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.     

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.     

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.     

Long-term serological follow-up after primary Coxiella burnetii infection in patients with vascular risk factors for chronic Q fever

We evaluated the long-term serological follow-up of patients with vascular risk factors for chronic Q fever that were previously Coxiella burnetii seropositive. C. burnetii phase I IgG titers were reevaluated in patients that gave informed consent or retrospectively collected in patients already deceased or lost to follow-up. Of 107 patients, 25 (23.4%) became seronegative, 77 (72.0%) retained a profile of past resolved Q fever infection, and five (4.7%) developed chronic Q fever. We urge clinicians to stay vigilant for chronic Q fever beyond two years after primary infection and perform serological testing based on clinical presentation.

     

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.     

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.     

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.     

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.     

Q fever during pregnancy: a narrative review

BackgroundCoxiella burnetii, the causative agent of Q fever, causes abortions in animals. Its effects on pregnancy in humans and the management of Q fever in pregnancy are uncertain.ObjectivesTo summarize data on the effects of Q fever on pregnancy in women, the effects of pregnancy on Q fever complications and the optimal screening and management of Q fever during pregnancy.SourcesWe searched for studies reporting on Q fever during pregnancy in women. We included randomized and observational studies, seroprevalence studies, case series and case reports, including clinical and histopathological studies.ContentThe accumulating data seems convincing that Q fever increases the risk of abortions in early pregnancy and prematurity or intrauterine fetal demise in late pregnancy. Data are based on sero-epidemiological associations of Q fever and adverse pregnancy outcomes and case reports showing the presence and effects of C. burnetii on the placenta and the fetus. Based on observational studies, acquisition of Q fever during pregnancy also increases the risk for maternal chronic Q fever. Treatment of recently infected women seems to improve these outcomes, based on case series only, but the optimal duration of treatment has not been studied. The efficacy of active surveillance during pregnancy, timing and frequency have not been determined in high-endemicity settings. Obstetricians should be aware of the risk for transmission of the disease during delivery. Currently available data are based mostly on case series and case reports, with some discrepancy between the French experience in chronic endemicity settings and Dutch experience in outbreak settings.ImplicationsSince infection with Q fever is largely asymptomatic, we believe that the accumulating information linking Q fever to adverse pregnancy outcomes justifies screening in the high-endemicity setting and treatment of infected women. High-quality research addressing the questions raised by this review is needed to determine the optimal public health policy.     

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.     

A combination of interferon-gamma and interleukin-2 production by Coxiella burnetii-stimulated circulating cells discriminates between chronic Q fever and past Q fever

Infection with Coxiella burnetii may lead to life-threatening chronic Q fever endocarditis or vascular infections, which are often difficult to diagnose. The present study aims to investigate whether measurement of in-vitro interferon-gamma (IFN-γ) production, a key cytokine in the immune response against C. burnetii, differentiates chronic from a past cleared infection, and whether measurement of other cytokines would improve the discriminative power. First, C. burnetii-specific IFN-γ production was measured in whole blood of 28 definite chronic Q fever patients and compared with 135 individuals with past Q fever (seropositive controls) and 908 seronegative controls. IFN-γ production was significantly higher in chronic Q fever patients than in controls, but with overlapping values between patients and seropositives. Secondly, the production of a series of other cytokines was measured in a subset of patients and controls, which showed that interleukin (IL)-2 production was significantly lower in patients than in seropositive controls. Subsequently, measuring IL-2 in all patients and all controls with substantial IFN-γ production showed that an IFN-γ/IL-2 ratio >11 had a sensitivity and specificity of 79% and 96%, respectively, to diagnose chronic Q fever. This indicates that a high IFN-γ/IL-2 ratio is highly suggestive for chronic Q fever. In an additional group of 25 individuals with persistent high anti-Coxiella phase I IgG titres without definite chronic infection, all but six showed an IFN-γ/IL-2 ratio <11. In conclusion, these findings hold promise for the often difficult diagnostic work-up of Q fever and the IFN-γ/IL-2 ratio may be used as an additional diagnostic marker.     

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.     

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.     

