Coxiella burnetii infection among subjects infected with HIV type 1 in the Central African Republic

Sixty-six sera from HIV-1-seropositive adult African subjects and 49 sera from HIV-seronegative age and sex matched healthy African controls living in Bangui, Central African Republic, were screened forCoxiella burnetii antibody by an indirect immunofluorescent antibody test. 16.7 % of HIV-infected patients and 16.3 % of the HIV-negative controls had positive IgG titres, with no significant difference between the two groups. Two of the seven HIV-infected patients seropositive forCoxiella burnetii for whom clinical data was available had a medical history compatible with symptomatic Q fever. These findings indicate that there is a high degree of exposure toCoxiella burnetii infection in Bangui. In individuals co-infected with HIV andCoxiella burnetii, cellular immunosuppression could favour symptomatic Q fever. Physicians should be aware of the possibility of symptomaticCoxiella burnetii infection among HIV-infected people, particularly in endemic regions for both infections such as in sub-saharan Africa.     

Comparison of immunofluorescence with enzyme immunoassay for detection of Q fever

To evaluate enzyme immunoassay (EIA) as an alternative to indirect immunofluorescence assay (IFA) to screen for Q fever in humans, 157 serum samples from patients suspected of having the disease were tested for immunoglobulin G antibodies toCoxiella burnetii. The agreement between the tests and the sensitivity of EIA were excellent (96.8% and 98.4%, respectively) when an IFAtiter of > 1/160 was considered positive. All serum samples with a titer of > 1/320 in the IFA were also positive by the EIA. The EIA seems to be an acceptable alternative to IFA for screening for Q fever.     

Validation of an enzyme immunoassay for serodiagnosis of acute Q fever

An enzyme immunoassay was validated for the serodiagnosis of acute Q fever. Minimum positive tests were determined for both serial dilutions and a single dilution of patient sera. To establish the specificity of the test, 152 serum samples were tested from individuals with no evidence of pastCoxiella burnetii infection. Diagnostic titers were set at 128 for the IgM and IgG responses to phase I, at 512 for the IgM response to phase II and at 1,024 for the IgG response to phase IICoxiella burnetii. These titers gave a falsepositive rate of 1 %. Alternatively, testing a single dilution of sera (1:128) gave specificities ranging from 97.3 to 98.7 %. Tests with the greatest sensitivities, using serially diluted early convalescent-phase sera, were the IgM (84 %) and IgG (80 %) responses to phase IICoxiella burnetii. At a single serum dilution, 92 % of early convalescent sera had a positive IgG response to phase IICoxiella burnetii. With a high specificity and good sensitivity, the EIA can be used to diagnose acute Q fever with a single convalescent serum specimen. The duration of a positive response was greater than five years.     

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.     

Acute meningoencephalitis as the sole manifestation of Q fever

The case of a 25-year old man who presented with meningoencephalitis as the sole clinical manifestation of Q fever is described. Serological studies revealed the presence of IgM and IgG antibodies toCoxiella burnetii. The patient responded favourably to a ten-day course of i.v. ceftriaxone and was discharged without any neurological sequelae.     

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     

Conventional viral cultures and shell vial assay for diagnosis of apparently culture-negativeCoxiella burnetii endocarditis

A patient with culture-negative endocarditis was diagnosed with Q fever endocarditis based on the results of serological tests and positive leukocyte cultures obtained using conventional viral cultures and the shell vial technique. This case report suggests that isolation ofCoxiella burnetii from blood may allow better diagnostic and therapeutical evaluation of patients with Q fever endocarditis. The use of both conventional and shell vial viral cultures is recommended for the isolation ofCoxiella burnetii from the blood of patients with apparently culture-negative endocarditis.     

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.     

