Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 40 Records) |
Query Trace: Beall BW[original query] |
---|
Recombinational exchange of M-fibril and T-pilus genes generates extensive cell surface diversity in the global group A Streptococcus population
Bessen DE , Beall BW , Hayes A , Huang W , DiChiara JM , Velusamy S , Tettelin H , Jolley KA , Fallon JT , Chochua S , Alobaidallah MSA , Higgs C , Barnett TC , Steemson JT , Proft T , Davies MR . mBio 2024 e0069324 Among genes present in all group A streptococci (GAS), those encoding M-fibril and T-pilus proteins display the highest levels of sequence diversity, giving rise to the two primary serological typing schemes historically used to define strain. A new genotyping scheme for the pilin adhesin and backbone genes is developed and, when combined with emm typing, provides an account of the global GAS strain population. Cluster analysis based on nucleotide sequence similarity assigns most T-serotypes to discrete pilin backbone sequence clusters, yet the established T-types correspond to only half the clusters. The major pilin adhesin and backbone sequence clusters yield 98 unique combinations, defined as "pilin types." Numerous horizontal transfer events that involve pilin or emm genes generate extensive antigenic and functional diversity on the bacterial cell surface and lead to the emergence of new strains. Inferred pilin genotypes applied to a meta-analysis of global population-based collections of pharyngitis and impetigo isolates reveal highly significant associations between pilin genotypes and GAS infection at distinct ecological niches, consistent with a role for pilin gene products in adaptive evolution. Integration of emm and pilin typing into open-access online tools (pubmlst.org) ensures broad utility for end-users wanting to determine the architecture of M-fibril and T-pilus genes from genome assemblies.IMPORTANCEPrecision in defining the variant forms of infectious agents is critical to understanding their population biology and the epidemiology of associated diseases. Group A Streptococcus (GAS) is a global pathogen that causes a wide range of diseases and displays a highly diverse cell surface due to the antigenic heterogeneity of M-fibril and T-pilus proteins which also act as virulence factors of varied functions. emm genotyping is well-established and highly utilized, but there is no counterpart for pilin genes. A global GAS collection provides the basis for a comprehensive pilin typing scheme, and online tools for determining emm and pilin genotypes are developed. Application of these tools reveals the expansion of structural-functional diversity among GAS via horizontal gene transfer, as evidenced by unique combinations of surface protein genes. Pilin and emm genotype correlations with superficial throat vs skin infection provide new insights on the molecular determinants underlying key ecological and epidemiological trends. |
Inter-species gene flow drives ongoing evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis
Xie O , Morris JM , Hayes AJ , Towers RJ , Jespersen MG , Lees JA , Ben Zakour NL , Berking O , Baines SL , Carter GP , Tonkin-Hill G , Schrieber L , McIntyre L , Lacey JA , James TB , Sriprakash KS , Beatson SA , Hasegawa T , Giffard P , Steer AC , Batzloff MR , Beall BW , Pinho MD , Ramirez M , Bessen DE , Dougan G , Bentley SD , Walker MJ , Currie BJ , Tong SYC , McMillan DJ , Davies MR . Nat Commun 2024 15 (1) 2286 Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection with invasive disease incidence and clinical manifestations comparable to the closely related species, Streptococcus pyogenes. Through systematic genomic analyses of 501 disseminated SDSE strains, we demonstrate extensive overlap between the genomes of SDSE and S. pyogenes. More than 75% of core genes are shared between the two species with one third demonstrating evidence of cross-species recombination. Twenty-five percent of mobile genetic element (MGE) clusters and 16 of 55 SDSE MGE insertion regions were shared across species. Assessing potential cross-protection from leading S. pyogenes vaccine candidates on SDSE, 12/34 preclinical vaccine antigen genes were shown to be present in >99% of isolates of both species. Relevant to possible vaccine evasion, six vaccine candidate genes demonstrated evidence of inter-species recombination. These findings demonstrate previously unappreciated levels of genomic overlap between these closely related pathogens with implications for streptococcal pathobiology, disease surveillance and prevention. |
Variation in pneumococcal invasiveness metrics is driven by serotype carriage duration and initial risk of disease
Metcalf BJ , Waldetoft KW , Beall BW , Brown SP . Epidemics 2023 45 100731 Streptococcus pneumoniae is an opportunistic pathogen that, while usually carried asymptomatically, can cause severe invasive diseases like meningitis and bacteremic pneumonia. A central goal in S. pneumoniae public health management is to identify which serotypes (immunologically distinct strains) pose the most risk of invasive disease. The most common invasiveness metrics use cross-sectional data (i.e., invasive odds ratios (IOR)), or longitudinal data (i.e., attack rates (AR)). To assess the reliability of these metrics we developed an epidemiological model of carriage and invasive disease. Our mathematical analyses illustrate qualitative failures with the IOR metric (e.g., IOR can decline with increasing invasiveness parameters). Fitting the model to both longitudinal and cross-sectional data, our analysis supports previous work indicating that invasion risk is maximal at or near time of colonization. This pattern of early invasive disease risk leads to substantial (up to 5-fold) biases when estimating underlying differences in invasiveness from IOR metrics, due to the impact of carriage duration on IOR. Together, these results raise serious concerns with the IOR metric as a basis for public health decision-making and lend support for multiple alternate metrics including AR. |
Low but Increasing Prevalence of Reduced Beta-lactam Susceptibility Among Invasive Group B Streptococcal Isolates, US Population-Based Surveillance, 1998-2018.
Kobayashi M , McGee L , Chochua S , Apostol M , Alden NB , Farley MM , Harrison LH , Lynfield R , Vagnone PS , Smelser C , Muse A , Thomas AR , Deng L , Metcalf BJ , Beall BW , Schrag SJ . Open Forum Infect Dis 2021 8 (2) ofaa634 BACKGROUND: Invasive group B Streptococcus (iGBS) isolates with mutations in the pbp2x gene that encodes penicillin binding protein 2x can have reduced beta-lactam susceptibility (RBLS) when susceptible by Clinical and Laboratory Standards Institute (CLSI) criteria. We assessed the emergence and characteristics of RBLS strains in US iGBS isolates. METHODS: We analyzed iGBS isolates from 8 multistate population-based surveillance sites from 1998 to 2018. During 1998-2014, phenotypic antimicrobial susceptibility was determined by broth microdilution; criteria for 6 antibiotics were used to identify RBLS, followed by whole-genome sequencing (WGS). WGS for all isolates was added in 2015; we used phenotypic and genotypic results of >2000 isolates to validate phenotypic RBLS criteria and genotypic predictions. Since 2016, WGS has been used to screen for RBLS with broth microdilution confirmation of predicted RBLS isolates. RESULTS: Of 28 269 iGBS isolates, 28 (0.1%) were nonsusceptible by CLSI criteria; 137 (0.5%) met RBLS criteria. RBLS isolates were detected in all Active Bacterial Core surveillance sites. The RBLS proportion increased, especially since 2013 (odds ratio, 1.17; 95% CI, 1.03-1.32); the proportion that were nonsusceptible remained stable. CONCLUSIONS: The RBSL proportion was low but increasing among US iGBS isolates. Ongoing monitoring is needed to detect emerging threats to prevention and treatment of GBS infections. |
M1UK lineage in invasive group A streptococcus isolates from the USA
Li Y , Nanduri SA , Van Beneden CA , Beall BW . Lancet Infect Dis 2020 20 (5) 538-539 Nicola N Lynskey and colleagues1 reported that a hypertoxigenic clone of emm1 group A streptococcus (M1UK), characterised by increased streptococcal pyrogenic exotoxin A (SpeA) production, has rapidly emerged in the UK since 2014. Large-scale genomic examinations of this M1UK clade indicated a single lineage in the global group A streptococcus genomic databases, with only one isolate identified in the USA in 2015.1,2 We investigated whether the M1UK lineage has expanded in the USA since 2015 using data from the Active Bacterial Core surveillance (ABCs) system of the US Centers for Disease Control and Prevention. |
Visualizing variation within Global Pneumococcal Sequence Clusters (GPSCs) and country population snapshots to contextualize pneumococcal isolates.
