Rat-bite fever

Rat-bite fever is an acute, febrile human illness caused by bacteria transmitted by rodents,

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Common Rat

Rat-bite fever (RBF) is an infectious disease caused by two different bacteria:

• Streptobacillus moniliformis, the only reported bacteria that causes RBF in North America (streptobacillary RBF)
• Spirillum minus, common in Asia (spirillary RBF, also known as sodoku)
• People typically become infected with these bacteria after contact with rodents carrying the bacteria. A person can also get infected through consumption of food or water contaminated with the urine and droppings of rodents carrying the bacteria. This is known as Haverhill fever.

If not treated, RBF can be a serious or even fatal disease.

Etiology (cause)

In North America, RBF is caused primarily by Streptobacillus moniliformis. These bacteria have the following microbiological features:

• Fastidiously growing bacteria
• Gram-negative, pleomorphic, non-sporulating, non-encapsulated rod
• Facultative anaerobes, except isolates from guinea pigs, which are obligate anaerobes.
• Non-motile
• Frequently in chains and tangled filaments with bulbous or “Monilia”-like swellings
• Spirillum minus more often cause RBF infections in Asia and are characterized as:

• Short, thick, motile spirochetes, having bipolar flagellar tufts

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Alberta Department of Public Health Rat Poster

Transmission

Streptobacillus moniliformis and Spirillum minus are commensal organisms that are part of the normal respiratory flora of rodents. Bacteria can be found in the oral, nasal, and conjunctival secretions, as well as animal urine. Either organism may be transmitted to humans through broken skin, bites, or scratches. Infection can also result from close contact with an infected rodent (without a reported bite or scratch), or ingestion of food or drink that have been contaminated with these bacteria. Infection that occurs as a result of ingestion is known as Haverhill fever, after a large bacterial outbreak that occurred in Haverhill, Massachusetts, in 1926, linked to contaminated unpasteurized milk products. Without early diagnosis and appropriate treatment, RBF can cause severe infections and death.

Signs and Symptoms

Any person who comes into contact with the bacteria that cause RBF is at risk for becoming sick with the disease. Remember, without early diagnosis and appropriate treatment, RBF can cause severe disease and death.

Risk factors

People who may be at greater risk for RBF infection include:

• Those who have pet rats or other rodents in their home
• People who have live or frozen feeder rats or other rodents in their home
• People who have been bitten or scratched by a rat or other rodent
• Those who work with rats or other rodents, such as at animal research laboratories or pet stores
• People who live or spend time in areas with rodent infestations
• Children who have contact with rodents

Children 5 years old or younger are at higher risk for infection with RBF because their immune systems may still be developing. Additionally, they are less likely to know how often they need to wash their hands, and how to properly do so. Infants and young children may place unclean fingers in their mouths or contaminate common household objects.

Adults ages 65 and older, women who are pregnant, or those with weakened immune systems who have difficulty fighting off infections (for example, people with cancer, HIV/AIDS, organ implants, or those taking certain medications such as steroids).

Clinical presentation

• 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, followed by polyarthritis in approximately 50% of patients. The incubation period for S. moniliformis typically ranges from 3 to 10 days. The signs and symptoms of Haverhill fever can differ slightly from Streptobacillary cases of RBF. Haverhill fever can be associated with more severe nausea, vomiting, and pharyngitis.

Symptoms caused by Spirillum minus infection usually occur 7 to 21 days after exposure to an infected animal. Patients are likely to have a history of travel outside of the United States and to Asia in particular. Following partial healing of a rat bite, common signs and symptoms include fever, ulceration at the bite site, lymphangitis, lymphadenopathy, and a distinct rash of purple or red plaques.

Complications

If untreated or not appropriately treated, RBF infections may result in soft tissue and solid-organ abscesses, septic arthritis, pneumonia, hepatitis, nephritis, meningitis, and endocarditis, myocarditis, or pericarditis. Complications involving endocarditis carry the highest risk for mortality.

Diagnosis and labs

RBF should be suspected in patients with fever, nausea, vomiting, joint pain, and rash, as well as a known or suspected history of rodent exposure.

S. moniliformis

• RBF is diagnosed by conducting culture isolation of S. moniliformis from blood, synovial fluid, other body fluids, affected tissues such as abscessed organs, or primary lesions.
• In the absence of a positive culture, Gram stain identification of pleomorphic gram-negative bacilli in appropriate specimens supports a preliminary diagnosis.
• Historically, serological assays were used for diagnostic purposes; however, validated serological tests for RBF determination in humans are currently not available.
• Due to changes in protocols, please contact the Bacterial Special Pathogens Branch at (404)-639-1711 or bspb@cdc.gov for specific information on how to test specimens for S. moniliformis.
• S. minus

• S. minus does not grow in artificial media. For this reason, diagnosis is made by identifying characteristic spirochetes in appropriate specimens using darkfield microscopy or differential stains.
• 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 (see Specimen Processing and Submission below).

Specimen Processing and Submission

• 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 Special Bacteriology Reference Laboratory website.

Treatment

• 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 develop Jarisch-Herxheimer reactions which can complicate penicillin treatment. Patients usually improve quickly once antibiotics are started. Without appropriate treatment, the mortality rate is about 10%.

• 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 given the need for rapid treatment and limited diagnostics for both diseases. This consideration applies to pediatric patients <8 years old as 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, this is based on older studies and no recent studies have been done to evaluate the effectiveness of combination treatment.

Prevention

You can lower your risk of becoming infected with RBF and other rodent diseases by avoiding direct contact with rodents, places with rodent infestations, or other areas where rodents may be present.

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