What is rat bite fever

Rat-bite fever also known as streptobacillosis, spirillary fever, bogger, and epidemic arthritic erythema, is an acute illness passed from rodent to human by rodent bite, urine or mucous secretions (Gupta M, Oliver TI. Rat-bite Fever (Streptobacillus moniliformis, Sodoku, Spirillum Minor) [Updated 2019 Feb 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK448197)). Rat-bite fever is a rare infectious disease and is caused by two different types of bacteria:

• Streptobacillus moniliformis, the only reported bacteria that causes rat bite fever in North America (streptobacillary rat bite fever) ¹
• Spirillum minus (Spirillum minor), common in Asia (spirillary rat bite fever, also known as Sodoku) ²

Most cases of rat-bite fever occur in Japan, but it has been seen in the United States, Europe, Australia, and Africa. The majority of cases are a result of a rat-bite. People typically become infected with these bacteria after exposure to the urine or bodily secretions of an infected rodent. These can come from the mouth, nose, or eyes. 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. Household pets such as dogs or cats exposed to rodents can carry the disease and infect humans. If a rodent bites a person, one should quickly and thoroughly wash and cleanse the wound area to reduce the risk of infection ³.

Symptoms of rat-bite fever include inflammation around the bite, fever, vomiting, headaches, and muscle aches. Joints can become painfully swollen and back pain can develop skin irritations can develop on the hands and feet. Wounds heal slowly, and symptoms come and go over the course of a few months.

The incubation period varies from 3 to 20 days but in most cases is less than a week. Some patients will report with non-specific symptoms of an upper respiratory tract infection.

On physical, the site of the bite will have healed with mild or no signs of inflammation. Localized lymph node enlargement is rare. If the site of the bite continues to show persistent inflammation and tenderness, another diagnosis should be suspected.

Fever as high as 102.2 °F to 105.8 °F (39 °C to 41 °C) has been reported. The fever may wax and wane. As the infection progresses, the individual will develop migratory polyarthralgia and myalgia. Both the large and small joints may be involved, but most patients experience inflammation at the knee and ankle joints at some point during the illness. In some patients, the migratory polyarthralgia may last several years.

About three-quarters of patients will develop a petechial or maculopapular rash. Also, there may be hemorrhagic vesicles on the extremities, which are tender to palpation.

If not treated, rat bite fever can be a serious or even fatal disease.

It is believed that rat bite fever is underdiagnosed and under-treated, chiefly because of the failure to consider the infection in the differential diagnosis. Untreated, the infection carries a mortality of more than 10% and hence, emergency department providers should know about its presentation. The organism, Streptobacillus moniliformis is very sensitive to penicillin.

When rate bite fever is treated promptly, the outcomes are good. However, untreated cases can have a mortality rate anywhere from 6-15%. Causes of death after rate bite fever include endocarditis, sepsis, pneumonitis, and adrenal gland failure. Very few people survive rat bite fever without treatment. The recovery after rat bite fever is often prolonged and may take weeks or months. Fortunately, less than a few dozen cases of rat bite fever have been reported in Europe and North America ⁴.

Figure 1. Rat bite fever rash

[Source ⁵ ]

How is rat-bite fever spread?

There are several ways that people can get rat bite fever:

1. Through bites or scratches from rodents carrying the bacteria. The bacteria can enter the body directly through a bite wound, open skin, or mucous membranes such as in the eyes, nose, or mouth
2. When handling rodents carrying the bacteria or through contact with their saliva, urine, or droppings
3. Through contact with surfaces that are contaminated with the bacteria. The bacteria can enter the body through open skin, such as cuts or scrapes, or mucous membranes such as in the eyes, nose, or mouth
4. Consuming food or drinks that have been contaminated with droppings or urine from a rodent carrying the bacteria

Rat bite fever is not spread from one person to another.

Rat bite fever can be a serious or even fatal disease. See your doctor right away if you have any of the signs or symptoms of rat bite fever.

In addition to rat bite fever, rodents can spread other diseases to people.

Other animals that may cause rat bite fever infection include:

• Gerbils
• Squirrels
• Weasels

Two types of bacteria can cause rat-bite infection ⁶.

