Tesis: "PNEUMOCOCCO"

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Amerighi, Fulvia. "Impact of S.pneumoniae type-I pilus and its subunits on bacterial adherence to human epithelial cells". Doctoral thesis, Università degli studi di Padova, 2013. http://hdl.handle.net/11577/3422591.

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S. pneumoniae is a human pathogen able to cause both invasive and non-invasive diseases as well as to colonize the nasopharyngeal tract of children and adults. Despite pneumococcus is a leading cause of morbidity and mortality worldwide, the pathogenic mechanisms exploited by S. pneumoniae are not yet clear. A critical step is colonization of the nasopharynx and the initial interaction of pneumococci with host cells. Recently, pili were discovered in gram-positive bacteria, mediating critical host-bacterial interactions, such as adherence to the epithelium, biofilm formation and translocation of host mucosal barriers. Thirty to 50% S. pneumoniae strains harbor pilus islet-1 (PI-1) coding for a surface exposed pilus reported to be important both for colonization and virulence. In particular it has been clearly demonstrated that pilus component RrgA is the major determinant for adhesion to epithelial cells in vitro whereas RrgB is important to allow the formation of the polymeric structure into which the adhesin is incorporated. The data reported in this work contribute to better define the involvement of S. pneumoniae pili in adhesion to human epithelial cells and providing evidence that anti-pilus antibodies are able to prevent bacterial adherence. In order to test the adhesive attitude of S.pneumoniae strains, we selected a panel of epithelial cell lines differing for their anatomical origin and the capacity to constitute polarized monolayers. Me180 cervical epithelial cells, characterized to form weak adherence junctions and thus expose basolateral surface, result the best model to study pneumococcal adhesiveness. This evidence led us to hypothesize that the pilus ligands may reside in some of the extracellular matrix components rather than in cell associated receptors. Once identified the most appropriate cellular model we started the characterization of pilus dependent adhesion by using TIGR4 mutants lacking pilus components or subpopulations derived from the wild type strain and differing only in pilus expression (highly or poorly piliated). The results reveal that piliated bacteria were drastically more adherent to cells compared to non piliated strains. However, both the lack of the pilus adhesion moiety (RrgA) or of the pilus backbone (RrgB) determined a dramatic reduction of adhesion, suggesting that both the presence of the adhesin and its correct spacing from the bacterial cell were equally important. In addiction we tested the pilus mediated adhesiveness of different pneumococcal strains that could be successfully divided into sub-populations highly (H) or poorly (L) expressing pili. By comparing the H sub-populations we noticed striking difference in their capacity to adhere to host cells. Conventional and immune electron microscopy studies reveal that the capsule thickness is inversely related with the bacterial ability to adhere to host cells likely due to the different exposure of pili on the bacterial surface. Moreover the deletion of the capsular locus in the poorly adherent strain 19FTaiwan14 results in a considerable increase in the adhesion to epithelial cells, at levels comparable to that of poorly capsulated TIGR4 strain. Additionally, in this study, we demonstrate that anti-pilus antibodies were able to significantly impair pneumoccal adhesion to human epithelial cells in strains prominently extruding pili from the capsule. Of interest, we found a monoclonal antibody against RrgA that was able to compete with adhesion in a similar manner with respect to the polyclonal serum against the whole protein. Epitope mapping experiments resulted in the identification of the possible binding region on the RrgA molecule, located in the c-terminal domain. At the moment we are trying to confirm this result by producing point-mutated forms of RrgA with the scope to select mutants that are not recognized by the functional monoclonal antibody and finally complement rrga ko strain with these sequences to confirm the importance of the epitope in the adhesion to human epithelial cells.
Streptococcus pneumoniae è un batterio Gram-positivo che fa parte della normale flora microbica che colonizza in modo asintomatico le vie respiratorie. Tuttavia questo microorganismo è anche uno dei principali patogeni umani, può, infatti, causare gravi infezioni del tratto respiratorio sia in forma non invasiva quali otite media, sinusite e polmonite che in casi più gravi forme invasive quali setticemia e meningite. Sebbene S. pneumoniae sia una delle principali cause di mortalità e morbilità nel mondo, i meccanismi patogenetici di questo batterio non sono ancora stati completamente chiariti. Un punto chiave è la colonizzazione del tratto nasofaringeo e l’interazione dei batteri con le cellule ospiti. A questo proposito, recentemente, sono state identificate nei batteri Gram-positivi delle strutture, note come pili, che svolgono un ruolo cruciale nell’interazione ospite-patogeno, sono infatti coinvolti in processi quali: adesione alle cellule epiteliali, formazione di biofilm e traslocazione degli epiteli. Una percentuale variabile tra il 30% e il 50% dei ceppi di S.pneumoniae contiene nel proprio DNA genomico un elemento genetico noto come pilus islet-1 (PI-1) che codifica per una struttura fibrillare, il pilo di tipo1, coinvolto nei processi di colonizzazione e virulenza. In dettaglio, è stato dimostrato che la sub-unità RrgA è coinvolta nell’adesione in vitro dei batteri alle cellule epiteliali mentre la sub-unità RrgB è il principale costituente della struttura del pilo, all’interno della quale è incorporata l’adesina. I dati riportati in questo lavoro contribuiscono a chiarire il ruolo svolto dal pilo nel meccanismo di adesione di Streptococcus pneumoniae alle cellule epiteliali e forniscono evidenze dell’attività degli anticorpi contro le componenti del pilo di inibire l’adesione dei batteri alle cellule ospiti. Al fine di valutare le capacità di adesione di Streptococcus pneumoniae, abbiamo selezionato una serie di linee cellulari provenienti da diversi distretti anatomici e con diversa capacità di formare un monostrato di cellule polarizzate in vitro. Tra le linee cellulari testate, il miglior modello per lo studio dell’adesione sono le ME180 (cellule epiteliali di cervice uterina) caratterizzate dal formare giunzioni lasse e quindi consentire l’esposizione di componenti della superficie basolaterale. Questo risultato ci fa ipotizzare che il ligando dei pili possa essere un elemento della matrice extracellulare o un recettore posto sulla superficie basolaterale delle cellule. Una volta identificato il modello cellulare ideale, abbiamo analizzato le capacità di adesione pilo-dipendenti di mutanti che mancano delle componenti del pilo e di sottopopolazioni isolate dal ceppo wild type che differiscono tra loro unicamente per una diversa espressione del pilo, una popolazione è altamente piliata, l’altra scarsamente piliata. I risultati mostrano che la popolazione piliata ha una capacità di aderire alle cellule molto più elevata rispetto alla popolazione non piliata. Inoltre abbiamo osservato che sia l’assenza dell’adesina (RrgA) che del backbone (RrgB) determinano una drastica riduzione dell’adesione sottolineando l’importanza per un corretto funzionamento del pilo sia della presenza dell’adesina che della sua localizzazione nella struttura del pilo. Successivamente abbiamo analizzato il contributo del pilo nell’adesione in diversi ceppi di Streptococcus pneumoniae selezionati sulla base della possibilità di poter isolare le due sottopopolazioni con diversa espressione del pilo (popolazione piliata e non piliata). Prendendo in esame le sottopopolazioni pilate dei ceppi selezionati abbiamo osservato notevoli differenze nella capacità di aderire alle cellule epiteliali. Per spiegare questo fenomeno abbiamo condotto studi di microscopia elettronica convenzionale e immuno-elettro microscopia che hanno evidenziato la presenza di una correlazione inversa tra lo spessore della capsula e le capacità adesive pilo-dipendenti, molto probabilmente dovuta alla diversa esposizione dei pili sulla superficie del batterio. Infatti, la delezione dell’intero locus capsulare in un ceppo che mostra scarsa capacità di adesione alle cellule epiteliali come il ceppo 19FTaiwan14, comporta un notevole aumento dell’adesione a livelli paragonabili al ceppo TIGR4 che è scarsamente capsulato. In questo lavoro abbiamo anche dimostrato che anticorpi prodotti contro le componenti del pilo sono in grado di inibire l’adesione dei batteri alle cellule epiteliali in ceppi in cui il pilo è molto esposto al di fuori della capsula e abbiamo identificato un anticorpo monoclonale anti-RrgA in grado di bloccare l’adesione dei batteri alle cellule ospiti in modo comparabile al siero policlonale prodotto contro l’intera proteina. Studi di epitope mapping hanno portato all’identificazione della regione di RrgA probabilmente coinvolta nel binding con l’anticorpo monoclonale, localizzata nel dominio c-terminale della proteina. Attualmente stiamo cercando di confermare questi risultati inserendo nella regione di RrgA che abbiamo identificato delle mutazioni puntiformi per ottenere forme mutate dell’epitopo che non vengano più riconosciute dal monoclonale e infine complementare il ceppo mutante rrga con queste sequenze per confermare l’importanza di questo epitopo nell’adesione alle cellule epiteliali umane.

