4.7 Article

Variation in Clinical Phenotype of Human Infection Among Genetic Groups of Blastomyces dermatitidis

Journal

JOURNAL OF INFECTIOUS DISEASES
Volume 207, Issue 5, Pages 814-822

Publisher

OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jis756

Keywords

Blastomyces dermatitidis; blastomycosis; virulence; population genetics; clinical phenotype; genetic groups

Funding

  1. Marshfield Clinic Research Foundation internal grant [SUL10209]
  2. Department of Pathology, Feinberg School of Medicine, Northwestern University, Evanston, Illinois

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Background. Blastomyces dermatitidis, the etiologic agent of blastomycosis, has 2 genetic groups and shows varied clinical presentation, ranging from silent infections to fulminant respiratory disease and dissemination. The objective of this study was to determine whether clinical phenotype and outcomes vary based on the infecting organism's genetic group. Methods. We used microsatellites to genotype 227 clinical isolates of B. dermatitidis from Wisconsin patients. For each isolate, corresponding clinical disease characteristics and patient demographic information were abstracted from electronic health records and Wisconsin Division of Health reportable disease forms and questionnaires. Results. In univariate analysis, group 1 isolates were more likely to be associated with pulmonary-only infections (P < .0001) and constitutional symptoms such as fever (P < .0001). In contrast, group 2 isolates were more likely to be associated with disseminated disease (P < .0001), older patient age (P < .0001), and comorbidities (P = .0019). In multivariate analysis, disease onset to diagnosis of > 1 month (P < .0001), older age at diagnosis (P < .0001), and current smoking status (P = .0001) remained predictors for group 2 infections. Conclusions. This study identified previously unknown associations between clinical phenotype of human infection and genetic groups of B. dermatitidis and provides a framework for further investigations of the genetic basis for virulence in B. dermatitidis.

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