
Mark van der LindenUniversity Hospital RWTH Aachen · Department of Medical Microbiology
Mark van der Linden
PhD
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207
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Introduction
Additional affiliations
February 2004 - July 2007
February 2004 - present
Publications
Publications (207)
As a potential side effect of the severe acute respiratory syndrome coronavirus type 2 pandemic, invasive group A Streptococcus (iGAS) infections in Europe have increased dramatically in both children and adults in the end of 2022. This epidemiological and molecular study describes the distributions of streptococcal genes encoding the M antigen (em...
Background:
In late 2022, health care institutions in Germany reported an unusual number of severe, invasive bacterial infections in association with a high incidence of viral respiratory infections.
Methods:
We analyzed routine data on invasive infections due to Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcu...
Purpose
In late 2022, a surge of severe S. pyogenes infections was reported in several European countries. This study assessed hospitalizations and disease severity of community-acquired bacterial infections with S. pyogenes, S. pneumoniae, N. meningitidis, and H. influenzae among children in North Rhine-Westphalia (NRW), Germany, during the last q...
Next-generation pneumococcal conjugate vaccines (PCVs) have been approved for use. The serotype distribution of pneumococcal isolates can vary between regions. To understand the potential impacts of new PCVs, we evaluated trends in invasive pneumococcal disease (IPD) among adults in Germany at a local level using Bayesian hierarchical logistic regr...
Background:
In late 2022, a surge of severe bacterial infections caused by S. pyogenes was reported in several European countries, including Germany. This study assessed disease burden and severity of hospitalizations for community-acquired bacterial infections with S. pyogenes, S. pneumoniae, N. meningitidis, and H. influenzae among children in No...
The identification of the novel pneumococcal serotype 7D by Neufeld quellung reaction requires significant expertise. To circumvent this, we developed a simple serotype-specific PCR method to discriminate serotype 7D from the closely related serotypes 7C, 7B and 40. The established PCR was validated with the strain collection of the German National...
Introduction
Two next-generation pneumococcal conjugate vaccines (PCVs), a 15- and a 20-valent PCV (PCV15 and PCV20), have recently been licensed for use in adults, and PCV15 has also been licensed in children. We developed a dynamic transmission model specific for Germany, with the aim to predict carriage prevalence and invasive pneumococcal disea...
This study evaluated the HiberGene Group B Streptococcus test, a CE-IVD-approved molecular assay for rapid detection of Streptococcus agalactiae [Group B Streptococcus (GBS)] in human clinical specimens. Performance of the assay in terms of specificity, sensitivity and genotype inclusivity was investigated using an extended specificity panel of 113...
[This corrects the article DOI: 10.1016/j.lanepe.2021.100126.].
Background
The incidence of invasive pneumococcal disease (IPD) decreased worldwide in 2020 and the first quarter of 2021, concurrent with non-pharmaceutical interventions (NPIs) intended to stymie transmission of SARS-CoV-2. In 2021, stringency of these NPI strategies has varied. We investigated age- and serotype-specific variations in IPD case co...
Epidemiological data on nasopharyngeal (NP) bacterial carriage in children in Germany are scarce. We prospectively characterized NP colonization to evaluate the impact of pneumococcal immunization. We longitudinally collected NP swabs from 2-month-old infants (visit 1; V1) at eight representative pediatric offices 10/2008-06/2009. The second swabs...
Background
Invasive pneumococcal disease (IPD) in people ≥60 years old is on the rise in Germany. There has been a recommendation for pneumococcal vaccination in this age group since 1998.
Methods
We determined the vaccination status of people ≥60 years old with IPD in Germany. We assessed vaccine effectiveness (VE) of the recommended 23-valent po...
We analyzed middle ear fluid (MEF) and nasopharyngeal swabs (NPS) from spontaneously ruptured acute otitis media (AOM) cases occurring in children under 5 years in Germany. The aim of the study was the assessment of disease burden and bacterial etiology in the era of routine pneumococcal vaccination. Furthermore, we aimed to compare isolates from M...
Background:
Serotype-specific diagnosis of pneumococcal community-acquired pneumonia in children under age 5 years would mark a major advancement for understanding pneumococcal epidemiology and supporting vaccine decision-making.
Methods:
A Luminex technology-based multiplex urinary antigen detection (UAD) diagnostic assay was developed and subs...
Background - Invasive pneumococcal disease (IPD) in people ≥60 years old is on the rise in Germany. There has been a recommendation for pneumococcal vaccination in this age group since 1998.
Methods - We determined the vaccination status of people ≥60 years old with IPD in Germany. We assessed vaccine effectiveness (VE) of the recommended 23-valent...
