Risk factors for Haemophilus influenzae and pneumococcal respiratory tract colonization in CVID

To the Editor: Disease-specific studies focused on infection risk in common variable immune deficiencies (CVIDs) are needed to define strategies for controlling respiratory infections predominantly due to bacteria such as Streptococcus pneumoniae and Haemophilus influenzae.1 Little information is available on the rate of airway bacterial carriage and its consequence in hypogammaglobulinemias. Despite IgG replacement, recurrent respiratory infections are common in CVID, possibly leading to chronic lung damage2 and poor quality of life.3 Thus, patients are often prescribed antibiotics and/or long-term antimicrobial prophylactic regimens. Several regimens are used including rotation or periodically changing antibiotics.4 However, antibiotics influence antimicrobial resistance among airway microbiota. In a recent meta-analysis on patients with chronic lung diseases, 30% of S pneumoniae showed resistance to macrolides.

Ukraine: The War Told Via the Stories of Those Fleeing Conflict

We have decided to create a collection of stories in this e-book, to offer a broad picture of what is happening, what the war means, and the reasons that in Ukraine, as in other parts of the world, push people to run from their nation homes. We also reflect on how much the "willingness to welcome" counts. Our aim is to attentively follow the facts today and build a shared memory for tomorrow that helps us avoid mistakes made in the past

Surveillance of invasive diseases caused by Streptococcus pneumoniae in Italy: evolution of serotypes and antibiotic resistance in different age groups before and after implementation of PCV7

Background: PCV7 has been available in Italy since 2001, however only in 2005 national recommendations were issued and vaccination was implemented with different modalities by the Regions. Objectives: Aim of this study was to describe changes in serotype distribution and antibiotic susceptibility of S. pneumoniae from invasive pneumococcal diseases (IPD) in the last decade. Study Design: S. pneumoniae isolates from IPD, collected through a national surveillance system, were serotyped and antibiotic susceptibility was determined by E-test. Data were analyzed according to age groups (5 years, >5-64 years, 65 years) and to 3 time periods: prior, during and after PCV7 implementation (2001- 2003, 2006-2008 and 2009-2011). Results: The percentage of PCV7 serotypes (vaccine serotypes, VS) decreased over the years not only in children (from 60% to 26%) but also in the other age groups. Penicillin resistance was rather low in 2001-2003 (7-12%), but peaked in children in 2006-2008 (24%), and decreased in 2009-2011, while erythromycin resistance slightly decreased over the 3 periods. Conclusions: PCV7 use has largely impacted the epidemiology of S. pneumoniae in Italy, with a decrease in VS in all age groups.The impact of PCV 13, available in Italy since the end of 2010, requires future evaluations

Complete genome sequence of a serotype 11A, ST62 Streptococcus pneumoniae invasive isolate

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus pneumoniae </it>is an important human pathogen representing a major cause of morbidity and mortality worldwide. We sequenced the genome of a serotype 11A, ST62 <it>S. pneumoniae </it>invasive isolate (AP200), that was erythromycin-resistant due to the presence of the <it>erm</it>(TR) determinant, and carried out analysis of the genome organization and comparison with other pneumococcal genomes.</p> <p>Results</p> <p>The genome sequence of <it>S. pneumoniae </it>AP200 is 2,130,580 base pair in length. The genome carries 2216 coding sequences (CDS), 56 tRNA, and 12 rRNA genes. Of the CDSs, 72.9% have a predicted biological known function. AP200 contains the pilus islet 2 and, although its phenotype corresponds to serotype 11A, it contains an 11D capsular locus. Chromosomal rearrangements resulting from a large inversion across the replication axis, and horizontal gene transfer events were observed. The chromosomal inversion is likely implicated in the rebalance of the chromosomal architecture affected by the insertions of two large exogenous elements, the <it>erm</it>(TR)-carrying Tn<it>1806 </it>and a functional prophage designated ϕSpn_200. Tn<it>1806 </it>is 52,457 bp in size and comprises 49 ORFs. Comparative analysis of Tn<it>1806 </it>revealed the presence of a similar genetic element or part of it in related species such as <it>Streptococcus pyogenes </it>and also in the anaerobic species <it>Finegoldia magna, Anaerococcus prevotii </it>and <it>Clostridium difficile</it>. The genome of ϕSpn_200 is 35,989 bp in size and is organized in 47 ORFs grouped into five functional modules. Prophages similar to ϕSpn_200 were found in pneumococci and in other streptococcal species, showing a high degree of exchange of functional modules. ϕSpn_200 viral particles have morphologic characteristics typical of the <it>Siphoviridae </it>family and are capable of infecting a pneumococcal recipient strain.</p> <p>Conclusions</p> <p>The sequence of <it>S. pneumoniae </it>AP200 chromosome revealed a dynamic genome, characterized by chromosomal rearrangements and horizontal gene transfers. The overall diversity of AP200 is driven mainly by the presence of the exogenous elements Tn<it>1806 </it>and ϕSpn_200 that show large gene exchanges with other genetic elements of different bacterial species. These genetic elements likely provide AP200 with additional genes, such as those conferring antibiotic-resistance, promoting its adaptation to the environment.</p

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

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 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

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

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

A new genetic element carrying the resistance determinant erm(TR) in Streptococcus pneumoniae

