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Oliveira, Ana Luísa Araújo. "Adventitious respiratory sounds in children with respiratory infection." Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/13734.
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Mestrado em FisioterapiaBackground: Lower respiratory tract infections (LRTI) are the leading cause of hospital visits in children under 5 years old. Therefore, there is an urgent and unmet need to develop objective, reliable and quick measures for respiratory paediatric assessment. Computerised adventitious respiratory sounds (ARS) have shown to be objective and reliable to assess/monitor respiratory diseases; however its application in children with LRTI is unknown. Aim: To characterise/compare ARS in healthy children and children with LRTI. Methods: A cross-sectional descriptive-comparative study was conducted in three healthcare institutions. Children were diagnosed by the paediatrician as healthy or with a LRTI and grouped according to their age (i.e, 0-2 years old or 3-5 years old). Socio-demographic and anthropometric data, type and severity of LRTI and cardio-respiratory parameters were collected. Respiratory sounds were recorded from the chest with a digital stethoscope following the Computerised Respiratory Sound Analysis guidelines. Wheezes’ location, mean number, type, frequency and occupation rate and crackles’ location, mean number, type, frequency, initial deflection width, two cycle duration, and largest deflection width were analysed per breathing phase. Results: Forty children enrolled in this study: 22 aged 0-2 years old (G1: 11 healthy; G2: 11 with LRTI) and 18 aged 3-5 years old (G3: 9 healthy; G4: 9 with LRTI). Few children, both healthy and with LRTI presented wheezes. In both age ranges, children with LRTI presented a higher percentage of the expiratory phase occupied by wheezes (G1: M 2.15 IQR 1.45 vs. G2: M 4.73 IQR 6.72 p=0.001; G3: M 2.80 IQR 3.27 vs. G4: M 5.17 IQR 15.99 p=0.07). Crackles were found in all children in at least one chest location. In both age ranges, children with LRTI presented more inspiratory crackles (G1: M 0.25 IQR 0.31 vs. G2: M 0.52 IQR 0.70; p<0.001; G3: M 0.50 IQR 0.49 vs. G4: M 0.70 IQR 0.21 p=0.03), especially fine crackles than healthy children (G1: M 0.07 IQR 0.13 vs. G2: M 0.18 IQR 0.42 p=0.001; G3: M 0.11 IQR 0.21 vs. G4: M 0.17 IQR 0.23 p=0.001). Coarse expiratory crackles were the most common type of crackle found in both healthy children (G1: M 0.33 IQR 0.56; G3: M 0.56 IQR 0.99) and children with LRTI (G2: M 0.33 IQR 0.56; G4: M 1.14 IQR 1.38). No differences were found for the remaining parameters. Conclusion: Healthy children and children with LRTI of different ages present ARS (i.e., crackles and wheezes). The occupation rate of wheezes and the mean number of crackles were the parameters that most differed between healthy children and children with LRTI in both age ranges. Therefore these ARS’ parameters may be the best criteria to discriminate the groups.
Enquadramento: As infeções respiratórias do tracto inferior (IRTI) são a principal causa de visitas/admissões hospitalares em crianças com idade inferior a 5 anos. Desta forma, verifica-se uma urgente necessidade de desenvolver medidas de avaliação respiratória pediátricas que sejam objetivas, fiáveis e de rápida aplicação. Os sons respiratórios adventícios (SRA) computorizados têmse revelado objetivos e fiáveis na avaliação/monitorização de doenças respiratórias; contudo a sua aplicação em pediatria é desconhecida. Objetivos: Caracterizar/comparar os SRA em crianças saudáveis e com IRTI. Métodos: Um estudo transversal descritivo-comparativo foi realizado em três instituições de saúde. As crianças foram diagnosticadas pelo pediatra como saudáveis ou com IRTI e agrupadas de acordo com a sua idade (i.e., 0-2 anos ou 3-5 anos). Dados antropométricos, sócio-demográficos, cardio-respiratório e tipo/severidade da IRTI foram recolhidos. Os sons respiratórios foram foram recolhidos no tórax com um estetoscópio digital, de acordo com as orientações internacionais. A localização, número médio, tipo, frequência e taxa de ocupação das sibilâncias e a localização número médio, tipo, frequência, initial deflection width, two cycle duration, e largest deflection width dos fervores foram analizados por fase respiratória. Resultados: Quarenta crianças participaram neste estudo: 22 com idades entre is 0-2 anos (G1: 11 saudáveis; G2: 11 com IRTI) e 18 com idades entre os 3-5 anos (G3: 9 saudáveis; G4: 9 com IRTI). Poucas crianças de ambos os grupos apresentaram sibilâncias. Para ambas as faixas etárias as crianças com IRTI apresentaram uma maior percentagem da expiração ocupada por sibilâncias (G1: M 2.15 IQR 1.45 vs. G2: M 4.73 IQR 6.72 p=0.001; G3: M 2.80 IQR 3.27 vs. G4: M 5.17 IQR 15.99 p=0.07). Todas as crianças apresentaram fervores em pelo menos um local de auscultação. Em ambas as faixas etárias, aqueles com IRTI apresentaram mais fervores inspiratórios (G1: M 0.25 IQR 0.31 vs. G2: M 0.52 IQR 0.70; p<0.001; G3: M 0.50 IQR 0.49 vs. G4: M 0.70 IQR 0.21 p=0.03), especialmente fervores crepitantes , (G1: M 0.07 IQR 0.13 vs. G2: M 0.18 IQR 0.42 p=0.001; G3: M 0.11 IQR 0.21 vs. G4: M 0.17 IQR 0.23 p=0.001). Os fervores expiratórios subcrepitantes foram os mais comuns entre todas as crianças (G1: M 0.33 IQR 0.56; G2: M 0.33 IQR 0.56; G3: M 0.56 IQR 0.99; G4: M 1.14 IQR 1.38).Não foram encontradas diferenças relativamente aos restantes parâmetros avaliados. Conclusão: Crianças saudáveis e com IRTI de diferentes faixas etárias apresentam SRA (i.e., sibilâncias e fervores). A taxa de ocupação das sibilâncias e o número de fervores foram as características que apresentaram mais diferenças entre os participantes saudáveis e os participantes com IRTI. Desta forma, conclui-se que estas características dos SRA poderão constituir os melhores critérios de discriminação entre os grupos.
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Del, Valle Mendoza Juana, Tapia Ángela Cornejo, Pablo Weilg, Eduardo Verne, Fuertes Ronald Nazario, Claudia Ugarte, Valle Luis J. del, and Toma´ s. Pumarola. "Incidence of Respiratory Viruses in Peruvian Children With Acute Respiratory Infections." John Wiley & Sons, 2015. http://hdl.handle.net/10757/347016.
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jdelvall@upc.edu.peAcute respiratory infections are responsible for high morbi–mortality in Peruvian children. However, the etiological agents are poorly identified. This study, conducted during the pandemic outbreak of H1N1 influenza in 2009, aims to determine the main etiological agents responsible for acute respiratory infections in children from Lima, Peru. Nasopharyngeal swabs collected from 717 children with acute respiratory infections between January 2009 and December 2010 were analyzed by multiplex RT-PCR for 13 respiratory viruses: influenza A, B, and C virus; parainfluenza virus (PIV) 1, 2, 3, and 4; and human respiratory syncytial virus (RSV) A and B, among others. Samples were also tested with direct fluorescent-antibodies (DFA) for six respiratory viruses. RT-PCR and DFA detected respiratory viruses in 240 (33.5%) and 85 (11.9%) cases, respectively. The most common etiological agents were RSV-A (15.3%), followed by influenza A (4.6%), PIV-1 (3.6%), and PIV-2 (1.8%). The viruses identified by DFA corresponded to RSV (5.9%) and influenza A (1.8%). Therefore, respiratory syncytial viruses (RSV) were found to be the most common etiology of acute respiratory infections. The authors suggest that active surveillance be conducted to identify the causative agents and improve clinical management, especially in the context of possible circulation of pandemic viruses
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Pruikkonen, H. (Hannele). "Viral infection induced respiratory distress in childhood." Doctoral thesis, Oulun yliopisto, 2015. http://urn.fi/urn:isbn:9789526207919.