Novel catalase-negative, Gram-stain-positive, beta-haemolytic, coccus-shaped organisms were isolated from Chacoan peccaries that died from respiratory disease. The initial API 20 Strep profiles suggested Streptococcus agalactiae with acceptable identification scores, but the 16S rRNA gene similarity (1548 bp) to available sequences of streptococci...
Background
The nasopharynx can from time to time accommodate otherwise pathogenic bacteria. This phenomenon is called asymptomatic carriage. However, in case of decreased immunity, viral infection or any other enhancing factors, severe disease can develop. Our aim in this study was to survey the nasal carriage rates of four important respiratory pa...
[This corrects the article DOI: 10.1371/journal.pone.0220453.].
Objectives:
Streptococcus agalactiae [group B streptococci (GBS)] have been considered uniformly susceptible to penicillin. However, increasing reports from Asia and North America are documenting penicillin-non-susceptible GBS (PRGBS) with mutations in pbp genes. Here we report, to the best of our knowledge, the first two PRGBS isolates recovered...
Background
A general recommendation for adult pneumococcal vaccination with 23-valent polysaccharide vaccine (PPV23) for adults 60 and older has been in place in Germany since 1998, but uptake has been low. Just over a decade after the implementation of an infant pneumococcal conjugate vaccine recommendation, we examined indirect protection effects...
Objective
The aim of this study was to determine the prevalence of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, group A Streptococcus (GAS), and Staphylococcus aureus in asymptomatic elderly people and to unravel risk factors leading to colonization.
Methods
A multi-centre cross-sectional study was conducted including...
Prevalence of H. influenzae and N. meningitidis.
(DOCX)
Questionnaire–original questions.
(DOCX)
Overview
The protective effect of infant pneumococcal conjugate vaccine (PCV) recommendation can be seen in Germany as a whole and in smaller regional groups. Comparisons between population-normalized geographic regions of Germany show different serotype distributions after program implementation, particularly in non-vaccine serotypes. The prior di...
Variables influencing pneumococcal vaccination status.
Multivariate logistic regression results showing any models with at least one factor which reached statistical significance with vaccination status as the outcome variable and the geographic and demographic variables as potential predictor variables. No variables were significantly associated i...
Distribution of demographic variables from the 2011 census.
Variables are displayed by geographic group (left) or by former political group (right).
(TIF)
Logistic regression results for the PCV7 group.
Univariate and multivariate ORs and 95% CIs are shown for three age cohorts: at least one dose (≥90 days old), n = 244, post primary series (149–449 days old), n = 110 , and post booster dose (>449 days old), n = 88. Variables that reached statistical significance in the multivariate models appear in...
Logistic regression results for the PCV10 group.
Univariate and multivariate ORs and 95% CIs are shown for three age cohorts: at least one dose (≥90 days old), n = 149, post primary series (149–449 days old), n = 74, and post booster dose (>449 days old), n = 46. Variables that reached statistical significance in the multivariate models appear in b...
Logistic regression results for the PCV13 group.
Univariate and multivariate ORs and 95% CIs are shown for three age cohorts: at least one dose (≥90 days old),n = 374, post primary series (149–449 days old), n = 177, and post booster dose (>449 days old), n = 147. Variables that reached statistical significance in the multivariate models appear in...
Full spreadsheet of data used for multiple regression analyses.
(XLSX)
Rising non-vaccine serotypes following PCV program implementation in Germany.
Cases of selected non-vaccine serotypes causing IPD in children under six per pneumococcal season, seen across the geographic analysis groups. While the proportion of all non-vaccine serotype IPD increased significantly in three of the four geographic groups and across al...
Young children – the main asymptomatic carriers of pneumococcus – are often the source of pneumococcal infections. PCV13 replaced PCV7 in 2010 in Hungary and it became a mandatory vaccine in 2014. In this work we surveyed the effect of vaccination in three groups: in healthy children under 7 years; in children of the same age but infected with pneu...
Refugee children in Germany are not routinely given a pneu-mococcal conjugate vaccine. Cases of invasive pneumo-coccal disease (IPD) in 21 refugee children were compared with those in 405 Germany-born children for 3 pneumococ-cal seasons. Refugee children had significantly higher odds of vaccine-type IPD and multidrug-resistant IPD than did Germany...
Discussion of the estimated incidence of invasive pneumococcal disease in refugee and Germany-born children.
Pneumococcal disease is an important cause of morbidity and mortality worldwide with a significant financial burden. Pneumococcal vaccines are available and recommended in many countries for at-risk populations including young children, the elderly and those with underlying medical conditions. The Hajj and Umrah mass gatherings attract millions of...
