4,294 research outputs found

    Characterization of pneumonia among children under five years of age hospitalized in Thimphu, Bhutan

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    [eng] The general objective of this thesis was to describe the epidemiology, aetiology, clinical presentation, and radiological findings of pneumonia among Bhutanese children to better characterize childhood pneumonia in Bhutan and to contribute to the understanding of this disease in the local context. This thesis also aimed to assess the diagnostic and prognostic performance of host-response biomarkers alone, combined, or in addition to clinical scoring scales to risk-stratify children hospitalized with pneumonia and predict their outcome. The first article acknowledges the need for local research in Bhutan and comments on the specific challenges experienced when trying to conduct it. The second article is a systematic review that summarizes current knowledge around childhood pneumonia in Bhutan and identifies knowledge gaps in this area. The findings of this review were used as the starting point to guide further research and to establish the objectives of the Respiratory Infections in Bhutanese Children (RIBhuC) study. We reported the findings of the RIBhuC study in articles 3 to 6 of this thesis. In brief, the RIBhuC study took place between 1 July 2017 and 30 June 2018. We prospectively enrolled all children between 2 and 59 months admitted to the Jigme Dorji Wangchuck National Referral Hospital (JDWNRH) in Thimphu with WHO-defined clinical pneumonia, provided parents or caregivers consented to study participation. On admission, we performed a comprehensive physical examination, including anthropometric and vital signs measurements. We recorded demographic and clinical data from medical files and through family interviews. We performed an antero-posterior chest radiograph within 24 hours of admission and classified children according to radiological findings following WHO radiological criteria. We collected blood samples upon enrolment or as soon as possible after enrolment for haematology, biochemistry, and bacterial culture, and two drops of blood on filter paper for the identification of Streptococcus pneumoniae by realtime polymerase chain reaction (RT-PCR). In addition, we measured plasma levels of eleven host-response biomarkers, including six markers of immune and endothelial activation: interleukin-6 (IL-6), interleukin-8 (IL-8), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), soluble tumour necrosis factor receptor 1 (sTNFR1), angiopoietin-2 (Angpt-2), and soluble fms-like tyrosine kinase 1 (sFlt1). Finally, we collected respiratory samples through nasopharyngeal washing for the molecular identification of seventeen respiratory viruses and four atypical bacteria and the detection and capsular typing of Streptococcus pneumoniae. The third article describes the aetiological profile and the demographic and clinical characteristics of this cohort of children admitted with WHO-defined clinical pneumonia. The fourth article reports data on the prevalence of pneumococcal nasopharyngeal carriers and on the pneumococcal serotypes circulating among Bhutanese children with clinical pneumonia before the introduction of the pneumococcal conjugate vaccine in the country. We identified and compared respiratory viruses among children with and without pneumococcal nasopharyngeal colonization to contribute to the understanding of the interplay between pneumococcal nasopharyngeal colonization and viral coinfections. The fifth article describes the radiological findings of the RIBhuC cohort and the differences in radiological outcomes by demographic characteristics, aetiology, clinical features, and host-response biomarker levels. We also evaluated the utility of hostresponse biomarkers in discerning between bacterial and viral pneumonia, taking radiological endpoint pneumonia as a proxy for bacterial aetiology. The sixth and last article of this thesis assessed the performance of a wide range of clinical characteristics, laboratory testing, clinical scoring scales, and host-response biomarkers to risk-stratify children with clinical pneumonia in Bhutan and predict their outcome.