Q fever endocarditis: a case report and review of the literature

The case of a 31-year-old man from Alberta diagnosed with Q fever endocarditis is presented. To the authors' knowledge, this is the first case of Q fever endocarditis diagnosed in the province of Alberta. The patient had undergone open valvulotomy for congenital aortic stenosis as an infant. He presented with congestive heart failure secondary to severe aortic regurgitation and underwent mechanical aortic valve replacement. Early failure of the mechanical prosthesis and numerous laboratory abnormalities prompted an investigation for endocarditis, which was initially negative. Markedly positive serology eventually established the diagnosis of chronic Q fever. The patient subsequently underwent a second aortic valve replacement following initiation of appropriate antimicrobials directed against Coxiella burnetii. The present report reviews the clinical presentation and diagnosis of Q fever endocarditis. It highlights the insidious and nonspecific nature of the presenting symptoms, and emphasizes the use of serology for diagnosis. Increased awareness and earlier diagnosis can significantly decrease the morbidity and mortality associated with this disease.     

Q fever bioprosthetic aortic valve endocarditis (PVE) successfully treated with doxycycline monotherapy

Q fever is a zoonotic infection caused by Coxiella burnetii. The most common clinical manifestation of acute Q fever infection is as an atypical community-acquired pneumonia. The pulmonary findings are accompanied by extrapulmonary findings, most typically an increase in serum transaminases and splenomegaly. Because C. burnetii is difficult to culture, the diagnosis of Q fever is usually made serologically. The diagnosis of acute Q fever atypical community-acquired pneumonia is made by demonstrating a fourfold or greater increase in titer between acute and convalescent specimens or by demonstrating elevated immunoglobulin (IgM) (phase II) titers. Chronic Q fever is manifested as granulomatous hepatitis or more commonly as culture-negative endocarditis (CNE). Chronic Q fever (CNE) is a difficult diagnosis because of difficulty in culturing the organism from the blood and the vegetations with Q fever CNE are small or absent. The diagnosis of chronic Q fever CNE is based on serology. Such patients commonly have highly elevated IgM and IgG titers (phase I/II) titers. Chronic Q fever CNE may involve native or prosthetic heart valves. Q fever prosthetic valve endocarditis is rare compared with native valve Q fever endocarditis. Q fever prosthetic valve endocarditis usually requires valve replacement for cure. We present a case of chronic Q fever bioprosthetic aortic valve endocarditis that was successfully treated with doxycycline monotherapy that did not require aortic valve replacement.     

Q Fever Endocarditis Presenting with Superior Mesenteric Artery Embolism and Renal Infarction

Q fever is a zoonotic disease with a reservoir in mammals, birds, and ticks. Acute cases in human beings can be asymptomatic, or they can present with a flu-like illness, pneumonia, or hepatitis. Approximately 5% of cases progress to chronic Q fever. Endocarditis, the most typical manifestation of chronic Q fever, is usually associated with small vegetations that occur in patients who have had prior valvular damage or who are immunocompromised. We present what we think is the first reported case of superior mesenteric artery embolism from Q fever endocarditis of the aortic valve, in a 39-year-old woman who needed surgical embolectomy and subsequent aortic valve replacement.     

Influence of etiology on the functional result of aortic valve replacement

The functional result of aortic valve replacement has been assessed in patients treated for isolated aortic incompetence. Using maximal oxygen uptake as an index of myocardial function, a significant difference (p less than .05) exists between the patients who had Q fever endocarditis on the one hand and those who had bacterial endocarditis or rheumatic fever on the other hand. We believe that permanent myocardial damage occurs as a result of bacterial endocarditis and rheumatic fever but because of the biological properties of Coxiella burnetii the myocardium is spared in Q fever endocarditis.     