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Godenzi, Luigi Walter Marco. "Campagna di sensibilizzazione e di promozione per la vaccinazione contro il pneumococco nel Canton Ticino /". [S.l.] : [s.n.], 2003. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.

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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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Tootla, Hafsah Deepa. "The Pneumococcus Urinary Antigen Test Kit: Use in the laboratory for the presumptive diagnosis of pneumococcal bacteraemia". Master's thesis, Faculty of Health Sciences, 2021. http://hdl.handle.net/11427/33048.

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Introduction: Culture remains the ‘gold standard' for diagnosis of Streptococcus pneumoniae bacteraemia. Time to definitive identification using culture is 24–48 hours, and prior antibiotic therapy, the ability of S. pneumoniae to self-autolyse and its fastidious nature can yield no growth on culture. Novel detection methods for invasive pneumococcal disease include PCR and antigen tests. We evaluated using a urine antigen test directly on selected blood cultures with appropriate Gram stain results, immediately after signalling positive for the rapid identification of S. pneumoniae bacteraemia. Method: We collected 212 blood cultures that had signalled positive with an automated blood culture system, and then yielded gram-positive cocci in pairs/chains or cocci with uncertain morphological arrangement. The BinaxNOW Streptococcus pneumoniae urinary antigen test, routine culture with optochin and real time lytA PCR was performed on all samples. Diagnostic accuracy analysis (sensitivity and specificity) of the antigen test and Gram stain with gram-positive cocci in pairs was each compared to culture positivity for S. pneumoniae, PCR positivity and the composite of culture or PCR positivity for S. pneumoniae as the reference standards. Results: S. pneumoniae (Spn) was cultured in 55 samples, gram-positive organisms other than S. pneumoniae (NSpn) in 140 samples and 17 samples had no growth (NG). Grampositive cocci in pairs was predominant on Gram stain in the Spn/NG groups whilst the minority in the NSpn group. In the Spn group, all except 1 sample which was antigen positive but PCR negative, were antigen and PCR positive. In the NSpn group, antigen and PCR was negative in 123 samples, antigen and PCR positive in 1 sample and antigen positive but PCR negative in the remaining 16 samples. In the NG group, antigen and PCR were positive in 16 samples and antigen positive but PCR negative in 1 sample. Sensitivity of the antigen test compared to culture, PCR or the composite of culture or PCR was 100%. Specificity was 87-88% but increased to 93-96% when used in subsets with gram-positive cocci in pairs or clinical history compatible with respiratory illness or meningitis. Sensitivity and specificity of the antigen test when compared to Gram stain using gram-positive cocci in pairs (69%-75% and 81% respectively) were both higher. Discussion and Conclusion: Accurate and rapid diagnosis of S. pneumoniae bacteraemia is challenging with current diagnostic tools. Specificity of the antigen test is mostly limited by crossreactivity with viridans streptococci, coagulase negative staphylococci and enterococcus species, but this can be overcome if Gram stain morphology and clinical history is available. Sensitivity and specificity of Gram stain alone in predicting S. pneumoniae bacteraemia is poor and is increased with use of the antigen test. The antigen test is a useful adjunctive tool improving diagnosis and turnaround time of S. pneumoniae bacteraemia. In settings like ours, where high-level resistance, defined as minimum inhibitory concentration ≥2μg/mL to penicillin is still relatively low (~7%), rapid de-escalation to penicillin in the appropriate clinical setting would be possible with the introduction of such test and could also potentially be a suitable alternative to molecular testing for S. pneumoniae identification in samples with no growth on culture.

