Q Fever:A Public Health Paradox

Emerging Zoonotic Diseases Summit, August 23, 2005Jennifer 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

• 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

• 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

• 1-3 week incubation• Asymptomatic infections occur• Nonspecific signs and symptoms

• fever• severe headache• myalgias• cough• fatigue• night sweats• rigors• nausea/vomiting

• 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%)

Acute Q fever

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

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

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

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)

The “8-Ball”Ft. Detrick, MD ca. 1968

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

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

Q fever Surveillance in the United States: Human Cases Reported by State Health Departments, 1978-1999

2

17

18167

1 (CT)

1 (DC)

3

12

2

1

11

13

187

5

5

4

10

3 3

23

19

15

15

7

n=436 Mean: 20 per year

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

Cases of Q fever in Humans Reported by State Health Departments, 1978-2004

* Years in which Q fever was a Nationally Reportable Disease

0

10

20

30

40

50

60

70

801

97

81

97

91

98

01

98

11

98

21

98

31

98

41

98

51

98

61

98

71

98

81

98

91

99

01

99

11

99

21

99

31

99

41

99

51

99

61

99

71

99

81

99

92

00

0*

20

01

*2

00

2*

20

03

*2

00

4*

Year

Nu

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of

Ca

se

s

National Reporting, 2000-2004Demographics

• 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

0.00

0.05

0.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0-9

10

-19

20

-29

30

-39

40

-49

50

-59

60

-69

70

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Age Group in Years

Inc

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Age Distribution of Q fever Casesin the United States, NETSS 2000-2004

p< 0.0001

Month of Illness Onset, Q fever Casesin the United States, NETSS 2000-2004

0

5

10

15

20

25

30

35

40Ja

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Ma

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Jun

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Month of Illness Onset

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Not Reportable 2000-2004

≥ 0.28 per million

< 0.28 per million

0.45

0.31

2.40

0.63

0.93

0.51

0.35

0.64

0.94

0.32

0.52

0.28 1.52

Average Annual Incidence of Q fever in Humans Reported by State Health Departments, 2000-2004

0.44

* Incidence calculated for years when Q fever was reportable.

0.28

0.42(MA)

1.33(DC)

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

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

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

Credit: Ralph A. Clevenger, 1999

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

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.

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)

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

AcknowledgmentsBob Holman, Division of Viral and Rickettsial Diseases, CDCViral and Rickettsial Zoonoses Branch, CDC

Especially: Herb ThompsonVrinda NargundMargaret BowmanTracey McCrackenCandace McCallJamie ChildsNETSS StaffState Health DepartmentsU.S. Veterinary Schools

Not Reportable 2000-2004

≥ 0.28 per million

< 0.28 per million

0.45

0.31

2.40

0.63

0.93

0.51

0.35

0.64

0.94

0.32

0.52

0.28 1.52

Average Annual Incidence of Q fever in Humans Reported by State Health Departments, 2000-2004

0.44

* Incidence calculated for years when Q fever was reportable.

0.28

0.42(MA)

1.33(DC)

Dairy Cows per Square Mile In the United States, 1998

5.8

13.3

10.6

5.1

5.0

8.9

37.67.8

9.3

5.0

5.4

21.4

11.8

20.1

0.0-2.0 per square mile

> 2.0 per square mile

6.5

24.1

60.187.6

30.1

53.6

51.0.

78.6

33.2

57.4

30.9

Beef Cattle per Square Mile In the United States, 1998

46.3

> 0.0- 15.0 per square mile

> 15 per square mile

59.5

76.7

38.2

5.5

4.77.3

5.15.1

3.4

5.8

3.3

Sheep per Square Mile In the United States, 1998

5.4

0.0-1.5 per square mile

> 1.5 per square mile

No reports