By Stan Deresinski, MD, FACP, FIDSA, Clinical Professor of Medicine, Stanford University, Hospital Epidemiologist, Sequoia Hospital, Redwood City, CA, Editor of Infectious Disease Alert.
Synopsis: Q fever is prevalent in farm animals, which are the prime source of infection. The diagnosis of Q fever generally requires a high index of suspicion and a depth of knowledge of serological and other methods of detection.
Sources: Georgiev M, et al. Q fever in humans and farm animals in four European countries, 1982 to 2010. Euro Surveill 2013 Feb 21;18(8). Centers for Disease Control and Prevention. National Center for Emerging and Zoonotic Infectious Diseases. Diagnosis and Management of Q Fever - United States, 2013: Recommendations from CDC and the Q Fever Working Group. MMWR 2013; 29:62(RR-03):1-30.
Q fever, caused by the Gram-negative obligate intracellular rickettsia-like Coxiella burnetii, is a zoonotic disease acquired in humans most often by inhalation of air contaminated by the excreta of infected animals, usually cattle, sheep, or goats. Close contact is not necessary. Thus, in the large recent Netherlands outbreak, living within 2 km of an affected farm was a risk factor for infection and, in one outbreak, cases were documented in individuals living 10 miles of an affected farm. Additional means of acquisition of infection include tick bites and ingestion of contaminated unpasteurized dairy product. Human-to-human transmission is rare. Sexual transmission and trans-placental infection have been reported.
The large outbreak of Q fever in the Netherlands that raged between 2007 and 2010 certainly caught the attention of many in Europe. Georgiev and colleagues have now examined available reports to assess the extent of this infectious disease in the Netherlands and 3 additional European countries (Bulgaria, France, and Germany) between 1982 and 2010.
The first report of Q fever in Europe involved cases in soldiers in the Balkans, including Bulgaria, in 1940, just a few years after the disease had first been identified in slaughterhouse workers in Australia. The first cases in Germany were identified shortly after World War II, followed by the Netherlands in 1956.
Studies of farm animals reported that the within-herd seroprevalence of C. burnetii in cattle ranged from 15% to 21% in the 4 countries, while the prevalence of seropositivity in goats ranged from 2.5% (Germany) to 88.1% (France) and that for sheep ranged from 3.5% (Netherlands) to 56.9% (Bulgaria). There were 2354 notified cases in the Netherlands in 2009, in the midst of their infamous outbreak.
Studies in humans reported that the seroprevalence rates in blood donors was 1%-4% in France, 12.2%-24.0% in the Netherlands, 22.0% in Germany, and 38.0% in Bulgaria. There were 29 outbreaks in humans recorded with (in 1964-2006) from 121 to >1000 serologically confirmed cases per outbreak and with a much larger number of cases in the 20087-2010 Netherlands epidemic.
Acute infection is symptomatic in approximately one-half of cases, with complaints of fever and other non-specific symptoms, including headache, which can be severe. Pneumonia is frequent and 85% have elevated serum hepatic transaminase levels; a variety of other manifestations are less frequent. Untreated, the fever lasts a median of 10 days, but resolves rapidly with administration of doxycycline (although doxycycline resistance has been reported). Infection during pregnancy is associated with an increased risk of miscarriage and preterm delivery.
Fewer than one in 20 patients with acute infection go on to develop chronic Q fever, with the highest risk in those with valvular heart disease, aortic aneurysm, or a vascular graft. Infective endocarditis due to C. burnetii may occur in 40% of patients with cardiac valve disease who develop acute Q fever. The usual small size of the vegetations in cases of Q fever endocarditis makes their detection by echocardiography difficult. Infection during pregnancy is associated with an increased risk of chronic illness. Persistent fatigue in the absence of evidence of active infection has been reported in some patients after acute Q fever.
Serum antibody to C. burnetii phase II antigens initially becomes detectable in most patients by the 3rd week of illness. Most cases of acute infection are diagnosed by serological testing, but to be definitive, this requires paired sera with a four-fold rise in phase II IgG antibody titer. C. burnetii DNA may be detected in blood by PCR during the first 2 weeks of illness and before antibiotic administration. The diagnosis of chronic Q fever requires a phase I antibody titer >1:1024 together with an identifiable site of infection, such as a heart valve. The need for clinical evidence beyond antibiody results is necessary because some patients with acute Q fever may develop serologic profiles consistent with chronic Q fever but that eventually regress. Thus, treatment should not be given based on increased titers alone. The organism can be detected in infected tissue by PCR, culture or immunohistochemistry.
Acute infection is treated with doxycycline for 14 days, except in pregnancy, when more prolonged trimethoprim-sulfamethoxaxole therapy is recommended. Chronic Q fever is treated with prolonged administration (18 months for endocarditis) with a combination of doxycycline and hydroxychloroquine.
Q-VAX, a human Q fever vaccine registered in Australia but not in Europe, was made available in the Netherlands in July 2010 to people at risk from chronic Q fever, including those with cardiac valve disease, aortic aneurysms, and vascular prostheses. The vaccination program, however, was first initiated in January 2011, after the outbreak had subsided. Q-VAX has been used in Australia since 1989 in humans whose occupation puts them at high risk of developing C. burnetii infection. It consists of a killed strain of a phase I strain of the organism. Studies suggest a high degree of efficacy, but with a significant risk of severe local reactions in individuals previously exposed to C. burnetii. As a consequence, potential vaccinees undergo prescreening that includes antibody and skin testing.
Q fever is uncommon in the U.S., but is undoubtedly under-diagnosed. In the absence of an obvious occupational exposure, testing for this infection is seldom done in patients with febrile respiratory illness. Testing for Q fever is part of the evaluation for culture negative endocarditis, but the detection of endocarditis itself may be difficult because of the relative insensitivity of echocardiography in this disease due to the frequently diminutive vegetations. The finding that C. burnetii may be detected in some abdominal aortic aneurysms in the absence of systemic evidence of infection is another example of the difficulties involved. On the other hand, over-diagnosis also occurs due to incorrect interpretation of antibody testing. This is why we need expert consultants.
1. Status of Q fever vaccination in humans. http://www.hse.gov.uk/aboutus/meetings/committees/acdp/021007/acdp87p7_3.pdf