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  1. Article ; Online: Analysis of a Combined HBHA and ESAT-6-Interferon-γ-Release Assay for the Diagnosis of Tuberculous Lymphadenopathies

    Françoise Mascart / Maya Hites / Emmanuelle Watelet / Gil Verschelden / Christelle Meuris / Jean-Luc Doyen / Anne Van Praet / Audrey Godefroid / Emmanuelle Petit / Mahavir Singh / Camille Locht / Véronique Corbière

    Journal of Clinical Medicine, Vol 12, Iss 2127, p

    2023  Volume 2127

    Abstract: Background and Objectives: The incidence of tuberculosis lymphadenopathy (TBLA) is increasing, and diagnostic procedures lack sensitivity and are often highly invasive. TBLA may be asymptomatic, and differential diagnosis with other adenopathies (ADPs) ... ...

    Abstract Background and Objectives: The incidence of tuberculosis lymphadenopathy (TBLA) is increasing, and diagnostic procedures lack sensitivity and are often highly invasive. TBLA may be asymptomatic, and differential diagnosis with other adenopathies (ADPs) is difficult. We evaluated a blood-cell interferon-γ release assay (IGRA) with two different stage-specific mycobacterial antigens for the differential diagnosis of ADP suspected of mycobacterial origin. Methods: Twenty-one patients were included and divided into three groups: (1) cervical/axillar ADP ( n = 8), (2) mediastinal ADP ( n = 10), and (3) disseminated ADP ( n = 3). The mycobacterial antigens used for the IGRA were the heparin-binding haemagglutinin (HBHA) and the early-secreted antigenic target-6 (ESAT-6), a latency-associated antigen and a bacterial replication-related antigen, respectively. Diagnosis of TBLA based on microbiological results and/or response to anti-TB treatment was obtained for 15 patients. Results: An IGRA profile highly suggestive of active TB (higher IFN-γ response to ESAT-6 compared to HBHA) was found for 3/6 TBLA patients from group 1, and for all the TBLA patients from groups 2 and 3, whereas this profile was not noticed in patients with a final alternative diagnosis. Conclusion: These results highlight the potential value of this combined HBHA/ESAT-6 IGRA as a triage test for the differential diagnosis of ADP.
    Keywords tuberculous lymphadenopathy ; IGRA ; HBHA ; ESAT-6 ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: SP-D and CC-16 Pneumoproteins' Kinetics and Their Predictive Role During SARS-CoV-2 Infection

    Margherita Tiezzi / Sofia Morra / Jimmy Seminerio / Alain Van Muylem / Audrey Godefroid / Noémie Law-Weng-Sam / Anne Van Praet / Véronique Corbière / Carmen Orte Cano / Sina Karimi / Véronique Del Marmol / Benjamin Bondue / Mariam Benjelloun / Philomène Lavis / Françoise Mascart / Philippe van de Borne / Alessandra K. Cardozo

    Frontiers in Medicine, Vol

    2022  Volume 8

    Abstract: BackgroundSurfactant protein D (SP-D) and pulmonary club cell protein 16 (CC-16) are called “pneumoproteins” and are involved in host defense against oxidative stress, inflammation, and viral outbreak. This study aimed to determine the predictive value ... ...

    Abstract BackgroundSurfactant protein D (SP-D) and pulmonary club cell protein 16 (CC-16) are called “pneumoproteins” and are involved in host defense against oxidative stress, inflammation, and viral outbreak. This study aimed to determine the predictive value of these pneumoproteins on the incidence of acute respiratory distress syndrome (ARDS) or death in patients with coronavirus disease-2019 (COVID-19).MethodsThis retrospective study included 87 patients admitted to an emergency department. Blood samples were collected on three time points (days 1, 5, and 14 from hospital admission). SP-D and CC-16 serum levels were determined, and univariate and multivariate analyses considering confounding variables (age, body mass index, tobacco use, dyspnea, hypertension, diabetes mellitus, neutrophil-to-lymphocyte ratio) were performed.ResultsBased on the multivariate analysis, SP-D level on D1 was positively and slightly correlated with subsequent development of ARDS, independent of body mass index, dyspnea, and diabetes mellitus. CC-16 level on D1 was modestly and positively correlated with fatal outcome. A rise in SP-D between D1 and D5 and D1 and D14 had a strong negative association with incidence of ARDS. These associations were independent of tobacco use and neutrophil-to-lymphocyte ratio.ConclusionsOverall, our data reveal that increase in SP-D levels is a good prognostic factor for patients with COVID-19, and that initial CC-16 levels correlated with slightly higher risk of death. SP-D and CC-16 may prove useful to predict outcomes in patients with COVID-19.
    Keywords COVID-19 ; club cell 16 protein ; surfactant protein D ; acute respiratory distress syndrome ; biomarker ; prognosis ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2022-02-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Proportions of interferon-γ-producing ascites lymphocytes in response to mycobacterial antigens

