RESUMO
This study evaluated the impact of human immunodeficiency virus (HIV) and combination antiretroviral therapy (cART) on immune activation during pregnancy in a Zambian cohort of HIV-exposed but uninfected children followed up from birth. Activated CD8+ T cells (CD38+ and HLA-DR+) were compared among HIV-uninfected (nâ =â 95), cART experienced HIV-infected (nâ =â 111), and cART-naive HIV-infected (nâ =â 21) pregnant women. Immune activation was highest among HIV-infected/cART-naive women but decreased during pregnancy. Immune activation HIV-infected women who started cART during pregnancy was reduced but not to levels similar to those in HIV-uninfected women. The effects of elevated maternal immune activation in pregnancy on subsequent infant health and immunity remain to be determined.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Antígenos HLA-DR , Humanos , Lactente , Recém-Nascido , Gravidez , GestantesRESUMO
BACKGROUND: The majority of pediatric human immunodeficiency virus (HIV) cases in Africa reflect maternal-to-child transmission. HIV exposed but uninfected (HEU) children have increased rates of morbidity and mortality when compared to HIV unexposed and uninfected (HUU) children. The mechanisms behind these unexpected trends are only partially understood but could be explained by the differences in the immune response to infections triggered by an altered immune system state. METHODS: Using quantitative reverse transcription polymerase chain reaction, we compared the nasopharyngeal carriage prevalence and density of Streptococcus pneumoniae (SP) and Pneumocystis jirovecii (PJ) between children living with HIV and HEU or HUU cases (pneumonia) and controls (without pneumonia). RESULTS: The cohort included 1154 children (555 cases and 599 matched controls). The SP carriage prevalence rates were similar between cases and controls. Among SP carriers with pneumonia, carriage density was increased among children living with HIV, versus HEU or HUU children (15.8, 4.7, and 3.6 × 105 copies/mL, respectively). The rate of PJ carriage was significantly higher among children living with HIV than among HEU and HUU children (31%, 15%, and 10%, respectively; Pâ <â .05), as was carriage density (63.9, 20.9, and 4.8 × 103 copies/mL, respectively; Pâ <â .05). CONCLUSIONS: Carriage prevalences and densities for SP and PJ show different kinetics in terms of their relationship with HIV exposure and clinical status, particularly for Pneumocystis jirovecii. This supports the theory that the increased morbidity and mortality observed among HEU children may reflect deficits not just in humoral immunity but in cell-mediated immunity as well.
Assuntos
Infecções por HIV , Pneumocystis carinii , Pneumonia , África , Estudos de Casos e Controles , Criança , Saúde da Criança , HIV , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Lactente , Streptococcus pneumoniaeRESUMO
BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of infant deaths. Its epidemiology in low- and middle-income countries is poorly understood. Risk factors associated with RSV-associated infant deaths that occur in community settings are incompletely known. METHODS: Community deaths for infants aged 4 days to 6 months were identified during a 3-year postmortem RSV prevalence study at the main city morgue in Lusaka, Zambia, where 80% of deaths are registered. This analysis focuses on the subset of deaths for which an abbreviated verbal autopsy was available and intended to sort deaths into respiratory or nonrespiratory causes by clinical adjudication. Posterior nasopharyngeal swab samples were collected within 48 hours of death and tested for RSV using quantitative reverse-transcription polymerase chain reaction. Associations between potential risk factors were determined as relative risks with 95% confidence intervals (CIs). RESULTS: We prospectively enrolled 798 community infant deaths with verbal autopsies and RSV laboratory results, of which 62 results were positive. The mean age of the infants was 10 weeks, and 41.4% of them were male. Of all deaths, 44% were attributed to respiratory causes. RSV was detected in 7.8% of the community infants and was significantly associated with respiratory deaths (risk ratio, 4.0 [95% CI, 2.2-7.1]). Compared with older infants, those aged 0-8 weeks had a 2.83 (95% CI, 1.30-6.15) increased risk of dying with RSV. The risk of RSV for the 0-8-week age group increased to 5.24 (1.56-33.14) with adjustment for demographics, parental education, and geography. RSV deaths were increased with domiciliary overcrowding and were concentrated in poor and dense neighborhoods in Lusaka (risk ratio, 2.00 [95% CI, 1.22-3.27]). CONCLUSION: RSV is a significant contributor to community respiratory deaths in this population, particularly in the first 3 months of life and in the more poor and dense parts of Lusaka.
Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Hospitalização , Humanos , Lactente , Masculino , Prevalência , Infecções por Vírus Respiratório Sincicial/epidemiologia , Fatores de Risco , Zâmbia/epidemiologiaRESUMO
BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections and child mortality. While RSV disease burden is highest in low- and middle-income countries, most knowledge about risk factors for fatal RSV disease comes from high-income settings. METHODS: Among infants aged 4 days to <6 months who died at University Teaching Hospital in Lusaka, Zambia, we tested nasopharyngeal swabs obtained postmortem for RSV using reverse transcriptase-quantitative polymerase chain reaction. Through a systematic review of death certificates and hospital records, we identified 10 broad categories of underlying medical conditions associated with infant deaths. We used backward-selection models to calculate adjusted and unadjusted risk ratios (RRs) for the association between each underlying condition and RSV status. RESULTS: From 720 infant deaths, 6% (44) were RSV-positive, 70% were <4 weeks old, and 54% were male. At least 1 underlying condition was found in 85% of infants, while 63% had ≥2. Prematurity/low birth weight (53% [384]) and complications of labor and delivery (32% [230]) were the most common conditions. Congenital cardiac conditions were significantly associated with an increased risk of RSV infection (4%, 32; adjusted RR: 3.57; 95% CI: 1.71-7.44). No other underlying conditions were significantly associated with RSV. CONCLUSIONS: Other than congenital cardiac conditions, we found a lack of association between RSV and underlying risk factors. This differs from high-income settings, where RSV mortality is concentrated among high-risk infants. In this population, birth-related outcomes are the highest mortality risk factors. Improved neonatal care remains crucial in the fight against neonatal mortality.
Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Criança , Hospitais de Ensino , Humanos , Lactente , Recém-Nascido , Masculino , Infecções por Vírus Respiratório Sincicial/epidemiologia , Fatores de Risco , Universidades , Zâmbia/epidemiologiaRESUMO
BACKGROUND: Although much has been learned about the pathophysiology of coronavirus disease 2019 (COVID-19) infections, pathology data from patients who have died of COVID-19 in low- and middle-income country settings remain sparse. We integrated minimally invasive tissue sampling (MITS) into an ongoing postmortem surveillance study of COVID-19 in deceased individuals of all ages in Lusaka, Zambia. METHODS: We enrolled deceased subjects from the University Teaching Hospital Morgue in Lusaka, Zambia within 48 hours of death. We collected clinical and demographic information, a nasopharyngeal swab, and core tissue biopsies from the lung, liver, and kidneys for pathologic analysis. Individuals were considered eligible for MITS if they had a respiratory syndrome prior to death or a COVID-19+ polymerase chain reaction (PCR) nasopharyngeal swab specimen. Samples were retested using quantitative reverse transcriptase PCR. RESULTS: From June to September 2020 we performed MITS on 29 deceased individuals. PCR results were available for 28/29 (96.5%) cases. Three had a COVID-19+ diagnosis antemortem, and 5 more were identified postmortem using the recommended cycle threshold cut-point <40. When expanding the PCR threshold to 40 ≤ cycle threshold (Ct) ≤ 45, we identified 1 additional case. Most cases were male and occurred in the community The median age at death was 47 years (range 40-64). Human immunodeficiency virus (HIV)/AIDS, tuberculosis, and diabetes were more common among the COVID-19+ cases. Diffuse alveolar damage and interstitial pneumonitis were common among COVID-19+ cases; nonspecific findings of hepatic steatosis and acute kidney injury were also prevalent in the COVID-19+ group. Vascular thrombi were rarely detected. CONCLUSIONS: Lung abnormalities typical of viral pneumonias were common among deceased COVID-19+ individuals, as were nonspecific findings in the liver and kidneys. Pulmonary vascular thrombi were rarely detected, which could be a limitation of the MITS technique. Nonetheless, MITS offers a valuable alternative to open autopsy for understanding pathological changes due to COVID-19.
