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1
Lee, Lai-ka, and 李勵嘉. "The pattern of invasive pneumococcal disease in Hong Kong, other parts of China, United States and Thailand : a focus on impact of pneumococcal vaccination : a systematic review." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206944.
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Objectives: By summarizing and comparing the pattern of invasive pneumococcal disease (IPD) in the 4 areas (namely Hong Kong, other parts of China, United States and Thailand) at different stages of implementation of universal pneumococcal vaccination, a snapshot picture could be obtained to visualize how pneumococcal vaccination has impacted upon various important measures, including the burden of IPD, prevalent serotypes, antimicrobial resistance, risk factors of IPD, to guide us on the next step to optimize our ability to combat against IPD.
Methods: To achieve the objective, a systematic search through PubMed, Medline, Cochrane Library, EmBase, CINAHL, and the China Journal Net (for Chinese journal articles to obtain a more comprehensive data for “other parts of mainland) has been performed. Articles were selected according to the inclusion and exclusion criteria, and in straight accordance to the literature search and article retrieval steps as described in the methodology. The quality of the articles was assessed by the STROBE (Strengthening the Reporting of Observational studies in Epidemiology) checklists.
Results:
In general, there was decline in IPD incidence after PCV vaccination, but the problem of serotype replacement and antimicrobial resistance was still an ongoing problem, which differs geographically.
Conclusion:
From the above data, we could see the significant impact on PCV on reduction of incidence in IPD as shown in United States, however, it was also very clear that unless development of non-serotype specific vaccine become available to us, we are still facing the problem of serotype replacement and that we need to have regular surveillance, as in the case of United States, to supply the data for timely replacement of new PCV combating the emerging serotypes, such that we would still be in the safe ground. In Hong Kong, the statutory reporting of IPD to Centre for Health and Protection (CHP) has been effective since 2/1/201443, after the start of universal immunization since October 2008, followed by PCV10 in 2009 and PCV13 in December 2011, we seems lacking behind on the surveillance. With the surveillance started by CHP, we hope to understand the Hong Kong situation better and with more published data for our local burden and serotype pattern of IPD.
It is interesting to note that the antimicrobial pattern does vary geographically, even in US with universal immunization. This suggests that while PCV was helping us to reduce the penicillin resistant strain, another more important factor – the practice of use of antibiotics- is still operating to effect on the overall antibiotic resistance. The pattern that rural Thailand was having much much less penicillin resistance as compared to urban Bangkok, where antibiotic is more readily available, also supports this explanation.published_or_final_version
Public Health
Master
Master of Public Health
2
Wu, Yunyan, and 吴云燕. "The immunogenicity and safety of 13-valent pneumococcal conjugate vaccine: a systematic review." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46943493.
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3
Fan, Hiu-yan, and 樊曉欣. "Economic evaluation of the second generation pneumococcal conjugate vaccine in children : a systematic review." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206903.
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Background
Pneumococcal disease, caused by Streptococcus pneumoniae (S. pneumoniae), leads to a great burden of morbidity and mortality globally, especially in developing countries. World Health Organization (WHO) estimated that 476,000 out of 8.8 million global annual deaths in children under 5 years old in 2008 were due to pneumococcal infection. Currently there are 2 second generation pneumococcal conjugate vaccines (PCVs) targeted at children, the 10-valent pneumococcal conjugate vaccine (PCV-10) and 13-valent pneumococcal conjugate vaccine (PCV-13) available in the market for the prevention of pneumococcal disease. Nowadays, about half of the countries already included PCVs into their National Immunization Programme (NIP) and around one-fourth are planning the introduction. The objective of this systematic review is to evaluate the cost-effectiveness of PCV-10 and PCV-13 so that the results could inform policy decisions of including PCVs into the NIP.
Methods
A systematic review was conducted by searching from 2 databases (PubMed and Medline) for the economic evaluation studies of the PCV-10 and PCV-13. Information of the design and characteristics of studies, burden of pneumococcal disease assumption, and baseline vaccine efficacy assumptions were extracted and results were presented in incremental cost-effectiveness ratio (ICER).
Results
Eleven studies were included, with 4 studies done in Europe, 3 in South America, 2 in Africa, 1 in Asia and 1 across North America and Europe. The results varied greatly among studies, with 5 of them reporting PCV-10 to be more cost-effective and/or cost-saving, while 4 of them reporting PCV-13 to be more cost-effective and/or cost-saving, and 2 of them concluded in a different way: PCV-10 was more cost-effective and cost-saving, however PCV-13 would lead to higher life-years gained (LYG) and/or disability-adjusted life years (DALYs) averted.
Conclusion
Due to the uncertainties in the clinical and epidemiological parameters, the unavailability of the data of local disease burden, and the analytical choices about endpoints which could significantly affect the input data, the results of the studies reviewed were contrasting from each other. Therefore, there was not enough evidence to show whether PCV-10 or PCV-13 was more cost-effective to be included into the NIP of children. Further research should be done on the sensitive variables of the cost-effectiveness ratio, as well as the local serotype distribution and disease burden should also be taken into account when planning the inclusion of PCVs into the NIP.published_or_final_version
Public Health
Master
Master of Public Health
4
Wong, Kwan-ting, and 王筠婷. "The cost-effectiveness of 13-valent pneumococcal conjugate vaccine for older adults : a systematic review." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206978.
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BACKGROUND: Despite the current recommendation by the Centre for Health Protection (CHP)of Hong Kong for adults aged 65 years or above to receive 23-valent pneumococcal polysaccharide vaccine (PPV23), pneumococcal disease(PD) has become the second leading causes of death in Hong Kong. A relatively new pneumococcal vaccine –13-valent pneumococcal conjugate vaccine (PCV13) was approved by the US Food and Drug Administration (FDA) in December 2011 and the European Medicines Agency (EMA) in July 2013 for the prevention of invasive disease caused by S. pneumoniae for older adults aged 50 years or above. It was shown to overcome some of the limitations of PPV23and potentially confer benefits to older adults in the prevention of PD.
OBJECTIVES: To systematically review available literatures to examine whether PCV13 is superior to PPV23 or no vaccination in terms of the cost-effectiveness in the prevention of PD in older adults aged 50 years or above.
METHODS: Two databases, PubMed and ISI Web of Science, were used to search for published journals. The year range of search in these databases was confined to10 years.
RESULTS: A total of 318studies were identified initially and 10studies were included in this systematic review. Studies were conducted in the US, Colombia and European Union (EU) countries e.g. Italy, Germany, Netherlands and Spain. Different perspectives including societal, payer and health system were considered. The use of PCV13 was compared to either PPV23 or no vaccination in older adults aged 50 years or above. The coverage of PCV13 ranged from 42.4% to 70%, conferring an efficacy between 58% and 93.9%. The cost-effectiveness of PCV13 was expressed through the number of avoided cases/deaths for PD including invasive pneumococcal disease(IPD), inpatient and outpatient community-acquired pneumonia (CAP) as well as the incremental cost-effectiveness ratios (ICERs),either in cost per quality-adjusted life-year (QALY) gained or cost per life-year gained (LYG).Overall, PCV13 is shown to avoid more pneumococcal cases compared to PPV23 or no vaccination and is cost-effective in older adults aged 50 years of above.
CONCLUSION: PCV13 is considered to be more cost-effective in older adults compared to PPV23 or no vaccination based on the current systematic review. Randomized controlled trials and cost-effectiveness evaluations are suggested to be conducted in Hong Kong and Asia-specific regions in order to obtain clinical and economic data of PCV13 in the Asian population. Policy-makers should also consider the effects of serotype replacement on the change in serotype distribution in local setting from time to time so that vaccines with appropriate serotype formulations could be researched.published_or_final_version
Public Health
Master
Master of Public Health
5
Mitchell, Patrick Kevin. "Pneumococcal Population Dynamics in the Conjugate Vaccine Era." Thesis, Harvard University, 2016. http://nrs.harvard.edu/urn-3:HUL.InstRepos:27201746.
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The introduction of pneumococcal conjugate vaccines (PCVs) in the early years of the 21st century have led to significant changes in pneumococcal epidemiology. Using transmission modeling and genomics based approaches, this dissertation evaluates alterations to the pneumococcal population through the PCV era. Chapter 1 presents a transmission model designed to examine factors that may influence the potential of a previously rare antibiotic resistant lineages to emerge following the introduction of a vaccine targeting more common resistant types, finding that such emergence is more likely in settings with high antibiotic use, high carriage burden, and frequent multiple carriage. Chapter 2 examines the population genomics of pediatric pneumococcal carriage before and after the introduction of PCV-13, finding that the non-vaccine type population composition experienced changes immediately following vaccine introduction but moved back towards its pre-vaccination state over time. Additionally, there is evidence that serotype 3, which is included in PCV-13, has persisted following vaccine introduction, though there are genetic differences between the pre- and post-vaccination population of this serotype. Chapter 3 compares isolates of a single non-vaccine serotype, 33F, collected from carriage and invasive disease, finding evidence that the invasive capacity of this serotype may have declined following the introduction of PCV-13 and that very closely related pairs isolates are disproportionately likely to both be from either carriage or disease. Together, these projects contribute to our understanding of how the pneumococcal population has and will continue to change as PCV use expands.
6
Coulibaly, Aissata. "Impact of Pneumococcal Conjugate Vaccine Thirteen Valent on the Reduction of Invasive Pneumococcal Disease." ScholarWorks, 2016. https://scholarworks.waldenu.edu/dissertations/2116.
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Many children under the age of 5 die each year of invasive pneumococcal disease. Childhood vaccination against this disease reduces morbidity and mortality. Despite the introduction of a pneumococcal conjugate vaccine (PCV13) in a central African country in 2011, all provinces have not yet been vaccinated. The purpose of this quantitative quasi-experimental study was to determine whether there was an association between the introduction of PCV13 and new cases of pneumococcal disease in 2 provinces in central Africa. The sample size for the study was 380. The theoretical framework for this study was the epidemic model supported by the concept of herd immunity. Key research questions examined the incidence of pneumococcal disease in children by age, gender, and province. The independent variables were age, gender, province, and introduction of PCV13. The dependent variable was incidence of invasive pneumococcal disease. The research questions were evaluated using chi-square test of independence and logistic regression. The results of the study indicated that vaccination with PCV13 significantly reduced incident cases of invasive pneumococcal diseases (aOR 0.333, 95% CI 0.628-0.177, p = 0.001). However, this association was not significant for age (aOR 0.574, 95% CI 1.186-0.278, p = .134), and there were no significant gender differences (aOR 1.047, 95% CI 1.929-0.569, p = 0.882). Positive social change may result by enabling the protection of more children in the central Africa country provinces that have not yet adopted using PCV13 and by introducing the vaccine in other African countries.
7
Perez, Federico. "Challenges And Opportunities To Protect Veterans From Pneumococcal Disease: A “Virtual Clinic” Improves Vaccination." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1512685624555677.
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Wadanambi, Arachchige Sanjay Harsha Jayasinghe. "Long-term impact and effectiveness of vaccines on invasive pneumococcal disease in Australian children." Thesis, The University of Sydney, 2019. http://hdl.handle.net/2123/20156.
Full textAbstract:
Pneumococcal disease is a leading cause of morbidity and mortality in children globally. Pneumococcal conjugate vaccines (PCVs), available since early 2000, had proven efficacy to prevent invasive pneumococcal disease (IPD)-the sever form of pneumococcal infections. For Australian children PCV had been publicly funded through the national immunisation program, initially in 2001 for those with increased disease risk which included Aboriginal and Torres Strait Islander children and from 2005 for all children. The schedule of PCV used in Australia comprising three doses at age 2, 4 and 6 months (called 3+0 schedule) was unique for a developed country. The first PCV used was one covering 7 serotypes of pneumococcus (7vPCV) and in 2011 a PCV that covered 6 more serotypes (13vPCV) replaced 7vPCV. Research contained in this thesis is the first to assess how well PCV prevented IPD among Australian children. After 9 years of combined PCV use IPD in young children declined by over 80%. Together with the added benefit of herd immunity that led to large reductions in IPD in older age groups there was a halving of the all-age total IPD burden. Vaccine effectiveness (VE) of 3 doses against vaccine-type IPD in infancy was ~90% for both PCVs. A major finding in this research was the 5 times higher odds of vaccine-type IPD if the last PCV dose was 24–36 months ago compared to within the last 12 months. This finding of waning VE was a vital piece of evidence that supported the recommendation to move the 3rd dose of 13vPCV in the 3+0 schedule to become a booster dose (i.e. 2+1 schedule) for Australian children from July 2018. Using a data linkage method the impact of PCVs on IPD in children with underlying medical conditions predisposing to pneumococcal infection was explored separately. This highlighted the persistent IPD burden in children with immunosuppression, splenic dysfunction and breach in the CSF barrier, possibly due to opportunistic infection from non-vaccine serotypes.
