january 2010 selected zoonotic diseases conference call
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National Center for Emerging and Zoonotic Infectious Diseases (proposed)
January 6, 2010
Selected Zoonotic Diseases Conference Call
Shauna L. Mettee, MSN, MPHEIS Officer, Enteric Diseases Epidemiology Branch, CDC404-639-5277 smettee@cdc.gov
Selected Zoonotic Diseases Conference Call
January 6, 2010
Human Salmonella Associated with Aquatic Frogs
It’s Not Easy Being Green–A Multistate Outbreak of Human
Salmonella Typhimurium Infections Associated with Aquatic
Frogs–United States, 2009
Outbreak Response and Prevention BranchDivision of Foodborne, Bacterial and Mycotic Diseases
National Center for Zoonotic, Vector-borne and Enteric Diseases Centers for Disease Control and Prevention
Shauna L. Mettee, RN, MSN, MPHLTJG, United States Public Health Service
Epidemic Intelligence Officer
*All results are preliminary and subject to change*
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Infections with the outbreak strain of Salmonella Typhimurium, by week of illness onset (n=83 for whom information was reported as of 12/31/09)*
No. of cases
Week of Illness Onset
*Some illness onset dates have been estimated from other reported information(Estimated onset dates range 4/9 – 12/11; Reported onset dates (n=48) range 5/24 – 11/30)
Illnesses that began during this time may not yet be reported
3-4 Cases
AZ1
CA5
FL1
GA1
ID1
IL5
MD3
MA3
MI4
MO4
NJ2
NY2
OH2
PA4
TN2
TX4
UT14
WA7
More than 4 Cases
Case Counts by States reporting Salmonella Typhimurium cases in cluster 0909MAJPX-1, as of Thursday, December 31, 2009
MN1
LA1
CO4 KY
1
NM1 MS
1
VA3
WI1
NE1
SD3
AL1
IN1
NV1
1-2 Cases
Demographics for cases of Salmonella Typhimurium cases in cluster 0909MAJPX-1, as of Thursday, December 31, 2009
Demographics n=85Age, range (median)* <1-54 (5)
< 5 years old 42 (50%)< 10 years old 66 (79%)
Gender**, n (%)Female 40 (49%)Male 41 (51%)
*not including 1 without age information
**not including 4 without gender information
Outcomes n=47Hospitalization
n (%) 16 (34%)
Results of Matched Case-Control Study
• Among 19 cases and 31 controls, illness was significantly associated with exposure to frogs (63% cases vs 3% controls, mOR=24.4, CI=4.0-infinity).
• Among 6 case-patients who knew the frog type, all reported African Dwarf Frogs.
Results of Environmental Sampling
• Environmental samples from aquariums containing African Dwarf Frogs in 4 patients’ homes yielded Salmonella Typhimurium isolates matching the outbreak strain. (CO, UT, OH, NM)
• Common breeder in California identified during traceback investigation– Environmental samples from breeder’s facility yielded
outbreak strain
Historical Case Investigation
• Asking states to interview historical cases from Jan 1, 2008 - present with revised case questionnaire.
PLEASE CONTACT
Shauna Mettee at 404-639-5277 or smettee@cdc.gov to obtain case
questionnaire
For more information
CDC Web Updatehttp://www.cdc.gov/salmonella/typh1209/index.html
MMWR – Jan 8, 2009Multistate Outbreak of Human Salmonella Typhimurium Infections Associated with Aquatic Frogs — United States, 2009
Contact: Shauna Mettee, smettee@cdc.gov
Acknowledgments
• CDC– Samir Sodha, Casey Barton Behravesh, Linda Capewell, Gwen
Ewald, Nancy Garrett, Brenda Le, Leslie Hausman, Ian Williams
• State and Local Health Departments: – Alabama, Arizona, California, Colorado, Florida, Georgia, Idaho,
Indiana, Illinois, Kentucky, Louisiana, Massachusetts, Maryland, Michigan, Minnesota, Missouri, Mississippi, Nebraska, Nevada, New Jersey, New Mexico, New York, Ohio, Pennsylvania, South Dakota, Tennessee, Texas, Utah, Virginia, Washington, and Wisconsin
Julia Murphy, DVM, MS, DACVPM Virginia Department of Health,804-864-8113 Julia.murphy@vdh.virginia.gov
Kim Mitchell, MPHMaryland Department of Health and Mental Hygiene, Center for Zoonotic and Vector-borne Diseases410-767-6618 kmitchell@dhmh.state.md.us
Peter Troell, MD, MPHFairfax County Health Department 703-246-2411 peter.troell@fairfaxcounty.gov
Selected Zoonotic Diseases Conference Call
January 6, 2010
Human Rabies Case in Virginia
Human Rabies, Virginia 2009
Julia Murphy, DVM, MS, DACVPM
State Public Health Veterinarian
Virginia Department of Health
Patient Background
42 y.o. male with no significant past medical history Physician involved primarily in teaching and research
Symptom onset October 23, 2009 Hot and cold flashes at work
October 24 Leg pain and backaches Spontaneous ejaculation Urinary incontinence
Patient Background
Presented to local ED on October 26 MRI of lumbar spine Discharged and referred to PCP