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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.

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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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FRANCO, Cáritas Marquez. "FATORES DE RISCO E EPIDEMIOLOGIA MOLECULAR DE Streptococcus pneumoniae NÃO SUSCETÍVEIS À PENICILINA ISOLADOS DE NASOFARINGE DE CRIANÇAS QUE FREQUENTAM CRECHES EM GOIÂNIA-GO, BRASIL". Universidade Federal de Goiás, 2009. http://repositorio.bc.ufg.br/tede/handle/tde/1586.

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Made available in DSpace on 2014-07-29T15:26:24Z (GMT). No. of bitstreams: 1 tese caritas medicina tropical.pdf: 1784866 bytes, checksum: b85c7ab5508fd90ff809159f179430cc (MD5) Previous issue date: 2009-02-17
Objectives: (i) to identify risk factors for S. pneumoniae penicillin nonsusceptible isolates (PNSp) in children attending day-care centers (DCCs) in Goiânia, Brazil and to assess the genetic patterns of pneumococcal isolates; (ii) to estimate the coverage for carriage serotypes for the 7-valente (PCV7) pneumococcal conjugate vaccine, and for the investigational 10 (PCV10) and 13-valent (PCV13) vaccines; (iii) to assess the genetic relatedeness between isolates expressing capsular type 14 and those non(sero)- typeable isolates (NTPn); (iv) to investigate if carriage isolates match genetically to any international pneumococcal clone (PMEN network). Methods: A cross-sectional survey of carriage PNSp was conducted among 1.192 children, 2 months to 5 years of age, attending 62 DCCs in Central Brazil. Capsular typing was performed in PNSp isolates (CLSI, 2007) and in a sample of isolates susceptible to penicillin (PSSp) matched to PNSp and DCCs whenever possible. Serotyping was performed by Quellung reactions and confirmed by multibead assay. NTPn isolates and serotype 14 were tested by PCR for capsule genes. Odds ratio for PNSp carriage and respective 95% confidence interval (95%CI) were assessed by logistic regression. Pulsed field gel electrophoresis (PFGE) was applied to assess the genetic similarity between PNSp serotype 14 and NTPn isolates. PCR was performed for the presence of pneumococcal capsule gene locus. For comparison purpose we also evaluated the genetic profile of PNSp serotype 14 invasive strains derived from the current pneumococcal invasive disease surveillance for the same pediatric population. Isolates were epidemiologically related if they shared ≥80% similarity on the dendrogram (Dice coefficient). A cluster was defined as three or more related isolates. Results: A total of 686 pneumococci were isolated for a colonization rate of 57.6% and 178 (25.8%) were PNSp. Among the PNSp isolates the usual common types were found: 14 (53%), 23F (10.2%), 6B (6%), 19F (4.8%) and 19A (4.2%). PSSp isolates displayed 30 different serotypes although serotype 14 was the most common. Overall a high prevalence of NTPn (11.1%) was observed with 62.9% PNSp. Serotypes coverage xvi for the PCV7, PCV10 and PCV13 vaccines were 55.2%, 55.9% and 65.1%, respectively. Being less than 24 months of age (OR=1.79; p=0.006), hospitalization in the previous three months (OR=2.19; p=0.025), and recurrent acute otitis media (OR=2.89; p=0.013) were independently associated with PNSp in a multivariate model. Among the 123 PNSp submitted to PFGE (106/carriage and 17/ invasive isolates) a major group of 34 serotype 14 strains (8 invasive and 26 carriage) was identified and found to be genetically related to the global pneumococcal clone Spain 9V-3 (82.7% similarity). All NTPn presented capsule gene locus and 10 (45.4%) of them presented capsule gene locus to type 14. Conclusions: (i) DCC attendees with history of recurrent AOM could significantly contribute to the spread of nasopharyngeal PNSp strains into the community; (ii) epidemiologic and molecular evidences support the findings that pneumococcal nonypeable carriage isolates are genetically similar to carriage and invasive isolates expressing capsular type 14; (iii) carriage and invasive isolates circulating in Goiânia belong to a serotype 14 variant of the Spain 9V -3 clone and play a critical role in the spread of PNSp strains to the entire pediatric community of Goiânia
Objetivo: (i) identificar fatores associados à colonização nasofaríngea por S. pneumoniae não suscetíveis à penicilina em crianças que frequentam creches no município de Goiânia-GO e caracterizar geneticamente as cepas não suscetíveis; (ii) determinar a cobertura das vacinas conjugadas pneumocócicas 7, 10 e 13 valente; (iii) avaliar o relacionamento genético entre cepas do sorotipo 14 e pneumococos não tipáveis (PnNT); (iv) identificar a presença de cepas colonizadoras relacionadas geneticamente aos clones internacionais de S. pneumoniae. Metodologia: Um estudo de prevalência de portador de pneumococo não suscetível à penicilina (SpNP) foi conduzido de agosto a dezembro de 2005, em 1192 crianças de dois a 59 meses de idade, atendidas em 62 creches em Goiânia. Os testes de suscetibilidade antimicrobiana seguiram as recomendações do CLSI de 2007 e a sorotipagem foi realizada pela reação de Quellung e confirmada por ensaio multibead. Isolados PnNT e do sorotipo 14 foram analisados por reação de PCR. Odds ratio para portador de SpNP e respectivos intervalos de 95% de confiança foram estimados por regressão logística. Para avaliar a similaridade genética entre os isolados de portador (sorotipo 14 e PnNT) e isolados invasivos (sorotipo 14) obtidos de crianças de Goiânia utilizou-se amostras de isolados invasivos de um estudo maior de vigilância populacional que vem sendo conduzido desde 2007. Assim, eletroforese em campo pulsado (PFGE) foi utilizada para a tipagem molecular. Definiu-se como linhagem a presença de três ou mais cepas resistentes com similaridade genética ≥ 80%. Resultados: S. pneumoniae foi isolado de 686 (57,6%) crianças das creches e 178 (25,9%) dessas eram portadoras de SpNS. Sorotipo 14 (53%), 23F (10,2%), 6B (6%), 19F (4,8%) e 19A (4,2%) estavam presentes em 78,2% dos PnNS. Detectou-se alta prevalência (11,1%) de isolados não tipáveis, dos quais 62.9% eram resistentes à penicilina. A cobertura dos sorotipos colonizadores para as vacinas 7-valente, 10- valente e 13-valente foi respectivamente 55,2%, 55,9% e 65,1%. Crianças menores de 24 meses de idade (OR=1,79; p=0,006), hospitalização nos últimos três meses (OR=2,19; p=0,025), e otite média aguda recorrente (OR=2,89; p=0,013) foram fatores xiv independentemente associados com SpNS na análise multivariada. Entre os 123 isolados submetidos à PFGE, 106 eram de nasofaringe de crianças das creches, dos quais 84 expressavam a cápsula tipo 14 e 22 eram isolados PnNT. Todas as cepas invasivas eram sorotipo 14. A maior linhagem agrupou 34 pneumococos do sorotipo 14, com 82,7% de similaridade, os quais foram geneticamente relacionados ao clone Spain 9V-3. Todas as cepas PnNT apresentaram locus para o gene da cápsula para o tipo 14. Houve uma diferença estatisticamente significante entre os valores da CIM para a penicilina entre as três principais linhagens (Krukal-Wallis, p<0,001). Conclusões: (i) crianças com otite média recorrente podem exercer papel importante na disseminação de pneumococos resistentes para a comunidade; (ii) Evidências genéticas apóiam os achados de que cepas de pneumococo não tipáveis assemelham-se ao genótipo das cepas do sorotipo 14; (iii) isolados de portadores e invasivos que circulam em Goiânia pertencem a um sorotipo 14 variante do clone Spain9V-3, responsável pela disseminação da resistência do pneumococo na população pediátrica de Goiânia

