archives@tulane.edu / Background: Prompt antiviral treatment of influenza virus infections can improve outcomes and reduce the likelihood of complications, particularly among children at high risk for complications. Recent, more stringent requirements for rapid influenza point-of-care test clinical sensitivity have implications for the impact and cost-effectiveness of outpatient influenza diagnosis and antiviral treatment. Objective: The objective of this research was to understand antiviral prescribing practices following and utilize these real-world probabilities to evaluate the cost effectiveness of rapid test-guided outpatient antiviral treatment in children. Methods: The analysis used data from patients presenting for outpatient care with influenza-like illness (ILI) collected through the Influenza Incidence and Surveillance Project (IISP). The first analysis used a retrospective case-control design to compare clinic, patient, and season characteristics that influenced the decision to prescribe influenza antiviral treatment following a negative rapid influenza detection test. The IISP data were then incorporated into cost-effectiveness analyses among high-risk and otherwise healthy children presenting for outpatient care with ILI. Results: The results from the first analysis demonstrated that clinicians prescribed influenza antivirals to 8.4% of all test-negative patients and that in age groups considered a proxy for high risk patients, prescribing was either less frequent among children aged <2 (aOR 0.4, 95% CI 0.3–0.6) or the same among adults aged ≥65 (aOR 0.9, 95% CI 0.7–1.3) compared with adults aged 18 to 64. The results from the antiviral cost-effectiveness analysis among healthy children showed that treatment guided by clinician judgement was cost saving compared to no treatment, but rapid testing produced the greatest benefit. Among high-risk children, test-guided treatment produced the greatest benefit and was cost effective. Results were sensitive to clinician diagnostic sensitivity, influenza prevalence and the probability a positive test or diagnosis would result in treatment. Conclusion: These studies indicated that clinical judgement continued to be used to prescribe antivirals for patients with suspected influenza, greatly impacting the associated costs of care. The decision to test for influenza should be contingent upon the results influencing treatment of the patient or high-risk contacts, or further costly diagnostic testing. / 1 / Ashley Fowlkes

Thesis (M.A.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / Outer membrane proteins from unencapsulated(nontypable) Haemophilus influenza were prepared by incubation with EDTA and shearing followed by molecular sieve chromatography in a lipooligosaccharide (LOS) disaggregating deoxycholate buffer. Outer membranes proteins collected were determined to be free of LOS by polyacrylamide gel electrophoresis and then covalently attached to cyanogen bromide activated Sepharose. Antibodies to outer membrane proteins were then isolated by affinity chromatography and characterized by enzyme-linked immunosorbant assay. These antibodies will prove useful for passive immunization experiments to establish the role of outer membrane proteins in host protection from infection with nontypable Haemophilus influenza. / 2031-01-01

It is, perhaps, ironical. that while influenza was probably the first animal virus to be studied in detail there is still little known concerning its behaviour. In many ways it represents a model of difficult immunization problems. Now that so many of the most lethal and dramatic of the infectious diseases are susceptible to control attention is being focused upon the control of the next rank of disorders. This includes those conditions which cause ill-health and discomfort only to such an extent that the cost and severity of measures of prevention must be carefully weighed against the effects of the disease process itself. The solution of the technical, administrative and ethical problems of influenza control will, in addition, greatly assist the struggle against numerous other ailments.

Cannabis is widely used for recreational and medicinal purposes. Inhalation of cannabis smoke is the predominant method of drug consumption, exposing the lungs to THC and CBD, as well as a plethora of toxic combustion products. Clinical observations suggest that cannabis smoking contributes to the development of respiratory symptoms and may play a role in the pathogenesis of inflammatory lung disease. However, the association between cannabis smoke, dysregulated pulmonary immunity, and the development of lung disease is inconclusive. To improve our understanding of this relationship, we developed novel mouse models to investigate the effect of cannabis smoke exposure on lung immunity. Using compositionally relevant cannabis strains, we established a mouse model of cannabis smoke exposure and validated that it delivers cannabis smoke by measuring cannabis smoke-associated metabolites in the blood. In our initial lung immune characterization, we demonstrated that acute cannabis smoke exposure induces modest changes to innate immune cellularity in the airways and lung tissue. Specifically, lung macrophage subpopulations were proportionally altered following smoke exposure. As well, we demonstrated that lung disease-associated mediators, including MDC, TARC, and VEGF, were dysregulated in cannabis smoke-exposed lung tissue. In addition to our initial characterization, we established a first-of-its-kind concurrent cannabis smoke exposure and influenza infection model. Using this model, we demonstrated that cannabis smoke exposure exacerbates weight loss following influenza infection. These increases in weight loss corresponded with dysregulated cellular responses and immune mediator expression. Cell types involved in early innate immune signaling, such as macrophages and dendritic cells, were significantly affected by concurrent exposure and infection. Additionally, anti-viral mediators. including IFNγ, IP-10, RANTES, and TNFα, were decreased in cannabis smoke-exposed, infected lung tissue. Collectively, we defined two novel models of cannabis smoke exposure that can be leveraged in future investigations on the inflammatory effects and associated health outcomes of cannabis smoke. / Thesis / Master of Science (MSc) / Cannabis is widely used for recreational and medical purposes. Smoking is the most popular method to consume the drug among users. However, little is understood about the effects of cannabis smoke on lung health, despite evidence suggesting that it may lead to negative health outcomes. To address this gap in knowledge, we developed two unique mouse models of cannabis smoke exposure. Using these models, we explored the effects of cannabis smoke on lung immune responses in healthy and influenza infected mice. Our findings suggested that lung immunity is altered following cannabis smoke exposure. Additionally, we found that overall health was worsened during influenza infection in cannabis smoke-exposed mice. This effect was associated with weakened viral immunity in the lungs. The models we developed and the findings using it thus far create the foundation for future studies on cannabis smoke and lung health.

