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Rat-Bite Fever


Larry M. Bush

, MD, FACP, Charles E. Schmidt College of Medicine, Florida Atlantic University;

Maria T. Vazquez-Pertejo

, MD, FACP, Wellington Regional Medical Center

Last full review/revision Nov 2020| Content last modified Sep 2022
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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 (of the streptobacillary form) 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.

The typical causative organism varies by geographic region:

  • US and Europe: Usually Streptobacillus moniliformis

  • Asia: Usually the spiral-shaped gram-negative rod 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. Migratory polyarthralgia or septic arthritis, usually affecting the large joints asymmetrically, develops in many patients within 1 week and, if untreated, may persist for several days or months. Fever may return, occurring irregularly over a period of weeks to months.

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

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. If the bite wound initially begins to heal, inflammation recurs at the site after 4 to 28 (usually > 10) days, accompanied by a relapsing fever and regional lymphadenitis. A red-brown occasionally 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 weeks, but febrile episodes rarely recur for > 1 year.

Diagnosis of Rat-Bite Fever

  • Clinical evaluation

  • Culture (of the streptobacillary form) and sometimes rising antibody titers

The diagnosis of rat-bite fever is clinical. The two forms usually can be differentiated clinically from one another:

  • Bite site: The bite site in streptobacillary rat-bite fever, if present, typically heals quickly, with minimal residual inflammation and without significant regional lymphadenopathy, whereas the bite site in spirillary rat-bite fever persists, becomes indurated, and may ulcerate, with associated regional lymphadenopathy.

  • Joints: In streptobacillary rat-bite fever, migratory polyarthralgia is frequent and septic arthritis of large joints occurs in some patients, whereas in spirillary rat-bite fever, joint manifestations are rare.

  • Skin: The rash in streptobacillary rat-bite fever is maculopapular, petechial, or purpuric and hemorrhagic vesicles that may develop on the peripheral extremities, especially the hands and feet, are very tender to palpation. The rash in spirillary rat-bite fever is red-brown macules with occasional urticaria.

Confirmation of streptobacillary rat-bite fever

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 week and are diagnostically important if the titer increases. Polymerase chain reaction (PCR) or enzyme-linked immunosorbent assay (ELISA) tests may be helpful. The white blood cell count ranges between 6,000 and 30,000/mcL (between 6 and 30 × 109/L). Nontreponemal syphilis serologic tests (Venereal Disease Research Laboratory [VDRL] or rapid plasma reagin [RPR] tests) may be falsely positive.

Confirmation of spirillary rat-bite fever

Diagnosis of spirillary rat-bite fever is confirmed by

  • Direct visualization 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/mcL (between 5 and 30 × 109/L).

The VDRL results are false-positive in half the patients. The disease may easily be confused with malaria Malaria Malaria is infection with Plasmodium species. Symptoms and signs include fever (which may be periodic), chills, rigors, sweating, diarrhea, abdominal pain, respiratory distress, confusion... read more or Borrelia recurrentis infection because both are characterized by relapsing fever.

Prognosis for Rat-Bite Fever

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

Treatment of Rat-Bite Fever

  • Penicillin or doxycycline

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

  • Amoxicillin 1 g orally every 8 hours

  • Procaine penicillin G 600,000 units IM every 12 hours

  • Penicillin V 500 mg orally 4 times a day

Doxycycline 100 mg orally every 12 hours for 14 days is used for patients allergic to penicillin. Erythromycin 500 mg orally 4 times a day may also be an effective alternative.

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

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