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Zanardo, Rafaela Tais. "Purificação do polissacarídeo capsular de Streptococcus pneumoniae de sorotipo 14". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-11032016-104211/.

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Streptococcus pneumoniae (pneumococo) é um importante patógeno humano, responsável por graves infecções das vias respiratórias. O principal fator de virulência desse microrganismo é a cápsula polissacarídica (PS), antígeno das vacinas atuais, que são elaboradas com os PS purificados de cepas de pneumococo prevalentes na população. O objetivo desse trabalho foi desenvolver um processo de purificação do PS do sorotipo 14, responsável por 39% das doenças em crianças de 0-6 anos no Brasil. A metodologia de purificação envolveu separação celular por microfiltração tangencial e concentração do microfiltrado com membrana de ultrafiltração tangencial de 50 kDa. O produto dessa etapa foi diafiltrado com dodecil sulfato de sódio em membrana de ultrafiltração tangencial de 30 kDa, seguido de precipitação com ácido tricloroacético a 5%, precipitação por etanol (20% e 60%) e cromatografia de troca aniônica. A pureza do PS foi avaliada pelo conteúdo de proteínas e ácidos nucleicos remanescentes e o tamanho por cromatografia de exclusão molecular. O PS foi obtido com pureza e tamanho requeridos pelos órgãos regulatórios e o rendimento final do processo foi de 65%.
Streptococcus pneumoniae (pneumococcus) is an important human pathogen responsible for severe respiratory tract infections. The main virulence factor of this microorganism is the capsular polysaccharide (PS), which is the antigen of all current vaccines, which are prepared with purified PS of pneumococcal strains prevalent in the population. The objective of this work was to develop a new purification process for PS of serotype 14, responsible for 39% of diseases in children of 0-6 years old in Brazil. The purification method involved cell separation by tangential microfiltration and concentration of cell-free culture broth containing PS by tangential ultrafiltration (50 kDa). The product of this step was diafiltrated with sodium dodecyl sulfate by tangential ultrafiltration (30 kDa), following by 5% trichloroacetic acid precipitation, 20% and 60% ethanol precipitation and anion exchange chromatography. The PS purity was evaluated by the content of residual proteins and nucleic acids, and the molecular mass by size exclusion chromatography. The purity and molecular mass requirements were achieved and the process global yield was 65%.

