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Background: Following outbreaks in other parts of the Netherlands, the Dutch border region of South Limburg experienced a large-scale outbreak of human Q fever related to a single dairy goat farm in 2009, with surprisingly few cases reported from neighbouring German counties. Late chronic Q fever, with recent spikes of newly detected cases, is an ongoing public health concern in the Netherlands. We aimed to assess the scope and scale of any undetected cross-border transmission to neighbouring German counties, where individuals unknowingly exposed may carry extra risk of overlooked diagnosis., Methods: (A) Seroprevalence rates in the Dutch area were estimated fitting an exponential gradient to the geographical distribution of notified acute human Q fever cases, using seroprevalence in a sample of farm township inhabitants as baseline. (B) Seroprevalence rates in 122 neighbouring German postcode areas were estimated from a sample of blood donors living in these areas and attending the regional blood donation centre in January/February 2010 (n = 3,460). (C) Using multivariate linear regression, including goat and sheep densities, veterinary Q fever notifications and blood donor sampling densities as covariates, we assessed whether seroprevalence rates across the entire border region were associated with distance from the farm., Results: (A) Seroprevalence in the outbreak farm's township was 16.1%. Overall seroprevalence in the Dutch area was 3.6%. (B) Overall seroprevalence in the German area was 0.9%. Estimated mean seroprevalence rates (per 100,000 population) declined with increasing distance from the outbreak farm (0-19 km = 2,302, 20-39 km = 1,122, 40-59 km = 432 and ≥60 km = 0). Decline was linear in multivariate regression using log-transformed seroprevalence rates (0-19 km = 2.9 [95% confidence interval (CI) = 2.6 to 3.2], 20 to 39 km = 1.9 [95% CI = 1.0 to 2.8], 40-59 km = 0.6 [95% CI = -0.2 to 1.3] and ≥60 km = 0.0 [95% CI = -0.3 to 0.3])., Conclusions: Our findings were suggestive of widespread cross-border transmission, with thousands of undetected infections, arguing for intensified cross-border collaboration and surveillance and screening of individuals susceptible to chronic Q fever in the affected area., (© 2020 The Authors. Transboundary and Emerging Diseases published by Blackwell Verlag GmbH.)