The rapid development of macrolide resistance in Streptococcus pneumoniae, particularly over the last decade, is of major clinical concern. The two main resistance mechanisms of macrolide resistance in S. pneumoniae are target site modification mediated by erm(B) and efflux mediated by mef genes. Recently the presence of another methylase gene, erm(A) subclass erm(TR), has been reported in few S. pneumoniae clinical cases from different part of the world. The erm(TR) gene is common in Streptococcus pyogenes but rare in S. pneumoniae. Although erm(TR) has been demonstrated to be transferable from S. pyogenes to other Gram-positive species, the genetic element carrying this resistance determinant has not been identified. Recently, a clinical S. pneumoniae isolate (AP200) carrying erm(TR) has been obtained from a patient with meningitis in Italy. In this work we have analysed the erm(TR)-carrying genetic element in AP200. This strain has been phenotypically and genotypically characterized. A DNA region of approximately 10kb, including erm(TR), was analysed by sequencing fragments obtained by inverse PCR and revealed 12 ORFs. Upstream erm(TR), an ORF coding for a regulatory protein of the TetR family, and two ORFs whose products are homologous to components of an efflux pump of the ABC type, were identified. Downstream erm(TR), 6 ORFs were found coding for products homolog respectively to a spectynomycin phosphotransferase, a cytidine deminase, a recombinase, two transposases and a relaxase. As we were sequencing the region carrying erm(TR) in AP200, the genomic sequence of a S. pyogenes strain (MGAS10750) carrying erm(TR) was deposited in GenBank. The sequence of MGAS10750 showed that erm(TR) was included in a genetic element of approximately 48 kb. PCR mapping of AP200 using primers based on MGAS10750 sequence, showed that the overall structure of the erm(TR)-element in AP200 was similar to that of MGAS10750. Analysis of the junction sequences suggested that the insertion of the element into the chromosome caused the same 3-nucleotides duplication both in AP200 and in MGAS10750. Examination of an erm(TR) deletion mutant indicated that the erythromycin resistance was mediated only by the presence of erm(TR) gene. The erm(TR)-element could be transferred from AP200 to an erythromycin susceptible pneumococcal strain by transformation but not by conjugation. In conclusion erm(TR) in S. pneumoniae AP200 appears to be contained in a genetic element similar to that of S. pyogenes MGAS10750. Probably this same genetic element may be responsible for dissemination of this macrolide resistance gene in the Streptococcus genus

New Genetic Element Carrying the Erythromycin Resistance Determinant erm(TR) in Streptococcus pneumoniae▿

erm(A) subclass erm(TR), a common macrolide resistance determinant in Streptococcus pyogenes but quite rare in Streptococcus pneumoniae, was found in a clinical S. pneumoniae isolate (AP200) from Italy. In this isolate, erm(TR) was found included in a genetic element approximately 56 kb in size that did not appear to be conjugative but could be transferred by transformation. An erm(TR)-containing DNA fragment of approximately 10 kb was sequenced and 12 open reading frames (ORFs) were identified. Upstream of erm(TR), a regulatory protein of the TetR family and the two components of an efflux pump of the ABC type were found. Downstream of erm(TR), there were ORFs homologous to a spectinomycin phosphotransferase, transposases, and a relaxase. Since the genomic sequence of S. pyogenes MGAS10750 carrying erm(TR) became available, comparison between the erm(TR)-containing genetic elements in AP200 and in MGAS10750 was performed. The region flanking erm(TR) in MGAS10750 showed identity with AP200 for 10 ORFs out of 12. PCR mapping using primers designed on the sequence of MGAS10750 confirmed that AP200 carries a genetic element similar to that of MGAS10750. In AP200 the genetic element was inserted inside an ORF homologous to spr0790 of S. pneumoniae R6, coding for a type I restriction modification system. Homologies between the insertion sites in AP200 and MGAS10750 consisted of eight conserved nucleotides, of which three were duplicated, likely representing target site duplication. The structure of the erm(TR)-carrying genetic element shows characteristics of a transposon/prophage remnant chimera. In AP200 this genetic element was designated Tn1806

HR-NMR and HR-MAS NMR analyses.

<p>Panel A: Backbone of <i>S. pneumoniae</i> serotype 11A and 11E polysaccharide. The proton at position C₄ of β-Gal residue O-acetylated at both position C₄ and C₆ (H₄^βGal-4,6OAc), which was used as probe for 11A strains detection, and the proton at position C₂ of the β-Glc residue (H₂^βGlc), which was used for peak normalization, are labeled. Panel B: Proton NMR spectrum in liquid phase of <i>S. pneumoniae</i> purified 11A polysaccharide and proton HR-MAS NMR spectra in heterogeneous phase of <i>S. pneumoniae</i> 11A (SSISP 11A/2, AP200) and 11E (MNZ269) isolates. Red arrows indicate the H₄^βGal-4,6OAc signal at 5.6 ppm. Panel C. Proton NMR spectra in liquid phase of <i>S. pneumoniae</i> 11A (AP366, AP200) and 11E (AP446) supernatants before and after treatment with NaOD. Red arrows indicate the H₄^βGal-4,6OAc signal at 5.6 ppm. Panel D: Proton HR-MAS NMR spectra in the heterogeneous phase of <i>S. pneumoniae</i> 11A isolates (PER191, PFC035, AP713, PN174). Red arrows indicate the H₄^βGal-4,6OAc signal at 5.6 ppm. Panel E: Proton HR-MAS NMR spectra in the heterogeneous phase of <i>S. pneumoniae</i> 11E isolates (AP278, PN259, PN066, SP335).</p