Assuntos
COVID-19 , Adulto , Autopsia , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Síndrome , Zâmbia/epidemiologiaRESUMO
BACKGROUND: 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.
Assuntos
Percas , Pneumonia , Animais , Teorema de Bayes , Estudos de Casos e Controles , Criança , Saúde da Criança , Pré-Escolar , Países em Desenvolvimento , Humanos , Lactente , Pulmão , Gravidade do Paciente , Pneumonia/diagnóstico , Pneumonia/etiologia , Pneumonia/prevenção & controle , Fatores de Risco , Staphylococcus aureusRESUMO
BACKGROUND: In 2015, pneumonia remained the leading cause of mortality in children aged 1-59 months. METHODS: Data from 1802 human immunodeficiency virus (HIV)-negative children aged 1-59 months enrolled in the Pneumonia Etiology Research for Child Health (PERCH) study with severe or very severe pneumonia during 2011-2014 were used to build a parsimonious multivariable model predicting mortality using backwards stepwise logistic regression. The PERCH severity score, derived from model coefficients, was validated on a second, temporally discrete dataset of a further 1819 cases and compared to other available scores using the C statistic. RESULTS: Predictors of mortality, across 7 low- and middle-income countries, were age <1 year, female sex, ≥3 days of illness prior to presentation to hospital, low weight for height, unresponsiveness, deep breathing, hypoxemia, grunting, and the absence of cough. The model discriminated well between those who died and those who survived (C statistic = 0.84), but the predictive capacity of the PERCH 5-stratum score derived from the coefficients was moderate (C statistic = 0.76). The performance of the Respiratory Index of Severity in Children score was similar (C statistic = 0.76). The number of World Health Organization (WHO) danger signs demonstrated the highest discrimination (C statistic = 0.82; 1.5% died if no danger signs, 10% if 1 danger sign, and 33% if ≥2 danger signs). CONCLUSIONS: The PERCH severity score could be used to interpret geographic variations in pneumonia mortality and etiology. The number of WHO danger signs on presentation to hospital could be the most useful of the currently available tools to aid clinical management of pneumonia.
Assuntos
Países em Desenvolvimento , Pneumonia , Criança , Pré-Escolar , Feminino , HIV , Hospitais , Humanos , Lactente , Pneumonia/epidemiologia , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Globally, most deaths due to childhood pneumonia occur at the community level. Some countries are still using oral co-trimoxazole, despite a World Health Organization recommendation of oral amoxicillin for the treatment of fast-breathing pneumonia in children at the community level. METHODS: We conducted an unblinded, cluster-randomized, controlled-equivalency trial in Haripur District, Pakistan. Children 2-59 months of age with fast-breathing pneumonia were treated with oral amoxicillin suspension (50 mg/kg/day) for 3 days in 14 intervention clusters and oral co-trimoxazole suspension (8 mg trimethoprim/kg and 40 mg sulfamethoxazole/kg/day) for 5 days in 14 control clusters by lady health workers (LHW). The primary outcome was treatment failure by day 4 for intervention clusters and by day 6 for control clusters. The analysis was per protocol. RESULTS: Out of the 15 749 cases enrolled in the study, 9153 cases in intervention and 6509 cases in control clusters were included in the analysis. Treatment failure rates were 3.6% (326) in intervention clusters and 9.1% (592) in control clusters. After adjusting for clustering, the risk of treatment failure was lower in intervention clusters (risk diï¬erence [RD] -5.5%, 95% confidence interval [CI] -7.4--3.7%) than in control clusters. Children with incomplete adherence had a small increase in treatment failure versus those with complete adherence (RD 2.9%, 95% CI 1.6-4.1%). No deaths or serious adverse events occurred. CONCLUSIONS: A 3-day course of oral amoxicillin, administered by LHWs, is an effective and safe treatment for fast-breathing pneumonia in children 2-59 months of age. A shorter course of amoxicillin improves adherence to therapy, is low in cost, and puts less pressure on antimicrobial resistance. CLINICAL TRIALS REGISTRATION: ISRCTN10618300.
