Improvement of pneumococcal pneumonia diagnostics by the use of rt-PCR on plasma and respiratory samples

Špik, Vesna Cvitković; Beović, Bojana; Pokorn, Marko; Torkar, Ana Drole; Vidmar, Darja; Papst, Lea; Seme, Katja; Kogoj, Rok; Premru, Manica Müller

doi:10.3109/00365548.2013.804631

Cited by 29 publications

(14 citation statements)

References 24 publications

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“…The South African study also used serum rather than whole blood [10]. In Slovenia, pneumococcal PCR was positive from plasma in 2 of 29 (6.9%) children with a nonpneumonia acute febrile illness for which a nonpneumococcal cause was identified [19]. Both of the children who tested positive were colonized with pneumococcus.…”

Section: Discussionmentioning

confidence: 99%

Detection of Pneumococcal DNA in Blood by Polymerase Chain Reaction for Diagnosing Pneumococcal Pneumonia in Young Children From Low- and Middle-Income Countries

Morpeth

Knoll

Scott

et al. 2017

Clinical Infectious Diseases

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Background.We investigated the performance of polymerase chain reaction (PCR) on blood in the diagnosis of pneumococcal pneumonia among children from 7 low- and middle-income countries.Methods.We tested blood by PCR for the pneumococcal autolysin gene in children aged 1–59 months in the Pneumonia Etiology Research for Child Health (PERCH) study. Children had World Health Organization–defined severe or very severe pneumonia or were age-frequency–matched community controls. Additionally, we tested blood from general pediatric admissions in Kilifi, Kenya, a PERCH site. The proportion PCR-positive was compared among cases with microbiologically confirmed pneumococcal pneumonia (MCPP), cases without a confirmed bacterial infection (nonconfirmed), cases confirmed for nonpneumococcal bacteria, and controls.Results.In PERCH, 7.3% (n = 291/3995) of cases and 5.5% (n = 273/4987) of controls were blood pneumococcal PCR-positive (P < .001), compared with 64.3% (n = 36/56) of MCPP cases and 6.3% (n = 243/3832) of nonconfirmed cases (P < .001). Blood pneumococcal PCR positivity was higher in children from the 5 African countries (5.5%–11.5% among cases and 5.3%–10.2% among controls) than from the 2 Asian countries (1.3% and 1.0% among cases and 0.8% and 0.8% among controls). Among Kilifi general pediatric admissions, 3.9% (n = 274/6968) were PCR-positive, including 61.7% (n = 37/60) of those with positive blood cultures for pneumococcus.Discussion.The utility of pneumococcal PCR on blood for diagnosing childhood pneumococcal pneumonia in the 7 low- and middle-income countries studied is limited by poor specificity and by poor sensitivity among MCPP cases.

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Section: Discussionmentioning

confidence: 99%

Detection of Pneumococcal DNA in Blood by Polymerase Chain Reaction for Diagnosing Pneumococcal Pneumonia in Young Children From Low- and Middle-Income Countries

Morpeth

Knoll

Scott

et al. 2017

Clinical Infectious Diseases

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“…106 Several studies have described substantially enhanced detection of S pneumoniae in blood samples using real time PCR targeting the lytA gene of the pneumococcus, compared with blood culture. [107][108][109] However recent results from the multicenter Pneumonia Etiology Research for Child Health (PERCH) study showed both poor sensitivity (64%; 36/56 microbiologically confirmed pneumococcal pneumonia cases were PCR positive) and specificity (5.5%; 273/4987 of non-pneumonia controls were PCR positive). 110 These results illustrate the need for Reducing contamination of samples Samples that are less likely to be contaminated by upper respiratory flora may be less prone to problems of interpretation.…”

