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1.
São Paulo; s.n; 2023. 23 p.
Thesis in Portuguese | Coleciona SUS, Sec. Munic. Saúde SP, HSPM-Producao, Sec. Munic. Saúde SP | ID: biblio-1532801

ABSTRACT

A pneumonia adquirida na comunidade (PAC) é a infecção aguda do parênquima pulmonar que ocorre no meio comunitário. A PAC representa a maior causa de morbidade e mortalidade em todo o mundo em crianças abaixo de cinco anos. Nesta faixa etária, a etiologia viral é a mais comum; porém, dentre as causas bacterianas, o Streptoccocus pneumoniae é o mais prevalente. As manifestações clínicas variam de acordo com o patógeno, hospedeiro e da gravidade da doença, sendo geralmente descrita com tosse, febre e desconforto respiratório. A PAC complicada é a pneumonia que, apesar do uso de antibióticos, evolui com complicações locais ou sistêmicas. Nos pacientes hospitalizados, as hemoculturas devem ser consideradas para auxiliar no diagnóstico etiológico e planejamento terapêutico. O tratamento inicial deve ser iniciado empiricamente com antibióticos. Caso haja necessidade de hospitalização, hemoculturas devem ser consideradas para auxiliar na propedêutica. Após implementação das vacinas pneumocócicas, principalmente após introdução da vacina pneumocócica 13 valente (PCV 13), houve redução significativa dos casos de pneumonia bacteriana e também da necessidade hospitalização. Diante de tal realidade, a elaboração do trabalho possui como objetivo a melhora dos procedimentos e a padronização dos atendimentos da população pediátrica com um quadro clínico sugestivo pneumonia adquirida na comunidade, que procura o serviço de Pronto Atendimento Infantil do Hospital do Servidor Público Municipal de São Paulo (HSPM), ao construir um protocolo clínico de atendimento específico para a doença. O presente trabalho objetiva elaborar um protocolo clínico de atendimento de pneumonia adquirida na comunidade no Hospital do Servidor Público Municipal de São Paulo, contribuindo na assistência médica dos pacientes pediátricos. Apesar do grande avanço com a introdução das vacinas pneumocócicas, a PAC ainda representa uma importante causa de mortalidade na população infantil, sendo fundamental a elaboração de protocolos clínicos para abordar corretamente os pacientes que recorrem a um Pronto Socorro Infantil. Protocolos clínicos são diretrizes fundamentadas nas melhores práticas para a abordagem e tratamento de determinadas doenças, baseadas em evidência científica. O presente trabalho objetiva a melhora dos procedimentos e a uniformização dos atendimentos da população pediátrica com pneumonia, que procura o serviço de Pronto Atendimento Infantil do Hospital do Servidor Público Municipal de São Paulo (HSPM), com a construção de um protocolo clínico de atendimento específico para a doença, a partir da revisão de literatura atualizada, cujo período de vigência seguirá os progressos científicos sobre o tema. Palavras-chave: Pneumonia Adquirida da Comunidade. Protocolos clínicos. Pediatria. Serviços Médicos de Emergência. Vacinas Pneumocócicas


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Pediatrics/standards , Pneumonia/complications , Pneumonia/mortality , Pneumonia, Pneumococcal/diagnosis , Respiratory Syncytial Viruses/pathogenicity , Respiratory Tract Diseases/diagnosis , Clinical Protocols/standards , Pneumonia, Bacterial/drug therapy , Cough/diagnosis , Pneumococcal Vaccines/therapeutic use , Parenchymal Tissue/physiopathology , Medical Assistance/standards , Anti-Bacterial Agents/administration & dosage , Noxae/analysis
4.
Cells ; 10(11)2021 11 07.
Article in English | MEDLINE | ID: mdl-34831290

ABSTRACT

The bronchial vascular endothelial network plays important roles in pulmonary pathology during respiratory viral infections, including respiratory syncytial virus (RSV), influenza A(H1N1) and importantly SARS-Cov-2. All of these infections can be severe and even lethal in patients with underlying risk factors.A major obstacle in disease prevention is the lack of appropriate efficacious vaccine(s) due to continuous changes in the encoding capacity of the viral genome, exuberant responsiveness of the host immune system and lack of effective antiviral drugs. Current management of these severe respiratory viral infections is limited to supportive clinical care. The primary cause of morbidity and mortality is respiratory failure, partially due to endothelial pulmonary complications, including edema. The latter is induced by the loss of alveolar epithelium integrity and by pathological changes in the endothelial vascular network that regulates blood flow, blood fluidity, exchange of fluids, electrolytes, various macromolecules and responses to signals triggered by oxygenation, and controls trafficking of leukocyte immune cells. This overview outlines the latest understanding of the implications of pulmonary vascular endothelium involvement in respiratory distress syndrome secondary to viral infections. In addition, the roles of infection-induced cytokines, growth factors, and epigenetic reprogramming in endothelial permeability, as well as emerging treatment options to decrease disease burden, are discussed.