Gladstone RA , Lo SW , Goater R , Yeats C , Taylor B , Hadfield J , Lees JA , Croucher NJ , van Tonder AJ , Bentley LJ , Quah FX , Blaschke AJ , Pershing NL , Byington CL , Balaji V , Hryniewicz W , Sigauque B , Ravikumar KL , Almeida SCG , Ochoa TJ , Ho PL , du Plessis M , Ndlangisa KM , Cornick JE , Kwambana-Adams B , Benisty R , Nzenze SA , Madhi SA , Hawkins PA , Pollard AJ , Everett DB , Antonio M , Dagan R , Klugman KP , von Gottberg A , Metcalf BJ , Li Y , Beall BW , McGee L , Breiman RF , Aanensen DM , Bentley SD . Microb Genom 2020 6 (5) Knowledge of pneumococcal lineages, their geographic distribution and antibiotic resistance patterns, can give insights into global pneumococcal disease. We provide interactive bioinformatic outputs to explore such topics, aiming to increase dissemination of genomic insights to the wider community, without the need for specialist training. We prepared 12 country-specific phylogenetic snapshots, and international phylogenetic snapshots of 73 common Global Pneumococcal Sequence Clusters (GPSCs) previously defined using PopPUNK, and present them in Microreact. Gene presence and absence defined using Roary, and recombination profiles derived from Gubbins are presented in Phandango for each GPSC. Temporal phylogenetic signal was assessed for each GPSC using BactDating. We provide examples of how such resources can be used. In our example use of a country-specific phylogenetic snapshot we determined that serotype 14 was observed in nine unrelated genetic backgrounds in South Africa. The international phylogenetic snapshot of GPSC9, in which most serotype 14 isolates from South Africa were observed, highlights that there were three independent sub-clusters represented by South African serotype 14 isolates. We estimated from the GPSC9-dated tree that the sub-clusters were each established in South Africa during the 1980s. We show how recombination plots allowed the identification of a 20 kb recombination spanning the capsular polysaccharide locus within GPSC97. This was consistent with a switch from serotype 6A to 19A estimated to have occured in the 1990s from the GPSC97-dated tree. Plots of gene presence/absence of resistance genes (tet, erm, cat) across the GPSC23 phylogeny were consistent with acquisition of a composite transposon. We estimated from the GPSC23-dated tree that the acquisition occurred between 1953 and 1975. Finally, we demonstrate the assignment of GPSC31 to 17 externally generated pneumococcal serotype 1 assemblies from Utah via Pathogenwatch. Most of the Utah isolates clustered within GPSC31 in a USA-specific clade with the most recent common ancestor estimated between 1958 and 1981. The resources we have provided can be used to explore to data, test hypothesis and generate new hypotheses. The accessible assignment of GPSCs allows others to contextualize their own collections beyond the data presented here. |
Multistate, population-based distributions of candidate vaccine targets, clonal complexes, and resistance features of invasive Group B Streptococci within the US: 2015-2017.
McGee L , Chochua S , Li Z , Mathis S , Rivers J , Metcalf B , Ryan A , Alden N , Farley MM , Harrison LH , Snippes Vagnone P , Lynfield R , Smelser C , Muse A , Thomas AR , Schrag S , Beall BW . Clin Infect Dis 2020 72 (6) 1004-1013 BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis and an important cause of invasive infections in pregnant and nonpregnant adults. Vaccines targeting capsule polysaccharides and common proteins are under development. METHODS: Using whole genome sequencing (WGS), a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6,340 invasive GBS recovered during 2015-2017 through population-based Active Bacterial Core surveillance (ABCs) in eight states. RESULTS: Six serotypes accounted for 98.4% of isolates (21.8% Ia, 17.6% V, 17.1% II, 15.6% III, 14.5% Ib, 11.8% IV). Most (94.2%) isolates were in eleven clonal complexes (CCs) comprised of multilocus sequence types (MLSTs) identical or closely related to STs 1, 8, 12, 17, 19, 22, 23, 28, 88, 452 and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with non-susceptibility to one or more beta-lactam antibiotics. Genes conferring resistance to macrolides and/or lincosamides were found in 56% of isolates; 85.2% of isolates had tetracycline resistance genes. Two isolates carrying vanG were vancomycin-nonsusceptible (MIC 2microg/ml). Nearly all isolates possessed capsule genes, 1-2 of the three main pilus gene clusters, and one of four homologous Alpha/Rib family determinants. Presence of hvgA virulence gene was primarily restricted to serotype III/CC17 isolates (465 isolates), but 8 exceptions (7 IV/CC452 and 1 IV/CC17) were observed. CONCLUSIONS: This first comprehensive, population-based quantitation of strain features in the United States suggests current vaccine candidates should have good coverage. Beta-lactams remain appropriate for first line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring. |
Genome-wide association analyses of invasive pneumococcal isolates identify a missense bacterial mutation associated with meningitis.
