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We prospectively studied the feasibility and effectiveness of sputum induction in obtaining good quality sputum and its subsequent bacterial yield in children with clinically suspected acute lower-respiratory-tract infection (aLRTI). Good quality sputum was collected in 89/98 (91%) patients. Sputum cultures revealed ≥1 bacterial pathogens in 22 cases (25%). Adverse events were infrequent and mild (6%). Sputum induction is feasible in young children and leads to an increased number of etiological diagnoses of aLRTI.

Coxiella burnetii, the causative agent of Q fever, is recognized by TLR2. TLR10 can act as an inhibitory receptor on TLR2-derived immune responses. Therefore, we investigated the role of TLR10 on C. burnetii-induced cytokine production and assessed whether genetic polymorphisms in TLR10 influences the development of chronic Q fever. HEK293 cells, transfected with TLR2, TLR10 or TLR2/TLR10, and human peripheral blood mononuclear cells (PBMCs) in the presence of anti-TLR10, were stimulated with C. burnetii. In both assays, the absence of TLR10 resulted in increased cytokine responses after C. burnetii stimulation. In addition, the effect of single nucleotide polymorphisms (SNPs) in TLR10 was examined in healthy volunteers whose PBMCs were stimulated with C. burnetii Nine Mile or the Dutch outbreak isolate C. burnetii 3262. Individuals bearing SNPs in TLR10 displayed increased cytokine production upon C. burnetii 3262 stimulation. Furthermore, 139 chronic Q fever patients and 220 controls were genotyped for TLR10 N241H, I775V and I369L. None of these polymorphisms were associated with increased susceptibility to chronic Q fever. In conclusion, TLR10 has an inhibitory effect on in vitro cytokine production by C. burnetii, but the presence of TLR10 polymorphisms does not lead to an increased risk of developing chronic Q fever., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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.)

The aim of this study was to evaluate the quality of life in patients with vascular chronic Q fever at time of diagnosis and during follow-up. Based upon the SF-36 questionnaire, the mean physical and mental health of each patient were assessed at 3-month intervals for up to 18 months. A total of 26 patients were included in the study. At time of diagnosis, the mean physical health and mental health score was 50·6 [95% confidence interval (CI) 46·7-54·4] and 44·6 (95% CI 41·6-47·5), respectively. During treatment, the mean physical health score declined significantly by 1·7 points each 3 months (P < 0·001) to 40·8 (95% CI 34·4-45·1). The mean mental health score significantly and steadily increased towards 51·2 (95% CI 46·9-54·3) during follow-up (P = 0·026). A total of 23% of patients were cured after 18 months of follow-up. In conclusion, quality of life at time of diagnosis for patients with vascular chronic Q fever is lower compared to a similar group of patients, matched for age and gender, with an aortic abdominal aneurysmal disease, and physical health decreases further after starting treatment. Considering the low percentage of cure, the current treatment of vascular chronic Q fever patients may require a separate strategy from that of endocarditis in order to increase survival.

Background: Q fever is an infection caused by Coxiella burnetii. Persistent infection (chronic Q fever) develops in 1%-5% of patients. We hypothesize that inefficient recognition of C. burnetii and/or activation of host-defense in individuals carrying genetic variants in pattern recognition receptors or adaptors would result in an increased likelihood to develop chronic Q fever., Methods: Twenty-four single-nucleotide polymorphisms in genes encoding Toll-like receptors, nucleotide-binding oligomerization domain-like receptor-2, αvβ3 integrin, CR3, and adaptors myeloid differentiation primary response protein 88 (MyD88), and Toll interleukin 1 receptor domain-containing adaptor protein (TIRAP) were genotyped in 139 patients with chronic Q fever and in 220 controls with cardiovascular risk-factors and previous exposure to C. burnetii. Associations between these single-nucleotide polymorphisms and chronic Q fever were assessed by means of univariate logistic regression models. Cytokine production in whole-blood stimulation assays was correlated with relevant genotypes., Results: Polymorphisms in TLR1 (R80T), NOD2 (1007fsX1), and MYD88 (-938C>A) were associated with chronic Q fever. No association was observed for polymorphisms in TLR2, TLR4, TLR6, TLR8, ITGAV, ITGB3, ITGAM, and TIRAP. No correction for multiple testing was performed because only genes with a known role in initial recognition of C. burnetii were included. In the whole-blood assays, individuals carrying the TLR1 80R-allele showed increased interleukin 10 production with C. burnetii exposure., Conclusions: Polymorphisms in TLR1 (R80T), NOD2 (L1007fsX1), and MYD88 (-938C>A) are associated with predisposition to development of chronic Q fever. For TLR1, increased interleukin 10 responses to C. burnetii in individuals carrying the risk allele may contribute to the increased risk of chronic Q fever., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Serological follow-up of acute Q-fever patients is important for detection of chronic infection but there is no consensus on its frequency and duration. The 2007-2009 Q-fever epidemic in the Netherlands allowed for long-term follow-up of a large cohort of acute Q-fever patients. The aim of this study was to validate the current follow-up strategy targeted to identify patients with chronic Q-fever., Methods: A cohort of adult acute Q-fever patients, diagnosed between 2007 and 2009, for whom a twelve-month follow-up sample was available, was invited to complete a questionnaire and provide a blood sample, four years after the acute episode. Antibody profiles, determined by immunofluorescence assay in serum, were investigated with a special focus on high titres of IgG antibodies against phase I of Coxiella burnetii, as these are considered indicative for possible chronic Q-fever., Results: Of the invited 1,907 patients fulfilling inclusion criteria, 1,289 (67.6%) were included in the analysis. At any time during the four-year follow-up period, 58 (4.5%) patients were classified as possible, probable, or proven chronic Q-fever according to the Dutch Q-fever Consensus Group criteria (which uses IgG phase I ≥1:1,024 to as serologic criterion for chronic Q-fever). Fifty-two (89.7%) of these were identified within the first year after the acute episode. Of the six patients that were detected for the first time at four-year follow-up, five had an IgG phase I titre of 1:512 at twelve months., Conclusions: A twelve-month follow-up check after acute Q-fever is recommended as it adequately detects chronic Q-fever in patients without known risk factors. Additional serological and clinical follow-up is recommended for patients with IgG phase I ≥1:512, as they showed the highest risk to progress to chronic Q-fever.

