1 figure omitted
Rat-bite fever (RBF) is a rare, systemic illness caused by infection
with Streptobacillus moniliformis. RBF has a case-fatality
rate of 7%-10% among untreated patients.1S.
moniliformis is commonly found in the nasal and oropharyngeal flora
of rats. Human infection can result from a bite or scratch from an infected
or colonized rat, handling of an infected rat, or ingestion of food or water
contaminated with infected rat excreta.1 An abrupt onset of fever,
myalgias, arthralgias, vomiting, and headache typically occurs within 2-10
days of exposure and is usually followed by a maculopapular rash on the extremities.1 This report summarizes the clinical course and exposure history of
two rapidly fatal cases of RBF identified by the CDC Unexplained Deaths and
Critical Illnesses (UNEX) Project in 2003. These cases underscore the importance
of (1) including RBF in the differential diagnoses of acutely ill patients
with reported rat exposures and (2) preventing zoonotic infections among persons
with occupational or recreational exposure to rats.
Florida. In early September 2003, a previously
healthy woman aged 52 years visited an emergency department (ED) with a 2-day
history of headache, abdominal pain, diarrhea, lethargy, right axillary lymphadenopathy,
progressive myalgias, and pain in her distal extremities. On physical examination,
she was afebrile and hypotensive (blood pressure: 82/40 mmHg) with left-sided
abdominal tenderness and scleral icterus; no rash was noted. Laboratory tests
indicated a mildly elevated white blood cell count of 13,800 cells/μL
(normal: 5,000-10,000 cells/μL), thrombocytopenia (71,000 platelets/μL
[normal: 130,000-500,000 platelets/μL]), elevated alanine aminotransferase
of 112 U/L (normal: 20-52 U/L), elevated aspartate aminotransferase of 154
U/L (normal: <40 U/L), elevated total bilirubin of 5.8 mg/dL (normal: 0.2-1.2
mg/dL), elevated blood urea nitrogen of 55 mg/dL (normal: 7-23 mg/dL), and
elevated creatinine of 2.9 mg/dL (normal: 0.7-1.5 mg/dL).
The patient was admitted to the intensive care unit, where she became
increasingly hypoxic with marked anemia (hemoglobin: 8.6 g/dL [normal: 12-16
g/dL]) and increasingly severe thrombocytopenia (32,000 platelets/μL).
She was treated with ciprofloxacin, metronidazole, and vancomycin for possible
gram-negative sepsis and received two blood transfusions; however, she died
approximately 12 hours after admission. A maculopapular rash was noted postmortem.
No autopsy was performed.
Peripheral blood smears obtained before death revealed abundant neutrophils
and intracellular collections of filamentous bacteria. Premortem blood from
a tube containing no additives or separators was inoculated onto a blood agar
plate and incubated in CO2 at 95°F (35°C). After 72 hours,
the culture demonstrated slight growth of gram-negative filamentous bacteria.
UNEX was contacted for assistance, and diagnostic specimens were submitted
to CDC for further laboratory evaluation. At CDC, the isolate was subcultured
onto media enriched with 20% solution of sterile normal rabbit serum and incubated
in a candle jar for 48 hours. Biochemical analyses identified the bacterial
isolate as S. moniliformis. The 16S rRNA gene sequences
amplified from DNA extracted from the patient’s blood and the bacterial
isolate were consistent with S. moniliformis.
The patient had been employed at a pet store. She was bitten on her
right index finger by a rat in the store 2 days before symptom onset and 4
days before arriving at the ED. She self-treated the wound by using antiseptic
ointment immediately after being bitten. In addition, she had regular contact
with several pet rats, cats, a dog, and an iguana at her home; however, no
bites from these animals were reported. None of the animals were tested for S. moniliformis.
Washington. In late November 2003, a previously
healthy woman aged 19 years was pronounced dead on arrival at a hospital ED.
No laboratory studies were performed in the ED. An acquaintance reported that
the patient had experienced a 3-day history of fever, headache, myalgias,
nausea, and profound weakness without cough, vomiting, diarrhea, or rash.
Before her transport to the ED, she exhibited anxiety, confusion, and labored
breathing. ED staff noted that she appeared jaundiced. The body was transported
to the coroner’s office, where an autopsy was performed.
Cultures of blood and tissue from autopsy were negative for pathogenic
organisms. A toxicology screen was negative. Serologic assays for leptospirosis,
Epstein-Barr virus, cytomegalovirus, and viral hepatitis were negative for
recent infection. Histopathology revealed findings suggestive of a systemic
infectious process that included disseminated intravascular coagulopathy and
inflammatory cell infiltrates in the liver, heart, and lungs. UNEX was contacted
for assistance, and project staff facilitated the submission of diagnostic
specimens to CDC for further laboratory evaluation. Immunohistochemical assays
performed at CDC for Leptospira spp., Bartonella quintana, spotted fever and typhus group rickettsiae, flaviviruses,
hantaviruses, and influenza viruses were negative. Clusters of filamentous
bacteria were identified in sections of the liver and kidney by using a silver
stain. The 16S rRNA gene sequence amplified from DNA extracted from paraffin-embedded,
formalin-fixed samples of liver and kidney was consistent with S. moniliformis.