Quiescent Q fever endocarditis exacerbated by cardiac surgery and corticosteroid therapy

Q fever endocarditis occurs in up to 11% of patients infected by Coxiella burnetti. Major clues for the diagnosis are culture-negative endocarditis, hepatic involvement, rash, and thrombocytopenia. Characteristically, the diagnosis is delayed. In our patient, Q fever endocarditis occurred without previously recorded signs of infection. Fever, rash, and hepatic involvement all occurred following aortic valve replacement. The histologic picture of the excised valve was consistent with endocarditis, and serologic tests disclosed elevated IgA and IgG antiphase 1 antibody titers against C burnetti, compatible with Q fever endocarditis. It is assumed that the exacerbation of quiescent Q fever endocarditis was caused by cardiac surgery and steroid therapy.     

Risks factors and prevention of Q fever endocarditis.

Coxiella burnetii causes acute and chronic Q fever. To evaluate the risk factors of development of chronic endocarditis following Q fever and to assess the best preventive therapy, a retrospective study of patients diagnosed as having Q fever during 1985-2000 was conducted. Twelve patients with acute Q fever who developed endocarditis and 102 patients with Q fever endocarditis were included in the study. When compared to 200 control patients with acute Q fever, preexisting valvular disease (P<10(-7)), especially a prosthetic valve (P=.01), were encountered more often among patients with endocarditis. Among patients with valvular defects, we estimate the risk of developing endocarditis to be 39%. A combination of doxycycline plus hydroxychloroquine was better at preventing the development of endocarditis than doxycycline alone (P=.009). Our results should encourage physicians to detect valvular lesions in patients with acute Q fever and to search for acute Q fever in patients with a valvulopathy and unexplained fever. A proper treatment for such patients and a scheduled follow-up should reduce the risk of developing endocarditis.     

Apparent recurrence of Q fever endocarditis following homograft replacement of aortic valve

A 39-year-old man with aortic stenosis and regurgitation developed Q fever endocarditis. After 15 weeks of chemotherapy with tetracycline the damaged aortic valve was replaced with a homograft. Organisms were present in the excised valve. Some months later the valve began to leak and the endocarditis recurred fatally. Because of the nature of rickettsial infection neither a course of chemotherapy nor an operation can guarantee a cure of Q fever endocarditis. Chemotherapy should be continued indefinitely even after operation.     

Apparent recurrence of Q fever endocarditis following homograft replacement of aortic valve

A 39-year-old man with aortic stenosis and regurgitation developed Q fever endocarditis. After 15 weeks of chemotherapy with tetracycline the damaged aortic valve was replaced with a homograft. Organisms were present in the excised valve. Some months later the valve began to leak and the endocarditis recurred fatally. Because of the nature of rickettsial infection neither a course of chemotherapy nor an operation can guarantee a cure of Q fever endocarditis. Chemotherapy should be continued indefinitely even after operation.     

Q fever endocarditis: the Mayo Clinic experience

OBJECTIVES: To report the Mayo Clinic experience of Q fever endocarditis. BACKGROUND: Q fever endocarditis is rare in North America with few case reports in the literature. The Centers for Disease Control lists Q fever as a reportable illness but does not differentiate endocarditis as a syndrome in its database. METHODS: A search of the database for elevated Q fever IgG serology at our institution was conducted from December 1980 to December 2005. Patients with elevated serologies were retrospectively identified and their medical records were reviewed to determine which cases met criteria for a diagnosis of endocarditis. RESULTS: Eight patients with elevated serology were identified. One case failed to meet criteria and was therefore excluded. All patients presented with fever and had previously diagnosed valvular disease. Only 3 patients had valvular vegetations on transesophageal echocardiography. All 7 patients were treated with antimicrobial therapy, which was not uniform. Six required surgical intervention on the affected valves, and 2 required multiple valve surgeries. Follow-up ranged from 1 to 17 years. CONCLUSIONS: Q fever endocarditis is a rare disease in the United States, where no reliable reporting exists. Q fever endocarditis involves underlying abnormal native valves or prosthetic valves. Vegetations are small or absent. Relapses are common. Surgeries are common adding to morbidity and cost. The chronicity of the syndrome and its high morbidity mandate an increased awareness of the condition in patients with culture-negative endocarditis or unexplained perivalvular leaks detected by echocardiography. Appropriate diagnosis and tailored treatment are likely to reduce the need for repeat surgeries.     

