Abstract
ABSTRACT Despite the advanced PCR-based assays available, a fraction of the pediatric respiratory infections remain unexplained every epidemic season, and there is a perception that novel viruses might be present in these specimens. We systematically collected samples from a prospective cohort of pediatric patients with respiratory infections, that returned negative results by validated molecular RT–PCR assays, and studied them with a target-independent, high-throughput sequencing-based approach. We also included a matched cohort of children with no symptoms of respiratory infection, as a contrast study population. More than fifty percent of the specimens from the group of patients with unexplained respiratory infections were resolved. However, the higher rate of detection was not due to the presence of novel viruses, but to the identification of well-known viral respiratory pathogens. Our results show that already known viral pathogens are responsible for the majority of cases that remain unexplained after the epidemic season. High-throughput sequencing approaches that use pathogen-specific probes are easier to standardize because they ensure reproducible library enrichment and sequencing. In consequence, these techniques might be desirable from a regulatory standpoint for diagnostic laboratories seeking to benefit from the many advantages of these sequencing technologies.
Highlights
The rate of discovery of new microbes and of new associations of microbes with health and disease has accelerated significantly in the last decade [1,2,3,4]
Despite the advanced PCR-based assays available, a fraction of the pediatric respiratory infections remain unexplained every epidemic season, and there is a perception that novel viruses might be present in these specimens
Our results show that already known viral pathogens are responsible for the majority of cases that remain unexplained after the epidemic season
Summary
The rate of discovery of new microbes and of new associations of microbes with health and disease has accelerated significantly in the last decade [1,2,3,4]. Many factors are contributing to this phenomenon including those that favour the true emergence of new pathogens as well as new technologies and paradigms that enable their detection and characterization [5,6,7]. New molecular technologies based on high-throughput sequencing (HTS) have facilitated discovery [7,8,9,10]. Appreciation that more than 75% of emerging infectious diseases represent zoonoses has had an impact [11]. The current accepted vision is that we are in a position to tackle effectively the problem of the detection of the “unknown known” (e.g. the unexpected rare pathogen) while true reliable agnostic pathogen discovery for detection of the “unknown unknown” (e.g. a true novel pathogen) is still an art
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