Li Y , Metcalf BJ , Chochua S , Li Z , Walker H , Tran T , Hawkins PA , Gierke R , Pilishvili T , McGee L , Beall BW . Nat Commun 2019 10 (1) 178 Bacterial mutations predisposing pneumococcus to causing meningitis, a more severe form of invasive pneumococcal disease (IPD), are largely unknown. Knowledge of such mutations may improve our understanding of pathogenesis and inform preventive strategies. Here we report a pneumococcal pbp1b gene mutation (pbp1bA641C causing N214T change in PBP1b transglycosylase domain) that is associated with meningitis in an exploratory cohort of IPD patients (n = 2054, p = 6.8 x 10(-6)), in an independent confirmatory cohort (n = 2518, p = 2.3 x 10(-6)), and in a combined analysis (n = 4572, p = 3.0 x 10(-10)). Patients infected by the pbp1b641C genotype pneumococci show 2.8-fold odds (95% CI 1.7 to 4.8) of meningitis compared to those infected by non-pbp1b641C pneumococci, after controlling for pneumococcal serotype, antibiotic resistance, and patient age. The pbp1bA641C change results in longer time needed for bacterial killing by antibiotic treatment and shows evidence of being under positive selection. Thus, a pneumococcal mutation conferring increased antibiotic tolerance is associated with meningitis among IPD patients. |
Epidemiology of invasive early-onset and late-onset group B streptococcal disease in the United States, 2006 to 2015: Multistate laboratory and population-based surveillance
Nanduri SA , Petit S , Smelser C , Apostol M , Alden NB , Harrison LH , Lynfield R , Vagnone PS , Burzlaff K , Spina NL , Dufort EM , Schaffner WS , Thomas AR , Farley MM , Jain JH , Pondo T , McGee L , Beall BW , Schrag SJ . JAMA Pediatr 2019 173 (3) 224-233 Importance: Invasive disease owing to group B Streptococcus (GBS) remains an important cause of illness and death among infants younger than 90 days in the United States, despite declines in early-onset disease (EOD; with onset at 0-6 days of life) that are attributed to intrapartum antibiotic prophylaxis (IAP). Maternal vaccines to prevent infant GBS disease are currently under development. Objective: To describe incidence rates, case characteristics, antimicrobial resistance, and serotype distribution of EOD and late-onset disease (LOD; with onset at 7-89 days of life) in the United States from 2006 to 2015 to inform IAP guidelines and vaccine development. Design, Setting, and Participants: This study used active population-based and laboratory-based surveillance for invasive GBS disease conducted through Active Bacterial Core surveillance in selected counties of 10 states across the United States. Residents of Active Bacterial Core surveillance areas who were younger than 90 days and had invasive GBS disease in 2006 to 2015 were included. Data were analyzed from December 2017 to April 2018. Exposures: Group B Streptococcus isolated from a normally sterile site. Main Outcomes and Measures: Early-onset disease and LOD incidence rates and associated GBS serotypes and antimicrobial resistance. Results: The Active Bacterial Core surveillance program identified 1277 cases of EOD and 1387 cases of LOD. From 2006 to 2015, EOD incidence declined significantly from 0.37 to 0.23 per 1000 live births (P < .001), and LOD rates remained stable (mean, 0.31 per 1000 live births). Among the mothers of 1277 infants with EOD, 617 (48.3%) had no indications for IAP and did not receive it, and 278 (21.8%) failed to receive IAP despite having indications. Serotype data were available for 1743 of 1897 patients (91.3%) from 7 sites that collect GBS isolates. Among these isolates, serotypes Ia (242 [27.3%]) and III (242 [27.3%]) were most common. Among patients with LOD, serotype III was most common (481 [56.2%]), and this increased from 2006 to 2015 from 0.12 to 0.20 cases per 1000 live births (P < .001). Serotype IV caused 53 cases (6.2%) of EOD and LOD combined. The 6 most common serotypes (Ia, Ib, II, III, IV, and V) caused 881 EOD cases (99.3%) and 853 LOD cases (99.7%). No beta-lactam resistance was identified; 359 isolates (20.8%) tested showed constitutive clindamycin resistance. In 2015, an estimated 840 EOD cases and 1265 LOD cases occurred nationally. Conclusions and Relevance: The rates of LOD among US infants are now higher than EOD rates. Combined with addressing IAP implementation gaps, an effective vaccine covering the most common serotypes might further reduce EOD rates and help prevent LOD, for which there is no current public health intervention. |
Molecular Epidemiology, Ecology, and Evolution of Group A Streptococci.
Bessen DE , Smeesters PR , Beall BW . Microbiol Spectr 2018 6 (5) The clinico-epidemiological features of diseases caused by group A streptococci (GAS) is presented through the lens of the ecology, population genetics, and evolution of the organism. The serological targets of three typing schemes (M, T, SOF) are themselves GAS cell surface proteins that have a myriad of virulence functions and a diverse array of structural forms. Horizontal gene transfer expands the GAS antigenic cell surface repertoire by generating numerous combinations of M, T, and SOF antigens. However, horizontal gene transfer of the serotype determinant genes is not unconstrained, and therein lies a genetic organization that may signify adaptations to a narrow ecological niche, such as the primary tissue reservoirs of the human host. Adaptations may be further shaped by selection pressures such as herd immunity. Understanding the molecular evolution of GAS on multiple levels-short, intermediate, and long term-sheds insight on mechanisms of host-pathogen interactions, the emergence and spread of new clones, rational vaccine design, and public health interventions. |
Validation of ß-lactam minimum inhibitory concentration predictions for pneumococcal isolates with newly encountered penicillin binding protein (PBP) sequences.
Li Y , Metcalf BJ , Chochua S , Li Z , Gertz RE Jr , Walker H , Hawkins PA , Tran T , McGee L , Beall BW . BMC Genomics 2017 18 (1) 621 BACKGROUND: Genomic sequence-based deduction of antibiotic minimum inhibitory concentration (MIC) has great potential to enhance the speed and sensitivity of antimicrobial susceptibility testing. We previously developed a penicillin-binding protein (PBP) typing system and two methods (Random Forest (RF) and Mode MIC (MM)) that accurately predicted beta-lactam MICs for pneumococcal isolates carrying a characterized PBP sequence type (phenotypic beta-lactam MICs known for at least one isolate of this PBP type). This study evaluates the prediction performance for previously uncharacterized (new) PBP types and the probability of encountering new PBP types, both of which impact the overall prediction accuracy. RESULTS: The MM and RF methods were used to predict MICs of 4309 previously reported pneumococcal isolates in 2 datasets and the results were compared to the known broth microdilution MICs to 6 beta-lactams. Based on a method that specifically evaluated predictions for new PBP types, the RF results were more accurate than MM results for new PBP types and showed percent essential agreement (MICs agree within +/-1 dilution) >97%, percent category agreement (interpretive results agree) >93%, major discrepancy (sensitive isolate predicted as resistant) rate < 1.2%, and very major discrepancy (resistant isolate predicted as sensitive) rate < 1.4% for all 6 beta-lactams. The identification of new PBP types over time was well approximated by a diminishingly increasing curve (Pearson's r = 0.99) and minimally impacted overall MIC prediction performance. CONCLUSIONS: MIC prediction using the RF method could be an accurate alternative of phenotypic susceptibility testing even in the presence of previously uncharacterized PBP types. |
Cross-resistance to lincosamides, streptogramins A and pleuromutilins in Streptococcus agalactiae isolates from the USA.
