RESUMEN
BACKGROUND: Oral human papillomavirus (HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. METHOD: A cross-sectional analysis of 5496 20-59-year-old participants in the 2009-2012 National Health and Nutrition Examination Survey was performed. Associations with oral HPV infection were assessed using multivariable logistic regression for oral microbiome α-diversity (within-sample diversity), and using principal coordinate analysis and permutational multivariate analysis of variance for ß-diversity (between-sample heterogeneity). RESULTS: Overall, for α-diversity, a lower number of observed amplicon sequence variants (adjusted odds ratio [aOR] = 0.996; 95% confidence interval [CI] = .992-.999) and reduced Faith's phylogenetic diversity (aOR = 0.95; 95% CI = .90-.99) were associated with high-risk oral HPV infection. ß-diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045). There were differential associations when stratified by sex. CONCLUSIONS: Both oral microbiome α-diversity and ß-diversity were marginally associated with oral HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.
Asunto(s)
Microbiota , Boca , Encuestas Nutricionales , Infecciones por Papillomavirus , Humanos , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/microbiología , Masculino , Femenino , Adulto , Estudios Transversales , Persona de Mediana Edad , Boca/microbiología , Boca/virología , Adulto Joven , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/clasificación , Estados Unidos/epidemiologíaRESUMEN
This paper is concerned with using multivariate binary observations to estimate the probabilities of unobserved classes with scientific meanings. We focus on the setting where additional information about sample similarities is available and represented by a rooted weighted tree. Every leaf in the given tree contains multiple samples. Shorter distances over the tree between the leaves indicate a priori higher similarity in class probability vectors. We propose a novel data integrative extension to classical latent class models with tree-structured shrinkage. The proposed approach enables (1) borrowing of information across leaves, (2) estimating data-driven leaf groups with distinct vectors of class probabilities, and (3) individual-level probabilistic class assignment given the observed multivariate binary measurements. We derive and implement a scalable posterior inference algorithm in a variational Bayes framework. Extensive simulations show more accurate estimation of class probabilities than alternatives that suboptimally use the additional sample similarity information. A zoonotic infectious disease application is used to illustrate the proposed approach. The paper concludes by a brief discussion on model limitations and extensions.
Asunto(s)
Algoritmos , Teorema de Bayes , ProbabilidadRESUMEN
The COVID-19 pandemic has spread through the US during the last few months exposing healthcare providers to possible infection. Here we report testing of emergency department (ED) healthcare providers (HCP) for exposure to COVID-19 through lateral flow point of care (POC) and lab-based enzyme-linked immunosorbent assay (ELISA), and RTq-PCR for evidence of acute infection. 138 ED HCP were tested between May 26th (approximately one month after the peak of COVID-19 first wave of cases) and June 14th. Enrolled ED HCP represented about 70% of the total ED HCP workforce during the study period. Subjects were tested with a POC COVID-19 antibody test, and standard ELISA performed by a university-based research lab. Subjects also provided a mid-turbinate swab and a saliva specimen for RTq-PCR. All subjects provided demographic information, past medical history, information about personal protective equipment (PPE) use, COVID-19 symptoms, as well as potential COVID-19 exposures during the previous 4 weeks, both in the ED, and outside the clinical setting. None of the HCP had positive RT-PCR results; 7 HCP (5%) had positive IgG for COVID-19; there was strong agreement between the lab-based ELISA (reference test) and the POC Ab test (P ≤ 0.0001). For the POC Ab test there were no false negatives and only one false positive among the 138 participants. There was no significant difference in demographic/ethnic variables, past medical history, hours worked in the ED, PPE use, or concerning exposures between seropositive and seronegative individuals. Moreover, there was no significant difference in reported symptoms between the two groups during the previous four weeks. The rate of COVID-19 seroconversion in our ED was 5% during the month following the pandemic's first wave. Based on questionnaire responses, differences in demographics/ethnicity, medical history, COVID-19 exposures, and PPE use were not associated with ED HCP having been infected with SARS-CoV-2. In the setting of our limited cohort of subjects the COVID-19 POC Ab test performed comparably to the ELISA lab-based standard.
