Colonization Density of the Upper Respiratory Tract as a Predictor of Pneumonia—Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii

Abstract

BackgroundThere is limited information on the association between colonization density of upper respiratory tract colonizers and pathogen-specific pneumonia. We assessed this association for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii.MethodsIn 7 low- and middle-income countries, nasopharyngeal/oropharyngeal swabs from children with severe pneumonia and age-frequency matched community controls were tested using quantitative polymerase chain reaction (PCR). Differences in median colonization density were evaluated using the Wilcoxon rank-sum test. Density cutoffs were determined using receiver operating characteristic curves. Cases with a pathogen identified from lung aspirate culture or PCR, pleural fluid culture or PCR, blood culture, and immunofluorescence for P. jirovecii defined microbiologically confirmed cases for the given pathogens.ResultsHigher densities of H. influenzae were observed in both microbiologically confirmed cases and chest radiograph (CXR)-positive cases compared to controls. Staphylococcus aureus and P. jirovecii had higher densities in CXR-positive cases vs controls. A 5.9 log10 copies/mL density cutoff for H. influenzae yielded 86% sensitivity and 77% specificity for detecting microbiologically confirmed cases; however, densities overlapped between cases and controls and positive predictive values were poor (<3%). Informative density cutoffs were not found for S. aureus and M. catarrhalis, and a lack of confirmed case data limited the cutoff identification for P. jirovecii.ConclusionsThere is evidence for an association between H. influenzae colonization density and H. influenzae–confirmed pneumonia in children; the association may be particularly informative in epidemiologic studies. Colonization densities of M. catarrhalis, S. aureus, and P. jirovecii are unlikely to be of diagnostic value in clinical settings.

Metagenomic next-generation sequencing of samples from pediatric febrile illness in Tororo, Uganda

“…We found no significant difference in the SDI of upper airway samples between patients with (mean SDI = 0.51, IQR 0.37-0.65) or without (mean SDI = 0.51, IQR = 0.42-0.65; p = 0.86) diagnoses of respiratory infection (S1 Fig). [25][26][27].…”

Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping

“…S2) and the MS analyses were performed using inclusion lists with the hundred highest ranking species-unique peptides identified in the discovery phase. The number of bacterial cells per ml of sample ranged from 100 to 1 million cells/ml, reflecting the variation in the number of bacteria cells typical for nasopharyngeal/nasal swab samples; bacterial loads vary during different phases of infection and are also dependent on the pathogen (41,42). The selected range was considered to realistically reflect both weakly-and strongly-infected samples.…”

Challenges in the diagnosis of paediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group

“…For example, PERCH investigators found an average of 3·8 pathogens in all children with severe pneumonia (3·9 pathogens in those with a positive chest X-ray) and 3·6 pathogens in healthy controls, so it can be difficult to disentangle the root cause. 88 However, even with the best of methods, it is common to not find any pathogens in a substantial proportion of pneumonia episodes.…”

“…This problem is further exacerbated by the increasing recognition that childhood pneumonia is multipathogenic. 88 However, the presence of lobar consolidation, which has been recommended as an endpoint for vaccine studies, 91 might be indicative of bacterial disease.…”