Rat bite fever: a misnomer?

Abstract

We report a case of rat bite fever (Streptobacillus moniliformis) in a young man who presented generally unwell with pyrexia, vomiting, arthralgia and deranged liver function. Two weeks before his illness he had disposed of a dead rat but was not bitten by it. This zoonotic infection was treated with broad spectrum antibiotics and he made a complete recovery. It is a rarely diagnosed but likely common infection given the frequent contact between humans and rodents. In the past, confirmation of the organism has been difficult due its dislike of culture mediums, but the advent of polymerase chain reaction (PCR) testing has allowed reliable isolation. Appropriate treatment is important because there is an associated mortality from secondary endocarditis.

Background

Our case highlights the relatively non-specific clinical presentation of rat bite fever (Streptobacillus moniliformis) and, given the microbiological difficulties associated with it, the importance of the history in the evaluation of deranged liver function.

It also shows that rat bite fever may be a misnomer as even fleeting contact with rodents may be sufficient to contract the disease.

On searching available literature in Medline it would also seem to be the first reported case in the UK for 6 years.¹ This probably reflects the difficulties in confirming a diagnosis rather than the scarcity of the disease, as the organism is so common in rodents and human contact with them also relatively frequent. However, with polymerase chain reaction (PCR) techniques now available it remains an entity to be borne in mind, as it can cause a wide spectrum of readily treatable symptoms with possible fatal sequelae if not identified.

Case presentation

A 23-year-old man was admitted with a 3 day history of rigors, abdominal pain, vomiting, headache and right shoulder pain. He had no significant travel history or exposure to unwell contacts. There was no significant past medical history. He took no prescribed or over-the-counter medications and had not taken any for a number of months. He worked as a sales assistant in a supermarket and drank approximately 15 units of alcohol per week. He denied any risk factors for transmissible viral hepatitides.

On examination, he had a swinging pyrexia. He was not jaundiced. There were no rashes. He had some right upper quadrant tenderness but there was no organomegaly. There was no obvious clinical focus of infection; his chest was clear, heart sounds normal; and he had no neurological signs. Examination of his right shoulder was unremarkable.

Investigations

Investigations revealed raised inflammatory markers with an initial white cell count of 12×10⁹ cells/l (normal range (NR) 3–10×10⁹ cells/l) and C reactive protein 333 mg/l (normal <5 mg/l). His liver function tests demonstrated a hepatitic picture with an alkaline phosphatase 130 IU/l (NR 45–120 IU/L), aspartate transaminase 278 IU/l (NR 0–40 IU/l), alanine transaminase 339 IU/l (NR 0–40 IU/l), γ-glutamyltransferase 210 IU/l (NR 11–50 IU/l), albumin 41 g/l (NR 36–52 g/l) and INR 1.3. His chest radiograph showed clear lung fields and urine dipstick was positive for blood, protein and ketones.

Treatment

Subsequent to admission his temperature spiked at 39°C and he developed tachycardia and tachypnoea. He was empirically treated with oral amoxicillin/clavulanic acid and erythromycin to cover a possible urinary tract infection or atypical pneumonia. He made a rapid clinical recovery over the course of a few days and his liver enzymes started to improve slowly. Subsequent investigations included negative urine culture, normal abdominal ultrasound scan and blood cultures. The blood cultures proved to be particularly interesting as they had a weak growth of a Gram variable rod of unknown significance. The appearances were possibly consistent with Streptobacillus moniliformis, and so the samples were sent for PCR testing.

Outcome and follow-up

On further questioning, the patient had disposed of a dead rat 2 weeks before his illness. He was not scratched or bitten by it. On the basis of the microbiology findings and the supportive clinical scenario a diagnosis of rat bite fever was made. He was discharged once he started feeling better. On follow-up in clinic 6 weeks later, he had made a complete recovery and his liver enzymes had returned to normal. PCR results were available at this time which confirmed S moniliformis.

Discussion

Rat bite fever is a rare zoonosis caused by S moniliformis in the west and Spirillium minus in Asia. It may also be referred to as Haverhill fever (after a protracted outbreak in a Massachusetts town in 1926), or Sodoku (meaning ‘rat poison’ in Japanese). Both organisms are commonly found in the oropharyngeal flora of rats and other rodents; they may be cultured from swabs of wild and laboratory animals with an incidence of between 50–100%.² Infection of humans typically, but not exclusively as our case demonstrates, follows a bite or scratch by an infected animal. It is well documented that the organism can be transferred by any close contact or infected water supplies.^3–5 Approximately 30% of patients with rat bite fever do not report being bitten or scratched by a rat.⁶ As it is not a notifiable disease, the exact incidence in the UK is not known, but transfer rates following a bite are thought to be 10%⁵ with untreated mortality standing at approximately 13%.⁷

The illness usually presents after about 2 weeks, typically with fever, arthralgias and a rash which may be macular, papular or petechial, but seems to favour the hands and feet.⁸ “Published complications of rat bite fever include endocarditis, myocarditis, pericarditis, systemic vasculitis, polyarteritis nodosa, meningitis, hepatitis, nephritis, amnionitis, pneumonia, and focal abscesses”.⁷ The majority of the fatal cases are accounted for by patients who develop endocarditis, usually in those with pre-existing valvular heart disease.⁹

S moniliformis is sensitive to penicillins, cephalosporins,¹⁰ macrolides and tetracycline.¹¹ However, the organism can represent a challenge to culture in the laboratory as sodium polyanethol sulfonate, used as an anticoagulant in commercially available sampling systems, is effective at limiting its growth.¹² This is probably the major barrier to diagnosis since S moniliformis is a highly pleomorphic Gram negative rod, which may stain positively on Gram stain. Furthermore, on account of its clump-like appearances on microscopy, it may be dismissed as proteinaceous debris.¹³ It will therefore usually require confirmation by PCR techniques.¹⁴

Learning points

• This case emphasises the importance of the history in the diagnosis of non-specific illness and deranged liver function.

• Infection with Streptobacillus moniliformis is probably much more common than is reported and may be contracted from rodents without being bitten by one.

• Rat bite fever has an associated mortality from endocarditis, but responds to broad spectrum antibiotics.