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Colonization Density of the Upper Respiratory Tract as a Predictor of Pneumonia-Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, and Pneumocystis jirovecii. 2017
Daniel E Park, and
Henry C Baggett, and
Stephen R C Howie, and
Qiyuan Shi, and
Nora L Watson, and
W Abdullah Brooks, and
Maria Deloria Knoll, and
Laura L Hammitt, and
Karen L Kotloff, and
Orin S Levine, and
Shabir A Madhi, and
David R Murdoch, and
Katherine L O'Brien, and
J Anthony G Scott, and
Donald M Thea, and
Dilruba Ahmed, and
Martin Antonio, and
Vicky L Baillie, and
Andrea N DeLuca, and
Amanda J Driscoll, and
Wei Fu, and
Caroline W Gitahi, and
Emmanuel Olutunde, and
Melissa M Higdon, and
Lokman Hossain, and
Ruth A Karron, and
Abdoul Aziz Maiga, and
Susan A Maloney, and
David P Moore, and
Susan C Morpeth, and
John Mwaba, and
Musaku Mwenechanya, and
Christine Prosperi, and
Mamadou Sylla, and
Somsak Thamthitiwat, and
Scott L Zeger, and
Daniel R Feikin, and
Department of International Health, International Vaccine Access Center, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
There 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. In 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. Higher 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. There 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.
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