[spa] El objetivo principal de esta tesis fue identificar y reducir las lagunas de conocimiento sobre la epidemiologia, la etiologia, la presentacion clinica y los hallazgos radiologicos de la neumonia infantil en Butan para caracterizar esta enfermedad y contribuir a su comprension en el contexto local. Esta tesis tambien tuvo como objetivo evaluar el rol diagnostico y pronostico de ciertos biomarcadores por si solos, combinados o en adicion a escalas de puntuacion clinica para estratificar el riesgo de los ninos hospitalizados con neumonia y predecir su resultado clinico. El primer artículo senala la necesidad de realizar investigacion a nivel local y comenta los desafios especificos encontrados en un pais como Butan para llevarla a cabo. El segundo artículo es una revision sistematica que resume el conocimiento actual sobre la neumonia infantil en Butan y que identifica las lagunas de conocimiento en este campo. Se utilizaron los resultados de esta revision y las carencias de conocimiento para enfocar los objetivos del estudio RIBhuC (del ingles Respiratory Infections in Bhutanese Children). Se detallan los principales hallazgos del estudio RIBhuC en los artículos 3 a 6 de esta tesis. El estudio RIBhuC se llevo a cabo entre el 1 de julio del 2017 y el 30 de junio del 2018 en el Hospital Nacional de Referencia Jigme Dorji Wangchuck, en Thimphu. Se recluto prospectivamente a todos los ninos entre 2 y 59 meses ingresados por neumonia clinica segun los criterios de la OMS, siempre que los padres o cuidadores aceptaran participar en el estudio. Al ingreso, se realizo un examen fisico completo incluyendo mediciones antropometricas y toma de signos vitales. Se recogieron datos demograficos y clinicos mediante entrevistas con los familiares y a partir del expediente medico. Se realizo una radiografia de torax anteroposterior en las primeras 24 horas del ingreso y se 20 clasificaron los ninos segun los criterios radiologicos de la OMS. Se recogieron muestras de sangre en el momento del reclutamiento, o lo antes posible despues del reclutamiento, para analisis de hematologia y bioquimica, cultivo bacteriano, e identificacion de Streptococcus pneumoniae mediante la reaccion en cadena de la polimerasa en tiempo real a partir de dos gotas de sangre recogidas en papel de filtro. Tambien se midieron los niveles plasmaticos de once biomarcadores de respuesta del huesped, incluyendo seis marcadores de activacion endotelial e inmune: la interleucina-6 (IL-6), la interleucina-8 (IL-8), el receptor de activacion soluble expresado en celulas mieloides-1 (sTREM-1), el receptor soluble del factor de necrosis tumoral 1 (sTNFR1), la angiopoyetina-2 (Angpt-2), y la tirosina quinasa-1 soluble similar a fms (sFlt1). Finalmente, se recogieron muestras respiratorias mediante lavado nasofaringeo para la identificacion molecular de 17 virus respiratorios y 4 bacterias atipicas, asi como para la deteccion y tipificacion capsular neumococica. El tercer artículo describe el perfil etiologico y las caracteristicas demograficas y clinicas de esta cohorte de ninos butaneses ingresados con neumonia clinica. El cuarto artículo presenta la prevalencia de portadores nasofaringeos neumococicos y los serotipos neumococicos circulantes entre los ninos butaneses ingresados con neumonia clinica antes de la introduccion de la vacuna antineumococica conjugada en el pais. Comparamos la prevalencia y tipos de virus respiratorios entre ninos con y sin colonizacion nasofaringea neumococica para contribuir a la comprension de la interaccion entre la colonizacion nasofaringea neumococica y las coinfecciones virales. El quinto artículo describe los hallazgos radiologicos y evalua las diferencias en cuanto a caracteristicas demograficas, etiologicas, clinicas y niveles de biomarcadores segun las caracteristicas radiologicas. En este articulo, tambien se evalua la utilidad de biomarcadores para diferenciar entre neumonia bacteriana y viral, considerando el hallazgo de neumonia radiologica (condensacion, derrame pleural o ambos) como indicador de neumonia bacteriana. El sexto y último artículo de esta tesis evalua el rendimiento de caracteristicas clinicas, pruebas de laboratorio, escalas de puntuacion clinica y biomarcadores para estratificar el riesgo pronostico de los ninos con neumonia clinica en el momento del ingreso y predecir su resultado clinico

