The sexual dimorphism of anticardiolipin autoantibodies in acute Q fever patients

ObjectivesQ fever is a zoonotic disease caused by Coxiella burnetii which affects men more than women (sex ratio men/women: 2.2). Acute Q fever complications are associated with elevation of anticardiolipin (aCL) antibodies. Here, we investigate the sexual dimorphism of aCL antibodies during acute C. burnetii infection.MethodsIgG aCL antibodies were evaluated at the time of Q fever serological diagnosis with enzyme-linked immunosorbent assay. Results were analysed according to sex.ResultsAmong the 1323 patients with Q fever tested for aCL, 1013 had acute Q fever (692 men/321 women) and 310 had persistent focalized infection (226 men/84 women). In cases of acute Q fever, men presented a significantly higher proportion of positive aCL antibodies (351/692, 50.7%) than women (113/321, 35.2%) (p <0.05). In addition, men had significantly higher aCL antibodies levels than women (p <0.001).ConclusionsWe highlight a relationship between sex and markers of autoimmunity during Q fever. Further investigations are necessary to better understand the mechanisms of this sexual dimorphism.     

Fluorescence in situ hybridization for detecting Coxiella burnetii in tissue samples from chronic Q fever patients

ObjectiveDetection of the intracellular bacterium Coxiella burnetii, causative agent of chronic Q fever, is notoriously difficult. Diagnosis of and duration of antibiotic treatment for chronic Q fever is partly determined by detection of the bacterium with polymerase chain reaction (PCR). Fluorescence in situ hybridization (FISH) might be a promising technique for detecting C. burnetii in tissue samples from chronic Q fever patients, but its value in comparison with PCR is uncertain. We aim to assess the value of FISH for detecting C. burnetii in tissue of chronic Q fever patients.MethodsFISH and PCR were performed on tissue samples from Dutch chronic Q fever patients collected during surgery or autopsy. Sensitivity, specificity, and overall diagnostic accuracy were calculated. Additionally, data on patient and disease characteristics were collected from electronic medical records.ResultsIn total, 49 tissue samples from mainly vascular walls, heart valves, or placentas, obtained from 39 chronic Q fever patients, were examined by FISH and PCR. The sensitivity and specificity of FISH compared to PCR for detecting C. burnetii in tissue samples from chronic Q fever patients was 45.2% (95% confidence interval (CI), 27.3% – 64.0%) and 84.6% (95% CI, 54.6% – 98.1%), respectively. The overall diagnostic accuracy was 56.8% (95% CI, 42.2% - 72.3%). Two C. burnetii PCR negative placentas were FISH positive. Four FISH results (8.2%) were deemed inconclusive because of autofluorescence.ConclusionWith an overall diagnostic accuracy of 57.8%, we conclude that FISH has limited value in the routine diagnostics of chronic Q fever.     

Q fever and pregnancy: disease, prevention, and strain specificity

The link between fetal morbidity and Q fever and the necessity of long-term antibiotics for Coxiella burnetii infection during pregnancy have been recently questioned in the Netherlands, where the clone responsible for the Q fever outbreak harbors the QpH1 plasmid. In this context, we assessed pregnancy outcomes according to antibiotic administration in a new series and compared the plasmid type between isolates associated with abortion and other clinical isolates to determine if there is a link between genotype and abortion in humans. All French patients who received a diagnosis of Q fever during pregnancy at the French National Referral Centre for Q Fever from 2006 through July 2011 were included. On the other hand, the plasmid types of 160 clinical isolates, including seven isolates from patients who experienced an abortion, were compared. The differences between the QpDV and QpH1 plasmid sequences were analyzed. Acute Q fever was a cause of fetal morbidity, and the absence of long-term cotrimoxazole therapy was associated with fetal death (p?<?0.0001). Genotypic analysis showed that the QpDV plasmid was more frequent in isolates associated with abortion (p?=?0.03). A comparison of the plasmid sequences revealed that four QpDV proteins had no direct counterparts in QpH1, with two whose functions were not present in QpH1. The different obstetrical morbidity of C. burnetii relative to different geographical areas could be related to strain specificity, possibly based on differences in plasmid sequences, or to a failure of public health authorities to detect early miscarriages.     

