Publications by authors named "Stefanie Desmet"

31 Publications

Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.

Lancet Digit Health 2021 06;3(6):e360-e370

Irish Meningitis and Sepsis Reference Laboratory, Children's Health Ireland at Temple Street, Dublin, Ireland; Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin, Ireland.

Background: Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic.

Methods: In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed.

Findings: 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 837 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27-0·37]) and 82% at 8 weeks (0·18 [0·14-0·23]) following the week in which significant changes in population movements were recorded.

Interpretation: The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide.

Funding: Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Pública de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France).
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http://dx.doi.org/10.1016/S2589-7500(21)00077-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166576PMC
June 2021

Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project.

Microorganisms 2021 Apr 2;9(4). Epub 2021 Apr 2.

National Public Health Organisation, 15123 Athens, Greece.

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.
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http://dx.doi.org/10.3390/microorganisms9040742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066045PMC
April 2021

Serotype Distribution of Remaining Pneumococcal Meningitis in the Mature PCV10/13 Period: Findings from the PSERENADE Project.

Microorganisms 2021 Apr 1;9(4). Epub 2021 Apr 1.

Department of Clinical Microbiology, Landspitali-The National University Hospital, Hringbraut, 101 Reykjavik, Iceland.

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites ( = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites ( = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.
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http://dx.doi.org/10.3390/microorganisms9040738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066874PMC
April 2021

Changes in Invasive Pneumococcal Disease Caused by Serotype 1 Following Introduction of PCV10 and PCV13: Findings from the PSERENADE Project.

Microorganisms 2021 03 27;9(4). Epub 2021 Mar 27.

National Centre for Immunisation Research and Surveillance and Discipline of Child and Adolescent Health, Children's Hospital Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Westmead, NSW 2145, Australia.

serotype 1 (ST1) was an important cause of invasive pneumococcal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containing ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) comparing the pre-PCV10/13 period to each post-PCV10/13 year by site using a Bayesian multi-level, mixed-effects Poisson regression and all-site IRRs using a linear mixed-effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all-site IRR was 0.05 (95% credibility interval 0.04-0.06) for all ages, 0.05 (0.04-0.05) for <5 years of age, 0.08 (0.06-0.09) for 5-17 years, 0.06 (0.05-0.08) for 18-49 years, 0.06 (0.05-0.07) for 50-64 years, and 0.05 (0.04-0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3+0 schedule constrains generalizability and data from these settings are needed.
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http://dx.doi.org/10.3390/microorganisms9040696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066231PMC
March 2021

Underlying factors in paediatric invasive pneumococcal disease in Belgium - Authors' reply.

Lancet Infect Dis 2021 02;21(2):170

Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Unité de Maladies Infectieuses Pédiatriques, Brussels, Belgium.

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http://dx.doi.org/10.1016/S1473-3099(20)30940-3DOI Listing
February 2021

In-depth analysis of pneumococcal serotypes in Belgian children (2015-2018): Diversity, invasive disease potential, and antimicrobial susceptibility in carriage and disease.

Vaccine 2021 01 9;39(2):372-379. Epub 2020 Dec 9.

Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Background: Changes in serotype distribution have been described after the switch from the 13-valent pneumococcal conjugate vaccine (PCV13) to the 10-valent pneumococcal conjugate vaccine (PCV10) in Belgium.

Aim: To describe serotype's invasive disease potential and the detailed evolution of serotype distribution and antimicrobial susceptibility of pneumococcal isolates (carriage and IPD) in children up to 30 months of age over a period during and after the vaccine switch (2015-2018).

Methods: S. pneumoniae strains isolated from the nasopharynx of healthy children attending day-care centres (DCCs) and strains from normally sterile sites of children with IPD were serotyped (Quellung-reaction) and antimicrobial susceptibility testing was performed. Invasive disease potential was defined as the serotype-specific odds ratio (OR).

Results: The highly invasive (OR > 1) serotypes 12F, 1, 3, 24A/B/F, 33F, 19A, and 9N were not frequently carried (<7.5% of carriage strains). Different serotypes dominated in carriage (23B, 23A, 11A, 15B) versus IPD (12F, 19A, 10A, 33F). PCV13 vaccine serotypes increased in carriage (5.4% (25/463) in period 1 vs 10.3% (69/668) in period 3) and in IPD (7.3% (8/110 in period 1 vs 23.9% (34/142) in period 3) due to an increase (p < 0.01) in serotype 19A. The penicillin non-susceptibility of 19A was lower (p = 0.02) in carriage (6.8%) than in IPD (23.5%). Erythromycin and tetracycline non-susceptibility were more frequent (p < 0.01) in IPD (26.0%; 23.0%) compared to carriage strains (18.2%; 14.5%) and penicillin non-susceptibility increased over the three year study period (carriage: 13.4%, 19.8%, 18.5%, p = 0.05; IPD: 11.8%, 15.0%, 20.4%, p = 0.02).