Subject(s)
Endothelial Cells/pathology , Oxidative Stress , Respiratory Distress Syndrome/pathology , Virus Diseases/pathology , Epigenesis, Genetic , Humans , Influenza A Virus, H1N1 Subtype/physiology , Pulmonary Edema/genetics , Pulmonary Edema/pathology , Pulmonary Edema/virology , Respiratory Distress Syndrome/genetics , Respiratory Distress Syndrome/virology , Respiratory Syncytial Viruses/pathogenicity , SARS-CoV-2/pathogenicity , Virus Diseases/genetics , Virus Diseases/virology
5.
Viruses ; 13(10)2021 10 13.
Article in English | MEDLINE | ID: mdl-34696488

ABSTRACT

Respiratory syncytial virus (RSV) is a seasonal mucosal pathogen that infects the ciliated respiratory epithelium and results in the most severe morbidity in the first six months of life. RSV is a common cause of acute respiratory infection during infancy and is an important early-life risk factor strongly associated with asthma development. While this association has been repeatedly demonstrated, limited progress has been made on the mechanistic understanding in humans of the contribution of infant RSV infection to airway epithelial dysfunction. An active infection of epithelial cells with RSV in vitro results in heightened central metabolism and overall hypermetabolic state; however, little is known about whether natural infection with RSV in vivo results in lasting metabolic reprogramming of the airway epithelium in infancy. To address this gap, we performed functional metabolomics, 13C glucose metabolic flux analysis, and RNA-seq gene expression analysis of nasal airway epithelial cells (NAECs) sampled from infants between 2-3 years of age, with RSV infection or not during the first year of life. We found that RSV infection in infancy was associated with lasting epithelial metabolic reprogramming, which was characterized by (1) significant increase in glucose uptake and differential utilization of glucose by epithelium; (2) altered preferences for metabolism of several carbon and energy sources; and (3) significant sexual dimorphism in metabolic parameters, with RSV-induced metabolic changes most pronounced in male epithelium. In summary, our study supports the proposed phenomenon of metabolic reprogramming of epithelial cells associated with RSV infection in infancy and opens exciting new venues for pursuing mechanisms of RSV-induced epithelial barrier dysfunction in early life.


Subject(s)
Respiratory Mucosa/metabolism , Respiratory Mucosa/virology , Respiratory Syncytial Virus Infections/metabolism , Child, Preschool , Cohort Studies , Epithelial Cells/metabolism , Epithelial Cells/virology , Female , Humans , Infant , Infant, Newborn , Male , Metabolomics/methods , Nasal Cavity/metabolism , Nasal Cavity/virology , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/pathogenicity , Respiratory Tract Infections/virology
6.
Biomed Res Int ; 2021: 9956078, 2021.
Article in English | MEDLINE | ID: mdl-34541002

ABSTRACT

BACKGROUND: Respiratory syncytial virus (RSV) infects infants and children, predisposing them to development of asthma during adulthood. Epithelial neuroendocrine phenotypes may be associated with development of asthma. This study hopes to ascertain if RSV infection promotes epithelial neuroendocrine phenotypes through the NODAL signaling pathway. METHODS: The GSE6802 data set was obtained from the GEO database, and the differential genes were analyzed using the R language. An in vitro model was constructed with RSV infected human respiratory epithelial cells, and then real-time qPCR and immunofluorescence were used to detect the expression of different epithelial biomarkers and airway neuropeptides. The acute and chronic infection model of RSV infection was established by intranasal injection of RSV into guinea pigs. Immunohistochemistry and Western blot were used to detect the expression of pulmonary neuroendocrine cells markers ENO2 and neuropeptides. RESULTS: The expression levels of ENO2, SP, CGRP, and NODAL/ACTRII were significantly higher in the RSV infection group than those of the control group, which were abrogated by siRNA-NODAL. In vivo, we found that the expression levels of ENO2, SP, and CGRP were significantly higher than that of the control group. CONCLUSION: RSV promotes epithelial neuroendocrine phenotypes through the NODAL signaling pathway.


