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Bernard Beall

Publications and source records attributed to Bernard Beall.

At least 37 records · Page 2Linked to original sources
PubMed2005

Age influences the emm type distribution of pediatric group A streptococcal pharyngeal isolates.

BACKGROUND: emm types 12, 1, 28, 3, 4, 2 and 6 (in that order) are the types most commonly associated with uncomplicated group A streptococcal (GAS) pharyngitis in the United States, together accounting for approximately 78% of isolates. OBJECTIVE: To determine whether the distribution of common pharyngeal group A streptococcal GAS types differs at various ages throughout childhood. STUDY DESIGN: We emm typed 3356 GAS isolates collected from the United States and Canada during 3 streptococcal seasons (2000-2003). Variations in prevalence by age for the 7 most prevalent emm types and the "uncommon" category (all types accounting for <5% of the total number of isolates) were analyzed and assessed for significance by chi2. RESULTS: The proportion of uncommon isolates increased significantly with increasing age from 18% in group 1 to 37% in group 4 (P = 0.001). We found a significant decrease in the proportion of the common pharyngeal emm types, specifically emm 12 and emm 4 type isolates, with increasing age (P = 0.001 and P = 0.003, respectively); there was no significant decline in the prevalence of other common pharyngeal types (emm 1, 2, 3, 6 and 28) with increasing age. CONCLUSION: Age-related changes in emm type distribution of pharyngeal GAS are present in childhood; these changes may reflect acquisition of immunity to more common types as a consequence of exposure early in life, but this remains to be demonstrated.

Adolescent↗
PubMed2005

Interspecies recombination in type II topoisomerase genes is not a major cause of fluoroquinolone resistance in invasive Streptococcus pneumoniae isolates in the United States.

Mutations in the topoisomerase type II enzymes account for fluoroquinolone resistance in Streptococcus pneumoniae. These mutations can arise spontaneously or be transferred by intraspecies or interspecies recombination, primarily with viridans streptococci. We analyzed the nucleotide sequences of the quinolone resistance-determining regions of 49 invasive levofloxacin-resistant pneumococcal isolates and did not find any evidence for interspecies recombination.

Anti-Bacterial Agents↗
PubMed2005

Multivalent group A streptococcal vaccine elicits bactericidal antibodies against variant M subtypes.

Group A streptococci cause a wide spectrum of clinical illness. One of several strategies for vaccine prevention of these infections is based on the type-specific M protein epitopes. A multivalent M protein-based vaccine containing type-specific determinants from 26 different M serotypes is now in clinical trials. Recent epidemiologic studies have shown that, within some serotypes, the amino-terminal M protein sequence may show natural variation, giving rise to subtypes. This raises the possibility that vaccine-induced antibodies against the parent type may not be as effective in promoting bactericidal killing of variant subtypes. In the present study we used rabbit antisera against the 26-valent M protein-based vaccine in bactericidal tests against M1, M3, and M5 streptococci, which were represented by multiple subtypes. We show that the vaccine antibodies effectively promoted in vitro bactericidal activity despite the fact that the M proteins contained naturally occurring variant sequences in the regions corresponding to the vaccine sequence. Our results show that the variant M proteins generally do not result in significant differences in opsonization promoted by rabbit antisera raised against the 26-valent vaccine, suggesting that a multivalent M protein vaccine may not permit variant subtypes of group A streptococci to escape in a highly immunized population.

Amino Acid Sequence↗
PubMed2005

Clonal association between Streptococcus pneumoniae serotype 23A, circulating within the United States, and an internationally dispersed clone of serotype 23F.