Real-Time PCR with Serum Samples Is Indispensable for Early Diagnosis of Acute Q Fever

The world''s largest Q fever outbreak is ongoing in The Netherlands with around 3,000 confirmed cases since the first half of 2007. Increased awareness has resulted in early referral of patients for diagnostics. An important drawback to serological diagnosis of acute Q fever is the lag phase in antibody response. Therefore, we evaluated the performance of a real-time PCR for detection of Coxiella burnetii DNA using serum samples from patients with acute Q fever. PCR, targeting IS1111, was retrospectively performed on acute-phase and follow-up convalescent-phase serum samples from 65 patients with acute Q fever as diagnosed by immunofluorescence assay. The results obtained by PCR were related to disease stage as defined by subsequent appearance of phase II IgM, phase II IgG, phase I IgM, and phase I IgG (IgM-II, IgG-II, IgM-I, and IgG-I, respectively) antibodies and time since onset of disease. In addition, we analyzed seronegative acute-phase serum samples from patients with inconclusive Q fever serology, because no convalescent-phase serum samples were available. PCR was scored positive in 49/50 (98%) seronegative sera, 9/10 (90%) sera with isolated IgM-II antibodies, 3/13 (23%) sera with IgM-II/IgG-II antibodies, 2/41 (5%) sera with IgM-II/IgG-II/IgM-I antibodies, 0/15 (0%) sera with IgM-II/IgG-II/IgM-I/IgG-I antibodies, and 0/1 (0%) serum sample with IgM-II/IgG-II/IgG-I antibodies. The latest time point after onset of disease in which C. burnetii DNA could be detected was at day 17. In patients with inconclusive Q fever serology, PCR was positive in 5/50 (10%) cases. We conclude that real-time PCR with serum samples is indispensable for early diagnosis of acute Q fever. C. burnetii DNA becomes undetectable in serum as the serological response develops.Q fever, an infection caused by the bacterium Coxiella burnetii, results in a self-limiting disease in 40 to 50% of infected cases. Pneumonia is the predominant presenting symptom in acute Q fever, although fever and hepatitis are also frequently observed (9, 10). Failure to diagnose acute Q fever and delay in treatment may lead to prolonged morbidity and increased hospital admission rates (4, 7, 11, 14).During three consecutive years, large Q fever epidemics occurred in an area in the south of The Netherlands where the disease was formerly not prevalent (11). In 2007 there were a total of 191 confirmed cases reported, in 2008 a total of 998, and in 2009 more than 2,000 confirmed cases were reported, which ranks the outbreak as the largest Q fever epidemic recorded to date. The affected area has a large density of dairy goats, of which a number have tested positive for Q fever. Next to the differences in sizes of the epidemics, the interval between onset of disease and date of diagnosis decreased from a median of 77 days in 2007 to 29 days in 2008 and 17 days in 2009 (12). Moreover, the hospital admission rates were reduced from 40% in 2007 to 20% in 2008 (11). Both observations are most likely due to increased awareness among physicians in the affected area resulting in early submission of clinical samples to the laboratory, subsequent earlier diagnosis, and probably fewer undiagnosed cases. The majority of diagnostic samples from both epidemics were submitted to our laboratory, which lies in the center of the epidemic area and serves a catchment area of roughly 500,000 persons in a semirural district supporting two hospitals and surrounding general practitioners.The gold standard for serological diagnosis of an infectious disease is either a seroconversion or a 4-fold rise in antibody titer. The reference test for serological diagnosis of Q fever is the immunofluorescence assay (IFA) (8). Antibodies are expressed against phase II antigens during the acute infection and against phase I antigens in the established infection. For both antigens, IgM antibody production precedes IgG production, and thus three phases can be distinguished in acute Q fever: a seronegative phase followed by IgM/IgG phase II seroconversion during the acute infection and subsequent IgM/IgG phase I seroconversion in the established infection. However, an important drawback to serological diagnosis of acute Q fever is the lag phase in antibody response of 7 to 15 days after onset of clinical symptoms (8).Apart from serology, C. burnetii-specific PCR of serum samples can be an additional tool to diagnose Q fever in the early acute phase, but conflicting sensitivities have been reported (3, 13). Here, we evaluated the performance of an in-house-developed real-time PCR assay for detection of C. burnetii DNA in serum samples from patients with acute Q fever.     

