Endocarditis after Acute Q Fever
Endocarditis after Acute Q Fever
Abstract & Commentary
By Patricia Cristofaro, MD, and Maria Mileno, MD Patricia Cristofaro is Assistant Professor, Department of Infectious Diseases, Brown University, and Maria Mileno is Director, Travel Medicine, The Miriam Hospital, Associate Professor of Medicine and Infectious Diseases, Director, International Travelers’ Clinic, Brown University School of Medicine. Dr. Cristofaro reports no financial relationship relevant to this field of study, and Dr. Mileno is a consultant for GlaxoSmithKline, and does research for Merck.
This article originally appeared in the June 2006 issue of Travel Medicine Advisor. It was edited by Frank Bia, MD, MPH, and peer reviewed by Lin H. Chen, MD. Dr. Bia is Professor of Medicine and Laboratory Medicine; Co-Director, Tropical Medicine and International Travelers’ Clinic, Yale University School of Medicine, and Dr. Chen is Assistant Professor, Harvard Medical School; Director, Travel Resource Center, Mount Auburn Hospital, Cambridge, MA. Dr. Bia is a consultant for Pfizer and Sanofi Pasteur, and receives funds from Johnson & Johnson, and Dr. Chen reports no financial relationship relevant to this field of study.
Synopsis: Acute Q fever may progress to endocarditis in patients with clinically silent valvulopathy. Those at risk require either extended antibiotic prophylaxis or close serological follow-up. All patients with acute Q fever should undergo transthoracic echocardiography, or in some instances transesophageal echocardiography, to exclude occult valvular abnormalities.
Source: Fenollar F, et al. Endocarditis after Acute Q Fever in Patients with Previously Undiagnosed Valvulopathies. Clin Infect Dis. 2006;42:818-821.
Fenollar and colleagues report 3 cases of Coxiella burnetii (Q fever) endocarditis which occurred in patients with previously undetected, clinically silent cardiac valvular abnormalities, months to years after documented acute Q fever. These subtle valvulopathies included bicuspid aortic valve, mitral valve prolapse, and minimal valvular leaks.1
Patient 1: A 45-year-old male physician was diagnosed with acute Q fever in May 1998, having presented with acute hepatitis and a positive serological test. He had no detected cardiac murmur. He received doxycycline 200 mg daily for 3 weeks and remained healthy until November 2003, when he experienced dyspnea without fever. The murmur of aortic insufficiency was appreciated on auscultation. Transesophageal echocardiography (TEE) confirmed aortic insufficiency and revealed a bicuspid aortic valve. Standard blood cultures were negative. Coxiella burnetii serology revealed anti-phase I antibodies characteristic of chronic Q fever. The severity of his aortic insufficiency was such that he required valvular replacement. C. burnetii was identified by immunohistochemical staining of the valve specimen; PCR and cultures of this specimen were also positive. He received doxycycline (200 mg/day) and hydroxychloroquine (600 mg per day) and remains well.
Patient 2: A 53-year-old woman presented in July 2003, with hepatitis and Q fever serologies characteristic of acute infection (elevated anti-phase II antibodies). She had no significant medical history; no heart murmur was noted. She received doxycycline 200 mg daily for 3 weeks. Two months later, during September 2003, she presented with fever. Mitral valve prolapse, associated with mitral valve vegetations, was found on TEE. Q fever serology was then characteristic of chronic Q fever, with the presence of anti-phase I IgM antibodies. Standard blood cultures remained negative; however, serum PCR was positive for C. burnetii. She also received a regimen of oral doxycycline and hydroxychloroquine and is doing well.
Patient 3: A 50-year-old man was diagnosed with acute Q fever in July 2004, having presented with both hepatitis and serum anti-phase II C. burnetii IgM titer of 1:1600. He also was treated with doxycycline 200 mg daily for 3 weeks. Medical history and physical exam were unremarkable. A transthoracic echocardiogram (TTE) was completely normal. Six months later, in February 2005, he presented with fever. Transesophageal echo revealed mitral valve vegetation but only trivial mitral regurgitation. C. burnetii serology had evolved to anti-phase I antibodies. He, too, was begun on a regimen of doxycycline and hydroxychloroquine and has remained well.
Fenollar et al conclude that when acute Q fever is diagnosed, it is essential to diagnose any concurrent cardiac valvulopathy, no matter how subtle. With this in mind, all such patients should be subjected to at least transthoracic echocardiography. Those at especially high risk should have transesophageal echocardiography because it affords more sensitive and accurate valvular visualization. Among these are those individuals > 60 years in age and those with a family history of either aortic valve disease or bicuspid aortic valve. Those individuals with abnormal valves should receive either specific long-term antibiotic prophylaxis against the evolution of Q fever or follow-up serology every 3 months, for at least 2 years. A combination of doxycycline (200 mg per day) plus hydroxychloroquine (600 mg per day) administered for 12 months has been suggested as the prophylactic regimen.