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COVID-19/epidemiología , Servicio de Urgencia en Hospital , Personal de Salud/estadística & datos numéricos , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/virología , Exposición Profesional/estadística & datos numéricos , Centros Médicos Académicos , Adulto , Estudios de Cohortes , Femenino , Humanos , Masculino , Estados UnidosRESUMEN
Many pneumonia etiology case-control studies exclude controls with respiratory illness from enrollment or analyses. Herein we argue that selecting controls regardless of respiratory symptoms provides the least biased estimates of pneumonia etiology. We review 3 reasons investigators may choose to exclude controls with respiratory symptoms in light of epidemiologic principles of control selection and present data from the Pneumonia Etiology Research for Child Health (PERCH) study where relevant to assess their validity. We conclude that exclusion of controls with respiratory symptoms will result in biased estimates of etiology. Randomly selected community controls, with or without respiratory symptoms, as long as they do not meet the criteria for case-defining pneumonia, are most representative of the general population from which cases arose and the least subject to selection bias.
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Diseño de Investigaciones Epidemiológicas , Neumonía/etiología , Proyectos de Investigación , Infecciones del Sistema Respiratorio , Niño , Interpretación Estadística de Datos , Femenino , Humanos , Masculino , Estudios Multicéntricos como Asunto , Neumonía/epidemiología , Neumonía Bacteriana/epidemiología , Neumonía Viral/epidemiología , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/etiología , Factores de Riesgo , Sesgo de SelecciónRESUMEN
The Pneumonia Etiology Research for Child Health (PERCH) study is the largest multicountry etiology study of pediatric pneumonia undertaken in the past 3 decades. The study enrolled 4232 hospitalized cases and 5325 controls over 2 years across 9 research sites in 7 countries in Africa and Asia. The volume and complexity of data collection in PERCH presented considerable logistical and technical challenges. The project chose an internet-based data entry system to allow real-time access to the data, enabling the project to monitor and clean incoming data and perform preliminary analyses throughout the study. To ensure high-quality data, the project developed comprehensive quality indicator, data query, and monitoring reports. Among the approximately 9000 cases and controls, analyzable laboratory results were available for ≥96% of core specimens collected. Selected approaches to data management in PERCH may be extended to the planning and organization of international studies of similar scope and complexity.
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Exactitud de los Datos , Recolección de Datos , Sistemas de Administración de Bases de Datos , Neumonía/diagnóstico , Neumonía/etiología , África , Asia , Estudios de Casos y Controles , Niño , Técnicas de Laboratorio Clínico , Humanos , Internacionalidad , Neumonía Bacteriana/diagnóstico , Neumonía Viral/diagnósticoRESUMEN
In pneumonia, specimens are rarely obtained directly from the infection site, the lung, so the pathogen causing infection is determined indirectly from multiple tests on peripheral clinical specimens, which may have imperfect and uncertain sensitivity and specificity, so inference about the cause is complex. Analytic approaches have included expert review of case-only results, case-control logistic regression, latent class analysis, and attributable fraction, but each has serious limitations and none naturally integrate multiple test results. The Pneumonia Etiology Research for Child Health (PERCH) study required an analytic solution appropriate for a case-control design that could incorporate evidence from multiple specimens from cases and controls and that accounted for measurement error. We describe a Bayesian integrated approach we developed that combined and extended elements of attributable fraction and latent class analyses to meet some of these challenges and illustrate the advantage it confers regarding the challenges identified for other methods.