Alterations in PBP2a have been recognized in cefotaxime-resistant laboratory mutants and β-lactam-resistant clinical isolates of Streptococcus pneumoniae. DNA sequencing revealed fundamental differences between these two settings. Internal stop codons in pbp2a occurred in all three laboratory mutants analyzed, caused by a mutation in pbp2a of mutan...
Objective:
To identify a potential nadir of the impact of pneumococcal conjugate vaccination (PCV) in infancy on invasive pneumococcal diseases (IPD) in children under 16 in Germany.
Methods:
Active surveillance on IPD based on two independent data sources with capture-recapture correction for underreporting. Annual incidence rates by age group,...
Streptococcus pyogenes (GAS) is one of the major human pathogenic bacteria that cause a wide range of diseases. Currently, increased incidence of streptococcal invasive infections is observed worldwide. In this study, we focused on the prevalence of genes encoding superantigens and type M proteins in the population of GAS strains from invasive vers...
A nationwide laboratory-based surveillance study of invasive S. pyogenes infections was conducted in Germany. Invasive isolates (n = 719) were obtained between 2009 and 2014. Most isolates were obtained from blood (92.1%). The proportions of isolates from cerebrospinal fluid, pleural fluid, synovial fluid and peritoneal fluid were 3.9%, 1.8%, 1.7%...
Diagnoses, complications, underlying conditions, emm types, and superantigen genes in 719 cases of invasive Group A Streptococcus disease in Germany from 2009–2014.
(XLSX)
Streptococcus pneumoniae is a major cause of bacterial pneumonia, sepsis and meningitis worldwide. Prevalence of levofloxacin-resistant S. pneumoniae isolates in Germany and associated mutations in the quinolone resistance determining regions (QRDRs), as well as serotype distribution and multi locus sequence types (MLST) are shown. 21,764 invasive...
Streptococcus pneumoniae is a major pathogen that causes different invasive pneumococcal diseases (IPD). The pneumococcal polysaccharide capsule is a main virulence factor. More than 94 capsule types have been described, but only a limited number of capsule types accounted for the majority of IPD cases before the introduction of pneumococcal vaccin...
Background:
In this study we calculate the effectiveness of pneumococcal conjugate vaccines (PCV) against invasive pneumococcal disease (IPD) among children under the age of two years using the indirect cohort method. We also discuss the timeliness of vaccination and the residual cases of vaccine type IPD.
Methods and findings:
From July 2006 un...
During 2010-2014, we enrolled 511 patients with suspected bacterial meningitis into surveillance in 2 districts of northern Togo. We identified 15 persons with Streptococcus suis infection; 10 had occupational contact with pigs, and 12 suffered neurologic sequelae. S. suis testing should be considered in rural areas of the African meningitis belt.
Streptococcus pneumoniae is a rare cause of urinary tract infection. Between January 2010 and December 2014 26 urine samples from 18 different patients contained S. pneumoniae at the Department for Infectious Diseases, University Hospital of Heidelberg. Patient age varied between three and 72 years. 13 patients were male and five were female. Past...
Invasive group A streptococcal (GAS) infections constitute an important epidemiological problem. Many cases occur in women during the postnatal period. The objective of this study was to evaluate the presence of the genes responsible for production of iron-chelating protein (perR) and superantigens (speA, speB, speC, speF, speG, speH, speI, speJ, s...
For epidemiological and surveillance purposes, it is relevant to monitor the distribution and dynamics of Streptococcus pneumoniae serotypes. Conventional serotyping methods do not provide rapid or quantitative information on serotype loads. Quantitative serotyping may enable prediction of the invasiveness of a specific serotype compared to other s...
Objective:
To assess the vaccine effectiveness (VE) of PCV13 for invasive pneumococcal disease (IPD) regarding the extra six serotypes with a 3+1 schedule in Germany.
Methods:
Active surveillance for IPD in children <16 years eligible for PCV13 vaccination. We used the Broome method and logistic regression to estimate VE.
Results:
Data on 164/...
The etiological diagnosis of infections caused by Streptococcus pneumoniae has been expanded by non-culture methods, including the detection of pneumococcal DNA in biological samples and the identification of C polysaccharide in urine. The basis for these methods and their use and limitations in the recognition of infections of pneumococcal etiolog...
Long-term complications and a case mortality rate of 7.5% make meningitis caused by Streptococcus pneumoniae a serious clinical threat. In 2006, a general pneumococcal conjugate vaccination (PCV) recommendation was issued for all children under 2 years in Germany. Here, we investigate serotype changes in meningitis cases after this vaccine recommen...
After the introduction of conjugate vaccines, a strong rearrangement of pneumococcal serotypes was observed globally. Probably most concerning was the emergence of serotype 19A, which has not only high invasive disease potential, but also high antibiotic resistance. In the current study we focused on the increased prevalence of serotype 19A after t...