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.     

Q fever endocarditis; not always expected

Q fever endocarditis is a chronic disease with protean manifestations. The clinical and serological manifestations of nine patients diagnosed as having Q fever endocarditis during a 19-year period are reviewed. Four patients (44%) required valve replacement due to congestive heart failure. Three of these four patients were diagnosed as having Q fever endocarditis only after elective valve surgery, by histopathological examination of the valve and subsequent serological tests. Prior to surgery they were afebrile and had no other symptom or sign indicative of endocarditis. The antibiotic treatment and the decreasing titres of Q fever antibodies of all nine patients during several years of follow-up are summarized. Careful assessment of heart valves for histopathological evidence of inflammation is suggested, even after elective replacement. If found, clinical and laboratory evaluation should include determination of anti-Coxiella burnetti antibodies.     

Epidemiological study of Q fever in humans, ruminant animals, and ticks in Cyprus using a geographical information system

A cross-sectional study of Q fever was conducted in a representative sample of the human and animal population in Cyprus in order to assess the seroprevalence of Q fever and the prevalence of related risk factors. A total of 583 human and 974 ruminant animal serum samples were collected and tested for the detection of antibodies against Coxiella burnetii phase II antigen using an indirect immunofluorescent assay. One hundred forty-one ticks were collected from the infested animals examined; the polymerase chain reaction and the shell-vial technique were used to detect and isolate C. burnetii. Standardized questionnaires were used to obtain information concerning inhabitants and their animals. A geographical information system was used to identify high-risk regions. The prevalence of IgG antibodies against C. burnetii phase II antigen was estimated at 52.7% for humans, 48.2% for goats, 18.9% for sheep, and 24% for bovines. C. burnetii was detected in 11 (7.8%) ticks. Using the geographical information system, two villages were identified as high-risk regions on the basis of high seroprevalence rates of IgG antibodies in humans and animals. Risk factors related to Q fever seropositivity were identified by logistic regression analysis and included age, residence, occupation, use of manure in the garden, ownership of animals (especially goats), and the presence of tick-infested or aborting animals. Q fever poses an occupational hazard to humans living in close contact with sheep and/or goats. In parallel, ticks should be considered an important aspect in the epidemiology of Q fever and should be further studied to better elucidate their role.     

Comparison of ELISA and indirect immunofluorescent antibody assay detecting <Emphasis Type="Italic">Coxiella burnetii</Emphasis> IgM phase II for the diagnosis of acute Q fever

A commercially available enzyme-linked immunosorbent assay (ELISA) detecting Coxiella burnetii phase II-specific IgM for the diagnosis of acute Q fever was compared with indirect immunofluorescent antibody assay (IFA). IFA is the current reference method for the detection of antibodies against C. burnetii, but has disadvantages because the judgment of fluorescence is subjective and tiring, and the test is expensive and automation is not possible. To examine whether phase II IgM ELISA could be used as a screening assay for acute Q fever, we compared the sensitivity and specificity of IFA and ELISA. The sensitivity of the IFA and ELISA tests were 100 and 85.7%, respectively, with a specificity of 95.3 and 97.6%, respectively. Because of the high sensitivity and specificity of the ELISA in combination with the practical disadvantages of the IFA, we introduced a new algorithm to screen samples of patients with symptoms of acute Q fever infection.     