Chronic sternal wound infection and endocarditis with Coxiella burnetii.

Chronic Q fever is most commonly associated with culture-negative endocarditis and less frequently with infection of vascular grafts, infection of aneurysms, hepatitis, pulmonary disease, osteomyelitis, and neurological abnormalities. We report a case of chronic sternal wound infection, polyclonal gammopathy, and mixed cryoglobulinemia in which Q fever endocarditis was subsequently diagnosed. Polymerase chain reaction analysis of the wound tissue was positive for Coxiella burnetii DNA, and treatment of the endocarditis resulted in prompt healing of the wound. Chronic Q fever can occur without epidemiological risk factors for C. burnetii exposure and can produce multisystem inflammatory dysfunction, aberrations of the immune system, and persistent wound infections.     

Chronic Q fever endocarditis.

Eight patients with chronic Q fever endocarditis were treated with tetracycline for up to 40 months. In addition, five of these patients received co-trimoxazole. Six patients had prosthetic valves. Two patients who had Q fever endocarditis on their native valves required valve replacement because of haemodynamic difficulties: in only one did the Q fever endocarditis contribute to the haemodynamic difficulty. One patient died. It is suggested that medical treatment is continued until clinically and haematologically there is no evidence of endocarditis and the Q fever phase 1 antibody titre is less than 200. No recurrence of Q fever endocarditis has been detected in three of our patients who have now stopped treatment.     

Q fever endocarditis

Q fever endocarditis, which is seen most often in Great Britain and Australia, has been rarely observed in the United States. A patient with an eight month febrile illness who had signs and symptoms of endocarditis and serologic studies diagnostic of Q fever endocarditis is reported. A history of extensive travel makes it unclear where he originally contracted the disease. Q fever endocarditis is probably underdiagnosed and should be looked for in any case of culture negative endocarditis or chronic fever of unknown origin.     

Silent Q fever endocarditis. Report of a case]

A murmur of aortic regurgitation was discovered in an asymptomatic patient who had suffered from an acute Coxiella Burnetti infection several months before hand. Transoesophageal echocardiography, serology and direct immunofluorescence of the aortic valve confirmed the diagnosis of Q fever endocarditis. Treatment with Vibramycin and Plaquenil was instituted after aortic valve replacement. Cardiac complications of Q fever should be recognised as they may remain asymptomatic for long periods of time. Transthoracic and transoesophageal echocardiography should be widely used in acute forms of Q fever and systematic in chronic infections with Coxiella Burnetti.     

Deficient transendothelial migration of leukocytes in Q fever: the role played by interleukin-10

Chronic Q fever is characterized by deficient cell-mediated immune response, lack of granulomas, and dysregulation of the cytokine network. Altered transendothelial migration (TM) of peripheral-blood mononuclear cells might account for impaired immune response. TM of lymphocytes and monocytes was decreased in patients with Q fever endocarditis, compared with that in patients recovering from acute Q fever and in control subjects. This defect is related to interleukin (IL)-10, a cytokine involved in the chronic evolution of the disease; neutralizing anti-IL-10 antibodies corrected TM of mononuclear cells from patients with Q fever endocarditis. IL-10 may account for deficient protective immunity in patients with Q fever endocarditis by impairing TM.     

Q fever endocarditis in the United States.

A patient with Q fever endocarditis, which is almost unknown in the United States, was followed for a total of 32 months; the study was begun 3 1/2 months before aortic valve replacement. Diagnosis was confirmed by serology, visualization of Coxiella burnetii in excised aortic valve tissue by direct and immunofluorescence staining, and isolation of C. burnetii from aortic valve tissue. Serum antibodies against phase I and phase II antigens of C. burnetii were identified. Almost all phase I and phase II antibodies were IgG. These findings are compared with those in an uncomplicated case of acute Q fever. New findings on the immune response to chronic Q fever are presented.     