Chronic Q fever, caused by Coxiella burnetii, has high mortality and morbidity rates if left untreated. Controversy about the diagnosis of this complex disease has emerged recently. We applied the guideline from the Dutch Q Fever Consensus Group and a set of diagnostic criteria proposed by Didier Raoult to all 284 chronic Q fever patients included in the Dutch National Chronic Q Fever Database during 2006–2012. Of the patients who had proven cases of chronic Q fever by the Dutch guideline, 46 (30.5%)would not have received a diagnosis by the alternative criteria designed by Raoult, and 14 (4.9%) would have been considered to have possible chronic Q fever. Six patients with proven chronic Q fever died of related causes. Until results from future studies are available, by which current guidelines can be modified, we believe that the Dutch literature-based consensus guideline is more sensitive and easier to use in clinical practice.

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., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

On the day that Great Britain declared war on Germany in 1914, the Irish physician and bacteriologist Adrian Stokes travelled to London to volunteer. One week later he left for France with the first British troops as an officer with the Royal Army Medical Corps. He spent most of the First World War attached to No. 1 Mobile Bacteriological Laboratory at the Remy Siding British-Canadian field hospital in Flanders. In April 1916, he was confronted with an outbreak of trench jaundice, also known as epidemic jaundice (Weil's disease). Conditions in the trenches contributed to the hundred cases identified by Stokes in a short period. In 1917, he was the first to publish (in The Lancet) the finding that the bacterium Spirochaeta icterohaemorrhagiae, the causative agent of epidemic jaundice, could be isolated from the kidneys of rats. A subsequent rat control campaign in the trenches successfully curbed the disease.

Background: The extracellular domains of cytokine receptors are released during inflammation, but little is known about the shedding of Toll-like receptors (TLR) and whether they can be used as diagnostic biomarkers., Methods: The release of sTLR2 and sTLR4 was studied in in-vitro stimulations, as well as in-vivo during experimental human endotoxemia (n = 11, 2 ng/kg LPS), and in plasma of 394 patients with infections (infectious mononucleosis, measles, respiratory tract infections, bacterial sepsis and candidemia) or non-infectious inflammation (Crohn's disease, gout, rheumatoid arthritis, autoinflammatory syndromes and pancreatitis). Using C-statistics, the value of sTLR2 and sTLR4 levels for discrimination between infections and non-infectious inflammatory diseases, as well as between viral and bacterial infections was analyzed., Results: In-vitro, peripheral blood mononuclear cells released sTLR2 and sTLR4 by exposure to microbial ligands. During experimental human endotoxemia, plasma concentrations peaked after 2 hours (sTLR4) and 4 hours (sTLR2). sTLR4 did not correlate with cytokines, but sTLR2 correlated positively with TNFα (rs = 0.80, P < 0.05), IL-6 (rs = 0.65, P < 0.05), and IL-1Ra (rs = 0.57, P = 0.06), and negatively with IL-10 (rs = -0.58, P = 0.06), respectively. sTLR4 had a similar area under the ROC curve [AUC] for differentiating infectious and non-infectious inflammation compared to CRP: 0.72 (95% CI 0.66-0.79) versus 0.74 (95% CI 0.69-0.80) [P = 0.80], while sTLR2 had a lower AUC: 0.60 (95% CI 0.54-0.66) [P = 0.0004]. CRP differentiated bacterial infections better from viral infections than sTLR2 and sTLR4: AUC 0.94 (95% CI 0.90-0.96) versus 0.58 (95% CI 0.51-0.64) and 0.75 (95% CI 0.70-0.80), respectively [P < 0.0001 for both]., Conclusions: sTLRs are released into the circulation, and suggest the possibility to use sTLRs as diagnostic tool in inflammatory conditions.

The Meuse-Argonne offensive, a decisive battle during the First World War, is the largest frontline commitment in American military history involving 1.2 million U.S. troops. With over 26,000 deaths among American soldiers, the offensive is considered "America's deadliest battle". The Meuse-Argonne offensive coincided with the highly fatal second wave of the influenza pandemic in 1918. In Europe and in U.S. Army training camps, 1918 pandemic influenza killed around 45,000 American soldiers making it questionable which battle should be regarded "America's deadliest". The origin of the influenza pandemic has been inextricably linked with the men who occupied the military camps and trenches during the First World War. The disease had a profound impact, both for the military apparatus and for the individual soldier. It struck all the armies and might have claimed toward 100 000 fatalities among soldiers overall during the conflict while rendering millions ineffective. Yet, it remains unclear whether 1918 pandemic influenza had an impact on the course of the First World War. Still, even until this day, virological and bacteriological analysis of preserved archived remains of soldiers that succumbed to 1918 pandemic influenza has important implications for preparedness for future pandemics. These aspects are reviewed here in a context of citations, images, and documents illustrating the tragic events of 1918., (© 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

The aim of this study was to describe specific histological findings of the Coxiella burnetii-infected aneurysmal abdominal aortic wall. Tissue samples of the aneurysmal abdominal aortic wall from seven patients with chronic Q fever and 15 patients without evidence of Q fever infection were analysed and compared. Chronic Q fever was diagnosed using serology and tissue PCR analysis. Histological sections were stained using haematoxylin and eosin staining, Elastica van Gieson staining and immunohistochemical staining for macrophages (CD68), T lymphocytes (CD3), T lymphocyte subsets (CD4 and CD8) and B lymphocytes (CD20). Samples were scored by one pathologist, blinded for Q fever status, using a standard score form. Seven tissue samples from patients with chronic Q fever and 15 tissue samples from patients without Q fever were collected. Four of seven chronic Q fever samples showed a necrotizing granulomatous response of the vascular wall, which was characterized by necrotic core of the arteriosclerotic plaque (P = 0.005) and a presence of high numbers of macrophages in the adventitia (P = 0.007) distributed in typical palisading formation (P = 0.005) and surrounded by the presence of high numbers of T lymphocytes located diffusely in media and adventitia. Necrotizing granulomas are a histological finding in the C. burnetii-infected aneurysmal abdominal aortic wall. Chronic Q fever should be included in the list of infectious diseases with necrotizing granulomatous response, such as tuberculosis, cat scratch disease and syphilis., (© 2014 The Authors. International Journal of Experimental Pathology © 2014 International Journal of Experimental Pathology.)

