Transcript Outbreak of Whatever—State X, 2004
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
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Acute, progressive encephalitis Virus transmitted through animal bite
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Almost universally fatal and incurable
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Hydrophobia, hypersalivation, altered mental status, anxiety, and agitation
Prevention
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Postexposure Prophylaxis (PEP)
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Rabies immunoglobulin
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Vaccine
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Animal control and vaccination programs Human cases rare in developed countries
Public Health Impact
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>55,000 human rabies cases annually
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Highest burden in Asia and Africa
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40,000 PEP treatments administered every year in the United States
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$1,634 – $8,415 per individual treated
Case History
October 5, 2009
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43-year-old previously healthy man Presented to employee health clinic
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Fever and cough
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Vital signs and physical examination unremarkable
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Prescribed antibiotics for presumed bronchitis
October 6, 2009
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Worsening fever and chills New onset chest pain and left arm numbness
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Decreased grip strength of left hand
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EKG showed no signs of cardiac ischemia
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Asked to return the following day
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Advised to seek medical attention if symptoms worsened
October 6, 2009
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Presented to a local Emergency Department Chest and back pain described as “spasm”
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Evaluation similarly unremarkable
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Cardiac ischemia and pulmonary embolus ruled out
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Prescribed narcotics and muscle relaxants for presumed musculoskeletal pain
October 7, 2009
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Returned to same Emergency Department Worsening pain and back spasms
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Akathisia and motor restlessness attributed to side effects of muscle relaxant
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Hospital admission advised but the patient returned home
October 8, 2009
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Presented for follow-up with primary care physician
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Patient exhibited prominent muscle fasciculations, fever, tachycardia, and hypotension
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Admitted directly to hospital with concerns for sepsis
October 9-19, 2009
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Rapid mental status deterioration requiring endotracheal intubation for airway protection
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Transferred to a referral hospital in Kentucky
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No etiology was identified Hospital course complicated by bradycardia, hypotension, rhabdomyolysis, and renal failure requiring hemodialysis
October 20, 2009
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Brain death was diagnosed based on physical examination, electroencephalogram, and apnea testing
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Ventilatory support withdrawn and patient died
Differential Diagnosis
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Rabies thought unlikely given the absence of animal exposure
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One day prior to the patient’s death
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CDC contacted for consultation
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Antemortem samples submitted for diagnostic testing
Preliminary Results
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Rabies specific antibodies in serum Diagnosis expected to be confirmed at autopsy
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Pathologists concerned about the biosafety risks of performing an autopsy on a patient with suspected rabies
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Infectious aerosols
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Contamination of autopsy facilities
Investigative Team
Postmortem Findings
Postmortem Findings
Postmortem Findings
Postmortem Findings
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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
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Identify contacts
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Risk assessment
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Recommendations for postexposure prophylaxis
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Clarify patient’s exposure history and identify the source of infection
Public Health Response
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159 contacts identified (147 healthcare providers)
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All contacts received:
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Counseling Informational handout A standardized risk assessment form
Public Health Response
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18 potential exposures identified
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14 healthcare providers, 2 family members, and 2 coworkers
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All 18 were recommended to receive PEP and all completed the vaccination series
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To date, none of the 159 persons has developed rabies
Public Health Response
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No specific source of rabies virus exposure Mechanic in a rural farming community in southern Indiana
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Mentioned seeing a bat after removing a tarpaulin from a tractor
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Never reported a bite or nonbite exposure
Targets for Education and Outreach
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Pathologists
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Guidelines for safely performing autopsies on patients with suspected rabies
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Clinicians
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Education on how to recognize and diagnose human rabies
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Public
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Avoid exposures to bats and other potentially rabies-infected wildlife
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Seek prompt medical attention after potential exposures
Education and Outreach
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Acknowledgments
CDC Rabies Team
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Charles Rupprecht
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Andres Velasco-Villa Lillian Orciari
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Michael Niezgoda Pam Yager CDC Infectious Disease Pathology Branch
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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
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Indiana State Dept of Health
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Jennifer House
