Laboratory for Pathology and Medical Microbiology PAMM

Veldhoven, Netherlands

Laboratory for Pathology and Medical Microbiology PAMM

Veldhoven, Netherlands
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van der Hoek W.,National Institute for Public Health and the Environment RIVM | Schneeberger P.M.,Robert Bosch GmbH | Oomen T.,National Institute for Public Health and the Environment RIVM | Wegdam-Blans M.C.,Laboratory for Pathology and Medical Microbiology PAMM | And 8 more authors.
Eurosurveillance | Year: 2012

From 2007 to 2009, the Netherlands faced large seasonal outbreaks of Q fever, in which infected dairy goat farms were identified as the primary sources. Veterinary measures including vaccination of goats and sheep and culling of pregnant animals on infected farms seem to have brought the Q fever problem under control. However, the epidemic is expected to result in more cases of chronic Q fever among risk groups in the coming years. In the most affected area, in the south of the country, more than 12% of the population now have antibodies against Coxiella burnetii. Questions remain about the follow-up of acute Q fever patients, screening of groups at risk for chronic Q fever, screening of donors of blood and tissue, and human vaccination. There is a considerable ongoing research effort as well as enhanced veterinary and human surveillance.


Schoffelen T.,Radboud University Nijmegen | Sprong T.,Canisius Wilhelmina Hospital | Bleeker-Rovers C.P.,Radboud University Nijmegen | Wegdam-Blans M.C.A.,Laboratory for Pathology and Medical Microbiology PAMM | And 10 more authors.
Clinical Microbiology and Infection | Year: 2014

Infection with Coxiella burnetii may lead to life-threatening chronic Q fever endocarditis or vascular infections, which are often difficult to diagnose. The present study aims to investigate whether measurement of in-vitro interferon-gamma (IFN-γ) production, a key cytokine in the immune response against C. burnetii, differentiates chronic from a past cleared infection, and whether measurement of other cytokines would improve the discriminative power. First, C. burnetii-specific IFN-γ production was measured in whole blood of 28 definite chronic Q fever patients and compared with 135 individuals with past Q fever (seropositive controls) and 908 seronegative controls. IFN-γ production was significantly higher in chronic Q fever patients than in controls, but with overlapping values between patients and seropositives. Secondly, the production of a series of other cytokines was measured in a subset of patients and controls, which showed that interleukin (IL)-2 production was significantly lower in patients than in seropositive controls. Subsequently, measuring IL-2 in all patients and all controls with substantial IFN-γ production showed that an IFN-γ/IL-2 ratio >11 had a sensitivity and specificity of 79% and 96%, respectively, to diagnose chronic Q fever. This indicates that a high IFN-γ/IL-2 ratio is highly suggestive for chronic Q fever. In an additional group of 25 individuals with persistent high anti-Coxiella phase I IgG titres without definite chronic infection, all but six showed an IFN-γ/IL-2 ratio <11. In conclusion, these findings hold promise for the often difficult diagnostic work-up of Q fever and the IFN-γ/IL-2 ratio may be used as an additional diagnostic marker. Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.


Wegdam-blans M.C.A.,Laboratory for Pathology and Medical Microbiology PAMM | Ter woorst J.F.,Catharina Hospital | Klompenhouwer E.G.,Catharina Hospital | Teijink J.A.,Catharina Hospital | Teijink J.A.,Maastricht University
European Journal of Cardio-thoracic Surgery | Year: 2012

Chronic Q fever infections, caused by Coxiella burnetii, are associated with cardiovascular complications, mainly endocarditis and vascular (graft) infections. We report a case of a patient with a C. burnetii infected thoracic aorta graft treated initially in a conservative way. However, surgical excision of the infected graft was eventually necessary. This case report highlights the challenges regarding the treatment of patients with chronic vascular C. burnetii infections. In the absence of practical guidelines, treatment is tailored to the individual patient. Furthermore, we want to emphasize the need to include chronic Q fever in the differential diagnosis in patients with culture negative aortitis, especially in the regions with Q fever epidemics in the recent past. © The Author 2012. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.