Conclusion: Only some of the serotypes with high invasive disease potential (serotype 1, 3, 19A) in Belgium are included in PCV10 and/or PCV13. This reinforces the need for continuous monitoring, both in healthy children as in children with IPD, to better understand the dynamics of pneumococcal disease, to optimise the composition and implementation of PCVs.
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http://dx.doi.org/10.1016/j.vaccine.2020.11.044DOI Listing
January 2021

Successful double-lung transplantation from a donor previously infected with SARS-CoV-2.

Lancet Respir Med 2021 03 1;9(3):315-318. Epub 2020 Dec 1.

Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium; Department of Chronic Diseases and Metabolism, Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Lung Transplant Unit, KU Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1016/S2213-2600(20)30524-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831530PMC
March 2021

No SARS-CoV-2 carriage observed in children attending daycare centers during the intial weeks of the epidemic in Belgium.

J Med Virol 2021 03 17;93(3):1828-1831. Epub 2020 Dec 17.

Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Campus Drie Eiken, Wilrijk, Belgium.

To gain knowledge about the role of young children attending daycare in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, a random sample of children (n = 84) aged between 6 and 30 months attending daycare in Belgium was studied shortly after the start of the epidemic (February 29th) and before the lockdown (March 18th) by performing in-house SARS-CoV-2 real-time polymerase chain reaction. No asymptomatic carriage of SARS-CoV-2 was detected, whereas common cold symptoms were common (51.2%). Our study shows that in Belgium, there was no sign of early introduction into daycare centers at the moment children being not yet isolated at home, although the virus was clearly circulating. It is clear that more evidence is needed to understand the actual role of young children in the transmission of SARS-CoV-2 and their infection risk when attending daycare.
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http://dx.doi.org/10.1002/jmv.26689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753838PMC
March 2021

Antibody response against SARS-CoV-2 spike protein and nucleoprotein evaluated by four automated immunoassays and three ELISAs.

Clin Microbiol Infect 2020 Nov 31;26(11):1557.e1-1557.e7. Epub 2020 Jul 31.

Clinical Department of Laboratory Medicine and National Reference Centre for Respiratory Pathogens, University Hospitals Leuven, Leuven, Belgium; Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium. Electronic address:

Objectives: The aim was to determine the antibody response against SARS-CoV-2 spike protein and nucleoprotein using four automated immunoassays and three ELISAs for the detection of total Ig antibodies (Roche) or IgG (Abbott, Diasorin, Snibe, Euroimmun, Mikrogen) in COVID-19 patients.

Methods: Sensitivity and dynamic trend to seropositivity were evaluated in 233 samples from 114 patients with moderate, severe or critical COVID-19 confirmed with PCR on nasopharyngeal swab. Specificity was evaluated in 113 samples collected before January 2020, including 24 samples from patients with non-SARS coronavirus infection.

Results: Sensitivity for all assays was 100% (95% confidence interval 83.7-100) 3 weeks after onset of symptoms. Specificity varied between 94.7% (88.7-97.8) and 100% (96.1-100). Calculated at the cut-offs that corresponded to a specificity of 95% and 97.5%, Roche had the highest sensitivity (85.0% (79.8-89.0) and 81.1% (76.6-85.7), p < 0.05 except vs. Abbott). Seroconversion occurred on average 2 days earlier for Roche total Ig anti-N and the three IgG anti-N assays (Abbott, Mikrogen, Euroimmun) than for the two IgG anti-S assays (Diasorin, Euroimmun) (≥50% seroconversion day 9-10 vs. day 11-12 and p < 0.05 for percent seropositive patients day 9-10 to 17-18). There was no significant difference in the IgG antibody time to seroconversion between critical and non-critical patients.

Discussion: Seroconversion occurred within 3 weeks after onset of symptoms with all assays and on average 2 days earlier for assays detecting IgG or total Ig anti-N than for IgG anti-S. The specificity of assays detecting anti-N was comparable to anti-S and excellent in a challenging control population.
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http://dx.doi.org/10.1016/j.cmi.2020.07.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834107PMC
November 2020

Dynamic changes in paediatric invasive pneumococcal disease after sequential switches of conjugate vaccine in Belgium: a national retrospective observational study.

Lancet Infect Dis 2021 01 20;21(1):127-136. Epub 2020 Jul 20.

Hôpital Universitaire des Enfants Reine Fabiola, Unité de Maladies Infectieuses Pédiatriques, Université Libre de Bruxelles, Brussels, Belgium.

Background: Ten-valent and 13-valent pneumococcal conjugate vaccines (PCVs) have shown important benefits by decreasing invasive pneumococcal disease caused by vaccine serotypes. Belgium had an uncommon situation with sequential use of PCV7, PCV13, and PCV10 in the childhood vaccination programmes between 2007 and 2018. We aimed to analyse the changes in incidence of invasive pneumococcal disease and serotype distribution in children throughout this period.