9
Arana, Jorge E. "Comparison of Post-Licensure Safety Surveillance of 13-Valent Pneumococcal Conjugate Vaccine and 7-Valent Pneumococcal Conjugate Vaccine: Data from the Vaccine Advere Event Reporting System (Vaers)." Digital Archive @ GSU, 2011. http://digitalarchive.gsu.edu/iph_theses/159.
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Comparison of Post-licensure safety surveillance of 13-Valent Pneumococcal Conjugate vaccine and 7-Valent Pneumococcal Conjugate vaccine: Data from the Vaccine Adverse Event Reporting System (VAERS).
Background: On February 24, 2010, Food and Drug Administration (FDA) licensed a 13-valent pneumococcal conjugate vaccine (Prevnar 13®, [PCV13]) for use among children aged 6 weeks--71 months. The Advisory Committee on Immunization Practices (ACIP) recommended PCV13 routine vaccination of all children aged 2--59 months, children aged 60--71 months with underlying medical conditions, with PCV13 replacing PCV7 for all doses.
Methods: We searched case reports to the Vaccine Adverse Event Reporting System (VAERS), a US passive surveillance system, for adverse events (AEs) reported after immunization with PCV13 vaccine from February 24, 2010 through February 24, 2011 for persons vaccinated from February 24, 2010 through December 31, 2010 and compared them with AEs reported by persons who were vaccinated with PCV7.
Results: VAERS received 1503 reports of AEs after PCV13; multiple vaccines were given in 79.0% of reports. One hundred eighty (11.9%) were coded as serious, including nineteen reports of death. The most frequently reported symptoms were injection site reactions, fever, irritability and vomiting. Seven hundred fifty-eight (50.4%) reports comprised males. Most reports (37.7%) were from children 1-2 years. Total number of reports received for PCV13 was very similar to those received after vaccination with PCV7.
Conclusions: AEs reported to VAERS following 13-valent pneumococcal conjugate vaccine were consistent with AEs previously observed in pre-licensure trials. We did not identify any major safety concerns or outcomes.
10
Kwambana, Brenda Anna. "Infant nasopharyngeal microbial ecology and the pneumococcal conjugate vaccine." Thesis, University of Leicester, 2011. http://hdl.handle.net/2381/10049.
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11
Ohtola, Jennifer A. "Pneumococcal Vaccination in Aging HIV-Infected Individuals." University of Toledo Health Science Campus / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=mco1435076215.
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12
Li, Tsz-wai, and 李梓維. "Efficacy of combined influenza and 23-valent pneumococcal polysaccharide vaccines in chronic smokers." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/202310.
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Background
Chronic smokers are at risk of premature death associated with underlying pulmonary or cardiovascular diseases. Dual influenza and pneumococcal vaccination has been shown to prevent death and hospitalization secondary to pulmonary or cardiovascular diseases in elderly persons. Its effect in chronic smokers remained unknown.
Methods
This is a prospective randomized open-labeled trial conducted from April 2010 to March 2013, comprising adult patients aged less than 50 years who were chronic smokers. Subjects were randomly assigned into 4 groups. Group 1 (study group) patients received both trivalent influenza vaccine (TIV) and the 23-valent polysaccharide pneumococcal vaccine (PPV). There were 3 control groups: Group 2 patients received the TIV only. Group 3 patients received the PPV only and Group 4 patients did not receive any vaccines. The TIV used was the Vaxigrip® (Sanofi Pasteur, France) and the PPV used was the Pneumovax®23 (Merck, USA). All enrolled patients were follow-up for 24 months post vaccination. Patient details, Charlson comorbidity index, medications, subsequent hospitalization, diagnosis and mortality were recorded and analyzed.
Results
A total of 1006 subjects were enrolled and completed the study (Group PPV+TIV: 250; Group TIV: 254, Group PPV: 250 and Group None: 259). The baseline demographics and Charlson comorbidity index were similar among subjects in the 4 groups. The median age was 48 years and 85.9% were male patients. Significantly fewer subjects who received the dual vaccination (Group PPV+TIV) were hospitalized (p<0.001), with shorter mean length of stay (p<0.001), and less frequent hospitalization (p<0.001) for cardiovascular or respiratory diseases than no vaccination (Group None) or single vaccination (Group TIV and Group PPV). Multivariate analysis demonstrated that dual vaccination with PPV + TIV was the only independent factor associated with reduced risk of hospitalization (p<0.001; relative risk 0.288; 95% CI 0.101-0.154). There was no difference in mortality rate among the groups. Both vaccinations were well tolerated and no serious adverse events were reported.
Conclusion
Dual influenza and pneumococcal vaccinations prevented chronic smokers against hospitalization secondary to pulmonary or cardiovascular causes. Annual influenza and a single pneumococcal vaccination should be promoted among chronic smokers.published_or_final_version
Microbiology
Master
Master of Medical Sciences
13
Chan, Tuen-ching, and 陳端正. "Seasonal influenza and pneumococcal vaccination in institutionalized older adults." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/207606.
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Influenza (IV) and pneumococcal polysaccharide vaccination (PPV) may reduce hospitalization and mortality but the effectiveness of these vaccines in older adults (≥65 years) is controversial. This thesis includes seven parts with a total of ten studies studying different aspects regarding IV and PPV in institutionalized older adults - the group with the highest infection-related morbidity and mortality.
In Part I, we presented the controversies about effectiveness of influenza and pneumococcal vaccination in institutionalized older adults.
In Part II, we studied a retrospective cohort of 1737 older adults showing that nursing home residence is independent risk factor of infection-related mortality and hospitalization.
In Part III, the second and third studies were systematic reviews showing that IV and PPV could reduce pneumonia and death..
In Part IV, we evaluated the effectivenss of IV and PPV through prospective cohorts. The fourth study was a prospective cohort study of 1859 institutionalized older adults showing that IV significantly reduced mortality and hospitalization. The fifth study was a prospective cohort study of 532 institutionalized older adults showing that when the IV strain does not match the circulating strain, PPV provided additional protection in reducing mortality.
In Part V, the sixth study was a randomized controlled trial of 100 institutionalized older adults showing that intradermal IV has better immunogenicity than intramuscular vaccination without compromising safety.
In Part VI, we identified factors that may affect clinical effectiveness of IV. The seventh and eighth studies were prospective cohort studies of 711 institutionalized older adults showing that vaccine efficacy declined with increasing impaired functional status and renal function.
In Part VII, we identified determinants of receiving IV and PPV in institutionalized older adults. The ninth study was a cross-sectional study of 155 institutionalized older adults showing that encouragement from nHCWs was a major facilitator of receiving vaccination. The tenth study was a cross-sectional study of 1300 nHCWs showing that 40.2% of nHCWs had encouraged residents to receive vaccination.
In conclusion, ten studies from this thesis demonstrated that IV and PPV are effective in preventing hospitalization and reducing mortality in institutionalized older adults. Different strategies in improving its effectivenss and acceptance were suggested.published_or_final_version
Medicine
Master
Doctor of Medicine
14
Clutterbuck, Elizabeth Ann. "The human B cell response to a pneumococcal conjugate vaccine." Thesis, Open University, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.446115.
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15
Iyer, Anita Sridhar. "Response to Pneumococcal-Polysaccharide Vaccine PPV23 in HIV-Positive Individuals." University of Toledo Health Science Campus / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=mco1437416478.
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Poerschke, Gabriele. "Key issues of evidence-based vaccinology as illustrated by pneumococcal vaccine development." Thesis, Click to view the E-thesis via HKUTO, 2001. http://sunzi.lib.hku.hk/hkuto/record/B3197076X.
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Hamaluba, Mainga. "Streptococcus pneumoniae : nasopharyngeal carriage and vaccine studies in the UK and Nepal." Thesis, University of Aberdeen, 2015. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=230502.
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Streptococcus pneumoniae is one of the leading causes of morbidity and mortality in children under 5. Low-income countries are disproportionally affected and data in these settings are lacking. Effective strategies to control disease include infant immunisation with pneumococcal protein-polysaccharide conjugate vaccines. However, ongoing surveillance of carriage and disease are important to understand the impact of vaccination within communities. This thesis evaluated nasopharyngeal (NP) carriage in 3 generations, following introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the UK. NP carriage was also compared between rural and urban Nepalese children and a novel method of delayed culture and transport was assessed. Finally, the immunogenicity of a 10-valent pneumococcal conjugate vaccine administered in a 2-dose priming schedule without a booster was compared to a 3-dose priming schedule with a booster in Nepalese infants. Key findings include carriage rates in UK children being similar to pre-PCV7 (7 valent pneumococcal conjugate vaccine) carriage rates at 47% with low carriage rates in seen in adults. PCV7 serotypes accounted for 1.5% of carriage isolates in children, 0% in parents and 15.4% in older adults. In Nepalese children carriage was higher in a rural (69.2%) compared to an urban setting (40.9%) and delayed culture and transport using silica desiccant packets (SDP) provided a reliable, albeit underestimated, estimate of carriage. Finally this author demonstrated that following primary immunisation and boosting, there was no difference in immune responses to serotypes 1, 5 and 14 with a 2 dose priming schedule compared to a 3-dose schedule. At 2-4 years of age a significantly higher proportion of vaccinees in the 2+1 group had ≥0·2µg/mL IgG for serotypes 1, 5, 6B and 18C compared to vaccinees in the 3+0 group.
18
Kunda, N. K. "Dry powder inhalation of pneumococcal vaccine using polymeric nanoparticles as carriers." Thesis, Liverpool John Moores University, 2014. http://researchonline.ljmu.ac.uk/4462/.
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Streptococcus pneumoniae is the leading bacterial cause of pneumococcal diseases, of which pneumonia is the main cause of death amongst the immunocompromised, elderly over the age of 50 and children under the age of 5. Although vaccines such as pneumococcal polysaccharide vaccine 23, pneumococcal conjugate vaccine 7, 10 and 13 are available, they are expensive to produce and distribute. Moreover, the variation in serotype distribution across geographical locations and rise in dominance of disease due to non-vaccine serotype coverage has led to significant attention towards the development of alternate vaccine candidates such as pneumococcal surface protein A (PspA). A potential dry powder vaccine formulation containing polymeric nanoparticles (NPs) adsorbed with PspA4Pro and formulated into nanocomposite microparticles (NCMPs) using L-leucine (L-leu) to be delivered via inhalation was developed. Poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, NPs with either anionic or cationic surface charge of optimum size (~200-250 nm) to be effectively taken up by the lung dendritic cells (DCs) were successfully produced. The NPs were then surface adsorbed with PspA4Pro (~20 µg of PspA4Pro per mg of NPs) and spray-dried using L-leu as a microcarrier to produce NCMPs with a product yield of 55.55±6.64% for the PspA4Pro adsorbed anionic NPs/NCMPs and 53.98±2.23% for the PspA4Pro adsorbed cationic NPs/NCMPs. The NCMPs produced had a corrugated and wrinkled surface morphology. The aerosol properties of anionic NPs/NCMPs determined using a Next Generation Impactor displayed a fine particle fraction (FPF) of 74.31±1.32% and mass median aerodynamic diameter (MMAD) of 1.70±0.03 μm indicating that the majority of the dose would be deposited in the respirable airways of the lungs. The anionic and cationic PGA-co-PDL NPs upon incubation with DCs for 1 h showed an effective uptake as visualised using confocal microscopy. Furthermore, the anionic NPs/NCMPs were well tolerated by the A549 cell line with a cell viability of 87.01±14.11% at 1.25 mg/ml concentration, whereas the cationic NPs/NCMPs showed a cell viability of 75.76±03.55% at 156.25 µg/ml concentration upon 24 h exposure. The PspA4Pro released from the optimised formulations largely maintained its structure as determined using SDS-PAGE and circular dichroism, and the relative antigenicity measured using ELISA was 0.97±0.20 and 0.85±0.05 for anionic and cationic formulations, respectively. Overall, the results obtained indicate the use of these NPs as novel carriers for pulmonary vaccine delivery against pneumococcal diseases.