    Sophie Henrard / Véronique Corbière / Liliane Schandené / Martine Ducarme / Anne Van Praet / Emmanuelle Petit / Mahavir Singh / Camille Locht / Violette Dirix / Françoise Mascart

    PLoS ONE, Vol 14, Iss 4, p e

    A help for early diagnosis of peritoneal tuberculosis in a low TB incidence country.

    2019  Volume 0214333

    Abstract: Background Peritoneal tuberculosis (TB) remains difficult to diagnose because of its non-specific clinical features and the lack of efficient microbiological tests. As delayed diagnosis is associated with high mortality rates, new diagnostic tools are ... ...

    Abstract Background Peritoneal tuberculosis (TB) remains difficult to diagnose because of its non-specific clinical features and the lack of efficient microbiological tests. As delayed diagnosis is associated with high mortality rates, new diagnostic tools are needed. Methods and findings We investigated for 24 patients prospectively enrolled with a possible diagnosis of peritoneal TB, the diagnostic value of the analysis of IFN-γ production by peritoneal fluid lymphocytes in response to a short in vitro stimulation with mycobacterial antigens. The patients were classified in two groups: non-TB and confirmed or highly probable TB. Diagnosis of TB was based on microbiological and histopathological criteria and/or a favorable response to anti-TB treatment. The IFN-γ production by peritoneal CD4+ T lymphocytes was analyzed by flow cytometry after an overnight in vitro stimulation with three different mycobacterial antigens, purified protein derivative (PPD), heparin-binding haemagglutinin (HBHA) or early-secreted-antigen-target-6 (ESAT-6). The percentages of PPD-, HBHA- or ESAT-6-induced IFN-γ-producing peritoneal fluid CD4+ T lymphocytes were higher in the TB group than in the non-TB group (p = 0.0007, p = 0.0004, and p = 0.0002 respectively). Based on cut-off values determined by ROC curve analysis of the results from TB and highly probable TB compared to those of non-TB patients, the sensitivity of these three tests was 100% with a specificity of 92%. Conclusions The analysis of mycobacterial-induced IFN-γ production by peritoneal lymphocytes is a promising tool to reliably and rapidly diagnose peritoneal TB. Further studies should be performed on larger cohorts of patients in high-TB-incidence countries to confirm the clinical value of this new diagnostic approach for peritoneal TB.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2019-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Uncovering Distinct Primary Vaccination-Dependent Profiles in Human Bordetella Pertussis Specific CD4+ T-Cell Responses Using a Novel Whole Blood Assay

    Eleonora E. Lambert / Véronique Corbière / Jacqueline A. M. van Gaans-van den Brink / Maxime Duijst / Prashanna Balaji Venkatasubramanian / Elles Simonetti / Martijn Huynen / Dimitri D. Diavatopoulos / Pauline Versteegen / Guy A. M. Berbers / Françoise Mascart / Cécile A. C. M. van Els

    Vaccines, Vol 8, Iss 225, p

    2020  Volume 225

    Abstract: To advance research and development of improved pertussis vaccines, new immunoassays are needed to qualify the outcome of Bordetella pertussis (Bp) specific CD4+ T-cell differentiation. Here, we applied a recently developed whole blood assay to evaluate ... ...

    Abstract To advance research and development of improved pertussis vaccines, new immunoassays are needed to qualify the outcome of Bordetella pertussis (Bp) specific CD4+ T-cell differentiation. Here, we applied a recently developed whole blood assay to evaluate Bp specific CD4+ T-cell responses. The assay is based on intracellular cytokine detection after overnight in vitro Bp antigen stimulation of diluted whole blood. We show for the first time that CD4+ T-cell memory of Th1, Th2, and Th17 lineages can be identified simultaneously in whole blood. Participants ranging from 7 to 70 years of age with different priming backgrounds of whole-cell pertussis (wP) and acellular pertussis (aP) vaccination were analyzed around an acellular booster vaccination. The assay allowed detection of low frequent antigen-specific CD4+ T-cells and revealed significantly elevated numbers of activated and cytokine-producing CD4+ T-cells, with a significant tendency to segregate recall responses based on primary vaccination background. A stronger Th2 response hallmarked an aP primed cohort compared to a wP primed cohort. In conclusion, analysis of Bp specific CD4+ T-cell responses in whole blood showed separation based on vaccination background and provides a promising tool to assess the quantity and quality of CD4+ T-cell responses induced by vaccine candidates.
    Keywords Bordetella pertussis ; whole blood assay ; CD4+ T-cells ; Th polarization ; Th cytokines ; booster vaccination ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2020-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article: Persistence at one year of age of antigen-induced cellular immune responses in preterm infants vaccinated against whooping cough: Comparison of three different vaccines and effect of a booster dose