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Teorema de Bayes , Modelos Estadísticos , Neumonía/epidemiología , Neumonía/etiología , Investigación Biomédica , Estudios de Casos y Controles , Niño , Salud Infantil , Técnicas de Diagnóstico del Sistema Respiratorio , Diseño de Investigaciones Epidemiológicas , Humanos , Neumonía/diagnóstico , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/epidemiología , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Sensibilidad y EspecificidadRESUMEN
BACKGROUND.: Variable adherence to standardized case definitions, clinical procedures, specimen collection techniques, and laboratory methods has complicated the interpretation of previous multicenter pneumonia etiology studies. To circumvent these problems, a program of clinical standardization was embedded in the Pneumonia Etiology Research for Child Health (PERCH) study. METHODS.: Between March 2011 and August 2013, standardized training on the PERCH case definition, clinical procedures, and collection of laboratory specimens was delivered to 331 clinical staff at 9 study sites in 7 countries (The Gambia, Kenya, Mali, South Africa, Zambia, Thailand, and Bangladesh), through 32 on-site courses and a training website. Staff competency was assessed throughout 24 months of enrollment with multiple-choice question (MCQ) examinations, a video quiz, and checklist evaluations of practical skills. RESULTS.: MCQ evaluation was confined to 158 clinical staff members who enrolled PERCH cases and controls, with scores obtained for >86% of eligible staff at each time-point. Median scores after baseline training were ≥80%, and improved by 10 percentage points with refresher training, with no significant intersite differences. Percentage agreement with the clinical trainer on the presence or absence of clinical signs on video clips was high (≥89%), with interobserver concordance being substantial to high (AC1 statistic, 0.62-0.82) for 5 of 6 signs assessed. Staff attained median scores of >90% in checklist evaluations of practical skills. CONCLUSIONS.: Satisfactory clinical standardization was achieved within and across all PERCH sites, providing reassurance that any etiological or clinical differences observed across the study sites are true differences, and not attributable to differences in application of the clinical case definition, interpretation of clinical signs, or in techniques used for clinical measurements or specimen collection.
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Técnicas de Laboratorio Clínico/normas , Neumonía/diagnóstico , Neumonía/etiología , Manejo de Especímenes/normas , Bangladesh , Niño , Interpretación Estadística de Datos , Diseño de Investigaciones Epidemiológicas , Femenino , Gambia , Hospitales , Humanos , Internacionalidad , Kenia , Masculino , Malí , Estudios Multicéntricos como Asunto/normas , Neumonía/tratamiento farmacológico , Neumonía/prevención & control , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/epidemiología , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Sudáfrica , Tailandia , ZambiaRESUMEN
BACKGROUND.: Induced sputum (IS) may provide diagnostic information about the etiology of pneumonia. The safety of this procedure across a heterogeneous population with severe pneumonia in low- and middle-income countries has not been described. METHODS.: IS specimens were obtained as part a 7-country study of the etiology of severe and very severe pneumonia in hospitalized children <5 years of age. Rigorous clinical monitoring was done before, during, and after the procedure to record oxygen requirement, oxygen saturation, respiratory rate, consciousness level, and other evidence of clinical deterioration. Criteria for IS contraindications were predefined and serious adverse events (SAEs) were reported to ethics committees and a central safety monitor. RESULTS.: A total of 4653 IS procedures were done among 3802 children. Thirteen SAEs were reported in relation to collection of IS, or 0.34% of children with at least 1 IS specimen collected (95% confidence interval, 0.15%-0.53%). A drop in oxygen saturation that required supplemental oxygen was the most common SAE. One child died after feeding was reinitiated 2 hours after undergoing sputum induction; this death was categorized as "possibly related" to the procedure. CONCLUSIONS.: The overall frequency of SAEs was very low, and the nature of most SAEs was manageable, demonstrating a low-risk safety profile for IS collection even among severely ill children in low-income-country settings. Healthcare providers should monitor oxygen saturation and requirements during and after IS collection, and assess patients prior to reinitiating feeding after the IS procedure, to ensure patient safety.
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Neumonía/diagnóstico , Neumonía/etiología , Manejo de Especímenes/efectos adversos , Esputo , Bacterias/aislamiento & purificación , Preescolar , Femenino , Humanos , Lactante , Masculino , Oxígeno , Pobreza , Manejo de Especímenes/métodosRESUMEN
BACKGROUND.: It is standard practice for laboratories to assess the cellular quality of expectorated sputum specimens to check that they originated from the lower respiratory tract. The presence of low numbers of squamous epithelial cells (SECs) and high numbers of polymorphonuclear (PMN) cells are regarded as indicative of a lower respiratory tract specimen. However, these quality ratings have never been evaluated for induced sputum specimens from children with suspected pneumonia. METHODS.: We evaluated induced sputum Gram stain smears and cultures from hospitalized children aged 1-59 months enrolled in a large study of community-acquired pneumonia. We hypothesized that a specimen representative of the lower respiratory tract will contain smaller quantities of oropharyngeal flora and be more likely to have a predominance of potential pathogens compared to a specimen containing mainly saliva. The prevalence of potential pathogens cultured from induced sputum specimens and quantity of oropharyngeal flora were compared for different quantities of SECs and PMNs. RESULTS.: Of 3772 induced sputum specimens, 2608 (69%) had <10 SECs per low-power field (LPF) and 2350 (62%) had >25 PMNs per LPF, measures traditionally associated with specimens from the lower respiratory tract in adults. Using isolation of low quantities of oropharyngeal flora and higher prevalence of potential pathogens as markers of higher quality, <10 SECs per LPF (but not >25 PMNs per LPF) was the microscopic variable most associated with high quality of induced sputum. CONCLUSIONS.: Quantity of SECs may be a useful quality measure of induced sputum from young children with pneumonia.