Hawkins PA , Law CS , Metcalf BJ , Chochua S , Jackson DM , Westblade LF , Jerris R , Beall BW , McGee L . J Antimicrob Chemother 2017 72 (7) 1886-1892 Background: Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of meningitis, sepsis and pneumonia in neonates in the United States. GBS also causes invasive disease in older infants, pregnant women, children and young adults with underlying medical conditions, and older adults. Resistance to lincosamides in the absence of erythromycin resistance is rare in GBS, but has been previously reported in clinical isolates, both on its own or in combination with resistance to streptogramins A and pleuromutilins (L/LSA/LSAP phenotypes). Objectives: To retrospectively screen the Active Bacterial Core surveillance (ABCs) GBS isolate collection for these phenotypes in order to identify the causal genetic determinants and determine whether their frequency is increasing. Methods: Based on MIC data, 65 (0.31%) isolates susceptible to erythromycin (MIC ≤0.25 mg/L) and non-susceptible to clindamycin (MIC ≥0.5 mg/L) were identified among 21186 GBS isolates. Genomic DNA was extracted and WGS was performed. The presence of 10 genes previously associated with LSA resistance was investigated by read mapping. Results: Forty-nine (75%) isolates carried the lsa (C) gene and expressed the LSAP phenotype, and 12 (18%) carried both the lnu (B) and lsa (E) genes and expressed the LSAP phenotype. The four remaining isolates were negative for all determinants investigated. Conclusions: While the overall observed frequency of these phenotypes among our GBS isolates was quite low (0.31%), this frequency has increased in recent years. To the best of our knowledge, this is the first time the LSAP phenotype has been reported among GBS isolates from the USA. |
Genomic epidemiology of penicillin non-susceptible pneumococci with non-vaccine serotypes causing invasive disease in the USA.
Andam CP , Mitchell PK , Callendrello A , Chang Q , Corander J , Chaguza C , McGee L , Beall BW , Hanage WP . J Clin Microbiol 2017 55 (4) 1104-1115 Conjugate vaccination against seven pneumococcal serotypes (PCV7) reduced disease prevalence due to antibiotic resistant strains throughout the 2000s; however, disease caused by resistant non-vaccine type (NVT) strains increased. Some of these emerging strains were derived from vaccine types (VT) that had changed their capsule by recombination. The introduction of vaccine targeting 13 serotypes (PCV13) in 2010 has led to concern that this scenario will repeat itself. We generated high quality draft genomes from 265 isolates of NVT pneumococci not susceptible to penicillin (PNSP) in 2009 and compared them with 581 isolates from 2012-2013, collected by the Active Bacterial Core surveillance (ABCs) of the Centers for Disease Control and Prevention (CDC). Of the seven sequence clusters (SCs) identified, three SCs fell into a single lineage associated with serogroup 23, which had an origin in 1908 as dated by coalescent analysis and included isolates with a divergent 23B capsule locus. Three other SCs represented relatively deep-branching lineages associated with serotypes 35B, 15A and 15BC. In all cases, resistant clones originated prior to 2010, indicating that PNSP are at present dominated by descendants of NVT clones present before vaccination. With one exception (15BC/ST3280), these SCs were related to clones identified by the Pneumococcal Molecular Epidemiology Network (PMEN). We conclude that post-vaccine diversity in NVT PNSP between 2009 and 2013 was driven mainly by the persistence of pre-existing strains rather than through de novo adaptation, with few cases of serotype switching. Future surveillance is essential to document long-term dynamics and resistance of NVT PNSP. |
Penicillin-Binding Protein Transpeptidase Signatures for Tracking and Predicting ß-Lactam Resistance Levels in Streptococcus pneumoniae.
Li Y , Metcalf BJ , Chochua S , Li Z , Gertz RE Jr , Walker H , Hawkins PA , Tran T , Whitney CG , McGee L , Beall BW . mBio 2016 7 (3) beta-Lactam antibiotics are the drugs of choice to treat pneumococcal infections. The spread of beta-lactam-resistant pneumococci is a major concern in choosing an effective therapy for patients. Systematically tracking beta-lactam resistance could benefit disease surveillance. Here we developed a classification system in which a pneumococcal isolate is assigned to a "PBP type" based on sequence signatures in the transpeptidase domains (TPDs) of the three critical penicillin-binding proteins (PBPs), PBP1a, PBP2b, and PBP2x. We identified 307 unique PBP types from 2,528 invasive pneumococcal isolates, which had known MICs to six beta-lactams based on broth microdilution. We found that increased beta-lactam MICs strongly correlated with PBP types containing divergent TPD sequences. The PBP type explained 94 to 99% of variation in MICs both before and after accounting for genomic backgrounds defined by multilocus sequence typing, indicating that genomic backgrounds made little independent contribution to beta-lactam MICs at the population level. We further developed and evaluated predictive models of MICs based on PBP type. Compared to microdilution MICs, MICs predicted by PBP type showed essential agreement (MICs agree within 1 dilution) of >98%, category agreement (interpretive results agree) of >94%, a major discrepancy (sensitive isolate predicted as resistant) rate of <3%, and a very major discrepancy (resistant isolate predicted as sensitive) rate of <2% for all six beta-lactams. Thus, the PBP transpeptidase signatures are robust indicators of MICs to different beta-lactam antibiotics in clinical pneumococcal isolates and serve as an accurate alternative to phenotypic susceptibility testing. IMPORTANCE: The human pathogen Streptococcus pneumoniae is a leading cause of morbidity and mortality worldwide. beta-Lactam antibiotics such as penicillin and ceftriaxone are the drugs of choice to treat pneumococcal infections. Some pneumococcal strains have developed beta-lactam resistance through altering their penicillin-binding proteins (PBPs) and have become a major concern in choosing effective patient therapy. To systematically track and predict beta-lactam resistance, we obtained the sequence signatures of PBPs from a large collection of clinical pneumococcal isolates using whole-genome sequencing data and found that these "PBP types" were predictive of resistance levels. Our findings can benefit the current era of strain surveillance when whole-genome sequencing data often lacks detailed resistance information. Using PBP positions that we found are always substituted within highly resistant strains may lead to further refinements. Sequence-based predictions are accurate and may lead to the ability to extract critical resistance information from nonculturable clinical specimens. |
A systematic and functional classification of Streptococcus pyogenes that serves as a new tool for molecular typing and vaccine development.
