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Coinfection of Mycoplasma pneumonia with chronic Q fever in a nurse deployed to operation Iraqi freedom: a case study.

Q fever is considered a worldwide zoonosis due to the intracellular rickettsia, Coxiella burnetii. In the United States, data has shown a 3.1% seroprevalence. (1) However, prevalence rates vary widely among countries based on their ability to conduct proper surveillance. For example, rates are noted to be 18.3% in Morocco, 32.3% in Turkey, and 10% to 37% in northeast Africa. (2-4) Cautiously, these estimates may underestimate the true incidence of disease due to its polymorphic clinical presentation. (5)

Typically, Q fever is considered an occupational hazard affecting persons in greatest contact with farm or laboratory animals. The reservoir includes a variety of wild and domestic mammals, birds, and arthropods. (5) Urine, feces, milk, and birth products of infected animals are the main sources for transmission. Human infections primarily originate from either inhalation of contaminated aerosols or ingestion of raw milk products. The route of inhalation may occur directly from parturient fluids of infected animals during the birthing process. (5) Additionally, it is highly resistant to harsh environments up to several weeks, and prevailing wind patterns have been known to transport this organism great distances from its source. (5) As a result, Q fever may occur in patients without history of animal contact. Furthermore, the long incubation period (14-21 days) of this disease contributes to its elusive presentation in both acute and chronic progression. (6)

In acute cases, the most common clinical presentation is usually a self-limited febrile illness of unknown origin; however, there are degrees of its severity. Complications include but are not limited to granulomatous hepatitis, atypical pneumonia, and meningoencephalitis. (7) Although not reported in the United States, progressive chronic fatigue has also been described in England and Australia; however, this syndrome is not considered diagnostic of an ongoing infection. (8-10)

Rarely does chronic Q fever develop (1% of acute cases). It may occur, however, more often (39%) in patients with preexisting cardiac valvulopathy. (11) This may be defined by a clinical evolution more than 6 months duration with the presence of phase 1 immunoglobulin (Ig) G C. burnetti antibodies. (5) The most common clinical manifestation of chronic infection is endocarditis involving the aortic and mitral valves. (5) Interestingly, the majority of patients who develop chronic Q fever are older men (aged over 40 years) even though both genders may have similar exposures. (7) Risk factors include immunosuppressed or immunocompromised persons, pregnancy, and vascular abnormalities. Nonetheless, preexisting valvulopathy, specifically prosthetic heart valves, remain the most predominant risk factor. (5,11,12) Without treatment, phase 1 IgG titers remain persistently high along with further clinical deterioration. (11,13)

Diagnosis is primarily made by serologic testing. The method of choice is immunofluorescence assay. (5,14) In the acute phase, phase 2 IgG and IgM antibodies are usually elevated around 1-2 weeks after the onset of symptoms, and around 90% of all cases seroconvert by the third week. (15) A phase 2 IgG antibody titer of 1:200 or more and a phase 2 IgM antibody titer of 1:50 or more are highly suggestive of an acute infection. (15) In contrast, the phase 1 IgG antibodies are predominant during chronic infections. In this stage, titers of 1:800 or more are considered to be significant. (15) Antibodies generally peak around 1-2 months after the onset of symptoms. (15) Gradually, the titers usually decrease in the following year; but IgG antibodies may persist while IgM antibodies disappear. (15) When high levels of phase 1 antibodies remain positive, chronic Q fever is highly suggestive. (15)


On March 31, 2011, a 39-year-old white female complained of generalized myalgias, nausea, headache, night sweats, subjective fevers, and chills for the past day followed by fatigue. Vitals were remarkable for slightly elevated heart rate (107) and temperature (101.9[degrees]F). Her occupation was described as an Army Reserve nurse deployed to Mosul, Iraq, in a combat support hospital. She had no significant past medical or recent surgical history. She denied any sick contacts to either humans or animals. She also denied any contact to unusual food or water sources. Intravenous fluids improved her condition with no significant physical exam findings. Urine pregnancy test, blood counts, chemistries, rapid influenza, monospot test, and chest x-ray were all within normal limits. Despite the negative influenza swab, symptoms were consistent with a flu-like diagnosis. Consequently, the patient was prescribed a 5-day course of oseltamivir.

Two days later, her symptoms progressed to nausea, vomiting, and physical exam findings of cool, clammy skin. Although her blood cultures were negative, she was noted to have elevated liver enzymes: alanine aminotransferase (ALT 443), aspartate aminotransferase (AST 288) and alkaline phosphatase (AP 364). Yet, her right upper quadrant ultrasound was interpreted as normal. Zofran and intravenous fluids were given along with outpatient management.