19
Skull, Susan. "Effectiveness of influenza and pneumococcal vaccination against hospitalisation for community-acquired pneumonia among persons >65 years /." Connect to thesis, 2007. http://repository.unimelb.edu.au/10187/1998.
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Although there are well-documented benefits from influenza vaccine and 23-valent pneumococcal polysaccharide vaccine (23vPPV) against invasive pneumococcal disease and laboratory confirmed influenza, their effectiveness against pneumonia remains controversial for community-based persons aged >=65years. At the time of this research, within Australia, only the government of Victoria publicly funded these vaccines for elderly persons. With continued growth of the elderly population, the subsequent adoption of an Australia-wide program, and increasing uptake of similar programs in other countries, there is a need for data clarifying the impact of vaccination on pneumonia. This research estimates incremental vaccine effectiveness of 23vPPV over and above influenza vaccine against hospitalisation with community-acquired pneumonia (CAP) in the elderly.
20
Morrow, Adrienne. "The burden of pneumococcal disease in the Canadian population before routine use of the 7-valent pneumococcal conjugate vaccine." Thesis, Université Laval, 2006. http://www.theses.ulaval.ca/2006/23767/23767.pdf.
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21
Xu, Hui, and 徐晖. "Review on global disease burden of pneumonia in young children and pneumococcal vaccination policy." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48426799.
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Pneumonia is one of the top causes of deaths in children younger than 5 years of age. According to WHO estimation, globally there are nearly 2 millions young children who die from pneumonia every year, and more than 70% of these deaths occurred in Africa and Southeast Asia. Pneumonia caused by Streptococcus pneumoniae (also called pneumococcus) is a vaccine preventable disease, accounting for 39% of community-acquired pneumonia. There are two types of pneumococcal vaccines that are pneumococcal polysaccharide vaccine (PPV) and pneumococcal conjugate vaccines (PCV). The latter one is routinely advised for children younger than five years.
The aims of this paper are to review the global disease burden caused by Streptococcus pneumoniae in children younger than 5 years and to gather vaccine program information globally. For narrative review and policy analysis, WHO websites, other websites of health organizations or institutions, and literatures from Pubmed were reviewed, using key words “children pneumonia”, “Streptococcus pneumoniae”, “pneumonia vaccine”, “pneumococcal conjugate vaccine ”, “PCV-7”, “7-valent PCV”, “PCV-13”, “13-valent PCV”.
Numerous literatures have reported that obvious incidence decrease of invasive pneumococcal diseases (IPD) in young children after PCV vaccination. In July 2000 PCV-7 (“7-valent pneumococcal conjugate vaccine”) was incorporated into National Immunization Program (NIP) in United States. Although since then the incidence of IPD caused by vaccine-covered serotypes markedly decreased, those caused by non-vaccine-covered serotypes were found substantially increased. In February 2010, PCV-13 (“13-valent pneumococcal conjugate vaccine”) replaced PCV-7 in NIP in United States. With a wider range of serotypes, PCV-13 was expected to be more effective than PCV-7 in children under 5. Using modeling method, many scholars estimated that PCV-13 was likely to be more cost-effective in reported settings when herd immunity was taken into consideration.
Schedule of vaccine was another issue that needs to be investigated. There are three schedules commonly adopted by health authorities: 2 primary doses with 1 booster dose (2p+1), and 3 primary doses with 1 booster (3p+1) or without 1 booster dose (3p+0). In individual report, it seems three schedules were all effective. From result of systematic review, more evidence supported to use 3p+0 schedule (and 3p+1 schedule). However, emerging evidences are in support of 2p+1 schedule tool. WHO recommended both 3p+0 and 2p+1 schedule. If the country with high incidence rate in young infant (less than 32 weeks) 2p+1 schedule may not provide adequate protection for special individual serotype. In addition 2p+1 schedule may also lead to lower antibody level between the second primary dose and the booster dose, but the booster dose could induce higher antibody level, which is important for protecting certain serotypes. Countries should consider local factors and choose suitable vaccine schedule accordingly.
In terms of global PCV programs, around 80 countries have already added PCV into their NIP, 58 countries (30%) were planning to introduce the program; nevertheless remaining 51 countries (26%) of countries have no schedule to introduce it yet. Most countries that have implemented PCV programs were western industrialized countries. With support from Global Alliance for Vaccines and Immunization (GAVI), 15 eligible African countries have had routine PCV programs. Comparatively, in Asia, India and China, two countries with the largest population and largest number of IPD cases in the world, have no PCV program to the children. Even industrialized economies like Japan and Taiwan have not implemented yet. Asia was lagging behind for decades. PCV program needs to be prioritized in Asian countries. Asian governments should consider investing more in PCV programs (high-income countries) and/or cooperating with other organizations such as GAVI (low-income countries) to increase the coverage of PCVs in children under 5 and to protect them from pneumococcal diseases.published_or_final_version
Public Health
Master
Master of Public Health
22
Usuf, Effua Abigail. "The introduction of pneumococcal conjugate vaccine into the Gambia : carriage and costs." Thesis, London School of Hygiene and Tropical Medicine (University of London), 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.590562.
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Lock, Robert Arthur. "Studies on virulence proteins of Streptococcus Pneumoniae /." Title page, summary and table of contents only, 1989. http://web4.library.adelaide.edu.au/theses/09PH/09phl813.pdf.
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Parameswar, Archana R. "Towards development of a fully synthetic conjugate vaccine investigation of structural analogs of Streptococcus pneumoniae serogroup 6 /." Diss., St. Louis, Mo. : University of Missouri--St. Louis, 2008. http://etd.umsl.edu/r3161.
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Vanghelof, Joseph C. "PNEUMOCOCCAL CONJUGATE VACCINE 13 COVERAGE IN CHILDREN, HIGH-RISK ADULTS 19-64 YEARS OF AGE, AND ADULTS OVER 65 YEARS OF AGE IN A COMMERCIALLY INSURED U.S. POPULATION." UKnowledge, 2017. http://uknowledge.uky.edu/pharmacy_etds/76.
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This thesis aimed to elucidate the demographic characteristics associated with elevated or reduced rates of pneumococcal conjugate 13 (PCV13) vaccination.
A retrospective cohort study was performed using the Truven Health MarketScan® Database. Three cohorts were created corresponding to populations for which the CDC recommends PCV13 vaccination. Cohort 1: children < 36 months of age. Cohort 2: adults 19-64 years of age with high infection risk. Cohort 3: adults > 65 years of age. Odds of having a PCV13 claim were calculated for each cohort.
For Cohort 1, 78% out of a total of 353,214 subjects had a sufficient number of PCV13 doses to meet CDC recommendations. For Cohort 2, 3.7% out of a total of 673,157 subjects had a PCV13 claim. For Cohort 3, 18% of 1,262,531 subjects had a PCV13 claim. Odds of vaccination were generally lower in younger subjects, those with fewer outpatient claims, and those with residence in the Northeast and South regions. In Cohort 2, odds were reduced in subjects with generalized malignancy. Gender and urban residence were poor predictors of vaccination status.
By understanding the demographic factors associated with lower rates of vaccination, clinicians may more effectively direct their efforts to increase pneumococcal vaccination coverage.
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Kyaw, Moe Hein. "Epidemiology of pneumococcal disease in Scotland : implications for vaccine prevention policies and strategies." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/28385.
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Methods: Review of laboratory data collected through a national network of diagnostic laboratories covering the entire population of Scotland, was reviewed to examine the epidemiological characteristics of pneumococcal disease. Cross-sectional surveys were conducted to explore pneumococcal polysaccharide vaccination practices. Results: The incidence of invasive pneumococcal disease is highest in young children aged less than 2 years (44.9/105 persons) and in the elderly aged 65 years and above (28.4/105) persons. The incidence of pneumococcal meningitis is highest in children aged less than 2 years (11.8/105 persons). There was a 3-fold increase in the prevalence of penicillin (from 4.2% in 1992 to 12.6% in 1999) and erythromycin (from 5.6% in 1994 to 16.3% in 1999) non-susceptible pneumococcal isolates. Regional differences in the prevalence of antibiotic non-susceptible pneumococci correlated weakly with the rate of penicillin prescription, but not with erythromycin prescription. Pneumococci are the leading cause of invasive non-meningeal bacterial disease and the second leading cause of bacterial meningitis in Scotland after introduction of Hib conjugate vaccine in the national vaccination programme. The formulation of current pneumococcal polysaccharide vaccine covers the serotypes responsible for the majority of invasive and non-invasive disease in Scotland. Coverage of invasive and non-invasive serotypes by pneumococcal conjugate vaccines was substantially higher in younger age groups (5 years and less) than in older aged groups. All polysaccharide and conjugate pneumococcal vaccines cover nearly all serotypes associated with invasive and non-invasive resistant pneumococcal disease. General practitioners and hospital doctors have an adequate knowledge of pneumococcal polysaccharide vaccination.
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Bahuaud, Mathilde. "Vaccination anti-pneumococcique chez les sujets à risque d'infections invasives à pneumocoques et prévention de l'hyporéponse Immunogenicity and persistence of the 13-valent pneumococcal conjugate vaccine (PCV13) in patients with untreated smoldering multiple myeloma (SMM): a pilot study Immunogenicity and persistence of a prime-boost re-vaccination strategy for pneumococcal vaccines in patients with rheumatoid arthritis Pneumococcal vaccination in patients with systemic lupus erythematosus: a multicenter placebo-controlled randomized double-blind study Prevention of hyporesponsiveness by modulation of schedule and doses of pneumococcal vaccine immunization." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB067.