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Santos, Tanila Wood dos. "Análise da resposta celular induzida no pulmão pela imunização de camundongos com vacinas pneumocócicas híbridas PspA-PLY". Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-10122014-103341/.

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Streptococcus pneumoniae é responsável por milhões de mortes anuais no mundo todo. As vacinas atuais são baseadas em polissacarídeos capsulares e apresentam cobertura limitada. Assim, diversas proteínas tem sido estudadas como alternativas vacinais, dentre as quais se destacam PspA e PLY. Os objetivos deste estudo foram caracterizar produção de anticorpos e a resposta celular induzida pela imunização com vacinas híbridas PspA-PLY em modelo de pneumonia. Os anticorpos apresentaram elevada capacidade de ligação a pneumococos expressando PspAs de família 2, bem como um aumento na deposição de complemento nestes isolados. A imunização com as proteínas híbridas protegeu os camundongos do desafio sistêmico com pneumococo contendo PspA de família 2. Foi desenvolvido um modelo de pneumonia lobar em camundongos, onde a imunização com PspA-PLY induziu um aumento de IL-6 e TNF nos pulmões após o desafio, levando a uma redução no número de bactérias nos pulmões dos animais. Os dados sugerem que a fusão de PspA à PLY é capaz de ampliar a cobertura protetora a isolados expressando PspAs distintas, e que essa mesma vacina á capaz de proteger os animais contra pneumonia, pela indução precoce de citocinas como IL-6 e TNF-a nos pulmões.
Streptococcus pneumoniae is responsible for millions of deaths annually around the globe. The current vaccines are based on capsular polysaccharides, and have limited coverage. Thus, several proteins have been investigated as alternative vaccines, including PspA and PLY. The present study aimed at characterizing the antibody production and cellular immune response induced by mouse immunization with PspA-PLY hybrid vaccines in a pneumonia model. The induced antibodies demonstrated a strong recognition of pneumococci expressing family 2 PspA molecules, as well as an enhancement in complement deposition in their surface. Immunization with the fusion protein protected mice from systemic challenge with a pneumococcal isolate bearing a family 2 PspA. A model of lobar pneumonia was developed in BALB/c mice, where the immunization with the PspA-PLY fusion induced an increase in IL-6 and TNF-a production in the lungs after pneumococcal challenge, leading to a reduction on bacteria load in the lungs of immunized mice. The data suggests that fusion of PspA to PLY is capable of increasing vaccine coverage aginst pneumococcal infection with isolates bearing family 2 PspAs, and confer protection in mice against pneumonia, by the early production of IL-6 and TNF-a in the lungs.

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Medeiros, Marta Inês Cazentini. "Sorotipos e perfil de resistência antimicrobiana do Streptococcus pneumoniae: implicações clínicas na doença invasiva e no programa nacional de imunização (1998-2013)". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/22/22132/tde-28012016-144027/.