Methods: Streptococcus pneumoniae isolates were obtained from patients with invasive pneumococcal disease in Belgium between 2007 and 2018 by the national laboratory-based surveillance. Paediatric invasive pneumococcal disease incidence, serotype distribution, and antimicrobial susceptibility were analysed in periods during which PCV7 (2009-10), PCV13 (2013-14), both PCV13 and PCV10 (2015-16), and PCV10 (2017-18) were used. Incidence rates and trends were compared. Vaccination status was collected. For a subset of serotype 19A isolates, multilocus sequence type was identified.

Findings: After a decrease in PCV7 serotype invasive pneumococcal disease was observed during the PCV7 period, total paediatric invasive pneumococcal disease incidence significantly declined during the PCV13 period (-2·6% monthly, p<0·0001). During the PCV13-PCV10 period (2015-16), the lowest mean in paediatric invasive pneumococcal disease incidence was achieved, but the incidence increased again during the PCV10 period (2017-18), especially in children younger than 2 years (+1·7% monthly; p=0·028). This increase was mainly due to a significant rise in serotype 19A invasive pneumococcal disease incidence in the PCV10 period compared with the PCV13 period (p<0·0001), making serotype 19A the predominant serotype in paediatric invasive pneumococcal disease in the PCV10 period. Genetic diversity within the 2017-18 serotype 19A collection was seen, with two predominant clones, ST416 and ST994, that were infrequently observed before PCV10 introduction. In 2018, among children younger than 5 years with invasive pneumococcal disease who were correctly vaccinated, 37% (37 of 100) had PCV13 serotype invasive pneumococcal disease, all caused by serotype 19A and serotype 3.

Interpretation: After a significant decrease during the PCV13 period, paediatric invasive pneumococcal disease incidence increased again during the PCV10 period. This observation mainly resulted from a significant increase of serotype 19A cases. During the PCV10 period, dominant serotype 19A clones differed from those detected during previous vaccine periods. Whether changes in epidemiology resulted from the vaccine switch or also from natural evolution remains to be further elucidated.

Funding: The Belgian National Reference is funded by the Belgian National Institute for Health and Disability Insurance and the whole genome sequencing by an investigator-initiated research grant from Pfizer.
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http://dx.doi.org/10.1016/S1473-3099(20)30173-0DOI Listing
January 2021

Laboratory information system requirements to manage the COVID-19 pandemic: A report from the Belgian national reference testing center.

J Am Med Inform Assoc 2020 08;27(8):1293-1299

Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.

Objective: The study sought to describe the development, implementation, and requirements of laboratory information system (LIS) functionality to manage test ordering, registration, sample flow, and result reporting during the coronavirus disease 2019 (COVID-19) pandemic.

Materials And Methods: Our large (>12 000 000 tests/y) academic hospital laboratory is the Belgian National Reference Center for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. We have performed a moving total of >25 000 SARS-CoV-2 polymerase chain reaction tests in parallel to standard routine testing since the start of the outbreak. A LIS implementation team dedicated to develop tools to remove the bottlenecks, primarily situated in the pre- and postanalytical phases, was established early in the crisis.

Results: We outline the design, implementation, and requirements of LIS functionality related to managing increased test demand during the COVID-19 crisis, including tools for test ordering, standardized order sets integrated into a computerized provider order entry module, notifications on shipping requirements, automated triaging based on digital metadata forms, and the establishment of databases with contact details of other laboratories and primary care physicians to enable automated reporting. We also describe our approach to data mining and reporting of actionable daily summary statistics to governing bodies and other policymakers.

Conclusions: Rapidly developed, agile extendable LIS functionality and its meaningful use alleviates the administrative burden on laboratory personnel and improves turnaround time of SARS-CoV-2 testing. It will be important to maintain an environment that is conducive for the rapid adoption of meaningful LIS tools after the COVID-19 crisis.
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http://dx.doi.org/10.1093/jamia/ocaa081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197526PMC
August 2020

Vertebral Osteomyelitis or Infected Abdominal Aortic Endograft? A Rare Case of Q Fever.

Ann Vasc Surg 2020 Aug 28;67:568.e9-568.e12. Epub 2020 Mar 28.

Department of Vascular Surgery, University Hospitals Leuven, Leuven, Belgium. Electronic address:

Coxiella burnetii is the etiological agent of Q fever, a zoonosis. Vascular infections are associated with significant morbidity and mortality. Osteoarticular Q fever infections are rare. We describe a case of vertebral osteomyelitis with associated infection of an abdominal aortic endograft, caused by C. burnetii. Most probably, an initial pyogenic vertebral osteomyelitis extended locally to the endograft. Treatment consisted of antibiotic therapy and surgical resection of the infected aortic endograft and in situ reconstruction with autogenous superficial femoral vein grafts.
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http://dx.doi.org/10.1016/j.avsg.2020.03.018DOI Listing
August 2020

How nasopharyngeal pneumococcal carriage evolved during and after a PCV13-to-PCV10 vaccination programme switch in Belgium, 2016 to 2018.