Asunto(s)
Neumonía Bacteriana/diagnóstico , Neumonía/diagnóstico , Neumonía/etiología , Neumonía/microbiología , Esputo/citología , Esputo/microbiología , Bacterias/aislamiento & purificación , Bacterias/ultraestructura , Salud Infantil , Preescolar , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/etiología , Células Epiteliales/ultraestructura , Femenino , Hospitalización , Humanos , Lactante , Recién Nacido , Masculino , Neutrófilos/ultraestructura , Neumonía Bacteriana/microbiología , Infecciones del Sistema Respiratorio/diagnóstico , Infecciones del Sistema Respiratorio/microbiología , Saliva/citología , Saliva/microbiología , Manejo de EspecímenesRESUMEN
BACKGROUND.: Chest radiographs (CXRs) are frequently used to assess pneumonia cases. Variations in CXR appearances between epidemiological settings and their correlation with clinical signs are not well documented. METHODS.: The Pneumonia Etiology Research for Child Health project enrolled 4232 cases of hospitalized World Health Organization (WHO)-defined severe and very severe pneumonia from 9 sites in 7 countries (Bangladesh, the Gambia, Kenya, Mali, South Africa, Thailand, and Zambia). At admission, each case underwent a standardized assessment of clinical signs and pneumonia risk factors by trained health personnel, and a CXR was taken that was interpreted using the standardized WHO methodology. CXRs were categorized as abnormal (consolidation and/or other infiltrate), normal, or uninterpretable. RESULTS.: CXRs were interpretable in 3587 (85%) cases, of which 1935 (54%) were abnormal (site range, 35%-64%). Cases with abnormal CXRs were more likely than those with normal CXRs to have hypoxemia (45% vs 26%), crackles (69% vs 62%), tachypnea (85% vs 80%), or fever (20% vs 16%) and less likely to have wheeze (30% vs 38%; all P < .05). CXR consolidation was associated with a higher case fatality ratio at 30-day follow-up (13.5%) compared to other infiltrate (4.7%) or normal (4.9%) CXRs. CONCLUSIONS.: Clinically diagnosed pneumonia cases with abnormal CXRs were more likely to have signs typically associated with pneumonia. However, CXR-normal cases were common, and clinical signs considered indicative of pneumonia were present in substantial proportions of these cases. CXR-consolidation cases represent a group with an increased likelihood of death at 30 days post-discharge.
