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Human Rabies — Kentucky/Indiana,
2009
LCDR Brett W. Petersen, MD, MPH
United States Public Health Service
Epidemic Intelligence Service
Poxvirus and Rabies Branch
Centers for Disease Control and Prevention
Rabies
• Acute, progressive encephalitis
• Virus transmitted through animal bite
• Almost universally fatal and incurable
• Hydrophobia, hypersalivation, altered
mental status, anxiety, and agitation
Prevention
• Postexposure Prophylaxis (PEP)
– Rabies immunoglobulin
– Vaccine
• Animal control and vaccination programs
• Human cases rare in developed countries
Public Health Impact
• >55,000 human rabies cases annually
– Highest burden in Asia and Africa
• 40,000 PEP treatments administered every
year in the United States
– $1,634 – $8,415 per individual treated
Case History
October 5, 2009
• 43-year-old previously healthy man
• Presented to employee health clinic
• Fever and cough
• Vital signs and physical examination
unremarkable
• Prescribed antibiotics for presumed
bronchitis
October 6, 2009
• Worsening fever and chills
• New onset chest pain and left arm numbness
• Decreased grip strength of left hand
• EKG showed no signs of cardiac ischemia
• Asked to return the following day
• Advised to seek medical attention if
symptoms worsened
October 6, 2009
• Presented to a local Emergency Department
• Chest and back pain described as “spasm”
• Evaluation similarly unremarkable
• Cardiac ischemia and pulmonary embolus
ruled out
• Prescribed narcotics and muscle relaxants
for presumed musculoskeletal pain
October 7, 2009
• Returned to same Emergency Department
• Worsening pain and back spasms
• Akathisia and motor restlessness attributed
to side effects of muscle relaxant
• Hospital admission advised but the patient
returned home
October 8, 2009
• Presented for follow-up with primary care
physician
• Patient exhibited prominent muscle
fasciculations, fever, tachycardia, and
hypotension
• Admitted directly to hospital with concerns
for sepsis
October 9-19, 2009
• Rapid mental status deterioration requiring
endotracheal intubation for airway protection
• Transferred to a referral hospital in Kentucky
• No etiology was identified
• Hospital course complicated by bradycardia,
hypotension, rhabdomyolysis, and renal
failure requiring hemodialysis
October 20, 2009
• Brain death was diagnosed based on
physical examination, electroencephalogram,
and apnea testing
• Ventilatory support withdrawn and patient
died
Differential Diagnosis
• Rabies thought unlikely given the absence of
animal exposure
• One day prior to the patient’s death
– CDC contacted for consultation
– Antemortem samples submitted for diagnostic
testing
Preliminary Results
• Rabies specific antibodies in serum
• Diagnosis expected to be confirmed at
autopsy
• Pathologists concerned about the biosafety
risks of performing an autopsy on a patient
with suspected rabies
– Infectious aerosols
– Contamination of autopsy facilities
Investigative Team
Postmortem Findings
Postmortem Findings
Postmortem Findings
Postmortem Findings
• Rabies viral RNA detected by RT-PCR
• Typed as a variant common to the tricolored
bat (Perimyotis subflavus)
© Melvin Tuttle, Bat Conservation International
Public Health Response
• Identify contacts
– Risk assessment
– Recommendations for postexposure prophylaxis
• Clarify patient’s exposure history and
identify the source of infection
Public Health Response
• 159 contacts identified (147 healthcare
providers)
• All contacts received:
– Counseling
– Informational handout