Euro Surveill 2020 02;25(5)

The members of the NPcarriage Study Group are listed at the end of the article.

BackgroundThe current carriage study was set up to reinforce surveillance during/after the PCV13-to-PCVC10 switch in Belgium.AimThis observational study monitored carriage of (Sp) serotypes, particularly those no longer covered (3, 6A, 19A), as well as (Hi), because PCV10 contains the non-typeable Hi protein D.MethodsA total of 2,615 nasopharyngeal swabs from children (6-30 months old) attending day care were collected in three periods over 2016-2018. Children's demographic and clinical characteristics and vaccination status were obtained through a questionnaire. Sp and Hi were identified by culture and PCR. Pneumococcal strains were tested for antimicrobial (non-)susceptibility by disc diffusion and serotyped by Quellung-reaction (Quellung-reaction and PCR for serotypes 3, 6A, 19A).ResultsThe carriage prevalence of Sp (> 75%) remained stable over the successive periods but that of Hi increased (87.4%, 664 Hi-carriers/760 in 2016 vs 93.9%, 895/953 in 2017-2018). The proportion of non-PCV13 vaccine serotypes decreased (94.6%, 438 isolates/463 in 2016 vs 89.7%, 599/668 in 2017-2018) while that of PCV13-non-PCV10 vaccine serotypes (3 + 6A + 19A) increased (0.9%, 4 isolates/463 in 2016 vs 7.8%, 52/668 in 2017-2018), with serotype 19A most frequently identified (87.9%, 58/66 isolates). Non-susceptibility of pneumococci against any of the tested antibiotics was stable over the study period (> 44%).ConclusionsDuring and after the PCV13-to-PCV10 vaccine switch, the proportion of non-PCV13 serotypes decreased, mainly due to a serotype 19A carriage prevalence increase. These results complement invasive pneumococcal disease surveillance data, providing further basis for pneumococcal vaccination programme policy making.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.5.1900303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014673PMC
February 2020

The impact of childhood 13-valent pneumococcal conjugate vaccination on overall invasive pneumococcal disease, including the oldest old.

Acta Clin Belg 2020 Jan 30:1-8. Epub 2020 Jan 30.

Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, Belgium.

Our aim was to compare serotype distribution in invasive pneumococcal disease (IPD) in the Belgian population before and after introduction of the 13-valent conjugte vaccine (PCV13) in the national childhood vaccination schedule. Serotyping was performed on 12,534 pleural fluid and bacteraemic Streptococcus pneumoniae isolates sent to the National Reference Centre. We compared the distribution of serotypes (ST)/serogroups (SG) between the periods before (2007-2010) and after (2012-2015) the introduction of PCV13, in children and adults of different age groups, including older individuals (65-84 and ≥85 years). The introduction of PCV13 in the childhood immunization program resulted in a reduction of 16% of all IPD-isolates. The prevalence of PCV13-SG decreased in all age groups: from 81% to 53% (p < 0.0001) in children <18 years, and from 69% to 53% (p < 0.0001) in individuals aged 18-64. This effect was also observed in age groups 65-84 (64% to 50%, p < 0.0001) and ≥85 years (63% to 47%; p < 0.0001). The proportion of IPD cases caused by non-PCV13 SG increased from 31% to 49% between the two periods, indicating replacement with non-vaccine SG. The coverage rate for the 23-valent polysaccharide vaccine (PPV23) in all age groups remains as high as 89% for the total group. After introduction of PCV13, a reduction of PCV13-serotypes occurred in IPD in all age groups. This supports the rationale to combine the effect of PCV13 with the broader coverage of PPV23 as a vaccination strategy for adults.
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http://dx.doi.org/10.1080/17843286.2020.1721131DOI Listing
January 2020

What is the risk of missing legionellosis relying on urinary antigen testing solely? A retrospective Belgian multicenter study.

Eur J Clin Microbiol Infect Dis 2020 Apr 14;39(4):729-734. Epub 2019 Dec 14.

Department of Medical Microbiology, AZ Sint-Jan Hospital, Ruddershove 10, 8000, Bruges, Belgium.

Currently, diagnosis of legionellosis relies mainly on urinary antigen testing (UAT) for Legionella pneumophila serogroup 1 (Lp1). However, this test has several limitations, particularly missing non-Lp1 infections. The purpose of this large multicenter study was to investigate the risk of missing legionellosis relying on UAT solely. Molecular results of Legionella detection as part of a first-line (syndromic) testing algorithm for severe respiratory tract infections were investigated retrospectively and compared with UAT results in 14 Belgian laboratories. Overall, 44.4% (20/45) UAT results appeared false negative and were reclassified as legionellosis based on PCR findings [Legionnaires' disease, 37.5% (15/40); Pontiac fever, 100% (5/5)]. A total of 39.4% (26/66) diagnosis probably would have been missed or delayed without a syndromic approach, as UAT or specific molecular testing for Legionella was not requested by the clinician. Furthermore, we confirmed the higher sensitivity of molecular Legionella detection in lower respiratory tract compared with upper respiratory tract specimens (p = 0.010).
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http://dx.doi.org/10.1007/s10096-019-03785-8DOI Listing
April 2020

Performance and potential clinical impact of Alfred60 (Alifax®) for direct antimicrobial susceptibility testing on positive blood culture bottles.

