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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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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”

  • 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


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


Environmental Persistence large vacuole harboring about 20

  • 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


Transmission large vacuole harboring about 20

  • 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)


Acute Q fever large vacuole harboring about 20

  • 1-3 week incubation

  • Asymptomatic infections occur

  • Nonspecific signs and symptoms

    • fever

    • severe headache

    • myalgias

    • cough

    • fatigue

    • night sweats

    • rigors

    • nausea/vomiting


Acute Q fever large vacuole harboring about 20

  • 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%)


Chronic Q fever large vacuole harboring about 20

  • 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


Diagnosis large vacuole harboring about 20

  • 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


Q fever and Bioterrorism large vacuole harboring about 20

  • 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


History of Q fever Bioweapons Research large vacuole harboring about 20

  • 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)


The “8-Ball” large vacuole harboring about 20

Ft. Detrick, MD

ca. 1968


Q fever Outbreaks large vacuole harboring about 20

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


Q fever Seroprevalence large vacuole harboring about 20

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


Q fever Surveillance in the United States: large vacuole harboring about 20

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


Current Surveillance for Q fever large vacuole harboring about 20

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


Cases of Q fever in Humans Reported by large vacuole harboring about 20

State Health Departments, 1978-2004

* Years in which Q fever was a Nationally Reportable Disease


National Reporting, 2000-2004 large vacuole harboring about 20

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


Age Distribution of Q fever Cases large vacuole harboring about 20

in the United States, NETSS 2000-2004

p< 0.0001


Month of Illness Onset, Q fever Cases large vacuole harboring about 20

in the United States, NETSS 2000-2004


< 0.28 per million large vacuole harboring about 20

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.


Summary: Human Surveillance large vacuole harboring about 20

  • 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


Why is Surveillance so difficult? large vacuole harboring about 20

  • 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


Why is Surveillance so important? large vacuole harboring about 20

  • 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


Credit: Ralph A. Clevenger, 1999 large vacuole harboring about 20


Q fever: Investigation Challenges large vacuole harboring about 20

  • 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


Q fever: A Public Health Paradox large vacuole harboring about 20

  • 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.


Prevention large vacuole harboring about 20

  • 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)


Discussion large vacuole harboring about 20

  • 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


Acknowledgments large vacuole harboring about 20

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


< 0.28 per million large vacuole harboring about 20

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.


Dairy Cows per Square Mile In the United States, 1998 large vacuole harboring about 20

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


Beef Cattle per Square Mile In the United States, 1998 large vacuole harboring about 20

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


Sheep per Square Mile In the United States, 1998 large vacuole harboring about 20

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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