Pediatric Digital Auscultation and Diagnosis of Viral, Bacterial, and Mixed Etiology Severe Pneumonia
Open AccessBackground: Pneumonia and antimicrobial resistant infections are both leading causes of morbidity and mortality globally. There is a paucity of information regarding patterns and prevalence of pathogen co-detection in the upper respiratory tract (URT) of children with pneumonia in low- and middle-income countries. Furthering our understanding of pathogen co-detection may improve interpretability of increasingly common molecular diagnostics and also inform antibiotic stewardship practices, especially in the context of detecting commonly colonizing bacteria. Digital auscultation may provide utility in antibiotic stewardship algorithms. However, there is limited information on comparability of digitally recorded and remotely classified lung sounds and conventional analog auscultation. In this dissertation, we explore co-detection patterns in the URT, compare digital and conventional auscultation classification, and evaluate associations between digital auscultation classifications with URT viral and bacterial detection.Methods: This dissertation leveraged the Pneumonia Etiology for Child Health (PERCH) study, a case-control study of pediatric pneumonia etiology based in seven low- and middle-income country settings, along with the Digital Auscultation Substudy nested within PERCH. In our first analysis, we evaluated the patterns and prevalence of co-detections of 17 pathogens in the nasopharynx and oropharynx using logistic regression and decision tree analyses. High-density (HD) qPCR thresholds were utilized for some pathogens to optimize distinction between case and control prevalence (for S. pneumoniae, H. influenzae) or based on informative density thresholds from the decision tree analysis (for S. aureus, P. jirovecii, and cytomegalovirus). We evaluated clinical outcomes for co-detections of interest. In the second analysis, we evaluated the concordance of digitally recorded and remotely classified lung sounds with conventional analog auscultation classifications using prevalence- and bias-adjusted kappa values. In the third analysis, we evaluated associations between case-control status for each auscultation classification with pathogen detection, using multinomial logistic regression. Results: Cases more frequently had co-detection of multiple pathogens compared with controls (71.9% vs. 59.4%, aOR=1.52, p<0.001). Although many co-detections were associated with case status, only two pairs were observed more frequently than expected given overall prevalence (HD-H. influenzae with either HD-S. pneumoniae or influenza A/B/C). Cases with medium-density (MD) CMV with either HD-P. jirovecii or HD-S. aureus had higher mortality. Concordance between conventional and digital auscultation was fair to moderate for classifying abnormal lung sounds. Crackles on both conventional and digital auscultation were associated with increased severity, and wheeze was associated with milder disease. HD-S. pneumoniae, human metapneumovirus, and respiratory syncytial virus were associated with case status regardless of auscultation classification. Wheezing cases were more likely to have detection of parainfluenza virus 1/2/3/4 and rhinovirus, whereas cases with crackles-only were more likely to have HD-B. pertussis, H. influenzae, and P. jirovecii detected. Compared to cases without wheeze, wheezing cases had higher odds of viral detection (aOR=2.4, 95%CI 1.5-3.8) and lower odds of bacteria-only (aOR=0.58, 95%CI 0.34-0.98). Conclusion: Although co-detection of pathogens in the upper respiratory tract is common, only a few co-detections are associated with case status or severity when accounting for expected co-detection given overall prevalence. Digital auscultation is comparable to conventional analog auscultation, while adding potential benefits such as providing remote auscultation capacity to LMIC settings. Digital auscultation may differentiate pneumonia cases from controls, and to a certain extent viral from bacterial causes of pneumonia; this diagnostic value may contribute to antibiotic stewardship efforts within larger diagnostic algorithms in lower-risk patients.
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