Sanderson-Smith M , De Oliveira DM , Guglielmini J , McMillan DJ , Vu T , Holien JK , Henningham A , Steer AC , Bessen DE , Dale JB , Curtis N , Beall BW , Walker MJ , Parker MW , Carapetis JR , Van Melderen L , Sriprakash KS , Smeesters PR . J Infect Dis 2014 210 (8) 1325-38 Streptococcus pyogenes ranks among the main causes of mortality from bacterial infections worldwide. Currently there is no vaccine to prevent diseases such as rheumatic heart disease and invasive streptococcal infection. The streptococcal M protein that is used as the substrate for epidemiological typing is both a virulence factor and a vaccine antigen. Over 220 variants of this protein have been described, making comparisons between proteins difficult, and hindering M protein-based vaccine development. A functional classification based on 48 emm-clusters containing closely related M proteins that share binding and structural properties is proposed. The need for a paradigm shift from type-specific immunity against S. pyogenes to emm-cluster based immunity for this bacterium should be further investigated. Implementation of this emm-cluster-based system as a standard typing scheme for S. pyogenes will facilitate the design of future studies of M protein function, streptococcal virulence, epidemiological surveillance, and vaccine development. |
Deriving group A Streptococcus typing information from short-read whole-genome sequencing data.
Athey TB , Teatero S , Li A , Marchand-Austin A , Beall BW , Fittipaldi N . J Clin Microbiol 2014 52 (6) 1871-6 Typing of group A Streptococcus (GAS) is crucial for infection control and epidemiology. While whole-genome sequencing (WGS) is revolutionizing the way that bacterial organisms are typed, it is necessary to provide backward compatibility with currently used typing schemas to facilitate comparisons and understanding of epidemiological trends. Here, we sequenced the genomes of 191 GAS isolates representing 42 different emm types and used bioinformatics tools to derive commonly used GAS typing information directly from the short-read WGS data. We show that emm typing and multilocus sequence typing can be achieved rapidly and efficiently using this approach, which also permits the determination of the presence or absence of genes associated with GAS tissue tropism. We also report on how the WGS data analysis was instrumental in identifying ambiguities present in the commonly used emm type database hosted by the U.S. Centers for Disease Control and Prevention. |
Non-pneumococcal mitis-group streptococci confound detection of pneumococcal capsular serotype-specific loci in upper respiratory tract
Carvalho Mda G , Pimenta FC , Moura I , Roundtree A , Gertz RE Jr , Li Z , Jagero G , Bigogo G , Junghae M , Conklin L , Feikin DR , Breiman RF , Whitney CG , Beall BW . PeerJ 2013 1 e97 We performed culture-based and PCR-based tests for pneumococcal identification and serotyping from carriage specimens collected in rural and urban Kenya. Nasopharyngeal specimens from 237 healthy children <5 years old (C-NPs) and combined nasopharyngeal/oropharyngeal specimens from 158 adults (A-NP/OPs, 118 HIV-positive) were assessed using pneumococcal isolation (following broth culture enrichment) with Quellung-based serotyping, real-time lytA-PCR, and conventional multiplexed PCR-serotyping (cmPCR). Culture-based testing from C-NPs, HIV-positive A-NP/OPs, and HIV-negative A-NP/OPs revealed 85.2%, 40.7%, and 12.5% pneumococcal carriage, respectively. In contrast, cmPCR serotypes were found in 93.2%, 98.3%, and 95.0% of these sets, respectively. Two of 16 lytA-negative C-NPs and 26 of 28 lytA-negative A-NP/OPs were cmPCR-positive for 1-10 serotypes (sts) or serogroups (sgs). A-NP/OPs averaged 5.5 cmPCR serotypes/serogroups (5.2 in HIV-positive, 7.1 in HIV-negative) and C-NPs averaged 1.5 cmPCR serotypes/serogroups. cmPCR serotypes/serogroups from lytA-negative A-NP/OPs included st2, st4, sg7F/7A, sg9N/9L, st10A, sg10F/10C/33C, st13, st17F, sg18C/18A/18B/18F, sg22F/22A, and st39. Nine strains of three non-pneumococcal species (S. oralis, S. mitis, and S. parasanguinis) (7 from A-OP, 1 from both A-NP and A-OP, and 1 from C-NP) were each cmPCR-positive for one of 7 serotypes/serogroups (st5, st13, sg15A/15F, sg10F/10C/33C, sg33F/33A/37, sg18C/18A/18B/18F, sg12F/12A/12B/ 44/46) with amplicons revealing 83.6-99.7% sequence identity to pneumococcal references. In total, 150 cmPCR amplicons from carriage specimens were sequenced, including 25 from lytA-negative specimens. Amplicon sequences derived from specimens yielding a pneumococcal isolate with the corresponding serotype were identical or highly conserved (>98.7%) with the reference cmPCR amplicon for the st, while cmPCR amplicons from lytA-negative specimens were generally more divergent. Separate testing of 56 A-OPs and 56 A-NPs revealed that approximately 94% of the positive cmPCR results from A-NP/OPs were from OP microbiota. In contrast, A-NPs yielded >2-fold more pneumococcal isolates than A-OPs. Verified and suspected non-pneumococcal cmPCR serotypes/serogroups appeared to be relatively rare in C-NPs and A-NPs compared to A-OPs. Our findings indicate that non-pneumococcal species can confound serotype-specific PCR and other sequence-based assays due to evolutionarily conserved genes most likely involved in biosynthesis of surface polysaccharide structures. |
Invasive pneumococcal disease among children with and without sickle cell disease in the United States, 1998-2009
Payne AB , Link-Gelles R , Azonobi I , Hooper WC , Beall BW , Jorgensen JH , Juni B , Moore M . Pediatr Infect Dis J 2013 32 (12) 1308-12 BACKGROUND: Children with sickle cell disease (SCD) are at increased risk of illness and death from invasive pneumococcal disease (IPD). The introduction in 2000 of the 7-valent pneumococcal conjugate vaccine (PCV7) and penicillin prophylaxis for children with SCD has greatly reduced the incidence of IPD in this population. However, a recent report suggested an increase in cases of IPD in children with SCD. METHODS: Using data from Active Bacterial Core Surveillance (ABCs), we analyzed trends in hospitalizations, mortality, and serotype among children with SCD compared with other children. We used neonatal screening data to estimate SCD population denominators for each ABCs site. RESULTS: From 1998-2009, 3,069 cases of IPD occurred among African-American children less than 18 years of age in the ABCs catchment area. Of these, 127 (4.1%) had SCD identified by medical chart review and 185 (6.0%) had one or more IPD risk factors, excluding SCD. Rates of IPD among children with SCD declined by 53% (1,118 versus 530 per 100,000) while the overall rates among African-American children declined by 74% (54 to 14 per 100,000). For all time periods, children with SCD and IPD were more likely to be hospitalized (84%-92% versus 31%-56%) and more likely to die (6%-17% versus 1%-2%) than children with no risk factors. CONCLUSIONS: While the rate of IPD in children with SCD has dropped dramatically since PCV7 introduction, the rate of IPD in children with SCD remains higher than that of the general population of African-American children, pointing to the need for more effective prevention efforts to prevent IPD in children with SCD. |
Pneumococcal capsular switching: a historical perspective.
