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Rat-Bite Fever

By Larry M. Bush, MD, Affiliate Professor of Clinical Biomedical Sciences; Affiliate Associate Professor of Medicine, Charles E. Schmidt College of Medicine, Florida Atlantic University; University of Miami-Miller School of Medicine
Maria T. Perez, MD, Associate Pathologist, Department of Pathology and Laboratory Medicine, Wellington Regional Medical Center, West Palm Beach

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Rat-bite fever is caused by either Streptobacillus moniliformis or Spirillum minus. Symptoms of the streptobacillary form include fever, rash, and arthralgias. The spirillary form causes relapsing fever, rash, and regional lymphadenitis. Diagnosis is clinical and confirmed by culture and sometimes rising antibody titers. Treatment is with penicillin or doxycycline.

Rat-bite fever is transmitted to humans in up to 10% of rat bites. However, there may be no history of rat bite. Rat-bite fever is most commonly caused by rat bites but can be caused by the bite of any rodent or of a carnivore that preys on rodents. Both the streptobacillary and spirillary forms affect mainly urban dwellers living in crowded conditions and biomedical laboratory personnel. In the US and Europe, rat-bite fever is usually due to Streptobacillus moniliformis; in Asia, it is usually due to the spirochete Spirillum minus.

Streptobacillary rat-bite fever

Streptobacillary rat-bite fever is caused by the pleomorphic gram-negative bacillus S. moniliformis, an organism present in the oropharynx of healthy rats. Epidemics have been associated with ingestion of unpasteurized milk contaminated by S. moniliformis(Haverhill fever), but infection is usually a consequence of a bite by a wild rat or mouse. Other rodents and weasels have also been implicated.

The primary wound usually heals promptly, but after an incubation period of 1 to 22 (usually < 10) days, a viral-like syndrome develops abruptly, causing chills, fever, vomiting, headache, and back and joint pains. Most patients develop a morbilliform, petechial, or vesicular rash on the hands and feet about 3 days later. Polyarthralgia or arthritis, usually affecting the large joints asymmetrically, develops in many patients within 1 wk and, if untreated, may persist for several days or months. Fever may return, occurring irregularly over a period of weeks to months.

Bacterial endocarditis and abscesses in the brain or other tissues are rare but serious. Some patients have infected pericardial effusion and infected amniotic fluid.

Haverhill fever (erythema arthriticum epidemicum) resembles percutaneously acquired rat-bite fever, but with more prominent pharyngitis and vomiting.

Diagnosis of streptobacillary rat-bite fever is confirmed by culturing the organism from blood or joint fluid. Measurable agglutinins develop during the 2nd or 3rd wk and are diagnostically important if the titer increases. PCR or enzyme-linked immunosorbent assay (ELISA) tests may be helpful. The WBC count ranges between 6,000 and 30,000/μL. Nontreponemal syphilis serologic tests (Venereal Disease Research Laboratory [VDRL] or rapid plasma reagin [RPR] tests) may be falsely positive. The streptobacillary form usually can be differentiated clinically from the spirillary form.

Treatment of streptobacillary rat-bite fever involves one of the following given for 7 to 10 days:

  • Amoxicillin 1 g po q 8 h

  • Procaine penicillin G 600,000 units IM q 12 h

  • Penicillin V 500 mg po qid

Erythromycin 500 mg po qid may be used for patients allergic to penicillin. Doxycycline 100 mg q 12 h for 14 days is an alternative.

Patients with S. moniliformis endocarditis require high-dose penicillin G plus either streptomycin or gentamicin.

Untreated, rat bite fever has a case fatality rate of about 10%.

Spirillary rat-bite fever (sodoku)

S. minus infection is acquired through a rat bite or occasionally a mouse bite. Ingestion of the organism does not cause disease. The wound usually heals promptly, but inflammation recurs at the site after 4 to 28 (usually > 10) days, accompanied by a relapsing fever and regional lymphadenitis. A roseolar-urticarial rash sometimes develops but is less prominent than the streptobacillary rash. Systemic symptoms commonly accompany fever, but arthritis is rare. In untreated patients, 2- to 4-day cycles of fever usually recur for 4 to 8 wk, but febrile episodes rarely recur for > 1 yr.

Diagnosis of spirillary rat-bite fever is by

  • Direct visualization or culture of Spirillum from blood smears or tissue from lesions or lymph nodes

  • Giemsa stain or darkfield examination of blood from inoculated mice

Direct visualization is required because S. minus cannot be cultured on synthetic media. The WBC count ranges between 5,000 and 30,000/μL.

The VDRL results are false-positive in half the patients. The disease may easily be confused with malaria or Borrelia recurrentis infection; both are characterized by relapsing fever.

Treatment of spirillary rat-bite fever is the same as for the streptobacillary form.