Objectives: Chronic 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., Methods: A 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)., Results: Complications 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)., Conclusions: In 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., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: After primary infection with Coxiella burnetii, patients may develop acute Q fever, which is a relatively mild disease. A small proportion of patients (1%-5%) develop chronic Q fever, which is accompanied by high mortality and can be manifested as infected arterial or aortic aneurysms or infected vascular prostheses. The disease can be complicated by arterial fistulas, which are often fatal if they are left untreated. We aimed to assess the cumulative incidence of arterial fistulas and mortality in patients with proven chronic Q fever., Methods: In a retrospective, observational study, the cumulative incidence of arterial fistulas (aortoenteric, aortobronchial, aortovenous, or arteriocutaneous) in patients with proven chronic Q fever (according to the Dutch Chronic Q Fever Consensus Group criteria) was assessed. Proven chronic Q fever with a vascular focus of infection was defined as a confirmed mycotic aneurysm or infected prosthesis on imaging studies or positive result of serum polymerase chain reaction for C. burnetii in the presence of an arterial aneurysm or vascular prosthesis., Results: Of 253 patients with proven chronic Q fever, 169 patients (67%) were diagnosed with a vascular focus of infection (42 of whom had a combined vascular focus and endocarditis). In total, 26 arterial fistulas were diagnosed in 25 patients (15% of patients with a vascular focus): aortoenteric (15), aortobronchial (2), aortocaval (4), and arteriocutaneous (5) fistulas (1 patient presented with both an aortocaval and an arteriocutaneous fistula). Chronic Q fever-related mortality was 60% for patients with and 21% for patients without arterial fistula (P < .0001). Primary fistulas accounted for 42% and secondary fistulas for 58%. Of patients who underwent surgical intervention for chronic Q fever-related fistula (n = 17), nine died of chronic Q fever-related causes (53%). Of patients who did not undergo any surgical intervention (n = 8), six died of chronic Q fever-related causes (75%)., Conclusions: The proportion of patients with proven chronic Q fever developing primary or secondary arterial fistulas is high; 15% of patients with a vascular focus of infection develop an arterial fistula. This observation suggests that C. burnetii, the causative agent of Q fever, plays a role in the development of fistulas in these patients. Chronic Q fever-related mortality in patients with arterial fistula is very high, in both patients who undergo surgical intervention and patients who do not., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Importance: Q fever remains widespread throughout the world; the disease is serious and causes outbreaks and deaths when complications are not detected. The diagnosis of Q fever requires the demonstration of the presence of Coxiella burnetii and the identification of an organic lesion., Objective: To describe the hitherto neglected clinical characteristics of Q fever and identifying risk factors for complications and death., Design, Setting, and Participants: This prospective cohort study conducted from January 1, 1991, through December 31, 2016, included patients treated at the French National Reference Center for Q fever with serologic findings positive for C burnetii and clinical data consistent with C burnetii infection. Clinical data were prospectively collected by telephone. Patients with unavailable clinical data or an unidentified infectious focus were excluded., Main Outcomes and Measures: Q fever complications and mortality., Results: Of the 180 483 patients undergoing testing, 2918 had positive findings for C burnetii and 2434 (68.8% men) presented with clinical data consistent with a C burnetii infection. Mean (SD) age was 51.8 (17.4) years, and the ratio of men to women was 2.2. At the time of inclusion, 1806 patients presented with acute Q fever, including 138 with acute Q fever that progressed to persistent C burnetii infection, and 766 had persistent focalized C burnetii infection. Rare and hitherto neglected foci of infections included lymphadenitis (97 [4.0%]), acute Q fever endocarditis (50 [2.1%]), hemophagocytic syndrome (9 [0.4%]), and alithiasic cholecystitis (11 [0.4%]). Vascular infection (hazard ratio [HR], 3.1; 95% CI, 1.7-5.7; P < .001) and endocarditis (HR, 2.4; 95% CI, 1.1-5.1; P = .02) were associated with an increased risk of death. Independent indicators of lymphoma were lymphadenitis (HR, 77.4; 95% CI, 21.2-281.8; P < .001) and hemophagocytic syndrome (HR, 19.1; 95% CI, 3.4-108.6; P < .001). The presence of anticardiolipin antibodies during acute Q fever has been associated with several complications, including hepatitis, cholecystitis, endocarditis, thrombosis, hemophagocytic syndrome, meningitis, and progression to persistent endocarditis., Conclusions and Relevance: Previously neglected foci of C burnetii infection include the lymphatic system (ie, bone marrow, lymphadenitis) with a risk of lymphoma. Cardiovascular infections were the main fatal complications, highlighting the importance of routine screening for valvular heart disease and vascular anomalies during acute Q fever. Routine screening for anticardiolopin antibodies during acute Q fever can help prevent complications. Positron emission tomographic scanning could be proposed for all patients with suspected persistent focused infection to rapidly diagnose vascular and lymphatic infections associated with death and lymphoma, respectively.

Background: Forms of presentation of Q fever vary widely across Spain, with differences between the north and south. In the absence of reported case series from Galicia (north-west Spain), this study sought to describe a Q-fever case series in this region for the first time, and conduct a systematic review to analyse all available data on the disease in Spain., Methods: Patients with positive serum antibodies to Coxiella burnetii from a single institution over a 5-year period (January 2011-December 2015) were included. Patients with phase II titres above 1/128 (or documented seroconversion) and compatible clinical criterial were considered as having Q fever. Patients with clinical suspicion of chronic Q-fever and IgG antibodies to phase I-antigen of over 1/1024, or persistently high levels six months after treatment were considered to be cases of probable chronic Q-fever. Systematic review: We conducted a search of the Pubmed/Medline database using the terms: Q Fever OR Coxiella burnetii AND Spain. Our search yielded a total of 318 studies: 244 were excluded because they failed to match the main criteria, and 41 were discarded due to methodological problems, incomplete information or duplication. Finally, 33 studies were included., Results: A total of 155 patients, all of them from Galicia, with positive serological determination were located during the study period; 116 (75%) were deemed to be serologically positive patients without Q fever and the remaining 39 (25%) were diagnosed with Q fever. A potential exposure risk was found in 2 patients (5%). The most frequent form of presentation was pneumonia (87%), followed by isolated fever (5%), diarrhoea (5%) and endocarditis (3%). The main symptoms were headache (100%), cough (77%) and fever (69%). A trend to a paucisymptomatic illness was observed in women. Hospital admission was required in 37 cases, and 6 patients died while in hospital. Only 2 patients developed chronic Q-fever. Systematic review: Most cases were sporadic, mainly presented during the winter and spring, as pneumonia in 37%, hepatitis in 31% and isolated fever in 29.6% of patients. In the north of Spain, 71% of patients had pneumonia, 13.2% isolated fever and 13% hepatitis. In the central and southern areas, isolated fever was the most frequent form of presentation (40%), followed by hepatitis (38.4%) and pneumonia (17.6%). Only 31.7% of patients reported risk factors, and an urban-environment was the most frequent place of origin. Overall mortality was 0.9%, and the percentage of patients with chronic forms of Q-fever was 2%., Conclusions: This is the first study to report on a Q-fever case series in Galicia. It shows that in this region, the disease affects the elderly population -even in the absence of risk factors- and is linked to a higher mortality than reported by previous studies. While pneumonia is the most frequent form of presentation in the north of the country, isolated fever and hepatitis tend to be more frequent in the central and southern areas. In Spain, 32% of Q-fever cases do not report contact with traditional risk factors, and around 58% live in urban areas.