Q Fever in the Greek Island of Crete: Detection, Isolation, and Molecular Identification of Eight Strains of Coxiella burnetii from Clinical Samples

Over a period of 6 years (1989 to 1995), serum samples from 3,300 patients suspected to be infected by Coxiella burnetii were assayed for the presence of antibodies against antigen phase II of the microorganism by the indirect immunofluorescence antibody technique (IFAT). One hundred fifty-two cases were recorded, and blood samples from 17 patients were cultured for the isolation of the pathogen. By a centrifugation shell vial technique, eight strains were isolated from patients suffering from acute Q fever. The microorganism was detected in the cultures by IFAT, by Gimenez staining, and by the cytopathogenic effect on Vero and human embryonic lung (HEL) cells. PCR followed by restriction fragment length polymorphism analysis was used to confirm the diagnosis and identify the Coxiella burnetii strains within the cell cultures as well as to compare them with reference strains. In order to avoid time-consuming cultures, to achieve direct detection of Coxiella burnetii in clinical samples (blood, buffy coat, etc.), and to increase the specificity and sensitivity of the detection, nested PCR was performed. The first step of DNA extraction was performed with the QIAamp blood kit 250. For the second step of the PCR assays, the conditions of temperature and times of recycling were properly modified, and the microorganism was detected within 4 h. Our study demonstrates that Q fever is an endemic disease in Crete and that the diagnosis of Coxiella burnetii infection can be rapidly achieved by the detection of the microorganism in buffy coat samples by nested PCR. Although the presenting symptoms of the disease in this study differed from those in other studies, the Cretan strains do not differ genotypically from the reference strains (Nine Mile and Q212).     

Association between serological evidence of past Coxiella burnetii infection and atherosclerotic cardiovascular disease in elderly patients

Q fever, caused by Coxiella burnetii, may cause vascular complications, but the role that this infection may play in the development of atherosclerotic cardiovascular disease remains unknown. This study examined the association between Q fever serology and cardiovascular disease in a region where Q fever is endemic. A case-control study was conducted in the Hospital Universitario de Burgos (Spain) between February 2011 and June 2012. A total of 513 samples were tested, from 454 hospitalized patients ≥65 years old, of whom 164 were cases (patients with prevalent or incident coronary heart, cerebrovascular or peripheral artery, disease) and 290 controls (patients without cardiovascular disease). Serum IgG antibody phase II titres against Q fever were determined by immunofluorescence assay. Seropositivity (titres ≥1:256) was detected in 84/164 (51.2%) cases and in 109/290 (37.6%) controls (p = 0.005; OR, 1.7; 95% CI, 1.1–2.5). This ratio increases when adjusted for sex, hypertension, dyslipidaemia, smoking, diabetes and atrial fibrillation (OR, 2.6; 95% CI, 1.5–4.7). The geometric mean titre (GMT) for C. burnetii phase II assay was higher in cases than in controls (p = 0.004). We found no significant relationship between cardiovascular disease and C. pneumoniae, and Cytomegalovirus seropositivity (both determined by the IgG ELISA method). In conclusion, serological evidence of past Q fever is associated with atherosclerotic cardiovascular disease in elderly patients in an endemic region.     

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.     

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     

Interlaboratory Evaluation of Different Extraction and Real-Time PCR Methods for Detection of Coxiella burnetii DNA in Serum