Subject(s)
Neuroendocrine Cells/metabolism , Nodal Signaling Ligands/metabolism , Respiratory Syncytial Virus Infections/physiopathology , Animals , Asthma/metabolism , Cell Differentiation , Cell Line , China , Databases, Factual , Databases, Genetic , Disease Models, Animal , Epithelial Cells/metabolism , Epithelial Cells/virology , Guinea Pigs , HeLa Cells , Humans , Lung/metabolism , Neuroendocrine Cells/virology , Neuropeptides/metabolism , Nodal Protein/genetics , Nodal Protein/metabolism , Nodal Protein/physiology , Nodal Signaling Ligands/genetics , Phenotype , Respiratory Syncytial Virus Infections/metabolism , Respiratory Syncytial Viruses/pathogenicity , Signal Transduction
7.
J Med Virol ; 93(11): 6116-6123, 2021 11.
Article in English | MEDLINE | ID: mdl-34375002

ABSTRACT

Virus invasion activates the host's innate immune response, inducing the production of numerous cytokines and interferons to eliminate pathogens. Except for viral DNA/RNA, viral proteins are also targets of pattern recognition receptors. Membrane-bound receptors such as Toll-like receptor (TLR)1, TLR2, TLR4, TLR6, and TLR10 relate to the recognition of viral proteins. Distinct TLRs perform both protective and detrimental roles for a specific virus. Here, we review viral proteins serving as pathogen-associated molecular patterns and their corresponding TLRs. These viruses are all enveloped, including respiratory syncytial virus, hepatitis C virus, measles virus, herpesvirus human immunodeficiency virus, and coronavirus, and can encode proteins to activate innate immunity in a TLR-dependent way. The TLR-viral protein relationship plays an important role in innate immunity activation. A detailed understanding of their pathways contributes to a novel direction for vaccine development.


Subject(s)
Immunity, Innate , Pathogen-Associated Molecular Pattern Molecules/metabolism , Toll-Like Receptors/immunology , Toll-Like Receptors/metabolism , Viral Proteins/metabolism , Virus Diseases/immunology , Viruses/immunology , Animals , HIV/immunology , HIV/metabolism , HIV/pathogenicity , Hepacivirus/immunology , Hepacivirus/metabolism , Hepacivirus/pathogenicity , Herpesviridae/immunology , Herpesviridae/metabolism , Herpesviridae/pathogenicity , Humans , Measles virus/immunology , Measles virus/metabolism , Measles virus/pathogenicity , Pathogen-Associated Molecular Pattern Molecules/chemistry , Respiratory Syncytial Viruses/immunology , Respiratory Syncytial Viruses/metabolism , Respiratory Syncytial Viruses/pathogenicity , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Viral Proteins/chemistry , Virus Diseases/virology , Viruses/metabolism , Viruses/pathogenicity
8.
Sci Rep ; 11(1): 17193, 2021 08 25.
Article in English | MEDLINE | ID: mdl-34433834

ABSTRACT

This paper addresses the development of predictive models for distinguishing pre-symptomatic infections from uninfected individuals. Our machine learning experiments are conducted on publicly available challenge studies that collected whole-blood transcriptomics data from individuals infected with HRV, RSV, H1N1, and H3N2. We address the problem of identifying discriminatory biomarkers between controls and eventual shedders in the first 32 h post-infection. Our exploratory analysis shows that the most discriminatory biomarkers exhibit a strong dependence on time over the course of the human response to infection. We visualize the feature sets to provide evidence of the rapid evolution of the gene expression profiles. To quantify this observation, we partition the data in the first 32 h into four equal time windows of 8 h each and identify all discriminatory biomarkers using sparsity-promoting classifiers and Iterated Feature Removal. We then perform a comparative machine learning classification analysis using linear support vector machines, artificial neural networks and Centroid-Encoder. We present a range of experiments on different groupings of the diseases to demonstrate the robustness of the resulting models.


Subject(s)
Computer Simulation , Influenza, Human/virology , Picornaviridae Infections/virology , Respiratory Syncytial Virus Infections/virology , Transcriptome , Virus Shedding , Biomarkers/metabolism , Gene Regulatory Networks , Humans , Influenza, Human/genetics , Influenza, Human/metabolism , Machine Learning , Orthomyxoviridae/pathogenicity , Orthomyxoviridae/physiology , Picornaviridae Infections/genetics , Picornaviridae Infections/metabolism , Respiratory Syncytial Virus Infections/genetics , Respiratory Syncytial Virus Infections/metabolism , Respiratory Syncytial Viruses/pathogenicity , Respiratory Syncytial Viruses/physiology , Rhinovirus/pathogenicity , Rhinovirus/physiology
9.
Inflammation ; 44(6): 2476-2485, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34453228