Chronic Q Fever in the Netherlands 5 Years after the Start of the Q Fever Epidemic: Results from the Dutch Chronic Q Fever Database

Coxiella burnetii causes Q fever, a zoonosis, which has acute and chronic manifestations. From 2007 to 2010, the Netherlands experienced a large Q fever outbreak, which has offered a unique opportunity to analyze chronic Q fever cases. In an observational cohort study, baseline characteristics and clinical characteristics, as well as mortality, of patients with proven, probable, or possible chronic Q fever in the Netherlands, were analyzed. In total, 284 chronic Q fever patients were identified, of which 151 (53.7%) had proven, 64 (22.5%) probable, and 69 (24.3%) possible chronic Q fever. Among proven and probable chronic Q fever patients, vascular infection focus (56.7%) was more prevalent than endocarditis (34.9%). An acute Q fever episode was recalled by 27.0% of the patients. The all-cause mortality rate was 19.1%, while the chronic Q fever-related mortality rate was 13.0%, with mortality rates of 9.3% among endocarditis patients and 18% among patients with a vascular focus of infection. Increasing age (P = 0.004 and 0.010), proven chronic Q fever (P = 0.020 and 0.002), vascular chronic Q fever (P = 0.024 and 0.005), acute presentation with chronic Q fever (P = 0.002 and P < 0.001), and surgical treatment of chronic Q fever (P = 0.025 and P < 0.001) were significantly associated with all-cause mortality and chronic Q fever-related mortality, respectively.     

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.     

Seroprevalence of Q fever in a district located in the west Black Sea region of Turkey

Q fever is a worldwide zoonosis caused by Coxiella burnetii. In Turkey, it has been reported from the late 1940s that Q fever is endemic in humans and animals. Our objective was to evaluate the seroprevalence in Samsun Tekkeköy (north Turkey), where an outbreak of Q fever occurred in 2002. In this cross-sectional study, subjects were selected by the random proportional sampling method. All subjects were healthy with no specific symptoms and tested by the microimmunofluorescent antibody test. In total, we tested 407 subjects; 33 (8.1%) of them were identified as past evidence of infection and 22 (5.4%) were considered as evolutive form of Q fever (17 acute and five chronic forms). The seroprevalence was significantly higher among people over 30 years of age, hunters, and slaughters than the others (p?=?0.001, p?=?0.034, and p?=?0.006, respectively). We found 13.5% seropositivity among healthy subjects, confirming that Q fever is prevalent in our region and is often asymptomatic.     

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.     

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.     

Serological follow-up in patients with aorto-iliac disease and evidence of Q fever infection

The aim of this study was to provide data on the risk of developing chronic Q fever in patients with aorto-iliac disease and evidence of previous Q fever infection. Patients with an aortic and/or iliac aneurysm or aorto-iliac reconstruction (aorto-iliac disease) and evidence of previous Q fever infection were included. The presence of phase I and II Coxiella burnetii IgG antibodies was assessed periodically using immunofluorescence assay. A total of 111 patients with aorto-iliac disease were divided into three groups, based upon the serological profile [mean follow-up: 16?±?9 months (mean?±?standard deviation)]. Group 1 consisted of 30 patients with a serological trace of C. burnetii infection (negative IgG phase I, IgG phase II titer of 1:32). Of these, 36.7 % converted to serological profile matching past resolved Q fever. Group 2 included 49 patients with negative IgG phase I titer and IgG phase II titer ≥1:64. No patients developed chronic Q fever, but 14.3 % converted to a positive IgG phase I titer. Group 3 consisted of 32 patients with positive IgG phase I and positive IgG phase II titers, of which 9.4 % developed chronic Q fever (significantly different from group 2, p?=?0.039). The IgG phase I titer increased in 28.1 % of patients (from 1:64 to 1:4,096). The risk of developing chronic Q fever in patients with aorto-iliac disease and previous Q fever infection with a positive IgG phase I titer was 9.4 %. The IgG phase I titer increases or becomes positive in a substantial number of patients. A standardized serological follow-up is proposed.     

Targeted screening as a tool for the early detection of chronic Q fever patients after a large outbreak

In the aftermath of the Dutch Q fever outbreak, an increasing number of patients are being diagnosed with chronic Q fever. Most of these patients are unaware of being infected with Coxiella burnetii, the causative agent of Q fever. To find patients in an earlier, asymptomatic stage, a targeted screening strategy (TSS) for patients with risk factors for chronic Q fever was started in the southeast region of Noord-Brabant. In total, 763 patients were tested using an IgG phase II indirect fluorescent antibody test (IFAT), of which 52 (7 %) patients tested positive. Ten of these 52 patients displayed a chronic Q fever serological profile. All of these 10 patients had a heart valve(s) or (endo-)vascular prosthesis. All except one were asymptomatic. Suggestive signs for chronic infections on positron emission tomography–computed tomography (PET-CT) were demonstrated in 5 (50 %) of these patients. Forty-two out of the 52 patients with a positive screening test showed a past Q fever serological profile. After a year of follow-up (every 3 months), none of these patients showed elevation of antibody titres and no new chronic Q fever patients were found in this group. A targeted screening programme is a useful instrument for detecting patients at risk of developing chronic Q fever.