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Deux vaccins sont actuellement disponibles pour la prévention des infections invasives à pneumocoques (IIP) : un vaccin polysaccharidique Pneumovax® (PPV23) et un vaccin conjugué Prevenar13® (PCV13), induisant respectivement une protection contre 23 et 13 sérotypes. Le PPV23 est considéré comme faiblement immunogène, en particulier chez les personnes âgées et les patients immunodéprimés. Le PCV13, en revanche, en raison de la conjugaison à une protéine porteuse, présente l'avantage d'induire une réponse immunitaire T-dépendante, non observée avec le vaccin PPV23. Dans notre travail nous avons donc évalué l'impact des stratégies vaccinales utilisant le PCV13 et le PPV23 sur différentes populations de patients à risque. Dans une première étude, nos résultats sur la vaccination anti-pneumococcique chez des patients atteints de myélome indolent (SMM) ont montré qu'une dose de PCV13 seul, induisait une réponse immune transitoire et de faible persistance. Ces résultats suggéraient l'utilisation d'un schéma vaccinal incluant plusieurs doses de PCV13 ou une association avec le PPV23. Depuis 2013, ce schéma combiné du PCV13 et du PPV23 est le schéma recommandé par la Haute Autorité de Santé en France chez les patients à risque, avec les délais suivants : une dose de PCV13 suivie d'une dose de PPV23, 8 semaines après. Nous avons par la suite étudié cette stratégie vaccinale combinée chez des patients à risque d'IIP : patients atteints de lupus érythémateux systémique (SLE) et patients atteints de polyarthrite rhumatoïde (PR). Nos résultats montrent une immunogénicité à court terme de la stratégie combinée, mais une protection qui ne persiste pas au-delà de deux ans. De façon surprenante, les taux d'anticorps 2 ans après la vaccination, sont inférieurs aux taux pré-vaccinaux pour les patients PR. Cet effet délétère du PPV23 sur la réponse vaccinale induite par le PCV13 est appelé hyporéponse. Ce phénomène, observé chez les patients PR, ne se retrouve pas chez les patients SLE dont la vaccination PPV23 a été effectuée plus à distance du PCV13. Ces résultats suggèrent que le schéma vaccinal plus tardif (c'est-à-dire une vaccination par le PPV23 six mois après le PCV13 au lieu de deux mois) inhiberait le phénomène d'hyporéponse. Dans une troisième partie, nous avons comparé différents schéma vaccinaux modulant les doses des vaccins et les délais d'injection chez des volontaires sains mais également dans un modèle murin d'hyporéponse développé au sein du laboratoire. Notre hypothèse était que la modulation du schéma vaccinal utilisant les 2 vaccins pouvait à la fois induire une protection à long terme et prévenir l'hyporéponse. Nos résultats ont montré que l'utilisation d'une dose diminuée de PPV23 ou l'injection concomitante des deux vaccins n'empêchaient pas l'hyporéponse. En revanche, en allongeant le délai entre le PCV13 et le PPV23, le phénomène d'hyporéponse est limité. Des études cliniques chez les patients à risque d'IIP sont nécessaires afin d'évaluer une stratégie combinée tardive, où le PPV23 serait reçu au moins 6 à 12 mois après le PCV13Two vaccines are currently available for the prevention of invasive pneumococcal diseases (IPD): a polysaccharide vaccine, Pneumovax® (PPV23) and a conjugate vaccine, Prevenar13® (PCV13), inducing protection against 23 and 13 serotypes, respectively. PPV23 is considered to be weakly immunogenic, particularly in the elderly and immunocompromised patients. PCV13, however, due to the conjugation to a carrier protein, has the advantage of inducing a T-dependent immune response, not observed with PPV23 vaccine. In our work, we therefore evaluated the impact of vaccine strategies using PCV13 and PPV23 on different populations of patients at risk of IPD. In a first study, our results on anti-pneumococcal vaccination in patients with smoldering myeloma (SMM) showed that a single dose of PCV13 induces a transient immune response and long term persistence. These results suggested the use of a vaccination schedule including several doses of PCV13 or association with the PPV23. Since 2013, this combined strategy of PCV13 and PPV23 is recommended by la Haute Autorité de Santé (HAS) for patients at risk, with the following delays: a dose of PCV13 followed by a dose of PPV23, 8 weeks later. We then studied this combined vaccine strategy in patients at risk of IPD: patients with systemic lupus erythematosus (SLE) and patients with rheumatoid arthritis (RA). Our results show a short-term immunogenicity of the combined strategy, but a protection that does not persist beyond two years. Surprisingly, antibody levels 2 years after vaccination are lower than pre-vaccine levels for RA patients. This negative effect of PPV23 on PCV13-induced immune response is called hyporesponsiveness. This phenomenon, observed in RA patients, is not found in SLE patients who received PPV23 vaccination at distance from PCV13. These results suggest that the delayed vaccination schedule (ie, PPV23 vaccination six months after PCV13 instead of two months) could inhibit the hyporesponsiveness phenomenon. In a third study, we compared different vaccine strategies modulating vaccine doses and injection times in healthy volunteers but also in a mouse model of hyporesponsiveness developed in our laboratory. Our hypothesis was that modulation of the vaccine schedule using both vaccines could both induce long-term protection and prevent hyporesponsiveness. Our results showed that decreased doses of PPV23 or concomitant injection of both vaccines did not prevent hyporesponsiveness. However, by increasing the delay between PCV13 and PPV23, the phenomenon of hyporesponsiveness is limited. Clinical studies in patients at risk of IPD are needed to evaluate a delayed combined strategy, where PPV23 would be received at least 6 to 12 months after PCV13
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Tunc, Melissa. "Evidence-Based Practice for Influenza and Pneumococcal Nurse-Driven Protocol." ScholarWorks, 2018. https://scholarworks.waldenu.edu/dissertations/5142.
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At the project site in New Jersey, eligible patients were leaving the hospital without receiving the influenza or pneumococcal vaccine. The field site has an established, evidence-based, nurse-driven protocol. The purpose of this project was to increase adherence to the current influenza and pneumococcal nurse-driven protocol on one medical-surgical unit. This unit had experienced low adherence rates to the nurse-driven protocol for vaccines, not reaching the New Jersey state target of 96% administration prior to discharge. The practice-focused question was: Will increasing awareness of evidence-based practice increase adherence to the influenza and pneumococcal vaccine protocol? A quality improvement plan was developed to address a gap in practice using the plan-do-study-act model. Internal vaccination data was the source of evidence used to drive this project. Baseline data was used from 2 months prior to the December 2017 start of the project. Once the quality improvement plan was implemented, data were collected and analyzed weekly with the quality improvement team. Findings for the pneumococcal vaccine demonstrated reaching 96% or higher while the influenza vaccine exceeded the state target reaching 100% of discharged patients being vaccinated. Implementing large surveillance boards into clinical rounds promoted increased adherence to the protocol, achieving a positive social change. Leadership worked directly with the staff to use evidence-based practice and promote nursing autonomy to administer the vaccines. An increased number of vaccinated patients leaving the medical-surgical unit was achieved.
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Vadesilho, Cintia Fiuza Marques. "Mapeamento de epitopos presentes em variantes dos antígenos vacinais PspA (Pneumococcal surface protein A) e PspC (Pneumococcal surface protein C) de Streptococcus pneumoniae." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-06122014-075950/.
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S. pneumoniae pode causar infecções do trato respiratório. Uma alternativa às vacinas conjugadas, que conferem proteção sorotipo-específica, seria uma vacina baseada em epitopos de diferentes variantes de antígenos como PspA e PspC. O objetivo deste trabalho foi a identificação de epitopos de variantes de PspA e PspC, utilizando a técnica peptide array, visando a síntese de um antígeno composto por múltiplos epitopos. Os resultados obtidos indicaram que anticorpos contra epitopos lineares de PspA reconhecem as regiões inicial N-terminal e rica em prolinas, mas estes epitopos parecem ser apenas marcadores de exposição ao pneumococo e epitopos conformacionais seriam os de fato protetores, como observado nos experimentos realizados com os Frags de 100 aminoácidos construídos a partir do PspARx1, especialmente aqueles presentes nas regiões dos Frags 2 e 4. Epitopos lineares de PspC parecem ser importantes na região de ligação à sIgA e FH. Assim, uma vacina proteica de ampla cobertura, poderia conter as regiões do Frag 2 de PspA e de ligação de sIgA e FH de PspC.S. pneumoniae can cause respiratory tract infections. An alternative to the conjugate vaccines, which confer serotype-specific protection, would be a vaccine based on epitopes of variants of antigens such as PspA and PspC. The objective of this study was to identify epitopes of variants of PspA and PspC, using the peptide array technique, aiming at the synthesis of a multi-epitope antigen. The results obtained with peptide arrays indicated that antibodies against linear epitopes of PspA recognize the initial N-terminal and proline-rich regions, but these epitopes seem to be only markers of exposure to pneumococcus and conformational epitopes would be in fact protective, as observed in the experiments with fragments of 100 amino acids constructed from PspARx1, especially those present in Frags 2 and 4. Linear epitopes of PspC seem to be important in the regions of sIgA and FH binding. Thus, a protein-based vaccine with broad coverage could contain the regions of Frag 2 of PspA and the regions of sIgA and FH binding of PspC.
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Greenfield, Hayley Maria. "Evaluation of pneumococcal conjugate vaccine (Prevenar®) inpatients with myeloma and chronic lymphocytic leukaemia." Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.507207.
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Infection with Streptococcus pneu1110niae is responsible for significant mortality in individuals with a defective humoral response. This diverse group includes patients with the haematological conditions myeloma and chronic lymphocytic leukaemia. Vaccination to prevent pneumococcal infection is recommended by the Department of Health for those individuals in whom disease is likely to be 'more common and/or more dangerous'. The currently recommended 23-valent polysaccharide vaccine has been shown to be poorly immunogenic in patients with myeloma and chronic lymphocytic leukaemia. Responses to vaccination may be improved by conjugation of polysaccharides to immunogenic carrier proteins. Prevenar©, a 7-valent conjugate vaccine has been demonstrated to be immunogenic both in young children and in adults following allogeneic bone marrow transplantation. These groups had both previously been shown to respond poorly to the 23-valent polysaccharide vaccine. A clinical trial was designed to evaluate the use of Prevenar in individuals with myeloma and chronic lymphocytic leukaemia. Serological response to the vaccine was the primary end-point determined by a recently evaluated pneumococcal serotype-specific Bioplex assay. In addition the serological response to the protein carrier was also evaluated using a newly developed assay. The vaccination programme resulted in statistically significant increases in serotype-specific antibody levels. For a proportion of trial participants this represented adequate protection. The immunogenicity of the conjugate vaccine was modest however when compared to the published data in other clinical scenarios. The suboptimal response was most likely to have been related to the deficient cell mediated and humoral immunity observed in this population. More detailed evaluation of these parameters may identify individuals who are more likely to respond to the conjugate vaccine.
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Moss, Samantha Jane. "Immunogenicity of the seven valent conjugate in UK term and preterm infants pneumococcal vaccine." Thesis, University of Newcastle upon Tyne, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.485803.
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Jaccard, Ruedin Hélène. "Invasive meningococcal and pneumococcal disease in Switzerland : cost-utility analysis of different vaccine strategies /." Neuchâtel : [s.n.], 2003. http://www.public-health-edu.ch/new/Abstracts/JRH_02.06.03.pdf.
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Tashani, Mohamed Nagmi. "Optimising Immune Responses To Conjugate Vaccines Among Vulnerable Populations: Infants And Hajj Travellers." Thesis, The University of Sydney, 2017. http://hdl.handle.net/2123/17307.
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Conjugate vaccines have been developed against some bacterial pathogens such as Haemophilus influenzae type b (Hib), Neisseria meningitidis, and Streptococcus pneumoniae. Conjugate vaccines are immunologically superior to the polysaccharides vaccines, but more expensive. They involve the joining of a purified polysaccharide moiety of bacterial capsule to a protein molecule known as carrier protein. The carrier protein enables the vaccines to elicit a T-cell response and thereby induce memory. The carrier protein has antigenic similarity to the components of diphtheria, tetanus and pertussis vaccine (DTP) or adult tetanus, diphtheria, and pertussis vaccine (Tdap). The concurrent or sequential administration of a conjugate vaccine with DTP antigen may have positive or negative immunological impacts; positive if it primes the immune system for a stronger response to the polysaccharide antigen, negative if a carrier overload results in suppression of the subsequently administered conjugate vaccine. Finding a conclusive evidence of the positive interaction (carrier priming) could be implemented to enhance the immunogenicity of a conjugate vaccine. This may contribute to reducing the number of doses required to adequately immunise infants in the hope that might lead to substantial economic savings through a reduced dosing regimen. The research reported here examines conjugate vaccine interactions with DTP and explores optimising the immune responses to conjugate vaccines among vulnerable populations. The study groups chosen were infants and adult Hajj pilgrims who are eligible to receive multiple vaccines, because of their vulnerability. The primary objective of this work was to examine and categorise conjugate and DTP vaccine interactions and establish whether they entail priming of -or interference - with antibody responses. Its secondary objective was to explore the uptake and barriers to receiving conjugate vaccines among Hajj pilgrims. Methods In this thesis, I present nine publications that explore both conjugate and DTP vaccine interactions and assess uptake of and barriers to conjugate vaccines. Publications #1 and #2 represent a thorough literature review of conjugate vaccine interaction with DTP and potential implications for vulnerable populations such as infants in developing countries. Publications #3-5 report a survey exploring pneumococcal vaccine uptake in Hajj travellers and assess the pilgrims’ knowledge about some travel related infectious diseases and their respective vaccines as well as addressing barriers to optimal vaccine uptake. Publication #6, a retrospective data analysis, provides evidence suggestive of clinical protection in infants as a result of positive interaction between DTP vaccine and pneumococcal conjugate vaccine (PCV). Publications #7-9, present the results of two one-year randomised controlled trials (RCTs) designed specifically to examine the sequential and concurrent interaction of Tdap upon two conjugate vaccines (the 13-valent PCV [PCV13] and the quadrivalent meningococcal conjugate vaccine [MCV4]) in adult Hajj pilgrims. Results The survey (Publication #3) demonstrated that the uptake of pneumococcal vaccine among Hajj pilgrims in the years 2011, 2012 and 2013 was suboptimal (28.5%, 28.7% and 14.2% respectively). Publication #4 showed that there were several misconceptions surrounding the vaccines and their respective infections. Moreover, immunisation providers were focusing more on classic vaccines against food-borne infections than on vaccines against respiratory infections, even though the latter are more common in Hajj settings (Publication #5). In regard to the conjugate vaccine interactions, the literature review (Publication #1) provided some evidence for positive interaction between DTP vaccine and PCV and Hib conjugate vaccines, especially in infants and young children, which was further supported by my retrospective data analysis in Australian infants (Publication #6). This interaction could be attributed to an immunological phenomenon known as ‘carrier priming’ which leads immunogenicity enhancement of a conjugate vaccine after prior exposure to DTP vaccine or one of its components. However, the literature review (Publication #1) findings were different and variable for adults. My detailed investigation through two RCTs involving adult travellers (Publications #7-9) showed that upon prior exposure to Tdap vaccine, there was a suppression in the immunogenicity of two subsequently administered conjugate vaccines (PCV13 and MCV4), irrespective of their carrier protein type: The first trial conducted in the year 2014 demonstrated that prior administration of Tdap vaccine significantly (p < 0.05) suppressed the subsequent geometric mean concentrations (GMTs) to six (3, 5, 18C, 4, 19A and 9V) of the 13 pneumococcal serotypes in PCV13 (Publication #7). The subsequent trial in 2015, showed that administering Tdap vaccine 3-4 weeks before the coadministration of (PCV13 and MCV4) significantly (p < 0.05) suppressed the GMTs to seven (1, 3, 4, 5, 14, 18C and 9V) of the 13 pneumococcal serotypes in PCV13, and significantly (p < 0.05) reduced the proportion of subjects achieving a ≥4-fold rise in serum bactericidal antibody (SBA) for serogroup W in MCV4 (Publications #8 and 9). A reverse effect was noted upon administering the conjugate vaccine before Tdap vaccine (Publications #7 and 8), enhancing the anti-diphtheria and anti-tetanus antibody response. No serious adverse events were reported either in concurrent or sequential administration of the trials’ vaccines. Conclusion Across all the publications’ analyses, the review article (Publication #1) and the retrospective data analysis in Australian infants (Publication #6) showed a promising role for carrier priming in children in enhancing the immunogenicity of the conjugate vaccines and reducing their costs, particularly for PCV (the most expensive conjugate vaccine). On the other hand, the trials in adults (Publications #7-9) demonstrated that there was suppression of PCV13 and MCV4 immune response in adults upon prior exposure to Tdap vaccine. In infants, there is a promising role for carrier priming. However, in adults when multiple vaccines are required, administering the conjugate vaccine with, or before Tdap vaccine might avoid interference to the conjugate vaccine immunogenicity, and could yield a better immune response to Tdap.
