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For further information, see CMDT Part 34-12: Typhus Group

KEY FEATURES

  • Rickettsia typhi, a ubiquitous pathogen recognized on all continents, is transmitted from rat to rat through the rat flea

  • Humans usually acquire the infection in an urban or suburban setting when bitten by an infected flea

  • Endemic typhus is usually self-limited

  • Rare human cases in the developed world occur in travelers, usually to Southeast Asia (significant underdiagnosis has been documented in Indonesia), Africa, or the Mediterranean area, although other pockets of infection are also known to occur in the Andes and the Yucatán

  • In the United States, cases are reported along the Gulf Coast

  • Sun exposure appears to correlate with increased exposure risk

CLINICAL FINDINGS

  • Fever, headache, myalgia, and chills

  • Relative bradycardia is reported

  • Maculopapular rash occurs in around 50% of cases; it is concentrated on the trunk, mostly sparing the palms and soles, and fades rapidly

  • Untreated infections last an average of 12–15 days

  • Rare presentations include pain or painful genital (Lipschutz) ulcers

  • Anemia, thrombocytopenia, leukopenia, hyponatremia, and elevated levels of liver enzymes commonly occur

  • If illness is acquired during early pregnancy, it may be associated with transaminitis and may have a favorable prognosis

  • Murine typhus acquired early in pregnancy may be associated with

    • Miscarriage

    • Preterm birth

    • Low birth weight

    • Maternal death

  • Differential diagnosis: Rocky Mountain spotted fever, COVID-19 (which is also associated with a multisystem inflammatory syndrome)

  • Complications

    • Pneumonia (most common), pleural effusion, and respiratory failure

    • Neurologic (peripheral facial paralysis, meningitis, ataxia, seizures)

    • Acute kidney injury, focal segmental glomerulosclerosis

    • Fulminant myocarditis

    • Multiorgan failure

    • Ocular findings, disseminated intravascular coagulation, and hemophagocytic lymphohistiocytosis syndrome are rare

DIAGNOSIS

  • Serologic confirmation may be necessary for differentiation, with complement-fixing or immunofluorescent antibodies detectable within 15 days after onset, with specific R typhi antigens

  • A fourfold rise in serum antibody titers between the acute and the convalescent phase is diagnostic, although cutoff values for diagnosis are not standardized

  • R typhi antigens frequently cross-react with those of R prowazekii; polymerase chain reaction (PCR) can distinguish between these two infections (depending on the sample type, the timing of sample collection, bacterial load, and severity of disease)

  • During the first week of illness, PCR is the most sensitive test if samples are taken before doxycycline administration

TREATMENT

  • Doxycycline

    • Dosage: 100 mg orally twice daily for 3 days (or until the patient is afebrile for 48 hours)

    • Drug of choice, except during pregnancy

  • Ciprofloxacin (500–750 mg orally twice daily) and ampicillin (500 mg orally three times daily) are reportedly successful in pregnant women

  • Azithromycin is frequently used but is not associated with improved fetal outcomes

  • Prognosis with treatment is excellent

  • Preventative measures are directed at control of rats and ectoparasites (rat fleas) with insecticides, rat poisons, and rat-proofing of buildings

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