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Matthew Ritchey Pam Pontones
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Jim Howell James Ignaut Kentucky Dept for Public Health
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John Poe Kraig Humbaugh Norton Hospital, Louisville, Kentucky
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Michael Nowacki
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Alicia Razzino Saint Catherine Regional Hospital, Charlestown, Indiana
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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
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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
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Provide a diagnosis Initiate and guide public health response
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Adds to our knowledge of the epidemiology of rabies
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Further understanding of disease
CSTE Definition of Animal Rabies
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Confirmed - a case that is laboratory confirmed
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Laboratory criteria for diagnosis:
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A positive direct fluorescent antibody test (preferably performed on central nervous system tissue)
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Isolation of rabies virus (in cell culture or in a laboratory animal)
CSTE Definition of Human Rabies
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Confirmed - a clinically compatible case that is laboratory confirmed
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Clinical description
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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
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Laboratory criteria for diagnosis
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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
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Isolation (in cell culture or in a laboratory animal) of rabies virus from saliva, cerebrospinal fluid (CSF), or central nervous system tissue, OR
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Identification of a rabies-neutralizing antibody titer greater than or equal to 5 (complete neutralization) in CSF
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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
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Laboratory criteria for diagnosis
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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
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Isolation (in cell culture or in a laboratory animal) of a lyssavirus from saliva or central nervous system tissue, OR
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Detection of lyssavirus RNA (using reverse transcriptase polymerase chain reaction [RT-PCR]) in saliva, CSF, or tissue, OR
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Identification of a rabies-binding antibody in the CSF, OR
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Identification of a rabies-binding antibody titer in the person’s serum AND no history of rabies vaccination
ACIP Definition of Rabies Exposure
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Bite exposure – most common and most dangerous route of exposure
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Bite from a rabid mammal
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Nonbite exposure – lower risk
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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
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Postexposure prophylaxis should be administered for either type of exposure
ACIP Definition of Rabies Exposure
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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
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These situations do not require administration of postexposure prophylaxis
Lab/Imaging Summary
Aerosol Transmission of Rabies
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Two hypothesized human cases occurring in research laboratory settings
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Two hypothesized human cases associated with caves
Aerosol Transmission of Rabies
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1972: 56y/o veterinarian died of rabies 2 weeks after homogenizing rabid goat brain using a blender known to produce a lingering aerosol
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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
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1977: 32y/o lab technician became ill after spraying suspensions of a modified live rabies virus in a pharmaceutical manufacturing machine
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The patient did not die but was left with severe neurologic sequelae
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The diagnosis was based on his neurologic symptoms and rising rabies Ab titers
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It is hypothesized that the virus involved had developed higher infectivity after passing through animal and tissue culture systems
Aerosol Transmission of Rabies
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1956: Entomologist studying the ecology of bats died of rabies after visiting several caves in central Texas
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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
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Raises the question of introduction of virus into the wound
Aerosol Transmission of Rabies
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1959: Mining engineer who frequented caves to evaluate them for guano mining and had visited a cave one month before the onset of symptoms
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One history states that he denied any bat bites but had a bleeding lesion on his face when leaving the cave
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Another states he was bitten but then later denied it
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In either case, the bleeding lesions raises the question of introduction of virus into the wound
Human-Human Rabies Transmission
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Organ and tissue transplantation resulting in rabies transmission has occurred among 16 transplant recipients
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Theoretically, human-to-human transmission could also occur in the same way as animal to-human transmission
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No laboratory-diagnosed cases of human-to human rabies transmission have been documented other than the transplant cases
Presumptive Abortive Human Rabies
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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
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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
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Use heavy or chain mail gloves to help prevent cuts or sticks from cutting instruments or bone fragments
New Recommendations
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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
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Limit participation to those directly involved in the procedure and collection of specimens
New Recommendations
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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
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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 HRIG + Rabies vaccine administered on days 0 and 3 Yes No Immunosuppressed?
No HRIG infiltrated at site of wound + Rabies vaccine administered on days 0, 3, 7, 14, and 28 HRIG infiltrated at site of wound + Rabies vaccine administered on days 0, 3, 7, and14