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Abstract Dyspnoea associated with respiratory infection is a common symptom in infancy and early childhood. Inspiratory stridor is the main symptom in cases of croup and expiratory wheezing in cases of bronchiolitis, obstructive bronchitis and acute asthma exacerbations. Dyspnoea associated with respiratory infection is a common cause of emergency department visits and unplanned hospital admissions among infants and preschool children. The assessment of dyspnea associated with acute childhood respiratory infection is largely subjective, and evidence regarding the severity of acute dyspnoea is needed in order to target hospital admissions more accurately. Wheezing associated with respiratory infection in infancy has been recognized as an important predictor of recurrent wheezing and asthma at school age. The aims of this study were to determine the risk factors for croup, to evaluate factors that reliably predict the need for hospitalizing children with acute wheezing and to find out whether respiratory infection with wheezing during infancy has a positive association with the development of asthma during childhood. The work included two register-based surveys and one prospective cohort study. It is concluded that a family history of croup is an exceptionally strong risk factor for croup and its recurrence in childhood. The early phase of bronchiolitis is unstable in infants below 6 months of age. These infants are most likely to need medical interventions in the first 5 days after onset of the disease. A positive respiratory syncytial -virus test result, a fever of more than 38°C and low initial oxygen saturation are predictors of the need for hospitalization and medical interventions. An initial oxygen saturation >93% effectively identifies children aged more than 6 months with mild wheezing, and this limit can be used to avoid unplanned hospital admissions. There is an association between early respiratory syncytial -virus infections and subsequent wheezing and asthma, in that such infections select children who are prone to wheezing and asthma before school age, but the symptoms tend to decrease with time and an early respiratory syncytial -virus infection will not permanently alter bronchial reactivityTiivistelmä Hengitysvaikeus on yleinen oire lapsilla virusten aiheuttamien hengitystieinfektioiden yhteydessä. Kurkunpäätulehdukseen liittyy sisäänhengitysvaikeus. Ilmatiehyttulehdukseen, ahtauttavaan keuhkoputkentulehdukseen ja akuuttiin astmakohtaukseen liittyy uloshengitysvaikeus. Hengitystieinfektioihin liittyvä hengitysvaikeus on yksi yleisimmistä syistä päivystyspoliklinikkakäynteihin ja äkillisiin sairaalahoitojaksoihin lapsipotilailla. Hengitystieinfektioiden taudinkulun tuntemisella ja hengitysvaikeuden vaikeusasteen arvioinnilla on tärkeä merkitys näiden potilaiden hoidon toteuttamisessa. Hengitystieinfektioon liittyvää hengitysvaikeutta on pidetty riskitekijänä astman kehittymiselle. Tämän tutkimuksen tarkoituksena oli selvittää kurkunpäätulehduksen riskitekijöitä ja sairaalahoitoon vaikuttavia tekijöitä hengitystieinfektioon liittyvän uloshengitysvaikeuden hoidossa sekä varhaislapsuudessa sairastetun hengitystieinfektion yhteyttä myöhempään astma- ja allergiasairastavuuteen. Tutkimukseen sisältyi kaksi rekisteriaineistoa ja yksi seurantatutkimusaineisto. Tutkimuksessa todettiin, että kurkunpäätulehduksen uusiutuminen on erittäin tavallista ja sisarusten ja vanhempien sairastama kurkunpäätulehdus on merkittävin riskitekijä kurkunpäätulehdukselle ja sen uusiutumiselle. Alle 6 kuukauden ikäisillä lapsilla ilmatiehyttulehduksen taudinkuva on epävakaa ensimmäisen 5 oirepäivän aikana. Kuume, matala happisaturaatioarvo ja respiratory syncytial -virusinfektio ennustavat osastohoidon ja invasiivisten toimenpiteiden tarvetta ilmatiehyttulehduksen yhteydessä. Yli 6 kuukauden ikäisillä lapsilla happisaturaatioarvo > 93 % ennustaa lievää taudinkuvaa hengitystieinfektioon liittyvän uloshengitysvaikeuden hoidossa. Käyttämällä tätä happisaturaatioarvoa raja-arvona, kun arvioidaan sairaalahoidon tarvetta, voidaan merkittävästi ja turvallisesti vähentää sairaalahoidon tarvetta lasten hengitystieinfektioon liittyvän uloshengitysvaikeuden hoidossa. Alle 6 kuukauden iässä sairastettu respiratory syncytial -virusinfektio on riskitekijä varhaislapsuudessa ilmeneville astmaoireille, mutta tämä riski vähenee iän myötä ja 8 vuoden iässä ei ole havaittavissa eroja astma- ja allergiasairastavuudessa, kun verrataan näitä potilaita muun hengitystieinfektion sairastaneisiin potilaisiin ja terveisiin kontrollipotilaisiin
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Hussain, Imran Raza. "The immunobiology of respiratory syncytial virus infection." Thesis, University of Southampton, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289569.
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Wrightson, John M. "Pathogen identification in lower respiratory tract infection." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:30c757ec-99b7-492e-a12e-ff996581863a.
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Treatment of lower respiratory tract infection (pneumonia and pleural infection) relies on the use of empirical broad spectrum antibiotics, primarily because reliable pathogen identification occurs infrequently. Another consequence of poor rates of pathogen identification is that our understanding of the microbiology of these infections is incomplete. This thesis addresses some of these issues by combining the acquisition of high quality lower respiratory tract samples, free from nasooropharyngeal contamination, with novel molecular microbiological techniques in an attempt to increase rates of pathogen identification. Four main areas are examined: (i) The role of so-called ‘atypical pneumonia’ bacteria in causing pleural infection. These pathogens have been previously identified in the pleural space infrequently and routine culture usually fails to isolate such bacteria. High sensitivity nested polymerase chain reaction (PCR) is a culture-independent technique which is used to undertake a systematic evaluation for these pathogens in pleural infection samples. (ii) The role of Pneumocystis jirovecii in pleural infection, either as a co-infecting pathogen or in monomicrobial infection. This fungus causes severe pneumonia, particularly in the immunosuppressed, but is increasingly recognised as a co-pathogen in community-acquired pneumonia, and is frequently isolated in the upper and lower respiratory tract in health. A high sensitivity real-time PCR assay is used to examine for this fungus. (iii) Ultra-deep sequencing of the 16S rRNA gene is used to perform a comprehensive microbial survey in samples taken from the multi-centre MIST2 study of pleural infection. The techniques employed allow analysis of polymicrobial samples and give very high taxonomic resolution, whilst incorporating methods to control for potential contamination. Further, these techniques provide confirmation of the results from the ‘atypical’ bacteria nested PCR study. (iv) Bedside ultrasound-guided percutaneous transthoracic needle aspiration (TNA) of consolidated lung is undertaken in patients with pneumonia, as part of the PIPAP study. An evaluation is undertaken of the efficacy and acceptability of TNA. Aspirate samples acquired are also processed using ultra-deep sequencing of the 16S rRNA gene. Other samples obtained as part of the PIPAP study, such as ‘control’ lung aspirates and ‘control’ pleural fluid samples, are similarly processed to enable calculation of sensitivity and specificity of the sequencing methodology.
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Clark, Tristan William. "The role of respiratory virus infection in adults hospitalised with acute respiratory illness." Thesis, University of Leicester, 2013. http://hdl.handle.net/2381/28098.
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Acute respiratory illness represents a large proportion of adult patients admitted to secondary care. Many of these patients have respiratory virus infection but the exact burden of disease in defined clinical groups is unknown. Rhino-enteroviruses are increasingly implicated in severe acute respiratory illness in adults and advances in molecular diagnostics have led the recognition of high strain diversity and to the discovery of a new species (HRV-C). Biomarkers such as procalcitonin and C reactive protein may be able to identify patients with acute respiratory illness without bacterial infection, in whom antibiotics can be safely withheld, and so reduce unnecessary antibiotic prescribing. Patients with acute respiratory illness were recruited from two acute hospital sites in Leicester between 2005 and 2008 and nasopharyngeal swabs were collected and tested for the presence of respiratory viruses using a newly developed comprehensive, multiplex real-time RT-PCR assay. Gene sequencing was performed on samples positive for rhinovirus RNA. Levels of the biomarkers CRP and Procalcitonin were measured on serum samples. A high incidence of viral infection was identified among adults hospitalised with acute respiratory illness (44%) with rhino-enteroviruses accounting for around half of all viruses isolated. The rate of viral infection amongst non-respiratory control patients was low (7%). Rhinovirus gene sequencing demonstrated that around a quarter of all rhinovirus infections were caused by HRV-C and that there was a high level of diversity of strains circulating during the study period. The biomarkers procalcitonin and CRP were both highly accurate in distinguishing patients with pneumonia from exacerbations of airways disease. The results of this work have implications for hospital infection control practices, rationalisation of antibiotic use and in certain circumstances the use of directed antiviral agents. Procalcitonin and CRP could both potentially be used to reduce inappropriate antibiotic prescribing in patients hospitalised with acute respiratory illness.
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Tong, Jie [Verfasser]. "Co-infection of respiratory epithelial cells by respiratory viruses and streptococci / Jie Tong." Hannover : Bibliothek der Tierärztlichen Hochschule Hannover, 2018. http://d-nb.info/1162715758/34.
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Shi, Ting. "Epidemiology of respiratory syncytial virus associated acute lower respiratory infection in young children." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/23610.
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Introduction Acute lower respiratory infection (ALRI) remains as a leading cause of childhood morbidity and mortality. With the continued universal vaccination campaign against bacterial pathogens, an increase in relative proportion of respiratory viruses contributing to ALRI is anticipated. Respiratory syncytial virus (RSV) has been recognised as the most common pathogen identified in young children presenting with ALRI as well as an important cause of hospital admission. This thesis aims to estimate the aetiological roles and attributable fractions of common respiratory viruses among ALRI cases and investigate the risk factors for RSV associated ALRI in young children. It also aims to estimate the global and regional incidence of RSV associated ALRI in both community and hospital based settings, and the possible boundaries for RSV associated ALRI mortality in children younger than five years old. Methods Systematic reviews were carried out separately for the following three research questions: aetiological roles of RSV and other common viruses in ALRI cases, risk factors for RSV associated ALRI and global/regional burden of RSV associated ALRI, formulating an overall picture of epidemiology of RSV associated ALRI in young children. They all focused on children younger than five years old. The identified studies were selected according to pre-defined inclusion and exclusion criteria. The whole process was conducted following the PRISMA guidelines for systematic review and meta-analysis. Unpublished data from RSV Global Estimates Network (RSV GEN) were collected from 45 leading researchers on paediatric pneumonia (primarily in developing countries). They either reanalysed data from their already published work with the pre-defined standardised case definitions or shared hitherto unpublished data from ongoing studies. Data from both systematic reviews and RSV GEN working group were included into further meta-analysis. Random effects model was consistently applied in all meta-analyses. Results There were 23 studies identified through literature search satisfying the eligibility criteria, investigated the viral aetiology of ALRI in young children. Strong evidence was observed for RSV in support of its causal contribution in children presenting with ALRI and the association was significant measured in odds ratio: 9.79 (4.98-19.27). Thus, the corresponding attributable fraction among the exposed was estimated as 90% (80%-95%), which means around 90% of RSV associated ALRI cases were in fact attributed to RSV in a causal path. In total, 27 studies (including 4 unpublished studies) were included and contributed to the analysis. Across these studies, 18 risk factors were described and 8 of them were observed to have significant associations with RSV infection: prematurity - gestational age < 37 weeks, low birth weight (< 2.5 kg), being male, having siblings, maternal smoking, history of atopy, no breastfeeding and crowding - > 7 persons in household. Overall, 304 studies met the selection criteria and were included to estimate the global and regional burden of RSV associated ALRI in young children. These included 73 published articles identified through Chinese language databases and 76 unpublished studies provided by RSV GEN working group, mainly from developing countries. It is estimated that in 2015, there were 33.0 (95% CI 20.6-53.2) million episodes of RSV associated ALRI occurring in children younger than 5 years old across the world. 30.5 (95% CI 19.5-47.9) million of them were in developing countries. 3.0 (95% CI 2.2-4.0) million cases were severe enough and warranted hospitalisation. Around 60,000 children died in the hospital settings with 99% of these deaths occurring in developing countries. The overall mortality from RSV associated ALRI was estimated about 131,000. Conclusion This thesis not only enhanced the epidemiological understanding of RSV in young children, but also provided important information for public health decision makers. It incorporated both data through systematic reviews of published articles in the past 20 years and more than 70 unpublished data sets shared by RSV GEN working group. The population based incidence, hospitalisation, mortality and risk factor data are essential to assess the various severity of illness in a specific age group and region, and inform local public health professionals regarding appropriate and prompt cases management, prevention and vaccine allocation strategies. National sentinel systems of RSV surveillance gathering structured and reasonably representative data are needed. Within the surveillance system, a universal definition regarding disease severity in various settings should be developed, and diagnostic methods with higher sensitivity and specificity should be applied.