Spirillosis

Rat-bite fever transmitted by the gram-negative coiled rod (Spirillum minor) is very rare and is found in Asia. Symptoms do not manifest for two to four weeks after exposure. The fever lasts longer and is recurring, often for months. Rectal pain and gastrointestinal symptoms are less severe or are absent. Penicillin is the treatment of choice.

Streptobacillosis

The streptobacillosis form of rat-bite fever is also known as epidemic arthritic erythema. It is a severe disease caused by Streptobacillus moniliformis and is transmitted by rat bite or ingestion of contaminated products (Haverhill fever). The incubation period is two to ten days. Haverhill fever begins with high fever, shivering, headache, and joint pain. Soon a rash appears. This rash is characterized by flat red bumps and red or purple spots. Arthritis of large joints can be seen. The organism may be cultured from the blood or articular fluid. The disease can be fatal if untreated due to malignant endocarditis, meningoencephalitis, or septic shock. Treatment is with penicillin, tetracycline, or doxycycline.

Who is at higher risk for rat bite fever

Any person who comes into contact with the bacteria that cause rat bite fever is at risk for becoming sick with the disease. Remember, without early diagnosis and appropriate treatment, rat bite fever can cause severe disease and death. People who may be at greater risk for rat bite fever 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 rat bite fever 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).

Annually, more than two million animal bites occur the United States, and rats are responsible for approximately 1%. The typical victim of rat bite fever is a child younger than five years old living in poverty. Pet store workers and laboratory technicians working with rats are also at risk. Over 200 cases of rat bite fever have been documented in the United States, but this underestimated the disease is not reportable to health departments. The risk of infection after a rat bite is about 10% and the mortality rate of untreated rat bite fever is approximately 15% ⁷.

Rat bite fever prevention

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

If you have a pet rat or other pet rodents in your home or establishment:

• Pick the right pet for your family. Pet rodents are not recommended for families with children 5 years old or younger, pregnant women, or people with weakened immune systems because these groups are at greater risk for serious illness.
• Always wash your hands immediately after touching, feeding, or caring for pet rodents or cleaning their habitats.
• Play safely. Do not kiss, nuzzle, or hold rodents close to your face. This can startle your rodents and also increase your chances of being bitten. Bites from pet rodents can spread germs and possibly make you sick.
• Never eat, drink, or smoke while playing with or caring for your pet.
• Be aware that pet rodents can shed germs that can contaminate surfaces in areas where they live and roam. You don’t have to touch pet rodents to get sick from their germs. Make sure rodent enclosures are properly secured and safe so your pet doesn’t get hurt or contaminate surfaces.
• Keep pet rodents and their supplies out of the kitchen or other areas where food is prepared, served, or consumed.
• Clean and disinfect rodent habitats and supplies outside your home when possible. If you clean rodent supplies indoors, use a laundry sink or bathtub and be sure to thoroughly clean and disinfect the area immediately after. Never clean rodent habitats or their supplies in the kitchen sink, other food preparation areas, or the bathroom sink.
• Talk to your veterinarian about your pet’s health. Your veterinarian can play a key role in helping you and your pets stay healthy.
• Tell your healthcare provider that you have been around pet rodents, whether at home or away from the home, especially if you are sick or have been bitten or scratched. Some rodent germs can cause serious and life-threatening illness in people.

Follow these safe handling tips to take special care of your small pet and keep your family safe and healthy.

If you have rodents used for pet food (feeder rodents) in your home or establishment:

Frozen or live rodents used for pet food, also called feeder rodents, can carry germs that can make people sick. This can happen even if the rodent looks clean and healthy. Freezing does not kill these germs. Follow these tips to safely handle feeder rodents.