ABSTRACT

Treg/Th17 cell imbalance and inflammatory response may occur in neonatal asthma. IL-35 and BCG have inhibitory effects on inflammatory responses in diseases. However, studies on neonatal asthma after combination of the two have not been reported so far. A respiratory syncytial virus (RSV)-induced neonatal asthma model was first developed in newborn mice. Pathological sections of lung tissue of asthmatic mice were observed by HE staining. Masson staining was used to observe the lung tissue and to compare the deposition of collagen fibers under bronchial epithelium in model mice. The expression of cytokines in serum was detected by ELISA. Giemsa staining analyzed each cell in bronchoalveolar lavage fluid (BALF). Flow cytometry was used to detect the differentiation and development of Treg and Th17 subgroups in BALF. The expression levels of inflammation-related factors were detected by RT-qPCR. Western blot was used to detect the expression of JNK pathway-related proteins. Recombinant IL-35-BCG improved the pathological response of asthmatic mice; inhibited the expression of IgE in serum, neutrophils, macrophages, and eosinophils in BALF; and increased the expression of lymphocytes. In addition, recombinant IL-35-BCG significantly inhibited Th17 differentiation, promoted Treg cell differentiation, and inhibited the expression of inflammatory factors in lung tissue homogenates, thereby reducing allergic airway inflammation. This process might be achieved by inhibiting the JNK signaling pathway. Recombinant IL-35-BCG can regulate Treg/Th17 cell imbalance and inflammatory response in asthmatic newborn mice induced by RSV through JNK signaling pathway, suggesting a new path to neonatal asthma treatment.


Subject(s)
Anti-Asthmatic Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Asthma/drug therapy , BCG Vaccine/pharmacology , Interleukins/pharmacology , Lung/drug effects , Respiratory Syncytial Virus Infections/drug therapy , T-Lymphocytes, Regulatory/drug effects , Th17 Cells/drug effects , Animals , Animals, Newborn , Asthma/immunology , Asthma/metabolism , Asthma/virology , Cytokines/metabolism , Disease Models, Animal , Female , Inflammation Mediators/metabolism , JNK Mitogen-Activated Protein Kinases/metabolism , Lung/immunology , Lung/innervation , Lung/virology , Mice, Inbred BALB C , Recombinant Proteins/pharmacology , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/metabolism , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/pathogenicity , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , T-Lymphocytes, Regulatory/virology , Th17 Cells/immunology , Th17 Cells/metabolism , Th17 Cells/virology
11.
Epidemiol Infect ; 149: e96, 2021 04 14.
Article in English | MEDLINE | ID: mdl-33849679

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. Prevention and control strategies require an improved understanding of SARS-CoV-2 dynamics. We did a rapid review of the literature on SARS-CoV-2 viral dynamics with a focus on infective dose. We sought comparisons of SARS-CoV-2 with other respiratory viruses including SARS-CoV-1 and Middle East respiratory syndrome coronavirus. We examined laboratory animal and human studies. The literature on infective dose, transmission and routes of exposure was limited specially in humans, and varying endpoints were used for measurement of infection. Despite variability in animal studies, there was some evidence that increased dose at exposure correlated with higher viral load clinically, and severe symptoms. Higher viral load measures did not reflect coronavirus disease 2019 severity. Aerosol transmission seemed to raise the risk of more severe respiratory complications in animals. An accurate quantitative estimate of the infective dose of SARS-CoV-2 in humans is not currently feasible and needs further research. Our review suggests that it is small, perhaps about 100 particles. Further work is also required on the relationship between routes of transmission, infective dose, co-infection and outcomes.


Subject(s)
COVID-19/transmission , SARS-CoV-2/pathogenicity , Viral Load , Adenoviridae/pathogenicity , Animals , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Chlorocebus aethiops , Communicable Disease Control , Coronavirus Infections/epidemiology , Coronavirus Infections/transmission , Coronavirus Infections/virology , Cricetinae , Enterovirus/pathogenicity , Ferrets , Humans , Macaca mulatta , Mice , Middle East Respiratory Syndrome Coronavirus/pathogenicity , Orthomyxoviridae/pathogenicity , Respiratory Syncytial Viruses/pathogenicity , Rhinovirus/pathogenicity , Severe acute respiratory syndrome-related coronavirus/pathogenicity , Severe Acute Respiratory Syndrome/epidemiology , Severe Acute Respiratory Syndrome/transmission , Severe Acute Respiratory Syndrome/virology , Virus Diseases/epidemiology , Virus Diseases/transmission , Virus Diseases/virology
12.
Proc Natl Acad Sci U S A ; 118(14)2021 04 06.
Article in English | MEDLINE | ID: mdl-33811145

