Is Higher Viral Load in the Upper Respiratory Tract Associated With Severe Pneumonia? Findings From the PERCH Study

Abstract

Background.The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of causality of pneumonia, we compared viral load in the URT of children with World Health Organization–defined severe and very severe pneumonia and age-matched community controls.Methods.In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted.Results.The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of <0.80 for all viruses, suggesting poor to fair discrimination between cases and controls. Fatal and very severe pneumonia cases did not have higher viral load than less severe cases for most viruses.Conclusions.Although we found higher viral loads among pneumonia cases than controls for some viruses, the utility in using viral load of URT specimens to define viral pneumonia was equivocal. Our analysis was limited by lack of a gold standard for viral pneumonia.

Reassessment of high prevalence human adenovirus detections among residents of two refugee centers in Kenya under surveillance for acute respiratory infections

“…Although our study lacked controls, similar findings might be expected. Studies have also found higher virus loads in patients with HAdV‐associated ARI than those of matched asymptomatic controls . Codetections with other respiratory viruses were also common among HAdV‐positive patients, consistent with other studies of childhood ARI .…”

“…Studies have also found higher virus loads in patients with HAdV-associated ARI than those of matched asymptomatic controls. [39][40][41] Codetections with other respiratory viruses were also common among HAdV-positive patients, consistent with other studies of childhood ARI. 37 This study had several important limitations.…”

Assessment of an Antibody-in-Lymphocyte Supernatant Assay for the Etiological Diagnosis of Pneumococcal Pneumonia in Children

“…Similar findings have been reported from other epidemiological settings (Scott et al, 1996;Johnson et al, 2010). We chose NP carriage (as detected by PCR) of influenza or parainfluenza virus, and RSV to represent viral pneumonia since carriage of these viruses was associated with radiographically-confirmed pneumonia in the PERCH study (Feikin et al, 2017a).…”

Association between semi-quantitative microbial load and respiratory symptoms among Thai military recruits: a prospective cohort study

“…Previous studies assessing the association of viral load with clinical symptoms of respiratory infections reported similar findings. Mean viral load for rhinovirus and six additional viruses was significantly higher in upper respiratory tract aspirates from children with pneumonia compared to healthy controls, but the overlap in viral load distribution was substantial [22]. In pediatric patients, high rhinovirus load was associated with the presence of lower respiratory tract symptoms [23,24], but a threshold for clinical relevance could only be determined if rhinovirus was the sole agent identified [24].…”