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Baynam, Gareth. "Genetic influences on vaccine response in children." University of Western Australia. School of Paediatrics and Child Health, 2008. http://theses.library.uwa.edu.au/adt-WU2008.0259.
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Vaccination is one of the most efficacious public health interventions1 and has been increasingly used to combat non-infectious diseases. Mechanisms underlying vaccine responses overlap with those regulating immune responses in health and disease. Therefore, an understanding of mechanisms underpinning these responses will have broad implications. Variation in immune response genes contributes to impaired vaccine responses2-4. Understanding the contribution of genetic variants to vaccine responses is likely to be particularly important in early life given the generalized functional immaturity of the immune system in infants and the highly variable kinetics of its maturation over the first few years of life5-7. However, studies of genetic influences on early childhood vaccine responses are scarce. Since a number of genes from several pathways are likely to be important, a targeted approach is necessary. This thesis explored the effects and interactions of genes associated with atopy, as atopy, or the genetic risk for it, has been associated with modulation of early childhood vaccine responses. This thesis aimed to: 1) investigate genetic variants associated with atopy on early childhood vaccine responses; 2) examine interactions between these genetic variants and non-genetic factors; 3) approach developmental genetic influences on genetic effects and their interactions; and 4) extend findings on vaccine responses to other immunological phenotypes and disease outcomes.
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Elemraid, Mohamed Ahmed. "The impact of the pneumococcal conjugate vaccine on the epidemiology and aetiology of childhood pneumonia." Thesis, University of Newcastle upon Tyne, 2013. http://hdl.handle.net/10443/2026.
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Background: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced routinely in the UK in September 2006 and replaced by PCV13 from April 2010. Aims: To evaluate the impact of PCV7 on the incidence of all-cause community-acquired pneumonia (CAP) in children. Also to investigate the aetiology of CAP before and after the introduction of PCV as well as serotype the pneumococcal infections. Methods: Enrolled children were from North East England (excluding Cumbria) who were aged 0–16 years and presented with clinical and radiological features suggestive of pneumonia. Epidemiology survey was prospectively undertaken in 2008–2009 at 11 hospitals in North East England. Data were compared to those from a similar survey undertaken in the same hospitals in 2001–2002. Aetiology studies were prospectively conducted in 2001–2002 (pre-vaccine) and 2009–2011 (post-vaccine) in Newcastle and Middlesbrough. Investigations included culture, serology, immunofluorescence antibody, urinary pneumococcal antigen and PCR assays. Epidemiology Results: A total of 542 children were enrolled, of which 74% were aged <5 years. PCV7 uptake was 90.7%. The annual incidence of pneumonia was 11.8/10 000 (95% CI 10.9–12.9), and the hospitalisation rate was 9.9/10 000 (95% CI 9.0–10.9). Compared to 2001, there was a 19% (95% CI 8–29) reduction in the annual rate of CAP in those aged <5 years, and in those <2 years a 33.1% (95% CI 20–45) reduction in the annual incidence of CAP and 38.1% (95% CI 24–50) reduction in hospitalisation rates. However, for those unvaccinated aged ≥5 years, there was no difference in the annual incidence of CAP and hospitalisation rate between both surveys. Since 2001, the overall reduction in annual incidence was 17.7% (95% CI 8–26) and for hospitalisation 18.5% (95% CI 8–28). Aetiology Results A total of 401 children were enrolled; 241 and 160 respectively in the pre- and post- vaccine studies (73% aged <5 years), for whom at least one diagnostic investigation had been performed. Identification of a definite pathogen was higher post-vaccine (61%) than pre-vaccine (48.5%) [p=0.019]. Rates of bacterial infections were not different between post- and pre-vaccine (17.5% versus 24%, p=0.258). Viral (31%) and mixed infections (12.5%) found more often post-vaccine than pre-vaccine (19.5% [p=0.021] and 5% [p=0.015] respectively). Pneumococcal detection post-vaccine was substantially improved when PCR assays were used compared to culture (21.6% versus 6%, p=0.0004). A serotype was identified in 75% (18/24) post-vaccine including serotypes 1 (44.4%), 3 (27.8%), 19A (22.2%) and 7A/F (5.6%). Conclusions: PCV7 has reduced both the annual incidence and rate of hospitalisation of pneumonia in children, particularly those aged <2 years. Pneumococcal serotypes which are included in PCV13 but not PCV7 predominated. This suggests that the replacement with PCV13 likely to be associated with a reduction in the incidence of pneumococcal-related pneumonia. Continued surveillance is required to monitor for emerging serotypes.
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Puumalainen, Taneli. "An eleven valent diphtheria and tetanus-conjugated pneumococcal vaccine immunogenicity and safety in Filipino infants." Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/puumalainen/.
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Mezones, Holguín Edward, Aybara Carlos Canelo, Clark Andrew David, Janusz Cara Bess, Bárbara Jaúregui, Palza Seimer Escobedo, Adrian V. Hernandez, et al. "Cost-effectiveness analysis of 10- and 13-valent pneumococcal conjugate vaccines in Peru." Elsevier B.V, 2015. http://hdl.handle.net/10757/582635.
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Objective
To evaluate the cost-effectiveness of introducing the 10-valent pneumococcal conjugate vaccine (PCV10) versus the 13-valent PCV (PCV13) to the National Immunization Schedule in Peru for prevention of pneumococcal disease (PD) in children <5 years of age.
Methods
The integrated TRIVAC vaccine cost-effectiveness model from the Pan American Health Organization's ProVac Initiative (version 2.0) was applied from the perspective of the Government of Peru. Twenty successive cohorts of children from birth to 5 years were evaluated. Clinical outcomes were pneumococcal pneumonia (PP), pneumococcal meningitis (PM), pneumococcal sepsis (PS) and acute otitis media from any causes (AOM). Measures included prevention of cases, neurological sequelae (NS), auditory sequelae (AS), deaths and disability adjusted life years (DALYs). A sensitivity analyses was also performed.
Findings
For the 20 cohorts, net costs with PCV10 and PCV13 were US$ 363.26 million and US$ 408.26 million, respectively. PCV10 prevented 570,273 AOM; 79,937 PP; 2217 PM; 3049 PS; 282 NS; 173 AS; and 7512 deaths. PCV13 prevented 419,815 AOM; 112,331 PN; 3116 PM; 4285 PS; 404 NS; 248 AS; and 10,386 deaths. Avoided DALYs were 226,370 with PCV10 and 313,119 with PCV13. Saved treatment costs were US$ 37.39 million with PCV10 and US$ 47.22 million with PCV13. Costs per DALY averted were US$ 1605 for PCV10, and US$ 1304 for PCV13. Sensitivity analyses showed similar results. PCV13 has an extended dominance over PCV10.
Conclusion
Both pneumococcal vaccines are cost effective in the Peruvian context. Although the net cost of vaccination with PCV10 is lower, PCV13 prevented more deaths, pneumococcal complications and sequelae. Costs per each prevented DALY were lower with PCV13. Thus, PCV13 would be the preferred policy; PCV10 would also be reasonable (and cost-saving relative to the status quo) if for some reason 13-valent were not feasible.This study was presented at 9th International Symposium of Pneumococci and Pneumococcal Diseases, Hyderabad, India, March 2014, and supported by the National Council of Science, Technology and Technological Innovation of Peru (CONCYTEC) and International Clinical Epidemiology Network (INCLEN Trust)
This study was made possible through the financial support of the Instituto Nacional de Salud (National Institute of Health, Lima, Peru) and the PROVAC Initiative of the Pan American Health Organization (Washington, DC, USA).
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Webb, Silky Fanyelle. "Hospitalizations associated with pneumococcal infection within the Medicare population among vaccinated and non-vaccinated patients." [Tampa, Fla.] : University of South Florida, 2007. http://purl.fcla.edu/usf/dc/et/SFE0002032.
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Mastrodomenico, Jessica. "An Examination of the Socio-Demographic Characteristics Associated with Adult Vaccination Prevalence for Preventable Diseases in the United States." Digital Archive @ GSU, 2010. http://digitalarchive.gsu.edu/iph_theses/93.
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JESSICA MASTRODOMENICO
An Examination of the Socio-Demographic Characteristics Associated with Adult Vaccination Prevalence for Preventable Diseases in the United States
Background: An estimated 50,000 adults in the United States (U.S.) die each year from one of 10 vaccine preventable diseases. For those who survive vaccine preventable infections, health care costs and loss of income become more significant. While children in the U.S. aged 0-2 exhibit vaccine prevalence rates of almost 90%, some adult vaccine prevalence rates in the U.S. population are reported to be nearly 30-40% less than the goals set forth by Healthy People 2010. The purpose of this study was to examine the associations between socio-demographic characteristics of U.S. adults and adult vaccination prevalence for pneumococcal, hepatitis A, hepatitis B, tetanus, and pertussis.
Methods: Data from the 2008 National Health Interview Survey were assessed examining various health indicators and characteristics of non-institutionalized adults and children. The sample was restricted to adults ≥18 years of age. Odds ratios were calculated and multivariate logistic regression was also conducted. P-values of <0.05 and 95% confidence intervals were used to determine statistical significance.
Results: There were 21781 total observations; 19.3% received the pneumococcal vaccine, 9.4% received the hepatitis A vaccine, 27.2% received the hepatitis B vaccine, 55.1% received the tetanus vaccine, and 15.2% received the pertussis vaccine. Of the socio-demographic characteristics examined, age, health insurance, marital status, and education were significant for either all five or at least four of the vaccines included in this study. As one might expect those who reported health insurance and those who had a higher level of education usually had a higher likelihood of vaccine receipt as compared to those without health insurance and those with less than a high school education. Age associations varied due to age-related recommendations for certain vaccines such as pneumococcal (recommended for adults ≥65). Compared to the married population (referent), marital status results varied, but for reasons unclear. Whites, the referent group, were the most likely to be vaccinated as compared to Blacks, Hispanics/Latinos, and Asians. Hispanics/Latinos typically had the lowest likelihood of vaccination in this examination.
Conclusions: This study further explores the impact of socio-demographic disparities on vaccination status and adds new information to the literature regarding adult vaccination rates for preventable diseases. While research exists related to strengthening interventions such as patient reminder systems, those who do not see the same health care providers on a regular basis remain at risk for lower vaccination prevalence. It is important to better understand the role of social determinants of health, specifically in terms of vaccinations. Future research is needed to further characterize the association of socio-demographic factors with receipt of optional vaccines in adults.