Background: Evidence on the effectiveness of first-line treatment for chronic Q fever, tetracyclines (TET) plus hydroxychloroquine (HCQ), and potential alternatives is scarce., Methods: We performed a retrospective, observational cohort study to assess efficacy of treatment with TET plus quinolones (QNL), TET plus QNL plus HCQ, QNL monotherapy, or TET monotherapy compared to TET plus HCQ in chronic Q fever patients. We used a time-dependent Cox proportional hazards model to assess our primary (all-cause mortality) and secondary outcomes (first disease-related event and therapy failure)., Results: We assessed 322 chronic Q fever patients; 276 (86%) received antibiotics. Compared to TET plus HCQ (n = 254; 92%), treatment with TET plus QNL (n = 49; 17%), TET plus QNL plus HCQ (n = 29, 10%), QNL monotherapy (n = 93; 34%), or TET monotherapy (n = 54; 20%) were not associated with primary or secondary outcomes. QNL and TET monotherapies were frequently discontinued due to insufficient clinical response (n = 27, 29% and n = 32, 59%). TET plus HCQ, TET plus QNL, and TET plus QNL plus HCQ were most frequently discontinued due to side effects (n = 110, 43%; n = 13, 27%; and n = 12, 41%)., Conclusions: Treatment of chronic Q fever with TET plus QNL appears to be a safe alternative for TET plus HCQ, for example, if TET plus HCQ cannot be tolerated due to side effects. Treatment with TET plus QNL plus HCQ was not superior to treatment with TET plus HCQ, although this may be caused by confounding by indication. Treatment with TET or QNL monotherapy should be avoided; switches due to subjective, insufficient clinical response were frequently observed., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Coxiella burnetii vascular infections continue to be very severe diseases and no guidelines exist about their prevention. In terms of treatment, the benefit of the surgical removal of infected tissues has been suggested by 1 retrospective study.We present a case of a C burnetii abdominal aortic graft infection for which we observed a dramatic clinical and biological recovery after surgery. We thus performed a retrospective cohort study to evaluate the impact of surgery on survival and serological outcome for patients with Q fever vascular infections diagnosed in our center.Between 1986 and February 2015, 100 patients were diagnosed with Q fever vascular infections. The incidence of these infections has significantly increased over the past 5 years, in comparison with the mean annual incidence over the preceding 22 years (8.83 cases per year versus 3.14 cases per year, P = 0.001). A two-and-a-half-year follow-up was available for 66 patients, of whom 18.2% died. We observed 6.5% of deaths in the group of patients who were operated upon at 2 and a half years, in comparison with 28.6% in the group which were not operated upon (P = 0.02). Surgery was the only factor that had a positive impact on survival at 2 and a half years using univariate analysis [hazard ratio: 0.17 [95% CI]: [0.039-0.79]; P = 0.024]. Surgery was also associated with a good serological outcome (74.1% vs 57.1% of patients, P = 0.03). In the group of patients with vascular graft infections (n = 47), surgery had a positive impact on serological outcome at 2 and a half years (85.7% vs 42.9%, P < 0.001) [hazard ratio: 0.40 [95% CI]: [0.17-098]; P = 0.046] and tended to be associated with lower although not statistically significant mortality (11.1% vs 27.6% of deaths, P = 0.19).Surgical treatment confers a benefit in terms of survival following C burnetii vascular infections. However, given the high mortality of these infections and their rising incidence, we propose a strategy that consists of screening for vascular graft and aneurysms in the context of primary Q fever, to decide when to start prophylactic treatment, similar to the strategy recommended for the prophylaxis of Q fever endocarditis., Competing Interests: The authors have no conflicts of interest to disclose.