Objectives: The aim of this study was to estimate the seroprevalence of Q fever and prevalence of chronic Q fever in patients with abdominal aortic and/or iliac disease after the Q fever outbreak of 2007-2010 in the Netherlands., Methods: In November 2009, an ongoing screening program for Q fever was initiated. Patients with abdominal aortic and/or iliac disease were screened for presence of IgM and IgG antibodies to phase I and II antigens of Coxiella burnetii using immunofluorescence assay and presence of C. burnetii DNA in sera and/or vascular wall tissue using polymerase chain reaction (PCR)., Results: A total of 770 patients with abdominal aortic and/or iliac disease were screened. Antibodies against C. burnetii were detected in 130 patients (16.9%), of which 40 (30.8%) patients showed a serological profile of chronic Q fever. Three patients presented with acute Q fever, one of which developed to chronic Q fever over time. The number of aneurysm-related acute complications in patients with chronic Q fever was significantly higher compared to patients negative for Q fever (p = 0.013); 9.0% (30/333) vs. 30.0% (6/20). Eight out of 46 patients with past resolved Q fever (8/46, 17.4%) presented with aneurysm-related acute complications (no significant difference)., Conclusion: The prevalence of chronic Q fever in C. burnetii seropositive patients with abdominal aortic and/or iliac disease living in an epidemic area in the Netherlands is remarkably high (30.8%). Patients with an aneurysm and chronic Q fever present more often with an aneurysm-related acute complication compared to patients without evidence of Q fever infection., (Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

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.

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.

From 2007 to 2010, the Netherlands experienced the largest reported Q fever outbreak, with >4,000 notified cases. We showed previously that C-reactive protein is the only traditional infection marker reflecting disease activity in acute Q fever. Interleukin-6 is the principal inducer of C-reactive protein. We questioned whether increased C-reactive protein levels in acute Q fever patients coincide with increased interleukin-6 levels and if these levels correlate with the Coxiella burnetii DNA load in serum. In addition, we studied their correlation with disease severity, expressed by hospital admission and the development of fatigue. Interleukin-6 and C-reactive protein levels were analyzed in sera from 102 patients diagnosed with seronegative PCR-positive acute Q fever. Significant but weak negative correlations were observed between bacterial DNA loads expressed as cycle threshold values and interleukin-6 and C-reactive protein levels, while a significant moderate-strong positive correlation was present between interleukin-6 and C-reactive protein levels. Furthermore, significantly higher interleukin-6 and C-reactive protein levels were observed in hospitalized acute Q fever patients in comparison to those in nonhospitalized patients, while bacterial DNA loads were the same in the two groups. No marker was prognostic for the development of fatigue. In conclusion, the correlation between interleukin-6 and C-reactive protein levels in acute Q fever patients points to an immune activation pathway in which interleukin-6 induces the production of C-reactive protein. Significant differences in interleukin-6 and C-reactive protein levels between hospitalized and nonhospitalized patients despite identical bacterial DNA loads suggest an important role for host factors in disease presentation. Higher interleukin-6 and C-reactive protein levels seem predictive of more severe disease.

Background: From 2007 to 2009, The Netherlands experienced a major Q fever epidemic, with higher hospitalization rates than the 2-5% reported in the literature for acute Q fever pneumonia and hepatitis. We describe epidemiological and clinical features of hospitalized acute Q fever patients and compared patients presenting with Q fever pneumonia with patients admitted for other forms of community-acquired pneumonia (CAP). We also examined whether proximity to infected ruminant farms was a risk factor for hospitalization., Methods: A retrospective cohort study was conducted for all patients diagnosed and hospitalized with acute Q fever between 2007 and 2009 in one general hospital situated in the high incidence area in the south of The Netherlands. Pneumonia severity scores (PSI and CURB-65) of acute Q fever pneumonia patients (defined as infiltrate on a chest x-ray) were compared with data from CAP patients. Hepatitis was defined as a >twofold the reference value for alanine aminotransferase and for bilirubin., Results: Among the 183 hospitalized acute Q fever patients, 86.0% had pneumonia. Elevated liver enzymes (alanine aminotransferase) were found in 32.3% of patients, although hepatitis was not observed in any of them. The most frequent clinical signs upon presentation were fever, cough and dyspnoea. The median duration of admission was five days. Acute Q fever pneumonia patients were younger, had less co-morbidity, and lower PSI and CURB-65 scores than other CAP patients. Anecdotal information from attending physicians suggests that some patients were admitted because of severe subjective dyspnoea, which was not included in the scoring systems. Proximity to an infected ruminant farm was not associated with hospitalization., Conclusion: Hospitalized Dutch acute Q fever patients mostly presented with fever and pneumonia. Patients with acute Q fever pneumonia were hospitalized despite low PSI and CURB-65 scores, presumably because subjective dyspnoea was not included in the scoring systems.

