Karl Kristinsson

National University Hospital of Iceland | LSH · Department of Microbiology

Bacteriocins are antimicrobial peptides produced by bacteria to inhibit other bacteria in the surrounding environment. Streptococcus pneumoniae is a leading cause of disease worldwide and colonises the healthy human nasopharynx, where it competes for space and nutrients. Pneumococcal conjugate vaccines have reduced the incidence of disease, but the...

Background: The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases durin...

Bacteriocins are antimicrobial peptides produced by bacteria to inhibit other bacteria in the surrounding environment. Streptococcus pneumoniae is a leading cause of disease worldwide and colonises the healthy human nasopharynx, where it competes for space and nutrients. Pneumococcal conjugate vaccines have reduced the incidence of disease, but the...

From the beginning of the COVID-19 pandemic, it has claimed over 6 million lives, and globally the pandemic rages with detrimental consequences, with the emergence of new more infectious and possibly virulent variants. A clinical obstacle in this battle has been to determine when an infected individual has reached a non-infectious state. Severe Acu...

Background: Pneumonia is commonly caused by Streptococcus pneumoniae (pneumococcus) and associated with subsequent cardiovascular complications and increased mortality. Potential short-term survival benefits conferred by acetylsalicylic acid (ASA) use in pneumonia remain controversial, and long-term outcomes have not been studied. Objectives: To...

Background Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them. Methods Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n...

Background: Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them. Methods: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (...

A pressing concern in the SARS-CoV-2 epidemic and other viral outbreaks, is the extent to which the containment measures are halting the viral spread. A straightforward way to assess this is to tally the active cases and the recovered ones throughout the epidemic. Here, we show how epidemic control can be assessed with molecular information during...

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...

A detailed understanding of the antibody response against SARS-CoV-2 is of high importance, especially with the emergence of novel vaccines. A multiplex-based assay, analyzing IgG, IgM, and IgA antibodies against the receptor binding domain (RBD), spike 1 (S1), and nucleocapsid proteins of the SARS-CoV-2 virus was set up. The multiplex-based analys...

Introduction Streptococcus pneumoniae is a cause of infections that range in severity from acute otitis media (AOM) to pneumonia and invasive pneumococcal disease (IPD). The 10-valent pneumococcal conjugate vaccine (PHiD-CV10) was introduced into the Icelandic paediatric immunisation programme in 2011. The aim was to estimate the population impact...

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, s...

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,...

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 dist...

Streptococcus pneumoniae 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 ai...

Background Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis are leading causes of invasive diseases including bacteraemic pneumonia and meningitis, and of secondary infections post-viral respiratory disease. They are typically transmitted via respiratory droplets. We investigated rates of invasive disease due to these pat...

Background Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We measured antibodies in serum samples from 30,576 persons in Iceland, using six assays (including two pan-immunoglobulin [pan-Ig] assays), and we determined that the app...

Background: Antimicrobial resistance is a growing global health threat. To preserve the effectiveness of antimicrobials, it is important to reduce demand for antimicrobials. Objectives: The objective of the study was to screen the existing peer-reviewed literature to identify articles that addressed the potential impact of influenza or Pneumococcus...

Resistance to macrolide antibiotics is a global concern in the treatment of Streptococcus pyogenes (Group A Streptococcus , GAS) infections. In Iceland, since the detection of the first macrolide-resistant isolate in 1998, three epidemic waves of macrolide-resistant GAS infections have occurred with peaks in 1999, 2004, and 2008. We conducted whole...

Resistance to macrolide antibiotics is a global concern in the treatment of Streptococcus pyogenes (Group A Streptococcus, GAS) infections. In Iceland, since the detection of the first macrolide-resistant isolate in 1998, three epidemic waves of macrolide-resistant GAS infections have occurred with peaks in 1999, 2004, and 2008. We conducted whole...

Background During the current worldwide pandemic, coronavirus disease 2019 (Covid-19) was first diagnosed in Iceland at the end of February. However, data are limited on how SARS-CoV-2, the virus that causes Covid-19, enters and spreads in a population. Methods We targeted testing to persons living in Iceland who were at high risk for infection (m...

BACKGROUND Limited data exist on how SARS-CoV-2 enters and spreads in the general population. METHODS We used two strategies for SARS-CoV-2 testing: targeted testing of high-risk individuals (n=4,551) and a population screening (n=5,502). We sequenced SARS-CoV-2 from 340 individuals. RESULTS On March 22 2020, 528 had tested positive for SARS-CoV-...

Background Penicillin non-susceptible (PNSP) and multi-resistant pneumococci have been prevalent in Iceland since early nineties, mainly causing problems in treatment of acute otitis media. The 10-valent protein conjugated pneumococcal vaccine (PHiD-CV) was introduced into the childhood vaccination program in 2011. The aim of the study was to inves...

Introduction: Pneumococcus is an important respiratory pathogen. The 10-valent pneumococcal vaccine (PHiD-CV) was introduced into the Icelandic vaccination programme in 2011. The aim was to estimate the impact of PHiD-CV on paediatric hospitalisations for respiratory tract infections and invasive disease. Methods: The 2005-2015 birth-cohorts wer...