Streptococcus pneumoniae is an important pathogen in the United States and is associated with significant morbidity and mortality. Since the introduction of the seven-valent conjugate vaccine, a significant decline in pneumococcal disease has been reported. However, surveillance for pneumococcal disease remains essential, as the extent of cross protection against vaccine-related serotypes is still unclear. Further, any increase in non-vaccine-related serotypes also needs monitoring. We report on a new clonal association between a vaccine-related serotype, serotype 23A, obtained as part of the Active Bacterial Core surveillance, with an established internationally dispersed Pneumococcal Molecular Epidemiology Network (PMEN) clone, clone Colombia(23F)-26. Sixty-two isolates of serotype 23A collected from sterile sites during a 2-year period (2002 and 2003) were characterized. Twenty-one (34%) isolates were penicillin nonsusceptible, although none were fully resistant. Pulsed-field gel electrophoresis and multilocus sequence typing analysis showed that 24 (39%) of the serotype 23A isolates shared either genetic identity or high genetic relatedness with PMEN clone Colombia(23F)-26. Extensive variability was noted within the sequenced region of pbp2b in two penicillin-nonsusceptible isolates as well as in PMEN clone Colombia(23F)-26, suggesting that these isolates probably acquired penicillin resistance independently. The emergence of such new serotype and genotype associations highlights the dynamic nature of the pneumococcal population, necessitating continuous monitoring in the post-vaccine era.

Adolescent↗
PubMed2005

Six-month multicenter study on invasive infections due to Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis in Argentina.

During a 6-month period, 95 invasive infections due to Streptococcus pyogenes and group C or group G Streptococcus dysgalactiae subsp. equisimilis were recorded from 40 centers of 16 cities in Argentina. We describe here epidemiologic data available for 55 and 19 patients, respectively, associated with invasive infections due to S. pyogenes and S. dysgalactiae subsp. equisimilis. The associated isolates and 58 additional pharyngeal isolates were genotyped and subjected to serologic and/or antibiotic susceptibility testing. Group A streptococcal emm type distribution and strain association with toxic shock appeared to differ somewhat from results found within the United States; however, serologic characterization and sof sequence typing suggested that emm types found in both countries are reflective of shared clonal types.

Adult↗
PubMed2005

Use of pyrosequencing to differentiate Streptococcus pneumoniae serotypes 6A and 6B.

Accurate serotyping of Streptococcus pneumoniae remains important to monitor the changes in seroepidemiology of the organism over time. Though several PCR-based systems have been developed for this purpose, the cross-reactivity within serogroups often limits discrimination between types. All serogroup 6 isolates can be identified using a multiplex PCR system; however, due to the high sequence homology between the cps-6B and cps-6A loci, serotypes 6A and 6B cannot be differentiated by this method. We describe the use of pyrosequencing to reliably differentiate between serotypes 6A and 6B using a previously described single nucleotide polymorphism at codon 195 of the cps locus wciP gene. We observed complete concordance between capsular serotyping results and wciP pyrosequencing among 210 isolates examined, indicating that pyrosequencing is a rapid and accurate technique for deducing serotypes 6A and 6B.

Bacterial Capsules↗
PubMed2004

Group A streptococcal pharyngitis serotype surveillance in North America, 2000-2002.

Geographic and interseasonal heterogeneity of pharyngeal group A streptococcal (GAS) genotypes (emm types) is poorly characterized. We evaluated emm type and subtype distribution among pediatric pharyngitis isolates obtained from 9 sites in the United States during 2000-2001 (year 1) and from 10 sites in the United States and 1 site in Canada during 2001-2002 (year 2). The 7 predominant types were the same in both years, although their order changed. emm 12, 1, and 28 accounted for 49.2% of year 1 isolates, and emm 1, 12, and 4 accounted for 47.1% of year 2 isolates; 6 types accounted for 72.1% in year 1 and 69.4% in year 2. From year 1 to year 2, the proportions of emm 12 and 28 decreased and emm 1 and 6 increased. Striking intersite and interseasonal variations in the distribution of predominant emm types were observed. We conclude that the most-predominant GAS genotypes were similar for each year despite fluctuations, that intersite and intrasite variations in the distribution of emm types were apparent, and that emm type surveillance is needed as M protein vaccine development proceeds.