Objectives: The objective of this study was to investigate the antibiotic resistance patterns, including methicillin resistance, inducible macrolide-lincosamide-streptogramin B (MLSB ) resistance and Panton-Valentine leukocidin (PVL) toxin gene carriage among hospital-acquired Staphylococcus aureus (HA-SA) and community-acquired S. aureus (CA-SA), in Beira, Mozambique., Methods: In 2010-2011, two prospective surveillance studies were conducted on post-operative and burn wound infections at the Central Hospital of Beira and on skin and soft tissue abscesses at the São Lucas Health Centre. We cultured pus samples, identified suspected S. aureus isolates and performed antimicrobial susceptibility testing, including detection of MLSB resistance. Real-time polymerase chain reaction was used to detect mecA, Martineau and PVL genes., Results: The prevalence of hospital-acquired methicillin-resistant S. aureus (HA-MRSA) infection among 53 inpatients was 15.1%; the prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA) infection among 100 outpatients was 1.0%. Inducible MLSB resistance was present in 41.7% and 10.7% of HA-SA and CA-SA isolates, respectively. PVL toxin gene was detected in 81.1% of methicillin-susceptible S. aureus (MSSA) compared with 11.1% of methicillin-resistant S. aureus., Conclusions: Our study shows, for the first time in Mozambique, the emergence of HA-MRSA. The prevalence of CA-MRSA was low, whereas the rate of PVL toxin gene carriage in MSSA was high. The high rate of inducible MLSB resistance indicates the importance of performing routine D-tests. Overall, our results show the need of strengthening laboratory facilities to provide microbiological data for both directed therapy and surveillance., (© 2013 John Wiley & Sons Ltd.)

We report 2 patients with symptomatic aortic aneurysm and serologic evidence of acute Q fever with positive Coxiella burnetii PCR in blood/tissue. This suggests a role for acute Q fever in aneurysm progression. Diagnostic testing for Q fever infection in patients with symptomatic aneurysms in Q fever areas is recommended., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A case series of 14 patients with Raoultella bacteremia was compared with 28 Klebsiella oxytoca and 28 Klebsiella pneumoniae bacteremia cases. Forty-three percent of Raoultella bacteremia cases were associated with biliary tract disease, compared to 32% and 22% of patients with K. oxytoca and K. pneumoniae bacteremia, respectively.

Molecular pathogen detection from blood is still expensive and the exact clinical value remains to be determined. The use of biomarkers may assist in preselecting patients for immediate molecular testing besides blood culture. In this study, 140 patients with ≥ 2 SIRS criteria and clinical signs of infection presenting at the emergency department of our hospital were included. C-reactive protein (CRP), neutrophil-lymphocyte count ratio (NLCR), procalcitonin (PCT) and soluble urokinase plasminogen activator receptor (suPAR) levels were determined. One ml EDTA blood was obtained and selective pathogen DNA isolation was performed with MolYsis (Molzym). DNA samples were analysed for the presence of pathogens, using both the MagicPlex Sepsis Test (Seegene) and SepsiTest (Molzym), and results were compared to blood cultures. Fifteen patients had to be excluded from the study, leaving 125 patients for further analysis. Of the 125 patient samples analysed, 27 presented with positive blood cultures of which 7 were considered to be contaminants. suPAR, PCT, and NLCR values were significantly higher in patients with positive blood cultures compared to patients without (p < 0.001). Receiver operating characteristic curves of the 4 biomarkers for differentiating bacteremia from non-bacteremia showed the highest area under the curve (AUC) for PCT (0.806 (95% confidence interval 0.699-0.913)). NLCR, suPAR and CRP resulted in an AUC of 0.770, 0.793, and 0.485, respectively. When compared to blood cultures, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for SepsiTest and MagicPlex Sepsis Test were 11%, 96%, 43%, 80%, and 37%, 77%, 30%, 82%, respectively. In conclusion, both molecular assays perform poorly when one ml whole blood is used from emergency care unit patients. NLCR is a cheap, fast, easy to determine, and rapidly available biomarker, and therefore seems most promising in differentiating BSI from non-BSI patients for subsequent pathogen identification using molecular diagnostics.

Objectives: In the Netherlands, people at risk for chronic Q fever were vaccinated against Coxiella burnetii with the inactivated whole cell vaccine Q-vax®. We aimed to measure the immune responses to C. burnetii six and twelve months after vaccination in this relevant population., Methods: In 260 vaccinees, antibody responses were assessed by immunofluorescence assay (IFA), complement fixation test and ELISA. The cellular immune responses were assessed by measuring C. burnetii-specific interferon (IFN)-γ production in blood. Serological results of 200 individuals with past Q fever were used for comparison., Results: At six months, 46% of vaccinees showed low IFA antibody titres and 67% had a positive IFN-γ assay; At twelve months, both were 60%. In contrast, individuals with a past Q fever were seropositive in 99.5% at six and twelve months, with relatively higher IFA titres. Interestingly, vaccinees with positive IFN-γ assay pre-vaccination, showed a higher seroconversion rate than IFN-γ negative vaccinees: 74% vs. 41% (p < 0.001)., Conclusions: The immune response after Q-vax® vaccination is lower and restricted to a smaller proportion than found after past Q fever and than previously described after vaccination, suggesting decreased vaccine immunogenicity in this high-risk population. A positive IFN-γ assay before vaccination in seronegative vaccinees likely points to pre-existing immunity resulting in boosting by vaccination., (Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: Understanding which pathogens are associated with clinical manifestation of community-acquired pneumonia (CAP) is important to optimise treatment. We performed a study on the aetiology of CAP and assessed possible implications for patient management in the Netherlands., Methods: Patients with CAP attending the emergency department of a general hospital were invited to participate in the study. We used an extensive combination of microbiological techniques to determine recent infection with respiratory pathogens. Furthermore, we collected data on clinical parameters and potential risk factors., Results: From November 2007 through January 2010, 339 patients were included. Single bacterial infection was found in 39% of these patients, single viral infection in 12%, and mixed bacterial-viral infection in 11%. Streptococcus pneumoniae was the most frequently identified pathogen (22%; n=74). Infection with atypical bacteria was detected in 69 (20%) of the patients., Conclusion: Initial empirical antibiotics should be effective against S. pneumoniae, the most common pathogen identified in CAP patients. The large proportion of patients with infection with atypical bacteria points to the need for improved diagnostic algorithms including atypical bacteria, especially since these atypical bacteria are not covered by the first-choice antibiotic treatment according to the recently revised Dutch guidelines on the management of CAP.