ABSTRACT

Human respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection in children under 5 y of age. In the absence of a safe and effective vaccine and with limited options for therapeutic interventions, uncontrolled epidemics of RSV occur annually worldwide. Existing RSV reverse genetics systems have been predominantly based on older laboratory-adapted strains such as A2 or Long. These strains are not representative of currently circulating genotypes and have a convoluted passage history, complicating their use in studies on molecular determinants of viral pathogenesis and intervention strategies. In this study, we have generated reverse genetics systems for clinical isolates of RSV-A (ON1, 0594 strain) and RSV-B (BA9, 9671 strain) in which the full-length complementary DNA (cDNA) copy of the viral antigenome is cloned into a bacterial artificial chromosome (BAC). Additional recombinant (r) RSVs were rescued expressing enhanced green fluorescent protein (EGFP), mScarlet, or NanoLuc luciferase from an additional transcription unit inserted between the P and M genes. Mutations in antigenic site II of the F protein conferring escape from palivizumab neutralization (K272E, K272Q, S275L) were investigated using quantitative cell-fusion assays and rRSVs via the use of BAC recombineering protocols. These mutations enabled RSV-A and -B to escape palivizumab neutralization but had differential impacts on cell-to-cell fusion, as the S275L mutation resulted in an almost-complete ablation of syncytium formation. These reverse genetics systems will facilitate future cross-validation efficacy studies of novel RSV therapeutic intervention strategies and investigations into viral and host factors necessary for virus entry and cell-to-cell spread.


Subject(s)
Drug Resistance, Viral/genetics , Mutation , Respiratory Syncytial Viruses/genetics , Animals , Antiviral Agents/toxicity , Chlorocebus aethiops , Drug Resistance, Viral/immunology , Hep G2 Cells , Humans , Palivizumab/toxicity , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/immunology , Respiratory Syncytial Viruses/isolation & purification , Respiratory Syncytial Viruses/pathogenicity , Reverse Genetics/methods , Vero Cells
13.
Sci Rep ; 11(1): 1463, 2021 01 14.
Article in English | MEDLINE | ID: mdl-33446831

ABSTRACT

Respiratory syncytial virus (RSV) is responsible for a significant burden of severe acute lower respiratory tract illness in children under 5 years old; particularly infants. Prior to rolling out any vaccination program, identification of the source of infant infections could further guide vaccination strategies. We extended a dynamic model calibrated at the individual host level initially fit to social-temporal data on shedding patterns to include whole genome sequencing data available at a lower sampling intensity. The study population was 493 individuals (55 aged < 1 year) distributed across 47 households, observed through one RSV season in coastal Kenya. We found that 58/97 (60%) of RSV-A and 65/125 (52%) of RSV-B cases arose from infection probably occurring within the household. Nineteen (45%) infant infections appeared to be the result of infection by other household members, of which 13 (68%) were a result of transmission from a household co-occupant aged between 2 and 13 years. The applicability of genomic data in studies of transmission dynamics is highly context specific; influenced by the question, data collection protocols and pathogen under investigation. The results further highlight the importance of pre-school and school-aged children in RSV transmission, particularly the role they play in directly infecting the household infant. These age groups are a potential RSV vaccination target group.


Subject(s)
Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/genetics , Respiratory Syncytial Virus Infections/transmission , Adolescent , Bayes Theorem , Child , Child, Preschool , Family Characteristics , Female , Humans , Infant , Infant, Newborn , Kenya/epidemiology , Male , Models, Theoretical , Respiratory Syncytial Virus, Human/pathogenicity , Respiratory Syncytial Viruses/pathogenicity , Stochastic Processes
14.
Cell Rep ; 34(4): 108672, 2021 01 26.
Article in English | MEDLINE | ID: mdl-33503419

ABSTRACT

Extracellular vesicles (EVs) are increasingly appreciated as a mechanism of communication among cells that contribute to many physiological processes. Although EVs can promote either antiviral or proviral effects during viral infections, the role of EVs in virus-associated polymicrobial infections remains poorly defined. We report that EVs secreted from airway epithelial cells during respiratory viral infection promote secondary bacterial growth, including biofilm biogenesis, by Pseudomonas aeruginosa. Respiratory syncytial virus (RSV) increases the release of the host iron-binding protein transferrin on the extravesicular face of EVs, which interact with P. aeruginosa biofilms to transfer the nutrient iron and promote bacterial biofilm growth. Vesicular delivery of iron by transferrin more efficiently promotes P. aeruginosa biofilm growth than soluble holo-transferrin delivered alone. Our findings indicate that EVs are a nutrient source for secondary bacterial infections in the airways during viral infection and offer evidence of transkingdom communication in the setting of polymicrobial infections.