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Barasheed, Osamah Abdullah A. "Prevention of respiratory viral infection among Hajj pilgrims." Thesis, University of Sydney, 2020. https://hdl.handle.net/2123/23506.
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Hajj is one of the five basic tenets of Islam. Every practicing, financially and physically capable, Muslim is required to perform Hajj at least once in his/her lifetime. Each year up to three million people from more than 180 countries assemble in Mecca, Saudi Arabia, to perform Hajj pilgrimage. Severe crowding, shared accommodation, poor personal hygiene, and environmental pollution at Hajj may collectively lead to increased transmission of respiratory viruses. Influenza-like illness (ILI) is one of the most common medical presentations to primary care, mostly due to viral infection, in which pneumonia is the leading cause of hospital admission during Hajj. Therefore, I endeavoured to study the epidemiology of respiratory viruses among pilgrims including newly emergent viruses such as Middle East coronavirus (MERS-CoV) and assessed preventive strategies primarily focussing on facemasks effectiveness and evaluating influenza vaccine uptake. Methods To understand the epidemiology of respiratory infection during Hajj, a cross-sectional study was conducted among pilgrims from Saudi Arabia, Australia and Qatar. A nasal swab was collected from any participant who developed ILI to identify the causative agent. After that, we explored the possible preventive measures to reduce the transmission of respiratory viral infection such as influenza vaccine and facemasks. For influenza vaccine, an anonymous survey was conducted to assess the uptake of influenza vaccine, and explore the attitudes and barriers to, and perception of vaccination. At the same time, a pilot trial was conducted to explore the feasibility of establishing a large-scale trial to test the effectiveness of facemasks in preventing respiratory viral infection among Hajj pilgrims. The outcome of the pilot trial was encouraging and suggested that it was feasible to do a large-scale trial. Therefore, we conducted a large-scale randomised controlled trial (RCT) to test the effectiveness of facemasks in preventing respiratory viral infection over three consecutive Hajj seasons (2013, 2014, 2015). Results In 2013, we recruited 1038 pilgrims from Saudi Arabia, Australia and Qatar during the first day of Hajj and followed them closely for four days to comprehend the epidemiology of respiratory viral infection during the Hajj. About 11% of the pilgrims reported ILI; 38% of which had laboratory-confirmed viral infections. Rhinovirus was the commonest cause of ILI among Hajj pilgrims (25%) followed by influenza A (4%). Also, other types of viruses were reported such as adenovirus (2%), human coronavirus OC43/229E (2%) and parainfluenza virus 3, 1 (2%). MERS-CoV was considered a health risk at that year (2013), luckily, it was not detected in any sample in this study. The studies showed that influenza vaccine uptake was increased among Hajj pilgrims specifically the Australian. On the other hand, symptoms of respiratory infection were decreased. However, it is uncertain if this decrease is due to vaccination. Contrarily, facemasks uptake among Hajj pilgrims remained unchanged in the last 10 years with an average uptake of 50% according to a systematic review synthesised by myself and colleagues. Moreover, the large-scale RCT showed that pilgrims did not use facemasks adequately; and those who used facemasks had no statistically significant benefit against laboratory-confirmed or clinical viral respiratory tract infections. Conclusion Epidemiology of virus infection during Hajj showed that rhinovirus was the most common causative agent. Also, there were other respiratory viruses reported including influenza, adenovirus but not MERS-CoV. Influenza vaccine uptake is improving among Hajj pilgrims, while facemasks had lower uptake. Facemasks use did not prevent clinical or laboratory-confirmed respiratory viral infection during Hajj. This is may be due to poor compliance of pilgrims in using facemasks.
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Kristo, A. (Aila). "Acute rhinosinusitis during upper respiratory infection in children." Doctoral thesis, University of Oulu, 2005. http://urn.fi/urn:isbn:9514278720.
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Abstract
Acute rhinosinusitis is estimated to be one of the most common diseases in childhood. Still, the diagnostics and clinical relevance of this disease are controversial.
Bacterial rhinosinusitis cannot be differentiated from mere rhinitis on clinical grounds alone. Abnormal radiologic findings have been found to be common in child and adult volunteers without sinus symptoms and in adults during viral upper respiratory infection. In children, the results of the few placebo-controlled studies on the benefit of antimicrobial treatment of clinically diagnosed acute rhinosinusitis are controversial. Bacteriologic cultures obtained from the middle meatus by rigid nasal endoscopy have been introduced as a way to determine the bacteriology of the maxillary sinus in adults, but they have not been studied in children with acute symptoms.
In this thesis, incidental paranasal abnormalitites were found to be common in healthy school children examined by magnetic resonance imaging (MRI). Some of these abnormalities resolved during a follow-up period of 6 months, but new abnormalities appeared in some children. MRI abnormalities of the paranasal sinuses were found to be much more common in children with acute upper respiratory infections, and most of these abnormalities resolve spontaneously. Children with acute rhinosinusitis confirmed clinically and by imaging did not benefit from cefuroxime treatment as compared to placebo. Pathogenic bacteria (Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis) in the nasal middle meatus during acute upper respiratory infection predicted longer duration of the symptoms and signs of common cold.
Based on these findings, imaging methods should not be used in the diagnostics of acute rhinosinusitis in children. Similarily, incidental imaging findings of abnormalities in the paranasal sinuses or in children with symptoms of acute rhinosinusitis are not an indication for antimicrobial treatment. Because middle meatal pathogenic bacteria were found to predict prolonged symptoms of upper respiratory infection, a randomized controlled trial is needed to evaluate the clinical value of middle meatal culture in identifying the children who would benefit from antimicrobial treatment during acute respiratory infection.
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Manley, Grace C. A. "The roles of DUSPs in respiratory viral infection." Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/19257/.
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Mize, Maximillion. "Interleukin-17A Worsens Severe Murine Respiratory Mycoplasma Infection." Thesis, University of North Texas Health Science Center at Fort Worth, 2018. http://pqdtopen.proquest.com/#viewpdf?dispub=10843638.
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The purpose of these studies was to determine the role of Interleukin-17A (IL-17A) in the immune response to respiratory mycoplasma infection. Serum levels of IL-17A increase in disease-susceptible BALB/c mice, but not disease-resistant C57BL/6 mice, infected with Mycoplasma pulmonis. Increased serum IL-17A was associated with mycoplasma pathology during infection in BALB/c mice, including: the presence of pulmonary neutrophils, progressive weight loss, and the development of inflammatory lung lesions.
Neutralizing the function of IL-17A using monoclonal anti-IL-17A antibodies during mycoplasma infection reduced disease severity in disease-susceptible BALB/c mice, but not disease-resistant C57BL/6 mice. Providing daily intra-peritoneal injections of anti-IL-17A antibodies to BALB/c mice infected with M. pulmonis was effective at reducing weight loss, the prevalence of clinical signs, and the incidence of gross lesions. Histological lesions, characterized by the presence of pulmonary neutrophils, were also lower in infected BALB/c mice receiving anti-IL-17A antibodies daily. Bacterial burden remained unaffected in mice regardless of treatment. Neutralizing IL-17A throughout infection was effective at reducing late mycoplasma pathology, a period influenced by the actions of adaptive immunity and this is supported by a reduction in disease severity when infected BALB/c mice were provided intra-peritoneal injections of anti-IL-17A antibodies only after T-cells infiltrate the lungs.
Pulmonary T-cells, specifically CD4+ T-helper (Th17) cells, were the primary source of IL-17A throughout infection with M. pulmonis in disease-susceptible BALB/c mice. Although Th17 cells increased in the lung after infection, the Th17 response did not reach its peak until the later stages of infection and coincided with when the neutralization of IL-17A started to reduce the severity of disease. IL-17A+ T-cells did not express Retinoic Acid Related (RAR) Orphan Receptor-γt (RORγt), a signature Th17 transcription factor, after infecting BALB/c mice with M. pulmonis and suggests that RORγt is not a suitable marker to identify the IL-17A+ T-cells worsening mycoplasma disease.
