Rat-bite Fever

Synonyms: streptobacillary rat-bite fever, streptobacillosis, Haverhill fever, epidemic arthritic erythema, spirillary fever, sodoku

Rat-bite fever is a zoonosis usually caused by infection with the bacterium Streptobacillus moniliformis. Another form of rat-bite fever (more common in Asia where it is known as sodoku^[1]) is caused by infection with the Gram-negative bacterium Spirillum minus.^[2]

Rats are the usual hosts of the bacteria, with Streptobacillus moniliformis being carried in the pharyngeal flora of 10-100% of healthy wild and laboratory rats.^[1]Human infection is usually acquired through rat bites, scratches or handling (contact with urine, excreta or secretions from mouth, eye or nose).^[1]However, guinea pigs, weasels, gerbils, squirrels and ferrets may occasionally be responsible for human infection.^[1]

A variant of rat-bite fever is known as Haverhill fever (so called after the town in the USA in which there was an outbreak in 1926).^[1]It is thought to be caused by ingestion of milk or water contaminated with the bacteria via rat urine.^[2]Signs and symptoms are identical to those of rat-bite fever caused by S. moniliformis but there is no history of rat bite or exposure. Large groups of people may be affected; outbreaks can occur.

Person-to-person transmission of infection does not occur.^[2]

Epidemiology

• Rat-bite fever is rare.
• Rats throughout the world may carry S. moniliformis but the disease is most often reported in Asia, Europe and North America. 
• Rat-bite fever caused by S. minus is mainly reported in Asia.
• There are only 1-2 cases of rat-bite fever per year in the UK.^[2]
• People who keep rats as pets, as well as laboratory technicians and pet shop employees working with rats, are at increased risk.
• Children also seem to be particularly susceptible.^[3]

Presentation

A high index of suspicion is needed. Ask about exposure to rats or similar animals.

S. moniliformis infection

• The classic triad of symptoms is fever, rash and polyarthritis.
• The incubation period is usually less than seven days (but can be three days to three weeks).^[1]
• Evidence of the bite may have disappeared.
• Initially there is sudden high fever (38-41°) with rigors, nausea and vomiting, severe headache, sore throat, myalgia and joint pains.^[1]
• The fever usually resolves in three to five days but it can recur.^[1]
• A diffuse rash occurs in around 75% of cases. It can be maculopapular, petechial or purpuric. Haemorrhagic vesicles can develop on the extremities.^[1]The rash can be slow to resolve.
• An asymmetrical migratory polyarthralgia (large and small joints) occurs in around 50% of cases.^[1]Arthritis with joint pain, redness and swelling can occur.The polyarthralgia can last several years in some people.^[1]

S. minus infection

• Incubation period is usually longer (14-18 days).^[1]
• The rat-bite often ulcerates, and there is marked local lymphadenopathy.
• The fever is relapsing and remitting.
• A typical violaceous red-brown macular rash develops in 50% of people. Plaques and urticarial lesions may also be present.^[1]
• Joint involvement is rare.

Investigations

• FBC: leukocytosis.
• Bacterial culture: blood cultures, joint fluid or pus. S. minus may be isolated from the wound.
• Isolation of the organism can be difficult. The bacteria are slow-growing so it may take up to seven days for the culture to become positive. Media without sodium poly-anethol sulfonate (SPS) should be used because the anticoagulant can inhibit bacterial growth.^[2]
• Discussion with the microbiology laboratory is advised in suspected cases.^[4]
• PCR can also be used to identify the bacteria.^[4]

Differential diagnosis^[1]

These include:

• Sepsis due to streptococcal and staphylococcal bacteria.
• Lyme disease.
• Brucellosis.
• Rickettsial infections including Rocky Mountain spotted fever.
• Leptospirosis.
• Secondary syphilis.
• Viral infections including Epstein-Barr virus.
• Other causes of relapsing fever, including malaria and typhoid fever.
• Collagen vascular diseases.
• Drug reactions.

Management

• Penicillin is the first-line therapy.^[4]
• Tetracycline is an alternative in those who are penicillin-allergic.^{[1, 4]}

Complications^[1]

• Parotitis
• Tenosynovitis
• Bronchitis, pneumonia
• Metastatic abscesses, septicaemia
• Endocarditis, myocarditis, pericarditis 
• Vasculitis and polyarteritis nodosa
• Meningitis, encephalitis
• Nephritis
• Hepatitis

Prognosis

• If treated, prognosis is excellent and symptoms usually subside in a few days.
• Untreated, the mortality rate is approximately 10%.^[1]
• Arthritis may last for several months.^[1]

Prevention

• Avoiding contact with rats or rat-contaminated dwellings.
• Prophylactic antibiotics after a rat bite.