Eur J Clin Microbiol Infect Dis 2020 Jan 17;39(1):53-63. Epub 2019 Oct 17.

Department of Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.

Rapid pathogen identification (ID) and antimicrobial susceptibility testing (AST) of bacteria-causing bloodstream infections can improve patients' outcome. In this study, we evaluated the performance of Alfred60 (Alifax) which provides AST directly on positive blood culture (BC) bottles by light scattering. In a selected group of patients with a clinical suspicion of severe sepsis or at risk for infections with multiresistant organisms, we compared Alfred60 AST results with traditional AST results (Vitek2 (bioMérieux) or disk diffusion). Discrepancy analysis was performed by Etest (bioMérieux) or broth microdilution. In total, 222 samples were evaluated. On 595 susceptibility determinations, 93.4% showed categorical agreement (CA) with the standard method. Eighty-one percent of isolates showed a 100% categorical agreement (CA) which increased to 84.3% after discrepancy analysis. There were 8 very major discrepancies (VMD), 18 major discrepancies (MD), and 13 minor discrepancies (MiD). Most discrepant results were observed for piperacillin-tazobactam (15.6%) and clindamycin (18.9%). Analysis time was 6-6.5 h for a complete Alfred60 AST result. In addition, we evaluated the behavior of clinicians in adjusting antibiotic therapy according to the routine AST results. In 37% of all patients, antibiotic therapy was altered after reporting of AST result and adjustment was more frequent for Gram-negative than for Gram-positive isolates. With some improvements, Alfred60 provides accurate and rapid preliminary AST results for organisms causing bloodstream infections and may have at least a potential clinical benefit in about one-third of patients with severe sepsis, by delivering faster results compared with conventional methods.
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http://dx.doi.org/10.1007/s10096-019-03690-0DOI Listing
January 2020

Migrating a lab-developed MERS-CoV real-time PCR to 3 "Sample to Result" systems: experiences on optimization and validation.

Diagn Microbiol Infect Dis 2019 Aug 10;94(4):349-354. Epub 2019 Feb 10.

Department of Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address:

The goal of the study was to adapt our Middle East respiratory syndrome coronavirus (MERS-CoV) lab-developed test (LDT) to 3 "Sample to Result" (S2R) systems: BD MAX (BD), ELITe InGenius (ELITechGroup), and ARIES (Luminex). The BD MAX and InGenius system allowed use of lab-developed primers and TaqMan probes, while ARIES required conversion to MultiCode primers for melting curve analysis. Each device required ≤1 day of training and assay optimization. No discordant results were noted after analysis of 32 External Quality Control (EQC) samples. On a 10-fold dilution series of a MERS-CoV-positive EQC sample, InGenius obtained the highest detection rate. Laboratory technicians rated the ARIES as the user-friendliest. It also required the least hands-on time. BD MAX had the lowest turnaround time and highest throughput. While each device had distinguishing system properties with associated (dis)advantages, the 3 S2R systems were comparable in terms of assay development and validation.
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http://dx.doi.org/10.1016/j.diagmicrobio.2019.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127711PMC
August 2019

Donor-Related Nontuberculous Mycobacterial Interface Infection After Descemet Membrane Endothelial Keratoplasty.

Cornea 2019 May;38(5):632-634

Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium.

Purpose: To describe the first reported case of Mycobacterium chelonae-related interface keratitis after Descemet membrane endothelial keratoplasty (DMEK), successfully treated with DMEK exchange.

Methods: A case of donor-related DMEK interface keratitis, treated with medical therapy and DMEK exchange, was studied retrospectively.

Results: A patient with Fuchs endothelial dystrophy developed infectious interface keratitis after DMEK. In cultures of the donor cornea transport medium, M. chelonae was isolated. Subsequent clinical investigation showed early signs of infectious keratitis with multiple infiltrates at the donor-graft interface. Cultures at the cornea bank of origin also showed M. chelonae, indicating a donor-related infection. Because of unsuccessful medical therapy, the DMEK graft was exchanged 4.5 months after initial DMEK. After 2 weeks, some interface precipitates appeared. These precipitates regressed over the following months with continued medical therapy. Antibiotic therapy was successfully ended 5 months after DMEK exchange.

Conclusion: This case highlights the importance of early diagnosis and intensive treatment of nontuberculous mycobacterial interface keratitis. If intensive medical therapy is able to contain infection but fails to eradicate interface keratitis, DMEK exchange is a possible treatment option.
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http://dx.doi.org/10.1097/ICO.0000000000001895DOI Listing
May 2019

Follow-up of serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae in child carriage after a PCV13-to-PCV10 vaccine switch in Belgium.

