REAL-TIME MOLECULAR EPIDEMIOLOGIC ANALYSIS OF AN OUTBREAK OF STREPTOCOCCUS-PYOGENES INVASIVE DISEASE IN US AIR-FORCE TRAINEES

Objective.-To determine if molecular epidemiologic techniques, includi ng comparative automated DNA sequencing of polymorphic virulence genes , could be used in the course of a bacterial disease outbreak to unamb iguously determine clonal relationships among implicated strains. Desi gn.-Strains recovered from all patients with invasive infections and a sample of carriers were analyzed by multilocus enzyme electrophoresis and automated DNA sequencing of a gene encoding an extracellular prot ease and a highly polymorphic part of the streptokinase gene. Setting. -A US Air Force training facility in San Antonio, Tex. Patients.-A squ adron with about 800 Air Force trainees, including three recruits with invasive Streptococcus pyogenes infections. Results.-Multilocus enzym e electrophoresis and automated DNA sequencing of polymorphic virulenc e genes unambiguously defined person-to-person spread of an otherwise rare S pyogenes clone in the course of the disease outbreak and clarif ied strain relationships in real time. Conclusions.-Molecular strain c haracterization techniques can be employed rapidly in a disease outbre ak to definitively resolve complex relationships among pathogenic bact eria, infer patterns of clone spread, and help formulate rational publ ic health control measures. The approach has broad applicability to ot her infectious agents.