Wyres KL , Lambertsen LM , Croucher NJ , McGee L , von Gottberg A , Linares J , Jacobs MR , Kristinsson KG , Beall BW , Klugman KP , Parkhill J , Hakenbeck R , Bentley SD , Brueggemann AB . J Infect Dis 2013 207 (3) 439-49 BACKGROUND: Changes in serotype prevalence among pneumococcal populations result from both serotype replacement and serotype (capsular) switching. Temporal changes in serotype distributions are well documented, but the contribution of capsular switching to such changes is unknown. Furthermore, it is unclear to what extent vaccine-induced selective pressures drive capsular switching. METHODS: Serotype and multilocus sequence typing data for 426 pneumococci dated from 1937 through 2007 were analyzed. Whole-genome sequence data for a subset of isolates were used to investigate capsular switching events. RESULTS: We identified 36 independent capsular switch events, 18 of which were explored in detail with whole-genome sequence data. Recombination fragment lengths were estimated for 11 events and ranged from approximately 19.0 kb to ≥58.2 kb. Two events took place no later than 1960, and the imported DNA included the capsular locus and the nearby penicillin-binding protein genes pbp2x and pbp1a. CONCLUSIONS: Capsular switching has been a regular occurrence among pneumococcal populations throughout the past 7 decades. Recombination of large DNA fragments (>30 kb), sometimes including the capsular locus and penicillin-binding protein genes, predated both vaccine introduction and widespread antibiotic use. This type of recombination has likely been an intrinsic feature throughout the history of pneumococcal evolution. |
Molecular epidemiological investigation to determine the source of a fatal case of serotype 22F pneumococcal meningitis.
Lamaro-Cardoso J , de Lemos AP , Carvalho Mda G , Pimenta FC , Roundtree A , Motta L , Vieira MA , Sgambatti S , Thorn LK , Pessoa-Junior V , Minamisava R , Harrison LH , Beall BW , Brandileone MC , Andrade AL . J Med Microbiol 2012 61 686-92 A child's death due to pneumococcal meningitis after contracting the disease in an after-school programme prompted an investigation to assess nasopharyngeal (NP) carriage among her contacts. The serotype of the meningitis case isolate was determined, together with the serotypes of the NP specimens of contacts, comprising the case patient's brother, the case patient's after-school programme contacts and the brother's day-care centre (DCC) contacts. NP swabs from 155 children and 69 adults were obtained. Real-time PCR and conventional multiplex PCR (CM-PCR) assays were used to detect pneumococcal carriage and determine serotypes. Broth-enriched culture of NP specimens followed by pneumococcal isolation and Quellung-based serotyping were also performed. DNA extracts prepared from cerebrospinal fluid of the index case and from the NP strain isolated from the brother and from one attendee of the brother's DCC were subjected to genotyping. Pneumococcal carriage assessed by real-time PCR and culture was 49.6 and 36.6 %, respectively (P<0.05). Twenty-three serotypes were detected using CM-PCR, with serotypes 6A/6B, 14, 19F, 6C/6D, 22F/22A, 23F and 11A/11D being the most frequent. All eight serotype 22F/22A NP specimens recovered were from children attending the brother's DCC. The meningitis case isolate and the NP carriage isolate from the patient's brother were both serotype 22F and shared the same new multilocus sequence type (ST6403) with the attendee of the brother's DCC. CM-PCR proved to be useful for assessing carriage serotype distribution in a setting of high-risk pneumococcal transmission. The causal serotype appeared to be linked to the brother of the case patient and attendees of his DCC. |
Outbreak of bacterial meningitis among patients undergoing myelography at an outpatient radiology clinic
Chitnis AS , Guh AY , Benowitz I , Srinivasan V , Gertz RE Jr , Shewmaker PL , Beall BW , O'Connell H , Noble-Wang J , Gornet MF , Van Beneden C , Patrick SL , Turabelidze G , Patel PR . J Am Coll Radiol 2012 9 (3) 185-90 PURPOSE: To investigate an outbreak of bacterial meningitis at an outpatient radiology clinic (clinic A) and to determine the source and implement measures to prevent additional infections. METHODS: A case was defined as bacterial meningitis in a patient undergoing myelography at clinic A from October 11 to 25, 2010. Patients who underwent myelography and other procedures at clinic A during that period were interviewed, medical records were reviewed, and infection prevention practices were assessed. Case-patient cerebrospinal fluid (CSF) specimens, oral specimens from health care personnel (HCP), and opened iohexol vials were tested for bacteria. Bacterial isolates were compared using pulsed-field gel electrophoresis. A culture-negative CSF specimen was tested using a real-time polymerase chain reaction assay. RESULTS: Three cases were identified among 35 clinic A patients who underwent procedures from October 11 to 25, 2010. All case-patients required hospitalization, 2 in an intensive care unit. Case-patients had myelography performed by the same radiology physician assistant and technician on October 25; all patients who underwent myelography on October 25 were affected. HCP did not wear facemasks and reused single-dose iohexol vials for multiple patients. Streptococcus salivarius (a bacteria commonly found in oral flora) was detected in the CSF of 2 case-patients (1 by culture, 1 using real-time polymerase chain reaction) and in HCP oral specimens; 1 opened iohexol vial contained Staphylococcus epidermidis. Pulsed-field gel electrophoresis profiles from the case-patient S salivarius and the radiology physician assistant were indistinguishable. CONCLUSIONS: Bacterial meningitis likely occurred because HCP performing myelography did not wear facemasks; lapses in injection practices may have contributed to transmission. Targeted education regarding mask use and safe injection practices is needed among radiology HCP. |
Invasive pneumococcal disease and pandemic (H1N1) 2009, Denver, Colorado, USA
Nelson GE , Gershman KA , Swerdlow DL , Beall BW , Moore MR . Emerg Infect Dis 2012 18 (2) 208-16 Pneumococcal pneumonia was a complication during previous influenza pandemics but was not evident initially during pandemic (H1N1) 2009. During October 2009 in Denver, Colorado, USA, invasive pneumococcal disease (IPD) and pandemic (H1N1) 2009 peaked simultaneously, which suggests a link. We compared cases of IPD in October 2009 with cases in February 2009, the most recent peak month of seasonal influenza. During October 2009, we observed 58 IPD cases, which was 3x the average number of IPD cases that usually occur in October in Denver. Patients with IPD in October 2009 were younger and more likely to have chronic lung disease than patients who had IPD in February 2009; a total of 10/47 patients had influenza, and 33/53 patients had influenza-like illness. Thus, approximately 17%-62% cases of IPD may have been associated with pandemic (H1N1) 2009. Pneumococcal disease prevention strategies should be emphasized during future influenza pandemics. |
Streptococcus pneumoniae serotype 9A isolates contain diverse mutations to wcjE that result in variable expression of serotype 9V-specific epitope.