Wegdam-Blans M.C.A.,Laboratory for Pathology and Medical Microbiology PAMM | Stokmans R.A.,Catharina Hospital | Stokmans R.A.,Maastricht University | Tjhie J.H.T.,Laboratory for Pathology and Medical Microbiology PAMM | And 6 more authors.
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2013

In the aftermath of the Dutch Q fever outbreak, an increasing number of patients are being diagnosed with chronic Q fever. Most of these patients are unaware of being infected with Coxiella burnetii, the causative agent of Q fever. To find patients in an earlier, asymptomatic stage, a targeted screening strategy (TSS) for patients with risk factors for chronic Q fever was started in the southeast region of Noord-Brabant. In total, 763 patients were tested using an IgG phase II indirect fluorescent antibody test (IFAT), of which 52 (7 %) patients tested positive. Ten of these 52 patients displayed a chronic Q fever serological profile. All of these 10 patients had a heart valve(s) or (endo-)vascular prosthesis. All except one were asymptomatic. Suggestive signs for chronic infections on positron emission tomography-computed tomography (PET-CT) were demonstrated in 5 (50 %) of these patients. Forty-two out of the 52 patients with a positive screening test showed a past Q fever serological profile. After a year of follow-up (every 3 months), none of these patients showed elevation of antibody titres and no new chronic Q fever patients were found in this group. A targeted screening programme is a useful instrument for detecting patients at risk of developing chronic Q fever. © 2012 Springer-Verlag.


PubMed | Catharina Hospital, Canisius Wilhelmina Hospital, Netherlands Cancer Institute, Maastricht University and Laboratory for Pathology and Medical Microbiology PAMM
Type: Journal Article | Journal: Breast cancer research and treatment | Year: 2016

Breast cancer guidelines advise sentinel lymph node biopsy (SLNB) in patients with ductal carcinoma in situ (DCIS) on core biopsy at high risk of invasive cancer or in case of mastectomy. This study investigates the incidence of SLNB and SLN metastases and the relevance of indications in guidelines and literature to perform SLNB in order to validate whether SLNB is justified in patients with DCIS on core biopsy in current era. Clinically node negative patients diagnosed from 2004 to 2013 with only DCIS on core needle biopsy were selected from a national database. Incidence of SLN biopsy and metastases was calculated. With Fisher exact tests correlation between SLNB indications and actual presence of SLN metastases was studied. Further, underestimation rate for invasive cancer and correlation with SLN metastases was analysed. 910 patients were included. SLNB was performed in 471 patients (51.8 %): 94.5 % had pN0, 3.0 % pN1mi and 2.5 % pN1. Patients undergoing mastectomy had 7 % SLN metastases versus 3.5 % for breast conserving surgery (BCS) (p = 0.107). The only factors correlating to SLN metastases were smaller core needle size (p = 0.01) and invasive cancer (p < 0.001). Invasive cancer was detected in 16.7 % by histopathology with 15.6 % SLN metastases versus only 2 % in pure DCIS. SLNB showed metastases in 5.5 % of patients; 3.5 % in case of BCS (any histopathology) and 2 % when pure DCIS was found at definitive histopathology (BCS and mastectomy). Consequently, SLNB should no longer be performed in patients diagnosed with DCIS on core biopsy undergoing BCS. If definitive histopathology shows invasive cancer, SLNB can still be considered after initial surgery.


Wegdam-Blans M.C.A.,Laboratory for Pathology and Medical Microbiology PAMM | Kampschreur L.M.,University Utrecht | Delsing C.E.,Radboud University Nijmegen | Bleeker-Rovers C.P.,Radboud University Nijmegen | And 9 more authors.
Journal of Infection | Year: 2012

A review was performed to determine clinical aspects and diagnostic tools for chronic Q fever. We present a Dutch guideline based on literature and clinical experience with chronic Q fever patients in The Netherlands so far. In this guideline diagnosis is categorized as proven, possible or probable chronic infection based on serology, PCR, clinical symptoms, risk factors and diagnostic imaging. © 2011 The British Infection Association.