Adolescent↗
PubMed2004

Group A streptococci from a remote community have novel multilocus genotypes but share emm types and housekeeping alleles with isolates from worldwide sources.

Group A streptococci (GAS) cause several human diseases that differentially affect distinct host populations. Genotypes were defined by multilocus sequence typing and emm typing for 137 organisms collected from individuals in a remote aboriginal island community in tropical Australia and compared with >200 isolates obtained from sources elsewhere in the world. The majority of aboriginal-derived isolates shared emm types and housekeeping alleles with GAS isolates recovered from outside Australia, but these emm types and alleles were in novel combinations. There were many examples in which isolates from aboriginal and non-Australian subjects shared the same emm type, but for approximately 50% of emm types, the multilocus genotypes of isolates of the same emm type but from different regions were very different. A single emm type may typically define a single clone within the United States and on the remote island that is the focus of this study, but in many cases, these clones will be different, and this finding has implications for attempts to make global associations between emm types and certain disease manifestations.

Australia↗
PubMed2004

Reemergence of macrolide resistance in pharyngeal isolates of group a streptococci in southwestern Pennsylvania.

We previously reported on the emergence of macrolide-resistant pharyngeal isolates of group A streptococci (GAS) in our community. The purpose of the present study was to track longitudinal trends in macrolide resistance in these isolates in southwestern Pennsylvania. Testing for susceptibility to erythromycin and clindamycin was performed for all pharyngeal GAS isolates recovered at the Children's Hospital of Pittsburgh and a local pediatric practice between September 2001 and May 2002. Macrolide resistance phenotypes and genotypes were determined by double-disk diffusion and PCR, respectively. Strain relatedness was determined by field inversion gel electrophoresis and emm gene sequence typing. A total of 708 isolates of GAS were recovered during the study period; 68 (9.6%) were macrolide resistant, while all isolates were sensitive to clindamycin. The monthly prevalence of macrolide resistance ranged from 0 to 41%. Only 21 of 573 (3.7%) strains recovered from September 2001 through March 2002 were macrolide resistant. A sudden increase in the rate of macrolide resistance (47 of 135 isolates [35%]) was seen in April and May 2002. Sixty-two isolates demonstrated the M phenotype (resistance to macrolide antibiotics), and six isolates demonstrated the MLS(B) phenotype (resistance to most macrolide, lincosamide, and streptogramin B antibiotics); these isolates were confirmed to be mef(A) and erm(A), respectively. Three unique mef(A) clones and four unique erm(A) clones were identified among the resistant isolates. The MIC at which 50% of isolates are inhibited (MIC(50)) for the mef(A) strains was 16 micro g/ml, while the MIC(50) for erm(A) strains was 8 micro g/ml. The finding of high levels of macrolide resistance among pharyngeal isolates of GAS for a second successive year in our community raises the concern that this problem may be more common in the United States than was previously appreciated. Longitudinal surveillance of isolates from multiple centers is needed to define the prevalence of antimicrobial agent-resistant GAS in the United States.

Anti-Bacterial Agents↗
PubMed2004

Emergence of Streptococcus pneumoniae with very-high-level resistance to penicillin.