Objective: Since chronic Q fever often develops insidiously, and symptoms are not always recognized at an early stage, complications are often present at the time of diagnosis. We describe complications associated with vascular chronic Q fever as found in the largest cohort of chronic Q fever patients so far., Methods: Patients with proven or probable chronic Q fever with a focus of infection in an aortic aneurysm or vascular graft were included in this study, using the Dutch national chronic Q fever database., Results: A total of 122 patients were diagnosed with vascular chronic Q fever between April 2008 and June 2012. The infection affected a vascular graft in 62 patients (50.8%) and an aneurysm in 53 patients (43.7%). Seven patients (5.7%) had a different vascular focus. Thirty-six patients (29.5%) presented with acute complications, and 35 of these patients (97.2%) underwent surgery. Following diagnosis and start of antibiotic treatment, 26 patients (21.3%) presented with a variety of complications requiring surgical treatment during a mean follow-up of 14.1 ± 9.1 months. The overall mortality rate was 23.7%. Among these patients, mortality was associated with chronic Q fever in 18 patients (62.1%)., Conclusions: The management of vascular infections with C. burnetii tends to be complicated. Diagnosis is often difficult due to asymptomatic presentation. Patients undergo challenging surgical corrections and long-term antibiotic treatment. Complication rates and mortality are high in this patient cohort., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The objective of our study was to analyze the efficacy of autologous superficial femoropopliteal vein reconstruction for primary aortic or aortic graft infection., Methods: We performed a retrospective analysis of 14 patients treated for an infected aortic prosthesis or primary infected aorta between 2012 and 2014. Three patients had a primary mycotic aneurysm caused by a Salmonella or Coxiella burnetti infection. Seven patients were treated previously for aortic aneurysms with a conventional Dacron vascular prosthesis and 4 with an endovascular prosthesis. All infected prostheses were explanted via median laparotomy with subsequent debridement of the aortic aneurysm wall. Aortic reconstruction was performed with 1 or 2 superficial femoropopliteal veins, interpositioning the greater omentum when possible. The primary outcome measure was 30-day mortality. Secondary outcome measures were reoperation, operating time, amputation rate, length of intensive care unit (ICU) and hospital stay, reinfection rate, and limb edema requiring compression therapy., Results: The 30-day mortality was 28%. Two patients died of an abdominal sepsis, one patient of a cerebrovascular accident and another of a hypovolemic shock. One patient died at home 2 years after surgery of unknown cause. Four patients required a reoperation. The median intraoperative blood loss was 1,500 mL (500-8000). Median operating time was 364 min (264-524). Median length of ICU stay was 3.5 days (1-47), and median hospital stay was 20 days (10-47). There were no limb amputations. Mild edema of the donor leg was documented in 2 patients. Compression stockings were not worn by any patients. Postoperative antibiotic treatment was administered for at least 6 weeks. No recurrent infections were diagnosed., Conclusions: Autologous venous reconstruction of the aorta offers advantages over other therapeutic approaches and deserves a prominent place in the treatment of the primary infected aorta or an infected aortic prosthetic graft., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Two national surveillance systems capturing reports of fatal Q fever were compared with obtained estimates of Q fever underreporting in the United States using capture-recapture methods. During 2000-2011, a total of 33 unique fatal Q fever cases were reported through case report forms submitted to the Centers for Disease Control and Prevention and through U.S. death certificate data. A single case matched between both data sets, yielding an estimated 129 fatal cases (95% confidence interval [CI] = 62-1,250) during 2000-2011. Fatal cases of Q fever were underreported through case report forms by an estimated factor of 14 and through death certificates by an estimated factor of 5.2., (© The American Society of Tropical Medicine and Hygiene.)