Q fever and lymphadenopathy: report of four new cases and review

Coxiella burnetii, the causative agent of Q fever, is responsible for various clinical syndromes, but lymphadenitis has been described during Q fever in only three recent case reports. Four new cases of acute Q fever associated with lymphadenopathy are reported here, and these cases are discussed along with the three previously reported cases. Coxiella burnetii was isolated for the first time from a lymph node. Q fever should be considered an etiologic agent of lymphadenitis.     

Single nucleotide polymorphism (SNP) rs3751143 in P2RX7 is associated with therapy failure in chronic Q fever while rs7125062 in MMP1 is associated with fewer complications

ObjectivesChronic Q fever is a persistent infection with the intracellular bacterium Coxiella burnetii. Development of chronic Q fever is associated with single nucleotide polymorphisms (SNPs) in genes encoding for pattern recognition receptors, for phagolysosomal pathway components and for matrix metalloproteinases (MMPs). We evaluated the association of SNPs in these innate-immunity and MMP genes with clinical outcomes.MethodsSNPs were selected from previous association studies and analysed in a cohort of patients with chronic Q fever. The primary outcome was all-cause mortality; secondary outcomes were therapy failure and chronic Q fever–related complications. Subdistribution hazard ratios (SHR) were calculated.ResultsNineteen SNPs were analysed in 134 patients with proven and 29 with probable chronic Q fever. In multivariable analysis, none of the selected SNPs was associated with all-cause mortality. However, SNP rs3751143 located in P2RX7 appeared to be associated with therapy failure (SHR 2.42; 95% confidence interval, 1.16–5.05; p 0.02), which is in line with other reports, showing that a loss of function of the P2X7 receptor leads to inefficient killing of intracellular organisms. In addition, SNP rs7125062 located in MMP1, involved in the cleavage of extracellular matrix, was associated with fewer chronic Q fever–related complications such as acute aneurysms (SHR 0.49; 95% confidence interval, 0.29–0.83; p 0.008).ConclusionsA polymorphism in P2RX7, known to lead to loss of function of the receptor and inefficient killing of intracellular organisms, and a polymorphism in MMP1 were respectively associated with more therapy failures and fewer complications such as acute aneurysms in patients with chronic Q fever.     

Genetic variations in innate immunity genes affect response to Coxiella burnetii and are associated with susceptibility to chronic Q fever

ObjectivesChronic Q fever is a persistent infection, mostly of aortic aneurysms, vascular prostheses or damaged heart valves, caused by the intracellular bacterium Coxiella burnetii. Only a fraction of C. burnetii-infected individuals at risk develop chronic Q fever. In these individuals, a defective innate immune response may contribute to the development of chronic Q fever. We assessed whether genetic variations in genes involved in the killing machinery for C. burnetii by macrophages, contribute to the progression to chronic Q fever.MethodsThe prevalence of 66 single nucleotide polymorphisms (SNPs) in 31 genes pivotal in phagolysosomal maturation, bacterial killing and autophagy, was determined in 173 chronic Q fever patients and 184 controls with risk factors for chronic Q fever and serological evidence of a C. burnetii infection. Associations were detected with univariate logistic regression models. To assess the effect of these SNPs on innate responses to C. burnetii, the C. burnetii-induced cytokine production and basal reactive oxygen species production of healthy volunteers was determined.ResultsRAB7A (rs13081864) and P2RX7 loss-of-function SNP (rs3751143) were more common in chronic Q fever patients than in controls. RAB5A (rs8682), P2RX7 gain-of-function SNP (rs1718119), MAP1LC3A (rs1040747) and ATG5 (rs2245214) were more common in controls. In healthy volunteers, RAB7A (rs13081864) and MAP1LC3A (rs1040747) influenced the C. burnetii-induced cytokine production. RAB7A (rs13081864) modulated basal reactive oxygen species production.ConclusionsRAB7A (rs13081864) and P2RX7 (rs3751143) are associated with the development of chronic Q fever, whereas RAB5A (rs8682), P2RX7 (rs1718119), MAP1LC3A (rs1040747) and ATG5 (rs2245214) may have protective effects.     