Influenza-assoziierte Atemwegserkrankungen führen jedes Jahr zu zahlreichen Hospitalisierungen und Todesfällen. Der während der Pandemie 2009 zirkulierende Erreger Influenza A(H1N1)pdm09 führte zu zahlreichen, zum Teil schweren Komplikationen, insbesondere auch bei jüngeren Erwachsenen. In der vorliegenden Studie wurden Influenza-assoziierte Hospitalisierungen (IAH) hinsichtlich Krankheitsverlauf in den verschiedenen Altersgruppen sowie bei verschiedenen Erregern untersucht. Zudem erfolgte eine Analyse der direkten Krankheitskosten. Einen besonders schweren Verlauf zeigten Erwachsene mit Grunderkrankung zwischen 18-60 Jahren, die überwiegend mit dem Erreger Influenza A(H1N1)pdm09 infiziert waren. Ebenso waren schwangeren Patientinnen mit IAH mit dem Erreger A(H1N1)pdm09 selten, aber schwer betroffen. Bei Patienten von 18-60 Jahren mit dem Erreger Influenza A(H1N1)pdm09 entstanden die höchsten direkten Kosten im Vergleich zu den anderen Altersgruppen. / Influenza-associated respiratory disorders cause several hospitalizations and deaths every year. The pandemic virus Influenza A(H1N1)pdm09 caused several partly severe complications, especially for younger adults. In this study, we examined influenza-associated hospitalizations (IAH) regarding the course of disease in different age groups and to different virus types and -subtypes. Furthermore, we did a cost-analysis of influenza-associated hospitalizations. Especially severe influenza course occurred to adults aged 18-60 years with an underlying chronic condition, infected by influenza A(H1N1)pdm09. Also, pregnant women with IAH with influenza A(H1N1)pdm09 showed rare but severe complications. For patients aged 18-60 years infected by influenza A(H1N1)pdm09 occurred high costs compared to other age groups.

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Periodic introductions of influenza A viruses (IAVs) from wild birds contribute to emergence of novel strains that infect domestic poultry, lower mammals, and humans, but the mechanisms of emergence are unclear. The objectives of this dissertation research are to infer the genesis of two emerging IAVs, low pathogenic avian influenza (LPAI) H10N8 and highly pathogenic avian influenza (HPAI) H7N8 viruses, and to characterize the antigenic diversity and genetic evolution of contemporary H7 avian influenza viruses (AIVs) from North America. First, AIVs that are genetically close to the human H10N8 isolate were recovered at the live poultry market (LPM) visited by the first H10N8 patient. High seroprevalence of H10 virus was observed in ducks and chickens from five LPMs in the region. These findings suggested that LPM was the most probable source of human infection with the H10N8 virus, and this virus appeared to be present throughout the LPM system in the city. Second, the novel H7N8 virus most likely circulated among diving ducks in the Mississippi flyway during autumn 2015 and was subsequently introduced to Indiana turkey, in which it evolved from LPAI into HPAI. H4N8 IAVs from diving ducks possess a gene constellation comprising five H7N8–like gene segments. These findings suggest that viral gene constellations circulating among diving ducks could contribute towards the emergence of IAVs that can affect poultry. Diving ducks may serve as a unique reservoir, contributing to the maintenance, diversification, and transmission of IAVs in wild birds. Third, antigenic and genetic characterization of 93 H7 AIVs from North America showed limited antigenic diversity. Gradual accumulation of nucleotide and amino acid substitutions in the H7 gene of AIVs from wild and domestic birds caused a wide genetic diversity. These findings suggested that continuous genetic evolution has not led to significant antigenic diversity for contemporary H7 AIVs isolated from wild and domestic birds in North America. In summary, these findings not only improve our understanding of the ecology and evolution of IAVs but also provide information for formulation of effective disease prevention and control strategies.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2006. / Härtill 5 uppsatser.

Since 2012-2013 influenza season, World Health Organization (who) recommends the formulation of tetravalent vaccines. Globally, many countries already use tetravalent vaccines in their national immunization programs, while in Latin America only a small number. Two Influenza b lineages co-circulate, their epidemiological behavior is unpredictable. On average they represent 22.6% of influenza cases and more than 50% in predominant seasons. The lack of concordance between recommended and circulating strains was 25 and 32% in the 2010-2017 and 2000-2013 seasons, respectively. There are no clinical differences between influenza A and B. It occurs more frequently from five to 19 years of age. Influenza b has a higher proportion of attributable deaths than influenza a (1.1 vs. 0.4%), or 2.65 (95% ci 1.18-5.94). A greater number of hospitalizations when the strains mismatch (46.3 vs. 28.5%; p <.0001). Different evaluations have demonstrated its cost effectiveness. The compilation of this information supports the use of quadrivalent vaccines in Latin American countries. / Revisión por pares

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.