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.

We describe a case of Staphylococcus aureus sepsis after acupuncture for chronic fatigue syndrome (CFS). Sepsis is a rare, but potentially fatal complication of acupuncture. The most common cause of bacterial infection after acupuncture is S. aureus. The effectiveness of acupuncture for the treatment of CFS is not proven, therefore the potential benefits should be weighed against the risks.

Background: Chronic Q-fever, a condition with high morbidity and mortality, may develop after an acute infection with Coxiella burnetii (acute Q-fever). Several strategies have been suggested for early detection of chronic Q-fever, focusing on follow-up of known acute Q-fever patients and detection of asymptomatic or unknown chronic infections. As there is no international standard or consensus, the aims of this study were to summarise the available literature and assess the evidence for different follow-up and screening strategies., Design: We conducted a systematic review by searching PubMed and Embase. Twenty articles were included, of which fourteen only provided information on follow-up of known acute Q-fever cases, four presented data on identification of previously unknown C. burnetii infections, and two had information on both topics., Results: The conversion rate of acute to chronic Q-fever ranged from 0 to 5.0%. Most studies advised serological follow-up of acute Q-fever patients, but without consistent advice on optimum timing and duration. The recommendation to use echocardiography for all acute Q-fever patients to detect valvular damage remains controversial. Screening of high-risk patients in an outbreak setting is advised by studies investigating such strategy., Conclusions: There is sufficient evidence to support serological follow-up of all known acute Q-fever patients at least once during the first year following the acute infection, and more frequently in patients with known risk factors for chronic disease, such as heart valve- or vascular prosthesis. Screening of risk groups should be considered in outbreaks of Q-fever., (© 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Untreated chronic Q fever causes a high number of complications and deaths. We present cases of chronic Q fever that were not diagnosed until after the patients underwent cardiac valve surgery. In epidemic areas, Q fever screening of valve surgery patients secures early initiation of treatment and can prevent illness and death.

Study Objective: Absolute lymphocytopenia is recognised as an important hallmark of the immune response to severe infection and observed in patients with Legionnaires' disease. To explore the immune response, we studied the dynamics of peripheral blood lymphocyte subpopulations in the acute and subacute phase of LD., Methods and Results: EDTA-anticoagulated blood was obtained from eight patients on the day the diagnosis was made through detection of L. pneumophila serogroup 1 antigen in urine. A second blood sample was obtained in the subacute phase. Multiparametric flow cytometry was used to calculate lymphocyte counts and values for B-cells, T-cells, NK cells, CD4+ and CD8+ T-cells. Expression of activation markers was analysed. The values obtained in the subacute phase were compared with an age and gender matched control group. Absolute lymphocyte count (×10⁹/l, median and range) significantly increased from 0.8 (0.4-1.6) in the acute phase to 1.4 (0.8-3.4) in the subacute phase. B-cell count showed no significant change, while T-cell count (×10⁶/l, median and range) significantly increased in the subacute phase (495 (182-1024) versus 979 (507-2708), p = 0.012) as a result of significant increases in both CD4+ and CD8+ T-cell counts (374 (146-629) versus 763 (400-1507), p = 0.012 and 119 (29-328) versus 224 (107-862), p = 0.012). In the subacute phase of LD, significant increases were observed in absolute counts of activated CD4+ T-cells, naïve CD4+ T-cells and memory CD4+ T-cells. In the CD8+ T-cell compartment, activated CD8+ T-cells, naïve CD8+ T-cell and memory CD8+ T-cells were significantly increased (p<0.05)., Conclusion: The acute phase of LD is characterized by absolute lymphocytopenia, which recovers in the subacute phase with an increase in absolute T-cells and re-emergence of activated CD4+ and CD8+ T cells. These observations are in line with the suggested role for T-cell activation in the immune response to LD.

The Netherlands experienced an unprecedented outbreak of Q fever between 2007 and 2010. The Jeroen Bosch Hospital (JBH) in 's-Hertogenbosch is located in the centre of the epidemic area. Based on Q fever screening programmes, seroprevalence of IgG phase II antibodies to Coxiella burnetii in the JBH catchment area was 10·7% [785 tested, 84 seropositive, 95% confidence interval (CI) 8·5-12·9]. Seroprevalence appeared not to be influenced by age, gender or area of residence. Extrapolating these data, an estimated 40 600 persons (95% CI 32 200-48 900) in the JBH catchment area have been infected by C. burnetii and are, therefore, potentially at risk for chronic Q fever. This figure by far exceeds the nationwide number of notified symptomatic acute Q fever patients and illustrates the magnitude of the Dutch Q fever outbreak. Clinicians in epidemic Q fever areas should be alert for chronic Q fever, even if no acute Q fever is reported.

Background: Lymphocytopenia has frequently been described in patients with malaria, but studies on its association with disease severity have yielded conflicting results. The neutrophil/lymphocyte count ratio (NLCR) has been introduced as a parameter for systemic inflammation in critically ill patients and was found, together with lymphocytopenia, to be a better predictor of bacteraemia than routine parameters like C-reactive protein and total leukocyte count. In the present study, the predictive value of the NLCR and lymphocytopenia for severe disease was evaluated in patients with imported malaria., Methods: All patients diagnosed with malaria at the Harbour Hospital between January 1st 1999 and January 1st 2012 with differential white cell counts determined within the first 24 hours after admission were included in this retrospective study. Severe malaria was defined according to the WHO criteria. The performance of the NLCR and lymphocytopenia as a marker of severe malarial disease was compared back-to-back with that of C-reactive protein as a reference biomarker., Results: A total of 440 patients (severe falciparum malaria n = 61, non-severe falciparum malaria n = 259, non-falciparum malaria n=120) were included in the study. Lymphocytopenia was present in 52% of all patients and the median NLCR of all patients was 3.2. Total lymphocyte counts and NLCR did not differ significantly between groups. A significant correlation of total leukocyte count and NLCR, but not lymphocyte count, with parasitaemia was found. ROC analysis revealed a good negative predictive value but a poor positive predictive value of both lymphocytopenia and NLCR and performance was inferior to that of C-reactive protein. After complete parasite clearance a significant rise in total leukocyte count and lymphocyte count and a significant decrease in NLCR was observed., Conclusion: The NLCR was found to correlate with parasitaemia, but both lymphocytopenia and the NLCR were inferior to C-reactive protein as markers for severe disease in patients with imported malaria. The NLCR and lymphocytopenia are not useful as predictive markers for severe disease in imported malaria in the acute care setting.

