Browsing by Author "Feikin, Daniel R."
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Item The Etiology of Pneumonia From Analysis of Lung Aspirate and Pleural Fluid Samples: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study(Clinical Infectious Diseases, 2021) Ebruke, Bernard E.; Deloria Knoll, Maria; Haddix, Meredith; Zaman, Syed M. A.; Prosperi, Christine; Feikin, Daniel R.; Hammitt, Laura L.; Levine, Orin S.; O’Brien, Katherine L.; Murdoch, David R.; Brooks, W. Abdullah; Scott, J. Anthony G.; Kotloff, Karen L.; Madhi, Shabir A.; Thea, Donald M.; Baillie, Vicky L.; Jobayer Chisti, Mohammod; Dione, Michel; Driscoll, Amanda J.; Fancourt, Nicholas; Karron, Ruth A.; Le, Tham T.; Mohamed, Shebe; Moore, David P.; Morpeth, Susan C.; Mwaba, John; Mwansa, James; Sayeem Bin Shahid, Abu Sadat Mohammad; Sow, Samba O.; Tapia, Milagritos D.; Antonio, Martin; Howie, Stephen R. C.An improved understanding of childhood pneumonia etiology is required to inform prevention and treatment strategies. Lung aspiration is the gold standard specimen for pneumonia diagnostics. We report findings from analyses of lung and pleural aspirates collected in the Pneumonia Etiology Research for Child Health (PERCH) study. Methods. The PERCH study enrolled children aged 1–59 months hospitalized with World Health Organization–defined severe or very severe pneumonia in 7 countries in Africa and Asia. Percutaneous transthoracic lung aspiration (LA) and pleural fluid (PF) aspiration was performed on a sample of pneumonia cases with radiological consolidation and/or PF in 4 countries. Venous blood and nasopharyngeal/oropharyngeal swabs were collected from all cases. Multiplex quantitative polymerase chain reaction (PCR) and routine microbiologic culture were applied to clinical specimens. Results. Of 44 LAs performed within 3 days of admission on 622 eligible cases, 13 (30%) had a pathogen identified by either culture (5/44) or by PCR (11/29). A pathogen was identified in 12/14 (86%) PF specimens tested by either culture (9/14) or PCR (9/11). Bacterial pathogens were identified more frequently than viruses. All but 1 of the cases with a virus identified were coinfected with bacterial pathogens. Streptococcus pneumoniae (9/44 [20%]) and Staphylococcus aureus (7/14 [50%]) were the predominant pathogens identified in LA and PF, respectively. Conclusions. Bacterial pathogens predominated in this selected subgroup of PERCH participants drawn from those with radiological consolidation or PF, with S. pneumoniae and S. aureus the leading pathogens identified.Item Evaluation of Pneumococcal Load in Blood by Polymerase Chain Reaction for the Diagnosis of Pneumococcal Pneumonia in Young Children in the PERCH Study(Clinical Infectious Diseases, 2017) Deloria Knoll, Maria; Morpeth, Susan C.; Scott, J. Anthony G.; Watson, Nora L.; Park, Daniel E.; Baggett, Henry C.; Brooks, W. Abdullah; Feikin, Daniel R.; Hammitt, Laura L.; Howie, Stephen R. C.; Kotloff, Karen L.; Levine, Orin S.; O’Brien, Katherine L.; Thea, Donald M.; Ahmed, Dilruba; Antonio, Martin; Awori, Juliet O.; Baillie, Vicky L.; Chipeta, James; Deluca, Andrea N.; Dione, Michel; Driscoll, Amanda J.; Higdon, Melissa M.; Jatapai, Anchalee; Karron, Ruth A.; Mazumder, Razib; Moore, David P.; Mwansa, James; Nyongesa, Sammy; Prosperi, Christine; Seidenberg, Phil; Siludjai, Duangkamon; Sow, Samba O.; Tamboura, Boubou; Zeger, Scott L.; Murdoch, David R.; Madhi, Shabir A.Detection of pneumococcus by lytA polymerase chain reaction (PCR) in blood had poor diagnostic accuracy for diagnosing pneumococcal pneumonia in children in 9 African and Asian sites. We assessed the value of blood lytA quantification in diagnosing pneumococcal pneumonia. Methods. The Pneumonia Etiology Research for Child Health (PERCH) case-control study tested whole blood by PCR for pneumococcus in children aged 1–59 months hospitalized with signs of pneumonia and in age–frequency matched community controls. The distribution of load among PCR-positive participants was compared between microbiologically confirmed pneumococcal pneumonia (MCPP) cases, cases confirmed for nonpneumococcal pathogens, nonconfirmed cases, and controls. Receiver operating characteristic analyses determined the “optimal threshold” that distinguished MCPP cases from controls. Results. Load was available for 290 of 291 cases with pneumococcal PCR detected in blood and 273 of 273 controls. Load was higher in MCPP cases than controls (median, 4.0 × 103 vs 0.19 × 103 copies/mL), but overlapped substantially (range, 0.16–989.9 × 103 copies/mL and 0.01–551.9 × 103 copies/mL, respectively). The proportion with high load (≥2.2 log10 copies/mL) was 62.5% among MCPP cases, 4.3% among nonconfirmed cases, 9.3% among cases confirmed for a nonpneumococcal pathogen, and 3.1% among controls. Pneumococcal load in blood was not associated with respiratory tract illness in controls (P = .32). High blood pneumococcal load was associated with alveolar consolidation on chest radiograph in nonconfirmed cases, and with high (>6.9 log10 copies/mL) nasopharyngeal/oropharyngeal load and C-reactive protein ≥40 mg/L (both P < .01) in nonconfirmed cases but not controls. Conclusions. Quantitative pneumococcal PCR in blood has limited diagnostic utility for identifying pneumococcal pneumonia in individual children, but may be informative in epidemiological studies.