Rabies
is a viral infection of the central nervous system, usually
contracted from the bite of an infected animal, and is nearly
always fatal without proper postexposure prophylaxis (PEP) (1).
In October 2004, a previously healthy female aged 15 years in
Fond du Lac County, Wisconsin, received a diagnosis of rabies
after being bitten by a bat approximately 1 month before symptom
onset. This report summarizes the investigation conducted by the
Wisconsin Division of Public Health (WDPH), the public health
response in Fond du Lac County, and the patient's clinical
course through December 17. This is the first documented
recovery from clinical rabies by a patient who had not received
either pre- or postexposure prophylaxis for rabies.
While attending a church service
in September, the girl picked up a bat after she saw it fall to
the floor. She released the bat outside the building; it was not
captured for rabies testing, and no one else touched the bat.
While handling the bat, she was bitten on her left index finger.
The wound was approximately 5 mm in length with some blood
present at the margins; it was cleaned with hydrogen peroxide.
Medical attention was not sought, and rabies PEP was not
administered.
Approximately 1 month after the
bat bite, the girl complained of fatigue and tingling and
numbness of the left hand. These symptoms persisted, and 2 days
later she felt unsteady and developed diplopia (i.e., double
vision). On the third day of illness, with continued diplopia
and onset of nausea and vomiting, she was examined by her
pediatrician and referred to a neurologist. At that time, the
patient continued to have blurred vision and also had partial
bilateral sixth-nerve palsy. Magnetic resonance imaging (MRI)
with and without contrast and magnetic resonance angiography (MRA)
studies of her brain were normal, and the patient was sent home.
On the fourth day of illness, the
patient's symptoms continued, and she was admitted to a local
hospital for lumbar puncture and supportive care. On admission,
she was afebrile, alert, and able to follow commands. She had
partial sixth-nerve palsy, blurred vision, and unsteady gait.
Standard precautions for infection control were observed. Lumbar
puncture revealed a white blood cell count of 23 cells/µL
(normal: 0 cells/µL) with 93% lymphocytes, a red blood
cell count of 3 cells/µL (normal: 0 cells/µL), a
protein concentration of 50 mg/dL (normal: 15--45 mg/dL), and a
glucose concentration of 58 mg/dL (normal: 40--70 mg/dL). During
the next 36 hours, she had slurred speech, nystagmus, tremors of
the left arm, increased lethargy, and a temperature of 102oF
(38.9oC).
On the sixth day of illness, the
bat-bite history was reported, and rabies was considered in the
differential diagnosis. The patient was transferred to a
tertiary care hospital. Because rabies was recognized as a
possibility, expanded infection-control measures, including
droplet precautions and one-to-one nursing, were instituted at
time of transport. On arrival, the patient had a temperature of
100.9oF (38.3oC), impaired muscular
coordination, difficulty speaking, double vision, muscular
twitching, and tremors in the left arm. She was somewhat
obtunded but answered questions appropriately and complied with
commands.
Blood serum, cerebrospinal fluid
(CSF), nuchal skin samples, and saliva were submitted to CDC for
rabies testing. MRI with and without contrast and angiogram/venogram
sequences were normal. She had hypersalivation and was intubated.
Rabies-virus--specific antibodies were detected in the patient's
serum and CSF. Direct fluorescent antibody staining of nuchal
skin biopsies was negative for viral antigen, and rabies virus
was not isolated from saliva by cell culture. Rabies-virus RNA
was not detectable by reverse transcriptase polymerase chain
reaction assay of either sample. Therefore, identification of
the virus variant responsible for this infection was not
possible.
Clinical management of the
patient consisted of supportive care and neuroprotective
measures, including a drug-induced coma and ventilator support.
Intravenous ribavirin was used under an investigational
protocol. The patient was kept comatose for 7 days; during that
period, results from lumbar puncture indicated an increase in
antirabies IgG by immunofluorescent assay from 1:32 to 1:2,048.
Her coma medications were tapered, and the patient became
increasingly alert. On the 33rd day of illness, she was
extubated; 3 days later she was transferred to a rehabilitation
unit. At the time of transfer, she was unable to speak after
prolonged intubation. As of December 17, the patient remained
hospitalized with steady improvement. She was able to walk with
assistance, ride a stationary cycle for 8 minutes, and feed
herself a soft, solid diet. She solved math puzzles, used sign
language, and was regaining the ability to speak. The prognosis
for her full recovery is unknown.
