Streptobacillus moniliformis, a common representative of the nasopharyngeal flora of rodents, is the causative agent of the zoonosis rat bite fever. The clinical presentation with fever, migratory polyarthralgias and skin rash may establish a challenging differential diagnosis. The zoonosis has a potentially lethal course in a vulnerable population (children, low socioeconomic class) and a commonly available treatment (penicillin). The goal of this case report review is to outline common epidemiological factors and clinical presentation forms in order to increase clinical awareness and install fast antimicrobial treatment.
An 11-year-old girl is referred to the emergency department by her general practitioner because of a recurrent fever in the last two weeks, painful, swollen joints (left shoulder, elbow, knee and finger) and a fluctuating rash on the face and limbs. There are accompanying complaints of general malaise (earache, sore throat, reduced intake with one-time vomiting and diarrhea). The child’s medical history reports ADHD for which she is being treated with methylphenidate. The other family members are in good health and the travel history is negative. A tick bite was not noticed. At the time of clinical examination, the child is in good general condition with fever up to 39.0 °C. The examination confirms a mild pharyngitis with accompanying bilateral cervical adenopathies and a mild swelling of the proximal interphalangeal joint at the level of the left middle finger. There are no visable skin defects or splenomegaly [1-5]. A peripheral blood sample shows mild leucocytosis (12 700/ mm3) with absolute neutrophilia (10 130/mm3) and a minimal CRP increase (8.6mg/dl). Investigation with chest X-ray, urine sediment and culture and SARS-COV-2 and influenzae PCR all remain negative. Ultrasound investigation of the swollen proximal interphalangeal joint shows increased intra-articular fluid.
The girl is admitted to the pediatric ward for conservative management with fluid and antipyretic treatment. An infection of viral origin (Enterovirus, Parvovirus B19, Epstein-Barr virus) is suspected. Twenty hours after incubation, growth is detected in a pediatric blood culture bottle (Peds Plus Bactec BD). The gram stain shows filamentous gram-negative bacilli. Gray, small, shiny colonies appeared on blood agar after overnight incubation in 5% CO2 at 37 °C. Identification with MALDI-TOF-MS results in Streptobacillus moniliformis. Antimicrobial susceptibility testing was unsuccessful (no bacterial growth). The girl was treated with a two-week amoxicillin therapy, initially intravenously. After favorable clinical and biochemical evolution, she was further treated at home with amoxicillin per os. Reconstitutio ad integrim occurred. Only after thorough anamnesis it became clear that the child got bitten by her father’s pet rat two weeks before admission [6-10].
A search was conducted in the PubMed database using the terms ‘rat bite fever’, ‘Streptobacillus moniliformis’, ‘streptobacillosis’ and ‘epidemic arthritic erythema’ combined by the Boolean operator ‘OR’. This resulted in 101 hits. Inclusion criteria were case report, English or Dutch language, Europe, free full text article available and relevance to the subject. The following data were extracted from the 20 remaining case reports: age, area, rat exposition, incubation period, symptoms on day of admission, (duration of) antibiotic treatment, outcome.
In 11 out of 18 case reports, direct rat contact occurred in a domestic setting (direct contact with pet rats in nine cases and in precarious house conditions in two cases). Rat exposure was occasional in seven out of 18 case reports. Probably rat manipulation using gloves in an occupational setting makes transmission of Streptobacillus moniliformis less likely. In four cases, the index patient was a child. The time frame between direct rat contact (direct contact with rat excretions, rat bite or rooster scratch) and hospital admission varied between five and 21 days in nine cases. It is clear that a bite or scratch mark might not be visible anymore on the day of admission. The majority of cases presented with fever (17/20) and polyarthritis or polyarthralgia (15/20). A rash was described in 8/20 cases. Five cases had a complicated course (endocarditis, spondylodiscitis, osteomyelitis, peripheral ischemia). In the majority of cases, an infectious syndrome was suspected in the presence of fever and markedly increased inflammatory parameters [11-15].
Here blood sampling was performed, and antibiotic therapy was initiated empirically. However, in case five, there was a significant delay in the start of antibiotic therapy. Benzylpenicillin administration was started only seven days after hospital admission which resulted in gradual recovery and persistent damage to the right wrist and left-hand extensor tendons. This case presented with polyarthritis, and the patient was initially treated with corticosteroids and colchicine as the presumed diagnosis was median vessel vasculitis and gout respectively. In our case and in case 18, antibiotic therapy was only initiated after growth detection in blood cultures taken on admission. Gram stains showed gramnegative rods. This underlines the importance of blood culture sampling even in suspicion of a viral origin of fever. A neutrophilic formula and an elevated procalcitonin point in the direction of a bacterial origin. Laboratory diagnosis relies on the culturing of blood, purulent or synovial fluid or on 16S rDNA testing of suitable specimens. Ten blood cultures and 10 alternative cultures (synovial fluid, abcess fluid, aortic valve, blister fluid, and peroperative samples) yielded growth. In 11 cases, 16S rDNA was used in the diagnostic workup.Administration of various classes of antibiotics (B-lactams, cephalosporins macrolides) resulted in complete resolution. In 19 cases, hospital admission was necessary. Nineteen patients recovered and one patient died (Table 1) [16-19].