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As infecções por Streptococcus pneumoniae (pneumococo) ainda desafiam os sistemas de saúde em todo mundo. Este é um estudo observacional, de seguimento retrospectivo, que avaliou aspectos microbiológicos e clínicos das cepas de pneumococo isoladas de pacientes com doença invasiva pneumocócica (DIP) isolados nos Departamentos Regionais de Saúde (DRS) de Araraquara, Barretos, Franca e Ribeirão Preto, em um período de 16 anos (1998-2013). As informações foram obtidas junto ao Instituto Adolfo Lutz e, no banco de dados do Hospital das Clínicas de Ribeirão Preto (HCRP). Analisou-se 796 linhagens, com predominio do gênero masculino (58,9%), da faixa etária de 20 a menores de 60 anos de idade (32,2%) e do período de 2003 a 2010 (60,2%). As DIPs mais comuns foram a meningite (45,7%) e a pneumonia (45,0%). Quanto aos sorotipos mais frequentes, observou-se em 83,3%: 14, 3, 19F, 1, 6A, 6B, 23F, 9V, 18C, 19A, 12F, 4, 7F, 5, 22F, 11A, 8, 9N, 10A e 15C, sendo o 14 o mais comum nos quatro DRS estudados. Os sorotipos 14, 3 e 19F foram mais frequentes na meningite, enquanto os sorotipos 14, 3 e 1 na pneumonia. Após 2010, verificou-se diminuição dos sorotipos 14, 1, 23F e 5 e aumento de 12F, 11A e 8, não contidos na vacina. A resistência à penicilina foi de 14,8%, sendo 3,0% resistência intermediária e 11,8% de resistência plena. Para ceftriaxona, 5,3% foram não sensíveis. A sensibilidade ao cloranfenicol, eritromicina e ceftriaxona manteve-se acima dos 90%, no período estudado. O maior nível de resistência foi observado para Sulfametoxazol/trimetoprim (49,4%). Destaca-se o aumento dos sorotipos 12F, 11A e 8 após a vacinação, considerando que nenhum deles compõe as vacinas conjugadas disponíveis. Observou-se variabilidade de resistência entre os diferentes sorotipos de pneumococo. A DIP mais frequente nos pacientes cadastrados no HCRP foi a pneumonia (67,8%), seguida da meningite (22,9%) tendo como sorotipos mais frequentes 14, 6A, 23F, 1, 3, 18C, 19F, 12F, 4,9V, 6B e 19A. Destes pacientes 67,5% apresentaram cura sem sequelas, 6,9% tiveram algum tipo de sequela e 25,6% evoluíram para óbito. A pneumonia causou 18,2% dos óbitos, principalmente na faixa etária de 20 a menores de 60 anos de idade. Os sorotipos 12F, 14, 18C, 9V, 18A, 19A e 23F foram responsáveis por 64,9% dos óbitos por meningite, enquanto os sorotipos 3, 14, 9V, 6B, 23F e 19F estiveram envolvidos em 63,4% das mortes por pneumonia. Entre os pacientes que morreram 68,2% tinham algum tipo de comorbidade, sendo HIV/AIDS, alcoolismo e câncer as mais comuns. A faixa etária com 60 anos ou mais foi a mais significativa (OR=4,2) para o insucesso, independente da presença de comorbidade. A presença do sorotipo 18C foi fator de risco significativo tanto na análise bruta (OR=3,8), quanto ao ajustar por comorbidade (OR=5,0) ou ajustada por idade (OR=5,4). O mesmo ocorreu para o sorotipo 12F (respectivamente, OR=5,1, OR=5,0 e OR=4,7). Observou-se alterações na circulação de alguns sorotipos de pneumococo no período pós VPC10. Ressalta-se a importância da continuidade da vigilância das DIPs, afim de determinar oscilações clínicas e microbiológicas da doença. Além disto, na era das vacinas conjugadas, o contínuo monitoramento sobre a distribuição de sorotipos na população é necessário para a avaliação do impacto e adequação da imunização
Infections by Streptococcus pneumoniae (pneumococcus) are still a challenge to health systems worldwide. An observational retrospective study was developed to assess microbiological and clinical aspects of pneumococcus strains isolated from patients with invasive pneumococcal diseases (IPD) which were isolated in the Regional Health Departments (DRS) of Araraquara, Barretos, Franca and Ribeirão Preto, in a period of 16 years (1998-2013). Data were obtained at the Adolfo Lutz Institute and in databases of the Clinics Hospital of Ribeirão Preto (HCRP). A total of 796 strains were analyzed, with prevalence of male individuals (58.9%), aged between 20 and 60 years (32.2%), and in the period between 2003 and 2010 (60.2%). The most common IPD were meningitis (45.7%) and pneumonia (45.0%). Regarding the most frequent serotypes, in 83.3% they were: 14, 3, 19F, 1, 6A, 6B, 23F, 9V, 18C, 19A, 12F, 4, 7F, 5, 22F, 11A, 8, 9N, 10A and 15C, with 14 being the most common in the four DRS studied. Serotypes 14, 3 and 19F were more frequent in meningitis, whereas serotypes 14, 3 and 1 were more frequent in pneumonia. After 2010, there was a decrease in serotypes 14, 1, 23F and 5, and an increase in 12F, 11A and 8, which are not included in the vaccine. Resistance to penicillin was 14.8%, with 3.0% being intermediate, and 11.8% full resistance. For ceftriaxone, 5.3% were not sensitive. Sensitivity to chloramphenicol, erythromycin and ceftriaxone remained over 90% in the studied period. The highest level of resistance was observed for Sulfamethoxazole/trimethoprim (49.4%). It is noteworthy that there was an increase in the s serotypes 12F, 11A and 8 after vaccination, considering that none of them make up the combined vaccines available. Resistance varied among the different serotypes of pneumococcus. The most frequent IPD in the patients registered in the HCRP was pneumonia (67.8%), followed by meningitis (22.9%), with the most frequent serotypes being 14, 6A, 23F, 1, 3, 18C, 19F, 12F, 4, 9V, 6B and 19A. Of these patients, 67.5% were cured without sequela, 6.9% had some sort of sequela and 25.6% evolved to death. Pneumonia caused 18.2% of the deaths, mainly in the age range between 20 and 60 years. Serotypes 12F, 14, 18C, 9V, 18A, 19A and 23F were responsible for 64.9% of the deaths by meningitis, whereas serotypes 3, 14, 9V, 6B, 23F and 19F were involved in 63.4% of the deaths by pneumonia. Among the patients who died, 68.2% had some sort of comorbidity, with HIV/AIDS, alcoholism and cancer being the most common. The age range over 60 years was the most significant (OR=4.2) for failure, regardless of the presence of a comorbidity. The presence of serotype 18C was a significant risk factor both in the gross analysis (OR=3.8), and in the adjustment as for comorbidity (OR=5.0) or age (OR=5.4). This was also true for the serotype 12F (respectively, OR=5.1, OR=5.0 and OR=4.7). There were alterations in the circulation of some pneumococcus serotypes in the period after VPC10. it is emphasized the importance of continued monitoring of DIPs, in order to determine clinical and microbiological fluctuations of the disease. In addition, in the era of combined vaccines, it is necessary to keep monitoring the distribution of serotypes in the population to assess the impact and adequacy of immunization

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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/.

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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.

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11

Weisfelt, Martijn. "Pneumococcal meningitis in adults". [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2007. http://dare.uva.nl/document/39634.

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12

Terra, Vanessa Sofia Agostinho. "Pneumococcal interactions with mucin". Thesis, University of Leicester, 2011. http://hdl.handle.net/2381/9389.

