Limited Utility of Polymerase Chain Reaction in Induced Sputum Specimens for Determining the Causes of Childhood Pneumonia in Resource-Poor Settings: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study

Thea, Donald M.; Seidenberg, Phil; Park, Daniel E.; Mwananyanda, Lawrence; Fu, Wei; Shi, Qiyuan; Baggett, Henry C.; Brooks, W. Abdullah; Feikin, Daniel R.; Howie, Stephen R. C.; Knoll, Maria Deloria; Kotloff, Karen L.; Levine, Orin S.; Madhi, Shabir А.; O’Brien, Katherine L.; Scott, John A.; Antonio, Martín; Awori, Juliet O.; Baillie, Vicky L.; DeLuca, Andrea N.; Driscoll, Amanda J.; Higdon, Melissa M.; Hossain, Lokman; Jahan, Yasmin; Karron, Ruth A.; Kazungu, Sidi; Li, Mengying; Moore, David P.; Morpeth, Susan; Ofordile, Ogochukwu; Prosperi, Christine; Sangwichian, Ornuma; Sawatwong, Pongpun; Sylla, Mamadou; Tapia, Milagritos D.; Zeger, Scott L.; Murdoch, David R.; Hammitt, Laura L.

doi:10.1093/cid/cix098

Cited by 31 publications

(57 citation statements)

References 30 publications

(39 reference statements)

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“…Utilizing P. jirovecii detection from induced sputum PCR is widely accepted in clinical practice and would have expanded our sample of microbiologically confirmed cases [35, 36]. However, these diagnostic tests are typically carried out when Pneumocystis pneumonia is clinically suspected; findings from the PERCH study complicate the utility of induced sputum PCR as a confirmatory diagnostic tool in settings where nearly all cases had an induced sputum specimen collected [37]. …”

Section: Discussionmentioning

confidence: 99%

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

Park

Src

et al. 2017

Clinical Infectious Diseases

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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.

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Section: Discussionmentioning

confidence: 99%

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

Park

Src

et al. 2017

Clinical Infectious Diseases

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“…Induced sputum requires specialised equipment and can be onerous to collect, with evidence showing that it does not provide additional diagnostic information when using standard microbiology or molecular methods beyond that obtained from nasopharyngeal or oropharyngeal samples. 83,84 Serological tests can have variable sensitivities. Lung or pleural fluid aspirates are invasive and difficult to collect.…”

Section: Aetiology Detectionmentioning

confidence: 99%

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

Goodman¹,

Pervaiz²,

McCollum³

et al. 2019

The Lancet Respiratory Medicine

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Pneumonia is a leading killer of children younger than 5 years despite high vaccination coverage, improved nutrition, and widespread implementation of the Integrated Management of Childhood Illnesses algorithm. Assessing the effect of interventions on childhood pneumonia is challenging because the choice of case definition and surveillance approach can affect the identification of pneumonia substantially. In anticipation of an intervention trial aimed to reduce childhood pneumonia by lowering household air pollution, we created a working group to provide recommendations regarding study design and implementation. We suggest to, first, select a standard case definition that combines acute (≤14 days) respiratory symptoms and signs and general danger signs with ancillary tests (such as chest imaging and pulse oximetry) to improve pneumonia identification; second, to prioritise active hospital-based pneumonia surveillance over passive case finding or home-based surveillance to reduce the risk of non-differential misclassification of pneumonia and, as a result, a reduced effect size in a randomised trial; and, lastly, to consider longitudinal follow-up of children younger than 1 year, as this age group has the highest incidence of severe pneumonia.

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“…9,[12][13][14] However, there is ongoing concern whether the results reflect the exact cause of LRI. 17 In this study, Staphylococcus aureus and Streptococcus pneumonia were the most frequently detected bacterial agents. Although S. pneumonia was the most common bacteria identified in children with LRI, the clinical implication of S. aureus detection remains obscure 3 .…”

Section: Discussionmentioning

confidence: 75%

Prevalence of respiratory pathogens during two consecutive respiratory syncytial virus seasons at a tertiary medical care center

2019

Arch Argent Pediat

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Aim: To determine the etiological profiles of lower respiratory tract infection (LRI) in neonates during respiratory syncytial virus(RSV) season, and to define the clinical features of RSV-related infection and others. Methods: The retrospective study included newborn infants who were hospitalized for LRI during the two consecutive RSV seasons, and then tested for possible etiological agent by multiplex real-time polymerase chain reaction. All relevant data were reviewed, and the clinical characteristics of RSV-related infection were compared to those of others. Results: Of 224 patients, 160 (71 %) were positive for at least one potentially causative agent. Of them, 65 % had RSV, and 15 % had more than on ecausative agent (co-infection). The RSV group had more the findings of respiratory distress (p< 0.01), abnormal chest radiography (p< 0.01), need for intensive care (p< 0.01), and duration of oxygen requirement (p< 0.01) but less fever on admission and duration of antibiotic use (for both, p< 0.01), and no longer hospital stay. Need of intensive care nursery was more common in patients with co-infection than others (25 % vs. 6.5 %, p< 0.01). Conclusion: This study highlighted that RSV was the most frequent agent in neonates hospitalized for LRI during the season, with a more severe clinical course than other detected pathogens. The disease severity of RSV infection may have seemed to be increased by the presence of coinfection and abnormal chest radiography.

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Limited Utility of Polymerase Chain Reaction in Induced Sputum Specimens for Determining the Causes of Childhood Pneumonia in Resource-Poor Settings: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study

Abstract: SummaryAmong children with chest radiograph–confirmed pneumonia, polymerase chain reaction demonstrated relatively few additional pathogens in induced sputum specimens compared with nasopharyngeal/oropharyngeal specimens.

Cited by 31 publications

References 30 publications

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

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

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

Prevalence of respiratory pathogens during two consecutive respiratory syncytial virus seasons at a tertiary medical care center

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