Objectives: Isolation of Streptococcus pneumoniae from healthy children in Wadi Al Seer, Jordan before vaccination with prevenar.
Methods: Nasopharyngeal and throat swabs were colloected from 118 healthy children with age range from one to 50 months and mean age 13.4 months. Isolates were analysed for antimicrobial susceptibility, serotyping and ma...
A nationwide laboratory-based surveillance study of invasive S. pyogenes infections was conducted in Germany. Invasive isolates (n = 1,281) were obtained between 2003 and 2013. All isolates were susceptible to penicillin, cefotaxime and vancomycin. Tetracycline showed the highest rate of resistant or intermediate resistant isolates with 9.8%, follo...
Continuous nationwide surveillance of invasive pneumococcal disease (IPD) was conducted in Germany. A total of 22,208 isolates from invasive pneumococcal disease were collected between July 1, 1992 and June 30, 2013. The present study was conducted to analyze changes in antimicrobial susceptibility and pneumococcal vaccine coverage after the introd...
This study describes the effects of the introduction of universal infant pneumococcal conjugate vaccination in 2006 on invasive pneumococcal disease (IPD) among children and adults in Germany with a focus on the dynamics of serotype distribution in vaccinated and non-vaccinated age groups. Over a period of 22 years (1992-2014), microbiological diag...
This study presents an analysis of 1,491 serogroup 23 and 762 serogroup 15 isolates from invasive pneumococcal disease (IPD) in children and adults before and after the general recommendation for childhood pneumococcal conjugate vaccination in Germany in July 2006. Vaccination formulations used were PCV7 (from July 2006), PCV10 (from April 2009) an...
Objectives: Streptococcus pneumoniae (the pneumococcus) is one of the most important infectious causes of childhood mortality in the world. To prevent invasive infections, conjugated vaccines (PCVs) were developed. PCV7 was inserted in the national immunisation programme in 2009 as a voluntary but free vaccine. PCV13 replaced PCV7 in 2010, and was...
We assessed the impact of 10-valent and 13-valent pneumococcal vaccines (PCV10 and PCV13), which were introduced in Germany in 2009, on the incidence of meningitis and non-meningitis invasive pneumococcal disease (IPD) in children aged under 16 years in a population previously vaccinated with a seven-valent vaccine (PCV7). Surveillance of IPD (isol...
Over two million Muslim pilgrims assemble annually in Mecca and Medina, Saudi Arabia, to complete the Hajj. The large number of people in a crowded environment increases the potential for pneumococcal carriage amplification. We evaluated pneumococcal carriage prevalence with four cross-sectional studies conducted at beginning-Hajj (Mecca) and end-H...
The objectives of this study were to assess the current incidence of invasive pneumococcal disease (IPD) in Poland (2011-2013), where mass vaccination has not been implemented, and to characterize the Streptococcus pneumoniae isolates responsible for invasive infections by determining their serotype distribution and antimicrobial resistance pattern...
Continuous nationwide surveillance of invasive pneumococcal disease (IPD) was conducted in Germany. From July 1, 1997, to June 30, 2013, data on penicillin susceptibility were available for 20,437 isolates. 2,790 of these isolates (13.7 %) originate from patients with meningitis and 17,647 isolates (86.3 %) are from non-meningitis cases. A slight d...
Streptococcus pneumoniae is responsible for a significant amount of morbidity and mortality worldwide. Healthy carriers, mainly young children, are the most important sources of infections. In the current study, we aimed to determine the changes that have occurred since the introduction of PCV-7 in Hungary. Nasal specimens were collected from 1,022...
Otitis media is a common pediatric disease and the main reason for antibiotic prescription in children. Before implementation of routine childhood pneumococcal vaccination in Germany, serotypes contained in the seven-valent pneumococcal conjugate vaccine (PCV) were among the most frequent pneumococcal serotypes responsible for acute otitis media (A...
Background
Pneumococcal β-lactam resistance was first detected in Iceland in the late 1980s, and subsequently peaked at almost 25% of clinical isolates in the mid-1990s largely due to the spread of the internationally-disseminated multidrug-resistant PMEN2 (or Spain6B-2) clone of Streptococcus pneumoniae.
Results
Whole genome sequencing of an inte...
The multidrug-resistant Streptococcus pneumoniae Taiwan(19F)-14, or PMEN14, clone was first observed with a 19F serotype, which is targeted by the heptavalent polysaccharide conjugate vaccine (PCV7). However, 'vaccine escape' PMEN14 isolates with a 19A serotype became an increasingly important cause of disease post-PCV7. Whole genome sequencing was...