Delayed diagnosis of chronic Q fever and cardiac valve surgery

Untreated chronic Q fever causes a high number of complications and deaths. We reviewed cases of chronic Q fever that were not diagnosed until after the patients underwent cardiac valve surgery. In epidemic areas, Q fever screening of valve surgery patients secures early initiation of treatment and can prevent illness and death. Q fever, a zoonosis caused by the intracellular gram-negative bacterium Coxiella burnetii, occurs in outbreaks and is prevalent worldwide. Q fever has acute and chronic stages. Acute Q fever is a self-limiting febrile disease occurring in 40%–50% of C. burnetii–infected persons. Chronic Q fever can develop years after primary infection and occurs in 1%–5% of C. burnetii–infected persons. The most critical manifestations of chronic Q fever are endocarditis and infections of vascular prosthesis and aortic aneurysms. Persons with pre-existing valvular cardiac disease have a reported 40% risk of Q fever endocarditis when infected with C. burnetii.

During 2007–2010, an outbreak of >4,000 cases of acute Q fever occurred in the Netherlands. To increase understanding of the role of Q fever in valvular cardiac disease, we reviewed 3 cases of chronic Q fever and valvular cardiac disease requiring surgery in patients from the Netherlands. The diagnosis of chronic Q fever was not made until after the patients had elective cardiac valve surgery for progressive valvular dysfunction. We elected cases of chronic Q fever and valvular cardiac disease requiring surgery. The diagnosis of chronic Q fever was not made until after the elective surgery. Early diagnosis and antimicrobial drug treatment of Q fever endocarditis might have prevented surgery. Symptoms of Q fever endocarditis can be nonspecific, and vegetations are usually absent or small. As observed in the cases reviewed, C-reactive protein levels can be normal or only mildly elevated. The most frequent signs of Q fever endocarditis are a new valvular insufficiency or worsening of preexisting valvular insufficiency. C. burnetii–infected cardiac valves can appear normal on visual inspection, and on histologic evaluation.

Diagnosis of chronic Q fever is challenging. Chronic infection is determined on the basis of serologic testing and PCR of blood samples and, if available, tissue samples. In the absence of acute Q fever, PCR results positive for C. burnetii in blood or tissue prove chronic infection; however, the sensitivity of this test is only 50%–60% in patients with chronic Q fever. When cultured in cells, C. burnetii exhibits antigenic variation in which the virulent variant, called phase I, shifts to an avirulent variant, called phase II. During acute infection, antibodies to phase II antigens are detected first; persisting high levels of antibodies to phase II, and especially phase I antigens, are indicative of chronic Q fever. A phase I IgG titer >800 or >1,024, depending on the type of immunofluorescence assay used, has been internationally accepted for the serologic diagnosis of chronic Q fever.

Long-term antimicrobial drug treatment, preferably doxycycline plus hydroxychloroquine, is the treatment of choice for chronic Q fever. Treatment should continue for 18 months for native valves and 24 months for prosthetic valves, until a 4-fold decrease of phase I IgG titers and a complete clearance of phase II IgM are reached. If phase I IgG titers remain high or phase II IgM is detectable, treatment should be extended. The rates of morbidity and mortality among people with chronic Q fever are high, reaching >60% if treatment is delayed or not initiated. With adequate treatment, the mortality rate for Q fever endocarditis has declined to 5%. Chronic Q fever involving prosthetic valves is associated with a higher mortality rate, longer treatment, and elevated chance of complications. We advise preoperative serologic screening for chronic Q fever in all patients undergoing elective cardiac valve surgery in Q fever epidemic areas. If serologic test results are positive for C. burnetii antibodies, PCR of the excised valve should be performed.

Emerging Infectious Diseases
May 14, 2013

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