Clinical and Epidemiologic Features of Group A Streptococcal Pneumonia in Ontario, Canada

Muller, Matthew P.; Low, Donald E.; Green, Karen A.; Simor, Andrew E.; Loeb, Mark; Gregson, Daniel B.; McGeer, Allison

doi:10.1001/archinte.163.4.467

Cited by 72 publications

(58 citation statements)

References 53 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Statistical analysis evaluates the confounding factors affecting mice survival The variability in animal mortality and extent of bacteremia is not surprising and matches that reported in human infection [32][33][34] and in mice strains. 17 However, in this particular set of experiments, it was necessary to determine whether this variability reflects genetic differences between different BXD strains or whether it is mere biological variability caused by confounding factors like sex, body weight, animal age or experiment-to-experiment variability (due in part to differences in inoculum size or other experimental error).…”

Section: Resultssupporting

confidence: 68%

Susceptibility to severe streptococcal sepsis: use of a large set of isogenic mouse lines to study genetic and environmental factors

et al. 2007

View full text Add to dashboard Cite

Variation in responses to pathogens is influenced by exposure history, environment and the host's genetic status. We recently demonstrated that human leukocyte antigen class II allelic differences are a major determinant of the severity of invasive group A streptococcal (GAS) sepsis in humans. While in-depth controlled molecular studies on populations of genetically wellcharacterized humans are not feasible, it is now possible to exploit genetically diverse panels of recombinant inbred BXD mice to define genetic and environmental risk factors. Our goal in this study was to standardize the model and identify genetic and nongenetic covariates influencing invasive infection outcomes. Despite having common ancestors, the various BXD strains (n strains ¼ 33, n individuals ¼ 445) showed marked differences in survival. Mice from all strains developed bacteremia but exhibited considerable differences in disease severity, bacterial dissemination and mortality rates. Bacteremia and survival showed the expected negative correlation. Among nongenetic factors, age -but not sex or weight -was a significant predictor of survival (P ¼ 0.0005). To minimize nongenetic variability, we limited further analyses to mice aged 40-120 days and calculated a corrected relative survival index that reflects the number of days an animal survived post-infection normalized to all significant covariates. Genetic background (strain) was the most significant factor determining susceptibility (Pp0.0001), thus underscoring the strong effect of host genetic variation in determining susceptibility to severe GAS sepsis. This model offers powerful unbiased forward genetics to map specific quantitative trait loci and networks of pathways modulating the severity of GAS sepsis.

show abstract

Section: Resultssupporting

confidence: 68%

Susceptibility to severe streptococcal sepsis: use of a large set of isogenic mouse lines to study genetic and environmental factors

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Between 1992 and 2002, populationbased surveillance identified 255 invasive infections caused by serotype M3 isolates (9)(10)(11)16). The frequency of occurrence of invasive episodes in the 2000 peak (i.e., years 1998-2002) was twice that of the 1995 peak (i.e., years 1993-1997) (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To gain new insight into the molecular genetic basis of subclone emergence and disease epidemics and to study the relationship between bacterial strain genotype and patient disease phenotype on a genome-wide level, we analyzed 255 serotype M3 invasive isolates collected in an 11-year population-based surveillance study conducted in Ontario, Canada (9)(10)(11)16). The results provided understanding of the molecular events underlying bacterial epidemics.…”

mentioning

confidence: 99%

Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections

Beres

Sylva

Sturdevant

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

120

115

View full text Add to dashboard Cite

Molecular factors that contribute to the emergence of new virulent bacterial subclones and epidemics are poorly understood. We hypothesized that analysis of a population-based strain sample of serotype M3 group A Streptococcus (GAS) recovered from patients with invasive infection by using genome-wide investigative methods would provide new insight into this fundamental infectious disease problem. Serotype M3 GAS strains (n ‫؍‬ 255) cultured from patients in Ontario, Canada, over 11 years and representing two distinct infection peaks were studied. Genetic diversity was indexed by pulsed-field gel electrophoresis, DNA-DNA microarray, whole-genome PCR scanning, prophage genotyping, targeted gene sequencing, and single-nucleotide polymorphism genotyping. All variation in gene content was attributable to acquisition or loss of prophages, a molecular process that generated unique combinations of proven or putative virulence genes. Distinct serotype M3 genotypes experienced rapid population expansion and caused infections that differed significantly in character and severity. Molecular genetic analysis, combined with immunologic studies, implicated a 4-aa duplication in the extreme N terminus of M protein as a factor contributing to an epidemic wave of serotype M3 invasive infections. This finding has implications for GAS vaccine research. Genome-wide analysis of population-based strain samples cultured from clinically well defined patients is crucial for understanding the molecular events underlying bacterial epidemics.population genetics ͉ evolution ͉ phage ͉ subclone

show abstract

“…The variability in animal mortality and extent of bacteremia is not surprising and matches that reported in human infection (Davies et al, 1996;Basma et al, 1999;Muller et al, 2003) and in mice strains (Medina et al, 2001). However, in this particular set of experiments, it was necessary to determine whether this variability reflects genetic differences between different BXD strains or is it mere biological variability caused by confounding factors like sex, body weight, animal age, or experiment-to-experiment variability (due in part to differences in inoculum size or other experimental error).…”

Section: Statistical Analysis Evaluates the Confounding Factors Affecsupporting

confidence: 71%

Systems Biology Approach to Identifying Host Interactive Pathways Modulating the Severity of Streptococcal Sepsis

Abdeltawab¹

View full text Add to dashboard Cite

Clinical and Epidemiologic Features of Group A Streptococcal Pneumonia in Ontario, Canada

Abstract: Group A streptococcal pneumonia is a common form of invasive GAS disease but remains an uncommon cause of community-acquired pneumonia. Progression is rapid despite appropriate therapy. The incidence is similar to, and the case fatality rate higher than, that of necrotizing fasciitis.

Cited by 72 publications

References 53 publications

Susceptibility to severe streptococcal sepsis: use of a large set of isogenic mouse lines to study genetic and environmental factors

Susceptibility to severe streptococcal sepsis: use of a large set of isogenic mouse lines to study genetic and environmental factors

Genome-wide molecular dissection of serotype M3 group A Streptococcus strains causing two epidemics of invasive infections

Systems Biology Approach to Identifying Host Interactive Pathways Modulating the Severity of Streptococcal Sepsis

Contact Info

Product

Resources

About