Rickettsia typhi - Typhus Fever

Rickettsia typhi is the fleaborne etiologic agent of murine typhus (also called endemic typhus), a leading global source of undifferentiated febrile illness. Because the clinical features of murine typhus and other rickettsial diseases are indistinct, infection is often left undiagnosed or misidentified (eg, as malaria, dengue, or typhoid).  Infection by R. typhi is commonly diagnosed with two-step serologic testing, although other methods such as nucleic acid amplification testing (NAAT) and immunohistochemistry (IHC), when IHC is available, may also be used.

Quick Answers for Clinicians

What are common risk factors for exposure to Rickettsia typhi?

Rickettsia typhi is carried predominantly by rats and transmitted by their fleas, although animals such as opossums, cats, and dogs have also been documented as carriers. Additionally, cases of murine typhus typically arise in tropical and subtropical climates, particularly in coastal areas with large rat populations. Therefore, individuals with febrile illness who report exposure to potential animal carriers or their fleas, or who have traveled to or live in semitropical or tropical regions, should be considered for testing. 

What symptoms might prompt testing for Rickettsia typhi?

The symptoms of a Rickettsia typhi infection are nonspecific and can vary. Sudden fever with headache or rash radiating outward from the trunk are frequent characteristics of murine typhus.  Although rash often provokes suspicion of a rickettsial infection, it may be absent in 50-80% of cases, particularly in individuals with darker skin pigmentation. 

In addition to these primary signs, infected individuals may present with chills, myalgia, nausea, vomiting, anorexia, abdominal pain, cough, malaise, or an altered mental state. Rare severe cases may include pulmonary, renal, and neurologic symptoms.  

What are the limitations of serologic testing for Rickettsia typhi?

Serologic testing, often through immunofluorescence assays (IFAs), is the standard method to confirm a rickettsial infection. Diagnosis using serology requires both an acute sample, collected within a week of symptom onset, and a convalescent sample, taken 2-4 weeks after the acute sample. However, because serology does not provide an immediate diagnosis, initiation of treatment should be based on clinical and epidemiologic evidence. Furthermore, serologic testing cannot be used to distinguish between cross-reactive bacteria, including Rickettsia prowazekii, another typhus group rickettsia. Species-specific testing (eg, by polymerase chain reaction [PCR]) run in parallel is advised when possible, although species identification does not alter treatment recommendations. 

Is bacterial culture an option to identify a Rickettsia typhi infection?

Generally, no. Although bacterial culture is the most definitive means to distinguish various rickettsial bacteria, this testing must be conducted at a biosafety level 3 facility and is therefore not routinely available.

Indications for Testing

Testing for R. typhi is indicated in patients who have symptoms consistent with infection (eg, a persistent fever accompanied by headache or a rash spreading from the trunk), particularly those who have traveled to a tropical or semitropical region and/or report exposure to common carriers (eg, rats) or their fleas.  Symptoms usually occur within 7-14 days of exposure.

Laboratory Testing

Laboratory testing for R. typhi, a typhus group rickettsia, generally entails serology by immunofluorescence assay (IFA) but can also include NAAT and IHC testing. Although bacterial culture is possible, it is not routinely conducted due to heightened biosafety requirements.

Notably, the CDC strongly recommends against withholding treatment pending laboratory confirmation when a rickettsial infection is suspected.  Refer to the CDC for more information on testing for typhus fevers. 

Serology

Serologic testing of both immunoglobulin M (IgM) and IgG antibodies, often by IFA, is the standard method to confirm rickettsioses. Diagnosis by serology requires both an acute sample, collected within a week of symptom onset, and a convalescent sample, taken 2-4 weeks after the acute sample. Both samples should be tested by the same laboratory simultaneously to reduce variation. Upon comparison, a fourfold or greater increase in titers confirms a rickettsial infection. 

Because of possible cross-reactivity with R. prowazekii, R. felis, and (occasionally) R. rickettsii, serology cannot reliably differentiate between species. Species-specific testing run in parallel is advised when possible,  although bacterium identification does not alter treatment recommendations.

Nucleic Acid Amplification

NAAT by polymerase chain reaction (PCR) can be used to confirm an R. typhi infection and is most sensitive when conducted within a week of symptom onset.  Whole blood, buffy coat, plasma, and tissue samples are all suitable for the purposes of PCR testing.

The sensitivity of NAAT is affected by bacterial load  (ie, the severity and stage of infection), so this testing should be conducted before administering treatment,  ideally within the first 5 days of febrile illness.  During the acute phase, combining PCR with serology may increase diagnostic yield. 

Immunohistochemistry

IHC, which like IFA can be used to detect but not identify a rickettsial infection, is limited in availability to specialized laboratories, such as the CDC. For further information on sample collection, refer to the CDC’s guidelines on specimen collection  for rickettsial zoonoses.

ARUP Laboratory Tests

Recommended test to confirm the presence of a typhus group rickettsia

Medical Experts

Medical Reviewer

Jackson

Brian R. Jackson, MD, MS
Associate Professor of Pathology (Clinical); Adjunct Associate Professor, Biomedical Informatics, University of Utah
Medical Director, Support Services, IT, and Business Development, ARUP Laboratories

References

Additional Resources