Infectious Disease

Murine Typhus as a Result of Opossum Exposure

A 27-year-old woman presented to a Houston clinic with a chief complaint of fever and chills for 6 days. One week prior, she began having fevers of up to 39⁰C. She reported fatigue, myalgias, and anorexia, with a headache and nausea the night prior to presentation. She denied neck pain, photophobia, vomiting, diarrhea, joint pain or swelling, and upper respiratory symptoms.

Physical examination. Initially, the patient appeared fatigued but non-toxic and alert. She had a normal examination except for a temperature of 37.6 C.

Laboratory tests. A Monospot test was negative, and urinalysis was normal. Lab results revealed a low white blood cell count of 4200/μL (reference range, 4500-11,000) with 79% neutrophils and 49% bands, and low platelet count of 96,000/μL (reference range, 150,000-450,000).

She returned the next day with a rash, reported 2 episodes of vomiting, and remained febrile. The rash consisted of diffuse blanching pink macules 2 to 3 mm in size on her chest, abdomen, back, and arms.She then disclosed that she had been complaining to her landlord about opossums in her apartment.

Repeat complete blood count was similar to the first. Electrolytes, BUN, creatinine, and glucose levels were normal. Liver function tests revealed elevated ALT and AST at 284 and 365, respectively. After considering vector-borne and nonvector-borne illnesses, she was prescribed a 10-day course of doxycycline.

At her third clinic visit, she was hospitalized due to continued vomiting and dehydration. She improved on intravenous fluids and intravenous doxycycline and was discharged after 3 days on oral doxycycline.

Due to clinical suspicion, the patient was tested for IgM antibodies to Rickettsia typhi during the hospitalization. The titer 1:64 suggested an acute infection. The patient was diagnosed with and treated for murine typhus with a 10-day course of doxycycline and clinically improved. Three weeks later, the patient’s R typhi titers were 1:512.

Discussion. Murine typhus, also called endemic typhus or flea-borne typhus, is a zoonotic bacterial illness caused by Rickettsia typhi and Rickettsia felis. The vectors of R typhi and R felis are fleas, and the reservoirs are rats, cats, dogs, humans, and opossums.1 The bacteria can spread to humans when infected flea feces get into an open wound or are inhaled.1,2 Common symptoms manifesting 7 to 14 days after R typhi infection are fever, myalgias, arthralgias, headache, and rash. In many patients, the rash is diffuse and maculopapular, starts at the trunk, spreads to the extremities, and spares the palms and soles of the feet.1 In the United States, cases are concentrated in warm, coastal suburban areas, and the major route of infection involves opossums and cats.1 Less than 100 cases are reported each year in the United States, but the cases are endemic to California, Hawaii, and Texas.2 Due to the geographic location and lack of travel history in our patient, murine typhus was the most likely diagnosis.

The gold standard to diagnose murine typhus is an indirect fluorescent-antibody assay (IFA). A more than 4-fold increase in titer between acute and convalescent phase samples can be considered diagnostic for murine typhus.3The increase in titers in our patient confirmed the diagnosis. The recommended treatment for murine typhus is intravenous or oral doxycycline. Alternative treatments include chloramphenicol or quinolones.3

Several other conditions in addition to murine typhus were considered in the differential diagnosis of our patient, including infectious mononucleosis, dengue fever, Rocky Mountain spotted fever (RMSF), and ehrlichiosis. Infectious mononucleosis is a viral illness that was considered due to the patient’s nonspecific symptoms, rash, and age. The Monospot (heterophil) test performed was negative. However, the test is likely to be negative the first week of illness; serologies are more specific if infectious mononucleosis is suspected.4,5

Dengue fever is a mosquito-borne viral illness that causes a range of clinical presentations. Patients have high acute-onset fevers, rash, and a distinctive retro-orbital pain. The majority of dengue fever cases are found in Southeast Asia, but in the United States, cases are seen in people traveling from Central and South America.6 Our patient lacked typical symptoms of dengue fever and had no recent travel history.

RMSF and ehrlichiosis are bacterial illnesses spread by ticks. Most patients present with nonspecific symptoms like fever, headache, rash, myalgias, nausea, and vomiting. The geographical distribution of RMSF and ehrlichiosis in the United States is the Southeastern and South Central part of the country, with fewer than 1.5 cases per million people each of RMSF and ehrlichiosis.7,8 Although many of our patient’s symptoms were similar, the geographic distribution of these infections and the lack of a tick bite history made these diagnoses less likely.

Gina Duong, BA, is a medical student at McGovern Medical School, UTHSC Houston, in Texas.

Laura J. Benjamins, MD, MPH, is an associate professor of pediatrics at McGovern Medical School, UTHSC Houston, in Texas.

LaTanya Love, MD, is an associate professor of pediatrics at McGovern Medical School, UTHSC Houston, in Texas.

Holly D. Smith, MD, is an assistant professor of pediatrics at McGovern Medical School, UTHSC Houston, in Texas.

References:

  1. PenicheLara G, Dzul-Rosado, KR, Zavala Velázquez JE, Zavala-Castro J. Murine typhus: clinical and epidemiological aspects. Colomb Med (Cali). 2012;43(2): 175-180. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4001937.
  2. Adjemian J, Parks S, McElroy K, et al. Murine typhus in Austin, Texas, USA, 2008. Emerg Infect Dis. 2010;16(3):412-417. doi:10.3201/eid1603.091028.
  3. Civen R, Ngo V. Murine typhus: an unrecognized suburban vectorborne disease. Clin Infect Dis. 2008;46(6):913-918. doi:10.1086/527443.
  4. Balfour HH Jr, Dunmire SK, Hogquist KA. Infectious mononucleosis. Clin Transl Immunol. 2015;4(2):e33. doi:10.1038/cti.2015.1.
  5. Ebstein-Barr virus and infectious mononucleosis: laboratory testing. Centers for Disease Control and Prevention. http://www.cdc.gov/epstein-barr/laboratory-testing.html.Updated September 14, 2016.
  6. Mangold KA, Reynolds SL. A review of dengue fever: a resurging tropical disease. Pediatr Emerg Care. 2013;29(5): 665-669. doi:10.1097/PEC.0b013e31828ed30e.
  7. Ehrlichiosis: statistics and epidemiology. Centers for Disease Control and Prevention. https://www.cdc.gov/ehrlichiosis/stats/. Updated January 25, 2016.
  8. Rocky Mountain spotted fever (RMSF): statistics and epidemiology. Centers for Disease Control and Prevention. https://www.cdc.gov/rmsf/stats/index.html. Updated September 5, 2013.