Q fever is a worldwide zoonosis historically associated with exposure to infected livestock. This study summarizes cases of Q fever, a notifiable disease in the United States, reported to the Centers for Disease Control and Prevention through two national surveillance systems with onset during 2000-2012. The overall incidence rate during this time was 0.38 cases per million persons per year. The reported case fatality rate was 2.0%, and the reported hospitalization rate was 62%. Most cases (61%) did not report exposure to cattle, goats, or sheep, suggesting that clinicians should consider Q fever even in the absence of livestock exposure. The prevalence of drinking raw milk among reported cases of Q fever (8.4%) was more than twice the national prevalence for the practice. Passive surveillance systems for Q fever are likely impacted by underreporting and underdiagnosis because of the nonspecific presentation of Q fever., (© The American Society of Tropical Medicine and Hygiene.)

The potential role of cats in transmitting Coxiella burnetii to humans was highlighted in a Q fever outbreak, linked to a caesarean section in a breeding queen, in an Australian small animal veterinary hospital. The objectives of this study were to evaluate the C burnetii seroreactivity of the breeding queen and other cats residing at the same breeding cattery (n = 27) and to evaluate C burnetii infection of the breeding queen by molecular and histological methods. Three assays [complement fixation test (CFT), indirect immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA)] were used for serological evaluation. Additionally, uterine and ovarian samples collected from the breeding queen 11 weeks post-parturition were assessed by routine and specialised histological methods and polymerase chain reaction. The breeding queen showed strong seropositivity using CFT (titre 1/32), IFA (titre phase I 1/8192 and phase II 1/8192) and ELISA; however, the reproductive tract showed no evidence of pathology or C burnetii infection. A number of cattery-confined cats were identified as seropositive to phase II and/or phase I C burnetii. Serological detection of C burnetii in a breeding cattery linked to a Q fever outbreak indicates likely infection by this bacterium in Australian feline populations, re-confirming the relevance of this zoonosis.

Coxiella burnetii infections are mostly subclinical in cattle, but can occasionally be associated with abortion. In the present study, 100 aborted fetuses or stillborn calves that were submitted for postmortem examination between September 2007 and March 2008 were examined for infection with C burnetii. Samples of both pooled fetal tissues and placental cotyledon were tested using a real-time PCR assay. In addition, the sections of placental cotyledon were examined using immunohistochemistry (IHC). The IHC of four placentas was positive. The PCR results of the IHC-positive placentas were high positive (HP); the PCR results of the organs of these four fetuses and calves varied from low positive (LP) to HP. The four IHC-positive fetuses had a gestation length of seven to nine months. All four placentas had histological signs of inflammation, but only one of four placentas had gross pathological signs of inflammation possibly due to a concomitant infection with Bacillus licheniformis. Five other IHC-negative placentas had (high) positive PCR results; the PCR results of the organs of these fetuses were LP or negative. The present study indicates that C burnetii infections are detected in a limited percentage of aborted fetuses and stillborn calves by IHC. To assess the importance of placentas with PCR-positive and IHC-negative test results, more research is needed.

Coxiella burnetii, the causative agent of Q fever, is a zoonotic disease with potentially life-threatening complications in humans. Inhalation of low doses of Coxiella bacteria can result in infection of the host alveolar macrophage (AM). However, it is not known whether a subset of AMs within the heterogeneous population of macrophages in the infected lung is particularly susceptible to infection. We have found that lower doses of both phase I and phase II Nine Mile C. burnetii multiply and are less readily cleared from the lungs of mice compared to higher infectious doses. We have additionally identified AM resident within the lung prior to and shortly following infection, opposed to newly recruited monocytes entering the lung during infection, as being most susceptible to infection. These resident cells remain infected up to twelve days after the onset of infection, serving as a permissive niche for the maintenance of bacterial infection. A subset of infected resident AMs undergo a distinguishing phenotypic change during the progression of infection exhibiting an increase in surface integrin CD11b expression and continued expression of the surface integrin CD11c. The low rate of phase I and II Nine Mile C. burnetii growth in murine lungs may be a direct result of the limited size of the susceptible resident AM cell population.

