Dataset Information

A Bayesian Spatiotemporal Analysis of Pediatric Group A Streptococcal Infections.

ABSTRACT:

Background

Pharyngitis due to group A Streptococcus (GAS) is a common pediatric infection. Physicians might diagnose GAS pharyngitis more accurately when given biosurveillance information about GAS activity. The availability of geographic GAS testing data may be able to assist with real-time clinical decision-making for children with throat infections.

Methods

GAS rapid antigen testing data were obtained from the records of 6086 children at Boston Children's Hospital and 8648 children at Duke University Medical Center. Records included children tested in outpatient, primary care settings. We constructed Bayesian generalized additive models, in which the outcome variable was the binary result of GAS testing, and predictor variables included smoothed functions of patient location data and both cyclic and longitudinal time data.

Results

We observed a small degree of geographic heterogeneity, but no convincing clusters of high risk. The probability of a positive test declined during the summer months.

Conclusions

Future work should include geographic data about school catchments to identify whether GAS transmission clusters within schools.

SUBMITTER: Wang A

PROVIDER: S-EPMC6918452 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

A Bayesian Spatiotemporal Analysis of Pediatric Group A Streptococcal Infections.

Wang Angela A Fine Andrew M AM Buchanan Erin E Janko Mark M Nigrovic Lise E LE Lantos Paul M PM

Open forum infectious diseases 20191210 12

<h4>Background</h4>Pharyngitis due to group A <i>Streptococcus</i> (GAS) is a common pediatric infection. Physicians might diagnose GAS pharyngitis more accurately when given biosurveillance information about GAS activity. The availability of geographic GAS testing data may be able to assist with real-time clinical decision-making for children with throat infections.<h4>Methods</h4>GAS rapid antigen testing data were obtained from the records of 6086 children at Boston Children's Hospital and 86 ...[more]

PMID: 31867406

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Project description:Pediatric autoimmune neuropsychiatric disorders associated with streptococcus infections (PANDAS) originated from the observational work of Swedo and collaborators, who formalized their definition in 1998 in a set of operational criteria. The application of these criteria, which focuses on tics and obsessive-compulsive symptoms as core symptoms, has encountered difficulties, eventually leading to a high rate of misdiagnosis. In particular, the core feature represented by the association between newly diagnosed infections and neuropsychiatric symptom relapses in youths with this diagnosis could not be demonstrated by longitudinal studies. Exploratory studies aiming to identify clinical or cognitive features that could discriminate PANDAS from other pediatric obsessive-compulsive and tic disorders present methodological limitations, and therefore are not conclusive. Other behavioral features, in addition to obsessive-compulsive symptoms and tics, have been included in pediatric acute-onset neuropsychiatric syndromes (PANS) and childhood acute neuropsychiatric syndromes (CANS), two new concepts recently proposed in order to define a much broader clinical spectrum encompassing etiologically diverse entities. Given the uncertainties on the clinical definition of PANDAS, it is not surprising that evidence in support of a post-infectious, immune-mediated pathophysiology is also insufficient. Anti-dopamine receptor antibodies might be relevant to both Sydenham's chorea (SC)-the prototypical post-streptococcal neuropsychiatric disorder-and some rare forms of encephalitis targeting the basal ganglia specifically, but studies exploring their association with children fulfilling Swedo's criteria for PANDAS have been inconclusive. Moreover, we lack evidence in favor of the efficacy of antibiotic prophylaxis or tonsillectomy in patients fulfilling Swedo's criteria for PANDAS, whereas a response to immune-mediated treatments like intravenous immunoglobulins has been documented by one study, but needs replication in larger trials. Overall, the available evidence does not convincingly support the concept that PANDAS are a well-defined, isolated clinical entity subdued by definite pathophysiological mechanisms; larger, prospective studies are necessary to reshape the nosography and disease mechanisms of post-streptococcal acute neuropsychiatric disorders other than SC. Research is also under way to shed further light on a possible relationship between streptococcal infections, other biological and psychosocial stressors, and the complex pathobiology of chronic tic disorders.

Project description:Host genetic variations play an important role in several pathogenic diseases, and we have previously provided strong evidences that these genetic variations contribute significantly to differences in susceptibility and clinical outcomes of invasive Group A Streptococcus (GAS) infections, including sepsis and necrotizing soft tissue infections (NSTIs). Our initial studies with conventional mouse strains revealed that host genetic variations and sex differences play an important role in orchestrating the severity, susceptibility and outcomes of NSTIs. To understand the complex genetic architecture of NSTIs, we utilized an unbiased, forward systems genetics approach in an advanced recombinant inbred (ARI) panel of mouse strains (BXD). Through this approach, we uncovered interactions between host genetics, and other non-genetic cofactors including sex, age and body weight in determining susceptibility to NSTIs. We mapped three NSTIs-associated phenotypic traits (i.e., survival, percent weight change, and lesion size) to underlying host genetic variations by using the WebQTL tool, and identified four NSTIs-associated quantitative genetic loci (QTL) for survival on mouse chromosome (Chr) 2, for weight change on Chr 7, and for lesion size on Chr 6 and 18 respectively. These QTL harbor several polymorphic genes. Identification of multiple QTL highlighted the complexity of the host-pathogen interactions involved in NSTI pathogenesis. We then analyzed and rank-ordered host candidate genes in these QTL by using the QTLminer tool and then developed a list of 375 candidate genes on the basis of annotation data and biological relevance to NSTIs. Further differential expression analyses revealed 125 genes to be significantly differentially regulated in susceptible strains compared to their uninfected controls. Several of these genes are involved in innate immunity, inflammatory response, cell growth, development and proliferation, and apoptosis. Additional network analyses using ingenuity pathway analysis (IPA) of these 125 genes revealed interleukin-1 beta network as key network involved in modulating the differential susceptibility to GAS NSTIs.

Dataset Information

A Bayesian Spatiotemporal Analysis of Pediatric Group A Streptococcal Infections.

Background

Methods

Results

Conclusions

Publications

A Bayesian Spatiotemporal Analysis of Pediatric Group A Streptococcal Infections.

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