Rat bite fever is strongly underdiagnosed from both a clinical and a microbiological point of view. It is recommended to include rat bite fever in the differential diagnosis in the presence of a fever syndrome of unknown origin and anamnestic confirmed rat exposure. This diagnosis becomes more likely if polyarthralgia and rash are present simultaneously. In case of a clinical suspicion of rat bite fever the microbiology, department should be consulted and a bacterial 16S ribosomal DNA PCR should be conducted when necessary. Since most transmissions occur in a domestic setting, keeping rats as pets cannot be recommended.
- Frans J, Verhaegen J, Van Noyen R (2001) Streptobacillus moniliformis: case report and review of the literature. Acta Clinica Belgica 56(3): 187-190.
- Grude N, Tveten Y, Torp PØ, Laastad O (2001) Rat bite fever- a case report. Tidsskrift den norkse legeforening 121: 3057-3058.
- Downing ND, Dewnany GD, Radford PJ (2001) A rare and serious consequence of a rat bite. Annals of the Royal College of Surgeons of England 83(4): 279-280.
- Thong BY, Barkham TM (2003) Suppurative polyarthritis following a rat bite. Annals of the rheumatic diseases 62(9): 805-806.
- Tattersall RS, Bourne JT (2003) Systemic vasculitis following an unreported rat bite. Annals of the rheumatic diseases 62(7): 605-606.
- Dubois D, Robin F, Bouvier D, Delmas J, Bonnet R, et al. (2008) Streptobacillus moniliformis as the causative agent in spondylodiscitis and psoas abscess after rooster scratches. Journal of clinical microbiology 46(8): 2820-2821.
- Van Nood E, Peters SH (2005) Rat-bite fever. The Netherlands Journal of Medicine 63(8): 319-321.
- Andre JM, Freydiere AM, Benito Y, Rousson A, Lansiaux S, et al. (2005) Rat bite fever caused by Streptobacillus moniliformis in a child: human infection and rat carriage diagnosed by PCR. Journal of Clinical Pathology 58(11): 1215-1216.
- Kondruweit M, Weyand M, Mahmoud FO, Geissdörfer W, Schoerner C, et al. (2007) Fulminant endocarditis caused by Streptobacillus moniliformis in a young man. Journal of Thoracic and Cardiovascular Surgery 134(6): 1579-1580.
- Glasman PJ, Thuraisingam A (2009) Rat bite fever: a misnomer? British Medical Journal Case Reports.
- Loridant S, Jaffar Bandjee MC, La Scola B (2011) Shell vial cell culture as a tool for Streptobacillus moniliformis "resuscitation". The American Journal of Tropical Medicine and Hygiene 84(2): 306-307.
- Lu H, Van Beers EJ, Van den Berk GE (2012) Pythons and a palmar rash. The Netherlands Journal of Medicine 70(5): 230-233.
- Fenn DW, Ramoutar A, Jacob G, Bin Xiao H (2014) An unusual tale of rat-bite fever endocarditis. British Medical Journal Case Reports.
- Budair B, Goswami K, Dhukaram V (2014) Septic arthritis secondary to rat bite fever: a challenging diagnostic course. British Medical Journal Case Reports.
- Yu J, Elsayed S, Sun D (2017) A 44-year-old man with acute asymmetric polyarthritis and fever. Canadian Medical Association Journal 189(25): E861-E864.
- Eisenberg T, Poignant S, Jouan Y, Fawzy A, Nicklas W, et al. (2017) Acute Tetraplegia Caused by Rat Bite Fever in Snake Keeper and Transmission of Streptobacillus moniliformis. Emerging Infectious Diseases 23(4): 719-721.
- Pena E, Jordão S, Simões MJ, Oleastro M, Neves I (2019) A rare cause of vertebral osteomyelitis: the first case report of rat-bite fever in Portugal. Revista da Sociedade Brasileira de Medicina Tropical.
- Lund KMA, Steinbakk M (2020) A woman in her twenties with headache, fever and a rash. Tidsskrift den norkse legeforening 140(13).
- Smallbones M, Monem M, Baganeanu M, Okocha M, Sofat R (2020) Near-fatal Periprosthetic Infection with Streptobacillus moniliformis: Case and Review. Journal of Bone and Joint Infection 5(1): 50-53.