Assuntos
Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Pneumonia Bacteriana/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Administração Oral , Pré-Escolar , Esquema de Medicação , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Paquistão , Estudos Retrospectivos , Falha de TratamentoRESUMO
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.
Assuntos
Projetos de Pesquisa Epidemiológica , Pneumonia/etiologia , Projetos de Pesquisa , Infecções Respiratórias , Criança , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Estudos Multicêntricos como Assunto , Pneumonia/epidemiologia , Pneumonia Bacteriana/epidemiologia , Pneumonia Viral/epidemiologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/etiologia , Fatores de Risco , Viés de SeleçãoRESUMO
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.
Assuntos
Teorema de Bayes , Modelos Estatísticos , Pneumonia/epidemiologia , Pneumonia/etiologia , Pesquisa Biomédica , Estudos de Casos e Controles , Criança , Saúde da Criança , Técnicas de Diagnóstico do Sistema Respiratório , Projetos de Pesquisa Epidemiológica , Humanos , Pneumonia/diagnóstico , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Sensibilidade e EspecificidadeRESUMO
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.
Assuntos
Técnicas de Laboratório Clínico/normas , Pneumonia/diagnóstico , Pneumonia/etiologia , Manejo de Espécimes/normas , Bangladesh , Criança , Interpretação Estatística de Dados , Projetos de Pesquisa Epidemiológica , Feminino , Gâmbia , Hospitais , Humanos , Internacionalidade , Quênia , Masculino , Mali , Estudos Multicêntricos como Assunto/normas , Pneumonia/tratamento farmacológico , Pneumonia/prevenção & controle , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , África do Sul , Tailândia , ZâmbiaRESUMO
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.
Assuntos
Pneumonia/diagnóstico , Pneumonia/etiologia , Manejo de Espécimes/efeitos adversos , Escarro , Bactérias/isolamento & purificação , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Oxigênio , Pobreza , Manejo de Espécimes/métodosRESUMO
The Pneumonia Etiology Research for Child Health study was conducted across 7 diverse research sites and relied on standardized clinical and laboratory methods for the accurate and meaningful interpretation of pneumonia etiology data. Blood, respiratory specimens, and urine were collected from children aged 1-59 months hospitalized with severe or very severe pneumonia and community controls of the same age without severe pneumonia and were tested with an extensive array of laboratory diagnostic tests. A standardized testing algorithm and standard operating procedures were applied across all study sites. Site laboratories received uniform training, equipment, and reagents for core testing methods. Standardization was further assured by routine teleconferences, in-person meetings, site monitoring visits, and internal and external quality assurance testing. Targeted confirmatory testing and testing by specialized assays were done at a central reference laboratory.
Assuntos
Técnicas de Laboratório Clínico/normas , Pneumonia/diagnóstico , Pneumonia/etiologia , Manejo de Espécimes/normas , Algoritmos , Pré-Escolar , Confiabilidade dos Dados , Feminino , Infecções por HIV , Humanos , Lactente , Masculino , Pneumonia Bacteriana/diagnóstico , Pneumonia Viral/diagnóstico , Controle de Qualidade , Padrões de Referência , Infecções Respiratórias/etiologiaRESUMO
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.