Recently two related Streptococcus pyogenes strains with reduced susceptibility to ampicillin, amoxicillin and cefotaxime, antibiotics commonly used to treat S. pyogenes infections were reported. The two strains had the same nonsynonymous (amino acid-substituting) mutation in the pbp2x gene encoding penicillin-binding protein 2X (PBP2X). This conce...

Introduction: Preventing the spread of methicillin-resistant Staphylococcus aureus (MRSA) and understanding the pathophysiology and transmission is essential. This study describes an MRSA outbreak in a neonatal intensive care unit in Reykjavik, Iceland at a time where no screening procedures were active. Materials and methods: After isolating MRSA...

Vaccinations with the PHiD-CV pneumococcal vaccine started in Iceland in 2011. Protein D (PD) from H. influenzae , which is coded for by the hpd gene, is used as a conjugate in the vaccine, and can possibly provide protection against PD positive H. influenzae. We aimed to evaluate the effect of the PHiD-CV vaccination on H. influenzae in children,...

Streptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. Although a number of large-scale genomic studies of bacterial pathogens have been published, the relationships among the genome, transcriptome, and virulence in large bacteri...

Understanding the structure of a bacterial population is essential in order to understand bacterial evolution. Estimating the core genome (those genes common to all, or nearly all, strains of a species) is a key component of such analyses. The size and composition of the core genome varies by dataset, but we hypothesized that the variation between...

Comparison of the four study datasets in terms of the number of assembled contigs in each genome assembly.

Metadata and accession numbers associated with the 3,100 pneumococcal genomes analyzed in this study.

Metadata and accession numbers associated with the 1,000 non-pneumococcal Streptococcus spp. analyzed in this study.

Supercore genes found in all pneumococcal study genomes, plus the additional core genes shared by the Reykjavik, Southampton, and Boston pneumococci.

Associations between clonal complexes as defined by MLST and sequence clusters as defined by hierBAPS, stratified by geographical location.

Core genes identified in each of the four individual datasets.

Unique gene clusters identified in each of the four individual datasets.

Aim The aim was to estimate the impact of the 10‐valent pneumococcal vaccine (PHiD‐CV) on tympanostomy tube placements (TTP) in children under five years of age in Iceland. Methods This population based observational cohort study followed 11 consecutive birth‐cohorts 2005‐2015 from birth until their fifth birthday. Population registries were merge...

The introduction of pneumococcal conjugate vaccines (PCV) into childhood vaccination programs has reduced carriage of vaccine serotypes and pneumococcal disease. The 10-valent PCV was introduced in Iceland in 2011. The aim of this study was to determine PCV impact on the prevalence of serotypes, genetic lineages and antimicrobial-resistant pneumoco...

Background Infections due to antibiotic-resistant bacteria are threatening modern health care. However, estimating their incidence, complications, and attributable mortality is challenging. We aimed to estimate the burden of infections caused by antibiotic-resistant bacteria of public health concern in countries of the EU and European Economic Are...

Background: Antimicrobial resistance is a public-health threat and antimicrobial consumption is the main contributor. The ten-valent pneumococcal conjugate vaccine (PHiD-CV10) was introduced into the Icelandic vaccination program in 2011. The aim was to estimate the vaccine impact of PHiD-CV10 on outpatient antimicrobial prescriptions in children....

Background: Despite a risk-based peripartum chemoprophylaxis approach in Iceland since 1996, Streptococcus agalactiae (GBS) remains an important cause of early-onset (<7 days, EOD) and late-onset disease (7 days to 3 months, LOD). Methods: We studied GBS invasive disease in children <1 year in Iceland in 1976-2015. Bacteria (n=98) were character...

Vaccination with pneumococcal conjugate vaccines (PCVs) disrupts the pneumococcal population. Our aim was to determine the impact of the 10-valent PCV on the serotypes, genetic lineages and antimicrobial susceptibility of pneumococci isolated from children in Iceland. Pneumococci were collected between 2009-2017 from the nasopharynx of healthy chil...

Knowledge about pneumococcal carriage, antibacterial resistance, serotype prevalence, and prevalence of invasive pneumococcal disease (IPD) after introduction of pneumococcal conjugate vaccines (PCVs) is lacking in the Faroe Islands. PCV-7 was introduced in 2008 and PCV-13 in 2010. The aim was to obtain knowledge on serotypes and antimicrobial resi...

Background: The 10-valent pneumococcal conjugate vaccine (PHiD-CV10) was introduced in Iceland in 2011, without catch-up. The aim of this study was to estimate vaccine impact on acute otitis media (AOM). Methods: In this whole-population study, all primary care visits due to AOM from 2005-2015 in children less than three years of age were includ...

Background The microbial etiology of community-acquired pneumonia (CAP) is often unclear in clinical practice, and previous studies have produced variable results. Population-based studies examining etiology and incidence are lacking. This study examined the incidence and etiology of CAP requiring hospitalization in a population-based cohort as wel...

