Clinical FAQs

Several diseases are included in the generic term “typhus fever,” such as flea-borne (murine) typhus, epidemic (louse-borne) typhus, and scrub typhus.

Flea-borne typhus (caused by Rickettsia typhi) occurs in tropical and subtropical areas and is transmitted to humans via infected fleas and flea feces. Although an uncommon disease in the United States, there are areas of the country where flea-borne typhus occurs more frequently, including southern California, Hawaii, and Texas.

Epidemic typhus (caused by Rickettsia prowazekii) can be transmitted by infected body lice, or by contact with flying squirrels. Epidemic typhus is extremely rare in the United States and is only associated with flying squirrel exposure. Sporadic cases of epidemic typhus are reported in Central Africa, Asia, and in Central and South America; the disease is often associated with overcrowded conditions where body lice may spread quickly.

Scrub typhus (caused by Orientia tsutsugamushi) is transmitted by infected chiggers and occurs predominantly in rural areas of Southeast Asia, Indonesia, China, Japan, India, and northern Australia.

Rickettsia typhi is shed in the feces of infected fleas. People become infected with R. typhi when infectious flea feces (flea dirt) are scratched or rubbed into broken skin. Less than 5% of patients will recall a fleabite or flea exposure in the one to two weeks preceding illness. Dust carrying infectious flea dirt can also be inhaled or inoculated into mucus membranes around the eye.

Person-to-person transmission has not been documented.

The most common symptoms include an abrupt onset of fever, headache, myalgia, nausea, and vomiting. Almost all patients report fever. Rash occurs in about one half of patients, and typically appears at the end of the first week of the illness, lasting 1–4 days. Early rash is often described as a maculopapular eruption on the trunk that spreads peripherally, sparing the palms of the hands and soles of the feet. Because rash may vary among individuals or be absent altogether, rash should not be relied upon for diagnosis. The rash is often faint and may be difficult to identify on darker pigmented skin.

Although usually a self-limited disease, recommended treatment with doxycycline shortens the duration of symptoms. When not treated with appropriate antibiotics, fever can last up to 2–3 weeks and illness may become severe. The severity of symptoms varies widely, and flea-borne typhus can be fatal in as many as 5% of patients.

Doxycycline is the drug of choice for the treatment of adults and children for all rickettsial diseases, including flea-borne typhus. Some patients experience photosensitivity, nausea or vomiting while taking doxycycline; true anaphylactic reactions to doxycycline are rare. Chloramphenicol is an alternative treatment, but oral formulations are no longer available in the United States and the parenteral formulation has limited availability. Limited clinical reports suggest ciprofloxacin or levofloxacin also might be effective alternatives in adults.

Serologic testing

Flea-borne typhus is diagnosed most commonly using serologic tests. Commercial serology is available for typhus group rickettsioses. The indirect immunofluorescence antibody (IFA) assay is the preferred serologic test as IFA can provide quantitative results. Since IFA assays measure antibody levels, two paired specimens must be compared. The paired samples consist of an acute specimen (collected in the first two weeks of illness or while the patient is experiencing symptoms) and a convalescent specimen (collected two to four weeks later). Confirmation requires a fourfold rise in IgG antibody titers between the two appropriately timed specimens. For rickettsial diseases, IgM antibodies are less reliable and should not be used alone.

Rickettsia typhi antigens cross-react with closely related typhus group Rickettsia species (i.e. R. prowazekii).  While cross-reactivity among different typhus group species may be more pronounced, cross-reaction with spotted fever group Rickettsia also has been reported. Because of this cross-reactivity, IFA cannot provide species-specific results.

Molecular testing

Flea-borne typhus can also be diagnosed using molecular assays, such as polymerase chain reaction (PCR). PCR can be performed on acute whole blood samples, though sensitivity might be low in early illness. Because PCR detects bacterial DNA, the ability to detect also declines with treatment. A positive PCR test is confirmatory, but a negative test does not rule out the possibility of infection.

Immunohistochemistry on fixed tissue samples and PCR on fresh tissue is available.

Treatment decisions are based on clinical signs and symptoms; do not delay treatment with doxycycline pending laboratory confirmation.

A stationary titer (or less than a four-fold change in titer) between appropriately timed acute and convalescent serum samples is suggestive of prior exposure and not current disease. Interpretation of samples collected outside of the appropriate time frame is difficult.

A single titer, whether positive or negative, is insufficient evidence to confirm or rule out flea-borne typhus. Because IFA measures antibody levels, it is common for results to be non-reactive during the first week of illness, when most patients seek care. It can take an average of 7–10 days following illness onset for antibodies to reach detectable levels.

A single titer, whether positive or negative, is insufficient evidence to confirm flea-borne typhus. The timing of sample collection in relation to illness onset is important when interpreting a positive serology result. A single elevated titer might be reflective of past exposure, unrelated to the current illness. Without an acute sample to establish a baseline, a single titer cannot accurately identify a recent illness.

A single elevated antibody titer is never sufficient to confirm acute infection with a rickettsial pathogen. A diagnosis of flea-borne typhus is confirmed by a fourfold or greater increase in antibody titer in samples collected 2–4 weeks apart, during acute and convalescent phases of illness. Laboratory confirmation of flea-borne typhus using serology requires paired serum samples. Disease confirmation is critical for studying the changing epidemiology of rickettsial diseases like flea-borne typhus, and for developing effective prevention strategies and public health outreach activities.

Currently, flea-borne typhus is not nationally notifiable condition; however, your state may require notification. Please check with your state and local health departments about reportable diseases.

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 fleas and wear EPA-registered insect repellent labeled for use against fleas when spending time outside.

Brill Zinsser disease is caused by recrudescence of R. prowazekii (the causative agent of epidemic typhus). There is no evidence to suggest that chronic disease or recrudescence occurs following infection with R. typhi (the causative agent of flea-borne typhus).

Multiple Rickettsia species have been identified in the cat flea (Ctenocephalides felis), including: R. typhi and R. felis. While R. typhi is a known human pathogen, the significance of other flea-borne rickettsiae currently is unknown.