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Epidemiology of Q Fever Among U.S. Military Personnel During Operation Iraqi Freedom (OIF)
Stephanie L. Scoville, DrPH
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Introduction
• Zoonotic disease caused by Coxiella burnetii
• Endemic in nearly every country
• Livestock are the major reservoir
• Primarily an occupational hazard
• Licensed vaccine not available in the U.S.
• Notifiable disease in U.S. as of 1999
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Historical Background
• 1935: First outbreak of Q (for query) fever among slaughterhouse workers in Queensland
• 1935: Organism isolated from ticks collected along Nine Mile Creek in Montana
• 1938: Connection between the groups made when a lab-acquired Q fever infection occurred in Montana
• Organism named in honor of Harold Cox and Macfarlane Burnet
Bacteriology
• Obligate intracellular, gram-negative bacterium
• Replicates in phagolysosome
• Sporelike form can persist in the environment
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Modes of Transmission
• Inhalation of aerosolized bacteria excreted by infected animals– Primarily domesticated ruminants (cattle,
goats, and sheep)– Also associated with camelids, cats, and
wildlife
• Ingestion (raw milk) possible route
• Tick bites unlikely
Acute Illness
• Flu-like illness, pneumonia, or hepatitis are most common
• Asymptomatic infections may occur
• Atypical manifestations possible
• Infection may persist in an asymptomatic state
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Chronic Q Fever
• Appears to be uncommon and may not develop until years after initial infection
• Endocarditis is the most common manifestation
• Higher risk for immunocompromised patients and those with pre-existing cardiac valvulopathy
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Chronic Q Fever
• Diagnosis is usually serologic and not standardized
• Treatment requires ≥ 18 months of doxycycline plus hydroxychloroquine
• Unite' des Rickettsies researchers* proposed follow-up strategy in 2007 to obtain early diagnosis of chronic infection
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*Landais C, Fenollar F, Thuny F, Raoult D. From acute Q fever to endocarditis: serological follow-up strategy. Clin Infect Dis. 2007 May 15;44 (10):1337-1340.
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Strategy for diagnosing Q fever
Reference: Hartzell J. D. et.al. Mayo Clin Proc. 2008;83:574-579
© 2008 Mayo Foundation for Medical Education and Research
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Military Significance
• Outbreaks occurred among British and American troops during World War II
• Only three cases diagnosed among U.S. military personnel during the Persian Gulf War
• First recognized among U.S. military personnel during OIF during pneumonia investigation in summer 2003
• Potential biological warfare threat
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Possible Exposures During OIF
• Foot patrols• Search operations• Helicopter operations• Explosive attacks• Controlled detonations of weapons caches• Recovery operations after explosions• Sleeping in stables, wool factories, or local
homes
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Q Fever in OIF-Deployed Soldiers: An Emerging Disease
of Military Importance
Alicia D. Anderson, DVM, MPH
Major, Veterinary Corps, U.S. Army
Note: Data from the following three slides were copied from a Note: Data from the following three slides were copied from a presentation prepared for the Force Health Protection Conference, presentation prepared for the Force Health Protection Conference, August 2004August 2004
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Severe Pneumonitis EPICON
• 3/19 seropositive for Q fever by IFA
CASE P2 IgM P1 IgM P2 IgG P1 IgG
1 Neg 1:64 1:1024 1:512
2 Neg 1:512 1:128 Neg
3 1:512 1:512 >1:1024 >1:1024
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Follow-up Q Fever Serosurvey
• Serosurvey of 22 service members diagnosed with non-severe pneumonia while deployed
• Pre- and post-deployment stored sera used to determine seroconversion
• 5/22 seroconverted while deployed
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Serosurvey Results
CASE P2 IgM P1 IgM P2 IgG P1 IgG
4 1:256 >1:1024 1:256 Neg
5 >1:1024 >1:1024 1:512 Neg
6 1:512 1:256 1:512 Neg
7 1:64 1:32 1:64 Neg
8 >1:1024 1:512 >1:1024 1:128
• Summary: 8/41 (19%) with pneumonia tested for Q fever were seropositive
Pre-deployment antibody titers negative
Seroepidemiologic Survey of Q Fever Among U.S. Military Personnel
During OIF
MAJ Troy Baker, MD, MPH
Walter Reed Army Institute of Research
Division of Preventive Medicine
Note: Data from the following four slides were modified from a Note: Data from the following four slides were modified from a presentation prepared for an informal meeting at NNMC Bethesda, presentation prepared for an informal meeting at NNMC Bethesda, February 2008February 2008
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Objective
• Determine the burden of undiagnosed Q fever among U.S. military personnel deployed in support of OIF
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Methods
• Created list of ICD-9 codes consistent with Q fever symptoms
• Identified 970 potential cases that had been hospitalized in Iraq from 2003 through 2004 through PASBA
• Sent 920 de-identified pre- and post-deployment serum specimens to WRAIR from the DoDSR
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Laboratory Testing
• Specimens re-aliquoted at WRAIR and shipped to USAFSAM for IFA testing
• Post-deployment specimens considered “potentially positive” if IFA titer ≥1:16 – Pre-deployment specimens were
subsequently tested – Positive seroconversion required at least a 4-
fold elevation in titers
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Top 3 Diagnoses with Seroconversion
Diagnosis
Total
#
Positive
# (%)
Fever NOS 235 45 (19)
Pneumonia* 98 14 (14)
Viral Infection NOS 95 12 (13)
All 920 95 (10)
*organism not specified
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OIF Q Fever References
1. Anderson AD, Smoak B, Shuping E, et al. Q fever and the US military. Emerg Infect Dis. 2005;11:1320-1322.
2. Leung-Shea C, Danaher PJ. Q fever in members of the United States armed forces returning from Iraq. Clin Infect Dis. 2006;43:e77-82.
