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
• 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
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%)
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
15
7
23
11
5
18
2
7
2
4
3
1
181
17
13
12
1
1 (CT)
3
67
5
5
10
19
3
n=436
Mean: 20 per year
1 (DC)
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
80
60
50
40
30
20
10
0
1978
1979
1980
1981
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000*
2001*
2002*
2003*
2004*
Number of Cases
70
Year
* Years in which Q fever was a Nationally Reportable Disease
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
0.45
0.40
0.35
0.30
0.25
0.20
0.15
0.10
0.05
Age Group in Years
p< 0.0001
70+
60-69
50-59
40-49
30-39
20-29
10-19
0.00
0-9
Incidence per million persons
Age Distribution of Q fever Cases
in the United States, NETSS 2000-2004
Month of Illness Onset, Q fever Cases
in the United States, NETSS 2000-2004
35
30
25
20
15
10
Month of Illness Onset
December
November
October
September
August
July
June
May
April
March
February
5
0
January
Number of Cases
40
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
0.35
0.45
0.28
0.32
0.28
1.52
0.52
< 0.28 per million
≥ 0.28 per million
Not Reportable 2000-2004
* Incidence calculated for years when Q fever was reportable.
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
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
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
0.35
0.45
0.28
0.32
0.28
1.52
0.52
< 0.28 per million
≥ 0.28 per million
Not Reportable 2000-2004
* Incidence calculated for years when Q fever was reportable.
1.33
(DC)
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
5.4
9.3
8.9
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
46.3
60.1
87.6
30.1
78.6
76.7
59.5
33.2
38.2
57.4
51.0.
53.6
30.9
> 0.0- 15.0 per square mile
> 15 per square mile
Sheep per Square Mile In the United States, 1998
3.4
7.3
5.4
4.7
5.1
5.1
3.3
5.5
5.8
No reports
0.0-1.5 per square mile
> 1.5 per square mile