Commentary
Q fever represents a nearly worldwide zoonosis caused by the Gram negative, obligate intracellular coccobacillus, Coxiella burnetii. Transmission is largely by aerosol; inhalation of virtually a single bacterium may lead to infection. Indeed, C. burnetii is listed by the CDC as a Category B bioterrorism agent in part because of this efficiency of transmission.2 The most common mode of transmission is through inhalation of aerosols originating from the infected products of conception of goats, sheep, cats, and cattle at the time of birth or miscarriage. Cases have also occurred from exposure to hay, straw, dust, and wool that had been in contact with infected animals. Exposure by aerosol has been documented as far as 18 kilometers from the infected source. There is occasional blood-borne and, rarely, person-to-person transmission; consumption of unpasteurized cheese has also been linked to Q fever.3
At least 50% of acute Q fever cases are completely asymptomatic, manifesting themselves solely by seroconversion. The most common clinical syndromes are: a flu-like illness with fever, headache, myalgias, pneumonia, and hepatitis.4 The current recommended therapy is oral doxycycline 200 mg daily for 3 weeks. Although most patients recover completely from Q fever, even without treatment, 1% will go on to develop chronic disease. The majority of these patients will have endocarditis. However, other endovascular infections, osteomyelitis, or joint infections are also possible. Host factors that predispose to these sequelae are pre-existing cardiac and vascular abnormalities, prosthetic valves, grafts, or joint prostheses, and immunosuppressive illnesses such as coexistent malignancy or HIV. Acute Q fever would be expected to result in endocarditis in one-third of individuals with underlying valvular disease.5
The transformation from acute to chronic Q fever can be diagnosed by observing the evolution of Q fever serology. Acute infection is characterized by antibodies directed against phase II antigens on the organism. On the other hand, chronic Q fever is diagnosed by detection of antibodies directed against phase I antigens. A titer of antiphase I IgG antibody of > 1:800 and an IgA titer of > 1:100 are diagnostic of chronic Q fever.6
Endocarditis is a serious, indeed life-threatening, illness which, untreated, may mandate cardiac surgery as for patient one. It is estimated that risk for the development of endocarditis in patients with known valvulopathy and acute Q fever is about 39%. In a previous publication, Fenollar et al proposed that patients with acute Q fever and known cardiovascular defects be treated with combination doxycycline/hydroxychloroquine therapy for one year and followed every 3 months for at least 2 years.7
In the more recent article summarized above, Fenollar et al describe 3 patients with normal cardiac findings on physical exam, including one with a normal transthoracic echo who went on to develop chronic Q fever endocarditis. The underlying valvulopathies, later discovered by transesophageal echocardiography,8 included mitral valve prolapse, minimal valvular leak, and bicuspid aortic valve. Had underlying pathology been detected earlier, antibiotic prophylaxis and/or close follow-up would have prevented clinical disease.
Conversely, Q fever must be considered a possible etiology of culture-negative endocarditis, accounting for about 5% of these cases. We present a patient from the Miriam Hospital, Providence, RI, in whom Q fever developed in the setting of hypertrophic cardiomyopathy. We know of no other similar case report, but we feel this illustrates the range of underlying pathology which must be considered as predispositions to this disease.
Our patient: A 40-year-old woman with hypertrophic cardiomyopathy, diagnosed at age 20, worked in Kingston, Jamaica from 1993 to 1995, where she taught impoverished children living in improvised housing. She had extensive contact with goats and unpasteurized goat milk. Although she had no documented history of Q fever, in 1996, she had a documented episode of aseptic meningitis. Q fever serologic testing was not performed at that time. In September 2000, she developed fatigue, complete heart block, fever to 102° F, and drenching sweats. Although TTE was similar to a previous study done in March 2000, TEE was remarkable for new mitral valve findings: myxomatous mitral leaflets with a one centimeter, pedunculated mass at the anterior mitral leaflet near the septum, suggesting a vegetation. She also had a thickened aortic valve with severe aortic insufficiency. Several extended blood cultures were negative. C. burnetii serum antibody titers were anti- IgG phase I ≥ 1:20148; IgG phase II ≥ 1:2048; IgM phase I 1:64; IgM phase II < 1:16. She has responded over time to extended doxycycline/hydroxychloroquine treatment with size reduction of the vegetation, and no further fever or progression of her aortic insufficiency.
Endocarditis is a serious, not uncommon, yet potentially preventable complication of acute Q fever. Every effort should be made to identify those individuals at risk, including careful, sensitive echocardiography to identify occult cardiac disease. Prolonged antibiotic therapy and/or close serological and clinical observation of these individuals are both reasonable and important strategies to prevent the progression of this disease and the development of life-threatening sequelae.
References
1. Fenollar, F, et al. Endocarditis after Acute Q Fever in Patients with Previously Undiagnosed Valvulopathies. Clin Infect Dis. 2006;42:818-821.
2. CDC. Emergency Preparedness & Response. www.bt.cdc.gov
3. Raoult D, Marrie T. Q Fever. Clin Infect Dis. 1995;20:489-495.
4. Raoult D, et al. Q Fever 1985-1998. Clinical and Epidemiologic Features of 1383 Infections. Medicine (Baltimore). 2000;79:109-123.
5. Brouqui P, et al. Chronic Q Fever. Ninety-Two Cases from France, Including 27 Cases Without Endocarditis. Arch Intern Med. 1993;153:642-648.
6. Dupont HT, et al. Q Fever Serology: Cutoff Determination for Microimmunofluorescence. Clin Diagn Lab Immunol. 1994;1:189-196.
7. Fenollar F, et al. Risks Factors and Prevention of Q Fever Endocarditis. Clin Infect Dis. 2001;33:312-316.
8. Jortner R, et al. Transesophageal Echocardiography in the Diagnosis of Q-fever Endocarditis. Am Heart J. 1994;128:827-831.
Acute Q fever may progress to endocarditis in patients with clinically silent valvulopathy. Those at risk require either extended antibiotic prophylaxis or close serological follow-up. All patients with acute Q fever should undergo transthoracic echocardiography, or in some instances transesophageal echocardiography, to exclude occult valvular abnormalities.Subscribe Now for Access
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