Clinical Overview of Rat Bite Fever (RBF)

Key points

People can get RBF from rodents carrying the bacteria. Rat-bite fever (RBF) is an infectious disease caused by two different bacteria: Streptobacillus moniliformisn and Spirillum minus.

Two people wearing white coats and goggles look at a microscope in a lab setting

Overview

RBF is known to be rare in the United States. Currently, rat bite fever is not reportable in any U.S. state or territory and is not nationally notifiable.

Recent case reports have highlighted the emerging risk for RBF among infants, children and teens. These populations are more likely to have contact with pet rodents. Cases in pet stores or animal research laboratories are sometimes reported.

Causes

In North America, RBF is caused primarily by Streptobacillus moniliformis. These bacteria have several microbiological features; fastidiously growing, gram-negative, pleomorphic, non-sporulating, non-encapsulated rod, facultative anaerobes, non-motile, and tangled filaments with bulbous or "Monilla"-like swellings.

Spirillum minus more often cause RBF infections in Asia and are characterized as short, thick, motile spirochetes, having bipolar flagellar tufts.

How it spreads

Streptobacillus moniliformis and Spirillum minus are commensal organisms. The bacteria can be found in the oral, nasal, and conjunctival secretions and animal urine. Both organisms may be transmitted to people through broken skin, bites, or scratches. Infection can also result from close contact with an infected rodent (without a bite of scratch).

A person can also get RBF if they ingest food or drink contaminated with these bacteria.

Clinical features

Initial symptoms of S. moniliformis are non-specific and include fever, chills, myalgia, headache, and vomiting. Patients may develop a maculopapular rash on the extremities around 2 to 4 days after fever onset. 50% of patients then develop polyarthritis.

The incubation period for S. moniliformis typically ranges from 3 to 10 days. The signs and symptoms of Haverhill fever, caused by S. moniliformis, primarily in North America, differs slightly from Streptobacillary cases of RBF. Haverhill fever can be associated with more severe nausea, vomiting, and pharyngitis.

Symptoms caused by S. minus infection usually occur 7 to 21 days after exposure to an infected animal. Patients likely traveled abroad, particularly to Asia.

Following partial healing of a rat bite, common signs and symptoms include:

  • fever
  • ulceration at the bite site
  • lymphangitis
  • lymphadenopathy
  • distinct rash of purple or red plaques

If untreated or not appropriately treated, RBF infections may result in:

  • soft tissue and solid-green abscesses
  • septic arthritis
  • pneumonia
  • hepatitis
  • nephritis
  • meningitis
  • endocarditis, myocarditis, or pericarditis

Complications involving endocarditis carry the highest risk for mortality.

Testing and diagnosis

You should consider testing a patient for RBF if the patient has been around rodents and presents symptoms of the disease. Common symptoms are fever, nausea, vomiting, joint pain and rash.

RBF is diagnosed by conducting culture isolations of S. moniliformis from:

  • blood
  • synovial fluid
  • other body fluids
  • affected tissues (abscessed organs)
  • primary lesions

In cases where a positive culture is absent, identifying pleomorphic gram-negative bacilli through Gram staining in suitable specimens can support an initial diagnosis.

S minus does not grow in artificial media. Diagnosis is made by identifying characteristic spirochetes in specimens using darkfield microscopy or differential stains.

Sometimes RBF is suspected in a severe illness or death without a diagnosis. As a healthcare provider, you can then ask for diagnostic help from their state public health laboratories or CDC.

If RBF is suspected in a severe illness or death, but a diagnosis has not been made, physicians can consider requesting diagnostic assistance from their state public health laboratories or CDC.

Whole blood and joint aspirate fluid are specimens of choice for S. moniliformis diagnosis. Specimens should be collected before initiating antimicrobial therapy.

Due to changes in protocols, please contact the Bacterial Special Pathogens Branch at (404)-639-1711 for specific information on how to test specimens for S. moniliformis.

For detailed information on how to submit specimens for testing at CDC, visit the Infectious Disease Laboratory website.

Treatment and recovery

There is limited research on the effectiveness of specific antibiotics to treat RBF. However, S. moniliformis is generally susceptible to several antibiotics. These include:

  • penicillins
  • cephalosporins
  • carbapenems
  • aztreonam
  • clindamycin
  • erythromycin
  • nitrofurantoin
  • bacitracin
  • doxycycline
  • tetracycline
  • teicoplanin
  • vancomycin

Intravenous penicillin G given for 7 or more days, then oral penicillin, is usually recommended for the treatment of RBF. However, patients can experience adverse reactions to penicillin treatment which usually improve quickly once antibiotics are started.

In patients allergic to penicillin, doxycycline or streptomycin are alternative choices.

RBF can present similarly to other febrile rash illnesses, such as Rocky Mountain Spotted Fever (RMSF). If RBF and RMSF are both in differential diagnosis, doxycycline should be considered as first-line treatment. This is because there is a need for rapid treatment and limited diagnostics for both diseases. This consideration applies to pediatric patients <8 years old. Dental staining is not a risk when using doxycycline for less than 14 days.

Endocarditis is a rare complication and may require combination therapy with both intravenous penicillin G and streptomycin or gentamicin for effective treatment. However, no recent studies have been done to evaluate the effectiveness of combination treatment.