Host transcriptional analysis to improve the diagnosis of group A streptococcal pharyngitis.

Current diagnostic methods used to evaluate patients with pharyngitis for the presence of group A Streptococcus (GAS) do not discriminate between acute infection and asymptomatic carriage, potentially resulting in overuse of antibiotics. Host response as measured by the transcriptomic profile of peripheral blood leukocytes could make this distinction, and could also distinguish between GAS and viral infection. We used RNA sequencing to generate transcriptomes from whole blood samples from 37 children, including 10 with acute GAS pharyngitis, 5 asymptomatic GAS carriers, 3 with adenoviral pharyngitis, 3 with pharyngitis of unknown etiology, and 16 asymptomatic children negative for GAS. Transcriptional profiles from each group were distinct . 1357 genes were upregulated in the children with symptomatic GAS compared to those with asymptomatic carriage. A panel of 13 genes distinguished between children with acute GAS and all others with 91% accuracy. The gene encoding CD177, a marker of neutrophil activation, was markedly overexpressed in children with acute GAS and has potential as a diagnostic biomarker. We conclude that measurement of host response is highly promising to improve the diagnosis of GAS pharyngitis and could help limit unnecessary antibiotic use. Overall design: A total of 37 subjects were included in the RNA-seq transcriptional analysis, of which 10 cases were with group A Streptococcus (GAS) infection, 3 cases with adenovirus infection, 3 other cases with pharyngitis by other cause, 5 controls with GAS colonized, 3 controls with positive of non-adenovirus, and 13 controls with negative of viruses tested. We comparied the GAS cases with controls and with all other subjects in terms of transcriptional changes.