Broeren M.A.C.,Maxima Medical Center | Maas Y.,Laboratory for Pathology and Medical Microbiology PAMM | Retera E.,Laboratory for Pathology and Medical Microbiology PAMM | Arents N.L.A.,Laboratory for Pathology and Medical Microbiology PAMM
Clinical Microbiology and Infection | Year: 2013

The rise in antimicrobial resistance has become a serious global health problem. Restrictive use of antibiotics seems the only option to temper this accession since research in new antibiotics has halted. Antimicrobial stewardship programmes rely on quick access to susceptibility data. This study evaluated the concept of bacterial cell count monitoring as a fast method to determine susceptibility. Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus strains were tested for amoxicillin/piperacillin and gentamicin by three conventional methods (VITEK2®, Etest® and broth-macrodilution). Bacterial cell count monitoring reliably predicted susceptibility after 90min for Escherichia coli and after 120min for Pseudomonas aeruginosa and Staphylococcus aureus without any minor, major or very major discrepancies. Time-to-result was reduced by 74%, 83% and 76%, respectively. Bacterial cell count monitoring shows great potential for rapid susceptibility testing. © 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.


Wegdam-Blans M.C.A.,Laboratory for Pathology and Medical Microbiology PAMM | Wielders C.C.H.,Robert Bosch GmbH | Wielders C.C.H.,National Institute for Public Health and the Environment | Meekelenkamp J.,Robert Bosch GmbH | And 6 more authors.
Clinical and Vaccine Immunology | Year: 2012

In this study, we compared Coxiella burnetii IgG phase I, IgG phase II, and IgM phase II detection among a commercially available enzyme-linked immunosorbent assay (ELISA) (Virion/Serion), an indirect fluorescent antibody test (IFAT) (Focus Diagnostics), and a complement fixation test (CFT) (Virion/Serion). For this, we used a unique collection of acute- and convalescentphase sera from 126 patients with acute Q fever diagnosed by positive Coxiella burnetii PCR of blood. We were able to establish a reliable date of onset of disease, since DNA is detectable within 2 weeks after the start of symptoms. In acute samples, at t = 0, IFAT demonstrated IgM phase II antibodies in significantly more sera than did ELISA (31.8% versus 19.7%), although the portion of solitary IgM phase II was equal for IFAT and for ELISA (18.2% and 16.7%, respectively). Twelve months after the diagnosis of acute Q fever, 83.5% and 62.2% of the sera were still positive for IgM phase II with IFAT and ELISA, respectively. At 12 months IFAT IgG phase II showed the slowest decline. Therefore, definitive serological evidence of acute Q fever cannot be based on a single serum sample in areas of epidemicity and should involve measurement of both IgM and IgG antibodies in paired serum. Based on IgG phase II antibody detection in paired samples (at 0 and 3 months) from 62 patients, IFAT confirmed more cases than ELISA and CFT, but the differences were not statically significant (100% for IFAT, 95.2% for ELISA, and 96.8% for CFT). This study demonstrated that the three serological tests are equally effective in diagnosing acute Q fever within 3 months of start of symptoms. In follow-up sera, more IgG antibodies were detected by IFAT than by ELISA or CFT, making IFAT more suitable for prevaccination screening programs. Copyright © 2012, American Society for Microbiology. All Rights Reserved.