Calix JJ , Oliver MB , Sherwood LK , Beall BW , Hollingshead SK , Nahm MH . J Infect Dis 2011 204 (10) 1585-95 BACKGROUND: Streptococcus pneumoniae is a significant pathogen capable of expressing protective and antigenically diverse capsules. To better understand the molecular basis of capsular antigenic diversity, we investigated the hypothetical serological role of wcjE, which encodes a capsule O-acetyltransferase, in the vaccine-targeted serotype 9V and related serotype 9A. METHODS: We inactivated wcjE by recombination in a serotype 9V strain and determined wcjE sequences of 11 serotype 9A clinical isolates. We determined the antigenic phenotypes of these pneumococcal strains with serogroup 9-specific antibodies and flow cytometry. RESULTS: Inactivation of wcjE in a serotype 9V strain resulted in expression of the 9A phenotype. Each serotype 9A clinical isolate contained a distinct mutation to wcjE. Flow cytometry showed that some 9A isolates (herein named 9Aalpha) expressed trace amounts of 9V-specific epitopes whereas others (named 9Abeta) did not express any. Recombination with 9Aalpha wcjE alleles into a 9Abeta strain conferred partial expression of 9V-specific epitopes. CONCLUSIONS: Each serotype 9A strain independently arose from a serotype 9V strain. Furthermore, clinical isolates identified as 9A can contain mutations to wcjE that are either partially functional or completely nonfunctional, demonstrating a previously unidentified antigenic heterogeneity of serotype 9A isolates. |
Serotype and genotype distributions of pneumococcal carriage isolates recovered from Brazilian children attending day-care centres.
Pimenta FC , Carvalho MG , Gertz RE Jr , Bastos-Rocha CG , Oliveira LS , Lacerda Pigosso L , Lima JA , Marquez Franco C , Andrade AL , Beall BW . J Med Microbiol 2011 60 1455-9 Pneumococcal nasopharyngeal carriage isolates recovered from Brazilian children attending day-care centres in 2005 were assessed for serotype, genotype and penicillin susceptibility phenotype. As 124 of the 253 isolates (49 %) were characterized previously with respect to serotype and penicillin susceptibility, the primary objectives were to examine clonal associations and penicillin susceptibility within major serotypes and to assess the suitability of conventional multiplex PCR for deducing carriage serotypes within this population. Using a combination of PCR-based serotyping and the Quellung reaction, serotypes were identified for 81 % (205/253) of the isolates, with serogroups or types 14, 6, 23F, 19F and 18 being predominant. Included within the 205 isolates successfully serotyped by PCR were 28 isolates that had become non-viable. Forty-eight isolates were non-typable using both the PCR method and the Quellung reaction. Penicillin non-susceptibility was observed within 16 of the 18 multilocus sequence types detected. Thus, this study provides further evidence from a diverse collection of pneumococcal clones that PCR-based serotype deduction is useful for providing supportive evidence for pneumococcal conjugate vaccine implementation. |
Quadriplex real-time polymerase chain reaction (lytA, mef, erm, pbp2b(wt)) for pneumococcal detection and assessment of antibiotic susceptibility.
Srinivasan V , du Plessis M , Beall BW , McGee L . Diagn Microbiol Infect Dis 2011 71 (4) 453-6 A quadriplex real-time polymerase chain reaction assay was developed for detecting pneumococci, penicillin susceptibility, and macrolide/lincosamide resistance. The assay was sensitive for all 4 targets (<10 copies) and correlated with antimicrobial susceptibilities in 172/180 isolates and 28/29 culture-positive clinical specimens. For 29 lytA-positive culture-negative specimens, the assay allowed interpretation of antimicrobial susceptibility. |
Geographic variation in invasive pneumococcal disease following pneumococcal conjugate vaccine introduction in the United States
Rosen JB , Thomas AR , Lexau CA , Reingold A , Hadler JL , Harrison LH , Bennett NM , Schaffner W , Farley MM , Beall BW , Moore MR . Clin Infect Dis 2011 53 (2) 137-43 BACKGROUND: Rates of invasive pneumococcal disease (IPD) varied among the United States before pneumococcal conjugate vaccine (PCV7) introduction. We compared trends in IPD rates among diverse US sites over 10 years since PCV7 introduction. METHODS: Patients with IPD of all ages were identified through active population and laboratory-based surveillance in 8 geographic areas under continuous surveillance during 1998-2009. Isolates were serotyped. IPD incidence rates and percent changes were calculated by site, serotype group, age, and year. RESULTS: Reductions in rates of IPD ranged, by site, from 19 to 29.9 cases per 100,000 population during 1998-1999 to 11.2-18.0 cases per 100,000 population during 2009 (rate reduction, 5.1-15.3 cases per 100,000 population). Reductions in IPD rates among children aged <5 years ranged from 35.7 to 117.2 cases per 100,000 population across the sites. Reductions in rates of IPD due to PCV7 serotypes were seen in all age groups at all sites, ranging from 12 to 21.4 cases per 100,000 population during 1998-1999 to <2 cases per 100,000 population during 2009 (92%-98% reductions). Serotype 19A rates ranged from 0.4 to 1.5 cases per 100,000 population during 1998-1999 to 1.3 to 3.4 cases per 100,000 population during 2009 (rate difference, 0.9-2.8 cases per 100,000 population); modest increases were observed for most age groups across the sites. Rates of IPD due to all other serotypes ranged from 6.3 to 10.3 cases per 100,000 population during 1998-1999 to 8.3-13.6 cases per 100,000 population during 2009 (rate difference, -0.4 to 5.7 cases per 100,000 population). Across the sites, the greatest rate increases were seen in the 50-64 and >65 year age groups. CONCLUSIONS: Reductions in IPD due to vaccine serotypes were consistent across sites. Changes in serotype 19A and all other serotypes were variable. Although relative increases in non-vaccine type serotypes were large in some sites, absolute rate increases were small. |
Application of TaqMan low-density arrays for simultaneous detection of multiple respiratory pathogens.