The effect of neutralizing IL-17A was mimicked in disease-susceptible BALB/c mice depleted of neutrophils during M. pulmonis infection. Depleting neutrophils in BALB/c mice infected with M. pulmonis abrogated weight loss while reducing the appearance of both clinical signs and gross lesions. IL-17A promotes pathology during disease utilizing various mechanisms, one of which is to mobilize and activate neutrophils; however, the IL-17A failed to worsen mycoplasma disease in the absence of neutrophils during M. pulmonis infection in BALB/c mice. These results suggest that IL-17A relies only upon neutrophil recruitment and activation to exacerbate mycoplasma disease. Supporting this, combining the neutralization of IL-17A with the depletion of neutrophils failed to lessen disease severity beyond what either treatment could achieve alone. These findings underscore IL-17A or neutrophils as targets for inhibition to reduce the severity of disease during mycoplasma infection.
Both IL-4 and IL-17A increase in the lungs of BALB/c mice infected with M. pulmonis and there are Th17 cells that secrete IL-4. In STAT6 KO mice that respond poorly to IL-4 and generate defective Th2-mediate immunity, neutralizing IL-17A also reduced inflammatory damage during M. pulmonis infection. Treating STAT6 KO mice with anti-IL-17A antibodies during M. pulmonis infection reduced weight loss, the prevalence of clinical signs, and incidence of inflammatory lesions. Like wild-type mice, the pathologic effect of IL-17A manifested during the later stages of M. pulmonis infection in STAT6 KO mice and coincided with the activation of adaptive immunity. Neutralizing IL-17A also failed to change mycoplasma numbers during infection in STAT6 KO mice. IL-17A is highlighted as an independent contributor to mycoplasma pathology with no impact on mycoplasma clearance; inhibiting the activation of Th2- and Th17-mediated immune responses could increase resistance by permitting the development of protective responses during infection.
This work emphasizes the importance of IL-17A and Th17 cells as an autonomous immune response worsening neutrophil-mediated pathology during late mycoplasma infection in susceptible mice. Monoclonal antibodies that neutralize the function of IL-17A could reduce the severity of disease during mycoplasma infection in man and animals. Directly targeting neutrophils may also lessen the negative impact IL-17A has on mycoplasma pathology. Vaccines that do not activate IL-17A-mediated immunity could reduce the susceptibility to mycoplasma infection and allow for the development of immune responses that lead to mycoplasma clearance. IL-17A functions to worsen disease severity without impacting mycoplasma clearance, and so IL-17A is identified as a contributor to pathology during infection.
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Cline, Troy. "Innate Immune Mechanisms of Controlling Respiratory Virus Infection." The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1262099397.
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Deacon, Jill. "Antimicrobial nanotherapies for respiratory infection in cystic fibrosis." Thesis, Queen's University Belfast, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.695326.
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This thesis presents the design, development and efficacy of antimicrobial nanotherapies, to overcome the challenges faced by conventional antimicrobial delivery for the treatment of Pseudomonas aeruginosa respiratory infections in cystic fibrosis (CF). In the CF lungs, mucus and biofilms pre.sent complex barriers to the optimal delivery of antimicrobial therapy, leading to low antimicrobial exposure to resident bacteria and inadequate eradication. Respiratory disease, associated with chronic respiratory infection, is ultimately the main cause of morbidity and mortality in CF patients. There is a need to develop improved antimicrobial and anti-biofilm therapies in this patient group. Firstly, alginate/chitosan polymeric nanoparticle (NP) delivery vehicles for the antimicrobial tobramycin were formulated. Tobramycin NPs demonstrated antimicrobial efficacy against laboratory and clinically isolated strains of P. aeruginosa in vitro and in vivo against infected Galleria mellonella. Next, functionalisation of the mucolytic DNase to tobramycin NPs was investigated with the aim to improve penetration of the mucus and biofilm barriers, to increase the accessibility of tobramycin to the difficult-to-reach sites of infection. Functional activity of both drugs was established against DNA, P. aeruginosa strains and in CF sputum. DNase functionalisation was found to improve the sputum penetration of NPs and these DNase tobramycin NPs possessed anti microbia! activity in sputum samples from CF patients. Finally, the antimicrobial activity of the developed nanotherapies against P. aeruginosa biofilms was studied. DNase tobramycin NPs have the potential to target both the biofilm matrix and bacterial cells through the combined DNA degradation and bactericidal actions of DNase and tobramycin. Against established P. aeruginosa biofilms, both tobramycin NPs and DNase tobramycin NPs were found to be effective antimicrobial agents. The developed antimicrobial nanotherapies represent a promising therapeutic strategy for improving tobramycin delivery to mucus-embedded, biofilm-associated respiratory infections in CF.
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Brown, Helen. "Host responses to respiratory infection in cystic fibrosis." Thesis, University of Bath, 2001. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.392017.
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Xie, Xiaojian. "Evaporation and movement of respiratory droplets in indoor environments." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B40987802.
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Agoti, Charles Nyaigoti. "Genetic diversity of respiratory syncytial virus (RSV) in relation to infection and re-infection." Thesis, Open University, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.664468.
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Background. Respiratory syncytial virus (RSV) causes recurrent epidemics in communities and repeated reinfections of individuals throughout life. The extent to which this is a consequence of antigenic diversity of the virus caused by genetic evolution is poorly defined. Clarification of these phenomena has implications for our understanding of RSV persistence and vaccine control. Further, studying RSV epidemics genetic composition contributes to understanding of the transmission dynamics of this virus. Methods. RSV positive specimens were available from the freezer archives of three epiderrnologic studies in KVifi District, Coastal Kenya, undertaken between 2002 and 2012. Selected specimens were nucleotide sequenced in the highly variable attachment (G) protein gene (n=917) or for whole genomes (n=83), and phylogenetically analyzed. This analysis was supported by a set of contemporaneous sequences from around the world deposited in GenBank. Results. The genetic relatedness of virus sequences from infection-reinfection pairs from individuals followed within a birth c.ohort (2.002-05) revealed that the vast majoritY (>90%, 48/53) differed by either RSV group, genotype or G amino acid sequence. However, the genotype temporal distribution amongst re-infections mirrored the contemporaneous distribution in the wider study population.
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Graham, Neil M. H. "Psychosocial factors in the epidemiology of acute respiratory infection /." Title page, contents, thesis synopsis and summary only, 1987. http://web4.library.adelaide.edu.au/theses/09MD/09mdg741.pdf.
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Snelgrove, Robert. "Manipulation of the myeloid immune compartment during respiratory infection." Thesis, Imperial College London, 2007. http://hdl.handle.net/10044/1/11917.
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Droniou, Magali Eliane. "Localisation of human respiratory syncytial virus proteins during infection." Thesis, University of Warwick, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.487956.
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Human respiratory syncytial vilUs (hRSV) is an important pathogen causing respiratory disease, affecting predominantly the infant and elderly populations. No effective vaccine or anti-viral treatment is yet available against this virus. hRSV is a negative-sense, nonsegmented RNA virus, which encodes II proteins. The N, P, Land M2-1 proteins constitute the viral polymerase and the M2-2 protein acts as a regulatory element in the balance between transcription and replication. The G protein allows attachment of the virus to cellular glycosaminoglycans receptors, and the F protein mediates entry of the virus into the cell. The M protein drives virus assembly and budding of progeny virions, and the non-structural proteins NSI and NS2 act as antagonists of the interferon system. The SH protein has been shown to possess anti-apoptotic properties. Some of hRSV proteins have been shown to play additional roles to the ones described. Since protein function and intracellular localisation are linked, analysis of viral protein movement within infected cells may lead to information regarding the functions of the proteins studied. hRSV protein localisation was elucidated by immunostaining of viral proteins for which antibodies were available. This confirmed the hRSV N, P and M2-1 proteins distribution to cytoplasmic inclusion bodies and uncovered the additional diffuse presence of these viral proteins in the cytoplasm and into small cytoplasmic inclusions with distinct morphological characteristics. The M2-1 protein was also faintly detected in the nucleus of infected cells. To acquire an insight into the dynamics of viral proteins during infection in live cells, the hRSV proteins were tagged with either the green fluorescent protein or its spectral variants, for introduction into virus by reverse genetics. Initially, a codon-optimized synthetic G gene was generated and introduced in the pre-existing G-deleted hRSV strain RS-S2 antigenomic. eDNA clone. Infectious recombinant rRS-S2syG virus, expressing the synthetic G gene, was successfully recovered and exhibited altered growth kinetics compared to both wild-type virus hRSV strain RS-S2 and recombinant rRS-S2 vilUs bearing a deletion of the G gene. Since the G protein was correctly expressed and localised, this suggested that the sequence or structure of the authentic genomic RNA is important for virus replication. The hRSV N, P, L, M2-1, NSI and NS2 proteins were tagged at both amino- and carboxy-termini with a fluorescent marker. The N, P and L fusion proteins retained some binding activities, as characterised by their correct localisation to inclusion bodies in hRSV superinfected cells. The localisation observed within the inclusion bodies was shown to follow specific patterns which varied within the same cell population, indicative of a dynamic rearrangement of protein distribution within the inclusion bodies. However, the loss of activity in minigenome transcription experiments observed for all tagged N, P and L proteins prevented their introduction into recombinant virus. In contrast, the carboxytagged M2-1 protein retained the majority of the wild-type transcriptional enhancement properties. The NSI protein, when expressed alone, was found to follow two distinct localisation patterns within the cell population, being principally observed as present in the nucleus and cytoplasm or in a lesser proportion of cells, exclusively in the cytoplasm. The NS2 protein, when expressed alone, showed a perinuclear accumulation of granular appearance. However, the aberrant intracellular localisation of fluorescentlytagged NSI and NS2 proteins, compared to wild-type NS1/2 prevented the introduction into recombinant viruses. Investigating the role of the ubiquitin-proteasome pathway in hRSV infection, it was found that the previously described rapid turnover of the NS2 protein was due its degradation by the proteasome complex. The NS1 protein was also found to be targeted to the proteasome, while the rate of ubiquitination was fomid to be increased during hRSV infection.