Objectives: A prospective surveillance study was conducted to investigate the epidemiology and patterns of antibiotic resistance among uropathogens from hospitalised children in Beira, Mozambique. Additionally, information regarding determinants of a urinary tract infection (UTI) was obtained., Methods: Bacterial species identification, antimicrobial susceptibility testing and extended-spectrum beta-lactamase testing were performed for relevant bacterial isolates., Results: Analysis of 170 urine samples from 148 children yielded 34 bacterial isolates, predominantly Escherichia coli and Klebsiella spp., causative of a urinary tract infection in 29 children; 30/34 isolates (88.2%) from 26/29 children (89.7%) were considered highly resistant micro-organisms (HRMOs). No significant determinants of urinary tract infection with HRMOs were detected when analysing gender, antibiotic use during hospital admission and HIV status., Conclusion: This study shows, for the first time in Mozambique, an extremely high prevalence of HRMOs among uropathogens from hospitalised children with a urinary tract infection.

Starting August 2012, an increase in Cryptosporidium infections was reported in the Netherlands, the United Kingdom and Germany. It represented a 1.8 to 4.9-fold increase compared to previous years. Most samples were C. hominis IbA10G2. A case–control study was performed in the Netherlands but did not identify an endemic source. A case–case study in the north of England found travel abroad to be the most common risk factor.

Large outbreaks of Q fever in The Netherlands have provided a unique opportunity for studying longitudinal serum antibody responses in patients. Results are presented of a cohort of 344 patients with acute symptoms of Q fever with three or more serum samples per patient. In all these serum samples IgM and IgG against phase 1 and 2 Coxiella burnetii were measured by an immunofluorescence assay. A mathematical model of the dynamic interaction of serum antibodies and pathogens was used in a mixed model framework to quantitatively analyse responses to C. burnetii infection. Responses show strong heterogeneity, with individual serum antibody responses widely different in magnitude and shape. Features of the response, peak titre and decay rate, are used to characterize the diversity of the observed responses. Binary mixture analysis of IgG peak levels (phases 1 and 2) reveals a class of patients with high IgG peak titres that decay slowly and may represent potential chronic cases. When combining the results of mixture analysis into an odds score, it is concluded that not only high IgG phase 1 may be predictive for chronic Q fever, but also that high IgG phase 2 may aid in detecting such putative chronic cases.

The emergence of tetanus in wounded soldiers during the first months of the First World War (WWI) resulted from combat on richly manured fields in Belgium and Northern France, the use of modern explosives that produced deep tissue wounds and the intimate contact between the soldier and the soil upon which he fought. In response, routine prophylactic injections with anti-tetanus serum were given to wounded soldiers removed from the firing line. Subsequently, a steep fall in the incidence of tetanus was observed on both sides of the conflict. Because of fatal serum anaphylaxis associated with administration of serum at a time when purification methods still needed to be improved, it must be presumed that tens to hundreds of men might have died as a result of the routine administration of anti-tetanus serum during WWI. Yet anti-tetanus serum undoubtedly prevented life threatening tetanus among several hundred thousands of wounded men, making it one of the most successful preventive interventions in wartime medicine. After the abrupt fall in tetanus incidence in 1914 due to introduction of anti-tetanus serum, the incidence of the disease tended to become even lower as the war went on. This was probably due to earlier and more thorough surgical treatment, consisting of opening, cleaning, excision and drainage of wounds as early as possible. In this overview, recent battlefield findings from the Meuse-Argonne offensive in 1918 are used to illustrate common practices employed in the prevention of tetanus during WWI.

Background: The pathophysiological mechanisms which contribute to an increased risk of community-acquired pneumonia (CAP) in patients using proton pump inhibitors are not well established., Aim: To examine differences in microbial etiology in patients with CAP between patients with and without proton pump inhibitor (PPI) therapy and its possible impact on disease severity., Methods: All individuals consulting the emergency care unit were prospectively registered and underwent chest radiography. Sputum, urine, nose-throat swabs and blood samples were obtained for microbial evaluation. We evaluated the association between use of proton pump inhibitors, etiology of CAP and severity of illness with multivariate regression analysis., Results: The final cohort comprised 463 patients, 29% using proton pump inhibitors (PPIs). Pathogens regarded as oropharyngeal flora were more common in CAP patients using PPI therapy compared to those who did not (adjusted OR: 2.0; 95% CI: 1.22-3.72). Patients using proton pump inhibitors more frequently had an infection with Streptococcus pneumoniae (28% vs. 14%) and less frequently with Coxiella burnetii (8% vs. 19%) compared to nonuser of PPI. Adjusted for baseline differences, the risk of PPI users being infected with S. pneumonia was 2.23 times (95% CI: 1.28-3.75) higher compared to patients without PPI's. No risk between PPI use and any other microbial pathogen was found. There was no difference in severity of CAP between patients with and without using PPI therapy., Conclusions: Proton pump inhibitor therapy was associated with an approximately 2-fold increased risk to develop community-acquired pneumonia possibly as a result of S. pneumoniae infection., (© 2012 Blackwell Publishing Ltd.)