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The nasopharynx is covered by mucin. Mucin is a glycoprotein and the carbohydrate moieties are potential fermentable substrates for Streptococcus pneumoniae. Previous in vitro studies showed that S. pneumoniae can grow on mucin. This study was undertaken to investigate how S. pneumoniae degrades the mucin carbohydrates to mono and disaccharides for subsequent fermentation. In silico search of pneumococcal genome identified fourteen putative glycosidases. Pneumococcal mutants of each were made and tested for growth in defined medium with mucin as the only source of carbon. Of these, two genes SPD0065 and SPD0247 were chosen for further study. Consequently two novel glycosidases were described, β-galactosidase (BgaC), encoded by gene SPD0065 and a 6-phospho-β-glucosidase (BglA) encoded by gene SPD0247. The knocked-out mutants SPD0065M and SPD0247M could not grow in Sicard’s defined medium supplemented with mucin and exhibited decreased enzymatic activity when compared to the wild type D39. Since gene SPD0562 had been previously identified as encoding a β-galactosidase (BgaA), the relative contribution of BgaA and BgaC to total β-galactosidase activity was investigated by introducing mutations in these genes individually and together. Mutation in the individual genes resulted in significant decrease in the enzymatic activity but the double mutation did not totally abolished activity. BgaC had specificity for galactose (β1,3)-N-acetylgalactosamine. Furthermore, BgaC released galactose from desialylated fetuin. The expression of SPD0065 and SPD0247 in S. pneumoniae grown in mucin containing medium or harvested from tissues from infected animals was significantly up-regulated compared to growth in glucose containing medium. When the mutants were tested in vivo, it was noted that SPD0065M had attenuated growth in the nasopharynx and SPD0247M in the lungs. In this study was demonstrated that BgaC has a role in the sequential deglycosylation of host glycoproteins and that BglA is involved in the further degradation of mucin-derived sugars.

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13

Félix, Sofia. "Pneumococcal adaptation during invasion". Doctoral thesis, Universidade Nova de Lisboa. Instituto de Tecnologia Química e Biológica António Xavier, 2020. http://hdl.handle.net/10362/110094.

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"Streptococcus pneumoniae, or the pneumococcus, frequently colonizes the human nasopharynx, particularly in children. From the nasopharynx, the pneumococcus can transit to other body sites and cause disease such as otitis media, pneumonia, bacteremia and meningitis. Multivalent pneumococcal conjugate vaccines (PCV), targeting pneumococcal capsular types, or serotypes, have been designed and implemented since 2001, to reduce the incidence of pneumococcal disease worldwide. (...)"
N/A

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14

van, Tonder Andries J. "Pneumococcal genomics and evolution". Thesis, University of Oxford, 2016. https://ora.ox.ac.uk/objects/uuid:de6ba2cc-a1a6-4c86-ad43-6e4e785be46a.

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Streptococcus pneumoniae (the 'pneumococcus') is a global pathogen responsible for nearly a million deaths each year in children under the age of five. The polysaccharide capsule or serotype is the primary pneumococcal virulence factor and is encoded by the cps locus. The introduction of pneumococcal conjugate vaccines has led to a significant reduction in the prevalence of invasive diseases caused by vaccine serotypes and a concomitant reduction of vaccine serotypes recovered from the nasopharynx of healthy children, although the overall rates of carriage have remained constant due to the replacement of vaccine serotypes with non-vaccine serotypes. The increasing numbers of genomes from large well-characterised pneumococcal datasets allows for key biological questions related to the pneumococcus, such as capsular diversity, to be examined in unprecedented detail. This thesis describes the application of genomics to investigating important aspects of pneumococcal biology including the pan-genome, cps locus diversity and genomic regions potentially associated with invasive disease. The first part of the thesis described a Bayesian decision model for estimating bacterial core genomes. This model was applied to genome datasets from five different bacterial species. The same model was later used to estimate core genomes for four different pneumococcal carriage datasets. These estimated core genomes were then compared and revealed a very small shared core genome of 303 genes. The results also highlighted the unexpected diversity of a pneumococcal dataset from Thailand. The second part of the thesis examined the diversity of the cps locus starting with serogroup 6 and in particular the recently described novel serotype 6E. This analysis revealed that the majority of what had previously been described as serotype 6B pneumococci were in fact serotype 6E and serological assays demonstrated that vaccine-induced serotype 6B antibodies were able to kill serotype 6E pneumococci. The analysis of cps loci was then extended to consider the diversity of 49 serotypes and included 5,405 genomes in the analyses. These analyses revealed several hybrid and putative novel serotypes. The final part of the thesis used a genome-wide association study to identify 89 candidate loci significantly associated with invasive disease. The results in this thesis showed that large numbers of genome sequences could provide a detailed insight into important aspects of pneumococcal biology.

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Gritzfeld, Jenna. "Experimental human pneumococcal carriage". Thesis, University of Liverpool, 2015. http://livrepository.liverpool.ac.uk/2013340/.

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Pneumococcal disease is preceded by nasopharyngeal colonization, which is also the source of transmission. Current pneumococcal conjugate vaccines protect against invasive disease and reduce carriage in children, but are less effective against mucosal disease and have limited serotype coverage. There is an urgent need for new vaccines and colonization has been suggested as an alternative endpoint in vaccine licensure. Experimental human pneumococcal carriage, although potentially risky, offers a way to examine colonization in the context of vaccination. Experimental carriage also allows the investigation of the impact of a pathogen on the immunological complexity and normal microbiota of humans, both of which cannot be done using animal models. We developed a safe and reproducible method of experimental human pneumococcal carriage, described bacteriological and immune factors associated with carriage, and examined the density and duration of experimental carriage. The data presented in this thesis show that experimental human pneumococcal carriage was safe and reproducible. There were important bacteriological differences between pneumococcal strains that affected carriage. Asymptomatic upper respiratory tract viral infection increased both the risk of pneumococcal colonization and the levels of mucosal Factor H, leading to increased colonization density. This model will be useful in further studies of pneumococcal pathogenicity and host protection against carriage and disease. The model may also be used to select vaccine candidates by protective efficacy in blocking experimental carriage.

