Changes in Clinical Presentation and Epidemiology of Respiratory Pathogens Associated With Acute Respiratory Illness in Military Trainees After Reintroduction of Adenovirus Vaccine

Yun, Heather C.; Young, Adam N.; Caballero, Manuel Y.; Lott, Lisa; Cropper, Thomas L.; Murray, Clinton K.

cal diagnostic terms suggesting LRTI, including both bronchitis and pneumonia. It is likely that most of those labelled "pneumonia" were never confirmed with radiographs, and absence of fever with these argues against that diagnosis in this young, otherwise healthy population. The predominant organism identified among these was rhinovirus, which, while not classically associated with lower respiratory disease in healthy adults, has been described including within military training populations [28, 29] . Nevertheless, the combination of increased LRTI diagnoses, and the increase in cough as well as physical exam findings of the same, provide signal of an increase in LRTI post-VI which should be explored with targeted research. It is also considerable that, despite a relatively broad panel of respiratory pathogens targeted with molecular methods, >50% post-VI had no pathogen detected. Some of these may have been noninfectious, as suggested by the increase in clinical diagnostic terms relating to allergies, but this represents a significant research gap. The nature of respiratory illness itself in basic military trainees has changed after reintroduction of Ad vaccine, transitioning from a febrile pharyngitis marked by systemic signs and symptoms, to an afebrile, cough and coryza predominant illness. The ecologic niche occupied by vaccine-serotype Ad in this population was remarkable, causing approximately 70% of all FRI historically and with 80% of trainees infected by the end of training [4, 11] . During Ad VI in 1971, molecular methods for pathogen surveillance were not available; despite this, serotype shift was observed. Initially, Ad4 was the only serotype included in the vaccine program, but Ad7 was later added after this emerged and replaced Ad4 as the predominant cause of FRI [5] . Since that time, dozens of additional Ad serotypes and other respiratory viral pathogens such as bocavirus and human metapneumovirus have been identified. Respiratory pathogens cause outbreaks, which may come and go independently of a vaccine program's effect, so changes in frequency must be interpreted with caution. However, it is reassuring that Ad14 has not yet reemerged in this population and, in fact, decreased in frequency since VI, a finding which has been corroborated by others, and potentially related to crossprotection with Ad7 immunity [9, 16] . The decrease in frequency of influenza A was driven by the unusually high number of influenza A cases in 2009, which contributed 63 to the total of 76 during the entire study. The trend toward a decrease in S. pyogenes (with no changes in antibiotic prophylaxis during the study period) is potentially biologically plausible with viral coinfection increasing the likelihood of streptococcal illness, although specific associations between Ad and S. pyogenes have not been established, and rates of S. pyogenes illness are not known to have changed during the first iteration of the Ad vaccine program. The small increases seen in detection of M. pneumoniae, bocavirus and coronavirus OC43 may be due to chance alone or natural variation, but bear further observation. Most significant was the increase seen in detections of rhinovirus, which increased as a proportion of detected pathogens, in rates of positive tests among those tested for rhinovirus, and in raw numbers despite fewer overall enrollments. Rhinovirus may be associated with decreased probability of detecting other respiratory viral pathogens, includin