Epidemiology of Q Fever Among U.S. Military Personnel During Operation Iraqi Freedom (OIF) Stephanie L. Scoville, DrPH.

Epidemiology of Q Fever Among U.S. Military Personnel During Operation Iraqi Freedom (OIF)

Stephanie L. Scoville, DrPH

2

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

33

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

44

55

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

66

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

77

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

88

*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.

9

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

10

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

11

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

1212

1313

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

1515

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

1616

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

1717

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

1919

Objective

• Determine the burden of undiagnosed Q fever among U.S. military personnel deployed in support of OIF

2020

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

2121

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

2222

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

2323

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.

2424

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

2525

2626

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)

2727

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

2828

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

2929

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

3030

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

3131

3232

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

3333

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

3434

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)

3535

Risk Factors

• Various occupational specialties to include administrative, aviation, infantry, and medical personnel

• Transmission primarily via inhalation

• No temporal or geographic clustering

3636

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

3737

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)

3838

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

39

Contact info:[email protected]

301-319-9684DSN 285-9684