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Glover, David Tawayne. "Pneumococcal choline-binding protein A its role in virulence and its utility as a Streptococcus pneumoniae vaccine antigen /." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2007p/glover.pdf.
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O'Grady, Kerry-Ann. "Pneumonia in Indigenous children in the Northern Territory, Australia, and the effectiveness of pneumococcal conjugate vaccine : 1997 - 2005." Thesis, University of Melbourne, 2008. http://purl.org/au-research/grants/nhmrc/359341.
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Silva, Junior Jailton de Azevedo. "Impacto da vacina pneumocócica conjugada 10-valente (PCV10) na meningite pneumocócica na região metropolitana de Salvador, Bahia." reponame:Repositório Institucional da FIOCRUZ, 2015. https://www.arca.fiocruz.br/handle/icict/14244.
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Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
INTRODUÇÃO: Em 2010, a vacina conjugada 10-valente (PCV10) foi incorporada ao programa nacional de imunizações (PNI) brasileiro. Este imunobiológico confere imunização contra os dez principais tipos capsulares de Streptococcus pneumoniae, patógeno responsável por diversas manifestações clínicas e com elevada contribuição nas taxas de incidência e mortalidade por meningite, que é a condição clínica mais grave. OBJETIVO: O presente estudo teve como objetivo avaliar o impacto da PCV10 na epidemiologia da meningite pneumocócica na região metropolitana de Salvador (RMS) Bahia, comparando o período anterior (2008-2010) e posterior (2011-2013) a sua utilização, bem como realizar uma caracterização molecular minuciosa a partir de uma série histórica (1996-2012) entre os isolados resistentes a penicilina (PNSSP com CIM≥ 0,125 μg/mL) e para os sorotipos não-vacinais (2008-2012). MATERIAL E MÉTODOS: Foram incluídos todos casos de meningite pneumocócica confirmados laboratorialmente no período entre 1996 a 2013. Taxas de incidência para a Salvador e RMS foram calculadas com base nos dados populacionais do IBGE/2010. A determinação do tipo capsular foi realizada através da técnica de Multiplex-PCR e/ou reação de Quellung. A sensibilidade a nove antimicrobianos foi testada através das técnicas disco-difusão, microdiluição e E-test. Para caracterizar o perfil molecular foram aplicadas as técnicas de genotipagem de PFGE e MLST. RESULTADOS: Um total de 939 casos de meningite pneumocócica foram identificados no período de 1996- 2013, sendo que 70 casos ocorrem entre 2011 a 2013 (período pós-vacinal). A incidência de meningite pneumocócica em todas as faixas etárias na RMS reduziu de 0,70 casos/100.000 habitantes para 0,59 casos/100.000 habitantes considerando o período de três anos antes e após a vacinação com PCV10 [p< 0,05; RR IC 95%: 1,46 (1,03-2,05)]. Esta redução foi significativa na faixa etária de 0-2 anos e nos casos por sorotipos relacionados à PCV10. Não houve aumento significativo de casos por sorotipos não vacinais nesta casuística, apesar do surgimento de casos por sorotipos não-vacinais não detectados anteriormente na série histórica de MP (10F, 21, 22F, 15A e 24F). Os isolados resistentes à penicilina analisados na série histórica se restringiram a 13 sorotipos, entre os quais: 14 (45,1 %; 78/173), 23F (19,1%; 33/173), 6B (14,4 %; 25/173), 19F (9,2 %; 16/173) e 19A (5,2 %; 9/173). 94% dos casos nãosusceptíveis à penicilina (PNSSP) foram de sorotipos vacinais. Os grupos clonais caracterizados pelo PFGE/MLST predominantes ao longo dos anos foram representados pelo sorotipo 14, denominado grupo A/ST 66 [35,3 % (61/173)] e grupo GK/ST 156 [4.6 % (8/173)], este último associado com níveis elevados de resistência a penicilina e ceftriaxona. Não foram detectados grupos clonais emergentes associados a tipos capsulares não-vacinais. CONCLUSÕES: Estes achados sugerem que a introdução da PCV10 modificou a epidemiologia da meningite pneumocócica na população estudada.
INTRODUCTION: In 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Brazilian national immunization program (NIP). This immunobiological provides immunization against the main ten capsular types of Streptococcus pneumoniae, the pathogen responsible for different clinical manifestations and high contribution in the incidence and mortality from meningitis, which is the most severe clinical condition. OBJECTIVE: This study aimed to evaluate the impact of PCV10 in the epidemiology of pneumococcal meningitis in the metropolitan area of Salvador (RMS) Bahia, comparing the previous (2008-2010) and after (2011-2013) periods its use, as well as conduct a thorough molecular characterization from a historical series (1996-2012) among isolates resistant to penicillin (PNSSP with CIM≥ 0.125 g / ml) and nonvaccine serotypes (2008-2012). MATERIAL AND METHODS: We included all cases of pneumococcal meningitis laboratory confirmed for the period 1996 to 2013. Incidence rates for Salvador and RMS were calculated based on population data from IBGE/2010. The capsular type determination was performed by multiplex PCR and/or Quellung reaction. Isolates Nine antibiotics were tested by disk-diffusion test, broth micro-dilution and E-test. To characterize the molecular profiling techniques were applied genotyping PFGE and MLST. RESULTS: A total of 939 cases of pneumococcal meningitis were identified during 1996-2013 period, with 70 cases occurring between 2011-2013 (post-vaccination period). The incidence of pneumococcal meningitis in all age groups in the RMS decreased from 0.70 cases / 100,000 inhabitants to 0.59 cases / 100,000 inhabitants considering the three-year period before and after vaccination with PCV10 [p <0.05; RR 95% CI: 1.46 (1.03 to 2.05)]. This reduction was significant in the age group 0-2 years and in cases by serotypes related to PCV10. There was no significant increase in cases by serotypes not vaccine in this series, despite the emergence of cases by serotypes not-vaccine previously undetected in the historical series of MP (10F, 21, 22F, 15A and 24F). The penicillin resistant isolates analyzed the historical series were restricted to 13 serotypes, including: 14 (45.1%; 78/173), 23F (19.1%; 33/173), 6B (14.4%; 25/173), 19F (9.2%, 16/173) and 19A (5.2%, 9/173). 94% of nonsusceptible to penicillin cases (PNSSP) were vaccine serotypes. Clonal groups characterized by PFGE / MLST predominant over the years have been represented by serotype 14, group called A / ST 66 [35.3% (61/173)] and Group GK / TS 156 [4.6% (8/173) ], the latter associated with elevated levels of penicillin and ceftriaxone resistance. Not were detected emerging clonal groups associated with capsular types non-vaccination. CONCLUSIONS: These findings suggest that the introduction of PCV10 changed the epidemiology of pneumococcal meningitis in the population studied.
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Veras, Maria Amélia de Sousa Mascena. "Um estudo caso-controle da efetividade da vacina polissacarídica antipneumococo em adultos infectados pelo HIV, São Paulo, Brasil." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/5/5137/tde-10102014-102755/.
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Introdução: Pessoas infectadas pelo vírus da imunodeficiência humana (HIV) têm alto risco de desenvolver doença pneumocócica. Infecções invasivas pelo Streptococcus pneumoniae (pneumococo) lideram a morbidade e a mortalidade entre crianças, idosos e pessoas com doenças de base que comprometem o sistema imune ou diminuem a função esplênica. A infecção pelo HIV está associada a um aumento de até dez vezes na incidência das pneumonias bacterianas no mundo. S. pneumoniae é o agente mais comum identificado. A imunização contra S. pneumoniae tem sido recomendada para indivíduos infectados pelo HIV em vários países, incluindo o Brasil, onde a vacina de polissacarídeos antipneumococo com 23 sorotipos (PPV-23) está sendo utilizada desde 1993. A efetividade da vacina de polissacarídeos antipneumococo varia entre 60 a 80% entre adultos com função imunológica relativamente normal. Entre adultos infectados pelo HIV, os estudos realizados até o momento apresentam resultados inconclusivos ou mesmo contraditórios. Objetivo: o objetivo deste estudo é avaliar a efetividade da vacina de polissacarídeos antipneumococo 23-valente (PPV-23) em uma amostra da população adulta infectada pelo HIV, em São Paulo. Métodos: Estudo de caso controle, tipo caso-incidente, entre adultos infectados pelo HIV, em São Paulo. A exposição é ter sido vacinado com a vacina 23 valente e o desfecho é infecção invasiva causada pelo S. pneumoniae. Caso: pessoa infectada pelo HIV, >=18 anos de idade, com doença invasiva por pneumococo, diagnosticada por meio de cultura positiva (isolamento de S. pneumoniae) em material biológico obtido de qualquer fluido corporal normalmente estéril. Controle: pessoa infectada pelo HIV, com >=18 anos de idade, recebendo cuidados nas mesmas instituições, sem doença invasiva por pneumococo, com o mesmo nível de células T CD4+ no mesmo período do diagnóstico do caso, estratificadas por faixas (CD4<200; CD4>=200<=499; >=500) cels/mm3. Foram conduzidas análise univariada e regressão logística condicional. Resultados: 79 casos e 241 controles foram incluídos, média de 39 anos, 63% do sexo masculino, mais de 50% com escolaridade entre média e fundamental, 63,5% brancos, 19% vivendo em condições precárias de habitação. Idade, sexo e raça não diferiram entre casos e controles. Bacteremia foi a manifestação clínica mais freqüente. Fatores de risco associados à doença pneumocócica incluíram: uso de alcool, de drogas injetáveis, ter menor nível de escolaridade, condições precárias de habitação, contato próximo com criança <10 anos e hospitalizações prévias por pneumonia. O uso de anti-retrovirais e a vacina antipneumocócica estiveram associados com uma diminuição do risco. A efetividade da vacina foi de aproximadamente 65% (OR=0,35 IC95%:0,18-0,70). Após ajustar por alguns fatores associados à doença invasiva (uso de drogas injetáveis, hospitalização prévia por pneumonia e uso de ARV), o possível efeito protetor da vacina (OR=, EV=54%) perdeu sua significância estatística (IC95% 0,27-1,13). Amostras de 47 casos foram sorotipadas. Conclusão: Este é o primeiro estudo a avaliar a efetividade da vacina de polissacarídeos antipneumocócica entre os indivíduos infectados pelo HIV no Brasil, e a incluir dados sobre a distribuição dos sorotipos de pneumococo neste subgrupo. A vacina anti-pneumocócica e o uso de anti-retrovirais atuaram como fatores protetores contra doença pneumocócica invasiva. Estes resultados reforçam a recomendação do uso da vacina no Brasil, e indicam a necessidade de estudos com amostras maiores que possam elucidar de forma inequívoca o efeito da vacina antipneumocócica entre portadores do HIVBackground: HIV-infected individuals are at increased risk of bacterial pneumonia in general and of pneumonia due to S. pneumoniae in particular. S. pneumoniae is the leading cause of morbidity and mortality among children, elderly and those with underlying conditions that compromise the immune system or diminish the splenic function. HIV infection is associated to a tenfold increase in the incidence of bacterial pneumonias worldwide and S. pneumoniae is the most common causal agent identified. Immunization against S. pneumoniae with Polysaccharide pneumococcal vaccine is recommended for use in HIV-infected adults in Brazil. The effectiveness of PPV23 ranges from to approximately 30 to 80%, among those with normal immune function. Among HIV-infected adults, studies have suggested contradictory or inconclusive results. Objective: To assess the effectiveness of the 23-valent polysaccharide pneumococcal vaccine among HIV-infected adult patients in São Paulo, Brazil. Methods: A prospective matched case-control study among HIV-infected adults in São Paulo. Exposure is vaccination with PPV-23 and outcome is invasive disease. Case definition: HIV-infected individual over 18 years old, with invasive pneumococcal disease, defined as recovery of S. pneumoniae from a normally sterile site (e.g. such as blood, pleural fluid, spinal fluid, pericardial fluid). Controls: HIV-infected individuals over 18 years of age, with o history of documented or strong suspicion of invasive pneumococcal disease, receiving medical care at the same group of institutions, matched to the cases by level of CD4 lymphocyte cell counts, according to the following (<200; 200=500 cells/mm3), measured during the same period. Results: 79 cases and 241 controls were included; mean age of 39 years; 63% male; education level lower than high school for 50% of the sample; 63,5% whites, 19% reported living in \"sub-standard\" housing. Bacteremia was the most frequent clinical manifestation. Risk factors associated with invasie disease: alcohol use, IDU, lower level of education, \"sub-standard\" housing, close contact with child less than 10 years old and previous hospitalization with pneumonia. ARV use and pneumococcal vaccine were associated to decreased risk. Overall vaccine effectiveness was 65% (OR=0,35 IC95%:0,18-0,70). After adjustment for confounding factors (IDU, hospitalization with pneumonia, and ARV use) the point estimate for the effectiveness of 23-valent polysaccharide against all invasive pneumococcal infection was 45% (95% CI: <0% to 73%). Isolates from 47 were available for serotyping. 40 (85%) were of serotypes included in the PPV-23. All 11 isolates from previously vaccinated cases were of serotypes included in the vaccine. Conclusion To our knowledge this is the first study to evaluate vaccine effectiveness among HIV-infected persons in Brazil and the first to include data on pneumococcal serotype distribution among HIV-infected adults in Sao Paulo. Although we were not able to provide definitive answers regarding vaccine effectiveness among the specific population, we reinforce the role of anti-retroviral therapy on preventing invasive disease. Our findings support the continuity of the recommendation on immunizing HIV-infected patients with the polysaccharide vaccine at the same time that reinforces the need of more data on the subject
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Francis, Jacinta Piwen. "Maternal and neonatal immune responses to pneumococcal protein antigens in relation to risk for early upper respiratory tract (URT) pneumococcal carriage in a high-risk population in Papua New Guinea." University of Western Australia. School of Paediatrics and Child Health, 2009. http://theses.library.uwa.edu.au/adt-WU2010.0025.