On April 12, 2011, the patient had reoccurring myalgias; however, she now developed rhinitis, headache, anorexia and night sweats. She was afebrile on the visit but demonstrated sinus tachycardia (heart rate 125) that improved with an intravenous fluid bolus. She reported a history of persistent fevers as high as 102[degrees]F. Her physical exam was unremarkable. Although her urinalysis was normal, her blood counts were significant for decreased hemoglobin (Hgb 11) levels, hyperglycemia (glucose 200), elevated erythrocyte sedimentation rate (ESR 49) and c-reactive protein (CRP 24), but a resolving transaminitis (ALT 90, AST 36, AP 184).

During the second week of illness, the patient developed worsening erythematous, nonpruritic, but tender to palpation nodules on her bilateral legs (Figure 1). Initially, the primary diagnosis was presumed insect bites although no specific arthropod or species were identified. Follow-up 4 days later revealed nighttime 10/10 joint pains with nonresolving bilateral leg nodules and a progressive rash to both arms. The nodules now appeared confluent including a rash to both palms of the hands (Figure 2). A diagnosis of erythema nodosum was made. Additionally, she complained of wakening night sweats and "hot flashes" during daytime hours. Vitals were unremarkable as additional labs continued to reveal anemia (Hgb 9.6 with schistocytes) along with persistent elevation of inflammatory markers (ESR>140 and CRP 19.2). Other pertinent labs such as human immunodeficiency virus (HIV), hepatitis B and C, rapid plasma reagin, leishmaniasis cultures, liver function tests, and thyroid panel were all concluded as negative. Her pelvic exam was normal, and antigens for gonorrhea and chlamydia were also negative.



As a result, she was diagnosed with fever of unknown origin and evacuated to Landstuhl Regional Medical Center for further evaluation. Additional consultations revealed a negative tuberculin skin test, antistreptolysin O, hepatitis panel, nuclear antibody panel, ferritin, rheumatoid factor, histoplasma and coccidiodies antibody titers. The TORCH panel* revealed positive IgG antibodies for cytomegalovirus, herpes simplex virus, and rubella with no active lesions identified. Otherwise, her inflammatory markers were on a declining trend (CRP 3.16, ESR 65). Notably, her mycoplasma antibody was positive and she was treated for mycoplasma pneumoniae.

On day 41, C. burnetti results, shown in the Table, returned with a concern for Q fever. As a result, further cardiac testing was completed. An electrocardiogram revealed a sinus arrhythmia while an echocardiogram diagnosed a mild left atrial enlargement, insignificant pulmonary insufficiency, moderate eccentric mitral regurgitation, as well as mild to moderate tricuspid regurgitation. Detailed questioning failed to reveal any occupational or casual exposure to common Q fever vectors. The patient did not have any contact with livestock or likely animals. She had been quartered in an enclosed containerized housing unit (CHU) and denies any field exposure outside the combat support hospital housing area. Her CHU was located adjacent to a MEDEVAC helicopter landing zone where rotor downwash may have aerosolized soil particles that led to infection, although no other case reports were identified in her area of operations.

Based on the diagnosis of Q fever, the patient was treated with doxycycline for a 3-week course and returned to the combat theater to complete her tour. Initially, her phase 2 IgM titers were elevated consistent with an acute infection on day 41. Increasing phase 2 IgG titers followed on day 218 even after treatment. Later, her constitutional symptoms of fever, rash, and night sweats eventually resolved. However, follow-up serologies revealed persistent phase 1 IgG titers, consistent with a chronic infection.

Two years after diagnosis, the patient complained only of persistent arthralgias varying from 2 to 5 out of 10 on a visual analog pain scale, a common complication of chronic disease. Follow-up titers indicated decreasing IgM titers consistent with convalescence, shown in the Table. Additionally, her serologic inflammatory markers returned to normal levels. Repeat echocardiogram on January 24, 2013, showed mild thickening of the anterior leaflet of the mitral valve, but otherwise there were no significant changes in her condition or cardiac function.


Since Operation Iraqi Freedom began, there have been reports of over 100 cases of Q fever among deployed US military personnel ascertained through a Department of Defense medical database. (6,15-21) The most frequent presentation includes fever, pneumonia, or hepatitis. (8,22) Despite these typical nonspecific signs and symptoms of the disease, Q fever is also known to possess a wide spectrum of manifestations including 7 distinct presentations described by Raoult: fever, pneumonia, hepatitis, meningitis, meningoencephalitis, pericarditis, and myocarditis. (8) Although cases of acute cholecystitis have been associated with this disease in some medical literature, (23-26) it is not well described as part of the Q fever diagnosis. Consequently, this broad variation in clinical presentation can delay diagnosis and further treatment.