Background: Coxiella burnetii is a well-known cause of placentitis and subsequent abortion in ruminants, but there are no reports on the relationship with perinatal mortality. The study was performed to determine the influence of level and change of bulk tank milk (BTM) antibodies to C. burnetii on two outcomes associated with parturition in cattle: a) stillbirth; and b) stillbirth and neonatal mortality combined (perinatal death)., Methods: Twenty-four Danish dairy herds were tested repeatedly for antibodies to C. burnetii in BTM using a commercial ELISA. Samples were collected monthly from July 2008 to July 2009. Information on the 2,362 calvings occurring in the study period was obtained from the Danish Cattle Database. Two multilevel logistic regression models were created for the two outcomes stillbirth and perinatal mortality. One model included the level of BTM antibodies in a specified period before or after the outcome had occurred. The other model included the change in antibodies over time. These predictors were included both at herd and animal level. Furthermore, all models included parity and breed., Results: The individual monthly BTM antibody levels were highly correlated within herds. Consequently, changes in BTM antibody levels were not found to be associated with neither risk of stillbirth nor the risk of perinatal mortality. However, the risk of stillborn calves and perinatal death was higher with high level of BTM antibodies 8 to 9 months after the incident, but not outside this period., Conclusion: We conclude that the level of antibodies to C. burnetii in BTM may be associated with perinatal mortality, but the association was not persistent and should be investigated further.

Background: The management of patients with community-acquired pneumonia (CAP) who fail to improve constitutes a challenge for clinicians. This study investigated the usefulness of C-reactive protein (CRP) changes in discriminating true treatment failure from slow response to treatment., Methods: This prospective multicenter observational study investigated the behavior of plasma CRP levels on days 1 and 4 in hospitalized patients with CAP. We identified non-responding patients as those who had not reached clinical stability by day 4. Among them, true treatment failure and slow response situations were defined when initial therapy had to be changed or not after day 4 by attending clinicians, respectively., Results: By day 4, 78 (27.4%) out of 285 patients had not reached clinical stability. Among them, 56 (71.8%) patients were cured without changes in initial therapy (mortality 0.0%), and in 22 (28.2%) patients, the initial empirical therapy needed to be changed (mortality 40.9%). By day 4, CRP levels fell in 52 (92.9%) slow responding and only in 7 (31.8%) late treatment failure patients (p<0.001). A model developed including CRP behavior and respiratory rate at day 4 identified treatment failure patients with an area under the Receiver Operating Characteristic curve of 0.87 (CI 95%, 0.78-0.96)., Conclusion: Changes in CRP levels are useful to discriminate between true treatment failure and slow response to treatment and can help clinicians in management decisions when CAP patients fail to improve., (Copyright © 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Introduction: A large outbreak of acute Q fever has been reported in the Netherlands with over 3500 cases from 2007 to 2009, during which 749 patients were hospitalised. In foreign cohorts, reported mortality rates in patients hospitalised with acute Q fever, ranged from 0.9 to 2.4%. We analysed mortality among hospitalised patients with acute Q fever in the Netherlands., Methods: Physicians from hospitals in the afflicted region were asked to provide details about patients who died with a diagnosis of acute Q fever between 2007 and 2009., Results: Nine patients (seven males, median age 72 years) from six hospitals were reported, who died within approximately one month following hospitalisation for acute Q fever. Six definite acute Q fever cases and three probable cases were identified. Six patients presented with infiltrates on the chest X-ray and a median CURB-65 score of 3. Median time of hospitalisation was 13 days (range 1-33). All patients had serious, often coinciding, underlying conditions including chronic cardiovascular disease, chronic lung disease, diabetes mellitus and malignancy., Conclusion: The mortality rate of patients hospitalised because of acute Q fever was estimated at approximately 1%. Patients who died with acute Q fever were often male, of older age, and had chronic coinciding underlying conditions, which gives an a priori higher risk of death.