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[Truncated abstract] Pneumococcal exposure is high and life-long in developing countries including Papua New Guinea (PNG), with children under 2 years of age being at most risk for early upper respiratory tract pneumococcal carriage and infection. Deaths from pneumococcal diseases such as pneumonia and meningitis are common and likely the result of an absence of vaccination programmes. The need for effective and affordable pneumococcal vaccines has led to the testing of protein antigens including pneumolysin (Ply) and pneumococcal surface protein A (PspA) as novel vaccine antigens. Little is known on the immune responses to these proteins in humans, particularly in high-risk populations where such vaccines will be of most benefit. In this study, we examined the roles of naturally acquired antibody and cellular immune responses in mothers and newborns to Ply and PspA family 1 (PspA1) and family 2 (PspA2) in protection against or risk for early carriage in a high-risk PNG population. Antibodies to Ply, PspA1 and PspA2 were measured in plasmas of 241 mothers and 115 newborns (cords) from PNG, and 50 Australian mothers using an enzyme-linked immunosorbent assay (ELISA). Pernasal swabs were collected from PNG mothers at the time of delivery, one month post-partum, and weekly within the first month of life from their newborns to determine pneumococcal carriage. Cellular immune responses to Ply, PspA1 and PspA2, the TLR2/TLR4 ligands, LTA and LPS and to PHA were measured in cord blood mononuclear cells (CBMC) of 84 PNG versus 33 Australian newborns. Innate and T-cell cytokine responses in the PNG newborns were then analysed to determine their effect on infant pneumococcal carriage. ... No protective effect against infant pneumococcal carriage was observed with maternal and cord IgG levels for all antigens. Maternal carriage at time of delivery increased the risk for infant pneumococcal carriage in the first month of life (HR: 1.93, 95% CI 1.36 2.73, p = 0.001) with 70% of infants being colonised. Papua New Guinean newborns produced higher innate IL-10 and IFN-¿ (p = 0.003) and TNF-a (p < 0.001) to Ply compared to Australian newborns with no significant differences observed for IL-6 or IL-12. IFN-¿ responses to LPS and LTA (p = 0.005 and p < 0.001) were higher in PNG than Australian newborns, while IL-6, IL-10 (p < 0.001) and TNF-a (p = 0.002) to LPS with LTA-induced IL-6 and IL-10 (p < 0.001) were higher in Australian newborns. T-cell IL-5, IL-10, IL-13, IFN-¿, IL-6 and TNF-a response levels to PspA and PHA stimulation were significantly high in PNG newborns. No differences were observed for cytokine responses to Ply and PspA between PNG infant pneumococci carriers and non-carriers. Papua New Guinean infants are colonised by pneumococci very early in life and this may be influenced by high maternal carriage rates. PspA- and Ply-IgG levels are high in PNG mothers and undergo cross placental transfer but do not appear to be protective against early pneumococcal carriage. In PNG newborns, PspA elicits T-cell responses, while Ply drives more innate cellular responses, neither were demonstrated to have a protective effect against early carriage though further work is required to better define these and their relation to immune development in early childhood.
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Frazão, Nelson. "Massive shift in the pneumococcal nasopharyngeal flora after the 7-valent conjugate vaccine: epidemiological studies and testing pathogenic potential in animal models." Doctoral thesis, Universidade Nova de Lisboa. Instituto de Tecnologia Química e Biológica, 2010. http://hdl.handle.net/10362/5792.
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Dissertation presented to obtain the PhD degree in Biology/Molecular Biology by
Universidade Nova de Lisboa, Instituto de Tecnologia Química e BiológicaAlthough it exists mostly as a commensal bacterium colonizing the human nasopharynx, particularly in children, the Gram-positive bacterium Streptococcus pneumoniae, is also a major human pathogen that can cause a wide range of diseases, which include otitis media, sinusitis, pneumonia, and such life-threatening afflictions as bloodstream infection and meningitis. Created to protect children against pneumococcal disease, the 7-valent pneumococcal conjugate vaccine (PCV7) showed high efficacy in preventing disease caused by the serotypes included in the vaccine, the so-called vaccine types (VTs). Since colonization is an essential first step to develop pneumococcal disease, it is of importance to investigate the effect of this vaccine on the degree of colonization, on changes in the composition of the nasopharyngeal flora and the virulence potential of the non vaccine type (NVT) strains.(...)
Financial support from Fundação para a Ciência e a Tecnologia, Portugal through grant SFRH/BD/30103/2006 awarded to Nelson Frazão.
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Tostes, Rafaella Oliveira. "Avaliação da eficácia do antígeno PspA (Pneumococcal surface protein A) em modelo de co-colonização com diferentes linhagens de Streptococcus pneumoniae." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-25082016-102810/.
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Streptococcus pneumoniae é o patógeno causador de diversas doenças com alta mortalidade e morbidade, como meningite e pneumonia. As vacinas disponíveis baseiam-se na resposta contra o polissacarídeo capsular (PS), porém possuem elevado custo e cobertura limitada aos sorotipos vacinais. O objetivo deste estudo foi avaliar a eficácia da imunização nasal com PspAs recombinantes de família 1 (rPspA1 e rPspA2) e de família 2 (rPspA3, rPspA4 e rPspA5) em um modelo de cocolonização da nasofaringe de camundongos, utilizando isolados que expressam diferentes PspAs (PspA1 ao PspA4). Esse modelo visa analisar a eficácia da vacinação frente à exposição a diferentes pneumococos, uma situação comum, especialmente em crianças. Os experimentos deste projeto avaliaram a colonização com misturas de isolados dos sorotipos 6B e 23F e expressando PspA1, PspA2, PspA3 ou PspA4, mostrando uma análise ampla da cobertura vacinal contra pneumococo das diferentes formulações contendo as variantes do antígeno PspA e a importância desse antígeno para o desenvolvimento de uma nova vacina.Streptococcus pneumoniae is the cause of several diseases with high mortality and morbidity, such as meningitis and pneumonia. The available vaccines are based on the response against the capsular polysaccharide (PS), but they have a high cost and coverage restricted to the vaccine serotypes. The purpose of this study was to evaluate the efficacy of nasal immunization with recombinant PspAs from family 1 (rPspA1 and rPspA2) and from family 2 (rPspA3, rPspA4 and rPspA5) in a model of co-colonization of the mouse nasopharynx, using isolates expressing different PspAs (PspA1 to PspA4). This model aims to analyze the effectiveness of vaccination upon exposure to different pneumococci, a common situation, especially in children. The experiments in this project assessed colonization with mixtures of isolates of serotypes 6B and 23F, expressing PspA1, PspA2, PspA3 or PspA4, showing a wide vaccination coverage analysis of different formulations containing the PspA variants against pneumococcus and the importance of this antigen to the development of a new vaccine.
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Ouldali, Naïm. "Impact à moyen terme de l'implémentation du vaccin conjugué pneumococcique 13 valences en pédiatrie : analyse de séries chronologiques interrompues." Thesis, Université de Paris (2019-....), 2020. https://wo.app.u-paris.fr/cgi-bin/WebObjects/TheseWeb.woa/wa/show?t=4437&f=28972.
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Introduction. Le bénéfice à moyen terme de l’implémentation des vaccins pneumococciques conjugués (VPCs) reste à préciser, du fait du remplacement sérotypique. Nous avons évalué en France, chez l’enfant, l’impact à moyen terme des VPC sur : (i) les méningites à pneumocoque, (ii) les pneumopathies aiguës communautaires (PAC), (iii) la dynamique de résistance aux antibiotiques des sérotypes pneumococciques dans le portage naso-pharyngé. Nous avons également évalué la qualité méthodologique de la littérature concernant l’impact des VPCs sur les infections pneumococciques. Méthodes. Nous avons exploité les données de 3 observatoires pédiatriques établis à l’échelle nationale : l’observatoire des méningites bactériennes de l’enfant (227 centres), l’observatoire des PAC (8 centres) et l’observatoire du portage pneumococcique (121 pédiatres de ville). Une analyse de séries chronologiques interrompues (SCI), promue par la Cochrane à la place des études avant-après, a été conduite, prenant en compte la tendance temporelle, la saisonnalité et l’autocorrélation des données, via des modèles de régression linéaire segmentée avec erreur auto-corrélée. Enfin, une revue systématique méthodologique a été conduite en incluant toutes les études évaluant l’impact des VPC sur les principales formes d’infections à pneumocoque à la fois chez l’enfant et l’adulte, via PubMed, Embase et les références des articles sélectionnés.Résultats. Après une baisse de l’incidence des méningites à pneumocoque de 38% (IC 95% [20 ; 56]) suite à l’implémentation du VPC13 en France, une remontée a été observée depuis Janvier 2015, principalement liée à l’émergence d’un sérotype non vaccinal. De la même manière, la fréquence des CAP a baissé de 44% (IC 95% [32 ; 56]) après l’implémentation du VPC13, mais depuis Juin 2014 seule une très modeste remontée a été observée. Pour le niveau de résistance des sérotypes pneumococciques, après une baisse notable suite au VPC13, une remontée progressive et constante est observée depuis Janvier 2014. Enfin, la revue systématique de la littérature a permis de sélectionner 377 études entre 2001 et 2018. Ces études utilisaient le design avant-après dans 78.5% des cas (N=296) contre 18.3% pour les SCI (N=69).Conclusion. L’impact à moyen terme des VPCs et les conséquences du remplacement sérotypique varient selon les pathologies pneumococciques. Ces résultats sont susceptibles d’évoluer dans les années à venir, nécessitant une surveillance continue. L’utilisation d’outils méthodologiques validés tels que les SCI reste minoritaire à ce jour, et doit être développée pour apprécier la complexité de l’évolution épidémiologique des infections pneumococciques au cours du tempsBackground. Due to serotype replacement, the long-term impact of pneumococcal conjugate vaccines (PCVs) implementation remains to be evaluated. We aimed to assess, in children, the impact of PCV13 implementation on: (i) pneumococcal meningitis, (ii) community acquired pneumonia (CAP), and (iii) antibiotic susceptibility of pneumococcal strains in nasopharyngeal carriage. Finally, we conducted a methodological systematic review of the literature on assessing the impact of PCVs implementation. Methods. We used the quasi-experimental interrupted time series (ITS) analysis design with data from three French surveillance systems: (i) the national network of pediatric bacterial meningitis (230 centres), (ii) the CAP pediatric network (8 pediatric emergency departments), and (iii) an ambulatory network of pneumococcal carriage (121 pediatricians). A segmented regression model with autoregressive error was used, taking into account pre-intervention time trend, seasonality and autocorrelation. The methodological systematic review included all studies assessing the impact of PCVs implementation in children and adults, using PubMed, Embase, and references of selected articles. Results. After a 38% (95% CI [20; 56]) decrease of pneumococcal meningitis incidence following PCV13 implementation in 2010 in France, a rebound was observed since January 2015, mainly linked to the emergence of non-PCV13 serotypes. CAP rate also decreased significantly following PCV13 implementation (44% decrease, 95% CI [32; 56]), but since June 2014, only a slight increase was observed since June 2014. Regarding pneumococcal susceptibility in carriage, after a significant reduction of penicillin non-susceptibility following PCV13 implementation, a steady increase is observed since January 2014. Finally, 377 studies were included in the systematic review, from 2001 to 2018. Among them, 296 (78,5%) used the before-after design, and only 69 (18,3%) used the ITS design. Conclusions. After an important impact of PCV13, the consequences of serotype replacement in France may vary between pneumococcal disease. These findings may still evolve in the coming years, underlining the need of continuous active surveillance of these outcomes. Despite Cochrane recommendations, the use of ITS to assess PCVs impact remains largely infrequent worldwide, and needs to be promoted to adequately analyze the complex evolution of this pathogen over time
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Svensson, Tobias. "Infectious and bleeding complications in patients with hematological malignancies : Studies on diagnosis and prevention." Doctoral thesis, Uppsala universitet, Hematologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-316461.