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Almond, Elizabeth Jennifer Philippa. "Epstein-Barr virus infection of the lower respiratory tract." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1989. http://hub.hku.hk/bib/B31208484.
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Weber, Martin Willi. "Infection with the respiratory syncytial virus in the Gambia." Thesis, Open University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262711.
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Van, der Heyde Yolande. "Lower respiratory tract infection in sudden unexpected infant deaths." Master's thesis, University of Cape Town, 2012. http://hdl.handle.net/11427/14391.
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Pneumonia due to polymicrobial infection is known to increase the severity and risk of fatality among young children. A retrospective study was undertaken on Sudden Unexpected Infant Death cases occurring, between 1 May and 30 September 2009, which were admitted to a medico-legal mortuary servicing the Cape Town western metropole. Published studies have shown the risk factors for lower respiratory tract infection to include lack of breast feeding, prenatal and environmental tobacco smoke exposure, prematurity, immunosuppression, underlying medical conditions and overcrowding. The present study was aimed at determining which of the known epidemiological factors were associated with SUDI death types admitted to this mortuary and to describe the associated histopathology. In addition, in the knowledge that drugs, specifically Methamphetamine are widely used on the Cape Flats from where almost all this mortuary's SUDI cases are derived, this study has attempted to find out whether or not the usage of drugs by the caregiver at the time of infant death was another independent risk factor in SUDI deaths.
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Hardisty, Gareth Rhys. "The effect of on-going and persistent infection on acute respiratory infection with influenza A." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/22080.
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Humans are subject to infection with a wide range of commensal and pathogenic organisms. Each pathogen requires an appropriate immune response to eliminate or control the invading organism and minimise pathology. Many pathogens have evolved strategies to subvert or manipulate the immune response and establish on-going infections. Similarly acute respiratory infection with virulent strains of influenza A virus are often poorly controlled by the immune system and can cause severe immunopathology and even fatality as a result of an inappropriate and excessive inflammatory response called a ‘cytokine storm’. Morbidity due to influenza infection and exacerbation by the immune response can vary greatly between individuals. The effect of underlying infection on the immune system could contribute to the variation in response. The aim of this project was therefore to determine if co-infection with two pathogens that establish on-going infections could alter the immune response to influenza A and impact the outcome of infection. Persistent infections with filarial helminths can cause debilitating disease and significantly impact the immune response toward a skewed TH2 or regulatory phenotype in order to control pathology. In contrast, infection with gammaherpesviruses in an immunocompetent host causes an initial inflammatory ‘anti-viral’ response before becoming an asymptomatic, latent infection. In an immunocompromised host, gammaherpesviruses can reactivate and lead to clinical presentation of disease. This suggests that these viruses require an on-going immune response to control all stages of infection. Both filarial helminths and gammaherpesviruses are common infections in human populations and therefore mouse models of these infections provide relevant systems to study their potential role in influenza virus infections. In a BALB/c murine co-infection model, latent infection with the rodent gammaherpesvirus MHV-68 led to significantly decreased weight loss and clinical signs following high dose infection with A/WSN/33, (a H1N1 influenza A virus). This was coupled with decreased immunopathology in the lung and fewer infiltrating lymphocytes in the alveolar spaces and around larger airways, although infectious virus titres were not significantly reduced. This response was coupled with a decreased production of inflammatory cytokines and chemokines in co-infected mice 6 days post infection which correlated with the amelioration of pathogenesis in these animals. A repeat of the study in 129Sv/Ev IFNγR knock out mice showed the same protective effect in the co-infected mice, suggesting IFNγ is not critical for the protective phenotype. Mice infected with latent MHV-68 alone showed a significant increase in expression of T cell chemokines in the lung and alveolar macrophages had a significantly increased production of suppressor of cytokine signalling (SOCS-1) suggesting latent MHV-68 infection may impact the phenotype of macrophages in the lung, modulating the response to influenza co-infection. A co-infection model with a persistent rodent filarial helminth, Litomosoides sigmodontis and A/WSN/33 was also established in BALB/c mice. The L4 developmental stage of L. sigmodontis infection had no impact on co-infection with A/WSN/33. Adult stage worms, however, appeared to have a protective effect against A/WSN/33 pathogenesis. Co-infected mice had significantly delayed weight loss and clinical signs 3-5 days post infection. CD4+ and CD8+ T cells in the lung draining lymph nodes had significantly reduced TH1 and TH2 phenotypes (measured by cytokine production) compared with singly infected controls. IFNγ secreting CD4+ T cells in the lungs of co-infected mice also secreted increased levels of IL-10, suggesting an increase in regulation of the inflammatory response to A/WSN/33. At the full patent stage of L. sigmodontis infection, co-infection with A/WSN/33 led to increased clinical signs and significantly exacerbated weight loss. CD4+ and CD8+ T cells in the lung draining lymph nodes were inflammatory in L. sigmodontis infected mice alone as well as co-infected mice and there were no differences in the percentage of CD4+ T cells in the lung secreting IL-10 and IFNγ between co-infected and influenza infected mice. A loss in regulatory responses during the patent stage of L. sigmodontis infection may therefore contribute to the loss of protection against A/WSN/33 at this time point within the co-infection model. Understanding the impact of an underlying infection on the immune system could provide immune mechanisms that could be exploited to increase vaccine efficacy against influenza and similarly help to provide better treatment for individuals infected with influenza A. These results may also help predict the outcome of influenza A infection in individuals already infected with highly immunogenic, on-going infections.
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Spyer, Moira Jane. "Respiratory syncytial virus host cell receptor interactions." Thesis, University of Reading, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269926.
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Xie, Xiaojian, and 解晓健. "Evaporation and movement of respiratory droplets in indoor environments." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40987802.
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Thomas, Linda D., and n/a. "Pseudomonas aeruginosa : development of a mucosal vaccine for respiratory infection." University of Canberra. Human & Biomedical Sciences, 2001. http://erl.canberra.edu.au./public/adt-AUC20061109.130804.
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Pseudomonas aeruginosa (P. aeruginosa) is a frequently isolated pathogen that
causes septicaemia and chronic respiratory infection. It exhibits a higher
mortality rate than other gram-negative bacteria and the need for effective
immunotherapy is emphasised by the frequency of antibiotic resistance
associated with this organism. Mucosal immunisation with a whole killed cell P.
aeruginosa vaccine has previously demonstrated a significant immune response
in both rodent studies and human trials. This study is a continuation of that
research, with the major goal being the identification of a purified protein antigen
that could form the basis of a mucosal vaccine against P. aeruginosa.
Specifically, the aims of this study were the development of purification
protocols for the isolation of previously untested protein antigens, assessment of
the efficacy of these antigens to enhance bacterial clearance in an animal model
of acute respiratory infection, determination of the immune parameters that are
associated with the resolution of P. aeruginosa respiratory infection and finally,
cloning of an identified antigen which demonstrated vaccine efficacy.
Protocols were established to isolate proteins for use as antigens in immune
response studies. The proteins purified in this study were Pa 13, Azurin, acyl
carrier protein (ACP), Amidase, Aminopeptidase, KatA and Pa70. These proteins
were used to immunise rats by intestinal intra-Peyer's patch (IPP) inoculation and
intratracheal (IT) boost. The immunisation protocol employed was designed to
target mucosal antigen-specific immune responses where the route of
immunisation, Peyer's patch (PP) intestinal inoculation, is akin to the oral
delivery of antigens to the gut-associated lymphoid tissue (96).
Investigations of a previously uncharacterised antigen, Pa60, later identified this
protein as the P. aeruginosa catalase, KatA. This study demonstrated enhanced
bacterial clearance of both homologous and heterologous challenge following
immunisation with KatA. The level of clearance demonstrated by KatA was
promising when compared to that of killed whole cell immunisation. KatA was
cloned and studies with the recombinant protein showed enhanced bacterial
clearance commensurate with that of the native protein.
Immunisations with other proteins identified four additional antigens which
enhanced bacterial clearance; Pa13, Pa40, Pa45 and Pa70. Amino acid sequence
analysis indicated that Pa13 may be a novel protein, whereas Pa40 was
determined to be amidase and Pa45, aminopeptidase. Pa70 was not successfully
sequenced. These proteins were effective in significantly enhancing bacterial
clearance of homologous P. aeruginosa challenge. For KatA, Pa13 and Pa70,
clearance was associated with a marked phagocytic cell recruitment. In contrast,
amidase and aminopeptidase demonstrated clearance with a minimal cellular
response. Proteins; azurin and ACP were non-protective, failing to clear a live P
aeruginosa challenge. Analysis of the antigen-specific responses of these nonprotective
proteins and comparison with those antigens which enhanced bacterial
clearance were used to determine factors that may contribute to the resolution of
an acute pulmonary infection.
The study has demonstrated that mucosal immunisation using purified protein
antigens can enhance the clearance of pulmonary infection with P. aeruginosa. It
has also contributed to the understanding of immune responses to newfound
antigens of P. aeruginosa and identified antigen-specific responses which
confirm their potential as vaccine candidates.
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McGill, Alison Kate. "The role of antigenic variation in respiratory syncytial virus infection." Thesis, University of Newcastle Upon Tyne, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391959.
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SÌarmaÌ„, RaviÌ„ndra. "Immuno-pathogenesis of bovine respiratory syncytial virus infection in lambs." Thesis, University of Liverpool, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316908.
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Muloiwa, Rudzani. "Epidemiology of pertussis in children hospitalised with respiratory tract infection." Doctoral thesis, Faculty of Health Sciences, 2021. http://hdl.handle.net/11427/33846.