    Vermeulen, Françoise / Camille Locht / Danièle Vermeylen / Eliane Damis / Françoise Mascart / Violette Dirix / Virginie Verscheure

    Vaccine. 2013 Apr. 08, v. 31, no. 15

    2013  

    Abstract: Due to their high risk of developing severe Bordetella pertussis (Bp) infections, it is recommended to immunize preterm infants at their chronological age. However, little is known about the persistence of their specific immune responses, especially of ... ...

    Abstract Due to their high risk of developing severe Bordetella pertussis (Bp) infections, it is recommended to immunize preterm infants at their chronological age. However, little is known about the persistence of their specific immune responses, especially of the cellular responses recognized to play a role in protection. We compared here the cellular immune responses to two major antigens of Bp between three groups of one year-old children born prematurely, who received for their primary vaccination respectively the whole cell vaccine Tetracoq® (TC), the acellular vaccine Tetravac® (TV), or the acellular vaccine Infanrix-hexa® (IR). Whereas most children had still detectable IFN-γ responses at one year of age, they were lower in the IR-vaccinated children compared to the two other groups. In contrast, both the TV- and the IR-vaccinated children displayed higher Th2-type immune responses, resulting in higher antigen-specific IFN-γ/IL-5 ratios in TC- than in TV- or IR-vaccinated children. The IFN-γ/IL-5 ratio of mitogen-induced cytokines was also lower in IR- compared to TC- or TV-vaccinated children. No major differences in the immune responses were noted after the booster compared to the pre-booster responses for each vaccine. The IR-vaccinated children had a persistently low specific Th1-type immune response associated with high specific Th2-type immune responses, resulting in lower antigen-specific IFN-γ/IL-5 ratios compared to the two other groups. We conclude that antigen-specific cellular immune responses persisted in one year-old children born prematurely and vaccinated during infancy at their chronological age, that a booster dose did not significantly boost the cellular immune responses, and that the Th1/Th2 balance of the immune responses is modulated by the different vaccines.
    Keywords antigens ; Bordetella pertussis ; cell-mediated immunity ; children ; cytokines ; immune response ; infancy ; infants ; interferon-gamma ; risk ; vaccination ; vaccines ; whooping cough
    Language English
    Dates of publication 2013-0408
    Size p. 1981-1986.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2013.02.004
    Database NAL-Catalogue (AGRICOLA)

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  6. Article: Humoral and B-cell memory responses in children five years after pertussis acellular vaccine priming

    Carollo, Maria / Alberto Eugenio Tozzi / Anne-Marie Buisman / Clara Maria Ausiello / Elisabetta Pandolfi / Françoise Mascart

    Vaccine. 2014 Apr. 11, v. 32, no. 18

    2014  

    Abstract: The resurgence of pertussis suggests the need for greater efforts in understanding the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of humoral and B-cell memory responses induced by primary ... ...

    Abstract The resurgence of pertussis suggests the need for greater efforts in understanding the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of humoral and B-cell memory responses induced by primary vaccination with two different acellular pertussis (aP) vaccines, hexavalent Hexavac® vaccine (Hexavac) (Sanofi Pasteur MSD) and Infanrix hexa® (Infanrix) (GlaxoSmithKline Biologicals). We evaluated the specific immune responses in the two groups of children, 5 years after primary vaccination by measuring the persistence of IgG and antibody secreting cells (ASC) specific for vaccine antigens. Part of the enrolled children received only primary vaccination, while others had the pre-school boost dose. A similar level of antigen-specific IgG and ASC was found in Infanrix and Hexavac vaccinated children. The mean IgG levels were significantly higher in children that received the pre-school boost as compared with children that did not receive the boost dose. A longer persistence after the pre-school boost of IgG-Pertussis Toxin (PT) and IgG-pertactin levels was observed in Infanrix primed children, but it was not statistically significant. More than 80% of children presented a positive ASC B memory response. Around 50% of children still presented protective IgG-PT levels which are reduced to 36% in no-boosted children. The pre-school booster dose restores the percentage of protected children above 50%. In conclusion our data underline the importance of giving a booster dose 5 years after primary vaccination and suggest the need for a new vaccine able to induce a long lasting protective response.
    Keywords antibodies ; antigens ; B-lymphocytes ; children ; immune response ; immunoglobulin G ; memory ; vaccination ; vaccines
    Language English
    Dates of publication 2014-0411
    Size p. 2093-2099.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2014.02.005
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Heparin-binding haemagglutinin, a new tool for the detection of latent Mycobacterium tuberculosis infection in hemodialysis patients.

