The primary objective of this study was to determine the role of picornavirus in flu-like episodes (temperature of >38.0°C plus one respiratory and one constitutional symptom) among otherwise healthy adults enrolled in a placebo-controlled, double-blind, randomized oseltamivir treatment study. Combined nasal and pharyngeal swabs were collected at baseline for influenza cultures and picornavirus reverse transcription (RT)-PCR. In addition, acute-and convalescent-serum samples were obtained for serological studies of common respiratory pathogens. From a total of 719 subjects enrolled in the clinical trial within 36 h of the onset of symptoms, 475 (66%) had evidence of recent influenza A or B virus infections by means of culture and/or serological testing. Of the 244 remaining patients, 36 (15%) presented a seroconversion for at least one of the common respiratory viruses or atypical pathogens. An RT-PCR assay for the picornavirus 5 noncoding region (NCR) was positive in a subset of 15 (19%) of 78 patients with flu-like illnesses of undetermined etiology. Sequence analysis of the picornavirus 5 NCR amplicons revealed that 14 (93%) of them had greater homology to rhinoviruses, whereas 1 (7%) was related to enteroviruses. Interestingly, median total symptom scores and oral temperatures of picornavirus-positive patients (n ؍ 15) and placebo-treated influenza virus-positive patients (n ؍ 161) were similar over a 3-week period. We conclude that, among the influenza virus-negative preselected cases of this study, rhinoviruses were relatively frequent pathogens associated with important respiratory and systemic symptoms.The Picornaviridae family, which contains single-stranded RNA viruses, is divided into various genera such as Rhinovirus, Enterovirus, and Hepatovirus. Rhinoviruses are the leading cause of the common cold, a highly prevalent and benign infection of the upper respiratory tract usually devoid of significant systemic symptoms. However, it has been recently suggested that rhinoviruses may also replicate in the tracheobronchial tree and may cause viral pneumonitis in selected settings (10,14,23). The full scope of the disease burden associated with rhinovirus infections has not been completely elucidated since virus isolation is difficult and serology testing is limited by the large number (Ͼ100) of viral serotypes. The recent development of reverse transcription (RT)-PCR assays based on amplification of the conserved 5Ј noncoding region (NCR) of picornaviruses has been shown to improve significantly the detection of rhinoviruses in clinical samples (1,12,13,25). In the present study, we used the latter approach to determine the role of picornaviruses in flu-like illnesses of adults enrolled in an influenza virus neuraminidase inhibitor trial based on a stringent clinical case definition.(This work was presented in part at the Third International Symposium on Respiratory Viral Infections, 1 December 2000, St. Lucia, West Indies [abstr. P4].)
MATERIALS AND METHODS
Study population.A placebo-controlled, doub...