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The availability of an effective vaccine against Bordetella pertussis substantially reduced the morbidity and mortality from pertussis, however, in the last decade there appears to have been a substantial increase in pertussis cases as reported mainly in high income countries. Although it is believed that the greatest burden of pertussis, including deaths, is in low- and middle-income countries (LMICs), there seem to be little data available to back this up. This thesis set out to find data that will give some insight into the burden of pertussis in a low- and middle-income setting in infants and children with severe lower respiratory tract infection (LRTI). Given the paucity of data in LMICs, the thesis starts by systematically searching for existing data that will give some indication of the possible extent of the pertussis problem in these countries. Secondly, a prospective study was conducted at a children's hospital. As hospital admission is a marker of severe disease, these children were targeted as the appropriate population in which to meaningfully conduct a primary study on the burden of pertussis. In addition to quantifying the burden by describing the prevalence of confirmed pertussis in this group of children, the study set out to look for potential factors that may be associated with increased risk of pertussis. LRTI are now commonly known to be associated with identification of multiple organisms in respiratory samples, this study aimed to also look at organisms that are detected with Bordetella pertussis; and investigate whether this association was in any way associated with severe disease or negative outcomes. Finally, as data has been emerging that in the context of immunisation, the clinical presentation of pertussis may no longer be following a classical pattern, this study hoped to identify clinical features that could be used to develop a more reliable clinical case definition of pertussis. 2 Chapter 1 gives a background that justifies the undertaking of this study as well as give a summary of the methods used to answer the question of the thesis. The chapter also gives an indication of the structure that the thesis follows. In chapter 2 a systematic review quantifies the burden of pertussis in LMICs using the best available data. In chapter 3 the burden of pertussis due to the two organisms known to cause the disease, Bordetella pertussis and Bordetella parapertussis, is described in some detail. In both this chapter and the earlier mentioned systematic review (chapter 2), the burden of pertussis is stratified by subgroups to identify potential risk factors. The issue of risk is formally and specifically taken up in the chapter that follows (chapter 4) where potential risk factors are analysed, and the independent impact for some of these factors is established. The last two results chapters (chapters 5 and 6) deal respectively with the conundrum of finding other respiratory organism in the same specimen with Bordetella pertussis and failure to find useful clinical criteria that can help with improved diagnosis of pertussis, specifically in children presenting with acute severe lower respiratory tract infection. While there is no established pattern noted between pertussis and most organisms, a few give signals of being independently associated with Bordetella pertussis even if the clinical relevance is not clear at the moment. In the final chapter of the thesis (chapter 7) I conclude the thesis by making an argument that although there are still knowledge gaps, the thesis gives a clear indication that pertussis remains a serious problem in LMICs especially for some groups that show increased risk of the disease or its severe consequences.
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Stokes, A. "Immune effector mechanisms in equine herpesvirus type-1 infection." Thesis, Open University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233248.
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Juntti, H. (Hanna). "Association of respiratory syncytial virus infection with asthma and atopic allergy." Doctoral thesis, University of Oulu, 2008. http://urn.fi/urn:isbn:9789514287947.
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Abstract
Respiratory syncytial virus (RSV) infection may be associated with the development of asthma and atopy. The aim of the present study was to investigate this association and the related immunological mechanisms.
Seventy-six children admitted to Oulu University Hospital in 1991–1994 for an RSV infection at an age of less than 12 months and healthy controls were called for a visit at the age of 6–10 years. Twenty subjects (26%) had asthma compared with 12 controls (16%) (difference 11%, 95% confidence interval (CI) –3% to 24%). Asthma had been diagnosed significantly earlier in the subjects. Eight per cent of the subjects had at least one positive skin prick test as compared with 43% of the controls (difference –35%, 95% CI –50% to –19%). Serum concentrations of interferon-γ and soluble intercellular adhesion molecule -1 were significantly higher among the subjects than among the controls and among the subjects with asthma or current wheezing than among the corresponding controls.
All children born in Finland in 1986–1995 were arranged in birth cohorts by month and year of birth and grouped by exposure to an RSV epidemic at age 0–6 months, resulting in 97 exposed and 23 unexposed cohorts. The proportions of children taking asthma medication or receiving special reimbursement for asthma medication in 1995–2002 were similar in the unexposed and exposed cohorts.
Altogether 47 children born between August and November 2001 with a cord blood sample taken were admitted to hospital (n = 26) or seen in an outpatient department (n = 21) for RSV infection before the age of six months. Twenty-eight children had some other respiratory viral infection and 84 children formed a group of healthy controls. High scores on a factor combining the cord blood interleukin-6 and interleukin-8 responses (as derived by factor analysis) were shown in logistic regression analysis to predict hospitalization for RSV infection by comparison with the healthy controls (odds ratio 2.29, 95% CI 1.21 to 4.33).
We suggest that RSV does not induce asthma but inborn features of immunity affect the severity of RSV infection and the postinfectious development of asthma.
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Hayes, Peter John. "The role of macrophages in respiratory syncytial virus infection of mice." Thesis, University of Newcastle Upon Tyne, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.358972.
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Hamal, Giuma Fituri. "Respiratory tract infection in infants and young children with bronchopulmonary dysplasia." Thesis, University of Liverpool, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365909.
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Sorensen, George Edwin Peter. "Host-virus interactions in porcine reproductive and respiratory syndrome virus infection." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/10040.
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Porcine reproductive and respiratory syndrome virus (PRRSV) is a rapidly evolving virus that has significant economic and welfare implications for the pig industry. Vaccination strategies have proved largely ineffective in controlling PRRSV, in some cases even reverting to virulence. An increasing body of evidence suggests a host genetic basis for PRRSV resistance so there is a need to examine the role of host genetics in a biologically relevant in vitro cell culture system. However, PRRSV research is inhibited by the current scarcity of suitable in vitro culture systems. With the aim of developing a convenient in vitro model, porcine bone marrow-derived macrophages (BMDM) were evaluated as a PRRSV cell culture system. BMDM were found to be highly permissive to Type I PRRSV and amenable to genetic manipulation. BMDM proved to be excellent cells for virus production, producing significantly higher titres of PRRSV than commonly used alternative cell types. Surprisingly, PRRSV entry into BMDM was found to be independent of both the prototypic PRRSV receptors, CD163 and CD169, providing further evidence for the existence of alternate PRRSV entry mechanisms in primary cell types. To explore the genetics of pig susceptibility to PRRSV, network-based analysis of host transcriptional datasets, following PRRSV challenge, revealed important differences in co-regulated gene pathways between samples from pigs with different PRRSV-permissiveness. These pathways included genes with important, recently characterised, anti-pathogen activities. The incorporation of network-based transcriptional analysis and published genetic variation data led to the identification of a member of the guanlyate binding protein family, GBP-1, as a candidate host gene involved in controlling PRRSV replication. Overexpression of GBP-1 in BMDM revealed a significant anti-PRRSV function for this protein. Further investigation of published genetic variation in GBP-1 suggested a potential role of this gene in PRRSV tolerance. The results presented in this thesis provide evidence for an alternate PRRSV entry pathway in a biologically relevant cell type. The discovery of a highly PRRSV-infectable cell type with potential for genetic manipulation adds a useful new tool to the area of PRRSV research. The identification of GBP-1 as a novel anti-viral protein with a significant inhibitory effect on PRRSV infection, together with genetic variation in this gene, prompts further research into the genetic basis for PRRSV resistance.
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Allman, Mark. "What influences the prescribing of antibiotics in lower respiratory tract infection?" Thesis, University of Bath, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.687300.
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Antibiotics are widely prescribed for patients with lower respiratory tract infection (LRTI) yet only a minority have a pneumonia which responds to antibiotic treatment. Unwarranted prescribing of antibiotics is associated with several problems aside from the financial implications of unnecessary treatment: increased incidence of hospital-acquired infections, including MRSA and Clostridium difficile and the problem of antibiotic resistance. The aim of this study was to investigate the influence of the history and examination findings on antibiotic prescribing where LRTI is the principal diagnosis, and to explore the attitudes towards antibiotic prescribing through an understanding of the clinician and patient experience. A mixed methodology study of adult hospitalised patients was employed, with a case series for the quantitative arm and thematic analysis employed for the qualitative arm of the research. Data was collected from patients’ medical notes using a coding matrix developed as part of a pilot study. Doctors were invited to participate in interviews to discuss the reasons for prescribing antibiotics in respiratory tract infection and a group of patients were interviewed for their views on antibiotics. 153 participants were enrolled into the quantitative arm and a further 10 in the qualitative arm. The data indicate that the diagnosis of LRTI and prescription of antibiotics is made on the recorded presence of a very small number of symptoms and signs, with 91% having shortness of breath, 77% having purulent sputum and 75% having a respiratory rate >20/minute. The parameters used to determine a bacterial cause for disease are often non-specific and can lead to inappropriate antibiotic prescribing. Antibiotic use must be targeted to those in whom there is benefit. To enable clinicians to do this they require access to pathology and x ray and these must be supported by expert input. In addition, rapid, reliable diagnostic testing for bacterial infections can assist.
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Molina, Barrios Ramón Miguel. "Porcine reproductive and respiratory syndrome virus understanding and managing persistent infection /." [Ames, Iowa : Iowa State University], 2008.
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Schmidt, Megan Elizabeth. "Assessing T cell responses in respiratory syncytial virus infection and vaccination." Diss., University of Iowa, 2019. https://ir.uiowa.edu/etd/6850.