Boonen K.J.M.,Catharina Hospital Eindhoven | Koldewijn E.L.,Catharina Hospital Eindhoven | Arents N.L.A.,Laboratory for Pathology and Medical Microbiology PAMM | Raaymakers P.A.M.,Catharina Hospital Eindhoven | Scharnhorst V.,Catharina Hospital Eindhoven
World Journal of Urology | Year: 2013

Purpose: To exclude urinary tract infections, culture is the gold standard method, although it is time consuming and costly. Current strategies using dipstick analysis are unsatisfactory as screening methods, because of inadequate sensitivity/specificity. Urine flow cytometry is an attractive alternative. To exclude urinary tract infections, a cutoff value to screen for negative cultures was determined. Methods: 281 outpatients (51 % male) of a general population visiting the urology department were included. Urine samples were measured by flow cytometry and compared with culture results and dipstick analysis. ROC analysis was performed to evaluate the screening performance of flow cytometry and dipstick analysis compared to culture. Results: 18 % of cultures were positive, defined as >104 colony forming units/mL. Bacterial count by flow cytometry alone provides the best sensitivity and specificity to exclude a urinary tract infection. A cutoff value of 60 bacteria/μL urine leads to a sensitivity of 100 % and a specificity of 60 %. Retrospectively, with a cutoff value of 60 bacteria/μL urine, 49 % of the cultures would have been redundant. 20 % of patients receiving antibiotics possibly had received those unnecessarily. The calculated percentage of false negatives was 0 % (95 % confidence interval 0-3.3 %). Conclusions: Urine flow cytometry is a reliable screening method to exclude urinary tract infections. With a cutoff value of 60 bacteria/μL urine, negative predictive value is 100 % and the calculated percentage of false negatives is 0 % (95 % confidence interval 0-3.3 %). Using flow cytometry as a screening method could lead to a reduction in cultures and antibiotics. © 2012 Springer-Verlag.


Wegdam-Blans M.C.A.,Laboratory for Pathology and Medical Microbiology PAMM | Vainas T.,Catharina Hospital | Van Sambeek M.R.,Catharina Hospital | Cuypers P.W.,Catharina Hospital | And 3 more authors.
European Journal of Vascular and Endovascular Surgery | Year: 2011

Introduction: Coxiella burnetii is a strict intracellular pathogen causing Q fever, a worldwide zoonosis with an extensive animal reservoir. Chronic Q fever infections are frequently associated with cardiovascular complications, mainly endocarditis, and also aortic aneurysms and vascular-graft infection. We present four cases of chronic Q fever infections and associated vascular complications, and review the literature to identify major symptoms and assess the prevalence, treatment and outcome in these challenging patients. Materials and methods: The demographic and clinical data of four patients presenting at our unit were analysed. PubMed was searched to identify articles describing patients with chronic Q-fever-associated vascular complications. Results: Combining our own with the published experience, 58 cases (49 male) of chronic Q-fever-associated vascular complications were identified. The average age of the patients was 64 years (range: 30-83 years). As many as 26 patients had vascular graft infections (25 Dacron/polytetrafluoroethylene (PTFE), one homograft) and 32 had infected aneurysms. The majority of these patients presented with fever (n = 40) and/or pain (n = 43). Weight loss and fatigue were seen in 25 and 14 patients, respectively. Aneurysm rupture, aorto-enteric fistulae and lower-limb embolisation were seen in nine, four and four patients, respectively. Concurrent endocarditis was seen in two patients, whereas, for 15 cases, this information was not available. Patients were treated with antibiotics for an average of 23 months (range 1-54 months). Treatment of infected vascular segments was described in 50 patients. Ten patients were treated conservatively whilst 40 underwent resection of the infected vessel and reconstruction with a graft. Major surgical complications (graft infection, n = 3;aorto-enteric fistula, n = 2; bleeding, n = 1; anastomotic leakage, n = 1; aortic dissection, n = 1; vertebral osteomyelitis, n = 3; graft thrombosis, n = 1; renal failure, n = 2; and pneumonia, n = 1) were reported in 11 cases (21%) and were not specified in 13. The overall mortality was 24% (14/58). Seven (18%) surgically treated patients died. Six of them died within 6 months of surgery and one patient at 3 years' follow-up. Seven out of 10 of the conservatively treated patients died within 3 years of diagnosis. Conclusion: Aneurysms associated with Q-fever infections tend to be complicated, requiring challenging surgical corrections, and long-term antibiotic treatment. Major complications and mortality rates are significant, especially in conservatively treated patients. © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

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