Subject(s)
Coinfection/microbiology , Extracellular Vesicles/metabolism , Nutrients/metabolism , Pseudomonas aeruginosa/metabolism , Respiratory Syncytial Viruses/pathogenicity , Humans
15.
Med Sci Monit ; 27: e928148, 2021 Jan 25.
Article in English | MEDLINE | ID: mdl-33493141

ABSTRACT

BACKGROUND Bronchiolitis is common in infants under 2 years of age. Most infections are caused by respiratory syncytial virus (RSV), but the importance of Mycoplasma pneumoniae (MP) in the etiology of bronchiolitis is unclear. MATERIAL AND METHODS We investigated the clinical characteristics of bronchiolitis caused by MP in 79 infants admitted to Shunde Women's and Children's Hospital of Guangdong Medical University and Sanshui Women's and Children's Healthcare Hospital from January 2016 to December 2018. Infection with MP was confirmed by the presence of serum immunoglobulin M. RESULTS The peak detection rates of MP in the years 2016, 2017, and 2018 were 19.2%, 21.3%, and 24.0%, respectively. In each year, the peak of MP infections occurred during June and July. MP-associated bronchiolitis was mainly seen in infants from 6 to 12 months of age. Compared with RSV-associated bronchiolitis, the age of patients with bronchiolitis associated with MP was significantly older and they had a shorter hospital stay (all P<0.01 or P<0.05). CONCLUSIONS Our study indicated that MP is an important cause of bronchiolitis, with peaks of occurrence during June and July every year. Pulmonary interstitial infiltration was a characteristic of this infection. Azithromycin treatment can shorten the course of MP-associated bronchiolitis. Investigation of the epidemiological characteristics of pediatric MP-associated bronchiolitis can help diagnose and treat the disease correctly.


Subject(s)
Bronchiolitis/epidemiology , Pneumonia, Mycoplasma/epidemiology , Bronchiolitis/diagnosis , China/epidemiology , Epidemiologic Studies , Female , Hospitalization , Humans , Infant , Infant, Newborn , Length of Stay , Male , Mycoplasma pneumoniae/pathogenicity , Pneumonia, Mycoplasma/complications , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Viruses/pathogenicity
16.
Acta Pharmacol Sin ; 42(10): 1630-1641, 2021 Oct.
Article in English | MEDLINE | ID: mdl-33495515

ABSTRACT

Respiratory syncytial virus (RSV) is leading cause of respiratory tract infections in early childhood. Gut microbiota is closely related with the pulmonary antiviral immunity. Recent evidence shows that gut dysbiosis is involved in the pathogenesis of RSV infection. Therefore; pharmacological and therapeutic strategies aiming to readjust the gut dysbiosis are increasingly important for the treatment of RSV infection. In this study, we evaluated the therapeutic effects of a probiotic mixture on RSV-infected mice. This probiotic mixture consisted of Lactobacillus rhamnosus GG, Escherichia coli Nissle 1917 and VSL#3 was orally administered to neonatal mice on a daily basis either for 1 week in advance or for 3 days starting from the day of RSV infection. We showed that administration of the probiotics protected against RSV-induced lung pathology by suppressing RSV infection and exerting an antiviral response via alveolar macrophage (AM)-derived IFN-ß. Furthermore, administration of the probiotics reversed gut dysbiosis and significantly increased the abundance of short-chain fatty acid (SCFA)-producing bacteria in RSV-infected mice, which consequently led to elevated serum SCFA levels. Moreover, administration of the probiotics restored lung microbiota in RSV-infected mice. We demonstrated that the increased production of IFN-ß in AMs was attributed to the increased acetate in circulation and the levels of Corynebacterium and Lactobacillus in lungs. In conclusion, we reveal that probiotics protect against RSV infection in neonatal mice through a microbiota-AM axis, suggesting that the probiotics may be a promising candidate to prevent and treat RSV infection, and deserve more research and development in future.