    Prognosis of cellular energy metabolism shifts in adolescents with community-acquired pneumonia

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    Pneumonia is one of the most severe respiratory pathology forms in children, which contributes significantly to infant mortality. The high risk of chronic bronchopulmonary process and child`s disability, in case of severe and complicated disease, requires careful pathophysiological change's analysis in community-acquired pneumonia (CAP) in children. In particular, for the prediction of these disorders in children with CAP are important the dysmetabolic phenomena study and the specific approaches development. The immediate aim of this work is to study the cellular energy metabolism (CEM) features and to develop approaches for the early bioenergetic disorders diagnostics in conditions of community-acquired pneumonia in adolescents.The aim of the study is to develop approaches for the early diagnosis of shifts in energy metabolism in children aged 14-18 years with CAP. An examination of 41 children aged 14-16 years with the definition of CEM indicators was conducted in order to develop an approach for predicting CEM disorders in community-acquired pneumonia using the method of logistic regression. A logistic regression method was used to develop a method for predicting CEM disorders in children with CAP. The characteristics of CEM in children with CAP were determined. A decrease in the succinate dehydrogenase activity and an increase in the lactate dehydrogenase / succinate dehydrogenase ratio in children with CAP relative to the reference parameters were observed, which indicated an inhibition of the anaerobic energy synthesis pathway. Two mathematical models for predicting CEM disorders in CAP based on logistic regression equations were proposed. The first mathematical model consisted of social and health characteristics and of pneumonia clinical course characteristics. In ROC analysis the area under the curve (AUC) was 0.82, diagnostic specificity – 71%, diagnostic sensitivity – 90%. The second model included only hematological parameters, AUC – 0.78, diagnostic specificity – 69%, diagnostic sensitivity – 81%. Thus, changes in CEM in children with CAP aged 14 – 18 years have been established. Two methods for predicting disorders of CEM in children with CAP have been developed, which can be applied to optimize the treatment of children with CAP aged 14-18 years

    Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines

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    Community-acquired pneumonia (CAP) is a major cause of death in developing countries and of morbidity in developed countries. The objective of the study was to define the causative agents among children hospitalized for CAP defined by WHO guidelines and to correlate etiology with clinical severity and surrogate markers. Investigations included an extensive etiological workup. A potential causative agent was detected in 86% of the 99 enrolled patients, with evidence of bacterial (53%), viral (67%), and mixed (33%) infections. Streptococcus pneumoniae was accounted for in 46% of CAP. Dehydration was the only clinical sign associated with bacterial pneumonia. CRP and PCT were significantly higher in bacterial infections. Increasing the number of diagnostic tests identifies potential causes of CAP in up to 86% of children, indicating a high prevalence of viruses and frequent co-infections. The high proportion of pneumococcal infections re-emphasizes the importance of pneumococcal immunizatio

    Factores de severidad de Neumonía Adquirida en la Comunidad en un hospital infantil del Caribe colombiano

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    Objective: To identify predisposing factors to developing severe pneumonia in hospitalized children diagnosed with community-acquired pneumonia hospitalized in Cartagena’s Napoleón Franco Pareja children’s Hospital. Methods: Analytical observational cross-sectional study performed in patients under 18 years. Data from surveys and records were analyzed. Univariate and bivariate analysis was performed. The variables are grouped according to the presence or absence of complications and analyzed by ji-square test. We calculated OR of each of the dummy variables to evaluate their association with complications. A P < 0.05 was considered statistically significant for all analyses. Results: 301 patients with severe pneumonia were included. Risk factors related to severity: age less than 3 months (OR: 4.86; CI 95%: 1,5 - 14.3; p = 0.004); exclusive breastfeeding for less than 6 months (CI:95% 7,7- 1,4; p = 0.0019); heart disease (OR: 5.37; CI 95%: 1,28- 19,88, p = 0.010); prematurity (OR: 1.62, CI 95%: 0.93- 6.69, p = 0.034); Incomplete vaccination (OR: 2.32; CI: 95% 1.07 - 5.10; p = 0.015). Conclusions: It was found increased severity risk, statistically significant, in patients less than 6 months breastfeeding, prematurity, heart disease, incomplete vaccination scheme, and positive blood culture with Sp. pneumoniaObjetivo: Identificar factores predisponentes a desarrollar neumonía severa en niños hospitalizados con diagnóstico de NAC en el Hospital Infantil Napoleón Franco Pareja de Cartagena Colombia. Materiales y métodos: Estudio observacional transversal analítico en pacientes menores de 18 años hospitalizados con neumonía adquirida en la comunidad. Se analizaron datos obtenidos de encuestas y registros clínicos. Se realizó un análisis descriptivo univariado y bivariado. Las variables se agruparon según la presencia o no de complicación y se analizaron a través de la prueba ji cuadrado. Se realizó el cálculo de OR de cada una de las variables dicotómicas para evaluar su asociación a complicaciones. Una P<0,05 fue considerada como estadísticamente significativa para todos los análisis. Resultados: Se incluyeron 301 pacientes con neumonía grave. Los factores de riesgo más relacionados con severidad fueron: edad menor de 3 meses (OR: 4,86; IC 95%: 1,5- 14,3; p 0,004); la lactancia materna exclusiva menor a 6 meses (IC 95%: 1,4- 7,7; p 0,0019); cardiopatía (OR: 5,37; IC 95%: 1,28- 19,88; p: 0,010); prematurez (OR: 1,62; IC: 0,93-6,69; p: 0,034); esquema incompleto de vacunación (OR: 2,32; IC 95%: 1,07-5,10: p: 0,015). Conclusiones: Se encontró aumento de riesgo de severidad en pacientes con lactancia materna menor de 6 meses, prematurez, cardiopatía, esquema de vacunación incompleto, y hemocultivo con Sp. Neumoniae positivo