    Rodrigue Dessein / Véronique Corbière / Joëlle Nortier / Max Dratwa / Karine Gastaldello / Agnieszka Pozdzik / Sophie Lecher / Bruno Grandbastien / Camille Locht / Françoise Mascart

    PLoS ONE, Vol 8, Iss 8, p e

    2013  Volume 71088

    Abstract: BACKGROUND: Patients with end-stage renal disease (ESRD) and latently infected with Mycobacterium tuberculosis (LTBI) are at higher risk to develop tuberculosis (TB) than healthy subjects. Interferon-gamma release assays (IGRAs) were reported to be more ... ...

    Abstract BACKGROUND: Patients with end-stage renal disease (ESRD) and latently infected with Mycobacterium tuberculosis (LTBI) are at higher risk to develop tuberculosis (TB) than healthy subjects. Interferon-gamma release assays (IGRAs) were reported to be more sensitive than tuberculin skin tests for the detection of infected individuals in dialysis patients. METHODS: On 143 dialysis patients prospectively enrolled, we compared the results from the QuantiFERON®-TB Gold assay (QFT), to those of an IGRA in response to in vitro stimulation of circulating mononuclear cells with the mycobacterial latency antigen Heparin-Binding Haemagglutinin purified from Mycobacterium bovis BCG (native HBHA, nHBHA). RESULTS: Seven patients had a past history of active TB and 1 had an undetermined result with both IGRAs. Among the other 135 patients, 94 had concordant results with the QFT and nHBHA-IGRA, 40.0% being negative and therefore not latently infected, and 29.6% being positive and thus LTBI. Discrepant results between these tests were found for 36 patients positive only with the nHBHA-IGRA and 5 only with the QFT. CONCLUSIONS: The nHBHA-IGRA is more sensitive than the QFT for the detection of LTBI dialysis patients, and follow-up of the patients will allow us to define the clinical significance of discrepant results between the nHBHA-IGRA and the QFT.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Both CD4+ and CD8+ Lymphocytes Participate in the IFN-γ Response to Filamentous Hemagglutinin from Bordetella pertussis in Infants, Children, and Adults

    Violette Dirix / Virginie Verscheure / Françoise Vermeulen / Iris De Schutter / Tessa Goetghebuer / Camille Locht / Françoise Mascart

    Clinical and Developmental Immunology, Vol

    2012  Volume 2012

    Abstract: Infant CD4+ T-cell responses to bacterial infections or vaccines have been extensively studied, whereas studies on CD8+ T-cell responses focused mainly on viral and intracellular parasite infections. Here we investigated CD8+ T-cell responses upon ... ...

    Abstract Infant CD4+ T-cell responses to bacterial infections or vaccines have been extensively studied, whereas studies on CD8+ T-cell responses focused mainly on viral and intracellular parasite infections. Here we investigated CD8+ T-cell responses upon Bordetella pertussis infection in infants, children, and adults and pertussis vaccination in infants. Filamentous hemagglutinin-specific IFN-γ secretion by circulating lymphocytes was blocked by anti-MHC-I or -MHC-II antibodies, suggesting that CD4+ and CD8+ T lymphocytes are involved in IFN-γ production. Flow cytometry analyses confirmed that both cell types synthesized antigen-specific IFN-γ, although CD4+ lymphocytes were the major source of this cytokine. IFN-γ synthesis by CD8+ cells was CD4+ T cell dependent, as evidenced by selective depletion experiments. Furthermore, IFN-γ synthesis by CD4+ cells was sometimes inhibited by CD8+ lymphocytes, suggesting the presence of CD8+ regulatory T cells. The role of this dual IFN-γ secretion by CD4+ and CD8+ T lymphocytes in pertussis remains to be investigated.
    Keywords Medicine ; R ; Internal medicine ; RC31-1245 ; Specialties of internal medicine ; RC581-951 ; Immunologic diseases. Allergy ; RC581-607
    Subject code 570
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Hindawi Publishing Corporation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Risk stratification of latent tuberculosis defined by combined interferon gamma release assays.