Asunto(s)
Neumonía/diagnóstico por imagen , Neumonía/etiología , Radiografía Torácica , Australia , Bangladesh , Salud Infantil , Preescolar , Femenino , Gambia , Humanos , Lactante , Recién Nacido , Internacionalidad , Kenia , Masculino , Malí , Neumonía/epidemiología , Neumonía/mortalidad , Neumonía Bacteriana/diagnóstico por imagen , Neumonía Bacteriana/epidemiología , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/epidemiología , Sudáfrica , Tailandia , Organización Mundial de la Salud , ZambiaRESUMEN
BACKGROUND.: Sputum microscopy and culture are commonly used for diagnosing the cause of pneumonia in adults but are rarely performed in children due to difficulties in obtaining specimens. Induced sputum is occasionally used to investigate lower respiratory infections in children but has not been widely used in pneumonia etiology studies. METHODS.: We evaluated the diagnostic utility of induced sputum microscopy and culture in patients enrolled in the Pneumonia Etiology Research for Child Health (PERCH) study, a large study of community-acquired pneumonia in children aged 1-59 months. Comparisons were made between induced sputum samples from hospitalized children with radiographically confirmed pneumonia and children categorized as nonpneumonia (due to the absence of prespecified clinical and laboratory signs and absence of infiltrate on chest radiograph). RESULTS.: One induced sputum sample was available for analysis from 3772 (89.1%) of 4232 suspected pneumonia cases enrolled in PERCH. Of these, sputum from 2608 (69.1%) met the quality criterion of <10 squamous epithelial cells per low-power field, and 1162 (44.6%) had radiographic pneumonia. Induced sputum microscopy and culture results were not associated with radiographic pneumonia, regardless of prior antibiotic use, stratification by specific bacteria, or interpretative criteria used. CONCLUSIONS.: The findings of this study do not support the culture of induced sputum specimens as a diagnostic tool for pneumonia in young children as part of routine clinical practice.
Asunto(s)
Microscopía/métodos , Neumonía Bacteriana/diagnóstico , Neumonía/diagnóstico , Neumonía/etiología , Infecciones del Sistema Respiratorio/diagnóstico , Esputo/microbiología , Adulto , Bacterias/aislamiento & purificación , Bacterias/ultraestructura , Preescolar , Infecciones Comunitarias Adquiridas/diagnóstico , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Neumonía/microbiología , Neumonía Bacteriana/microbiología , Infecciones del Sistema Respiratorio/microbiologíaRESUMEN
BACKGROUND.: Sputum examination can be useful in diagnosing the cause of pneumonia in adults but is less well established in children. We sought to assess the diagnostic utility of polymerase chain reaction (PCR) for detection of respiratory viruses and bacteria in induced sputum (IS) specimens from children hospitalized with severe or very severe pneumonia. METHODS.: Among children aged 1-59 months, we compared organism detection by multiplex PCR in IS and nasopharyngeal/oropharyngeal (NP/OP) specimens. To assess whether organism presence or density in IS specimens was associated with chest radiographic evidence of pneumonia (radiographic pneumonia), we compared prevalence and density in IS specimens from children with radiographic pneumonia and children with suspected pneumonia but without chest radiographic changes or clinical or laboratory findings suggestive of pneumonia (nonpneumonia group). RESULTS.: Among 4232 cases with World Health Organization-defined severe or very severe pneumonia, we identified 1935 (45.7%) with radiographic pneumonia and 573 (13.5%) with nonpneumonia. The organism detection yield was marginally improved with IS specimens (96.2% vs 92.4% for NP/OP specimens for all viruses combined [P = .41]; 96.9% vs 93.3% for all bacteria combined [P = .01]). After accounting for presence in NP/OP specimens, no organism was detected more frequently in the IS specimens from the radiographic pneumonia compared with the nonpneumonia cases. Among high-quality IS specimens, there were no statistically significant differences in organism density, except with cytomegalovirus, for which there was a higher quantity in the IS specimens from cases with radiographic pneumonia compared with the nonpneumonia cases (median cycle threshold value, 27.9 vs 28.5, respectively; P = .01). CONCLUSIONS.: Using advanced molecular methods with IS specimens provided little additional diagnostic information beyond that obtained with NP/OP swab specimens.