Our patient denied having typical risk factors including exposure to livestock or consumption of local meat or dairy products. However, it is known that direct exposure to the source is not necessary for an infection to occur. (8,21,22) Further, coinfection with mycoplasma pneumoniae is not well described in the literature. However, atypical pneumonia have been discussed in limited regions of the world (27) and more recently with investigations among HIV-infected patients. (28)

Additionally, chronic Q fever is infrequently reported among females. Her valvulopathy discovered on echocardiogram was considered mild to moderate without serious untoward symptoms or signs of endocarditis. There were no indications of a preexisting cardiac condition in her medical history. Once identified as an infection of C. burnetti, prompt treatment was initiated with direct follow-up. Subsequent laboratory studies confirmed resolution of her Q fever with an uncomplicated clinical course.

More importantly, Q fever is considered a category B biologic agent and is a potential threat to deployed Soldiers. (29) In this case, direct contact with infected animals is not required for military personnel to be considered exposed. Transmission factors within military populations include sleeping in barns, tick bites, and living near helicopter landing zones where environmental aerosols are generated. (16)

In conclusion, this case report is an important reminder to medical providers of the existence of a myriad of unique infectious sources among deployed Soldiers or those returning from abroad. A heightened awareness of this insidious disease will ensure prompt diagnosis and treatment ultimately preventing future complications. Lastly, the occupational and environmental history is a key determinant of success for any clinical practice.


(1.) Anderson AD, Kruszon-Moran D, Loftis AD, et al. Seroprevalence of Q fever in the United States, 2003-2004. Am J Trop Med Hyg. 2009;81(4):691-694.

(2.) Botros BA, Soliman AK, Salib AW, et al. Coxiella burnetii antibody prevalences among human populations in north-east Africa determined by enzyme immunoassay. J Trop Med Hyg. 1995;98(3):173-178.

(3.) Meskini M, Beati L, Benslimane A, Raoult D. Seroepidemiology of rickettsial infections in Morocco. Eur J Epidemiol. 1995;11(6):655-660.

(4.) Kilic S, Yilmaz GR, Komiya T, Kurtoglu Y, Karakoc EA. Prevalence of Coxiella burnetii antibodies in blood donors in Ankara, Central Anatolia, Turkey. New Microbiol. 2008;31(4):527-534.

(5.) Maurin M, Raoult D. Q fever. Clin Microbiol Rev. 1999;12(4):518-553.

(6.) Gleeson TD, Decker CF, Johnson MD, Hartzell JD, Mascola JR. Q fever in US military returning from Iraq. Am J Med. 2007;120(9):e11-e12.

(7.) Raoult D, Tissot-Dupont H, Foucault C, et al. Q fever 1985-1998. Clinical and epidemiologic features of 1,383 infections. Medicine (Baltimore). 2000;79(2):109-123.

(8.) Raoult D, Marrie T, Mege J. Natural history and pathophysiology of Q fever. Lancet Infect Dis. 2005;5(4):219-226.

(9.) Ayres JG, Flint N, Smith EG, et al. Post-infection fatigue syndrome following Q fever. QJM. 1998;91(2):105-123.

(10.) Ayres JG, Wildman M, Groves J, Ment J, Smith EG, Beattie JM. Long-term follow-up of patients from the 1989 Q fever outbreak: no evidence of excess cardiac disease in those with fatigue. QJM. 2002;95(8):539-546.

(11.) Fenollar F, Fournier PE, Carrieri MP, Habib G, Messana T, Raoult D. Risks factors and prevention of Q fever endocarditis. Clin Infect Dis. 2001;33(3):312-316.

(12.) Fenollar F, Thuny F, Xeridat B, Lepidi H, Raoult D. Endocarditis after acute Q fever in patients with previously undiagnosed valvulopathies. Clin Infect Dis. 2006;42(6):818-821.

(13.) Landais C, Fenollar F, Thuny F, Raoult D. From acute Q fever to endocarditis: serological follow-up strategy. Clin Infect Dis. 2007;44(10):1337-1340.

(14.) Fournier PE, Marrie TJ, Raoult D. Diagnosis of Q fever. J Clin Microbiol. 1998;36(7):1823-1834.

(15.) Leung-Shea C, Danaher PJ. Q fever in members of the United States armed forces returning from Iraq. Clin Infect Dis. 2006;43(8):e77-e82.

