january 2010 selected zoonotic diseases conference call

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1 National Center for Emerging and Zoonotic Infectious Diseases (proposed) January 6, 2010 Selected Zoonotic Diseases Conference Call

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Page 1: January 2010 Selected Zoonotic Diseases Conference Call

1

National Center for Emerging and Zoonotic Infectious Diseases (proposed)

January 6, 2010

Selected Zoonotic Diseases Conference Call

Page 2: January 2010 Selected Zoonotic Diseases Conference Call

Shauna L. Mettee, MSN, MPHEIS Officer, Enteric Diseases Epidemiology Branch, CDC404-639-5277 [email protected]

Selected Zoonotic Diseases Conference Call

January 6, 2010

Human Salmonella Associated with Aquatic Frogs

Page 3: January 2010 Selected Zoonotic Diseases Conference Call

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*

Page 4: January 2010 Selected Zoonotic Diseases Conference Call

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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

Page 5: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 6: January 2010 Selected Zoonotic Diseases Conference Call

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%)

Page 7: January 2010 Selected Zoonotic Diseases Conference Call

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.

Page 8: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 10: January 2010 Selected Zoonotic Diseases Conference Call

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 [email protected] to obtain case

questionnaire

Page 11: January 2010 Selected Zoonotic Diseases Conference Call

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, [email protected]

Page 12: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 13: January 2010 Selected Zoonotic Diseases Conference Call

Julia Murphy, DVM, MS, DACVPM Virginia Department of Health,804-864-8113 [email protected]

Kim Mitchell, MPHMaryland Department of Health and Mental Hygiene, Center for Zoonotic and Vector-borne Diseases410-767-6618 [email protected]

Peter Troell, MD, MPHFairfax County Health Department 703-246-2411 [email protected]

Selected Zoonotic Diseases Conference Call

January 6, 2010

Human Rabies Case in Virginia

Page 14: January 2010 Selected Zoonotic Diseases Conference Call

Human Rabies, Virginia 2009

Julia Murphy, DVM, MS, DACVPM

State Public Health Veterinarian

Virginia Department of Health

Page 15: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 16: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 17: January 2010 Selected Zoonotic Diseases Conference Call

Hospitalization

Agitated Required antipsychotic and 4 point restraints

Cardiac arrest requiring intubation Frothing at mouth and spitting

Multiple seizures

Page 18: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 19: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 20: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 21: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 22: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 23: January 2010 Selected Zoonotic Diseases Conference Call

Public Health Investigation

Two survey tools created Healthcare workers Coworkers, friends, family

VDH, Fairfax Health District, MD DHMH and DCDOH conducted exposure assessments

Page 24: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 25: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 26: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 27: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 28: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 29: January 2010 Selected Zoonotic Diseases Conference Call

Acknowledgements

Fairfax Health District Peter Troell Beth Miller-Zuber Bryant Bullock

MD Dept. of Health and Mental Hygiene Katherine Feldman Kim Mitchell Erin Jones

Page 30: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 31: January 2010 Selected Zoonotic Diseases Conference Call

Acknowledgements

CDC Charles Rupprecht Jesse Blanton Sergio Recuenco Richard Franka

Page 32: January 2010 Selected Zoonotic Diseases Conference Call

Jennifer House, DVM, MPH Indiana State Department of Health317-233-7272 [email protected]

John Poe, DVM, MPH Kentucky Department for Public [email protected]

Selected Zoonotic Diseases Conference Call

January 6, 2010

Human Rabies – A Joint Investigation with CDC, Indiana and Kentucky

Page 33: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 34: January 2010 Selected Zoonotic Diseases Conference Call

Case Report

• 43 year old white male• No history of previous severe illness• Resident of Southern Indiana• Died in a Kentucky hospital

Page 35: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 36: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 37: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 38: January 2010 Selected Zoonotic Diseases Conference Call

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

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Normal Human Brain – Ventral View

Patient X 10.25.2009

Page 42: January 2010 Selected Zoonotic Diseases Conference Call

Negri bodiesin neuron:hematoxylin and eosin stain

IHC stain for rabies virus

Page 43: January 2010 Selected Zoonotic Diseases Conference Call

Kentucky-Indiana 2009, rabies autopsy

Page 44: January 2010 Selected Zoonotic Diseases Conference Call

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

Page 45: January 2010 Selected Zoonotic Diseases Conference Call

Mary Grace Stobierski, DVM, MPH, DACVPM Michigan Department of Community Health517-335-8165 [email protected]

Kim Signs, DVMMichigan Department of Community Health517-335-8165 [email protected]

Selected Zoonotic Diseases Conference Call

January 6, 2010

Human Rabies Case in Michigan

Page 46: January 2010 Selected Zoonotic Diseases Conference Call

William H. Wunner, PhD Professor and Director of Outreach Educationand Technology TrainingThe Wistar Institute215-898-3854 [email protected]

Selected Zoonotic Diseases Conference Call

January 6, 2010

Overview of special collections on papers on rabies appearing in the journals Vaccine and PLoS NTD

Page 47: January 2010 Selected Zoonotic Diseases Conference Call

D. Craig Hooper, PhDAssociate Director, WHO Center for Neurovirology, Associate Professor, Departments of Cancer Biology and Neurological Surgery, Thomas Jefferson [email protected]

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

Page 48: January 2010 Selected Zoonotic Diseases Conference Call

Rabies virus clearance from the CNS requires antibody production in CNS tissues

D. Craig Hooper

Thomas Jefferson University

Page 49: January 2010 Selected Zoonotic Diseases Conference Call

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?

Page 50: January 2010 Selected Zoonotic Diseases Conference Call

Peak circulating rabies-specific antibody levels occur after the restoration of BBB integrity

Page 51: January 2010 Selected Zoonotic Diseases Conference Call

BBB permeability detected during rabies virus clearance is limited to fluid phase markers

Page 52: January 2010 Selected Zoonotic Diseases Conference Call

CVS-F3 clearance correlates with antibody synthesis in the CNS

Page 53: January 2010 Selected Zoonotic Diseases Conference Call

B cells in the CNS during CVS-F3 clearance

Page 54: January 2010 Selected Zoonotic Diseases Conference Call

B cells infiltrate the CNS tissues and produce antiviral antibodies in situ

T helper cells(CD4)

B cells(CD19)

Immunoglobulin(anti-Ig)

Page 55: January 2010 Selected Zoonotic Diseases Conference Call

Rabies virus-specific antibodies produced by B cells infiltrating the CNS differ from those produced in the periphery

Page 56: January 2010 Selected Zoonotic Diseases Conference Call

B cell growth/differentiation/maturation factors in the

RV infected CNS

Page 57: January 2010 Selected Zoonotic Diseases Conference Call

Germinal centers and Ig affinity maturation in the CNS?

Peanut agglutinin

Activation-induced cytidine deaminase (AID)

d10

d18

d24

control

Page 58: January 2010 Selected Zoonotic Diseases Conference Call

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?

Page 59: January 2010 Selected Zoonotic Diseases Conference Call

59

National Center for Emerging and Zoonotic Infectious Diseases (proposed)

January 6, 2010

Selected Zoonotic Diseases Conference Call