) may develop many years after recovery.
• Scrub typhus illness ranges from mild to severe, and is characterized by gradual onset of fever, chills, headache, myalgia (backache), cough, nausea and abdominal pain, and eschar at the site of the infecting bite. Persons who are not natives of endemic areas commonly develop regional lymphadenopathy and a maculopapular rash, while those who live in the area usually do not. Severe scrub typhus is characterized by encephalitis and pneumonia.
• Endemic (murine) typhus is characterized by several days of prodromal constitutional symptoms, followed by the abrupt onset of fever, chills, and nausea and vomiting. Pulmonary involvement is common and may include interstitial pneumonia, pleural effusion, and/or pulmonary edema.

Complications: Noted in discussions above.

Laboratory Findings: In epidemic louse-borne typhus, common lab findings include proteinuria, hematuria, and if complications occur, findings consistent with the complication. Endemic typhus lab findings may include anemia and leukopenia early and leukocytosis late.

Diagnosis: Indirect immunofluorescence assay (IFA) is used in the diagnosis of the typhus group of illnesses. Diagnosis of endemic typhus may also include skin biopsy, dot ELISA, blood DNA, or immunohistology. Diagnosis of scrub typhus may include PCR amplification of the infectious agent or blood DNA.

Differential Diagnosis: Other rickettsial infections and acute febrile illnesses.

Treatment: Epidemic louse-borne typhus may be treated with doxycycline 200 mg in a single dose or until the patient is afebrile for 24 hours. Scrub typhus may be treated with doxycycline 100 mg bid po for 7-14 days; or chloramphenicol 500 mg qid po for 7-14 days. Azithromycin is also effective. Endemic typhus may be treated with doxycycline 100 mg bid po for 7-14 days; or chloramphenicol 500 mg qid po for 7-14 days.

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References

Anne Frank Online: http://www.annefrank.com/

Bell, D. (1995). Tropical Medicine (4th ed.). Oxford: Blackwell Scientific.

Chin, J. (Ed.) (2000). Control of communicable diseases manual (17th ed.). Washington, DC: American Public Health Association.

Levin, M.J. (1999). Infections: Viral and rickettsial. In W.W. Hay, A.R. Hatward, M.J. Levin & J.M. Sondheimer (Eds.). Current Pediatric Diagnosis & Treatment (14th ed.) (pp. 960-994). Stamford Connecticut: Appleton & Lange.

Walker, D., Raoult, D., Brouqui, P., & Marrie, T. (1998). Rickettsial diseases. In A.S. Fauci, E. Braunwald, K.J. Isselbacher, J.D. Wilson, J.B. Martin, D.L. Kasper, S.L. Hauser, & D.L. Longo (Eds.). Harrison's Principles of Internal Medicine (14th ed.) (pp. 1045-1052). New York: McGraw-Hill.