(16.) Hartzell JD, Peng SW, Wood-Morris RN, et al. Atypical Q fever in US Soldiers. Emerg Infect Dis. 2007;13(8):1247-1249.

(17.) Hartzell JD, Wood-Morris RN, Martinez LJ, Trotta RF. Q fever: epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2008;83(5):574-579.

(18.) Faix DJ, Harrison DJ, Riddle MS, et al. Outbreak of Q fever among US military in western Iraq, June-July 2005. Clin Infect Dis. 2008;46(7):e65-e68.

(19.) Ellis SB, Appenzeller G, Lee H, et al. Outbreak of sandfly fever in central Iraq, September 2007. Mil Med. 2008;173(10):949-953.

(20.) Aronson NE, Sanders JW, Moran KA. In harm's way: infections in deployed American military forces. Clin Infect Dis. 2006;43(8):1045-1051.

(21.) Anderson AD, Smoak B, Shuping E, Ockenhouse C, Petruccelli B. Q fever and the US military. Emerg Infect Dis. 2005;11(8):1320-1322.

(22.) Parker NR, Barralet JH, Bell AM. Q fever. Lancet. 2006;367(9511):679-688.

(23.) Rolain JM, Lepidi H, Harle JR, et al. Acute acalculous cholecystitis associated with Q fever: report of seven cases and review of the literature. Eur J Clin Microbiol Infect Dis. 2003;22(4):222-227.

(24.) Reina-Serrano S, Jimenez-Saenz M, Herrerias-Gutierrez JM, Venero-Gomez J. Q fever-related cholecystitis: a missed entity?. Lancet Infect Dis. 2005;5(12):734-735.

(25.) Modol JM, Llamazares JF, Mate JL, Troya J, Sabria M. Acute abdominal pain and Q fever. Eur J Clin Microbiol Infect Dis. 1999;18(2):158-160.

(26.) Kelly RP, Byrnes DJ, Turner J. Acute, severe hepatitis due to Coxiella burneti infection. Med J Aust. 1986;144(3):151-152, 154.

(27.) Marrie TJ, Haldane EV, Noble MA, Faulkner RS, Martin RS, Lee SH. Causes of atypical pneumonia: results of a 1-year prospective study. CMAJ. 1981;125(10):1118-1123.

(28.) Marrie TJ, Peeling RW, Fine MJ, Singer DE, Coley CM, Kapoor WN. Ambulatory patients with community-acquired pneumonia: the frequency of atypical agents and clinical course. Am J Med. 1996;101(5):508-515.

(29.) Daya M, Nakamura Y. Pulmonary disease from biological agents: anthrax, plague, Q fever, and tularemia. Crit Care Clin. 2005;21(4):747-763,vii.

LTC Paul O. Kwon, MC, USA

Jason R. Pickett, MD

* A group of tests for toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and HIV, but it can also include other infections.

When this article was written, LTC Kwon was with the Department of Preventive Medicine, Madigan Army Medical Center, Tacoma, Washington. He is currently Chief of Preventive Medicine, US Army Medical Activity-Alaska, Fort Wainwright, Alaska.

Dr Pickett is an Assistant Professor, Department of Emergency Medicine, Wright State University, Dayton, Ohio. He is also a Major in the West Virginia Army National Guard where he serves as a battalion surgeon.
Results of serologic testing for presence of Coxiella burnetti.

Date           Phase 1 IgG         Phase 2 IgG         Phase 1 IgM

04/27/11       < 1:16              < 1:16                 1:1024
05/23/11       1:256               1:4096                 1:4096
11/03/11       1:1024              1:16384                 1:256
08/22/12 (a)   [greater than or    [greater than or      Negative
                 equal to] 1:256     equal to] 1:256
10/17/12 (a)   1:4096              1:8192              Negative (b)
04/11/13 (a)   1:128               1:128               Not Performed

Date           Phase 2 IgM     ESR   CRP

04/27/11          1:2048       65    3.16
05/23/11          1:2048       --     --
11/03/11           1:16        --     --
08/22/12 (a)     Negative      --     --

10/17/12 (a)     Negative      16    0.63
04/11/13 (a)   Not Performed   11    0.40

(a) All subsequent lab results from 08/22/2012 to 04/11/2103 were
processed by ARUP Laboratories (University of Utah, Salt Lake City).

(b) Although the test was deemed negative by the laboratory's
screening lab, titers were processed by the Director of Laboratory
Operations and read as 1:16.
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Author:Kwon, Paul O.; Pickett, Jason R.
Publication:U.S. Army Medical Department Journal
Article Type:Case study
Geographic Code:7IRAQ
Date:Jul 1, 2014
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