Q fever and spontaneous abortion

Q fever, caused by Coxiella burnetii, may result in abortions in infected animals and pregnant women. However, the role that Q fever plays in spontaneous abortions is still unknown. This study examined the association between Q fever serology and abortion in a region where Q fever is endemic. A case–control population-based study was conducted in General Yagüe Hospital (Burgos area, Spain) between June 2009 and July 2010. A total of 801 samples from 500 pregnant women were tested, of whom 273 had a spontaneous abortion and 227 gave birth. IgG and IgM antibody titres against Q fever were determined in their two phases (I and II) by immunofluorescence assay. Seropositivity (phase I IgG ≥1:16 or phase II IgG ≥1:80) was detected in 88/273 (32.2%) cases and 53/227 (23.3%) controls; p <0.01, OR 1.5, 95% CI 1.0–2.3. Seropositivity for both phases of IgG, compatible with recent or persistent infection, was detected in 55 (20.1%) vs 22 (9.7%); p <0.001, OR 2.3, 95% CI 1.3–3.9. High phase II IgG antibodies compatible with active or recent infection (titres ≥1:160) were detected in 27 (9.6%) vs 7 (3.1%); p <0.002, OR 3.4, 95% CI 1.4–8.0, respectively. Q fever was diagnosed in 14 (5.1%) cases. The risk of abortion associated with serological markers of active or recent Q fever in pregnant women was measurable and noticeable in this population, and accounted for 12% (95% CI 4–21%).     

Chronic Q fever-related complications and mortality: data from a nationwide cohort

ObjectivesChronic infection with Coxiella burnetii (chronic Q fever) can cause life-threatening conditions such as endocarditis, infected vascular prostheses, and infected arterial aneurysms. We aimed to assess prognosis of chronic Q fever patients in terms of complications and mortality.MethodsA large cohort of chronic Q fever patients was assessed to describe complications, overall mortality and chronic Q fever-related mortality. Chronic Q fever-related mortality was expressed as a case fatality rate (number of chronic Q fever-related deaths/number of chronic Q fever patients).ResultsComplications occurred in 166 of 439 (38%) chronic Q fever patients: in 61% of proven (153/249), 15% of probable (11/74), and 2% of possible chronic Q fever patients (2/116). Most frequently observed complications were acute aneurysms (14%), heart failure (13%), and non-cardiac abscesses (10%). Overall mortality was 38% (94/249) for proven chronic Q fever patients (median follow-up 3.6 years) and 22% (16/74) for probable chronic Q fever patients (median follow-up 4.7 years). The case fatality rate was 25% for proven (63/249) chronic Q fever patients and 4% for probable (3/74) chronic Q fever patients. Overall survival was significantly lower in patients with complications, compared to those without complications (p <0.001).ConclusionsIn chronic Q fever patients, complications occur frequently and contribute to the mortality rate. Patients with proven chronic Q fever have the highest risk of complications and chronic Q fever-related mortality. Prognosis for patients with possible chronic Q fever is favourable in terms of complications and mortality.     

Acute Acalculous Cholecystitis Associated with Q Fever: Report of Seven Cases and Review of the Literature

Q fever is a worldwide-occurring zoonosis caused by Coxiella burnetii. There are various clinical manifestations of acute Q fever, of which acute cholecystitis is a very rare clinical presentation. This study reports seven cases of acute cholecystitis associated with Coxiella burnetii and reviews two other cases from the literature. All patients were admitted to hospital for fever and abdominal pain in the right upper quadrant. Abdominal echography showed a distended gallbladder with biliary sludge without concrements in eight cases and with a single stone in one case. Diagnosis was made by specific serological investigation (microimmunofluorescence assay) for Coxiella burnetii. All nine patients were cured, six after laparoscopic cholecystectomy and three with antibiotics only. Histological examination of the gallbladders showed inflammation in five cases, although Coxiella burnetii was not detected by immunohistochemistry. The results show that laboratory investigations in patients admitted to hospital for symptoms consistent with acute acalculous cholecystitis should include a systematic search for Coxiella burnetii. Electronic Publication     

High Coxiella burnetii DNA Load in Serum during Acute Q Fever Is Associated with Progression to a Serologic Profile Indicative of Chronic Q Fever

