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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.

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Presentation on theme: "Human Rabies — Kentucky/Indiana, 2009 LCDR Brett W. Petersen, MD, MPH United States Public Health Service Epidemic Intelligence Service Poxvirus and Rabies."— Presentation transcript:

1 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

2 Rabies Acute, progressive encephalitis Virus transmitted through animal bite Almost universally fatal and incurable Hydrophobia, hypersalivation, altered mental status, anxiety, and agitation

3 Prevention Postexposure Prophylaxis (PEP) – Rabies immunoglobulin – Vaccine Animal control and vaccination programs Human cases rare in developed countries

4 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

5 Case History

6 October 5, year-old previously healthy man Presented to employee health clinic Fever and cough Vital signs and physical examination unremarkable Prescribed antibiotics for presumed bronchitis

7 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

8 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

9 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

10 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

11 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

12 October 20, 2009 Brain death was diagnosed based on physical examination, electroencephalogram, and apnea testing Ventilatory support withdrawn and patient died

13 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

14 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

15 Investigative Team

16 Postmortem Findings

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19 Rabies viral RNA detected by RT-PCR Typed as a variant common to the tricolored bat (Perimyotis subflavus) © Melvin Tuttle, Bat Conservation International

20 Public Health Response Identify contacts – Risk assessment – Recommendations for postexposure prophylaxis Clarify patient’s exposure history and identify the source of infection

21 Public Health Response 159 contacts identified (147 healthcare providers) All contacts received: – Counseling – Informational handout – A standardized risk assessment form

22 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

23 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

24 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

25 Education and Outreach

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30 Acknowledgments 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. 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

31 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

32 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

33 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)

34 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.

35 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.

36 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 transcriptase- polymerase 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

37 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

38 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

39 Lab/Imaging Summary

40 Aerosol Transmission of Rabies Two hypothesized human cases occurring in research laboratory settings Two hypothesized human cases associated with caves

41 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

42 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

43 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

44 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

45 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 animal- to-human transmission No laboratory-diagnosed cases of human-to- human rabies transmission have been documented other than the transplant cases

46 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

47 Abortive Human Rabies Timeline

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50 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

51 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

52 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

53 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

54 HRIG infiltrated at site of wound + Rabies vaccine administered on days 0, 3, 7, 14, and 28 Local Wound Treatment Risk Assessment Potential Rabies Virus Exposure Postexposure Prophylaxis Previously Vaccinated? Immunosuppressed? HRIG infiltrated at site of wound + Rabies vaccine administered on days 0, 3, 7, and14 No HRIG + Rabies vaccine administered on days 0 and 3 NoYes No Yes

55 NEW ACIP Recommendations


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