Subject(s)
Antiviral Agents/therapeutic use , Gastrointestinal Microbiome/physiology , Macrophages, Alveolar/metabolism , Probiotics/therapeutic use , Respiratory Syncytial Virus Infections/prevention & control , Animals , Dysbiosis/metabolism , Fatty Acids, Volatile/metabolism , Female , Interferon-beta/metabolism , Lung/metabolism , Lung/microbiology , Lung/pathology , Mice, Inbred BALB C , Respiratory Syncytial Viruses/pathogenicity
18.
Clin Microbiol Infect ; 27(7): 1037.e9-1037.e14, 2021 Jul.
Article in English | MEDLINE | ID: mdl-32950713

ABSTRACT

OBJECTIVES: Viral acute respiratory infection (ARI) remains a major global health problem, especially among children in low- and middle-income countries. The study was conducted to reveal aetiological significance of respiratory viruses among both non-hospitalized and hospitalized children. METHODS: A cohort study of children with ARI at the household, primary healthcare facility, and hospital levels was conducted alongside a hospital-based study including non-cohort children from 2014 to 2016 in the Philippines. The ARI cases were recorded at households and healthcare facilities, and a clinical investigation was performed. Nasopharyngeal swabs were collected from the symptomatic children and tested for respiratory viruses via polymerase chain reaction. Then, the association between healthcare facility utilization and viral detection was investigated. RESULTS: Overall, 18,514 ARI cases were enrolled in the cohort study, and samples were collected from 4735 of these cases. The hospital-based study detected 648 ARI cases, all of which were sampled. Rhinovirus (22.2%; 1052/4735) was most frequently detected followed by respiratory syncytial virus (12.0%; 566/4735). Enterovirus (adjusted odds ratio, 1.8; 95% confidence interval, 1.1-2.8), human metapneumovirus (2.1, 1.4-3.2), rhinovirus (2.1, 1.8-2.6), and respiratory syncytial virus (1.6, 1.2-1.9) were significantly more prevalent in the ARI cases at healthcare facilities than in those in households. Of all ARI cases, 0.6% required hospitalization while 1.8% were hospitalized among the respiratory syncytial virus-positive cases (3.8, 3.0-4.9). CONCLUSIONS: We determined the prevalence of respiratory viruses among children with ARIs at the household, primary healthcare facility, and hospital levels and the association with clinical characteristics. In particular, we discovered a significant disease burden and impact of respiratory syncytial virus infections as well as a considerable aetiological implication of rhinovirus infections.


Subject(s)
Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Virus Diseases/epidemiology , Virus Diseases/virology , Child, Preschool , Health Facilities , Hospitalization , Humans , Incidence , Infant , Infant, Newborn , Philippines/epidemiology , Prevalence , Prospective Studies , Respiratory Syncytial Viruses/isolation & purification , Respiratory Syncytial Viruses/pathogenicity , Respiratory Tract Infections/physiopathology , Rhinovirus/isolation & purification , Rhinovirus/pathogenicity , Virus Diseases/physiopathology , Viruses/classification , Viruses/genetics , Viruses/isolation & purification , Viruses/pathogenicity
19.
Pediatr Res ; 90(2): 335-340, 2021 08.
Article in English | MEDLINE | ID: mdl-33214672

ABSTRACT

BACKGROUND: Potentially, orally administered antibodies specific to enteric pathogens could be administered to infants to prevent diarrheal infections, particularly in developing countries where diarrhea is a major problem. However, to prevent infection, such antibodies would need to resist degradation within the gastrointestinal tract. METHODS: Palivizumab, a recombinant antibody specific to respiratory syncytial virus (RSV), was used in this study as a model for examining the digestion of neutralizing antibodies to enteric pathogens in infants. The survival of this recombinant IgG1 across digestion in 11 infants was assayed via an anti-idiotype ELISA and RSV F protein-specific ELISA. Concentrations were controlled for any dilution or concentration that occurred in the digestive system using mass spectrometry-based quantification of co-administered, orally supplemented, indigestible polyethylene glycol (PEG-28). RESULTS: Binding activity of Palivizumab IgG1 decreased (26-99%) across each phase of in vivo digestion as measured by both anti-idiotype and RSV F protein-specific ELISAs. CONCLUSION: Antibodies generated for passive protection of the infant gastrointestinal tract from pathogens will need to be more resistant to digestion than the model antibody fed to infants in this study, or provided in higher doses to be most effective. IMPACT: Binding activity of palivizumab IgG1 decreased (26-99%) across each phase of in vivo infant digestion as measured by both anti-idiotype and RSV F protein-specific ELISAs. Palivizumab was likely degraded by proteases and changes in pH introduced in the gut. Antibodies generated for passive protection of the infant gastrointestinal tract from pathogens will need to be more resistant to digestion than the model antibody fed to infants in this study, or provided in higher doses to be most effective. The monoclonal antibody IgG1 tested was not stable across the infant gastrointestinal tract. The observation of palivizumab reduction was unlikely due to dilution in the gastrointestinal tract. The results of this work hint that provision of antibody could be effective in preventing enteric pathogen infection in infants. Orally delivered recombinant antibodies will need to either be dosed at high levels to compensate for digestive losses or be engineered to better resist digestion. Provision of enteric pathogen-specific recombinant antibodies to at-risk infants could provide a new and previously unexplored pathway to reducing the infection in infants. The strategy of enteric recombinant antibodies deserves more investigation throughout medicine as a novel means for treatment of enteric disease targets.