Background: Q fever endocarditis caused by Coxiella burnetii is a potentially fatal disease characterised by a chronic evolution. To assess the long-term outcome and identify prognostic factors for mortality, surgical treatment, and serological changes in Q fever endocarditis, we did a retrospective study in the French National Referral Centre., Methods: Patients included were diagnosed with Q fever endocarditis at our centre from May, 1983, to June, 2006, and followed up for a minimum of 3 years for each patient, history and clinical characteristics were recorded with a standardised questionnaire. Prognostic factors associated with death, surgery, serological cure, and serological relapse were assessed by Cox regression analysis. Excised heart valve analysis was assessed according to duration of treatment., Findings: 104 patients were identified for inclusion in the study, although one was lost to follow-up; median follow-up was 100 months (range 37-310 months). 18 months of treatment was sufficient to sterilise the valves of all the patients except three, and 2 years of treatment sterilised all valves except one. In a multivariate Cox regression analysis, the major determinants associated with mortality were age (hazard ratio 1.11, 95% CI 1.05-1.18, p=0.003), stroke at diagnosis (7.09, 2.00-25.10, p=0.001), endocarditis on a prosthetic valve (6.04, 1.47-24.80, p=0.044), an absence of a four-times decrease of phase I IgG and IgA at 1 year (5.69, 1.00-32.22, p=0.049), or the presence of phase II IgM at 1 year (12.08, 3.11-46.85, p=0.005). Surgery was associated with heart failure (2.68, 1.21-5.94, p=0.015) or a cardiac abscess (4.71, 1.64-13.50, p=0.004). The determinants of poor serological outcome were male sex (0.47, 0.26-0.86, p=0.014), a high level of phase I IgG (0.65, 0.45-0.95, p=0.027), and a delay in the start of treatment with hydroxychloroquine (0.20, 0.04-0.91, p=0.037). Factors associated with relapse were endocarditis on a prosthetic valve (21.3, 2.05-221.86, p=0.01) or treatment duration less than 18 months (9.69, 1.08-86.72, p=0.042)., Interpretation: The optimum duration of treatment with doxycycline and hydroxychloroquine in Q fever endocarditis is 18 months for native valves and 24 months for prosthetic valves. This duration should be extended only in the absence of favourable serological outcomes. Patients should be serologically monitored for at least 5 years because of the risk of relapse., Funding: French National Referral Centre for Q Fever., (2010 Elsevier Ltd. All rights reserved.)

Background: Prosthetic valve endocarditis (PVE) is a serious complication of valve surgery., Aim: The aim of this study is to determine the diagnostic and therapeutic management for PVE., Methods: It's a retrospective study about 14 cases of PVE operated in the department of cardiovascular surgery of la Rabta hospital between January 1996 and December 2006., Results: In two cases, surgery was performed emergent, in the remnant cases surgery was elective. The coagulase-negative staphylococcus (CNS) is the predominant cause of these PVE.Surgery consisted on seven mitral prosthesis replacements and seven aortic prosthesis replacements.Hospital mortality was 50%., Conclusion: In conclusion attention should be made to prevent endocarditis when possible. In case of PVE, an early diagnosis a leads to earlier application of appropriate therapies and improved outcome.

Q fever is a zoonotic disease caused by Coxiella burnetii. Polymorphic, the disease may present as an acute or chronic infection. Vascular infections are the second most common form of chronic Q fever, following endocarditis. Herein, we studied the outcome of 30 new cases of aortic infection caused by C. burnetii using uni- and multivariate analyses. The outcome of ten cases previously reported by our team was also updated. Of these 40 patients, 32 had a follow-up of >or=3 years. Among them, the overall mortality was of 25% (8/32). Vascular rupture was significantly and independently (multivariate P=0.03) associated with a lethal issue, whereas vascular surgery was significantly associated with recovery (uni- and multivariate P<0.01). Our findings demonstrate the critical importance of surgery in the management of C. burnetii vascular infections.

Coxiella burnetii, the etiological agent of Q fever, has two phase variants. Phase I has a complete lipopolysaccharide (LPS), is highly virulent, and causes Q fever in humans and pathology in experimental animals. Phase II lacks an LPS O side chain, is avirulent, and does not grow well in immunocompetent animals. To understand the pathogenicity of Q fever, we investigated the roles of immune components in animals infected with Nine Mile phase I (NM I) or Nine Mile phase II (NM II) bacteria. Immunodeficient mice, including SCID mice (deficient in T and B cells), SCIDbg mice (deficient in T, B, and NK cells), nude mice (deficient in T cells), muMT mice (deficient in B cells), bg mice (deficient in NK cells), mice deficient in tumor necrosis factor alpha (TNF-alpha(-/-) mice), and mice deficient in gamma interferon (IFN-gamma(-/-) mice), were compared for their responses to infection. SCID, SCIDbg, nude, and IFN-gamma(-/-) mice showed high susceptibility to NM I, and TNF-alpha(-/-) mice showed modest susceptibility. Disease caused by NM I in SCID, SCIDbg, and nude mice progressed slowly, while disease in IFN-gamma(-/-) and TNF-alpha(-/-) mice advanced rapidly. B- and NK-cell deficiencies did not enhance clinical disease development or alter bacterial clearance but did increase the severity of histopathological changes, particularly in the absence of B cells. Mice infected with NM II showed no apparent clinical disease, but T-cell-deficient mice had histopathological changes. These results suggest that T cells are critical for clearance of C. burnetii, either NM I or NM II, that IFN-gamma and TNF-alpha are essential for the early control of infection, and that B cells are important for the prevention of tissue damage.

