Roleof Picornaviruses in Flu-Like Illnesses of Adults Enrolled in anOseltamivir Treatment Study Who Had No Evidence of Influenza VirusInfection

Abstract

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...

Practical Implementation of a Multiplex PCR for Acute Respiratory Tract Infections in Children

“…These findings are in line with reports that rhinovirus does cause a number of lower respiratory tract infections (21). In hematologic cancer patients requiring bronchoalveolar lavage, in bronchopulmonary dysplasia patients, and in adults and children with exacerbated asthma, rhinovirus proved to be a serious pathogen (4,6,8,14,24,29). Similar to a previous report, we found that more children with infected with rhinovirus had been ill no longer than 2 days before presentation compared to the RSV-infected children (P Ͻ 0.01 [chi-square analysis]), indicating more serious disease (22).…”

Influenza and rhinovirus infections among health‐care workers

“…The design of the study did not allow investigation of rhinovirus infection in patients with mild symptoms. However, Boivin and collaborators did assess the role of rhinoviruses as a frequent pathogen associated with important respiratory and systemic symptoms among health volunteers, during the influenza season 5 . Those results strongly suggested that rhinovirus contributed to the maintenance of the myth that inactivated influenza vaccine could cause the flu.…”

“…Other viruses usually more related to common cold clinical presentation may account for some misconception. In this context, Boivin et al 5 . reported the role of picornaviruses in flu‐like illnesses in adults.…”

Quantification of the Influenza Virus Load by Real‐Time Polymerase Chain Reaction in Nasopharyngeal Swabs of Patients Treated with Oseltamivir

“…The trial included ambulatory patients (13-70 years) who sought care within 48 h of the onset of a flu syndrome, which consisted of fever (temperature у37.8ЊC) plus у2 of the following symptoms: cough, sore throat, coryza, myalgia, headache, fatigue, and chills/sweats. The total-symptom score at baseline was calculated by recording the presence and severity of all flu symptoms on a 4-point scale [6,7]. All patients received 75 mg of oseltamivir twice a day for 5 days, with swabs collected before onset of treatment (day 1) and after 48 h of treatment with oseltamivir (day 3).…”