3. Faix D, Harrison D, Riddle M, et al. Outbreak of Q Fever among US Military in Western Iraq, June - July 2005. Clinical Infectious Diseases. 2008;46:e65-e68.
4. Gleeson TD, Decker CF, Johnson MD, et al. Q fever in US military returning from Iraq. Am J Med. 2007;120:e11-12.
5. Hartzell JD, Peng SW, Morris-Wood RN, et al. Atypical Q fever in US soldiers. Emerg Infect Dis. 2007;13:1247-1249.
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OIF Q Fever Published Cases (n=25)
• 8 Soldiers from Mar-Aug 03
• 1 Soldier in Sep 03 & 1 Airman in Sep 04
• 9 Marines from Jun-Jul 05
• 2 Marines in Nov 04 & 1 Marine in Sep 06
• 1 Soldier in Jul 06 & 2 Soldiers in Dec 06
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Department of Defense Reference Laboratory
• U.S. Air Force School of Aerospace Medicine (USAFSAM) Epidemiology Lab Service at Brooks City-Base, TX– Indirect immunofluorescence antibody (IFA)
test is the only FDA-approved test– IgG and IgM assay (Focus Diagnostics)
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DoD Research Assays
• Research Assays– Enzyme-linked immunosorbent assays used
by USAMRIID and NAMRU-3– Polymerase chain reaction (PCR) tests using
whole blood by USAMRIID– Joint Biological Agent Identification and
Diagnostic System (JBAIDS) PCR awaiting FDA clearance
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Diagnostic Challenges for Deployed Providers
• Significant time-lag for results (≥1 month) – CSH to LRMC to USAFSAM– Balad to WHMC to USAFSAM as of Feb 08
• Usually requires acute and convalescent specimen due to timing of seroconversion
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Clinical Practice Guidelines
• Developed by the AFIDS Q Fever Working Group, April 08– Acute disease treated with 21 days of 100 mg
doxycycline, twice daily– Follow-up serologic testing for at least two
years – Baseline transthoracic echocardiography
(TTE) for all cases upon redeployment
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Q Fever Surveillance During OIF
• Initiated by USACHPPM Feb 07
• Monitor patient encounters using the Theater Medical Data Store
• Collaborate with providers
• Receive weekly lab reports from USAFSAM (as of Jun 2008)
• Maintain a Q Fever Registry
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Surveillance Case Definition
• Clinical evidence of acute illness: – Acute fever– One or more of the following: fatigue, chills,
headache, acute hepatitis, pneumonia, or elevated liver enzyme levels
• Serologic evidence of recent or active infection:– 4-fold antibody endpoint titer increase, or– Phase II IgM titer ≥ 1:128,* or – Phase II IgG titer ≥ 1:256*
*If only a single sample was obtained
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USACHPPM Epidemiologic Questionnaire
• Self-administered• Emailed to patients when operationally feasible• Assesses risk factors:
– Demographics– Sleeping quarters– Modes of transportation– Local foods/beverages– Animals/insects– Tobacco use
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OIF Q Fever Epidemiology: U.S. Military Personnel
• 90 cases Jan 07-Jun 08 – All male– 80 Army, 5 Marine Corps, 4 Air Force, 1 Navy – Median age: 29 years (range: 19-47)– Rank: 41 NCOs, 35 Junior Enlisted, 14
Officers
• 53 cases with symptom onset in 2007 (average annual incidence of 3.4/10,000)
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Risk Factors
• Various occupational specialties to include administrative, aviation, infantry, and medical personnel
• Transmission primarily via inhalation
• No temporal or geographic clustering
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Q Fever Cases by Month and Service, Jul 07-Jun 08* (n=66)
0123456789
101112131415
Jul-07
Aug-07
Sep-07
Oct-07
Nov-07
Dec-07
Jan-08
Feb-08
Mar-08
Apr-08
May-08
Jun-08
USA USAF USMC USN
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Additional Cases
• U.S. civilian and contractor employees in Iraq (n=8)
• U.S. military personnel deployed to other locations– Afghanistan (n=2)– Ethiopia (n=1)
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Summary
• Q fever is a risk for travelers to Southwest Asia• Empiric doxycycline for suspected acute Q fever• Serodiagnostic testing (IFA) of acute and
convalescent samples• Reportable disease• Chronic Q fever is rare but possible• Serologic follow-up for at least two years and
baseline TTE