SEVERAL POSSIBLE METHODS OF TRANSFUSION: Q fever is a zoonosis due to Coxiella burnetii. Its interest as a potential biowarfare agent is in its possible transmission by inhalation of sprayed particles. This form of transmission would probably be used: the inhalation of 1 to 10 bacteria could provoke the development of an infection in humans. Another possible method of transmission in the context of a terrorist act would be the intentional introduction of the bacteria into foodstuff. A DISABLING WEAPON: However, C. burnetii has never been used as a biological weapon. The probability that this germ could be used is very low: indeed, the incubation of Q fever is very long, and the majority of the infections is asymptomatic and mortality is low. In fact C. burnetii would more likely be used as a disabling weapon.

We describe five cases of Q fever in pregnant women that were diagnosed during the last 3 years in the town of Martigues in Southern France. Analysis of our cases and the 18 other published cases shows that Q fever is a significant cause of morbidity and mortality in pregnancy. The disease may present as an acute or chronic infection and can be reactivated during subsequent pregnancies, as is seen with other mammals. In Martigues, Q fever is present in at least one per 540 pregnancies and constitutes the most significant public health problem related to intrauterine infections.

We studied 32 cases of Q fever endocarditis diagnosed in France between January 1985 and December 1989 to evaluate the efficacies of the different regimens of antibiotics used for treatment. Each patient was monitored during the treatment (range, 12 to 60 months), and clinical and biological information was computerized. Various treatments were prescribed, including doxycycline alone (9 cases) or in association with rifampin (4 cases), quinolones (16 cases), or sulfamethoxazole-trimethoprim (1 case). Two patients died before the beginning of the treatment. Nineteen patients had hemodynamic failure and subsequently underwent valve replacement. Nine valve tissue cultures were positive despite previous antibiotic treatment. In terms of their effects on mortality, the difference between doxycycline alone and doxycycline plus quinolones is statistically significant. We conclude that the addition of quinolones to doxycycline is beneficial. On the basis of clinical, serological, and valve tissue culture results, no treatment was able to cure Q fever endocarditis within 2 years, even with a combination of antibiotics. We advise a minimum duration of treatment of 3 years with therapy combining quinolones and doxycycline.

The susceptibility of inbred strains of mice to infection by phase I Coxiella burnetii, the aetiological agent of Q fever, was investigated by evaluating morbidity, mortality, antibody production and in vitro proliferative responses of splenic lymphocytes. Among the 47 strains of mice tested for morbidity and mortality to C. burnetii infection, 33 were resistant, 10 were of intermediate sensitivity, and four were sensitive. A/J mice exhibited the highest mortality, and surviving mice of this strain yielded high concentrations of viable rickettsiae from essentially all organs for more than 3 weeks after inoculation. However, A/J mice developed a protective immune response after vaccination with inactivated C. burnetii cells. Induction of gross pathological responses and antibody production were similar in sensitive mice (strain A/J) and resistant mice (strain C57BL/6J). The LD50 of phase I C. burnetii for A/J mice was about 1000-fold lower than that for the more resistant C57BL/6J mice. Mice of both strains developed antibody titres against phase I cells, phase II cells, and phase I lipopolysaccharide after the injection of one or more viable phase I organisms of C. burnetii; five or more rickettsiae caused splenomegaly that was almost proportional to the infecting dose. Suppression of in vitro proliferative responses of splenic lymphocytes to concanavalin A, a T-cell mitogen, was apparent after infection of sensitive A/J mice with as few as one to five phase I micro-organisms. However, suppression of proliferation of splenic lymphocytes from resistant C57BL/6J mice required 10(7) phase I C. burnetii.