Section: Value Of Different Specimen Types and Associated Diagnostic mentioning

confidence: 99%

“…Serological testing of blood specimens may be useful for epidemiological studies of the cause of pneumonia, where comparison of acute and convalescent titers may help identify the causative agent, [93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112] although the diagnostic value of a single specimen collected in the acute phase of the illness is generally limited. Pertussis serology may be a useful complementary diagnostic tool in older children and during the later phases of illness.…”

Section: Emerging Diagnosticsmentioning

confidence: 99%

Advances in the diagnosis of pneumonia in children

Zar

Andronikou

Nicol

2017

BMJ

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Pneumonia remains a major cause of childhood mortality and morbidity globally. Accurate diagnosis and attribution of the causes of pneumonia are important for measuring the burden of disease, implementing appropriate preventive or treatment strategies, and developing more effective interventions. This review summarizes recent diagnostic advances in radiological techniques, specimen collection, and laboratory methods. Although chest ultrasound and chest magnetic resonance imaging are promising modalities for radiological diagnosis, their role in clinical management and their impact on outcomes need further study. Rapid, highly sensitive, multiplex laboratory tests performed on upper respiratory tract samples or induced sputum can detect nucleic acid from potential pathogens in most children with pneumonia. However, it may be difficult to attribute causality because it is often impossible to distinguish between organisms colonizing or infecting the upper respiratory tract and those causing pneumonia. Currently available host biomarkers lack accuracy for distinguishing bacterial or mixed bacterial-viral infections from viral infections. New biomarkers derived from host transcriptional profile analysis may be more accurate but require validation. Prospective studies with appropriate control populations, including studies of clinical impact, are needed to improve our understanding of the role of tests. Although progress has been made in radiological techniques and laboratory testing, current methods for diagnosing and attributing the causes of pneumonia are suboptimal.

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“…The identification of S. pneumoniae can be significantly improved by using molecular biology methods which, albeit with some exceptions, have been found to be significantly more reliable than the traditional non-enriched cultures used in routine practice 59 and, although S. pneumoniae is bet sampled nasopharyngeally in infants and young children, 60 recent studies have shown that oropharyngeal sampling is better in older children, adolescents and adults. 61,62 Finally, it is still unclear exactly when the effect of a vaccine on carriage should be evaluated.…”

Section: Main Limitationsmentioning

confidence: 99%

Serological criteria and carriage measurement for evaluation of new pneumococcal vaccines

Principi

Esposito

2015

Human Vaccines & Immunotherapeutics

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The best method of evaluating the efficacy of a vaccine is to compare the incidence of the disease against which it is prepared in randomized, placebo-controlled clinical trials involving vaccinated and unvaccinated subjects. In the case of Streptococcus pneumoniae, the proposed alternatives are evaluations of the so-called "correlates of protection" (i.e. markers of the vaccine-induced immune response that predict protection from infection and disease) and nasopharyngeal carriage. The aim of this paper is to discuss the most important limitations of the immunological criteria suggested for licensing new pneumococcal vaccines, and comment on the use of carriage as an endpoint for evaluating efficacy. Data showed why the use of a single serological correlate of protection cannot be considered the best means of evaluating pneumococcal vaccines and highlighted the importance of using carriage for efficacy evaluation but in the meantime the need to develop new sensitive and specific methods.

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Improvement of pneumococcal pneumonia diagnostics by the use of rt-PCR on plasma and respiratory samples

Abstract: rt-PCR on plasma and other samples performed significantly better than culture for the detection of pneumococcal pneumonia (p < 0.0005) in children and adults.

Cited by 29 publications

References 24 publications

Detection of Pneumococcal DNA in Blood by Polymerase Chain Reaction for Diagnosing Pneumococcal Pneumonia in Young Children From Low- and Middle-Income Countries

Detection of Pneumococcal DNA in Blood by Polymerase Chain Reaction for Diagnosing Pneumococcal Pneumonia in Young Children From Low- and Middle-Income Countries

Advances in the diagnosis of pneumonia in children

Serological criteria and carriage measurement for evaluation of new pneumococcal vaccines

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