Penicillin resistance threatens the treatment of pneumococcal infections. We used sentinel hospital surveillance (1978 to 2001) and population-based surveillance (1995 to 2001) in seven states in the Active Bacterial Core surveillance of the Emerging Infections Program Network to document the emergence in the United States of invasive pneumococcal isolates with very-high-level penicillin resistance (MIC > or = 8 microg/ml). Very-high-level penicillin resistance was first detected in 1995 in multiple pneumococcal serotypes in three regions of the United States. The prevalence increased from 0.56% (14 of 2,507) of isolates in 1995 to 0.87% in 2001 (P = 0.03), with peaks in 1996 and 2000 associated with epidemics in Georgia and Maryland. For a majority of the strains the MICs of amoxicillin (91%), cefuroxime (100%), and cefotaxime (68%), were > or =8 microg/ml and all were resistant to at least one other drug class. Pneumonia (50%) and bacteremia (36%) were the most common clinical presentations. Factors associated with very highly resistant infections included residence in Tennessee, age of <5 or > or =65 years, and resistance to at least three drug classes. Hospitalization and case fatality rates were not higher than those of other pneumococcal infection patients; length of hospital stay was longer, controlling for age. Among the strains from 2000 and 2001, 39% were related to Tennessee(23F)-4 and 35% were related to England(14-)9. After the introduction of the pneumococcal conjugate vaccine, the incidence of highly penicillin resistant infections decreased by 50% among children <5 years of age. The emergence, clonality, and association of very-high-level penicillin resistance with multiple drug resistance requires further monitoring and highlights the need for novel agents active against the pneumococcus.

DNA-Cytosine Methylases↗
PubMed2004

Levofloxacin-resistant invasive Streptococcus pneumoniae in the United States: evidence for clonal spread and the impact of conjugate pneumococcal vaccine.

The emergence of fluoroquinolone resistance in sterile-site isolates of Streptococcus pneumoniae is documented in this study characterizing all invasive levofloxacin-resistant (MIC, > or = 8 mg/liter) S. pneumoniae isolates (n = 50) obtained from the Centers for Disease Control and Prevention Active Bacterial Core Surveillance from 1998 to 2002. Resistance among all isolates increased from 0.1% in 1998 to 0.6% in 2001 (P = 0.008) but decreased to 0.4% in 2002, while resistance among vaccine serotypes continued to increase from 0.3% in 1998 to 1.0% in 2002, suggesting that fluoroquinolones continue to exert selective pressure on these vaccine serotypes. Only 22% of resistant isolates were not covered by the conjugate vaccine serogroups. Multilocus sequence typing revealed that 58% of resistant strains were related to five international clones identified by the Pneumococcal Molecular Epidemiology Network, with the Spain(23F)-1 clone being most frequent (16% of all isolates). Thirty-six percent of the isolates were coresistant to penicillin, 44% were coresistant to macrolides, and 28% were multiresistant to penicillin, macrolides, and fluoroquinolones. Fifty percent of the isolates were resistant to any three drug classes. Ninety-four percent of the isolates had multiple mutations in the quinolone resistance-determining regions of the gyrA, gyrB, parC, and parE genes. In 16% of the isolates, there was evidence of an active efflux mechanism. An unusual isolate was found that showed only a single parE mutation and for which the ciprofloxacin MIC was lower (2 mg/liter) than that of levofloxacin (8 mg/liter). Our results suggest that invasive pneumococcal isolates resistant to levofloxacin in the United States show considerable evidence of multiple resistance and of clonal spread.

Anti-Bacterial Agents↗
PubMed2004

Multilocus sequence typing of Streptococcus pyogenes representing most known emm types and distinctions among subpopulation genetic structures.

A long-term goal is to characterize the full range of genetic diversity within Streptococcus pyogenes as it exists in the world today. Since the emm locus is subject to strong diversifying selection, emm type was used as a guide for identifying a genetically diverse set of strains. This report contains a description of multilocus sequence typing based on seven housekeeping loci for 495 isolates representing 158 emm types, yielding 238 unique combinations of sequence type and emm type. A genotypic marker for tissue site preference (emm pattern) revealed that only 17% of the emm types displayed the marker representing strong preference for infection at the throat and that 39% of emm types had the marker for skin tropism, whereas 41% of emm types harbored the marker for no obvious tissue site preference. As a group, the emm types bearing the emm pattern marker indicative of no obvious tissue site preference were far less likely to have two distinct emm types associated with the same sequence type than either of the two subpopulations having markers for strong tissue tropisms (P < 0.002). In addition, all genetic diversification events clearly ascribed to a recombinational mechanism involved strains of only two of the emm pattern-defined subpopulations, those representing skin specialists and generalists. The findings suggest that the population genetic structure differs for the tissue-defined subpopulations of S. pyogenes. The observed differences may partly reflect differential host immune selection pressures.

