Rat-Bite Fever

Etiology

Two types of bacteria can cause rat-bite fever and cause two separate types of illness.[6][7]

Spirillosis

Rat-bite fever transmitted by the gram-negative coiled rod (Spirillum minus) is very rare and is found in Asia. It is also called Sodoku. 

Streptobacillosis

Streptobacillosis is a more common form of rat-bite fever, and it is also known as epidemic arthritic erythema. It is caused by Streptobacillus moniliformis and is transmitted by rat bite or ingestion of contaminated products usually milk (Haverhill fever). 

Epidemiology

Annually, more than two million animal bites occur in 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. The risk of infection after a rat bite is about 10% [8][9][5]

Pathophysiology

Because of the relatively low incidence and low mortality rate, little information describing the pathogenesis of S. moniliformis exists. The organism is capable of producing morphological findings not associated with bacterial infections. An autopsy of rat bite fever victims demonstrates erythrophagocytosis, hepatosplenomegaly, interstitial pneumonia, lymph node sinus hyperplasia, endocarditis, and myocarditis along with degenerative changes in the kidneys and liver. Radiological data suggest that rat-bite fever might cause damage to physes and acrophyses of bones, similar to frostbite induced damage. Biopsy of skin lesions in rat bite fever has demonstrated leukocytoclastic vasculitis.

Histopathology

When there is suspicion of rat bite fever and if the cultures are negative, the bite site can be biopsied to isolate the organism. Streptobacillus moniliformis is a filamentous, highly pleomorphic, non-motile gram-negative organism. Under the microscope, it may appear straight but may have some irregular lateral bulbar swellings. The bacteria may be found in aggregates or chains. The colonies appear as "cotton ball" in culture media [10]

In case of Spirillum minus, the organism is a thick, short, tightly coiled rod and it is gram stain negative.[5]

History and Physical

The disease is best described based on the type of the infecting organism:

In the case of  Streptobacillus , the incubation period varies from 3 to 20 days, but in most cases, it's less than a week. The symptoms do not manifest for two to four weeks after exposure. The symptoms include fever, migratory polyarthritis, and rigors. The fever lasts longer and is recurring, often for months. The fever may wax and wane. The joints can become painfully swollen and back pain can also develop.  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 in the knee and ankle joints at some point during the illness. In some patients, the migratory polyarthralgia may last several years.  On physical examination; the site of the bite will appear to be 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. [5] About three-quarters of patients will develop a petechial or maculopapular rash and there may be hemorrhagic vesicles on the extremities, which are tender to palpation.[11]

In the case of Spirillosis, the incubation period is two to ten days. The bite site is indurated and may ulcerate and have lymphadenopathy unlike the case of Streptobacillus, where the lesions have mild inflammation and lymphadenopathy is rare.  Around 50 % of patients may have a red-brown colored violaceous, macular rash and rarely plaques [12]

Haverhill fever presents with similar symptoms like rat bite fever with the exception of lack of history of rat bite or contact with rats. Such individuals are more prone to have headaches, dizziness, and vomiting.

Evaluation

A high clinical suspicion is needed for diagnosing this entity. Streptobacillus moniliformis can be identified by culture. However, it is very difficult to be cultured. The specimen has to be inoculated in culture media that is devoid of Sodium Polyanethol Sulphonate which is an anticoagulant used in culture media because it inhibits the growth of the organism. Anaerobic culture bottles are suitable for the test since they do not contain Sodium Polyanethol Sulphonate.[13]

Spirillosis cannot be cultured, and it can be only identified using dark ground microscopy or Giemsa staining techniques. 

Treatment / Management

Avoid rodents, wash hands and face after contact and any scratches should be cleaned, and antiseptics applied. The effect of prophylactic chemoprophylaxis following rodent bites or scratches is unknown. Animal handlers, laboratory workers, sanitation, and sewer workers must take precautions against exposure. Wild rodents, dead or alive, should not be touched.[14] (B3)

Typically Intravenous Penicillin G at a dose of  200,000 units every 4 hours or Ceftriaxone 1 gram intravenously daily should be administered. Once the patient improves clinically, the Intravenous medications can be transitioned to either Penicillin V 500 Mg four times a day or Ampicillin 500 mg four times a day or Amoxicillin 500 mg three times a day. The total duration of antibiotics is 2 weeks. In Penicillin allergic patients, Doxycycline 100 mg twice a day either intravenously or orally can be substituted. 

Differential Diagnosis

• Meningococcemia
• Disseminated gonorrhea
• Lyme disease
• Brucellosis
• Ehrlichiosis
• Rickettsial infections

Prognosis

If the disease is untreated, the mortality rate is around 10%

Complications

• Endocarditis
• Fulminant sepsis
• Pneumonitis
• Meningitis
• Liver abscess
• Adrenal gland failure