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The role of postmortem studies in pneumonia etiology research.

ABSTRACT: The diagnosis of etiology in severe pneumonia remains a challenging area. Postmortem lung tissue potentially increases the sensitivity of investigations for identification of causative pathogens in fatal cases of pneumonia and can confirm antemortem microbiological diagnoses. Tissue sampling allows assessment of histological patterns of disease and ancillary immunohistochemical or molecular diagnostic techniques. It may also enhance the recognition of noninfectious conditions that clinically simulate acute pneumonia. Biobanking of lung tissue or postmortem culture isolates offers opportunities for new pathogen discovery and research into host-pathogen interactions. The Pneumonia Etiology Research for Child Health study proposes a percutaneous needle biopsy approach to obtain postmortem samples, rather than a full open autopsy. This has the advantage of greater acceptability to relatives, but risks greater sampling error. Both approaches may be susceptible to microbiological contamination or pathogen degradation. However, previous autopsy studies have confirmed the value of histological examination in revealing unsuspected pathogens and influencing clinical guidelines for the diagnosis and treatment of future pneumonia cases.

SUBMITTER: Turner GD

PROVIDER: S-EPMC3297548 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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The role of postmortem studies in pneumonia etiology research.

Turner Gareth D H GD Bunthi Charatdao C Wonodi Chizoba B CB Morpeth Susan C SC Molyneux Catherine S CS Zaki Sherif R SR Levine Orin S OS Murdoch David R DR Scott J Anthony G JA

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20120401

The diagnosis of etiology in severe pneumonia remains a challenging area. Postmortem lung tissue potentially increases the sensitivity of investigations for identification of causative pathogens in fatal cases of pneumonia and can confirm antemortem microbiological diagnoses. Tissue sampling allows assessment of histological patterns of disease and ancillary immunohistochemical or molecular diagnostic techniques. It may also enhance the recognition of noninfectious conditions that clinically sim ...[more]

PMID: 22403232

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Project description:BackgroundPneumonia remains the leading cause of death in young children globally. The changing epidemiology of pneumonia requires up-to-date data to guide both case management and prevention programs. The Gambia study site contributed a high child mortality, high pneumonia incidence, low HIV prevalence, Haemophilus influenzae type b and pneumococcal conjugate vaccines-vaccinated rural West African setting to the Pneumonia Etiology Research for Child Health (PERCH) Study.MethodsThe PERCH study was a 7-country case-control study of the etiology of hospitalized severe pneumonia in children 1-59 months of age in low and middle-income countries. Culture and nucleic acid detection methods were used to test nasopharyngeal/oropharyngeal swabs, blood, induced sputum and, in selected cases, lung or pleural fluid aspirates. Etiology was determined by integrating case and control data from multiple specimens using the PERCH integrated analysis based on Bayesian probabilistic methods.ResultsAt The Gambia study site, 638 cases of World Health Organization-defined severe and very severe pneumonia (286 of which were chest radiograph [CXR]-positive and HIV-negative) and 654 age-frequency matched controls were enrolled. Viral causes predominated overall (viral 58% vs. bacterial 28%), and of CXR-positive cases respiratory syncytial virus (RSV) accounted for 37%, Streptococcus pneumoniae 13% and parainfluenza was responsible for 9%. Nevertheless, among very severe cases bacterial causes dominated (77% bacterial vs. 11% viral), led by S. pneumoniae (41%); Mycobacterium tuberculosis, not included in "bacterial", accounted for 9%. 93% and 80% of controls ≥1 year of age were, respectively, fully vaccinated for age against Haemophilus influenzae and S. pneumoniae.ConclusionsViral causes, notably RSV, predominated in The Gambia overall, but bacterial causes dominated the severest cases. Efforts must continue to prevent disease by optimizing access to existing vaccines, and to develop new vaccines, notably against RSV. A continued emphasis on appropriate case management of severe pneumonia remains important.

Project description:BackgroundDespite recent declines in new pediatric HIV infections and childhood HIV-related deaths, pneumonia remains the leading cause of death in HIV-infected children under 5. We describe the patient population, etiology and outcomes of childhood pneumonia in Zambian HIV-infected children.MethodsAs one of the 9 sites for the Pneumonia Etiology Research for Child Health study, we enrolled children 1-59 months of age presenting to University Teaching Hospital in Lusaka, Zambia, with World Health Organization-defined severe and very severe pneumonia. Controls frequency-matched on age group and HIV infection status were enrolled from the Lusaka Pediatric HIV Clinics as well as from the surrounding communities. Clinical assessments, chest radiographs (CXR; cases) and microbiologic samples (nasopharyngeal/oropharyngeal swabs, blood, urine, induced sputum) were obtained under highly standardized procedures. Etiology was estimated using Bayesian methods and accounted for imperfect sensitivity and specificity of measurements.ResultsOf the 617 cases and 686 controls enrolled in Zambia over a 24-month period, 103 cases (16.7%) and 85 controls (12.4%) were HIV infected and included in this analysis. Among the HIV-infected cases, 75% were <1 year of age, 35% received prophylactic trimethoprim-sulfamethoxazole, 13.6% received antiretroviral therapy and 36.9% of caregivers reported knowing their children's HIV status at time of enrollment. A total of 35% of cases had very severe pneumonia and 56.3% had infiltrates on CXR. Bacterial pathogens [50.6%, credible interval (CrI): 32.8-67.2], Pneumocystis jirovecii (24.9%, CrI: 15.5-36.2) and Mycobacterium tuberculosis (4.5%, CrI: 1.7-12.1) accounted for over 75% of the etiologic fraction among CXR-positive cases. Streptococcus pneumoniae (19.8%, CrI: 8.6-36.2) was the most common bacterial pathogen, followed by Staphylococcus aureus (12.7%, CrI: 0.0-25.9). Outcomes were poor, with 41 cases (39.8%) dying in hospital.ConclusionsHIV-infected children in Zambia with severe and very severe pneumonia have poor outcomes, with continued limited access to care, and the predominant etiologies are bacterial pathogens, P. jirovecii and M. tuberculosis.

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The role of postmortem studies in pneumonia etiology research.

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The role of postmortem studies in pneumonia etiology research.

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