PCR is very effective in diagnosing acute Q fever in the early stages of infection, when bacterial DNA is present in the bloodstream but antibodies have not yet developed. The objective of this study was to further analyze the diagnostic value of semiquantitative real-time PCR (qPCR) in diagnosing acute Q fever in an outbreak situation. At the Jeroen Bosch Hospital, in 2009, qPCR testing for Coxiella burnetii DNA was performed for 2,715 patients suspected of having acute Q fever (positive, n = 385; negative, n = 2,330). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the qPCR assay were calculated for patients with negative qPCR results with a follow-up sample obtained within 14 days (n = 305) and qPCR-positive patients with at least one follow-up sample (n = 369). The correctness of the qPCR result was based on immunofluorescence assay results for samples submitted for qPCR and follow-up testing. The sensitivity of the Q fever qPCR assay was 92.2%, specificity 98.9%, PPV 99.2%, and NPV 89.8%. Patients who later developed serologic profiles indicative of chronic Q fever infection had significantly higher C. burnetii DNA loads during the acute phase than did patients who did not (P < 0.001). qPCR testing is a valuable tool for the diagnosis of acute Q fever and should be used in outbreak situations when the onset of symptoms is <15 days earlier. Special attention is needed in the follow-up monitoring of patients with high C. burnetii DNA loads during the acute phase, as this might be an indicator for the development of a serologic profile indicative of chronic infection.     

Dysregulation of Serum Gamma Interferon Levels in Vascular Chronic Q Fever Patients Provides Insights into Disease Pathogenesis

A large community outbreak of Q fever occurred in the Netherlands in the period 2007 to 2010. Some of the infected patients developed chronic Q fever, which typically includes pathogen dissemination to predisposed cardiovascular sites, with potentially fatal consequences. To identify the immune mechanisms responsible for ineffective clearance of Coxiella burnetii in patients who developed chronic Q fever, we compared serum concentrations of 47 inflammation-associated markers among patients with acute Q fever, vascular chronic Q fever, and past resolved Q fever. Serum levels of gamma interferon were strongly increased in acute but not in vascular chronic Q fever patients, compared to past resolved Q fever patients. Interleukin-18 levels showed a comparable increase in acute as well as vascular chronic Q fever patients. Additionally, vascular chronic Q fever patients had lower serum levels of gamma interferon-inducible protein 10 (IP-10) and transforming growth factor β (TGF-β) than did acute Q fever patients. Serum responses for these and other markers indicate that type I immune responses to C. burnetii are affected in chronic Q fever patients. This may be attributed to an affected immune system in cardiovascular patients, which enables local C. burnetii replication at affected cardiovascular sites.     

The prognostic value of serological titres for clinical outcomes during treatment and follow-up of patients with chronic Q fever

ObjectivesWe assessed the prognostic value of phase I IgG titres during treatment and follow-up of chronic Q fever.MethodsWe performed a retrospective cohort study to analyse the course of phase I IgG titres in chronic Q fever. We used a multivariable time-varying Cox regression to assess our primary (first disease-related event) and secondary (therapy failure) outcomes. In a second analysis, we evaluated serological characteristics after 1 year of therapy (fourfold decrease in phase I IgG titre, absence of phase II IgM and reaching phase I IgG titre of ≤1:1024) with multivariable Cox regression.ResultsIn total, 337 patients that were treated for proven (n = 284, 84.3%) or probable (n = 53, 15.7%) chronic Q fever were included. Complications occurred in 190 (56.4%), disease-related mortality in 71 (21.1%) and therapy failure in 142 (42.1%) patients. The course of phase I IgG titres was not associated with first disease-related event (HR 1.00, 95% CI 0.86–1.15) or therapy failure (HR 1.02, 95% CI 0.91–1.15). Similar results were found for the serological characteristics for the primary (HR 0.97, 95% CI 0.62–1.51; HR 1.12, 95% CI 0.66–1.90; HR 0.99, 95% CI 0.57–1.69, respectively) and secondary outcomes (HR 0.86, 95% CI 0.57–1.29; HR 1.37, 95% CI 0.86–2.18; HR 0.80, 95% CI 0.48–1.34, respectively).DiscussionCoxiella burnetii serology does not reliably predict disease-related events or therapy failure during treatment and follow-up of chronic Q fever. Alternative markers for disease management are needed, but, for now, management should be based on clinical factors, PCR results, and imaging results.     

Lack of pathotype specific gene in human Coxiella burnetii isolates

Human Q fever, due to the obligate intracellular bacterium Coxiella burnetii may be acute or chronic. The acute form is rarely fatal, although the chronic form, mostly represented by chronic Q fever endocarditis, is severe and usually fatal in lack of appropriate treatment. A correlation between the human disease state and plasmid types has been described, and specific DNA sequences unique to each plasmid type and which would code for specific pathotypes have been characterized. Because this gene specificity of the pathogenesis was hypothesized only on a small number of isolates, we evaluated seven reference isolates and 30 recent C. burnetii isolates from France for which all clinical data were available using the polymerase chain reaction by employing two specific primer sets. Our studies indicate that the previously described CbhE′ plasmid-gene is not unique to C. burnetii isolates associated with acute disease, which would mean that the hypothesis of the correlation between gene specificity and pathotype has to be revised.     