Little is known about the effect of timing of antibiotic treatment on development of IgG antibodies following acute Q fever. We studied IgG antibody responses in symptomatic patients diagnosed either before or during development of the serologic response to Coxiella burnetii. Between 15 and 31 May 2009, 186 patients presented with acute Q fever, of which 181 were included in this retrospective study: 91 early-diagnosed (ED) acute Q fever patients, defined as negative IgM phase II enzyme-linked immunosorbent assay (ELISA) and positive PCR, and 90 late-diagnosed (LD) acute Q fever patients, defined as positive/dubious IgM phase II ELISA and positive immunofluorescence assay (IFA). Follow-up serology at 3, 6, and 12 months was performed using IFA (IgG phase I and II). High IgG antibody titers were defined as IgG phase II titers of ≥1:1,024 together with IgG phase I titers of ≥1:256. At 12 months, 28.6% of ED patients and 19.5% of LD patients had high IgG antibody titers (P = 0.17). No statistically significant differences were found in frequencies of IgG phase I and IgG phase II antibody titers at all follow-up appointments for adequately and inadequately treated patients overall, as well as for ED and LD patients analyzed separately. Additionally, no significant difference was found in frequencies of high antibody titers and between early (treatment started within 7 days after seeking medical attention) and late timing of treatment. This study indicates that early diagnosis and antibiotic treatment of acute Q fever do not prohibit development of the IgG antibody response.

Chronic Q fever develops in 1 to 5% of patients infected with Coxiella burnetii. The risk for chronic Q fever endocarditis has been estimated to be ≈ 39% in case of preexisting valvulopathy and is potentially even higher for valvular prostheses. Since 2007, The Netherlands has faced the largest Q fever outbreak ever reported, allowing a more precise risk estimate of chronic Q fever in high-risk groups. Patients with a history of cardiac valve surgery were selected for microbiological screening through a cardiology outpatient clinic in the area where Q fever is epidemic. Blood samples were analyzed for phase I and II IgG against C. burnetii, and if titers were above a defined cutoff level, C. burnetii PCR was performed. Chronic Q fever was considered proven if C. burnetii PCR was positive and probable if the phase I IgG titer was ≥ 1:1,024. Among 568 patients, the seroprevalence of C. burnetii antibodies (IgG titer greater than or equal to 1:32) was 20.4% (n = 116). Proven or probable chronic Q fever was identified among 7.8% of seropositive patients (n = 9). Valve characteristics did not influence the risk for chronic Q fever. Patients with chronic Q fever were significantly older than patients with past Q fever. In conclusion, screening of high-risk groups is a proper instrument for early detection of chronic Q fever cases. The estimated prevalence of chronic Q fever is 7.8% among seropositive patients with a history of cardiac valve surgery, which is substantially higher than that in nonselected populations but lower than that previously reported. Older age seems to increase vulnerability to chronic Q fever in this population.

Epstein Barr virus (EBV)-related diseases encompass both acute infections that result in acute infectious mononucleosis and chronic infections that result in lymphoproliferative malignant diseases. While classical inflammatory parameters such as C-reactive protein (CRP) have proven their usefulness during bacterial and fungal infections, they are often low and nondiscriminatory in viral infections. Here, we show that IL-18 is markedly elevated during acute EBV infections and EBV-associated diseases, while ferritin concentrations are also elevated during acute EBV infection and correlate with IL-18. Therefore, IL-18 and ferritin may represent infection markers for viral infections such as EBV, similar to CRP for bacterial infections.

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.

Diagnosis of chronic Q fever is difficult. PCR and culture lack sensitivity; hence, diagnosis relies mainly on serologic tests using an immunofluorescence assay (IFA). Optimal phase I IgG cutoff titers are debated but are estimated to be between 1:800 and 1:1,600. In patients with proven, probable, or possible chronic Q fever, we studied phase I IgG antibody titers at the time of positive blood PCR, at diagnosis, and at peak levels during chronic Q fever. We evaluated 200 patients, of whom 93 (46.5%) had proven, 51 (25.5%) had probable, and 56 (28.0%) had possible chronic Q fever. Sixty-five percent of proven cases had positive Coxiella burnetii PCR results for blood, which was associated with high phase I IgG. Median phase I IgG titers at diagnosis and peak titers in patients with proven chronic Q fever were significantly higher than those for patients with probable and possible chronic Q fever. The positive predictive values for proven chronic Q fever, compared to possible chronic Q fever, at titers 1:1,024, 1:2,048, 1:4,096, and ≥1:8,192 were 62.2%, 66.7%, 76.5%, and ≥86.2%, respectively. However, sensitivity dropped to <60% when cutoff titers of ≥1:8,192 were used. Although our study demonstrated a strong association between high phase I IgG titers and proven chronic Q fever, increasing the current diagnostic phase I IgG cutoff to >1:1,024 is not recommended due to increased false-negative findings (sensitivity < 60%) and the high morbidity and mortality of untreated chronic Q fever. Our study emphasizes that serologic results are not diagnostic on their own but should always be interpreted in combination with clinical parameters.

Since 2007, the Netherlands has experienced a large Q fever outbreak. To identify and quantify risk factors for development of chronic Q fever after Coxiella burnetii infection, we performed a case-control study. Comorbidity, cardiovascular risk factors, medications, and demographic characteristics from 105 patients with proven (n = 44), probable (n = 28), or possible (n = 33) chronic Q fever were compared with 201 patients who had acute Q fever in 2009 but in whom chronic Q fever did not develop (controls). Independent risk factors for development of proven chronic Q fever were valvular surgery, vascular prosthesis, aneurysm, renal insufficiency, and older age.

