Respiratory viruses in children with invasive pneumococcal disease.

To the Editor—We read with interest the article by Watson et al. [1], which analyzes the association of respiratory virus infections with invasive pneumococcal disease using epidemiological surveillance data. Here, we report direct documentation of respiratory viruses in children with invasive pneumococcal disease. We performed a prospective study of the occurrence of rhinoviruses, enteroviruses, and respiratory syncytial virus (RSV) in hospitalized children during a 2month period during the autumn of 2005. Children 1 month old who were hospitalized at the Infectious Disease Ward of Turku University Hospital for any reason were eligible. Symptoms of these children were systematically documented. Nasal swab specimens were examined for the presence of rhinoviruses, enteroviruses, and RSV using previously described primers in a multiplex, real-time RT-PCR with SYBR green detection (Qiagen) and melting curve analysis [2, 3]. Amplifications were confirmed with hybridization assays using specific probes [3]. Viral antigen detection in nasopharyngeal aspirates [4], as well as blood cultures for bacteria (Bactec Peds Plus/F or Bactec Plus/F; BectonDickinson), were performed when clinically indicated. The study protocol was approved by the ethics committee of Turku University Hospital, and written, informed consent was obtained from the parents of all participating children. The study included 170 hospitalization episodes among 163 children. Nine cases of bacteremic pneumococcal infections were detected among these patients. The clinical characteristics are shown in table 1. Respiratory viruses were detected in 7 (78%) of the 9 children (3 enteroviruses, 2 rhinoviruses, and 2 RSV). Respiratory symptoms preceded the development of more severe illness with high fever, suggesting that viral infection paved the way for pneumococcal invasion. Our finding lends support to the epidemiologic and laboratory studies that link invasive pneumococcal disease with respiratory virus infections, in most cases with influenza virus or RSV infection [1, 5–7]. In a report published 20 years ago [8], respiratory viruses were detected in 40% of children with bacterial meningitis using serological methods (31%) and virus isolation (15%). Respiratory viruses have not been previously studied in children with invasive bacterial infection using sensitive PCR methods. Our findings suggest that rhinovirus and enterovirus infections may be important predisposing factors for invasive pneumococcal infections in children. Rhinoviruses are the most frequent cause of respiratory infections among children and adults [4, 9]. Enteroviruses are closely related to rhinoviruses, and recent studies using RT-PCR suggest that their role in respiratory infections is much more significant than previously realized [10, 11]. The association between rhinoviruses and enteroviruses and pneumococcal infections is also supported by epidemiologic data. The biphasic pattern of pneumococcal disease in children, with peaks in the autumn and spring and a decrease in the midwinter [12, 13], is remarkably similar to the seasonal pattern of rhinovirus and enterovirus infections [14]. Studies using surveillance data do not reveal the full impact of rhinoviruses and enteroviruses on the development of invasive bacterial infections, because these viruses are rarely searched for in patients with common respiratory infections using efficient RT-PCR methods. Systematic studies of these associations are needed, because it is likely that several currently unknown interactions between viral, bacterial, and host factors play important role in the pathogenesis of infectious diseases.