Subject(s)
Antiviral Agents/metabolism , Digestion , Gastrointestinal Tract/metabolism , Palivizumab/metabolism , Respiratory Syncytial Virus Infections/prevention & control , Respiratory Syncytial Viruses/immunology , Administration, Oral , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/metabolism , Antibodies, Viral/immunology , Antibodies, Viral/metabolism , Antiviral Agents/administration & dosage , Drug Stability , Enzyme-Linked Immunosorbent Assay , Female , Host-Pathogen Interactions , Humans , Infant, Newborn , Male , Palivizumab/administration & dosage , Protein Stability , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/pathogenicity
20.
Gac. sanit. (Barc., Ed. impr.) ; 34(5): 474-479, sept.-oct. 2020. tab, graf
Article in Spanish | IBECS | ID: ibc-198870

ABSTRACT

OBJETIVO: Describir si la información microbiológica del virus respiratorio sincitial (VRS) facilitada semanalmente por cuatro hospitales captura adecuadamente la estacionalidad del VRS en toda la comunidad. MÉTODO: Estudio descriptivo retrospectivo. Se compararon las detecciones de VRS en muestras respiratorias de pacientes (ingresados y no), de todos los grupos de edad, de los cuatro hospitales que forman parte del sistema de vigilancia microbiológica (SVM), con datos del Conjunto Mínimo Básico de Datos de hospitalización por bronquiolitis causada por VRS u otro microorganismo infeccioso, en pacientes menores de 5 años ingresados en cualquier hospital público de Galicia (temporadas 2008/2009 a 2016/2017). Se consideró como periodo de onda epidémica cuando la positividad de detecciones de VRS en el total de muestras respiratorias del SVM superó el 10%. Se calculó la sensibilidad del SVM como el porcentaje de ingresos ocurridos en la onda epidémica. RESULTADOS: La sensibilidad del SVM fue del 92% (86-96%) para los ingresos por bronquiolitis por VRS en cada temporada y del 79% (75-84%) para los ingresos por bronquiolitis totales. CONCLUSIONES: El SVM del VRS, basado en información de solo cuatro hospitales, mostró muy buena sensibilidad para predecir el inicio y el final de la onda anual de VRS en toda la comunidad autónoma. Estos resultados respaldan la utilización de esta información para alertar a todo el sistema sanitario del inicio de la onda


OBJECTIVE: To describe whether the microbiological information of the respiratory syncytial virus (RSV), provided by four hospitals on a weekly basis, adequately captures the seasonality of the RSV in the entire community. METHOD: Retrospective descriptive study. We compared the detection of RSV in respiratory samples of patients (hospitalized and not) from all age groups, from the 4 hospitals that are part of the microbiological surveillance system (MSS), with data from the Minimum Basic Data Set of hospitalization for bronchiolitis by RSV or another infectious organism, in patients under 5 years of age, admitted to any public hospital in Galicia (seasons 2008/2009 to 2016/2017). An epidemic wave period was considered when the positivity of RSV detections in the total respiratory samples of the SVM exceeded 10%. The sensitivity of the MSS was calculated as a percentage of admissions occurring in the epidemic wave. RESULTS: MSS sensitivity was 92% (86%-96%) for RSV bronchiolitis admissions in each season and 79% (75%-84%) for total bronchiolitis admissions. CONCLUSIONS: The RSV microbiological surveillance system, based on data from only 4 hospitals, showed very good sensitivity to predict the start and end of the annual RSV wave throughout the Galician region. These results support the use of this information to alert the entire health system of the onset of the wave


Subject(s)
Humans , Respiratory Syncytial Viruses/pathogenicity , Respiratory Syncytial Virus Infections/microbiology , Bronchiolitis/microbiology , Epidemiologic Surveillance Services , Microbiological Techniques/methods , Spain/epidemiology , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Tract Infections/microbiology , Sensitivity and Specificity , Retrospective Studies
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