The patient worked as a dog groomer and lived in an apartment with nine
pet rats. One pet rat with respiratory symptoms had recently been prescribed
oral doxycycline after having been evaluated at a veterinary clinic. Doxycycline
was subsequently used to treat a second ill rat. None of the rats were tested
for S. moniliformis. The patient had no known animal
bites during the 2 weeks preceding her death.
Reported by: WJ Pollock, MD, R Cunningham,
Baptist Hospital; J Lanza, MD, S Buck, MD, PA Williams, Escambia County Health
Dept, Pensacola; JJ Hamilton, MPH, R Sanderson, MA, Bur of Epidemiology, Florida
Dept of Health. D Selove, MD, T Harper, Thurston County Coroner’s Office;
DT Yu, MD, Thurston County Dept of Health, Olympia; M Leslie, DVM, J Hofmann,
MD, Washington Dept of Health. S Reagan, MPH, M Fischer, MD, A Whitney, MS,
C Sacchi, PhD, P Levett, PhD, M Daneshvar, PhD, L Helsel, R Morey, Div of
Bacterial and Mycotic Diseases; S Zaki, MD, C Paddock, MD, W Shieh, MD, J
Sumner, J Guarner, MD, Div of Viral and Rickettsial Diseases, National Center
for Infectious Diseases; D Gross, DVM, EIS Officer, CDC.
CDC Editorial Note: Although rapidly fatal
pediatric cases of RBF have been described previously,2,3 similar
mortality among adults has not been reported. Mortality attributed to severe
systemic complications (e.g., endocarditis, myocarditis, meningitis, pneumonia,
or multiple organ failure) has been documented in certain adult patients.1,4 Both patients described in this report died within 12 hours of presentation,
allowing little opportunity for assessment and treatment. These case reports
demonstrate that infection with S. moniliformis can
cause fulminant sepsis and death in previously healthy adults. As a result,
prevention of severe disease might depend on increasing the awareness of appropriate
risk-reduction activities and possible symptoms of RBF among persons who have
exposure to rats. Intravenous penicillin is the treatment of choice, and prompt
therapy can prevent severe complications.1 Because rapid laboratory
confirmation of infection with S. moniliformis might
not be possible, clinicians should consider initiating empiric therapy for
patients with a compatible clinical presentation and exposure history.
Clinicians should consider RBF in the differential diagnosis for unexplained
febrile illness or sepsis in patients reporting rat exposure. Initial symptoms
might be nonspecific (Box), but a maculopapular
rash and septic arthritis commonly develop.1,5 However, as demonstrated
by the cases in this report, patients can have severe disease before the onset
of typical symptoms. Despite its name, approximately 30% of patients with
RBF do not report having been bitten or scratched by a rat.1,5 Risk
factors for RBF include handling rats at home and in the workplace (e.g.,
laboratories or pet stores). RBF is rare in the United States, with only a
few cases documented each year.1,6,7 However, because RBF is not
a nationally notifiable disease, its actual incidence has not been well described.
In the cases described here, diagnosis of RBF was delayed in part because
of the inability to rapidly isolate or identify S. moniliformis. If infection with S. moniliformis is suspected,
specific media and incubation conditions should be used8 (Box).
In the absence of a positive culture, identification of pleomorphic gram-negative
bacilli in appropriate specimens might support a preliminary diagnosis.1 In the event of an unexplained death in a person with rat exposure,
performing an autopsy might also be critical to identifying an etiology.
Because of the high prevalence of colonization and asymptomatic infection
with S. moniliformis among rodents (Box), testing
and treatment of rats is not practical. Disease prevention should center on
risk reduction among persons with frequent rat exposure. Adherence to simple
precautions while handling rats can reduce the risk for RBF and other potential
rodent-borne zoonotic infections, wound infections, and injuries. Persons
should wear gloves, practice regular hand washing, and avoid hand-to-mouth
contact when handling rats or cleaning rat cages.1,9 If bitten
by a rat, persons should promptly clean and disinfect the wound, seek medical
attention, and report their exposure history. A tetanus toxoid booster should
be administered if ≥10 years have lapsed since the last dose.9,10
Clinicians should contact their state health departments for assistance
with diagnosis of unexplained deaths or critical illnesses and cases or clusters
of suspected RBF or other zoonotic infections. UNEX coordinates surveillance
for unexplained deaths possibly attributed to infection throughout the United
States. Cases are reported by a network of health departments, medical examiners/coroners,
pathologists, and clinicians. Epidemiologic and clinical data are collected,
and available clinical and pathologic specimens are obtained for reference
and diagnostic testing at state, CDC, and other laboratories. State and local
health departments may contact UNEX for assistance with the evaluation of
unexplained deaths that occur in their jurisdictions.
References: 10 available
Fatal Rat-Bite Fever—Florida and Washington, 2003. JAMA. 2005;293(9):1054-1056. doi:10.1001/jama.293.9.1054