Kodani M , Yang G , Conklin LM , Travis TC , Whitney CG , Anderson LJ , Schrag SJ , Taylor TH Jr , Beall BW , Breiman RF , Feikin DR , Njenga MK , Mayer LW , Oberste MS , Tondella ML , Winchell J , Lindstrom S , Erdman DD , Fields BS . J Clin Microbiol 2011 49 (6) 2175-82 The large and growing number of viral and bacterial pathogens responsible for respiratory infections poses a challenge for laboratories to provide rapid and comprehensive pathogen identification. We evaluated a novel application of the TaqMan(R) Low Density Array (TLDA) cards for real-time PCR detection of 21 respiratory pathogen targets. TLDA performance was compared to individual real-time PCR (IRTP) assays with the same primers and probes using 1) nucleic acids extracted from the 21 pathogen strains and 66 closely-related viruses and bacteria and 2) 292 clinical respiratory specimens. Using spiked samples, TLDA cards were about ten-fold less sensitive than the IRTP assays. Using 292 clinical specimens to generate 2238 paired individual assays, TLDA exhibited 89% sensitivity (95% confidence interval [CI] 86-92; 47-100 range per target) and 98% specificity (95% CI 97-99; 85-100 range per target) overall compared to IRTP real-time assays as the gold standard with a Ct cut-off of 43. The TLDA card approach offers promise for rapid and simultaneous identification of multiple respiratory pathogens for outbreak investigations and disease surveillance. |
Shifting genetic structure of invasive serotype 19A pneumococci in the United States
Beall BW , Gertz RE , Hulkower RL , Whitney CG , Moore MR , Brueggemann AB . J Infect Dis 2011 203 (10) 1360-8 BACKGROUND: Following 7-valent conjugate vaccine introduction in the United States in 2000, invasive serotype (sero19A) pneumococcal disease (IPD) emerged rapidly. Sero19A IPD incidence increased slightly during 2005-2008 (from 2.3 cases to 2.5 cases per 100,000 population), whereas sero19A penicillin resistance (defined as a minimum inhibitor concentration [MIC] ≥2 mug/mL) increased significantly (from 28.7% to 43.7%). To better understand changes, we characterized sero19A isolates recovered during 2004-2008. METHODS: We performed antimicrobial susceptibility testing on all 2767 sero19A IPD isolates identified through the Centers for Disease Control Active Bacterial Core surveillance during 2004-2008. We genotyped 1804 (96.3%) of 1874 sero19A isolates recovered during 2005-2007 and all 148 year 2008 sero19A isolates from children <5 years of age. RESULTS: Resistant clonal complex (CC) 320/271(19A) increased from 20.9% (115 of 550) to 32.9% (208 of 633; P < .001) of IPD isolates during 2005-2007, which paralleled increased sero19A penicillin resistance (from 28.7% [163 of 567 isolates] to 39.5% [261 of 661 isolates]; P < .001). Total IPD due to 320/271(19A) increased during 2005-2007 and increased from 2.1 to 3.6 cases per 100,000 population during 2005-2008 in children <5 years of age. The penicillin-susceptible/intermediate, putative vaccine-escape CC695(19A) increased from 7.5% (41 of 550) to 13.6% (85 of 633) of sero19A isolates during 2005-2007 (P = .002). CONCLUSIONS: Sero19A rates may have plateaued; however, clonal shifts are increasing resistance. Increased IPD caused by CC320/271(19A) and CC695(19A) could reflect additional selective advantages in addition to resistance. |
Serotype distribution and antimicrobial resistance of Streptococcus pneumoniae prior to introduction of the 10-valent pneumococcal conjugate vaccine in Brazil, 2000-2007
Menezes AP , Campos LC , Dos Santos MS , Azevedo J , Dos Santos RC , Carvalho Mda G , Beall BW , Martin SW , Salgado K , Reis MG , Ko AI , Reis JN . Vaccine 2011 29 (6) 1139-44 This study describes the serotype distribution and antibiotic resistance patterns among 397 S. pneumoniae meningitis case isolates recovered in Salvador, Brazil, during the period of 2000-2007, before introduction of the 10-valent pneumococcal conjugate vaccine. The active hospital-based surveillance showed a decline in the annual incidence rates of pneumococcal meningitis during the period of study, from 1.12 cases to 0.83 cases/100,000 persons for all age groups (P<0.001), with an overall case-fatality rate of 28.6% (113 of 395) for all patients and 41.9% (57 of 136) for those <5 years of age. Serotypes 14 (n=55; 13.9%), 3 (n=32; 8.1%), 23F (n=32; 8.1%), 19F (n=31; 7.8%), 6B (n=30; 7.6%), 18C (n=28; 7.1%), and 6A (n=20; 5%) were the most prevalent serotypes. In patients <5 years the estimated projected coverage of 7-, 10- and 13-valent conjugate vaccines was 74.3%, 75.7% and 83.1%, respectively. Antimicrobial susceptibility testing revealed that 22.1% (n=88) of isolates were non-susceptible to penicillin, 56% were non-susceptible to trimethoprim/sulphamethoxazole, and 29.6% were non-susceptible to tetracycline. Nonsusceptibility to penicillin and cefotaxime was detected solely among serotype 14 isolates (n=4; 1%). This study provides an important baseline to assess the impact of conjugate vaccine implantation on the epidemiology of meningitis due to Streptococcus pneumoniae in Salvador, Brazil. |
Pre- and post-conjugate vaccine epidemiology of pneumococcal serotype 6C invasive disease and carriage within Navajo and White Mountain Apache communities
Millar EV , Pimenta FC , Roundtree A , Jackson D , Carvalho MD , Perilla MJ , Reid R , Santosham M , Whitney CG , Beall BW , O'Brien KL . Clin Infect Dis 2010 51 (11) 1258-65 BACKGROUND: A second-generation 13-valent pneumococcal conjugate vaccine, PCV13, was recently licensed. Although PCV13 includes serotype 6A, the usefulness of that antigen may be limited by the emergence of a new serotype, 6C, which was identified among isolates initially characterized (Quellung reaction) as serotype 6A. The epidemiology of serotype 6C prior to and after 7-valent PCV (PCV7) introduction is incompletely understood. METHODS: We analyzed conventionally serotyped 6A (CS6A) pneumococci from invasive disease case patients of all ages and carriage isolates from children and adults obtained in population-based studies among Navajo and White Mountain Apache communities during 1994-2009. Samples were tested by triplex polymerase chain reaction to resolve serotypes 6C and 6A. RESULTS: A total of 74 invasive CS6A episodes occurred. All were retyped by polymerase chain reaction; 40 (54.1%) were serotype 6C. The mean annual incidence of serotype 6C invasive disease was 0.3 (95% confidence interval, 0.03-0.9), 0.7 (95% confidence interval, 0.2-1.3), and 1.5 (95% confidence interval, 1.0-2.1) cases per 100,000 population in the years prior to the PCV7 efficacy trial, during the time the PCV7 trial was conducted, and following PCV7 introduction and routine use, respectively ([Formula: see text]). In the routine vaccination era, 76% of invasive CS6As were serotype 6C; nearly all cases occurred in adults. The proportion of serotype 6C among CS6A carriage isolates increased from 42% to 61% to 94% in the prevaccine, early vaccine, and routine vaccination eras, respectively. CONCLUSION: In the PCV7 routine use era, virtually all serogroup 6 invasive pneumococcal disease and carriage strains among Navajo and White Mountain Apache communities are 6C. Monitoring and evaluation of this and other emerging serotypes among invasive disease and carriage isolates is warranted. |
- Page last reviewed:Feb 1, 2024
- Page last updated:Apr 22, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure