Clinical Overview of Murine Typhus

Background

Murine typhus is a flea-borne illness caused by the bacterium Rickettsia typhi. Murine typhus occurs worldwide, primarily in tropical and subtropical climates where rats (the primary animal reservoir) and rat fleas are present. People become infected with R. typhi when they come into contact with infected flea feces via scratched or abraded skin. Infection can also occur when mucous membranes are exposed to infected feces or when a patient inhales the feces. Infections often occur in areas where humans and host animals come into regular contact, including areas of low sanitation where rats are abundant. Most cases are reported from spring to early fall.

Several flea species have been identified as potential vectors for murine typhus, including the rat flea (Xenopsylla cheopis), cat flea (Ctenocephalides felis), and mouse flea (Leptopsyllia segnis). Opossums, cats, and dogs living in urban or suburban areas have also been implicated as host species for fleas carrying R. typhi in recent cases in the United States and Spain.

In the United States, most cases of murine typhus occur in Texas, California, and Hawaii.

Clinical characteristics

Symptoms usually begin 7–14 days following infection. Patients typically present with fever and headache or rash. Other symptoms include:

• Myalgia
• Anorexia
• Nausea
• Vomiting
• Abdominal pain
• Cough
• Altered mental status

Common laboratory findings include anemia, thrombocytopenia, leukopenia, hyponatremia, and elevated levels of liver enzymes. While most patients experience a self-limited illness, severe and fatal cases have been reported with pulmonary and neurologic manifestations.

Rash

The rash typically occurs at the end of the first week of the illness and lasts 1–4 days. It generally starts as a maculopapular eruption on the trunk and spreads peripherally, sparing the palms of the hands and soles of the feet. The appearance of the rash varies, or may be absent altogether and should not be relied upon for diagnosis.

Physician diagnosis

Due to the non-specific presentation of murine typhus and the unreliability of early diagnostic tests, treatment decisions should be made based on clinical presentation and epidemiologic settings. Murine typhus should be considered in patients with persistent fever, a history of exposure to fleas or flea hosts (such as rats, cats or opossums), or if there is a history of travel to tropical or semitropical regions.

When treated early, patients typically experience a less severe illness and shorter recovery time. Treatment should never be withheld pending diagnostic tests. Clusters of murine typhus have been reported in the United States, and suspected cases should be reported to the state or local health department to prevent further exposures.

Diagnostic Testing

Laboratory assays for the diagnosis of murine typhus diagnosis include:

• Indirect fluorescent antibody (IFA) assay
• Immunohistochemistry (IHC) on tissue biopsy specimens
• Polymerase chain reaction (PCR) assays using blood, plasma, or tissue specimens
• Isolation of R. typhi in culture

Paired serologic testing using IFA is the most common means of confirming murine typhus and can be used to detect IgG antibodies. Diagnosis is serologically confirmed by demonstrating a four-fold rise in antibody titer between acute and convalescent samples. Acute specimens are taken during the first week of illness and convalescent samples are taken 2–10 weeks later. IgM antibodies are not reliable and should not be used for the diagnosis of murine typhus. Detectable levels of IgG antibody generally do not appear until 7–10 days after the onset of illness. A stationary titer (defined as less than a four-fold change in titer) between appropriately timed acute and convalescent serum samples is suggestive of prior exposure and not recent infection.

PCR can detect R. typhi during acute illness, and is most sensitive when performed on specimens collected during the first week of illness, and prior to the start of doxycycline. However, PCR is insufficiently sensitive to rule out infection, and a negative PCR result should not dissuade clinicians from treating patients in whom murine typhus is suspected.

Because antibody titers may be persistently elevated in some individuals for years after their initial exposure or infection, only demonstration of recent changes in titers between paired specimens are considered to be a reliable retrospective serologic confirmation of acute murine typhus infection. R. typhi antigens frequently cross-react with those of R. prowazekii and R. felis, and less often with R. rickettsii.

IHC can be used to detect infection with typhus group Rickettsia (including R. prowazekii and R. typhi) in formalin-fixed tissue samples. PCR of whole blood or tissue can distinguish between infection with R. typhi and R. prowazekii although the sensitivity of these assays varies considerably based on the sample type, timing of sample collection, and the severity of disease.

Treatment

Doxycycline is the treatment of choice for suspected cases of murine typhus in adults and children of all ages. Recommended dosages of doxycycline:

• Adults: 100 mg twice per day
• Children under 45 kg (100 lbs.): 2.2 mg/kg body weight twice per day

Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement (usually 7–10 days).

Prevention and immunity

Patients who recover from R. typhi infection usually produce a robust immune response and typically retain elevated antibody titers for some months to years. However, it is unknown if this immune response leads to life-long immunity. Patients should avoid contact with fleas and wear EPA-registered insect repellentexternal icon labeled for use against fleas when spending time outside.

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