Delayed Diagnosis of Chronic Q Fever and Cardiac Surgery
Delayed Diagnosis of Chronic Q Fever and Cardiac Surgery
We reviewed 3 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 presented here, C-reactive protein levels can be normal or only mildly elevated (Table). 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, as demonstrated in the cases presented here, 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. For the cases reported here, preoperative diagnosis of chronic Q fever might have prevented the second valve replacement in case-patient 1 and the delay in treatment initiation in case-patients 2 and 3. 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.
Dr Kampschreur is an infectious disease fellow and PhD student at the Division of Medicine, Department of Internal Medicine and Infectious Diseases of the University Medical Center Utrecht. Her research topic is chronic Q fever in the Netherlands.
Conclusions
We reviewed 3 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 presented here, C-reactive protein levels can be normal or only mildly elevated (Table). 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, as demonstrated in the cases presented here, 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. For the cases reported here, preoperative diagnosis of chronic Q fever might have prevented the second valve replacement in case-patient 1 and the delay in treatment initiation in case-patients 2 and 3. 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.
Dr Kampschreur is an infectious disease fellow and PhD student at the Division of Medicine, Department of Internal Medicine and Infectious Diseases of the University Medical Center Utrecht. Her research topic is chronic Q fever in the Netherlands.