– A standardized risk assessment form
Public Health Response
• 18 potential exposures identified
– 14 healthcare providers, 2 family members, and 2
coworkers
• All 18 were recommended to receive PEP and
all completed the vaccination series
• To date, none of the 159 persons has
developed rabies
Public Health Response
• No specific source of rabies virus exposure
• Mechanic in a rural farming community in
southern Indiana
• Mentioned seeing a bat after removing a
tarpaulin from a tractor
• Never reported a bite or nonbite exposure
Targets for Education and Outreach
• Pathologists
– Guidelines for safely performing autopsies on
patients with suspected rabies
• Clinicians
– Education on how to recognize and diagnose
human rabies
• Public
– Avoid exposures to bats and other potentially
rabies-infected wildlife
– Seek prompt medical attention after potential
exposures
Education and Outreach
Acknowledgments
•
•
•
•
CDC Rabies Team
– Charles Rupprecht
– Andres Velasco-Villa
– Lillian Orciari
– Michael Niezgoda
– Pam Yager
CDC Infectious Disease Pathology
Branch
– Chris Paddock
– Sherif Zaki
– Clifton Drew
Staff members of the Clark County
Health Dept, Jeffersonville, Indiana
Staff members of the Louisville
Metro Dept of Public Health and
Wellness, Louisville, Kentucky
•
•
•
•
Indiana State Dept of Health
– Jennifer House
– Matthew Ritchey
– Pam Pontones
– Jim Howell
– James Ignaut
Kentucky Dept for Public Health
– John Poe
– Kraig Humbaugh
Norton Hospital, Louisville,
Kentucky
– Michael Nowacki
– Alicia Razzino
Saint Catherine Regional Hospital,
Charlestown, Indiana
– Catherine Biehle
The findings and conclusions in this report are those of the
author(s) and do not necessarily represent the official position of
the Centers for Disease Control and Prevention.
Question Responses
• Importance of autopsies for rabies, early diagnosis
• Definition of rabies diagnosis
• Could diagnosis have been made with antemortem
•
•
•
•
•
•
samples alone?
Definition of exposure
Lab/Imaging summary
Aerosol, human-human transmission
Texas case
How are rabies PPE guidelines different from normal
autopsy guidelines – WHO rabies autopsy guidelines
New ACIP recs
Importance of Autopsies for Rabies
• Provide a diagnosis
• Initiate and guide public health response
• Adds to our knowledge of the epidemiology
of rabies
• Further understanding of disease
CSTE Definition of Animal Rabies
• Confirmed - a case that is laboratory
confirmed
• Laboratory criteria for diagnosis:
– A positive direct fluorescent antibody test
(preferably performed on central nervous system
tissue)
– Isolation of rabies virus (in cell culture or in a
laboratory animal)
CSTE Definition of Human Rabies
• Confirmed - a clinically compatible case that
is laboratory confirmed
• Clinical description
– Rabies is an acute encephalomyelitis that almost
always progresses to coma or death within 10
days after the first symptom.
CSTE Definition of Human Rabies
• Laboratory criteria for diagnosis
– Detection by direct fluorescent antibody of viral
–
–
–
antigens in a clinical specimen (preferably the brain or
the nerves surrounding hair follicles in the nape of the
neck), OR
Isolation (in cell culture or in a laboratory animal) of
rabies virus from saliva, cerebrospinal fluid (CSF), or
central nervous system tissue, OR
Identification of a rabies-neutralizing antibody titer
greater than or equal to 5 (complete neutralization) in
CSF
Identification of a rabies-neutralizing antibody titer
greater than or equal to 5 (complete neutralization) in
the serum of an unvaccinated person.