Asunto(s)
Neumonía/diagnóstico , Neumonía/etiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Esputo/microbiología , Bacterias/genética , Bacterias/aislamiento & purificación , Salud Infantil , Niño Hospitalizado/estadística & datos numéricos , Preescolar , Infecciones Comunitarias Adquiridas/diagnóstico , Infecciones Comunitarias Adquiridas/microbiología , Infecciones Comunitarias Adquiridas/virología , Femenino , Recursos en Salud , Humanos , Lactante , Recién Nacido , Pulmón/diagnóstico por imagen , Pulmón/microbiología , Pulmón/virología , Masculino , Técnicas de Diagnóstico Molecular , Nasofaringe/microbiología , Nasofaringe/virología , Neumonía/microbiología , Neumonía/virología , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/microbiología , Neumonía Viral/diagnóstico , Neumonía Viral/microbiología , Sistema Respiratorio , Virus/genética , Virus/aislamiento & purificaciónRESUMEN
BACKGROUND.: Previous studies suggested an association between upper airway pneumococcal colonization density and pneumococcal pneumonia, but data in children are limited. Using data from the Pneumonia Etiology Research for Child Health (PERCH) study, we assessed this potential association. METHODS.: PERCH is a case-control study in 7 countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. Cases were children aged 1-59 months hospitalized with World Health Organization-defined severe or very severe pneumonia. Controls were randomly selected from the community. Microbiologically confirmed pneumococcal pneumonia (MCPP) was confirmed by detection of pneumococcus in a relevant normally sterile body fluid. Colonization density was calculated with quantitative polymerase chain reaction analysis of nasopharyngeal/oropharyngeal specimens. RESULTS.: Median colonization density among 56 cases with MCPP (MCPP cases; 17.28 × 106 copies/mL) exceeded that of cases without MCPP (non-MCPP cases; 0.75 × 106) and controls (0.60 × 106) (each P < .001). The optimal density for discriminating MCPP cases from controls using the Youden index was >6.9 log10 copies/mL; overall, the sensitivity was 64% and the specificity 92%, with variable performance by site. The threshold was lower (≥4.4 log10 copies/mL) when MCPP cases were distinguished from controls who received antibiotics before specimen collection. Among the 4035 non-MCPP cases, 500 (12%) had pneumococcal colonization density >6.9 log10 copies/mL; above this cutoff was associated with alveolar consolidation at chest radiography, very severe pneumonia, oxygen saturation <92%, C-reactive protein ≥40 mg/L, and lack of antibiotic pretreatment (all P< .001). CONCLUSIONS.: Pneumococcal colonization density >6.9 log10 copies/mL was strongly associated with MCPP and could be used to improve estimates of pneumococcal pneumonia prevalence in childhood pneumonia studies. Our findings do not support its use for individual diagnosis in a clinical setting.
Asunto(s)
Neumonía Neumocócica/diagnóstico , Neumonía Neumocócica/microbiología , Infecciones del Sistema Respiratorio/microbiología , Streptococcus pneumoniae/crecimiento & desarrollo , Streptococcus pneumoniae/aislamiento & purificación , Carga Bacteriana , Técnicas Bacteriológicas , Bangladesh , Estudios de Casos y Controles , Salud Infantil , Niño Hospitalizado , Preescolar , Femenino , Gambia , Humanos , Lactante , Recién Nacido , Kenia , Masculino , Malí , Neumonía Neumocócica/etiología , Reacción en Cadena de la Polimerasa , Infecciones del Sistema Respiratorio/diagnóstico , Sudáfrica , Streptococcus pneumoniae/genética , Tailandia , ZambiaRESUMEN
BACKGROUND.: Antibiotic exposure and specimen volume are known to affect pathogen detection by culture. Here we assess their effects on bacterial pathogen detection by both culture and polymerase chain reaction (PCR) in children. METHODS.: PERCH (Pneumonia Etiology Research for Child Health) is a case-control study of pneumonia in children aged 1-59 months investigating pathogens in blood, nasopharyngeal/oropharyngeal (NP/OP) swabs, and induced sputum by culture and PCR. Antibiotic exposure was ascertained by serum bioassay, and for cases, by a record of antibiotic treatment prior to specimen collection. Inoculated blood culture bottles were weighed to estimate volume. RESULTS.: Antibiotic exposure ranged by specimen type from 43.5% to 81.7% in 4223 cases and was detected in 2.3% of 4863 controls. Antibiotics were associated with a 45% reduction in blood culture yield and approximately 20% reduction in yield from induced sputum culture. Reduction in yield of Streptococcus pneumoniae from NP culture was approximately 30% in cases and approximately 32% in controls. Several bacteria had significant but marginal reductions (by 5%-7%) in detection by PCR in NP/OP swabs from both cases and controls, with the exception of S. pneumoniae in exposed controls, which was detected 25% less frequently compared to nonexposed controls. Bacterial detection in induced sputum by PCR decreased 7% for exposed compared to nonexposed cases. For every additional 1 mL of blood culture specimen collected, microbial yield increased 0.51% (95% confidence interval, 0.47%-0.54%), from 2% when volume was ≤1 mL to approximately 6% for ≥3 mL. CONCLUSIONS.: Antibiotic exposure and blood culture volume affect detection of bacterial pathogens in children with pneumonia and should be accounted for in studies of etiology and in clinical management.
