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Q Fever: A Public Health Paradox. Emerging Zoonotic Diseases Summit, August 23, 2005 Jennifer H. McQuiston, Viral and Rickettsial Zoonoses Branch Division of Viral and Rickettsial Diseases Centers for Disease Control and Prevention, Atlanta, GA. Background. “Query fever”

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slide1

Q Fever:

A Public Health Paradox

Emerging Zoonotic Diseases Summit, August 23, 2005

Jennifer H. McQuiston,

Viral and Rickettsial Zoonoses Branch

Division of Viral and Rickettsial Diseases

Centers for Disease Control and Prevention, Atlanta, GA

slide2

Background

  • “Query fever”
  • Worldwide zoonosis
  • Caused by Coxiella burnetii

- Gram-negative coccobacillus

- replicates in host macrophages and monocytes

  • Shed in birthing fluids, excreta, milk
  • Humans infected via inhalation, ingestion
slide3

Electron micrograph showing an infected monkey cell with one large vacuole harboring about 20 Coxiella burnetii bacteria. [Credit: R Heinzen, NIAID]

slide4

Environmental Persistence

  • Shed in the environment in a small cell form
  • that is very hardy (“spore-like”)
  • Resistant to pH changes, desiccation, UV light
  • Resistant to some common disinfectants
  • Remains viable in soil, dust for months to years
    • - isolated from barns, soil – culture, PCR
  • Raises questions regarding:
    • - environmental contamination
    • - appropriate cleaning/disinfection
slide5

Transmission

  • Ruminants most common source of human infection
    • - Cattle, sheep, goats
  • Domestic animals
    • - Cats
  • Wild Animals (rodents)
  • Birds (pigeons)
  • Ticks
  • Wind-borne environmental spread
    • - Can be spread several miles
    • down-wind from farms
  • Contact with contaminated products
    • - Straw
    • - Fertilizer
    • - Farm equipment
  • Human-to-human rare (OB/GYN, sexual)
slide6

Acute Q fever

  • 1-3 week incubation
  • Asymptomatic infections occur
  • Nonspecific signs and symptoms
    • fever
    • severe headache
    • myalgias
    • cough
    • fatigue
    • night sweats
    • rigors
    • nausea/vomiting
slide7

Acute Q fever

  • Nonspecific flu-like illness
  • Pulmonary Syndrome (~30%)
  • Hepatitis (30-60%)
  • Myocarditis, meningoencephalitis (rare)
  • Antibiotics may shorten course
  • Low mortality (< 1 %)
  • Treatment: Doxycycline
  • Chronic fatigue-like illness
  • - following acute infection in Australian
  • slaughterhouse workers (10%)
slide8

Chronic Q fever

  • Endocarditis
  • - latent infection
  • - < 1-2% of acute cases
  • - immunocompromised, heart valve disorders
  • at greater risk
  • - life-threatening, heart valve replacement may
  • be required
  • - treament: 18 months doxycycline,
  • hydroxychloroquine
  • Granulomatous hepatitis, osteomyelitis
slide9

Diagnosis

  • Serology
    • IFA, paired sera
    • Phase 2 antibody: acute infection
    • Phase I > Phase 2 antibody: chronic infection
    • Antibody can persist for a long time,
    • or take a while to develop
    • Commercial labs may incorrectly report low titers
    • as positive
  • Culture
    • Requires BSL-3, Select Agent
  • PCR, Immunohistochemistry
slide10

Q fever and Bioterrorism

  • Category B bioterrorism agent
    • - high morbidity
    • - inhalation route of transmission
    • - extreme persistence in environment
  • Previous development as an agent of biowarfare
  • Accessible – obtain from environment
slide11

History of Q fever Bioweapons Research

  • First agent studied by Fort Detrick’s bioweapons
  • program in 1954
  • Successfully developed an aerosol dispersion model
  • - demonstrated infectivity for animal subjects and
  • human volunteers in the “8-ball”
  • - successfully field-tested via aerosol
  • dispersion to human volunteers located
  • > 0.5 miles downwind
  • - developed dosage curves (1-10 units infective dose)
slide12

The “8-Ball”

Ft. Detrick, MD

ca. 1968

slide13

Q fever Outbreaks

in the United States

  • Occupational exposures most frequently cited
    • research facilities using parturient ruminants
    • slaughterhouses
    • farms
    • factories
  • Sheep implicated more frequently than other animals in
  • outbreaks
slide14

Q fever Seroprevalence

in the United States

  • Human Seroprevalence Studies :
    • - persons with livestock contact 7.8%
    • - general population 0.8%
    • - Risk Ratio 10.3 [95% CI 9.0-11.8])
  • Ruminant Seroprevalence Studies:
  • - bovine bulk tank: 26.3%
  • - cattle: 3.4%
  • - sheep: 16.5%
  • - goats: 41.6%
  • Vet school dairy herds, antibodies in milk
  • - 9/22 (38%) had titers ≥ 1:256
slide15

Q fever Surveillance in the United States:

Human Cases Reported by State Health Departments, 1978-1999

15

11

7

5

18

23

2

7

13

2

12

4

1 (CT)

3

3

1

1

67

5

181

5

1 (DC)

17

10

19

3

n=436 Mean: 20 per year

slide16

Current Surveillance for Q fever

in the United States

  • Q fever in animals is not reportable
  • Human disease was made reportable in 1999
    • - states report cases to CDC via NETSS
    • - data available for 2000-2004
slide17