    Véronique Corbière / Gaelle Pottier / Florence Bonkain / Kinda Schepers / Virginie Verscheure / Sophie Lecher / T Mark Doherty / Camille Locht / Françoise Mascart

    PLoS ONE, Vol 7, Iss 8, p e

    2012  Volume 43285

    Abstract: BACKGROUND: Most individuals infected with Mycobacterium tuberculosis develop latent tuberculosis infection (LTBI). Some may progress to active disease and would benefit from preventive treatment yet no means currently exists to predict who will ... ...

    Abstract BACKGROUND: Most individuals infected with Mycobacterium tuberculosis develop latent tuberculosis infection (LTBI). Some may progress to active disease and would benefit from preventive treatment yet no means currently exists to predict who will reactivate. Here, we provide an approach to stratify LTBI based on IFN-γ responses to two antigens, the recombinant Early-Secreted Antigen Target-6 (rESAT-6) and the latency antigen Heparin-Binding Haemagglutinin (HBHA). METHODS: We retrospectively analyzed results from in-house IFN-γ-release assays with HBHA (HBHA-IGRA) and rESAT-6 (rESAT-6-IGRA) performed during a 12-year period on serial blood samples (3 to 9) collected from 23 LTBI subjects in a low-TB incidence country. Both the kinetics of the absolute IFN-γ concentrations secreted in response to each antigen and the dynamics of HBHA/rESAT-6-induced IFN-γ concentrations ratios were examined. RESULTS: This analysis allowed the identification among the LTBI subjects of three major groups. Group A featured stable HBHA and rESAT-6-IGRA profiles with an HBHA/rESAT-6 ratio persistently higher than 1, and with high HBHA- and usually negative rESAT-6-IGRA responses throughout the study. Group B had changing HBHA/rESAT-6 ratios fluctuating from 0.0001 to 10,000, with both HBHA and rESAT-6 responses varying over time at least once during the follow-up. Group C was characterized by a progressive disappearance of all responses. CONCLUSIONS: By combining the measures of IFN-γ concentrations secreted in response to an early and a latency antigens, LTBI subjects can be stratified into different risk groups. We propose that disappearing responses indicate cure, that persistent responses to HBHA with HBHA/rESAT-6 ratios ≥ 1 represent stable LTBI subjects, whereas subjects with ratios varying from >1 to <1 should be closely monitored as they may represent the highest-risk group, as illustrated by a case report, and should therefore be prioritized for preventive treatment.
    Keywords Medicine ; R ; Science ; Q
    Subject code 150
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Pneumococcal aetiology and serotype distribution in paediatric community-acquired pneumonia.

    Iris De Schutter / Anne Vergison / David Tuerlinckx / Marc Raes / Julie Smet / Pierre R Smeesters / Jan Verhaegen / Françoise Mascart / Filip Surmont / Anne Malfroot

    PLoS ONE, Vol 9, Iss 2, p e

    2014  Volume 89013

    Abstract: Community-acquired pneumonia (CAP) is a major cause of morbidity in children. This study estimated the proportion of children with pneumococcal CAP among children hospitalised with CAP in Belgium and describes the causative serotype distribution after ... ...

    Abstract Community-acquired pneumonia (CAP) is a major cause of morbidity in children. This study estimated the proportion of children with pneumococcal CAP among children hospitalised with CAP in Belgium and describes the causative serotype distribution after implementation of the 7-valent pneumococcal conjugate vaccine. Children 0-14 years hospitalised with X-ray-confirmed CAP were prospectively enrolled in a multicentre observational study. Acute and convalescent blood samples were collected. Pneumococcal aetiology was assessed by conventional methods (blood or pleural fluid cultures with Quellung reaction capsular typing or polymerase chain reaction [PCR] in pleural fluid), and recently developed methods (real-time PCR in blood and World Health Organization-validated serotype-specific serology). A total of 561 children were enrolled. Pneumococcal aetiology was assessed by conventional methods in 539, serology in 171, and real-time PCR in blood in 154. Pneumococcal aetiology was identified in 12.2% (66/539) of the children by conventional methods alone but in 73.9% by the combination of conventional and recently developed methods. The pneumococcal detection rate adjusted for the whole study population was 61.7%. Serotypes 1 (42.3%), 5 (16.0%), and 7F(7A) (12.8%) were predominant. In conclusion, Streptococcus pneumoniae remains the predominant bacteria in children hospitalised for CAP in Belgium after implementation of 7-valent pneumococcal conjugate vaccine, with non-vaccine-serotypes accounting for the majority of cases. The use of recently developed methods improves diagnosis of pneumococcal aetiology.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2014-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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