Proposed New Case Definition
•
Laboratory criteria for diagnosis
– Detection by direct fluorescent antibody of lyssavirus
antigens in a clinical specimen (preferably the brain or the
nerves surrounding hair follicles in the nape of the neck),
OR
– Isolation (in cell culture or in a laboratory animal) of a
lyssavirus from saliva or central nervous system tissue, OR
– Detection of lyssavirus RNA (using reverse transcriptasepolymerase chain reaction [RT-PCR]) in saliva, CSF, or
tissue, OR
– Identification of a rabies-binding antibody in the CSF, OR
– Identification of a rabies-binding antibody titer in the
person’s serum AND no history of rabies vaccination
ACIP Definition of Rabies Exposure
• Bite exposure – most common and most
dangerous route of exposure
– Bite from a rabid mammal
• Nonbite exposure – lower risk
– The introduction of rabies virus (from saliva or
other potentially infectious material, e.g.,neural
tissue) into fresh, open cuts in skin or onto
mucous membranes
• Postexposure prophylaxis should be
administered for either type of exposure
ACIP Definition of Rabies Exposure
• Indirect contact and activities such as
petting or handling an animal, contact with
blood, urine or feces, and contact of saliva
with intact skin do not constitute exposures
• These situations do not require
administration of postexposure prophylaxis
Lab/Imaging Summary
Aerosol Transmission of Rabies
• Two hypothesized human cases occurring in
research laboratory settings
• Two hypothesized human cases associated
with caves
Aerosol Transmission of Rabies
• 1972: 56y/o veterinarian died of rabies 2
weeks after homogenizing rabid goat brain
using a blender known to produce a lingering
aerosol
– It is believed that he removed his mask to do
mouth pipetting of aliquots of the homogenate,
raising the question of mucous membrane
exposure
Aerosol Transmission of Rabies
• 1977: 32y/o lab technician became ill after
spraying suspensions of a modified live
rabies virus in a pharmaceutical
manufacturing machine
– The patient did not die but was left with severe
neurologic sequelae
– The diagnosis was based on his neurologic
symptoms and rising rabies Ab titers
– It is hypothesized that the virus involved had
developed higher infectivity after passing through
animal and tissue culture systems
Aerosol Transmission of Rabies
• 1956: Entomologist studying the ecology of
bats died of rabies after visiting several
caves in central Texas
– Death often attributed to aerosol transmission
– However, it was also reported that he had a
chronic skin eruption on his neck and that he
scratched or rubbed it while wearing the same
gloves he used to handle the bats
– Raises the question of introduction of virus into
the wound
Aerosol Transmission of Rabies
• 1959: Mining engineer who frequented caves
to evaluate them for guano mining and had
visited a cave one month before the onset of
symptoms
– One history states that he denied any bat bites
but had a bleeding lesion on his face when
leaving the cave
– Another states he was bitten but then later denied
it
– In either case, the bleeding lesions raises the
question of introduction of virus into the wound
Human-Human Rabies Transmission
• Organ and tissue transplantation resulting in
rabies transmission has occurred among 16
transplant recipients
• Theoretically, human-to-human transmission
could also occur in the same way as animalto-human transmission
• No laboratory-diagnosed cases of human-tohuman rabies transmission have been
documented other than the transplant cases
Presumptive Abortive Human Rabies
• 17y/o F in Texas
• Developed encephalitis 2 months following
•
•
exposure to bats
Rabies diagnosed based on positive serum
and CSF serology
Patient survived without intensive care or
serious sequelae
Abortive Human Rabies Timeline
1
New Recommendations
• Use personal protective equipment,
including an N95 or higher respirator, full
face shield, goggles, and gloves, as well as
complete body coverage with protective wear
• Use heavy or chain mail gloves to help
prevent cuts or sticks from cutting
instruments or bone fragments
New Recommendations
• Minimize aerosol generation by using a
handsaw rather than an oscillating saw and
avoiding contact of the saw blade with brain
tissue while removing the calvarium
• Limit participation to those directly involved
in the procedure and collection of specimens
New Recommendations
• Use ample amounts of a 10% sodium
hypochlorite solution during and after the
procedure to ensure decontamination of all
exposed surfaces and equipment
New Recommendations
• Previous vaccination against rabies is not
required for persons performing such
autopsies, and postexposure prophylaxis of
autopsy personnel is recommended only if
contamination of a wound or mucous
membrane with patient saliva or other
potentially infectious material (e.g., neural
tissue) occurs during the procedure
Potential Rabies Virus Exposure
Local Wound Treatment
Risk Assessment
Postexposure Prophylaxis
Previously Vaccinated?
Yes
No
No HRIG
Immunosuppressed?
+
Rabies vaccine administered on days 0 and 3
Yes
No
HRIG infiltrated at site of wound
HRIG infiltrated at site of wound
+
+
Rabies vaccine administered on days 0, 3, 7, 14, and 28
Rabies vaccine administered on days 0, 3, 7, and14
NEW ACIP Recommendations