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Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection and hospitalization in infants and young children, but no vaccine is currently available. CD4 and CD8 T cells are critical for mediating viral clearance but also contribute to immunopathology following an acute RSV infection. However, few RSV-derived CD4 and CD8 T cell epitopes in the commonly used C57BL/6 mouse strain have been described. I utilized an overlapping peptide library spanning the entire RSV proteome and intracellular cytokine staining for interferon-gamma (IFN-γ) to identify novel CD4 and CD8 T cell epitopes in C57BL/6 mice. I discovered and characterized two novel CD4 T cell epitopes and three novel CD8 T cell epitopes located within multiple RSV proteins. Overall, the novel RSV-derived CD4 and CD8 T cell epitopes identified in C57BL/6 mice will aid in future studies of RSV-specific T cell responses.
While CD8 T cells are important for viral clearance following an acute RSV infection, the contribution of memory CD8 T cells in providing protection against reinfection with RSV remains unclear. I used a prime-boost immunization approach to induce robust, systemic memory CD8 T cell responses in the absence of RSV-specific CD4 T cells and antibodies. I determined that high magnitude, systemic memory CD8 T cell responses efficiently reduced lung viral titers following RSV infection, but unexpectedly did so at the expense of severe and fatal immunopathology. The exacerbated disease was mediated by the rapid and excessive production of IFN-γ by memory CD8 T cells in the lung and airways. In contrast, I found that local immunization generated a large population of tissue-resident memory CD8 T cells in the lung that efficiently reduced lung viral titers in the absence of exacerbated disease. Additionally, I observed that pre-existing RSV-specific neutralizing antibodies prevented the immunopathology induced by high magnitude, systemic memory CD8 T cell responses following RSV infection. Prophylactic treatment with neutralizing antibodies against RSV efficiently restricted early virus replication, which resulted in a significant decrease in lung IFN-γ levels, memory CD8 T cell activation, and the frequency of IFN-γ producing CD8 T cells. Thus, my results demonstrate that high magnitude, systemic memory CD8 T cells induce lethal immunopathology following RSV infection, which can be prevented by pre-existing RSV-specific neutralizing antibodies. Overall, my results have important implications for the development of future RSV vaccines.
The development of a live-attenuated vaccine for RSV has been prevented by the inability to properly balance attenuation with immunogenicity and efficacy. Recently, a recombinant RSV strain lacking the gene that encodes the matrix (M) protein (RSV M-null) was developed. As the M protein is required for virion assembly following infection of a host cell, RSV M-null induces a single-cycle infection. I evaluated RSV M-null as a potential live-attenuated vaccine candidate by determining its pathogenicity, immunogenicity, and protective capacity in BALB/c mice compared to its recombinant wild-type control virus (RSV recWT). RSV M-null was sufficiently attenuated, as significantly reduced lung viral titers, weight loss, and pulmonary dysfunction were observed compared to mice infected with RSV recWT. Surprisingly, despite its attenuation, I found that RSV M-null infection induced effector T cell, germinal center B cell, serum antibody, and memory T cell responses of similar magnitude to that elicited by infection with RSV recWT. Importantly, RSV M-null immunization provided protection against secondary viral challenge by reducing lung viral titers as efficiently as immunization with RSV recWT. Overall, my results indicate that RSV M-null combines attenuation with high immunogenicity and efficacy and represents a promising novel live-attenuated RSV vaccine candidate.
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Bustami, Mona Ratib. "Reactive oxygen and nitrogen species in cystic fibrosis." Thesis, University of Bath, 2002. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248100.
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Woensel, Jacobus Bernardus Maria van. "Lower respiratory tract infection caused by respiratory syncytial virus the short-term and long-term efficacy of corticosteroids /." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2002. http://dare.uva.nl/document/63898.
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Al, Alwadhi Fahimah Kamil M. R. "Upper respiratory tract infection : implementation of multiple interventions on antibiotic prescribing for patients with upper respiratory tract infection in primary health care settings in United Arab Emirates." Thesis, University of Aberdeen, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.440096.
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Part I. Aims: The aims of part I of this research programme were to: measure the prevalence of antibiotic prescription for U.R.T.I. in Primary Health Care Centres in the United Arab Emirates; understand the rational behind antibiotic prescription; Evaluate the effect of different patient characteristics such as self treatment, age, education, occupation and gender; evaluate the effect of physician characteristics such as gender, communication and practice location; and to evaluate the degree of patient compliance and satisfaction with treatment. Main Conclusions: U.R.T.I. is one of the main reasons for patient visits and antibiotic prescription; physicians’ advice to patients regarding dosage and duration of the prescribed medication was limited; a significant association existed between patients’ expectation from practitioners and practitioners’ perception of patients’ expectations; poor compliance is strongly correlated with poor patient-doctor interaction; diagnoses were typically based on clinical findings; patient satisfaction is strongly linked to the level of communication. Part II. Aims: To measure the influence of introducing guidelines to doctors and educational leaflets to patients on reducing the level of prescribed antibiotics; and to investigate the effect of factors such as socio-demographic characteristics, signs, symptoms and patient self management. Main Results: The total number of antibiotic prescriptions for patients suffering from U.R.T.I. including sore throat was significantly reduced in the intervention group. Conclusions: A multi-dimensional interventional approach for reducing antibiotic prescription in U.A.E. clinics resulted in a significant positive outcome; and the significant reduction in antibiotic prescriptions indicates the willingness of physicians to follow guidelines and the willingness of patients to respond to educational information. Main Recommendations: Clinical guidelines are most effective if implemented as part of a systemic strategy, involving dissemination of guidelines by departmental heads and utilisation of computer generated reminders; physicians should be involved as part of the working group to develop guidelines; ongoing educational programmes for physicians; and a public educational campaign on the problem of over use of antibiotics is essential.
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Binns, Sarah Helen. "Studies on the epidemiology of Bordetella bronchiseptica infection in cats." Thesis, University of Liverpool, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243267.
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Ortiguerra, Ryan Gatdula. "Risk Factors Associated With Severe Acute Respiratory Infections Cases." ScholarWorks, 2016. https://scholarworks.waldenu.edu/dissertations/2749.
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The close proximity of the United States to the Mexican border poses a concern for communicable diseases because of the high flow of population movement. The purpose of this retrospective, quantitative study was to identify risks associated with respiratory diseases using an analysis of archived data from the Severe Acute Respiratory Illness (SARI) surveillance program. Based on the epidemiologic triangle theory, demographic and etiologic factors were analyzed to examine any associations with SARI in this population. Between 2010 and 2012, 798 subjects enrolled in this program, with 336 (42.1%) testing positive for respiratory pathogens. Chi square analysis determined that age (X2 (4, N = 786) = 255.361, p < 0.001), clinic location (X2 (3, N = 780) = 290.841, p < 0.001), and race/ethnicity (X2 (4, N = 762) = 1456.701, p < 0.001) showed significant associations with SARI in the population. The logistic regression model showed that the youngest age group (0-4) had the highest risk of developing SARI compared to other age groups (5-24 OR = 0.521, 95% CI [0.311-0.871]; 25-49 OR = 0.377, 95% CI [0.224-0.636]; 50-64 OR = 0.211, 95% CI [0.118-0.376]; >65 OR = 0.225, 95% CI [0.143-0.356]. African Americans were also at higher risk of developing SARI compared to Hispanic Americans (OR = 3.997, 95% CI [1.272-12.558]. This study promotes positive social change by informing efforts to increase vaccination and health literacy, improve the accessibility and availability of preventive health care in low socioeconomic communities, and promote healthy lifestyles among at-risk groups. These steps will improve the overall health of the communities along the U.S.-Mexico border region.
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Mulpuru, Sunita. "Does Respiratory Viral Testing in Adult Hospitalized Patients Impact Hospital Resource Utilization and Improve Patient Outcomes?" Thèse, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31165.
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Respiratory viral testing in hospitalized patients is thought to improve quality of care by reducing the use of diagnostic tests, guiding infection control precautions, and rationalizing antimicrobial therapies. Few small published studies have tested these assumptions, and have demonstrated conflicting results.
We conducted a retrospective cohort study of 24,567 hospitalizations using administrative data to determine the associations between viral testing, patient outcomes, and process of care.
Viral testing was not associated with improved mortality or length of stay in hospital, and resulted in more resource utilization. The test result did not influence the duration of isolation precautions. This implies that health care providers may not use the results of testing in making management decisions, or in guiding the use of isolation precautions. This study provides the foundation for further scientific evaluation and reform of our current respiratory infection control policy.
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Saravanos, Gemma Lea. "Unknowns of Severe Acute Respiratory Infection (SARI) in Australian Children: Enhancing understanding of epidemiology to inform disease prevention." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/27237.
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My doctoral research aimed to enhance understanding of the virology and clinical epidemiology of severe acute respiratory infection (SARI) in Australian children to inform disease prevention strategies. I first studied respiratory syncytial virus (RSV), a leading cause of acute lower respiratory infection in young children. Specifically, I aimed to estimate the incidence of respiratory syncytial virus (RSV) hospitalisations in the Australian population, examine the circulation and associated disease severity of RSV subtype infections, determine whether RSV infection contributes to deaths in Australian children, and determine if RSV infection can cause severe acute neurological disease. RSV served as an exemplar for other understudied viral SARI and I subsequently established a project designed to enhance understanding of SARI epidemiology in Australian children more broadly.
To estimate the incidence of hospitalisation in the Australian population, I led a retrospective epidemiological review of National Hospital Morbidity Database data for all RSV-associated hospitalisations in Australia from 2006 to 2015. In this study, 63,814 RSV-associated hospitalisations were identified in the Australian population. Of these, 94.9% were in children aged less than five years and the highest hospitalisation rate was for infants aged up to two months (2778 per 100,000 population). Hospitalisation rates were higher for adults aged 65 years and over than for people aged 5–64 years (incidence rate ratio [IRR] 6.6; 95% confidence interval [CI] 6.2 to 7.1) and were also higher for Indigenous Australians than for other Australians (IRR 3.3; 95% CI 3.2 to 3.5).