To provide community members
accurate information about rabies and its transmission, local
and state health officials held a press conference on October
21. Public health officials and community pediatricians visited
the patient's school to assess the need for rabies prophylaxis
among students. WDPH distributed assessment tools to the local
health department to screen health-care workers and community
contacts of the patient for exposure to potentially infectious
secretions. The patient's five family members, five of 35
health-care workers, and 27 of 55 community contacts received
rabies PEP, either because of exposure to the patient's saliva
during sharing of beverages or food items or after contact with
vomitus. No health-care workers at the tertiary care hospital
required PEP. Site inspection of the church revealed no ongoing
risk for exposure to bats.
Reported by: RE
Willoughby, MD, MM Rotar, Children's Hospital of Wisconsin,
Milwaukee; HL Dhonau, MD, KM Ericksen, Agnesian HealthCare, Fond
du Lac; DL Cappozzo, Fond du Lac County Health Dept; JJ
Kazmierczak, DVM, JP Davis, MD, Wisconsin Div of Public Health.
CE Rupprecht, VMD, Div of Viral and Rickettsial Diseases; AP
Newman, DVM, AS Chapman, DVM, EIS officers, CDC.
Editorial Note:
This case represents the sixth
known occurrence of human recovery after rabies infection;
however, the case is unique because the patient received no
rabies prophylaxis either before or after illness onset.
Historically, the mortality rate among previously unvaccinated
rabies patients has been 100% (2). The five previous
patients who survived were either previously vaccinated (3)
or received some form of PEP before the onset of illness (4--7).
As in this case, viral antigen was not detected nor was virus
isolated from those patients; increased antibody titers detected
in serum and CSF (inconsistent with vaccination alone) confirmed
the diagnosis of clinical rabies. Only one of the five patients
recovered without neurologic sequelae (4). No specific
course of treatment for rabies in humans has been demonstrated
to be effective, but a combination of treatments, which might
include rabies vaccine, rabies immune globulin, monoclonal
antibodies, ribavirin, interferon-alpha, or ketamine, has been
proposed (2). Given the lack of therapeutic utility
observed to date, and because the patient had
rabies-virus--neutralizing antibodies on diagnosis, a decision
was made to avoid use of immune-modulators (e.g., rabies
vaccine, rabies immune globulin, or interferon). However, the
particular benefits of the regimen received by this patient
remain to be determined.
The history of a bat bite 1 month
before this patient's illness suggests an etiology of
bat-associated rabies-virus variant. This is consistent with the
epidemiologic pattern of rabies in humans in the United States
during the preceding 2 decades. During 1980--2000, a total of 26
(74%) of rabies-virus variants obtained from patients in the
United States were associated with insectivorous bats, most
commonly silver-haired and eastern pipistrelle bats (8,9),
including a variant from a fatal case of rabies reported in
Wisconsin in 2000 (10).
In this case, only five
health-care workers received PEP. Previous reports of rabies
cases have noted large numbers of contacts being treated (8);
however, delivery of health care to a patient with rabies is not
an indication for PEP unless the mucuous membranes or open wound
of a health-care worker are contaminated by infectious material
(e.g., saliva, tears, CSF, or neurologic tissue). Adherence to
standard precautions for infection control will minimize the
risk for exposure (1).
Rabies in humans is preventable
with proper wound care and timely and appropriate administration
of PEP before onset of clinical disease (1).
PEP is recommended for all persons with a bite, scratch, or
mucous-membrane exposure to a bat, unless the bat tests negative
for rabies. When direct contact between a human and a bat has
occurred and the animal is not available for testing, PEP should
be administered when a strong probability of exposure exists.
However, if a bat bite is unrecognized or if the significance of
exposure is underestimated, medical intervention might not be
sought and appropriate treatment not administered. Once clinical
signs of rabies are evident, a progressive and usually fatal
encephalitis ensues.
This report underscores the need
for increasing public awareness to minimize the risk for rabies
following contact with bats and other wildlife. Persons bitten
by a potentially rabid animal should immediately 1) wash the
wound thoroughly with soap and water, 2) capture the animal (if
this can be done safely by avoiding direct contact) and submit
it for testing or quarantine, 3) contact local or state public
health officials, and 4) visit a physician for treatment and
evaluation regarding the need for PEP. Persons should not handle
or keep bats as pets and should keep bats away from living
quarters and public places. Despite the recovery of this
patient, no proven therapy for clinical rabies has been
established, and the reasons for recovery in this case are
unknown. Clinicians and the public should recognize the risk for
contracting rabies from any direct contact with bats and not
regard it as a curable disease on the basis of the outcome of
this case.
Acknowledgments
The findings in this report are
based on data reported by L Fitzpatrick, PharmD, Agnesian
HealthCare, Fond du Lac, Wisconsin. C Hanlon, VMD, I Kuzmin,
PhD, P Morrill, M Niezgoda, MS, L Orciari, MS, P Yager, Div of
Viral and Rickettsial Diseases, National Center for Infectious
Diseases, CDC.
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