Vaccine 2019 02 19;37(8):1080-1086. Epub 2019 Jan 19.

Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Background: A three year pneumococcal carriage study was set up in Belgium when the vaccination programme switched from a 13-valent (PCV13) to a 10-valent (PCV10) vaccine. We compared the first follow-up period (October 2016 - June 2017, year 2, Y2) for nasopharyngeal carriage, serotype distribution and antimicrobial susceptibility of S. pneumoniae with the baseline (January-July 2016, year 1, Y1).

Materials/methods: A single nasopharyngeal swab was taken in children (6-30 months), either attending one of the 112 day-care centres (DCCs), or visiting one of the 21 physicians for an acute otitis media (AOM). S. pneumoniae were cultured, screened for antimicrobial susceptibility, and serotyped.

Results: In Y2, 1218 samples were collected. The majority of the Y2-children (>85%) was vaccinated appropriately for their age. Children in Y2 received either PCV13 only (DCC: 23.5%; AOM: 24.6%), PCV10 only (DCC: 29.8%; AOM: 37.7%), or a mix of both vaccines (DCC: 31.9%; AOM: 25.4%). Pneumococcal carriage rates were high (Y2, DCC: 68.2%; AOM: 64.8%). Among carriers, prevalence of PCV13 serotypes was low (Y2 vs Y1, DCC: 3.5% vs 5.4%; AOM: 7.6% vs 7.7%). Although prevalence of PCV13-non-PCV10 serotypes did not increase significantly compared to Y1 (Y2 vs Y1, DCC: 1.6% vs 0.9%; Y2 vs Y1, AOM: 5.1% vs 0.0%), the proportion of serotypes 3, 6A, 19A among PCV13 serotype carriers in DCC was significantly higher in Y2 (46.2% vs Y1: 16.0%, p-value = 0.034). Serotypes 23B and 15B were the predominant non-vaccine serotypes (Y2). Among detected strains, non-susceptibility to at least one of five antibiotics tested (penicillin, tetracycline, erythromycin, levofloxacin, cotrimoxazole) was comparable to Y1 (Y2 vs Y1, DCC: 41.3% vs 42.4%; AOM: 49.4% vs 48.1%).

Conclusion: After completion of the PCV13-to-PCV10 vaccine switch in Belgium, the proportion of PCV13-non-PCV10 serotypes (mainly 19A) significantly increased among PCV13 serotype carriers in DCC, stressing the need for strengthened surveillance as the PCV10-vaccinated population grows.
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http://dx.doi.org/10.1016/j.vaccine.2018.12.068DOI Listing
February 2019

Switch in childhood pneumococcal vaccine in Belgium.

Lancet Infect Dis 2018 09;18(9):945-946

National Reference Centre for Streptococcus pneumoniae, University Hospitals Leuven, Campus Gasthuisberg, 3000 Leuven, Belgium.

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http://dx.doi.org/10.1016/S1473-3099(18)30484-5DOI Listing
September 2018

Switch in a childhood pneumococcal vaccination programme from PCV13 to PCV10: a defendable approach?

Lancet Infect Dis 2018 08 11;18(8):830-831. Epub 2018 Jul 11.

National Reference Centre for Streptococcus pneumoniae, University Hospitals Leuven, Campus Gasthuisberg, 3000 Belgium; Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1016/S1473-3099(18)30346-3DOI Listing
August 2018

Antibiotic Resistance Plasmids Cointegrated into a Megaplasmid Harboring the Carbapenemase Gene.

Antimicrob Agents Chemother 2018 03 23;62(3). Epub 2018 Feb 23.

University of Groningen, University Medical Center Groningen, Department of Medical Microbiology, Groningen, The Netherlands.

OXA-427 is a new class D carbapenemase encountered in different species of in a Belgian hospital. To study the dispersal of this gene, we performed a comparative analysis of two plasmids containing the gene, isolated from a strain and an complex strain. The two IncA/C2 plasmids containing share the same backbone; in the strain, however, this plasmid is cointegrated into an IncFIb plasmid, forming a 321-kb megaplasmid with multiple multiresistance regions.
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http://dx.doi.org/10.1128/AAC.01448-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826099PMC
March 2018

Nasopharyngeal s. pneumoniae carriage and density in Belgian infants after 9 years of pneumococcal conjugate vaccine programme.

Vaccine 2018 01 24;36(1):15-22. Epub 2017 Nov 24.

Centre for the Evaluation of Vaccination, Vaccine and Infectious Disease Institute, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Wilrijk, Belgium.