RSV subtype circulation and disease severity were examined in a single-centre, retrospective, observational study of children aged less than 16 years from 2014 to 2018. This study described subtype circulation of all RSV-A and RSV-B infections in children presenting to the study hospital. A random sample of children with RSV-A and RSV-B infections was selected and compared with respect to demographics, clinical features and clinical severity. We identified 3591 RSV subtype infections and found consistent co-circulation of subtypes with alternating predominance of either subtype. Demographic and clinical characteristics were similar between children presenting with either subtype. This study found no clear difference in disease severity between subtype infections.
The features and frequency of RSV-attributable deaths were assessed in a single-centre, retrospective, observational study in children aged less than 16 years over a 21 year period (1998–2018). All RSV-associated deaths were identified, reviewed and classified according to RSV contribution to death. A total of 20 RSV-attributable deaths were identified. The case fatality rate among hospitalised cases was 0.2% (20/9779), and the population RSV mortality rate estimated at 1.2 (95% CI 0.5 to 2.7) per million children aged less than 16 years in New South Wales. All children had at least one medical comorbidity, and over half the deaths occurred in children aged two years and over (11/20, 55%). Healthcare-associated RSV infection was common (11/20, 55%).
RSV-associated severe acute neurological disease was examined through a systematic review and aggregated case series conducted in accordance with the PRISMA framework and registered on PROSPERO (CRD42019125722). A total of 87 unique studies from 26 countries were identified and described a spectrum of RSV-associated severe acute neurological syndromes including proven encephalitis, acute encephalopathy, complex seizures, hyponatraemic seizures and immune-mediated disorders. Aggregation of data from 155 individual cases with RSV-associated severe acute neurological disease highlighted that the median age of cases was 11.0 months (interquartile range 2.0–21.5) and the majority were previously healthy (71/104, 68%). Most children recovered (81/122, 66%); however, some reports described partial recovery (33/122, 27%) and death (8/122, 7%). Twelve cases had RSV detected in a central nervous system sample providing strong evidence of causality.
The epidemiology of SARI in Australian children will be explored using two, large, routinely collected datasets; NSW respiratory syndromic data (1,237,072 individual presentations) and sentinel site laboratory data including 16 viral respiratory pathogens (29,890 virus specific detections). The virology and clinical epidemiology of syndromes and pathogens will be described. The associations between syndromes and pathogens will be examined. The utility of these data to be aggregated for developing a comprehensive, timely and robust SARI surveillance system will be assessed. Ethics and governance approvals for the project have been obtained, and the data has been released. Unpublished descriptive summary statistics are presented in this thesis.
My research on severe RSV disease has made a substantial and novel contribution to understanding RSV epidemiology and will inform the design of future disease prevention and surveillance. My established project examining SARI in Australian children will enhance understanding of the epidemiology of a variety of childhood respiratory syndromes and viruses. This will provide novel data to inform future research relating to disease prevention and surveillance of SARI more broadly.
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West, Keith Henry. "The effect of vaccination on the response to experimental infection with bovine respiratory syncytial virus infection in calves." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/NQ37923.pdf.
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Chauhan, Anoop Jivan. "Personal exposure to the air pollutant nitrogen dioxide and the risk of lower respiratory disease with upper respiratory infection." Thesis, University of Southampton, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266657.
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Davies, Bronwen J. "Physical activity and symptoms of upper respiratory tract infection in university students." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ61257.pdf.
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German, Matthew. "Tissue specific pathology associated with micronutrient supplementation during respiratory syncytial virus infection." Thesis, McGill University, 2012. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=106408.
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Micronutrients are increasingly appreciated as potent immunomodulators. Long used to 'treat' measles virus (MeV), vitamin A was recently shown to act through RIG-I to up-regulate type 1 interferons. Similar actions are seen with some (mumps virus and CDV) but not all members of the Paramyxoviridae. However, children infected with respiratory syncytial virus (RSV), a close relative of MeV, do worse when given pharmacological doses of vitamin A. RSV is known to elicit a pathologic Th2-biased response. Vitamin A also has a strong Th2-deviating influence. Our primary objective was to develop a small animal model of vitamin A deficiency and sufficiency in which we could assess the impact of vitamin A status and supplementation on RSV infection in vivo. Such a model will be of great use to characterize the mechanism of action of retinoids in this infection. We succeeded in the development of this model by restricting dietary retinol through 2 generations of BALB/c mice (ie: deficiency state) and introducing novel means to reliably attain a state of consistent vitamin A supplementation (ie: reconstituted & excess states). Preliminary data using this model suggested that there were marked differences in RSV pathology between deficient and sufficient mouse groups. Like the apparent situation in humans, infection in the vitamin A deficient mice was paradoxically less severe than in mice with a positive vitamin A status. This model and the data generated with it may be of particular interest in regions with diets high in vitamin A (North America in particular). Historically, very little attention has been given to possible negative effects of micronutrient 'over-nutrition'. The limited human data and the preliminary data from our new model brings into question whether or not we are 'priming' ourselves for more severe RSV infection than would otherwise occur. The data generated in this model may also be highly relevant to guide supplementation efforts in regions of the world that currently have less access to vitamin A.Les micronutriments sont des plus appréciés comme immunomodulateurs puissants. Longtemps utilisé pour traiter measles virus (MeV), la vitamine A a été récemment montré à agir par le biais de RIG-I pour réguler les interférons de type 1. Des actions similaires sont observés avec certains (canine distemper virus, CDV), mais pas tous les membres du Paramyxoviridae. Cependant, les enfants infectés par des voies respiratoire, respiratory syncycial virus (RSV), un proche cousine de MeV, faire pire lorsqu'il est administré des doses pharmacologiques de vitamine A. Le RSV est connu pour induire une résponse pathologique biaisée au Th2. La vitamine A est également une forte influence pour la Th2 déviation. Notre principal objectif était de développer un modèle animal de la carence en vitamine A et la suffisance dans lesquels nous pourrions évaluer l'impact du statut en vitamine A et de la supplémentation sur l'infection à RSV in vivo. Un tel modèle sera d'une grande utilité pour caractériser le mécanisme d'action des rétinoïdes dans cette infection. Nous avons réussi dans le développement de ce modèle en limitant le rétinol alimentaires grâce à deux générations de souris BALB / c (ie: état de carence) et en introduisant de nouveaux moyens de atteindre un état fiable de vitamine A cohérente supplémentation (ie: les Etats reconstitué & excès). Les données préliminaires utilisant ce modèle suggéré qu'il y avait des différences marquées dans la pathologie du RSV entre les groupes de souris déficientes et suffisante. Comme la situation apparente dans les humains, l'infection dans la vitamine A des souris déficientes en était paradoxalement moins sévère que dans les souris avec une vitamine positifs d'un statut. Ce modèle et les données générées avec elle peut être d'un intérêt particulier dans les régions où les régimes son riches en vitamine A (Amérique du Nord en particulier). Historiquement, très peu d'attention a été accordée aux effets négatifs possibles des micronutriments sur-nutrition. Les données humaines limitées et les données préliminaires de notre nouveau modèle remet en question si oui ou non nous sommes d'amorçage nous-mêmes pour l'infection à VRS plus sévères que se produirait autrement. Les données générées dans ce modèle peut également être très pertinentes pour guider les efforts de la supplémentation dans les régions du monde qui ont actuellement un accès moindre à la vitamine A.
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Munywoki, Patrick Kiio. "Transmission of respiratory syncytial virus in households : who acquires infection from whom?" Thesis, Open University, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607465.
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Households represent a setting of frequent and intense contacts and hence are conducive to the spread of respiratory viruses, such as respiratory syncytial virus (RSV). Infants are most vulnerable to severe RSV disease but a vaccine is oat yet available hence the need to explore alternate strategies of protecting them, Such strategies would require better understanding of who infects the infants. During the RSV season of200912010, we undertook a prospective study in rural Kenya involving 493 members of 47 households each with a child born after the preceding RSV epidemic and at least one elder sibling. Throughout the epidemic a nasopharyngeal swab (NPS) was collected every 3-4 days irrespective of symptoms, from all household members, and tested for a range of respiratory viruses including RSV using a molecular diagnostic assay. Partial sequencing of the attachment protein (G) gene from positive swabs was used to compare RSV strains within the household. In addition, once-a-week a specimen of oral fluid (OF) from around the gums was co11ected for RSV -specific antibodies screening and for assessment of sensitivity of the OF in detection of RSV using molecular diagnostics. This is the first prospective study to investigate introduction and transmission of RSV in families using molecular techniques over a complete RSV season. Analysis of RSV infection data is reported in this thesis with particular interest to identifying from where infants derive !.heir infection, estimating the duration of RSV shedding and identify factors influencing the recovery rates, and estimating parameters of RSV susceptibility and transmission probability. In addition, data on diagnostic performance of OF in detection of RSV by molecular methods is presented. A total of 16,924 NPS were collected, representing 86% of planned. RSV was detected in 40 (85%) households and 179 (36%) of the participants. In 28 of the 44 households with complete data, there was transmission of RSV to the infants experiencing their first epidemic. The probable source of RSV infection of the naive infants was a household member in at least 54% of the cases. Co-primary infection between a household member and the RSV -naive infant was ascribed in 4 of the cases. Older children were assigned the primary case for 11 (39%) of the infant cases and 10 (91 %) of these were attending school. The infants appeared to play a role transmitting the introduced infections to the other members of the household including to the mothers. These findings support vaccination strategies that target school age children and pregnant women. Both of these vaccination strategies can have profound benefits to RSV naive infants directly by augmenting neutralizing antibodies against RSV (immunization of the pregnant women) and indirectly by reducing transmission from siblings to RSV-naive infants. Results from this study provide increased confidence in the rationale for RSV vaccination of individuals who are not the key targets for protection