Assuntos
Pneumonia Bacteriana/diagnóstico , Pneumonia/diagnóstico , Pneumonia/etiologia , Pneumonia/microbiologia , Escarro/citologia , Escarro/microbiologia , Bactérias/isolamento & purificação , Bactérias/ultraestrutura , Saúde da Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/etiologia , Células Epiteliais/ultraestrutura , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Neutrófilos/ultraestrutura , Pneumonia Bacteriana/microbiologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/microbiologia , Saliva/citologia , Saliva/microbiologia , Manejo de EspécimesRESUMO
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.
Assuntos
Pneumonia/diagnóstico por imagem , Pneumonia/etiologia , Radiografia Torácica , Austrália , Bangladesh , Saúde da Criança , Pré-Escolar , Feminino , Gâmbia , Humanos , Lactente , Recém-Nascido , Internacionalidade , Quênia , Masculino , Mali , Pneumonia/epidemiologia , Pneumonia/mortalidade , Pneumonia Bacteriana/diagnóstico por imagem , Pneumonia Bacteriana/epidemiologia , Pneumonia Viral/diagnóstico por imagem , Pneumonia Viral/epidemiologia , África do Sul , Tailândia , Organização Mundial da Saúde , ZâmbiaRESUMO
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.
Assuntos
Microscopia/métodos , Pneumonia Bacteriana/diagnóstico , Pneumonia/diagnóstico , Pneumonia/etiologia , Infecções Respiratórias/diagnóstico , Escarro/microbiologia , Adulto , Bactérias/isolamento & purificação , Bactérias/ultraestrutura , Pré-Escolar , Infecções Comunitárias Adquiridas/diagnóstico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pneumonia/microbiologia , Pneumonia Bacteriana/microbiologia , Infecções Respiratórias/microbiologiaRESUMO
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.
Assuntos
Pneumonia/diagnóstico , Pneumonia/etiologia , Reação em Cadeia da Polimerase em Tempo Real , Escarro/microbiologia , Bactérias/genética , Bactérias/isolamento & purificação , Saúde da Criança , Criança Hospitalizada/estatística & dados numéricos , Pré-Escolar , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/virologia , Feminino , Recursos em Saúde , Humanos , Lactente , Recém-Nascido , Pulmão/diagnóstico por imagem , Pulmão/microbiologia , Pulmão/virologia , Masculino , Técnicas de Diagnóstico Molecular , Nasofaringe/microbiologia , Nasofaringe/virologia , Pneumonia/microbiologia , Pneumonia/virologia , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/microbiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/microbiologia , Sistema Respiratório , Vírus/genética , Vírus/isolamento & purificaçãoRESUMO
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.
Assuntos
Pneumonia Pneumocócica/diagnóstico , Pneumonia Pneumocócica/microbiologia , Infecções Respiratórias/microbiologia , Streptococcus pneumoniae/crescimento & desenvolvimento , Streptococcus pneumoniae/isolamento & purificação , Carga Bacteriana , Técnicas Bacteriológicas , Bangladesh , Estudos de Casos e Controles , Saúde da Criança , Criança Hospitalizada , Pré-Escolar , Feminino , Gâmbia , Humanos , Lactente , Recém-Nascido , Quênia , Masculino , Mali , Pneumonia Pneumocócica/etiologia , Reação em Cadeia da Polimerase , Infecções Respiratórias/diagnóstico , África do Sul , Streptococcus pneumoniae/genética , Tailândia , ZâmbiaRESUMO
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.
Assuntos
Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/microbiologia , Antibacterianos/administração & dosagem , Bactérias/genética , Bactérias/patogenicidade , Técnicas Bacteriológicas , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Internacionalidade , Masculino , Técnicas de Diagnóstico Molecular , Nasofaringe/microbiologia , Orofaringe/microbiologia , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/etiologia , Reação em Cadeia da Polimerase em Tempo Real , Escarro/microbiologia , Streptococcus pneumoniae/genéticaRESUMO
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.