    Severity factors of Acquired Pneumonia Community in a children's hospital in the Colombian Caribbean

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    Objective: Identify predisposing factors to develop severe pneumonia in hospitalized children diagnosed with community-acquired pneumonia hospitalized in Cartagena´s Napoleón Franco Pareja children´s Hospital.Methods: Analytical observational cross-sectional study performed in patients under 18 years. Data from surveys and records were analyzed. Univariate and bivariate analysis was performed. The variables are grouped according to the presence or absence of complications and analyzed by ji-square test. We were calculating OR of each of the dummy variables to evaluate their association with complications was performed. A P &amp;lt; 0.05 was considered statistically significant for all analyzes.Results: 301 patients with severe pneumonia were included. Risk factors related to severity: age less than 3 months (OR: 4.86; CI 95%: 1,5 - 14.3; p = 0.004); exclusive breastfeeding for less than 6 months (CI:95% 7,7- 1,4; p = 0.0019); heart disease (OR: 5.37; CI 95%: 1,28- 19,88, p = 0.010); prematurity (OR: 1.62, CI 95%: 0.93- 6.69, p = 0.034); Incomplete vaccination (OR: 2.32; CI: 95% 1.07 - 5.10; p = 0.015).Conclusions: It was found increased severity risk, statistical significantly, in patients less than 6 months breastfeeding, prematurity, heart disease, incomplete vaccination scheme, and positive blood culture with Sp. pneumoni

    Pneumonia in Children

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    Towards an evidence base in the treatment of severe febrile illness in East African children

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    Febrile illness is the primary cause of childhood outpatient attendance, admission to hospital and death in Africa. This series of studies were aimed at ascertaining the treatable causes of infection in children admitted to a district hospital typical of those found throughout East Africa, in an area of high transmission of malaria. The studies were also designed to determine the clinical correlates of infection and predictors of mortality, looking in particular at malaria, invasive bacterial disease and HIV infection. These studies also explored to what extent clinical examination by one group of staff was replicable by another.After informed consent a detailed history and structured examination was performed on all children admitted to the hospital. Blood was drawn for culture, microscopy for malaria, HIV testing, full blood count, bedside haemoglobin, blood glucose and lactate measurement and HRP-2 based rapid diagnostic test for falciparum malaria. Outcomes were recorded at death or discharge.Sufficient data was available on 3,639 children including 184 deaths (5.1%). Invasive bacterial disease was detected in 341 children (9.4%) and HIV in 142 (3.9%). Children with HIV and those with evidence of recent malaria were significantly more likely to have invasive bacterial disease. The most common organisms isolated were non-typhi Salmonella (46.9%), Strep, pneumoniae (16.4%) and Haemophilus influenzae b (11.4%). The most frequently encountered pathogen was P. falciparum, with 2,195 children found to have asexual parasitaemia (60.3%). Falciparum parasitaemia was detected in 100 children with invasive bacterial disease (29.3%). Falciparum malaria was detected in over half (51.6%) of childhood deaths, invasive bacterial disease was documented in 31.5%.In children with a positive blood slide for malaria, WHO severe malaria criteria identified 91.6% of the children that died. A multivariate analysis showed that signs of malnutrition, respiratory distress, altered consciousness, hypoxia according to pulse oximetry, hypoglycaemia, raised blood lactate, invasive bacterial disease and female sex were all associated with an increased risk of death. In children with negative blood slides signs of malnutrition, respiratory distress, altered consciousness, hypoglycaemia, raised blood lactate and invasive bacterial disease were all independently associated with mortality by multivariate analysis.WHO defined criteria of syndromes which would warrant antibiotics predicted 56% of cases of coinfection with invasive bacterial disease and malaria and 69.7% of cases of invasive bacterial disease in slide negative children. Treating all children with severe malaria for bacterial disease would result in 71% of children with coinfection being treated. In children with negative slides including severe anaemia or prostration as syndromes requiring antibiotic therapy would have resulted in 74.7% of children with invasive bacterial disease receiving antibiotic therapy. There was moderate agreement between staff over the presence of clinical signs in children, with hospital nurses performing as well as hospital clinical officers. Agreement was better in children over 18 months of age and in children who were not crying during examination.Current WHO guidelines on antibiotic use performed poorly in this setting. Gram negative infections were the most common cause of invasive infection and many of these are likely to be resistant to penicillin and other commonly used antibiotics. Consideration should be given to expanding the indications for antibiotic use and using more broad-spectrum antibiotics in severely ill children