• Avoid handling frozen or live rodents if you are at greater risk for serious illness. Children 5 years old or younger, pregnant women, and people with weakened immune systems are at greater risk.
• Always wash your hands right after handling frozen or live rodents or after touching anything that was in contact with these animals.
• Never eat, drink, or smoke while handling live or frozen rodents or caring for your pets.
• Clean and disinfect all surfaces and supplies that come into contact with rodents. Rodents can contaminate surfaces where they are thawed or anything they touch. You can get sick by touching contaminated surfaces; you don’t have to touch the rodents to get sick from their germs.
• Keep rodents and their supplies out of the kitchen or other areas where food is prepared, served, or consumed. Never use the kitchen sink or food preparation areas to thaw frozen rodents or to clean live rodent habitats. Do not thaw frozen rodents in the microwave.
• Clean rodent supplies outside your home when possible. If you clean rodent supplies indoors, use a laundry sink or bathtub, and be sure to thoroughly clean and disinfect the area immediately afterward.
• Select frozen rodents when possible to reduce the risk of injury to your or your pet. Never feed your pets wild rodents.
• Talk to your veterinarian about your pet’s health and diet. Your veterinarian can play a key role in helping you and your pets stay healthy.
• Tell your healthcare provider that you have been around rodents, whether at home or away from home, especially if you are sick or have been bitten or scratched. Some rodent germs can cause serious and life-threatening illness in people.

Follow these safe handling tips to help keep your pet’s mealtime safer and healthier.

If you handle rats in a pet store setting:

• Wear protective gear, such as gloves.
• Avoid touching your mouth and face after handling rodents.
• Wash your hands with soap and warm water for at least 20 seconds after handling rodents, their cages, bedding, urine, or droppings.

If you handle rats in a laboratory or animal research setting:

• Wear proper protective laboratory gear, including gloves, and follow appropriate safety precautions.
• Avoid touching your mouth and face after handling rodents.
• Wash your hands with soap and warm water for at least 20 seconds after handling rodents, their cages, bedding, urine, or droppings.

What to do if you’re bitten or develop rat bite fever signs and symptoms

If you are bitten or scratched, immediately clean the wound with soap and warm water. Then, contact a health care provider and tell the provider about your recent injury. If you were bitten at work, make sure to document the bite and report the incident to your supervisor. Remember, without early diagnosis and appropriate treatment, rat bite fever can cause severe disease and death.

If you develop any of the signs and symptoms of rat bite fever, even if you have not had a bite or scratch, immediately contact a health care provider and tell the provider about your contact with rodents.

Additional recommendations

Rodents may not be suitable to keep as pets or feeder animals in your home, classroom, or child care center. This is particularly true if your home or establishment has infants, young children, pregnant women, or people with weakened immune systems. People with weakened immune systems include the elderly and people with illnesses such as diabetes, HIV/AIDS, or cancer.

There are currently no laboratory tests that can accurately tell whether or not an animal is infected with S. moniliformis or S. minus. There is also no data to support the use of antibiotics to get rid of either S. moniliformis or S. minus in animals carrying these bacteria.

Isolated cases and outbreaks of Haverhill Fever can occur after people consume food or drinks that have been contaminated with rodent droppings or urine that contain the bacteria. It is important to remember that contaminated food and drink sources may look and smell normal. To prevent contamination, take steps to avoid rat infestations and keep domestic rodents out of kitchens and other areas where food and drink are prepared, served, or consumed.

Rats can carry the bacteria that cause rat bite fever without showing signs of illness. In addition to rat bite fever, contact with rodents can result in several other illnesses.

Rat bite fever symptoms in humans

Without early diagnosis and appropriate treatment, rat bite fever can cause severe disease and death. In addition to rat bite fever, contact with rodents can result in several other illnesses.

The early symptoms of rat bite fever can be similar to the symptoms of other medical conditions. Symptoms of rat bite fever are often different for the two types of disease: streptobacillary rat bite fever and spirillary rat bite fever (Sodoku).

Initial symptoms of Streptobacillus 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 Streptobacillus moniliformis typically ranges from 3 to 10 days. The signs and symptoms of Haverhill fever can differ slightly from Streptobacillary cases of rat bite fever. 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.

If untreated or not appropriately treated, rat bite fever 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.

