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

Feikin, Daniel R.; Fu, Wei; Park, Daniel E.; Shi, Qiyuan; Higdon, Melissa M.; Baggett, Henry C.; Brooks, W. Abdullah; Deloria Knoll, Maria; Hammitt, Laura L.; Howie, Stephen R. C.; Kotloff, Karen L.; Levine, Orin S.; Madhi, Shabir A.; Scott, J. Anthony G.; Thea, Donald M.; Adrian, Peter V.; Antonio, Martin; Awori, Juliet O.; Baillie, Vicky L.; DeLuca, Andrea N.; Driscoll, Amanda J.; Ebruke, Bernard E.; Goswami, Doli; Karron, Ruth A.; Li, Mengying; Morpeth, Susan C.; Mwaba, John; Mwansa, James; Prosperi, Christine; Sawatwong, Pongpun; Sow, Samba O.; Tapia, Milagritos D.; Whistler, Toni; Zaman, Khalequ; Zeger, Scott L.; O’ Brien, Katherine L.; Murdoch, David R.

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.