Antigens, Bacterial↗
PubMed2004

Group G streptococcal bacteremia in Jerusalem.

Group G Streptococcus (GGS) can cause severe infections, including bacteremia. These organisms often express a surface protein homologous to the Streptococcus pyogenes M protein. We retrospectively studied the characteristics of patients from the Hadassah Medical Center with GGS bacteremia from 1989 to 2000. Ninety-four cases of GGS bacteremia were identified in 84 patients. The median age was 62 years, 54% were males, and 92% had underlying diseases (35% had a malignancy, and 35% had diabetes mellitus). The most frequent source for bacteremia was cellulitis (61%). emm typing of 56 available isolates disclosed 13 different types, including 2 novel types. Six patients had recurrent bacteremia with two to four bacteremic episodes, five had chronic lymphatic disorders, and two had emm type stG840.0 in every episode. Recurrent bacteremia has not been described for invasive group A Streptococcus. We describe an entity of recurrent GGS bacteremia, which is associated with lymphatic disorders and possibly with emm stG840.0.

Adolescent↗
PubMed2003

Identification of superantigen genes speM, ssa, and smeZ in invasive strains of beta-hemolytic group C and G streptococci recovered from humans.

Group C and G Streptococcus dysgalactiae subspecies equisimilis (GCSE and GGSE) cause a substantial percentage of invasive disease caused by beta-hemolytic streptococci. To determine whether Streptococcus pyogenes superantigen (SAg) genes commonly exist within these organisms, 20 recent invasive GCSE and GGSE human isolates and one group G Streptococcus canis human isolate were tested for the presence of SAg genes speH, speJ, speL, speM, ssa and smeZ by polymerase chain reaction (PCR). Prior to this work, sequence-based evidence of the speM, ssa, and smeZ genes in GCSE, GGSE, and S. canis had not been documented. Eleven of the 21 isolates were PCR-positive for the presence of one to two of the SAgs speM, ssa, or smeZ, with four of these isolates carrying ssa+speM or ssa+smeZ. No isolate was positive for speH, speJ and speL. All six ssa-positive GGSE strains harbored the ssa3 allele, previously only found among S. pyogenes strains. All three smeZ-positive GGSE isolates carried one of two smeZ alleles previously only found within S. pyogenes, however the single S. canis isolate carried a new smeZ allele. All five GCSE and GGSE speM-positive isolates harbored a newly discovered speM allele. The identification of these SAgs within S. dysgalactiae subsp. equisimilis and S. canis with identical or near-identical sequences to their counterparts in S. pyogenes suggests frequent interspecies gene exchange between the three beta-hemolytic streptococcal species.

Antigens, Bacterial↗
PubMed2003

Array of M protein gene subtypes in 1064 recent invasive group A streptococcus isolates recovered from the active bacterial core surveillance.

Using sequence analysis to detect variation within the hypervariable M protein N terminus, we found 41 emm types encompassing 81 subtypes, among 1064 consecutive invasive group A streptococcus isolates from a recent multistate, population-based surveillance. Seventeen of the 30 emm types represented by multiple isolates displayed multiple subtypes. Most subtypes differed from reference strain emm sequences as a result of single base substitutions or other alterations likely to be stably inherited. The Centers for Disease Control and Prevention database (available at: http://www.cdc.gov/ncidod/biotech/strep/strepblast.htm) currently contains 225 distinct emm types encompassing 450 subtypes. Although this subtyping scheme increases specificity, limited variation within individual types favors introduction of M protein type-specific vaccines.

Amino Acid Sequence↗
PubMed2003

An outbreak of conjunctivitis due to atypical Streptococcus pneumoniae.

