Flea-Borne (Murine) Typhus: A Clinical Overview for Health Care Providers

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Flea-borne typhus, also called murine or endemic typhus, is caused by the bacterium Rickettsia typhi. It occurs worldwide, mainly in tropical and subtropical climates where rats, its main animal reservoir, and rat fleas live. In the United States most cases occur in Texas, California and Hawaii.

Key points for clinicians

Symptoms include fever, headache, rash, muscle aches, nausea, vomiting, abdominal pain, cough and altered mental status.
Decide to treat on clinical suspicion. Do not delay doxycycline while waiting for laboratory confirmation.
Confirmation relies mainly on serology showing a fourfold rise in antibody titer between acute and convalescent samples.

How people are infected

People are infected when feces from infected fleas get into scratched or abraded skin, reach the mucous membranes, or are inhaled. Infection is most likely where people and host animals are in regular contact, including places with poor sanitation and many rats. Most cases are reported from spring to early fall.

Several fleas can carry the infection, including the rat flea (Xenopsylla cheopis), cat flea (Ctenocephalides felis) and mouse flea (Leptopsylla segnis). In recent cases in the United States and Spain, opossums, cats and dogs in urban and suburban areas have been implicated as hosts of fleas carrying R. typhi.

Clinical features

Symptoms usually start 7–14 days after infection, typically with fever and headache or rash. Patients may also have muscle aches, loss of appetite, nausea, vomiting, abdominal pain, cough or altered mental status. Common laboratory findings are anemia, low platelets, low white cell count, low sodium and raised liver enzymes. Most illness resolves on its own, but severe and fatal cases with lung and nervous system involvement have been reported.

The rash usually appears at the end of the first week and lasts 1–4 days. It generally begins as a maculopapular eruption on the trunk and spreads outward, sparing the palms and soles. It varies in appearance or may not appear at all, so it should not be relied on for diagnosis.

Diagnosis

Because symptoms are nonspecific and early tests are unreliable, treatment decisions should rest on the clinical picture and the setting. Consider flea-borne typhus in a patient with persistent fever and exposure to fleas or flea hosts such as rats, cats or opossums, or recent travel to tropical or semitropical regions. Patients treated early usually have milder illness and recover faster. Never withhold treatment pending test results. Clusters have occurred in the United States, so suspected cases should be reported to the state or local health department to prevent further exposures.

Tests

indirect fluorescent antibody (IFA) assay on serum
polymerase chain reaction (PCR) on blood, plasma or tissue
immunohistochemistry (IHC) on tissue biopsies
culture isolation of R. typhi

Serology. Paired IFA testing for IgG antibodies is the most common way to confirm the diagnosis: a fourfold rise in titer between an acute sample from the first week of illness and a convalescent sample 2–10 weeks later. IgG usually becomes detectable only 7–10 days after onset. IgM results are unreliable and should not be used. A stationary titer, less than a fourfold change between properly timed samples, points to past exposure rather than recent infection. Because titers can stay high for years after exposure, only a change between paired samples reliably confirms acute infection. R. typhi antigens often cross-react with those of R. prowazekii and R. felis, and less often with R. rickettsii.

PCR can detect R. typhi during acute illness and is most sensitive on samples taken in the first week, before doxycycline is started. It is not sensitive enough to rule out infection, so a negative result should not stop treatment of a suspected case. PCR of blood, plasma or tissue can tell R. typhi from R. prowazekii, though its sensitivity varies widely with sample type, timing and severity of illness.

IHC can detect typhus group rickettsiae, including R. prowazekii and R. typhi, in formalin-fixed tissue.

Flowchart for testing a patient with suspected flea-borne typhus, from starting doxycycline and sending serum for IgG testing through PCR, repeat serology and reporting

CDC's diagnostic algorithm. Every patient starts doxycycline immediately and has serum sent for R. typhi IgG testing. After 72 hours or more of doxycycline, go straight to repeat serology 2–10 weeks after onset. Within 72 hours, send whole blood for PCR, and if there is a rash consider a skin biopsy for histopathology, PCR and IHC. A species-specific positive PCR is reported to the health department; a negative or genus-only result leads to repeat serology. A fourfold or greater rise in titer is reported; a smaller change is supportive but not definitive. Centers for Disease Control and Prevention.

Treatment

Doxycycline is the treatment of choice for suspected flea-borne typhus in adults and in children of all ages:

Patient	Dose
Adults	100 mg twice a day
Children under 45 kg (100 lb)	2.2 mg/kg body weight twice a day

Continue for at least 3 days after the fever breaks and until the patient is clearly improving, usually 7–10 days.

Immunity and prevention

People who recover usually mount a strong immune response and keep raised antibody titers for months to years, but whether this gives lifelong immunity is unknown. Patients should avoid contact with fleas and, when outdoors, use an EPA-registered insect repellent labeled for fleas.

Further training

CDC's Clinician Outreach and Communication Activity (COCA) call "Murine Typhus: A Re-emerging Threat in the United States" covers the disease's epidemiology, diagnosis and treatment, and Medscape offers the course "Tackling Murine Typhus: Are You Up to Date?"