Whole Genome Sequencing (WGS) has become an essential tool for public health surveillance and molecular epidemiology of infectious diseases and antimicrobial drug resistance. It provides precise geographical delineation of spread and enables incidence monitoring of pathogens at genotype level. Coupled with epidemiological and environmental investig...

Background: Acute otitis media non-responsive to antibiotics is most commonly caused by antibiotic-resistant Streptococcus pneumoniae and Haemophilus influenzae. A strategy for treating these infections with parenteral ceftriaxone was adopted at The Children's Hospital Iceland. The 10-valent pneumococcal H. influenzae Protein D-conjugate vaccine (...

Background: Since the introduction of pneumococcal conjugate vaccines, vaccine type pneumococcal carriage and disease has decreased world-wide. The aim was to monitor changes in the nasopharyngeal carriage of pneumococci, the distribution of serotypes and antimicrobial resistance in children before and after initiation of the 10-valent pneumococca...

Currently, data on Escherichia coli antibacterial susceptibilities in the Faroe Islands are lacking. The aim was to investigate the antibacterial susceptibilities of E. coli from patients with community-acquired urinary tract infections in the Faroe Islands, correlate with antibacterial sales, and compare with Iceland and Denmark. From 2009 to 2010...

Background Understanding the structure of a bacterial population is essential in order to understand bacterial evolution, or which genetic lineages cause disease, or the consequences of perturbations to the bacterial population. Estimating the core genome, the genes common to all or nearly all strains of a species, is an essential component of such...

A lack of sensitive tests and difficulties obtaining representative samples contribute to the challenge in identifying etiology in pneumonia. Upper respiratory tract swabs can be easily collected and analyzed with real-time PCR (rtPCR). Common pathogens such as S. pneumoniae and H. influenzae can both colonize and infect the respiratory tract, comp...

Background Information on pneumococcal serotype distribution before vaccination is a prerequisite for evaluation of vaccine effect. The aim was to investigate the prevalence of pneumococcal serotypes isolated from middle ear (ME), lower respiratory tract (LRT) and from invasive disease (IPD) in Iceland prior to implementation of ten-valent pneumoco...

This is the full supporting information that includes impersonalized relevant information of specimen aquisition and results. (XLSX)

The pneumococcus is a leading global pathogen and a key virulence factor possessed by the majority of pneumococci is an antigenic polysaccharide capsule (‘serotype’), which is encoded by the capsular (cps) locus. Approximately 100 different serotypes are known, but the extent of sequence diversity within the cps loci of individual serotypes is not...

Unlabelled: For over a century, a fundamental objective in infection biology research has been to understand the molecular processes contributing to the origin and perpetuation of epidemics. Divergent hypotheses have emerged concerning the extent to which environmental events or pathogen evolution dominates in these processes. Remarkably few studi...

Supplemental Materials and Methods. Download

Atlases for the three emm89 reference genomes. Shown from the outermost (1st) ring to the innermost (12th) ring are the following: ring 1, megabase pairs (black); ring 2, gene or operon landmarks; rings 3 and 4, coding sequences on the forward strand (light blue) and reverse strand (dark blue); rings 5, 7, and 9, BLAST nucleotide sequence compariso...

Genetic relationships among emm89 reference strains, with emm1 reference strain SF370 used as the rooting outgroup. Genetic relationships among the three emm89 reference strains and the seven outlier strains are shown using emm1 reference strain SF370 as an outgroup. Relationships were inferred based on 26,371 core SNPs by neighbor-network decompos...

Potential horizontal gene transfer (HGT) region donors. The genetic relationships among the three emm89 clade reference strains and 39 strains of 18 other emm-types for which there were complete genome sequences publically available as of 10 July 2015 are shown for each of the predicted recombination blocks (RB) separating the clades. Sequences fla...

Comparison of phages 11027.1 and 27061.1. Shown above is a percent identity plot, and below is a dot matrix alignment. The phages are similar over the 5′ first ~13 kb sequence, which includes the integrase, replication, and lytic/lysogenic regulatory genes; the phages diverge over most of the central portions encoding head and tail coat proteins an...

Strains and characteristics.

Genetic relationships among emm89 subclade 3D strains. Genetic relationships among the 33 subclade 3D strains are shown using clade 3 reference strain MGAS27061 as the outgroup. Relationships were inferred based on 157 core SNPs by neighbor-joining using SplitsTree. All subclade 3D strains differ from all progenitor clade 3 strains by an 18 kb regi...

Streptococcus pyogenes complete genome sequences.

RNAseq transcriptome analyses.

hasABC promoter variants. (A) hasABC promoter pattern variants identified among the emm89 clade 1 and clade 2 strains are illustrated. Patterns A and B account for 99% of the strains. Pattern B has a 38-bp deletion relative to pattern A which eliminates a putative Rho-independent terminator. In M1 strain MGAS2221, deletion of this terminator result...