Background: Query fever (Q fever) is a zoonotic infection, caused by the intracellular Gram-negative coccobacillus Coxiella burnetii. From 2007 until 2010, a large Q fever outbreak has occurred in the Netherlands. We studied traditional and less common inflammation markers in seronegative and seropositive patients with acute Q fever pneumonia to identify markers that distinguish different disease stages and predict disease severity., Methods: A total of 443 adult patients presenting at the Emergency Department with community-acquired pneumonia were included in a prospective etiologic study. Patients with acute Q fever pneumonia were identified by PCR and/or serology. Patient characteristics, clinical symptoms, pneumonia severity and inflammation markers were assessed upon presentation. Duration of symptoms, prior therapy and length of hospital stay were retrieved from the hospital information system., Results: In all, 40 patients with acute Q fever pneumonia were identified. Of these, 29 were seronegative and 11 seropositive at presentation. C-reactive protein (CRP) was the only inflammation marker increased in all seronegative and seropositive patients but no significant difference was observed between groups. In seronegative patients, hypophosphatemia was more common (p=0.01), and length of hospital stay was longer (p=0.02). However, there was no significant difference in pneumonia severity index. Furthermore, phosphate levels were inversely correlated with body temperature (p=0.003)., Conclusions: In acute Q fever pneumonia, CRP is the only traditional inflammation marker adequately reflecting disease activity. Patients with seronegative acute Q fever pneumonia present with hypophosphatemia and have prolonged length of hospital stay when compared to seropositive patients, suggesting an increased disease severity.

In 2005, Q fever was diagnosed on two dairy goat farms and 2 years later it emerged in the human population in the south of the Netherlands. From 2007 to 2010, more than 4,000 human cases were notified with an annual seasonal peak. The outbreaks in humans were mainly restricted to the south of the country in an area with intensive dairy goat farming. In the most affected areas, up to 15% of the population may have been infected. The epidemic resulted in a serious burden of disease, with a hospitalisation rate of 20% of notified cases and is expected to result in more cases of chronic Q fever among risk groups in the coming years. The most important risk factor for human Q fever is living close (<5 km) to an infected dairy goat farm. Occupational exposure plays a much smaller role. In 2009 several veterinary control measures were implemented including mandatory vaccination of dairy goats and dairy sheep, improved hygiene measures, and culling of pregnant animals on infected farms. The introduction of these drastic veterinary measures has probably ended the Q fever outbreak, for which the Netherlands was ill-prepared.

Background: In the Netherlands, Streptococcus suis is a rare cause of meningitis. Over the past few years, the number of reported cases worldwide has increased. The bacterium is mainly isolated in pigs, but humans can also become infected., Case Description: At the Emergency Department, a 60-year-old man presented with headache, confusion, fever and nuchal rigidity. He worked at a meat factory. Laboratory testing showed abnormalities linked to bacterial meningitis. S. suis was cultured from blood and cerebrospinal fluid. The patient was treated with dexamethasone, ceftriaxone and later benzylpenicillin intravenously. He recovered well, but had bilateral perceptive hearing loss as a sequela., Conclusion: Particularly people who are in close contact with pigs have an increased risk of S. suis infection. S. suis meningitis can be very severe and lead to serious complications and even death. Rapid diagnosis and adequate treatment are critical. Permanent hearing loss is the most frequent sequela.

Study Objective: The neutrophil-lymphocyte count ratio (NLCR) has been identified as a predictor of bacteremia in medical emergencies. The aim of this study was to investigate the value of the NLCR in patients with community-acquired pneumonia (CAP)., Methods and Results: Consecutive adult patients were prospectively studied. Pneumonia severity (CURB-65 score), clinical characteristics, complications and outcomes were related to the NLCR and compared with C-reactive protein (CRP), neutrophil count, white blood cell (WBC) count. The study cohort consisted of 395 patients diagnosed with CAP. The mean age of the patients was 63.4 ± 16.0 years. 87.6% (346/395) of the patients required hospital admission, 7.8% (31/395) patients were admitted to the Intensive Care Unit (ICU) and 5.8% (23/395) patients of the study cohort died. The NLCR was increased in all patients, predicted adverse medical outcome and consistently increased as the CURB-65 score advanced. NLCR levels (mean ± SD) were significantly higher in non-survivors (23.3 ± 16.8) than in survivors (13.0 ± 11.4). The receiver-operating characteristic (ROC) curve for NLCR predicting mortality showed an area under the curve (AUC) of 0.701. This was better than the AUC for the neutrophil count, WBC count, lymphocyte count and CRP level (0.681, 0.672, 0.630 and 0.565, respectively)., Conclusion: Admission NLCR at the emergency department predicts severity and outcome of CAP with a higher prognostic accuracy as compared with traditional infection markers.

Background: Recent outbreaks in the Netherlands allowed for laboratory follow-up of a large series of patients with acute Q fever and for evaluation of test algorithms to detect chronic Q fever, a condition with considerable morbidity and mortality., Methods: For 686 patients with acute Q fever, IgG antibodies to Coxiella burnetii were determined using an immunofluorescence assay at 3, 6, and 12 months of follow-up. Polymerase chain reaction (PCR) was performed after 12 months and on earlier serum samples with an IgG phase I antibody titer ≥ 1:1024., Results: In 43% of patients, the IgG phase II antibody titers remained high (≥ 1:1024) at 3, 6, and 12 months of follow-up. Three months after acute Q fever, 14% of the patients had an IgG phase I titer ≥ 1:1024, which became negative later in 81%. IgG phase I antibody titers were rarely higher than phase II titers. Eleven cases of chronic Q fever were identified on the basis of serological profile, PCR results, and clinical presentation. Six of these patients were known to have clinical risk factors at the time of acute Q fever. In a comparison of various serological algorithms, IgG phase I titer ≥ 1:1024 at 6 months had the most favorable sensitivity and positive predictive value for the detection of chronic Q fever., Conclusions: The wide variation of serological and PCR results during the follow-up of acute Q fever implies that the diagnosis of chronic Q fever, necessitating long-term antibiotic treatment, must be based primarily on clinical grounds. Different serological follow-up strategies are needed for patients with and without known risk factors for chronic Q fever.