Background: In Belgium, the infant pneumococcal conjugate vaccine (PCV) programme changed from PCV7 (2007-2011) to PCV13 (2011-2015) and to PCV10 (2015-2016). A 3-year nasopharyngeal carriage study was initiated during the programme switch in 2016. Main objective of the year 1 assessment was to obtain a baseline measurement of pneumococcal carriage prevalence, carriage density, serotype distribution and antibiotic resistance.

Materials/methods: Two infant populations aged 6-30 months and without use of antibiotics in the seven days prior to sampling were approached: (1) attending one of 85 randomly selected day-care centres (DCC); (2) presenting with AOM at study-trained general practitioners and paediatricians. Demographic and clinical characteristics were documented and a single nasopharyngeal swab was taken. S. pneumoniae were cultured, screened for antibiotic resistance and serotyped, and quantitative Taqman real-time PCR (qRT-PCR) targeting LytA was performed.

Results: Culture-based (DCC: 462/760; 60.8% - AOM: 27/39; 69.2%) and LytA-based (DCC: 603/753; 80.1% - AOM: 32/39; 82.1%) carriage prevalence was high. Average pneumococcal DNA load in LytA-positive day-care samples was 6.5 × 10 copies/µl (95%CI = 3.9-9.2 × 10, median = 3.5 × 10); DNA load was positively associated with signs of common cold and negatively with previous antibiotic use. Culture-based frequency of 13 pneumococcal vaccine (PCV) serotypes was 5.4% in DCC and 7.7% in AOM, with 19F and 14 being most frequent, and frequencies below 0.5% for serotypes 3, 6A, 19A in both populations. Predominant non-PCV serotypes were 23B and 23A in day-care and 11A in infants with AOM. In day-care, resistance to penicillin was rare (<0.5%) and absent against levofloxacin; 32.7% and 16.9% isolates were cotrimoxazole- and erythromycin-resistant respectively.

Conclusion: Four years after PCV13 introduction in the vaccination programme, PCV13 serotype carriage was rare in infants throughout Belgium and penicillin resistance was rare. Continued surveillance in the context of a PCV programme switch is necessary.
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http://dx.doi.org/10.1016/j.vaccine.2017.11.052DOI Listing
January 2018

Septic arthritis of the temporomandibular joint after acute otitis media in a child.

Quintessence Int 2017 ;48(10):809-813

Septic arthritis of the temporomandibular joint as a complication of acute otitis media is rare in the Western world. This report describes the case of a 7-year-old boy who had pain in his right ear and limited mouth opening, following the onset of acute otitis media. A contrast-enhanced computed tomography scan revealed right-sided mastoiditis and hydrops of the right temporomandibular joint, suggesting septic arthritis. Real-time PCR and microbiologic analysis identified Streptococcus pyogenes and Staphylococcus epidermidis in the joint aspirate. Treatment with arthrocentesis and antibiotics led to full recovery of temporomandibular joint function.
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http://dx.doi.org/10.3290/j.qi.a39032DOI Listing
October 2018

Candida and its dual lifestyle as a commensal and a pathogen.

Res Microbiol 2017 Nov - Dec;168(9-10):802-810. Epub 2017 Mar 2.

Department of Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; Department of Microbiology and Immunology, KU Leuven - University of Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address:

Candida spp. are part of the normal vaginal microflora in 20-30% of healthy women. However, if the balance between these yeasts and the host is disturbed, Candida spp. can cause vulvovaginal candidiasis (VVC), with Candida albicans being the major causative agent. Different studies have been performed in order to better understand Candida's dual lifestyle in the vagina. The potential of C. albicans to switch from the yeast cell morphology to its hyphal form is considered a key element in VVC pathogenesis. Candida spp. also express other virulence factors, such as hydrolytic extracellular enzymes and heat shock proteins and can form biofilms.
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http://dx.doi.org/10.1016/j.resmic.2017.02.005DOI Listing
July 2018

Analytical and clinical comparison of Elecsys syphilis (Roche) - Architect syphilis TP and reformulated Architect syphilis TP (Abbott) assay.

Diagn Microbiol Infect Dis 2017 Mar 9;87(3):210-212. Epub 2016 Dec 9.

Department of Laboratory Medicine, AZ St Jan Bruges, Bruges, Belgium. Electronic address:

The performance of Elecsys Syphilis was compared to Architect Syphilis TP and Reformulated Architect Syphilis TP. The overall sensitivity and specificity were 98.4% and 99.5%, 97.7% and 97.1%, and 99.2% and 99.7% respectively. The assays are comparable and considered adequate for syphilis screening.
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http://dx.doi.org/10.1016/j.diagmicrobio.2016.12.003DOI Listing
March 2017

How to treat a fulminant erysipelas and sepsis caused by Myroides odoratimimus: case report and literature review.

Acta Clin Belg 2017 Oct 20;72(5):331-335. Epub 2016 Oct 20.

a Department of Microbiology and Immunology, Laboratory of Bacteriology and Mycology , KU Leuven - University of Leuven, University Hospitals Leuven , Leuven , Belgium.

