Immunohistologic Demonstration of Coxiella burnetii in the Valves of Patients with Q Fever Endocarditis Philippe Brouaui, MD, PhD, Marseille, France, J. Stephen Dumler, MD, Baltimore, Maryland, Did&; Raoult, ‘Mb, PhD, Marseille, France PURPOSE: Cardiac valves that were resected from patients with Q fever endocarditis were examined by immunohistologic methods to correlate the presence of Coxiella burnetii in the valves with the histopathologic, serologic, microbiologic, and clinical findings. PATIENTS: Seventeen patients with serologic and microbiologic or clinical evidence of Q fever endocarditis who presented with cardiac failure secondary to valvular dysfunction and required valve replacement surgery were selected from the clinical records of the Unite des Rickettsies, Marseille, France. METHODS: Clinical data were collected by questionnaire. Serologic characterization was performed by indirect immunofluorescent antibody testing; shell vial cultivation of C burnetii was per;formedfrom resected valves and blood when available; and pathologic and immunohistologic testing for localization of C burnetii in resected valves were performed by standard methods using both polyclonal and monoclonal C burnetii antibodies. RESULTS: Demographic and clinical findings were typical of patients with Q fever endocarditis. Pure chronic inflammation or mixtures of acute and chronic inflammation were the most frequent inflammatory patterns present and were associated with fibrin deposition, necrosis, and fibrosis. Well-formed granulomas were not present, but the granulomatous inflammation observed in 6 of these 17 patients was associated with foreign body reactions or with valvular calcifications secondary to preexisting valvular damage and could not be directly attributed to infection. C burnetii were present nearly exclusively in macrophages in sites of inflammation and valvular injury and only in the vegetations. lmmunohistologic results confirmed the valve culture results in 10 of 14 cases. From the Unite des Rickettsies (PB, DRJ, Fact& de Medecine, Marseille, France, and the Department of Pathology (JSD), University of Maryland School of Medicine, Baltimore, Maryland. This work was suooorted in oart bv the Centre National de la Recherche Scientifioue (CNRSj, EPJb054. Reauests for reorints should be addressed to Didier Raoult, MD, PhD, Unite’des Rickettsies, Faculte de Medecine, Avenue J. Moulin] 13385 Marseille cedex 5, France. Manuscript submitted December 16, 1993 and accepted in revised form March 10, 1994 CONCLUSION: The pathologic findings in the valves of patients with Q fever endocarditis are nonspecific. The presence of empty or foamy macrophages is suggestive of infection by C burnetii; however, definitive identification rests upon the demonstration of the organism in the tissue by immunohistology. Q fever endocarditis probably results from infection of previously damaged heart valves. The finding of the absence of granulomas in these cases contrasts with the pathoiogic findings in patients with acute, self-limited Q fever and suggests an aberrant host immune response that permits persistence of the bacterium and chronic, prolonged valvular infection and injury. The pathologic findings and distribution of C burnetii in the damaged valve tissues explain the clinical findings of valve failure and occasional embolic episodes, as well as the frequent ability to isolate C burnetii from the peripheral blood of infected patients. lmmunohistology may be a valuable diagnostic tool in places where serology and culture are not available. Q fever is a disease caused by the rickettsia, CoxieUa burnetii. Despite reports of transmis- sion by parturient cats or wild rabbits,’ the most im- portant reservoirs of infection are generally accepted to be sheep and cattle.2 Transmission more likely oc- curs by the inhalation of infectious aerosols than by the ingestion of contaminated milk products, a situa- tion confounded by the prolonged survival of C bur- netii in the environment. The disease is a worldwide problem, and currently two clinical forms have been described: an acute illness with pneumonitis, granu- lomatous hepatitis, or undifferentiated fever, and a chronic illness in which culture-negative bacterial en- docarditis is the most frequent clinical expressionas C burnetii displays a phase variation phenomenon similar to that described for the Enterobacteriaceae, in which the smooth-type, phase I lipopolysaccharide (LPS) is found in the wild-type strains, and the rough- type phase II LPS are obtained only after in vitro cul- tivation or other laboratory manipulations. A high an- tibody titer against the phase I antigen of C bumetii is diagnostic of chronic Q fever.” Chronic Q fever is a seldom diagnosed disease; as of 1989, only 234 cases had been reported in the lit- erature.6 The pathology of Q fever endocarditis in humans has only infrequently been reported in the lit- November 1994 The AmericanJournal of Medicine@ Volume97 451