BACKGROUND: In February 2002, clinicians at the Dartmouth College Health Service recognized an outbreak of conjunctivitis; cultures of conjunctival swabs implicated Streptococcus pneumoniae. An investigation was begun to determine the extent of the outbreak, confirm the cause, identify modes of transmission, and implement control measures. METHODS: Investigators reviewed the health service's data base for diagnoses of conjunctivitis. Viral and bacterial cultures were obtained from ill students. Bile-soluble isolates that were susceptible to ethylhydrocupreine (optochin) and therefore were presumed to be pneumococci underwent serotyping, capsular staining, pulsed-field gel electrophoresis, a DNA probe, and multilocus sequence typing. A cohort study of risk factors was conducted with the use of the Internet. Control measures included distribution of alcohol-based hand gel and messages about prevention. RESULTS: Among 5060 students, 698 (13.8 percent) received a diagnosis of conjunctivitis from January 1, 2002, through April 12, 2002, including 22 percent of first-year students. Presumed pneumococci were isolated from 43.3 percent of conjunctival swabs (110 of 254); viral cultures performed on 85 specimens were negative. DNA probes and multilocus sequence typing confirmed that the organisms were pneumococci, although the bacteria did not have the characteristic capsule. On pulsed-field gel electrophoresis, strains were found to be identical to pneumococci that caused outbreaks of conjunctivitis in other parts of the country in 1980. Analysis of survey data from 1832 students indicated that close contact with a student with conjunctivitis, wearing contact lenses, membership on a sports team, and attending parties at or living in a fraternity or sorority house were associated with conjunctivitis. The rate of diagnosis of conjunctivitis declined after the implementation of control measures and after spring break. CONCLUSIONS: This large outbreak of conjunctivitis on a college campus was caused by an atypical, unencapsulated strain of S. pneumoniae that was identical to strains that had caused outbreaks two decades earlier.

Conjunctiva↗
PubMed2003

Molecular genetic analysis of a group A Streptococcus operon encoding serum opacity factor and a novel fibronectin-binding protein, SfbX.

The group A Streptococcus (GAS) sof gene encodes the serum opacity factor protein, which is capable of opacifying mammalian sera and binding at least two host proteins, fibronectin and fibrinogen. The sof gene exists in approximately 50% of clinical isolates, and there is a classical association of so-called nephritogenic strains with the opacity factor-positive phenotype. In both a type emm49 strain and a type emm12 strain, the sequences upstream of the 5' end of sof and downstream of the putative terminator were determined to be nearly identical to a region in the M type 1 genome approximately 10 kb upstream of the emm1 gene. This close genetic linkage is likely reflected in the strict correlation of opacity factor phenotype with specific emm genotypes. A new fibronectin-binding protein gene, sfbX, was discovered immediately downstream of sof in emm12 and emm49 strains and in several other sof-positive strains. The sof and sfbX genes were found to be expressed on the same transcription unit, which was correlated with the putative promoter and rho-independant terminator sequences that flank these two genes. The sfbX genes from different emm types are predicted to encode approximately 650-residue surface-bound proteins sharing 89 to 92% sequence identity. SfbX residues approximately 1 to 480 are not highly similar to those of other known proteins, with the closest match being the Staphylococcus aureus coagulase protein. The remaining portions of these proteins (residues 481 to 650) contain four putative fibronectin-binding repeats highly similar to those of other streptococcal fibronectin-binding proteins and a potential LP(X)SG cell wall anchor motif. Targeted in-frame allelic-exchange mutagenesis, complementation, and heterologous-expression studies found that serum opacification is encoded by sof alone and that sfbX encodes a fibronectin-binding function. A recombinant SfbX protein was found to bind immobilized fibronectin and to partially inhibit GAS adherence to fibronectin. The sfbX gene was found to be present only in sof-positive strains, and together these genes could influence the spectrum of tissues colonized by sof-positive GAS.

Amino Acid Sequence↗