    Serial lung ultrasounds in pediatric pneumonia in Mozambique and Pakistan

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    Lung ultrasound (LUS) is a promising point-of-care imaging technology for diagnosing and managing pneumonia. We sought to explore serial LUS examinations in children with chest-indrawing pneumonia in resource-constrained settings and compare their clinical and LUS imaging courses longitudinally. We conducted a prospective, observational study among children aged 2 through 23 months with World Health Organization Integrated Management of Childhood Illness chest-indrawing pneumonia and among children without fast breathing, chest indrawing or fever (no pneumonia cohort) at 2 district hospitals in Mozambique and Pakistan. We assessed serial LUS at enrollment, 2, 6, and 14 days, and performed a secondary analysis of enrolled children\u27s longitudinal clinical and imaging courses. By Day 14, the majority of children with chest-indrawing pneumonia and consolidation on enrollment LUS showed improvement on follow-up LUS (100% in Mozambique, 85.4% in Pakistan) and were clinically cured (100% in Mozambique, 78.0% in Pakistan). In our cohort of children with chest-indrawing pneumonia, LUS imaging often reflected the clinical course; however, it is unclear how serial LUS would inform the routine management of non-severe chest-indrawing pneumonia

    Community-acquired pneumonia in children: Aetiology, clinical features, and complications