We report a case of a 77-year old male who developed a fulminant erysipelas and sepsis, caused by Myroides odoratimimus. Selecting the optimal antibiotic therapy for the treatment of infections with M. odoratimimus is challenging due to limited clinical experience with this micro-organism and its reported multidrug-resistance. Review of previous studies concerning in vitro antibacterial susceptibility and clinical experience with M. odoratimimus resulted in six case reports describing bacteremia, soft tissue and bone infections, pneumonia and urinary tract infections. In vitro susceptibility to aminoglycosides, fluoroquinolones and trimethoprim/sulfamethoxazole is variable. Treatment of M. odoratimimus infections should be based on antimicrobial susceptibility testing results. In a majority of the case reports, including the present one, treatment with fluoroquinolones proved to be a good therapeutic option.
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http://dx.doi.org/10.1080/17843286.2016.1245173DOI Listing
October 2017

Comparison of PCR-Electrospray Ionization Mass Spectrometry with 16S rRNA PCR and Amplicon Sequencing for Detection of Bacteria in Excised Heart Valves.

J Clin Microbiol 2016 11 14;54(11):2825-2831. Epub 2016 Sep 14.

University Hospitals of Leuven, Clinical Department of Laboratory Medicine, Leuven, Belgium

Identification of the causative pathogen of infective endocarditis (IE) is crucial for adequate management and therapy. A broad-range PCR-electrospray ionization mass spectrometry (PCR-ESI-MS) technique was compared with broad-spectrum 16S rRNA PCR and amplicon sequencing (16S rRNA PCR) for the detection of bacterial pathogens in 40 heart valves obtained from 34 definite infective endocarditis patients according to the modified Duke criteria and six nonendocarditis patients. Concordance between the two molecular techniques was 98% for being positive or negative, 97% for concordant identification up to the genus level, and 77% for concordant identification up to the species level. Sensitivity for detecting the causative pathogen (up to the genus level) in excised heart valves was 88% for 16S rRNA PCR and 85% for PCR-ESI-MS; the specificity was 83% for both methods. The two molecular techniques were significantly more sensitive than valve culture (18%) and accurately identified bacteria in excised heart valves. In eight patients with culture-negative IE, the following results were obtained: concordant detection of Coxiella burnetii (n = 2), Streptococcus gallolyticus (n = 1), Propionibacterium acnes (n = 1), and viridans group streptococci (n = 1) by both molecular tests, detection of P. acnes by PCR-ESI-MS whereas the 16S rRNA PCR was negative (n = 1), and a false-negative result by both molecular techniques (n = 2). In one case of IE caused by viridans streptococci, PCR-ESI-MS was positive for Enterococcus spp. The advantages of PCR-ESI-MS compared to 16S rRNA PCR are its automated workflow and shorter turnaround times.
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http://dx.doi.org/10.1128/JCM.01240-16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5078563PMC
November 2016

Cladophialophora bantiana osteomyelitis in a renal transplant patient.

Med Mycol Case Rep 2016 Jun 9;12:17-20. Epub 2016 Jul 9.

Department of Microbiology and Immunology, Laboratory of Nephrology, KU Leuven - University of Leuven, Belgium; Department of Nephrology, Dialysis and Renal Transplantation, University Hospitals Leuven, Herestraat 49, Leuven 3000, Belgium.

Cladophialophora bantiana is a neurotropic dematiaceous fungus which rarely causes disseminated disease. We report a case of proven C. bantiana osteomyelitis in a renal transplant recipient, complicated with probable cerebral disease. Stable disease was reached after combined antifungal therapies, immune enhancement and amputation of the infected lower limb.
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http://dx.doi.org/10.1016/j.mmcr.2016.07.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995601PMC
June 2016

Minimal Coexpression of CD34+/CD56+ in Acute Promyelocytic Leukemia Is Associated With Relapse.

Am J Clin Pathol 2015 Aug;144(2):347-51

Hematology, AZ Delta Hospital Roeselare-Menen, Roeselare, Belgium; and.

Objectives: Surface CD56 expression on leukemic cells in acute promyelocytic leukemia (APML) is considered an indicator of poorer outcome even in patients receiving conventional treatment.

Methods: In the present case, at initial diagnosis, the hallmark phenotype of APML was found (strong CD33 and cytoplasmic MPO expression, absence of HLA-DR expression).

Results: Both CD34 and CD56 antigen expression was considered negative. The patient relapsed 3 years after reaching complete remission, and the hallmark surface antigen combination for APML was again found. In contrast, the leukemic cells now clearly coexpressed CD34 and CD56. Retrospective analysis revealed the presence of small CD34+ and CD56+ populations at initial diagnosis (<20%).

Conclusions: This case report suggests that the presence of a clone with minimal coexpression of CD34/CD56 in APML at initial diagnosis should not be neglected since it may be associated with earlier relapse.
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http://dx.doi.org/10.1309/AJCPBS3W1RJDGPZUDOI Listing
August 2015