Evidence of hydrophobia Gagging while drinking and showering
October 27 returned to same ED for evaluation of neurologic disorder / rabies Anxious and exhibited “bizarre” behavior Admitted
Hospitalization
Agitated Required antipsychotic and 4 point restraints
Cardiac arrest requiring intubation Frothing at mouth and spitting
Multiple seizures
Hospitalization
Rabies ante-mortem sampling Sent to CDC 10/29 early a.m. Rabies antigen detected in neck biopsy, 10/29
p.m. Sequenced as Indian canine virus, 10/30
Hospitalization
Milwaukee protocol initiated Induced coma Samples sent daily to CDC to monitor viral
load and antibody levels Frequent consultation with Dr. Willoughby
Normal blood and intracranial pressures became increasingly difficult to maintain
Hospitalization
Transcutaneous pacer, continuous renal dialysis and continual CSF draining required by November 12
Patient died November 20, 2009 after 24 days of hospitalization
Postmortem performed by hospital and samples sent to CDC
Possible Rabies Exposures
Travel to India July 3 – August 7, 2009 Father-in-law reported patient experienced
scratch or bite from unknown dog while jogging No post-exposure prophylaxis pursued Sequence consistent with Indian canine virus
Potential bat exposure Rabid bat in his workplace, but not in his building
Public Health Investigation
Potential exposure to others Hospital staff Wife and 2 children and family members Friends of the family Workplace exposures involving 3 clinical facilities
2 in Maryland 1 in Washington, DC
Infectious period: October 8 forward
Public Health Investigation
Two survey tools created Healthcare workers Coworkers, friends, family
VDH, Fairfax Health District, MD DHMH and DCDOH conducted exposure assessments
Surveys
Healthcare worker survey Contact with infectious materials Types of procedures performed PPE worn when performing procedures
Household and coworker survey Contact with infectious materials Activities shared with patient
Results
Hospital: Fairfax County HD (FHD) assessed 70 of 70 potentially exposed individuals 24 pursued PEP
17 met criteria for non-bite exposure 7 did not meet criteria but pursued PEP
Family: FHD assessed all family identified as having contact with the patient during the infectious period (n=6) 3 immediate and 3 additional family members All pursued PEP
Results
DC: 34 of 40 contacts at patient’s worksite assessed 2 close friends pursued PEP
MD: 63 of 63 contacts at patient’s worksites assessed Facility 1: 19/19 individuals assessed Facility 2: 44/44 individuals assessed No PEP pursued
PEP Summary, Human Rabies, Virginia, 2009
Exposure Group # Assessed # given PEP
VA Hospital 70 24
Family/friends 7 7
DC Facility 34 1
MD Facility #1 19 0
MD Facility #2 44 0
Total 174 32
Challenges and Lessons Learned
Public health involvement early in the process associated with potential human rabies cases is important
Outreach to pathologists in regard to autopsy procedures is important
Good to be familiar with the legal basis for information requested as part of a public health investigation
Acknowledgements
Fairfax Health District Peter Troell Beth Miller-Zuber Bryant Bullock
MD Dept. of Health and Mental Hygiene Katherine Feldman Kim Mitchell Erin Jones
Acknowledgements
DC Department of Health Chevelle Glymph Garret Lum Maria Hille
Florida Department of Health Carina Blackmore
New York City Department of Health Sally Slavinski
Acknowledgements
CDC Charles Rupprecht Jesse Blanton Sergio Recuenco Richard Franka
Jennifer House, DVM, MPH Indiana State Department of Health317-233-7272 jhouse@isdh.in.gov
John Poe, DVM, MPH Kentucky Department for Public Health502-564-3418john.poe@ky.gov
Selected Zoonotic Diseases Conference Call
January 6, 2010
Human Rabies – A Joint Investigation with CDC, Indiana and Kentucky
Human Rabies – A Joint Investigation with CDC, Indiana and Kentucky
Jennifer House, DVM, MPH Indiana State Department of Health
John Poe, DVM, MPH Kentucky Department for Public Health
Indiana Logo
Case Report
• 43 year old white male• No history of previous severe illness• Resident of Southern Indiana• Died in a Kentucky hospital
October 20091 2 3
4 5 6 7 8 9 10
11 12 13 14 15 16 17
18 19 20 21 22 23 24
25 26 27 28 29 30 31
Mechanical Ventilation
Mechanical Ventilation
Mechanical Ventilation
Employee HCP:Fever, Chills, Chest pain, arm numbness
ED:Chest pain, spasms in back, and chills
Left hospital against medical advice
ED:Chest Pain
Employee HCP:Fever & Cough
PCP:Muscle fasc., signs of sepsis
Admitted to Local Hospital-Placed on Resp Support
Transferred to tertiary care facility in KY
Condition continues to deteriorate