Asunto(s)
Antibacterianos/uso terapéutico , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/microbiología , Antibacterianos/administración & dosificación , Bacterias/genética , Bacterias/patogenicidad , Técnicas Bacteriológicas , Estudios de Casos y Controles , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Internacionalidad , Masculino , Técnicas de Diagnóstico Molecular , Nasofaringe/microbiología , Orofaringe/microbiología , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/etiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Esputo/microbiología , Streptococcus pneumoniae/genéticaRESUMEN
BACKGROUND.: 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. METHODS.: 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. RESULTS.: 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. CONCLUSIONS.: 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.
Asunto(s)
Haemophilus influenzae/crecimiento & desarrollo , Moraxella catarrhalis/crecimiento & desarrollo , Pneumocystis carinii/crecimiento & desarrollo , Neumonía Bacteriana/diagnóstico , Neumonía por Pneumocystis/diagnóstico , Infecciones del Sistema Respiratorio/microbiología , Staphylococcus aureus/crecimiento & desarrollo , Preescolar , Femenino , Infecciones por Haemophilus/diagnóstico , Infecciones por Haemophilus/microbiología , Haemophilus influenzae/genética , Haemophilus influenzae/aislamiento & purificación , Humanos , Lactante , Masculino , Moraxella catarrhalis/genética , Moraxella catarrhalis/aislamiento & purificación , Infecciones por Moraxellaceae/diagnóstico , Infecciones por Moraxellaceae/microbiología , Nasofaringe/microbiología , Orofaringe/microbiología , Pneumocystis carinii/genética , Pneumocystis carinii/aislamiento & purificación , Neumonía Bacteriana/diagnóstico por imagen , Neumonía Bacteriana/etiología , Neumonía Bacteriana/microbiología , Neumonía por Pneumocystis/microbiología , Neumonía Estafilocócica/diagnóstico , Neumonía Estafilocócica/microbiología , Reacción en Cadena de la Polimerasa , Curva ROC , Staphylococcus aureus/genética , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
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.
Asunto(s)
ADN Bacteriano/sangre , Neumonía Neumocócica/diagnóstico , Streptococcus pneumoniae/aislamiento & purificación , Niño Hospitalizado , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Internacionalidad , Masculino , N-Acetil Muramoil-L-Alanina Amidasa/genética , Neumonía Neumocócica/microbiología , Reacción en Cadena de la Polimerasa/métodos , Pobreza , Sensibilidad y Especificidad , Streptococcus pneumoniae/genéticaRESUMEN
BACKGROUND.: The etiologic inference of identifying a pathogen in the upper respiratory tract (URT) of children with pneumonia is unclear. To determine if viral load could provide evidence of causality of pneumonia, we compared viral load in the URT of children with World Health Organization-defined severe and very severe pneumonia and age-matched community controls. METHODS.: In the 9 developing country sites, nasopharyngeal/oropharyngeal swabs from children with and without pneumonia were tested using quantitative real-time polymerase chain reaction for 17 viruses. The association of viral load with case status was evaluated using logistic regression. Receiver operating characteristic (ROC) curves were constructed to determine optimal discriminatory viral load cutoffs. Viral load density distributions were plotted. RESULTS.: The mean viral load was higher in cases than controls for 7 viruses. However, there was substantial overlap in viral load distribution of cases and controls for all viruses. ROC curves to determine the optimal viral load cutoff produced an area under the curve of <0.80 for all viruses, suggesting poor to fair discrimination between cases and controls. Fatal and very severe pneumonia cases did not have higher viral load than less severe cases for most viruses. CONCLUSIONS.: Although we found higher viral loads among pneumonia cases than controls for some viruses, the utility in using viral load of URT specimens to define viral pneumonia was equivocal. Our analysis was limited by lack of a gold standard for viral pneumonia.