Cases of Q fever in Humans Reported by

State Health Departments, 1978-2004

* Years in which Q fever was a Nationally Reportable Disease

slide18

National Reporting, 2000-2004

Demographics

  • n = 255, Mean 64 cases per year
  • Gender: 195 (77%) Male
  • Age: mean, median 51 years
  • Race
    • White: 92%
    • Black: 6%
    • Asian: 2%
  • Hispanic: 13.4%
  • No significant difference in gender distribution
  • among age groups
slide19

Age Distribution of Q fever Cases

in the United States, NETSS 2000-2004

p< 0.0001

slide20

Month of Illness Onset, Q fever Cases

in the United States, NETSS 2000-2004

slide21

< 0.28 per million

Average Annual Incidence of Q fever in Humans

Reported by State Health Departments, 2000-2004

0.63

0.31

0.51

0.94

0.44

0.42

(MA)

2.40

0.93

0.64

1.33

(DC)

0.35

0.45

0.28

0.32

1.52

0.52

0.28

≥ 0.28 per million

Not Reportable 2000-2004

* Incidence calculated for years when Q fever was reportable.

slide22

Summary: Human Surveillance

  • Incidence of Q fever in humans is highest in the midwestern
  • and western states, and lower in the eastern U.S.
  • - differences in livestock densities do not offer
    • complete understanding
    • - complex interplay of agricultural practices, human population
    • density, and climactic factors
  • Demographics similar to previously published studies
  • - middle-aged male patients
  • - exception: no evidence of gender difference between adolescent
  • cases vs. adult cases
slide23

Why is Surveillance so difficult?

  • Nonspecific clinical signs
    • resembles a variety of other common illnesses
    • self-limiting in most cases
    • poor physician recognition
  • Requires laboratory confirmation for reporting
    • Serology requires paired serum specimens
    • - early specimens frequently negative
    • - patients rarely return to provide convalescent
    • samples
    • Physicians must request appropriate tests
slide24

Why is Surveillance so important?

  • Category B bioterrorism agent
  • - vital to establish endemic baseline levels
  • - need to understand background seroprevalence
  • before a BT event takes place
  • Current numbers of cases are under-reported
  • - true level of disease unknown
  • - level of serious disease (endocarditis) unknown
  • - economic burden of Q fever in humans and
  • animals is poorly assessed
  • - in Australia, considered the most
  • economically important zoonosis
slide26

Q fever: Investigation Challenges

  • All human cases should be investigated and reported
    • - Document geographic trends
    • - Recognize persons at high risk for endocarditis
    • - Assess source to determine outbreak potential
  • Investigating animal infection may be problematic
  • - Endemic in ruminants
  • - Serologic assessment difficult
  • - Phase 1 antibody may be more prominent
  • - Historically, only Phase 2 antibody was examined
  • - Cannot easily prevent or control infection in herds
slide27

Q fever: A Public Health Paradox

  • Difficulties in clinical and laboratory diagnosis make
  • adequate surveillance problematic.
  • However, because of bioterrorism potential and
  • possible serious outcomes in high-risk persons,
  • surveillance and reporting are critical.
  • Investigating sporadic human cases may not help
  • reduce risk
  • - there is often little that can be done to
  • minimize transmission in farm settings.
slide28

Prevention

  • Laboratory environments
  • - vaccination when possible (IND in U.S.)
  • - appropriate respiratory protection
  • Research environments with parturient ruminants
  • - Q fever-free animals
  • - employee biomonitoring program
  • - strict biocontainment
  • Farm/slaughterhouse situations:
  • - vaccine (Australia, not available in U.S.)
  • - attention to hygiene
  • - need for employee serologic monitoring?
  • General Public
  • - pasteurize milk products
  • - limit contact with parturient animals, especially
  • in public settings (petting zoos, etc)
slide29

Discussion

  • Q fever in humans is likely substantially underreported
    • - nonspecific clinical signs
    • - poor physician recognition
    • - difficult laboratory diagnosis
  • Surveillance for Q fever in the U.S. is improving
  • - made nationally reportable in 1999
  • - reporting increased by ~ 300% from 2000-2004
  • - reportable in 46 states in 2004
  • Future studies will improve our understanding of
  • geographic patterns of infection and risk
slide30

Acknowledgments

Bob Holman, Division of Viral and Rickettsial Diseases, CDC

Viral and Rickettsial Zoonoses Branch, CDC

Especially: Herb Thompson

Vrinda Nargund

Margaret Bowman

Tracey McCracken

Candace McCall

Jamie Childs

NETSS Staff

State Health Departments

U.S. Veterinary Schools

slide32

< 0.28 per million

Average Annual Incidence of Q fever in Humans

Reported by State Health Departments, 2000-2004

0.63

0.31

0.51

0.94

0.44

0.42

(MA)

2.40

0.93

0.64

1.33

(DC)

0.35

0.45

0.28

0.32

1.52

0.52

0.28

≥ 0.28 per million

Not Reportable 2000-2004

* Incidence calculated for years when Q fever was reportable.

slide33

Dairy Cows per Square Mile In the United States, 1998

5.1

24.1

10.6

5.0

37.6

21.4

7.8

5.8

20.1

8.9

9.3

5.4

13.3

5.0

6.5

11.8

0.0-2.0 per square mile

> 2.0 per square mile

slide34

Beef Cattle per Square Mile In the United States, 1998

46.3

60.1

87.6

30.1

38.2

78.6

59.5

57.4

51.0.

76.7

33.2

53.6

30.9

> 0.0- 15.0 per square mile

> 15 per square mile

slide35

Sheep per Square Mile In the United States, 1998

3.4

5.4

7.3

4.7

3.3

5.1

5.1

5.5

5.8

No reports

0.0-1.5 per square mile

> 1.5 per square mile

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