Symptoms and signs of streptobacillary rat bite fever include:

• Fever
• Vomiting
• Headache
• Muscle pain
• Joint pain or swelling (about 5 in 10 people with rat bite fever have this)
• Rash (occurs in about 3 out of 4 people with rat bite fever)

Symptoms usually begin 3 to 10 days after contact with the bacteria, but can be delayed as long as 3 weeks. By this time, any rodent bite or scratch wound that caused the infection has usually healed.

Within 2 to 4 days after fever begins, a rash may appear on the hands and feet. This rash looks like flat, reddened areas with small bumps. One or more joints may then become swollen, red, or painful.

The symptoms that develop with Haverhill Fever (the type of infection that can follow after consuming contaminated food or water) are similar to Streptobacillary rat bite fever, but may include more severe vomiting and sore throat.

Complications of streptobacillary rat bite fever can include:

• Abscesses (pockets of infected fluid) inside of the body, like in the belly (abdominal cavity)
• Infections of the liver (hepatitis) and kidneys (nephritis)
• Infections involving the lung (pneumonia)
• Infections involving the brain and nervous system (meningitis)
• Infections involving the heart (endocarditis, myocarditis, or pericarditis)

About 1 in 10 people who have streptobacillary rat bite fever infection die ⁸.

Symptoms and signs of spirillary rat bite fever (sodoku) can vary and often include:

• Fever (that may come and go or occur repeatedly)
• Swelling or formation of an ulcer at the bite wound (if present)
• Swollen lymph nodes (small glands that filter lymph, the clear fluid that circulates through the lymphatic system, and help fight infections)
• Rash (about 5 in 10 people with Sodoku have this) that can appear all over the body or only near the area of the bite wound (if present)

These symptoms usually occur 7-21 days after exposure to an animal carrying the bacteria.

If you have any of the symptoms of rat bite fever after contact with rats or other rodents, immediately see your health care provider. Make sure to tell your provider about your contact with rodents.

Rat bite fever possible complications

Rat-bite fever may cause these complications:

• Abscesses of the brain or soft tissue
• Infection of the heart valves
• Inflammation of the parotid (salivary) glands
• Inflammation of the tendons
• Inflammation of the heart lining

Rat bite fever diagnosis

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

Rat bite fever is diagnosed by detecting the bacteria in the skin, blood, joint fluid, or lymph nodes with antibody tests. Different tests should be run depending on the symptoms ³.

Streptobacillus moniliformis

• Rat bite fever is diagnosed by conducting culture isolation of Streptobacillus 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 rat bite fever determination in humans are currently not available.

Spirillum minus (Spirillum minor)

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

• Spirillum 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 from blood smears or tissue from lesions or lymph nodes.

If rat bite fever 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 the Centers for Disease Control and Prevention (CDC).

Rat bite fever treatment

If you develop any of the signs and symptoms of rat bite fever after coming in contact with rats or other rodents, immediately contact a health care provider. Make sure to tell your provider about your contact with rodents.

If your provider suspects that you have rat bite fever, he or she will treat you with antibiotics. Antibiotics can be highly effective at curing the rat bite fever disease if treatment is started soon after you become sick. It is important that you follow your doctor’s instructions on how to take your antibiotics, and that you take all of the medicine that your doctor prescribes to you, even if you start to feel better.

Without early diagnosis and appropriate treatment, rat bite fever can cause severe disease and death.

There is limited research on the effectiveness of specific antibiotics to treat rat bite fever. However, Streptobacillus 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 rat bite fever. 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.

Rat bite fever can present similarly to other febrile rash illnesses, such as Rocky Mountain Spotted Fever. If rat bite fever and Rocky Mountain Spotted Fever 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.

Rat bite fever prognosis

When proper treatment for rat-bite fever, the prognosis is good. Without treatment, the infection may resolve on its own, although it may take up to a year to do so. A particular strain of rat-bite fever in the United States can progress and cause complications that may be fatal. If untreated, streptobacillary rat-bite fever can result in infection in the lining of the heart, the spinal cord, brain, and lungs. Complications of rat bite fever have been reported. These reports include systemic vasculitis, myocarditis, endocarditis, nephritis, hepatitis, and pneumonia. Endocarditis carries the highest mortality as it is often mistaken for rheumatic valvular heart disease, resulting in a delay with appropriate antibiotics.

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