Asunto(s)
Neumonía Viral/diagnóstico , Neumonía Viral/virología , Infecciones del Sistema Respiratorio/virología , Carga Viral , Estudios de Casos y Controles , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Internacionalidad , Modelos Logísticos , Masculino , Nasofaringe/virología , Orofaringe/virología , Neumonía Viral/diagnóstico por imagen , Curva ROC , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitiales Respiratorios/crecimiento & desarrollo , Virus Sincitiales Respiratorios/aislamiento & purificación , Infecciones del Sistema Respiratorio/microbiología , Virus/crecimiento & desarrollo , Virus/aislamiento & purificación , Organización Mundial de la SaludRESUMEN
BACKGROUND.: 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.
Asunto(s)
Carga Bacteriana , ADN Bacteriano/sangre , Neumonía Neumocócica/diagnóstico , Neumonía Neumocócica/microbiología , Streptococcus pneumoniae/fisiología , Estudios de Casos y Controles , Preescolar , Femenino , Genes Bacterianos , Humanos , Lactante , Recién Nacido , Internacionalidad , Masculino , Nasofaringe/microbiología , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/aislamiento & purificaciónRESUMEN
BACKGROUND.: Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study. METHODS.: We measured serum CRP levels in cases with World Health Organization-defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for "confirmed" bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to "RSV pneumonia" (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases. RESULTS.: Among 601 human immunodeficiency virus (HIV)-negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity. CONCLUSIONS.: Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study.
Asunto(s)
Proteína C-Reactiva/análisis , Neumonía Bacteriana/diagnóstico , Neumonía Viral/diagnóstico , Bacterias/genética , Bacterias/aislamiento & purificación , Biomarcadores/sangre , Estudios de Casos y Controles , Preescolar , Infecciones Comunitarias Adquiridas/diagnóstico , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Nasofaringe/virología , Orofaringe/virología , Neumonía Bacteriana/microbiología , Neumonía Viral/virología , Reacción en Cadena de la Polimerasa , Curva ROC , Infecciones por Virus Sincitial Respiratorio/sangre , Virus Sincitial Respiratorio Humano/genética , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Few data exist describing pertussis epidemiology among infants and children in low- and middle-income countries to guide preventive strategies. METHODS: Children 1-59 months of age hospitalized with World Health Organization-defined severe or very severe pneumonia in 7 African and Asian countries and similarly aged community controls were enrolled in the Pneumonia Etiology Research for Child Health study. They underwent a standardized clinical evaluation and provided nasopharyngeal and oropharyngeal swabs and induced sputum (cases only) for Bordetella pertussis polymerase chain reaction. Risk factors and pertussis-associated clinical findings were identified. RESULTS: Bordetella pertussis was detected in 53 of 4200 (1.3%) cases and 11 of 5196 (0.2%) controls. In the age stratum 1-5 months, 40 (2.3% of 1721) cases were positive, all from African sites, as were 8 (0.5% of 1617) controls. Pertussis-positive African cases 1-5 months old, compared to controls, were more often human immunodeficiency virus (HIV) uninfected-exposed (adjusted odds ratio [aOR], 2.2), unvaccinated (aOR, 3.7), underweight (aOR, 6.3), and too young to be immunized (aOR, 16.1) (all P ≤ .05). Compared with pertussis-negative African cases in this age group, pertussis-positive cases were younger, more likely to vomit (aOR, 2.6), to cough ≥14 days (aOR, 6.3), to have leukocyte counts >20 000 cells/µL (aOR, 4.6), and to have lymphocyte counts >10 000 cells/µL (aOR, 7.2) (all P ≤ .05). The case fatality ratio of pertussis-infected pneumonia cases 1-5 months of age was 12.5% (95% confidence interval, 4.2%-26.8%; 5/40); pertussis was identified in 3.7% of 137 in-hospital deaths among African cases in this age group. CONCLUSIONS: In the postneonatal period, pertussis causes a small fraction of hospitalized pneumonia cases and deaths; however, case fatality is substantial. The propensity to infect unvaccinated infants and those at risk for insufficient immunity (too young to be vaccinated, premature, HIV-infected/exposed) suggests that the role for maternal vaccination should be considered along with efforts to reduce exposure to risk factors and to optimize childhood pertussis vaccination coverage.