Q fever endocarditis

Despite a worldwide distribution of Coxiella burnetii, only single cases of Q fever endocarditis have been reported outside Great Britain and Australia. We present 10 patients; five were female, only four had a history of environmental exposure, and the mitral valve was involved as commonly as the aortic valve. One patient had congenital aortic stenosis, and three patients had a prosthetic valve. We confirm the importance of hepatic involvement, thrombocytopenia and hypergammaglobulinemia as diagnostic features. Diagnosis was established by finding an elevated complement-fixing antibody to Phase I C. burnetii antigen. Tetracycline, with or without lincomycin or cotrimoxazole, was used in nine patients, and one patient received cotrimoxazole as the sole antibiotic agent. Optimal duration of therapy is unknown. In one patient, relapse followed when treatment was stopped after 18 months. Valve replacement was necessary in five patients, because of hemodynamic problems. Five patients died, and the mean survival is 36 months with a range of five to 66 months. We suggest that Q fever endocarditis is frequently missed, and we recommend clinicians to consider the diagnosis in all cases of culture-negative endocarditis.     

The value of follow-up after acute Q fever infection

This is a case report of a 53-year-old woman involved in an outbreak of Q fever, in whom Q fever endocarditis was diagnosed 18 months after acute Q fever infection. At the time of diagnosis, she was completely asymptomatic and without screening for chronic Q fever, this severe potentially life-threatening infection would probably not have been recognised until significant valvular destruction had taken place. Early diagnosis enabled prompt, potentially curative medical treatment to start without the need for valvular heart surgery. The authors advocate that serological monitoring should be carried out every 4 months for a period of 2 years after acute Q fever and patients with high phase 1 IgG titres (>800) be investigated further and/or followed more closely depending on the clinical scenario. The case report also discusses the use of complement fixation testing in the diagnosis of Q fever endocarditis. The authors recommend that in cases of culture negative endocarditis, a single negative complement fixation test is not sufficient to exclude the diagnosis of Q fever endocarditis. Micro-immunofluorescence or repeat complement fixation testing is recommended when Q fever endocarditis is suspected clinically.     

Chronic Q fever: An ongoing challenge in diagnosis and management

Chronic Q fever is a potentially fatal disease. The current difficulty in the diagnosis of this condition is discussed in the present article. A 51-year-old woman with a history of aortic valve replacement presented with complaints of feeling generally unwell, pyrexia and occasional unproductive cough over a period of several weeks. Phase 1 immunoglobulin G titre to Coxiella burnetii was initially detected at a low level (1:320, detected using immunofluorescence) and was not considered to be significant according to the modified Duke criteria. Later in the course of her illness, the patient’s antibody titre rose to a high level (1:1280). The issues regarding current laboratory diagnosis and management of Q fever are discussed. Chronic Q fever can be associated with an inadequate serological response. Close follow-up of cases is essential. The recommended serological criteria for the diagnosis of Q fever endocarditis needs to be revisited.     

Endocarditis due to Coxiella burnetti despite the absence of obvious exposure

Q?fever is an ubiquitous zoonotic disease caused by Coxiella burnetti, an intracellular Gram negative bacteria. It may present as an acute or a chronic disease course. Endocarditis due to Coxiella burnetti represents 1 to 5% of all infectious endocarditis. We report a 41-year-old man without obvious exposure history, who presented with a Q fever endocarditis.     

Q fever: a rare cause of endocarditis

Coxiella Burnetii endocarditis is very rare. It is the main complication of the chronic form of Q fever. Blood cultures are negative and clinical presentation very variable and diagnosis is essentially based on indirect immunofluorescence serum analysis. The authors report the case of a 19 year old patient with a history of rheumatic aortic regurgitation admitted for an episode of left ventricular failure in a context of long-term pyrexia without valvular vegetations or mutilation. The antiphase I Ig G antibody levels were significant. Treatment with doxycycline and fluoroquinolone was initiated. The clinical improvement was spectacular. Three months later, the patient underwent aortic valve replacement and histological examination of the valve showed subacute endocarditis on chronically fibrotic valvular disease. This is an interesting case by its rarity and its diagnostic and therapeutic problems.