Streptococcal pharyngitis: Diagnostic and statistical implications of a national clinical care standard on population outcomes

Streptococcus pyogenes is a significant clinical pathogen; the most common treatable cause of pharyngitis with many correlated complications including acute rheumatic fever. The microbial, clinical and statistical issues related to the proper diagnosis of S. pyogenes pharyngitis are complex. The understanding of how new diagnostic tests, the standards of study design and analysis, and national guidelines impact the overall diagnosis and treatment of S. pyogenes pharyngitis on a nationwide population basis is the scope of this thesis, which is a compilation of three distinct but related studies. Integral to the diagnosis of strep pharyngitis is an understanding of how diagnostic tests are evaluated and compared. The sensitivity of strep rapid antigen tests vary greatly and without standard study designs and gold standards of comparison, measures of these tests are not comparable. The first study compares two strep rapid antigen tests against a defined culture gold standard. The comparison culture gold standard that most accurately predicts truth in disease status is defined and the sensitivity and specificity of both rapid antigen tests are described. We propose that the "culture gold standard" for the comparison of rapid antigen tests for the diagnosis of S. pyogenes pharyngitis be defined as a least two separate swabs, plated on selective agar, and performed in a clinical microbiology laboratory. The second study uses the National Ambulatory Medical Care Survey (NAMCS) dataset from 1997--1999 to describe the compliance of clinicians to the American Academy of Pediatrics (AAP) guidelines for the diagnosis and treatment of S. pyogenes pharyngitis. This study shows that low compliance to these guidelines may lead to nearly a million cases of S. pyogenes pharyngitis being missed each year. The third study compares three diagnostic strategies, including the current AAP strategy and shows that ultimately clinicians must currently choose between the value of a higher sensitivity strategy or the value of a strategy that gives diagnostic information at the time of visit. In summary, this thesis attempts to review the microbiological, clinical and statistical issues that are integral to the diagnosis and treatment of S. pyogenes pharyngitis.