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    Pneumonia is an important cause of morbidity and hospitalization in children worldwide. Since the development of nucleic acid amplification techniques, rhinovirus (RV) is frequently detected in community-acquired pneumonia (CAP), but the causative role of RV in pneumonia is still questioned. Empyema is a severe complication of pneumonia, and the evaluation of its long-term consequences is necessary. We studied the viral aetiology of childhood CAP by searching for 18 respiratory viruses and six bacteria in sputum specimens (n = 76). The clinical characteristics and prevalence of RV pneumonia and its risk factors were evaluated by retrospectively comparing the medical record data of RV-positive (n = 82) and RV-negative (n = 231) children hospitalized for CAP. We also prospectively investigated viral and bacterial biomarker levels in children hospitalized for CAP (n = 24), focusing on RV pneumonia. Finally, we investigated the long-term outcome of childhood parapneumonic empyema (n = 26) at 3–19 years’ follow-up by a detailed interview, physical examination, lung imaging and lung function tests. Viruses were detected in 72%, bacteria in 91%, and both in 66% of children hospitalized for CAP. RV, human bocavirus, and human metapneumovirus were the most commonly found viruses. Treatment failures were documented in viral-bacterial co-infections. Young age and a history of preterm birth were associated with RV-positive pneumonia, but the clinical features of pneumonia were similar in RV-positive and RV-negative children. RV-positive children had elevated levels of bacterial biomarkers, but a viral biomarker myxovirus resistance protein A remained low. Lung magnetic resonance imaging showed abnormal findings in 92% and significant pleural scarring in 25% of the children recovered from empyema, but most patients had normal lung function, chest radiograph and clinical recovery. Viral-bacterial co-detections are common in childhood CAP and potentially associated with treatment failure. RV is commonly detected in young children with pneumonia and it is often associated with bacterial co-infection. Making the decision to withdraw antibiotics in children with pneumonia is challenging. Further studies and strategies are needed to differentiate viral from bacterial or mixed viral-bacterial pneumonia. The long-term recovery from parapneumonic empyema seems to be good with current treatment strategies.Lasten avosyntyinen keuhkokuume Keuhkokuume on maailmanlaajuisesti merkittävä lasten sairastavuuden ja sairaalahoidon aiheuttaja. Rinovirus (RV) on yleinen löydös lasten keuhkokuumeessa, mutta sen rooli keuhkokuumeen aiheuttajana on edelleen epäselvä. Empyeema on keuhkokuumeen vakava komplikaatio, jonka pitkäaikaisvaikutusten selvittäminen on tärkeää. Selvitimme lasten avosyntyisen keuhkokuumeen virusetiologiaa tutkimalla 18 viruksen ja kuuden bakteerin esiintyvyyttä yskösnäytteistä (n = 76). RV-keuhkokuumeen taudinkuvaa, esiintyvyyttä ja riskitekijöitä tutkittiin vertailemalla retrospektiivisesti keuhkokuumeen vuoksi sairaalahoitoon joutuneiden RV-positiivisten (n = 82) ja RV-negatiivisten (n = 231) lasten potilaskertomustietoja. Tutkimme myös virus- ja bakteerimerkkiaineiden tasoja lasten sairaalahoitoa vaativassa keuhkokuumeessa (n = 24), erityisesti RV-keuhkokuumeessa. Lasten empyeeman pitkäaikaisvaikutuksia selvitettiin 3–19 vuoden kuluttua sairastamisesta kliinisellä tutkimuksella sekä keuhkojen toimintakokeilla ja kuvantamisella (n = 26). Viruksia löydettiin 72 %:lta, bakteereja 91 %:lta ja molempia 66 %:lta lapsista, jotka tarvitsivat sairaalahoitoa keuhkokuumeen vuoksi. RV, bokavirus ja metapneumovirus olivat yleisimmin löydetyt virukset. Hoidon epäonnistumista havaittiin virus-bakteeriseka-infektioissa. Lapsen nuori ikä ja keskosuustausta olivat yhteydessä RV-positiiviseen keuhkokuumeeseen, mutta keuhkokuumeen taudinkuva oli samankaltainen RV-positiivisilla ja RV-negatiivisilla lapsilla. Bakteeri-infektion merkkiaineiden tasot olivat koholla mutta virusmerkkiaineen, myksovirusresistenssiproteiini A:n, pitoisuus veressä oli matala RV-positiivisilla lapsilla. Keuhkojen magneettikuvauksella havaittiin poikkeavia löydöksiä 92 %:lla ja merkittävää arpea keuhkopussissa 25 %:lla empyeeman sairastaneista lapsista, mutta kliininen paraneminen, keuhkojen toiminta ja keuhkokuva olivat valtaosalla normaalit. Virus-bakteerisekainfektiot ovat yleisiä lasten avosyntyisessä keuhkokuumeessa ja ovat mahdollisesti yhteydessä hoidon epäonnistumiseen. RV löytyy usein nuorilta keuhkokuumetta sairastavilta lapsilta ja usein yhdessä bakteeri-infektion kanssa. Päätös antibioottihoidon aloittamatta jättämisestä on haastava. Lisää tutkimuksia ja toimintasuunnitelmia tarvitaan virusinfektion erottamiseksi bakteeri- tai virus-bakteerisekainfektioista. Pitkäaikaisseurannassa empyeemasta paraneminen vaikuttaa hyvältä nykyisillä hoitokäytännöillä

    Legionella infections : a review of the literature and a prospective serological study of the incidence of Legionnaires disease at Groote Schuur Hospital

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    A prospective study of patients with pneumonia admitted to Groote Schuur Hospital took place over a one-year period in an attempt to assess the incidence of legionella pneumonia. Acute and convalescent serum samples were obtained from 113 patients. Eight patients (7,1%) showed a fourfold rise in antibody titre against Legionella pneumophila group 1 antigen by indirect immunofluorescent test (IFAT). The findings suggest that legionella pneumonia, although not common, should be considered in the aetiology of pneumonia at Groote Schuur Hospital. The results are presented and a review of the literature is undertaken
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