In the Netherlands, there is an ongoing and unparalleled outbreak of Q fever. Rapid and reliable methods to identify patients infected with Coxiella burnetii, the causative agent of Q fever, are urgently needed. We evaluated the performance of different DNA extraction methods and real-time PCR assays that are in use in seven diagnostic or reference laboratories in the Netherlands. A low degree of variation in the sensitivities of most of the developed real-time PCR assays was observed. However, PCR assays amplifying short DNA fragments yielded better results than those producing large DNA fragments. With regard to DNA extraction, the automated MagNA Pure Compact system and the manual QIAamp DNA mini kit consistently yielded better results than either the MagNA Pure LC system and NucliSens EasyMag (both automated) or the High Pure viral nucleic acid kit (manual). The present study shows that multiple combinations of DNA extraction kits and real-time PCR assays offer equivalent solutions to detect C. burnetii DNA in serum samples from patients suspected to have Q fever.Q fever is a worldwide zoonosis caused by Coxiella burnetii, an obligate intracellular bacterium (11). Whereas animals such as sheep and goats are generally asymptomatic carriers, infection with C. burnetii in these animals may become manifest by abortion. Although asymptomatic in ∼60% of infected persons, C. burnetii can cause serious illness in humans. Q fever can cause acute or chronic infection depending on the patient''s condition or immune status. Acute Q fever may present as a self-limiting flu-like atypical pneumonia accompanied by severe headache and sometimes hepatitis. Approximately 5% of all Q fever cases may progress in a chronic infection leading to life-threatening endocarditis (1, 3, 5, 7-9). C. burnetii is highly infectious and can survive for long periods in the environment. Human outbreaks have been associated with farms, slaughterhouses, and wind dispersion from farms where infected animals were kept. Ticks and pets, including cats and dogs, have also been demonstrated to be potential sources of Q fever (1, 4, 10).Laboratory diagnosis of Q fever is usually performed by serological methods such as the indirect immunofluorescence assay (IFA), complement fixation test (CFT), or enzyme-linked immunosorbent assay (ELISA), but these tests are of limited use in the early phase of the disease, as it may take up to 2 weeks for a detectable immune response to develop. Several PCR-based diagnostic methods, such as conventional PCR, nested PCR, or real-time PCR, have successfully been applied for the direct detection of C. burnetii DNA in clinical samples. The sequences targeted by these tests varied from plasmids (QpH1 or QpRS) to chromosomal genes, such as the isocitrate dehydrogenase gene (NADP) or the transposase gene of the C. burnetii IS1111a insertion element (3, 4, 14-16). The multicopy IS1111a insertion element is present in 20 copies in the genome of the C. burnetii Nine Mile RSA493 strain. Copy numbers per isolate vary and can reach up to ∼100 copies per genome (7). Due to the multicopy nature of this DNA element, it provides a highly sensitive target for detection of C. burnetii DNA in serum samples. Furthermore, real-time PCR can be useful for diagnosis of chronic Q fever, since in these patients C. burnetii DNA can be detected in serum over long periods of time (3).In the Netherlands, as of 2007, there is an unprecedented and ongoing outbreak of Q fever (12, 17). At present, more than 3,000 cases have been reported in the Netherlands. In order to improve diagnosis for Q fever, medical microbiology laboratories have implemented molecular methods to close the diagnostic gap between onset of the disease and the presence of specific antibodies in serum. The aim of this study was to compare the performances of different DNA extraction methods and real-time PCR assays, all targeting the C. burnetii IS1111a insertion element, that are being used in seven diagnostic or public health laboratories in the Netherlands.     

Immunological arousal during acute Q fever infection

Physicians often encounter patients who present with a vague clinical syndrome. A wide serological workup is often ordered, which may include tests for Coxiella burnetii in endemic areas. Often, the results of these tests pose new dilemma, with overlapping positive laboratory assays. The objective of this investigation was to characterise the serological overlap between acute Q fever and other infectious and immunological diseases. We retrospectively scanned the files of patients with a positive or equivocal immunoglobulin (Ig) M for C. burnetii phase II over a period of 8 years in a general hospital. Clinical and laboratory data, including antibodies to infectious agents and antibodies related to immunological states, were recorded. Anti-nuclear antibody (ANA), smooth muscle antibody (SMA) and rheumatoid factor were positive in 38%, 33.3% and 22.2% of the cases, respectively. In patients with acute Q fever, elevated IgM levels for Epstein–Barr Virus (EBV), cytomegalovirus (CMV), Mycoplasma pneumoniae, parvovirus, Bordetella pertussis, Rickettsia conorii and R. typhi were noted in 13.8%, 8.3%, 12.12%, 22.2%, 25%, 13% and 21.7% of cases, respectively. Acute Q fever induces a non-specific immunological arousal in a significant number of patients. This may interfere with diagnosis and delay treatment. Caution, clinical judgment and serological follow-up is warranted in such conditions.     

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%).