Full textAbstract:
The overall aim of this thesis is to improve knowledge about the prevention of infectious and bleeding complications in patients with hematological malignancies, primarily in those with chronic lymphocytic leukemia (CLL) and myelodysplatic syndrome (MDS). Hypogammaglobulinemia, impaired production of immunoglobulins (Ig), is an established risk factor for infection, but the impact of IgG pure subclass deficiency (IgG subclass deficiency with adequate production of IgG, IgA, and IgM) has been debated. In a retrospective single institution study, we concluded that pure IgG subclass deficiency in CLL patients is rare and is not associated with an increased risk of infection. Hence, routine analysis of IgG subclasses in patients with CLL is not warranted. There is no consensus on recommending vaccination against Streptococcus pneumoniae to CLL patients mainly because comparative studies are lacking. In our randomized trial, the efficacy of a conjugated pneumococcal vaccine on immune response was superior or equal to a polysaccharide vaccine for all pneumococcal serotypes common for the two vaccines. A conjugate pneumococcal vaccine should therefore be included in vaccination programs for patients with CLL. Bronchoalveolar lavage (BAL) is a well-established invasive method to identify the cause of pulmonary infiltrates in immunocompromised patients. In a retrospective trial, we have studied the diagnostic yield of BAL in patients with hematological malignancies. We concluded that BAL is highly useful in either verifying or excluding some of the important respiratory tract infections affecting these patients, particularly invasive pulmonary aspergillosis (IPA) and Pneumocystis jirovecii pneumonia (PJP). However, standardized procedures for BAL sampling should be continually revised to avoid unnecessary microbiological tests. Thrombocytopenia, an adverse prognostic factor in patients with MDS, can be aggravated by azacitidine, first-line treatment for high-risk MDS. Eltrombopag, a thrombopoietin-receptor agonist (TPO-R), alleviates thrombocytopenia in patients with immune thrombocytopenic purpura (ITP). In a phase I clinical trial, we concluded that the combination of eltrombopag and azacitidine in high-risk MDS patients with thrombocytopenia is feasible and well tolerated in doses up to 200 mg eltrombopag daily.
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Fernández, de Sevilla Estrach Mariona. "Características clínicas y microbiológicas de la enfermedad neumocócica invasiva pediátrica en Barcelona en la era de la vacuna heptavalente conjugada." Doctoral thesis, Universitat de Barcelona, 2012. http://hdl.handle.net/10803/107675.
Full textAbstract:
La enfermedad neumocócica invasiva (ENI) constituye un problema grave de Salud Pública en la edad infantil, con una morbimortalidad considerable. En los últimos años se han introducido vacunas adecuadas para la edad infantil (año 2001:vacuna heptavalente conjugada, PCV7, año 2010:vacunas decavalente y trecevalente conjugadas). Desde la comercialización de la PCV7 se ha observado una emergencia de la ENI por serotipos no incluidos en la PCV7 (SNV) en nuestro medio.
Esta tesis pretende a partir del análisis de la ENI que ha tenido lugar en los últimos años en nuestro medio (cuando la PCV7 era la única vigente) en una área sin vacunación sistemática, identificar los factores clínicos y microbiológicos asociados a la emergencia de ENI por SNV.
Los objetivos de la tesis son: determinar la incidencia de ENI en menores de 5 años en nuestro medio, sus principales características clínicas y microbiológicas y las características clínicas y moleculares de la ENI producida por el serotipo 19A.
Los 2 artículos publicados que componen la tesis y que permiten contestar estos objetivos son: 1/Clinical presentation of invasive pneumococcal disease in Spain in the era of heptavalent conjugate vaccine (Pediatr Infect Dis J. 2012; 31(2):124-8) y 2/ Emergence of invasive pneumococcal disease caused by multidrug-resistant serotype 19A among children in Barcelona (J Infect.2009; 59(2):75-82).
El primer artículo expone un estudio prospectivo en el que se incluyen los niños < 5 años con ENI diagnosticados en los hospitales Sant Joan de Déu y Vall d’Hebron. La recogida se hizo durante 3 años consecutivos (2007-2009). Se incluyen pacientes diagnosticados por cultivo y/o PCR.
Los principales resultados fueron:se incluyeron 319 pacientes, con una media de edad de 29.6 meses. Comparando las incidencias del 2007 y 2009 (76.2 y 109.9 casos/100000 habitantes,respectivamente) se observa un incremento del 44%. La principal manifestación clínica fueron las neumonías (79.6%), seguido de las meningitis (9.1%) y bacteriemias (7.8%). El diagnóstico se hizo por cultivo en 38.6% pacientes y en 61.4% por PCR en tiempo real. Pudo hacerse el serotipado en 300 casos, 91% eran SNV. El serotipo más frecuente fue el 1 (20.7%), seguido del 19A (15.7%) y el 3(12.3%). Una concentración mínima inhibitoria a la penicilina ≥ 0.12 g/ml se detectó en 34.4%. El secuenciotipo 306 expresando el serotipo 1 fue el más frecuente (20.3%).
El segundo artículo se centra en la caracterización del 19A. Este serotipo se asocia a multirresistencia a antibióticos por lo que su estudio es relevante. Se trata de un estudio prospectivo realizado entre 1997 y 2007 en el que se incluyen los niños < 18 años con ENI por 19A del Hospital Sant Joan de Déu. Los principales resultados fueron:comparando la época prevacunal (1997-2001) con la vacunal inicial (2002-2004) y la vacunal tardía (2005-2007) se observa un incremento de ENI causada por 19A: 1.7% vs 14.8% vs 21.9% respectivamente (p:0.002). Todos los 19A aislados en la época prevacunal fueron sensibles a la penicilina, mientras que en la vacunal tardía, 44% eran resistentes (p:0.01). Se detectaron 15 secuenciotipos diferentes expresando el 19A, 10 de los cuales eran secuenciotipos preexistentes asociados al 19A, incluyendo los multirresistentes ST320 y ST276.
Las principales conclusiones de la tesis son:
-La ENI continúa aumentando en Barcelona, la incidencia es mayor que la descrita previamente debido a la baja sensibilidad del cultivo.
-Los SNV fueron los responsables del 91% de los casos de ENI y la neumonía fue el principal diagnóstico.
-El 19A se está extendiendo rápidamente y se está convirtiendo en una causa importante de ENI en la era vacunal.
-El aumento del 19A se relaciona con la emergencia de clones sensibles y resistentes, varios de ellos relacionados con clones multirresistentes conocidos.Clinical and microbiological characteristics of pediatric invasive pneumococcal disease in Barcelona in the era of heptavalent conjugate vaccine The aim of this doctoral thesis is to analyze the rate of incidence, clinical presentation, serotype, and clonal distribution of invasive pneumococcal disease (IPD) in the era of heptavalent pneumococcal conjugate vaccine (PCV7) in Barcelona and to describe the epidemiology of IPD caused by Streptococcus pneumoniae serotype 19A. The 2 published articles that compose the thesis are: 1/Clinical presentation of invasive pneumococcal disease in Spain in the era of heptavalent conjugate vaccine (Pediatr Infect Dis J. 2012; 31(2):124-8) and 2/ Emergence of invasive pneumococcal disease caused by multidrug-resistant serotype 19A among children in Barcelona (J Infect.2009; 59(2):75-82). The first paper describes a prospective study comprising all children <5 years with IPD who were managed in 2 tertiary-care pediatric hospitals during 3 years (2007-2009). The diagnosis was made by positive culture and/or by real-time PCR. In this study, 319 patients were included. Comparing rates in 2007 and 2009 an increase of 44% was observed. The main clinical presentation was pneumonia (79.6%). Serotype study was performed in 300 episodes and 91% were non-PCV7 serotypes. The most frequent serotypes were 1 (20.7%), 19A (15.7%) and 3 (12.3%). Sequence type 306 expressing serotype 1 was the most frequent clonal type detected (20.3%). The second paper describes the clinical and molecular epidemiology of serotype 19A. This is a prospective study that includes all children <18 years with IPD caused by 19A who were admitted to a Children’s Hospital in Barcelona (1997-2007).Serotyping, antibiotic susceptibility and clonal analysis were performed. Comparing the pre-vaccine period (1997-2001) with the early vaccine period (2002-2004) and the late vaccine period (2005-2007) there was an increase of IPD caused by 19A. All 19A isolated in the pre-vaccine and early vaccine periods were penicillin susceptible, while in the late vaccine period, 44% were penicillin nonsusceptible (p:0.01).A clonal analysis revealed 15 different sequence types expressing serotype 19A.10 of them were pre-existing STs associated with 19A including the multidrug-resistant ST 320 and ST276. The main conclusions of the thesis are: -IPD continues to increase in Barcelona. -Non-PCV7 serotypes were responsible for 91% of episodes and pneumonia was the main clinical presentation. -There was an increase of IPD caused by 19A which was mainly related with the emergence of pre-existing clones several of them closely related with.
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Campos, Ivana Barros de. "Otimização do processo de produção e caracterização da vacina celular contra Streptococcus pneumoniae." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-19022015-093553/.
Full textAbstract:
S. pneumoniae é um patógeno de grande impacto em saúde pública e vacinas comerciais têm cobertura limitada e alto custo. Como alternativa, desenvolveu-se uma vacina celular de baixo custo, cuja produção envolve apenas a separação das bactérias do caldo e sua inativação. Neste trabalho, foram avaliados processos descontínuo, descontínuo alimentado e contínuo com reciclo de células, cuja produção de biomassa foi 3 vezes maior que a do descontínuo. Vacinas obtidas nos 3 processos foram utilizadas em ensaios de imunização de camundongos e induziram níveis similares de IgG e IL-17A. Anticorpos ligaram-se e induziram a deposição de moléculas do sistema complemento sobre a superfície do pneumococo. Ademais, induziram fagocitose de diferentes cepas encapsuladas da bactéria. Camundongos imunizados foram protegidos contra sepse após aspiração da cepa virulenta WU2. Portanto, o processo contínuo com reciclo permitiu a obtenção de maior número de doses sem alterar a qualidade da vacina e o ensaio opsonofagocítico poderia ser utilizado como potencial correlato de proteção.S. pneumoniae is a pathogen of great impact on public health and commercially available vaccines have limited coverage and high cost. As alternative, a low-cost whole cell vaccine was developed, whose production involves only the cell separation and inactivation. In this work, we evaluated batch, fed-batch and continuous cultivation with cell recycle. The biomass production was 3-fold higher in continuous process than batch. Vaccines obtained from these 3 processes were used to immunize mice and all vaccines induced comparable levels of IgG and IL-17A. Antibodies were able to bind and induce deposition of complement onto pneumococcal surface, besides to induce phagocytosis of several encapsulated pneumococcal strains in opsonophagocytic assays. Immunized mice were protected from fatal aspiration-sepsis using the virulent pneumococcal strain WU2. Therefore, the continuous process with cell recycle yielded a higher number of doses without altering the quality of the vaccine and opsonophagocytic assay could be used as a potential correlate of protection.