Flea-borne typhus
2026 Case Definition

Background

Flea-borne typhus (FBT), also called murine typus or endemic typhus, is a rickettsial disease caused by the bacteria Rickettsia typhi. FBT is transmitted to humans via infected fleas, most commonly the Oriental rat flea (Xenopsylla cheopsis) and cat flea (Ctenocephalides felis). Fleas become infected when they bite infected animals, such as rats, cats, or opossums. Once infected, fleas remain infected for life. Transmission to humans can occur when R. typhi-contaminated flea feces are scratched into a bite site or other abrasion in the skin, rubbed into a conjunctival membrane, or inhaled. Antibodies for rickettsial diseases can be cross-reactive, and patients are often tested using a rickettsial panel that may include detection of R. rickettsii and R. typhi immunoglobulin G (IgG) and/or immunoglobulin M (IgM) by indirect fluorescent antibody (IFA). As a result, jurisdictions may receive positive antibody results for both R. typhi and R. rickettsii with the same collection date for a single patient. The assay for detection of IgM antibodies is less specific than the assay for detection of IgG antibodies; consequently, the IgM IFA assay is more likely to produce a false positive result. IgM IFA tests should never be used as a standalone assay for rickettsial testing. Public health agencies should use a combination of IgG and IgM antibody titer levels, information about the location of possible exposures, clinical manifestations, and the incidence of a particular disease in the geographic areas of exposure to help determine the appropriate disease type for individual patients. Individuals should not be classified as cases for both FBT and spotted fever rickettsiosis based on serologic evidence alone.

Clinical Criteria

Tier 1 Clinical Evidence:

• Fever as reported by patient or healthcare provider.

Tier 2 Clinical Evidence:

• Two or more of the following clinical manifestations: Elevated liver enzymes (aspartate aminotransferase, alanine transaminase, or alkaline phosphatase), thrombocytopenia, hyponatremia, rash, headache, myalgia, cough, or nausea/vomiting.

Laboratory Criteria

Supportive Laboratory Evidence:

• Demonstration of typhus fever group rickettsial antigen in a biopsy or autopsy specimen by IHC methods in the absence of molecular confirmation, OR
• Serological evidence of elevated IgG antibody reactive with R. typhi antigen by IFA at a titer of ≥1:128 within 60 days of illness onset.

Presumptive Laboratory Evidence:

• Serological evidence of elevated IgG antibody reactive with R. typhi antigen by IFA at a titer of ≥1:128 with a negative or lower IgG antibody titer to spotted fever group Rickettsia antigens in a sample taken within 60 days of illness onset.

Confirmatory Laboratory Evidence:

• Detection of R. typhi deoxyribonucleic acid (DNA) in a clinical or autopsy specimen by molecular testing (e.g., nucleic acid amplification testing, metagenomic sequencing), OR
• Isolation of R. typhi from a clinical or autopsy specimen in cell culture with molecular confirmation, OR
• Serological evidence of a fourfold change* in IgG-specific antibody titer to R. typhi antigen by IFA in paired serum samples (one taken in the first two weeks after illness onset and a second taken 2 to 10 weeks after acute specimen collection)^†.

Note: The categorical labels used here to stratify laboratory evidence are intended to support the standardization of case classifications for public health surveillance. The categorical labels should not be used to interpret the utility or validity of any laboratory test methodology.

* A 4-fold change in titer is equivalent to a change of 2 dilutions (e.g., 1:64 to 1:256).

† A 4-fold rise in titer should not be excluded as confirmatory laboratory criteria if the acute and convalescent specimens are collected within 2 weeks of one another.

Epidemiologic Linkage

• Exposure to fleas or animals known to be at risk for flea-borne typhus infection^‡ within 30 days of illness onset or specimen collection date, OR
• Had a shared exposure site with a confirmed or probable case.

‡ Visit About Flea-borne Typhus for animals known to be at risk for flea-borne typhus infection. Absence of louse infestation or exposure to flying squirrels, geographic and seasonal distribution, and sporadic occurrence of the disease help to differentiate FBT from louse-borne typhus. In the U.S., rare cases of louse-borne typhus, also known as sylvatic typhus (ST), can occur when people are exposed to flying squirrels and their nests. Commercial labs do not offer R. prowazekii testing. If ST is suspected, a sample should be sent to CDC for Rickettsia molecular detection or typhus group serology testing.

Criteria to Distinguish a New Case from an Existing Case

• A person previously reported as a probable or confirmed case-patient may be counted as a new case-patient when there is an episode of new clinically compatible illness with confirmatory molecular laboratory evidence.

Probable

• Meets presumptive laboratory evidence AND meets tier 1 and tier 2 clinical evidence, OR
• Meets supportive laboratory evidence AND meets tier 1 and tier 2 clinical evidence AND meets epidemiologic linkage criteria.

Confirmed

• Meets confirmatory laboratory evidence AND meets tier 1 clinical evidence, OR
• Meets confirmatory laboratory evidence AND meets tier 2 clinical evidence.