Emerging evidence for Q fever in humans in Denmark: role of contact with dairy cattle

Until recently, Q fever was notified in very low numbers annually in Denmark and it was always considered to be acquired abroad. Preliminary reports now describe Coxiella burnetii in milk samples from Danish dairy cattle. Serum samples of a large cohort of farmers, veterinarians, inseminators and hoof trimmers, all having occupational contact with dairy cattle, were tested for the presence of IgG to phase I and phase II antigens of C. burnetii. In 39 of 359 individuals studied (11%), the presence of antibodies to C. burnetii was found. Veterinarians had the highest seropositivity rate (36%). This survey suggests that C. burnetii is a recently recognized domestic infection in Denmark and that risk of infection is associated with occupation.     

Emergence of Q Fever Arthritis in France

Osteoarticular infection is an uncommon presentation of Q fever. Positron emission tomography (PET) scanning is a valuable tool for the diagnosis of Coxiella burnetii graft prosthesis infection and endocarditis. Our objective was to test a series of culture-negative osteoarticular samples using molecular assays for Coxiella burnetii. We tested for C. burnetii by molecular assays targeting the IS1111 and the IS30A spacer regions, using culture-negative osteoarticular samples obtained in our laboratory between January 2011and December 2012. We examine a total of 1,410 osteoarticular samples, and we observed two cases of arthritis and subacromial bursitis caused by C. burnetii. The infections were localized using PET scanning, and the diagnosis was confirmed through serology. For one, a C. burnetii strain with a multispacer sequence type 8 genotype was isolated from synovial fluid culture. Q fever articular infections could be undiagnosed because of the long evolution of articular attack, and patients with high antibody titers against C. burnetii should be tested using PET scanning to localize the site of infection.     

Genotypic diversity of clinical Coxiella burnetii isolates from Portugal based on MST and MLVA typing

The temporal and spatial diversity of Coxiella burnetii genotypes associated with human and animal disease in Portugal was analysed using a 6-locus multiple-locus variable-number tandem repeat analysis (MLVA) and a 10-locus multi-spacer sequence typing (MST) panel. Fifteen cultured C. burnetii isolates from 13 Q fever patients and a stillborn goat and 6 additional PCR-positive ruminant tissue samples obtained during 2006–2011 were included in this study. Seven MLVA genotypes (types S–Y) were obtained, including 4 new MLVA types (U, V, W, and X), all corresponding to 3 MST profiles (types 4, 8, and 13) previously reported from France and Spain. MLVA types U–Y, all belonging to MST type 4, were found in acute Q fever patients from the districts of Évora, Faro, Lisbon, and Setúbal. Different MLVA types were associated with goats from Castelo Branco district (S) and chronic Q fever patients from both Castelo Branco and Lisboa districts (S and T), matching with MST types 13 and 8, respectively. In conclusion, a genotypic diversity of C. burnetii consistent with a non-outbreak situation was identified. The involvement of different genotypes in acute and chronic Q fever was found, linking one of the chronic genotypes to goats from the eastern region of the country.     

Q fever endocarditis: diagnostic approaches and monitoring of therapeutic effects

Summary The scope of current diagnostic methods for Q fever endocarditis includes serology, direct demonstration of Coxiella burnetii in the resected heart valve tissue, and animal inoculation studies. Illustrated by a clinical case report, the different methods are presented and discussed. Serology represents the primary method, using the techniques of complement fixation, indirect immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). The latter two techniques allow the detection of immunoglobulins G, M, and A to the phase I and II antigens of C. burnetii. After cardiac surgery, we visualized C. burnetii on smears and specifically stained it on histologic sections of the resected heart valve by light and electron microscopic immunohistochemistry. In addition, seroconversion in animals after inoculation with valve specimens confirmed the presence of C. burnetii in the heart valve. The antibody titers determined by ELISA correlated well with the patient's clinical course during the treatment period. Therefore it is suggested that its usefulness for monitoring the efficacy of antimicrobial agents in patients with Q fever endocarditis should be further evaluated.Abbreviations IFA indirect fluorescent antibody test - ELISA enzyme-linked immunosorbent assay - CF complement fixation - TMP/SMX trimethoprim/sulfamethoxazole - CDC Center for Disease Control - PAP peroxidase-antiperoxidase - PBS phosphate-buffered saline     