Patient died after being removed from life support
Autopsy performed
Patient has minor arm pain attributed to previous car accident but otherwise seems fine
Investigation
• Family, friends, co-workers interviewed for history and exposure to patient
• No history of animal bites• Told neighbor he ‘saw’ a bat (end of July)
– Did not mention a bite– Worked as a mechanic/welder– May not have recognized a bite or unaware of the
importance of being bitten
Investigation cont…
• Use standardized form– One for family/friends/co-workers– Different form for HCP
• Asked specific questions about potential saliva exposures
• Included a one page summary of risks and non-risks specific to exposures to human cases
• Also provided handouts and brochures on rabies virus
Rabies Post-Exposure Prophylaxis
• 159 close contacts- 100% counseled• 147 individually interviewed- 92.5%
• 23 identified that MAY have been exposed to saliva • 18 started/completed PEP
Normal Human Brain – Ventral View
Patient X 10.25.2009
Negri bodiesin neuron:hematoxylin and eosin stain
IHC stain for rabies virus
Kentucky-Indiana 2009, rabies autopsy
1) Rabies diagnosis is extremely difficult to obtain2) Rabies is not high on the list of differential
diagnoses for encephalitis3) Human encephalitides often go undiagnosed4) Many pathologists are reluctant to perform autopsies on
possible rabies cases5) Rabies is interpreted as an “animal disease” in a
primary care setting6) Joint federal, state and local health department collaboration is
critical for successful diagnosis and disease mitigation
Lessons Learned
Mary Grace Stobierski, DVM, MPH, DACVPM Michigan Department of Community Health517-335-8165 stobierskim@michigan.gov
Kim Signs, DVMMichigan Department of Community Health517-335-8165 signsk@michigan.gov
Selected Zoonotic Diseases Conference Call
January 6, 2010
Human Rabies Case in Michigan
William H. Wunner, PhD Professor and Director of Outreach Educationand Technology TrainingThe Wistar Institute215-898-3854 wunner@wistar.org
Selected Zoonotic Diseases Conference Call
January 6, 2010
Overview of special collections on papers on rabies appearing in the journals Vaccine and PLoS NTD
D. Craig Hooper, PhDAssociate Director, WHO Center for Neurovirology, Associate Professor, Departments of Cancer Biology and Neurological Surgery, Thomas Jefferson University215-503-1774douglas.hooper@jefferson.edu
Selected Zoonotic Diseases Conference Call
January 6, 2010
The Production of Antibody by Invading B Cells Is Required for the Clearance of Rabies Virus from the Central Nervous System
Rabies virus clearance from the CNS requires antibody production in CNS tissues
D. Craig Hooper
Thomas Jefferson University
1. Attenuated RV that spread to the CNS induce limited, therapeutic BBB permeability changes
2. BBB fails to “open” during lethal RV infections – few immune effectors reach the CNS and the virus is not cleared
Antibodies are the major effector in rabies immunity; how important is the BBB?
Peak circulating rabies-specific antibody levels occur after the restoration of BBB integrity
BBB permeability detected during rabies virus clearance is limited to fluid phase markers
CVS-F3 clearance correlates with antibody synthesis in the CNS
B cells in the CNS during CVS-F3 clearance
B cells infiltrate the CNS tissues and produce antiviral antibodies in situ
T helper cells(CD4)
B cells(CD19)
Immunoglobulin(anti-Ig)
Rabies virus-specific antibodies produced by B cells infiltrating the CNS differ from those produced in the periphery
B cell growth/differentiation/maturation factors in the
RV infected CNS
Germinal centers and Ig affinity maturation in the CNS?
Peanut agglutinin
Activation-induced cytidine deaminase (AID)
d10
d18
d24
control
Conclusions
1. The clearance of attenuated rabies viruses from CNS tissues is associated with limited fluid phase BBB permeability
2. Serum rabies virus-specific antibody titers peak after BBB integrity has largely been restored
3. B cells enter the CNS during the response to attenuated rabies viruses
4. B cell growth/differentiation/maturation factors are produced in the CNS and B cells transiently display germinal center markers
5. Rabies virus-specific antibodies produced in the CNS may differ from those produced in periphery (isotype, specificity?)
Are antibodies capable of clearing rabies virus from infected CNS tissues more commonly produced in CNS tissues?
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National Center for Emerging and Zoonotic Infectious Diseases (proposed)
January 6, 2010
Selected Zoonotic Diseases Conference Call
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