72-year-old man • fever • new-onset urinary frequency • altered mental state • Dx?

Incidence of murine typhus has declined in the United States since 1945 with the use of the insecticide dichlorodiphenyltrichloroethane (DDT). However, a recent rise in murine typhus cases—likely due to ecological changes—makes timely diagnosis and treatment essential.⁵ An epidemiologic study of 1762 confirmed cases in Texas from 2003 to 2013 found an increase in the number of cases and an expansion of the geographic areas impacted.³ Thus, in the work-up of acute fever of unknown origin, it is not unreasonable to include murine typhus in the differential.

Serologic testing with IFA is the preferred diagnostic method; however, a definitive diagnosis is not needed before treatment can be started.

Murine typhus can be difficult to diagnose due to nonspecific clinical manifestation.^3,4 A 2016 systematic review of 2074 patients reported common symptoms of fever, headache, malaise, chills, and myalgia.⁶ The most common laboratory abnormalities in adults were elevated aminotransferases, lactate dehydrogenase, hypoalbuminemia, and thrombocytopenia.⁶ A 4-fold increase in typhus group IgM or IgG-specific antibody titer by IFA is supportive of diagnosis.⁴ 

The differential diagnosis included urosepsis, prostatitis, syphilis, HIV, and meningitis. However, lack of response to broad-spectrum antibiotics and antifungals made a diagnosis of urologic infection unlikely. A negative sexually transmitted infection screen ruled out syphilis and HIV. An incidental, elevated INR and delirium prevented us from obtaining a lumbar puncture to test for meningitis.

Treatment may begin without a definitive diagnosis

Serologic testing with IFA is the preferred diagnostic method; however, a definitive diagnosis is not needed before treatment can be initiated. Doxycycline is the first-line therapy for all rickettsioses. Adults are advised to take doxycycline 200 mg orally once, followed by 100 mg twice daily until the patient improves, has been afebrile for 48 hours, and has received treatment for at least 7 days.⁷ Oral chloramphenicol is considered a second-line treatment; however it is not available in the United States and is associated with adverse hematologic effects.⁷

Our patient responded remarkably well to the doxycycline. After a 14-day course was completed, he was discharged to a skilled nursing facility for physical rehabilitation.

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