Risk factors of Q fever in sheep and goat flocks with history of abortion

The purpose of this study was to determine the individual- and flock-level risk factors of Q fever in sheep and goat flocks in Iran. A total of 970 sera including 803 ovine and 167 caprine samples from 43 sheep and goat flocks in the Southwest, Central, and Western Iran were collected randomly. A questionnaire was administered to each visited farm to gather information for investigation of suggested risk factors. The CHEKIT Q fever ELISA kit was used to identify specific antibodies against Coxiella burnetii in sheep and goats. The results showed that the flock level prevalence of Q fever was 100 %. Among the studied risk factors, significant association was observed for seropositivity with area, breed, and parity on individual level and presence of ticks on flock level. Central Iran significantly had the highest prevalence followed by Southwest and Western Iran which could be due to favorable climatic conditions for aerosol transmission of C. burnetii in this area. Native breed had the highest prevalence (28.9 %) of Q fever followed by mixed (22.2 %) and Afshari (13.3 %) breed (P?<?0.05). Seropositivity increased with parity, and third parity animals had the highest prevalence (29.3 %). There was significant association between presence of tick on the farm with seroprevalence of Q fever; farms with tick contamination had higher prevalence compared to tick-free farms (27.3 vs 20.3 %, respectively, P?=?0.04). In conclusion, the present study demonstrated the relatively high prevalence of Q fever in sheep and goat flocks in Iran. Further, the native breed and third parity animals on individual level and presence of tick on flock level are considered the most important risk factors for C. burnetii infection.     

Neutrophils Play an Important Role in Protective Immunity against Coxiella burnetii Infection

Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes the zoonotic disease Q fever. Although Q fever is mainly transmitted by aerosol infection, study of the immune responses in the lung following pulmonary C. burnetii infection is lacking. Neutrophils are considered the first immune cell to migrate into the lung and play an important role in host defense against aerosol infection with microbial pathogens. However, the role of neutrophils in the host defense against C. burnetii infection remains unclear. To determine the role of neutrophils in protective immunity against C. burnetii infection, the RB6-8C5 antibody was used to deplete neutrophils in mice before intranasal infection with C. burnetii. The results indicated that neutrophil-depleted mice developed more severe disease than their wild-type counterparts, suggesting that neutrophils play an important role in host defense against C. burnetii pulmonary infection. We also found that neither CXC chemokine receptor 2 (CXCR2) nor interleukin-17 (IL-17) receptor (IL-17R) deficiency changed the severity of disease following intranasal C. burnetii challenge, suggesting that keratinocyte-derived chemokine and IL-17 may not play essential roles in the response to C. burnetii infection. However, significantly higher C. burnetii genome copy numbers were detected in the lungs of IL-1R^−/− mice at 14 days postinfection. This indicates that IL-1 may be important for the clearance of C. burnetii from the lungs following intranasal infection. Our results also suggest that neutrophils are involved in protecting vaccinated mice from C. burnetii challenge-induced disease. This is the first study to demonstrate an important role for neutrophils in protective immunity against C. burnetii infection.     

Identification of protein candidates for the serodiagnosis of Q fever endocarditis by an immunoproteomic approach

Q fever is a worldwide zoonosis caused by Coxiella burnetii bacterium. Two clinical forms are present: acute Q fever and chronic disease, including endocarditis. Currently, the diagnosis of Q fever endocarditis is based on the detection of anti-phase I antibodies. The objective of the study was to identify candidate proteins for the serological diagnosis of endocarditis due to C. burnetii. The immunoreactivities of sera from 12 patients with C. burnetii infections, including the sera from patients with endocarditis and with the acute clinical form of Q fever, were compared with those of three control subjects who did not have Q fever. We identified 29 candidate antigenic proteins by mass spectrometry. Two proteins, arginine repressor and OmpH, were recognised exclusively by the sera of patients with Q fever endocarditis. These proteins are promising candidates for the development of serodiagnostic assays for Q fever endocarditis.