Murine Typhus in Returned Travelers

By Michele Barry, MD FACP, Senior Associate Dean for Global Health at Stanford University School of Medicine.

By Brian G. Blackburn, MD FACP, Clinical Assistant Professor in the Division of Infectious Diseases and Geographic Medicine at Stanford University School of Medicine, is Associate Editor for Infectious Disease Alert.

Drs. Barry and Blackburn report no financial relationships to this field of study.

Synopsis: Murine typhus, caused by Rickettsia typhi and transmitted by the rat flea, has emerged as an etiologic agent of undifferentiated febrile illness in returned travelers. This retrospective study found that most cases of murine typhus at a well-known reference center in France were diagnosed in travelers returning from Africa or Southeast Asia.

Source: Walter G, Botelho-Nevers E, Socolovschi C, et. al. Murine Typhus in Returned Travelers: A Report of Thirty-Two Cases. Am J Trop Med Hyg 2012;86:1049-53.

Murine typhus is an acute zoonotic infection caused by Rickettsia typhi, an obligate-intracellular Gram-negative bacterium belonging to the typhus group of rickettsiae. R. typhi infections occur worldwide, particularly in warm, humid coastal environments of the tropics; in the U.S., autochthonous transmission also occasionally occurs in Hawaii, Texas, and California. The rat flea, Xenopsylla cheopis is generally considered the primary vector. Humans are infected when rickettsia-laden flea feces are scratched into pruritic flea bite excoriations. The peri-domestic Rattus species is the critical vertebrate host that transmits the infection to fleas, although the rats do not usually show signs of illness even with high-level rickettsemia.

The authors at the World Health Organization Collaborative Center for Rickettsial Diseases in Marseilles, France retrospectively analyzed the epidemiological, clinical and biological characteristics of 32 patients with murine typhus who were diagnosed there during a three-year period (January 2008 to December 2010). A case was defined as a patient whose microimmunofluorescence serology was positive (single serum with IgM titer > 1:64 and/or IgG antibody titer > 1:128, or a >4-fold increase in titers between acute and convalescent sera). If cross-reactions were observed with other Rickettsia agents, a Western blot and cross-adsorption test were used to discriminate the species.

During the three-year study, 32 confirmed cases of murine typhus were discovered, and all were in returned travelers. During that time 42,276 sera were sent for evaluation to this reference laboratory for suspected rickettsial diseases from France and other countries. Thirteen (41%) of the 32 patients acquired murine typhus in Africa (Tunisia, Morocco, Ivory Coast, Central African Republic, Madagascar or Chad), and twelve (38%) acquired it in Southeast Asia (Indonesia, Philippines, Thailand, Cambodia, Vietnam, Myanmar or Laos). Tunisia and Indonesia were the two most common countries of exposure.

The classic triad of fever, headache and rash was seen in only four patients, although a rash was present in 15 patients (47%). Elevated serum transaminases were found in over half the patients and represented the most common laboratory abnormalities. Cytopenias were observed in 12 (38%) of the 32 patients, and renal failure in three (9%) patients. Contact with rodents was rarely reported (n=2 of 32), and almost half of the cases were diagnosed in August or September, which seemed to correlate with flea abundance in endemic areas as well as a time of increased travel for Europeans. Fever was found in all patients for whom data were available (31 of 31). Two patients had life-threatening illnesses, and three developed the hemophagocytic syndrome. All 32 patients recovered. The authors concluded that murine typhus should be considered a possible cause of febrile, undifferentiated illness in returning travelers.

Commentary

Rickettsial diseases are increasingly being recognized among international travelers. In a Geosentinel study of almost 7,000 ill returnees with fever as a chief complaint, rickettsial disease was seen in 2%.1 The taxonomy of Rickettsia species is fairly complex, but there are two species pathogenic for humans in the typhus group: R. prowazekii (epidemic louse-borne typhus) and R. typhi (murine typhus). Murine typhus, unlike African tick bite fever (caused by the spotted fever group rickettsia, R. africae — a relatively common cause of febrile illness in travelers returning from Southern Africa), does not present with a tell-tale eschar. Indeed, murine typhus is notoriously non-specific with fever, headache and an often poorly visible maculopapular exanthem; gastrointestinal symptoms appear to be common in children. The primary pathological lesion of R. typhi infection is an inflammatory vasculitis characterized by perivascular infiltration of lymphocytes, mast cells and macrophages. Thrombocytopenia and transaminitis are common. A recent report from Taiwan emphasized that fever with transaminitis is a clue to the diagnosis.2 The incubation period of murine typhus is 8 to 16 days, and rash occurs near the end of the first week of illness — beginning on the trunk and spreading peripherally, sparing the palms and soles. The majority of patients experience mild illness, although, as reported in this article, illness can be severe. One patient presented with septic shock and another with myocarditis. As in other rickettsial diseases, the presence of G6PD deficiency, hemoglobinopathies such as thalassemia, and advanced age can be associated with severe or even fatal disease. Although spontaneous recovery can occur without treatment, the drug of choice for murine typhus remains doxycycline, to hasten recovery.

References

  1. Jensenius M, et al. Multicenter GeoSentinel Analysis of Rickettsial Diseases in International Travelers, 1996-2008. Emer Infec Dis 2008;15:1791-1798
  2. Chang K, et al. Murine Typhus in Southern Taiwan During 1992-2009. Am J Trop Med Hyg 2012;87:141-147
  3. Walker DH. The Role of Host Factors in the Severity of Spotted Fever and Tyhus Rickettsioses, Ann NY Acad Sciences, 1990, 590:10-19