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16

Yau, Belinda. "Pathogenesis of pneumococcal meningitis". Thesis, The University of Sydney, 2014. http://hdl.handle.net/2123/12485.

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Streptococcus pneumoniae (SP) meningitis remains a significant cause of global childhood mortality, and a potential epidemic pathogen despite improving vaccinations schemes. Neuropathology in pneumococcal meningitis (PM) is attributed to both bacterial products and the host-mediated proinflammatory response. Proinflammatory cytokine interferon-gamma (IFNγ) is associated with macrophage activation and regulating MHC Class I expression in innate immunity. IFNγ gene knockout (GKO) mice inoculated with ~5 x 103 CFU of SP/mouse were significantly protected against fatal PM, compared to C57Bl/6 WT mice, in both serotype 3 WU2 and serotype 4 TIGR4 strains. TIGR4 PM was comparatively more virulent than WU2 PM. In murine PM, IFNγ regulated induction of chemokines MCP1, CXCL9, CXCL10, the IRGM1, IRGM3 proteins and nitric oxide synthase 2 (NOS2). In WU2 PM, production of IFNγ was attributed to infiltrating Natural Killer (NK) cells, and dependent upon activation of the inflammasome complex and interleukin-18. NOS2 GKO exhibited a significantly improved survival phenotype, and reduced blood brain barrier dysfunction, compared to WT mice. Intracellular staining revealed Ly6Chi monocytes and NK cells as the source of IFNγ-dependent NOS2 in PM. Overall, this thesis addresses IFNγ production and its contribution to experimental PM pathology.

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ROCHA, Cristyane Gonçalves Benicio Bastos. "Tipagem molecular de Streptococcus pneumoniae isolados da nasofaringe de crianças no contexto da vacinação pneumocócica". Universidade Federal de Goiás, 2010. http://repositorio.bc.ufg.br/tede/handle/tde/1565.

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Made available in DSpace on 2014-07-29T15:26:20Z (GMT). No. of bitstreams: 1 TeseCristyaneBenicio2010.pdf: 531193 bytes, checksum: 9a3d68036fe340ca60db84cb20f7066b (MD5) Previous issue date: 2010-02-18
Objectives (i) Present review article focusing on pneumococcal vaccines and carriage; (ii) to validate sequential multiplex PCR for identifying pneumococcal capsular serotypes from children attending day-care centers; (iii) determine the multilocus sequence typing; (iv) to identify the capsular types of multiple colonies of S. pneumoniae isolates from a single sample of nasopharyngeal secretions of children attending day-care centers in Goiânia. Materials and Methods S. pneumoniae was obtained from health children less than 5 years old attending 62 day care centers of Goiânia. The laboratory procedures were performed according to WHO recommendations. Were selected 217 isolates (penicillin resistant and sensitive) for capsular typing by multiplex PCR technique. MLST was performed for 55 isolates representing the serotypes detected and the different susceptibility patterns for penicillin. Quellung reaction was used for typing isolates serotypes 6A, 6B, 18C and the isolates not typed by multiplex PCR. For 28 presumptive pneumococcal positive NP swabs, 3 colonies were picked to acess possible serotype diversity. Eighty four pneumococci were identified by conventionally procedure and multiplex PCR was performed. Results Serotypes were deduced for 177/217 (81.6%) of the pneumococcal. The most frequent serogroups/serotypes were 14, 6, 23F, 19F and 18. Multiple serotypes were detected in 13 specimens. Were found 19 MLST types and two new ST. Forty (18.4%) were not serotyped by the multiplex PCR and quellung reaction. The analysis of three colonies from the same NP permitted the detection of differente serotypes in 7/28 (25%) NP samples. Conclusion (i) The multiplex PCR is simple and cost-effective method for detecting multiple serotypes in nasopharyngeal isolates; (ii) and thus might be useful for the monitoring of pneumococcal colonization over time; (iii) the use of multiplex PCR can further broaden our understanding of the dynamics of pneumococcal carriage, including multiple serotypes, the effect of vaccination on carriage, and transmission, as well as surveillance of IPD and co-colonization.
Objetivos: (i) Apresentar uma revisão focando as vacinas pneumocócicas e o portador de S. pneumoniae na nasofaringe; (ii) realizar a tipagem capsular de pneumococos colonizadores de nasofaringe de crianças de creches pela técnica de multiplex PCR; (iii) identificar o perfil MLST dos pneumococos isolados na nasofaringe; (iv) identificar os tipos capsulares de múltiplas colônias de S. pneumoniae isolados de uma única amostra de secreção da nasofaringe de crianças que frequentam creches do município de Goiânia pela técnica de multiplex PCR. Material e Métodos: Um estudo de prevalência de portador de pneumococo foi conduzido de agosto a dezembro de 2005, em crianças de dois a 59 meses de idade, atendidas em 62 creches em Goiânia. Os procedimentos laboratoriais para isolamento e identificação dos pneumococos foram realizados de acordo com as técnicas recomendadas pela Organização Mundial de Saúde. Foram selecionados 217 isolados (resistentes e sensíveis à penicilina) para a tipagem capsular pela técnica de multiplex PCR. O perfil MLST foi realizado para 55 isolados, representando os sorotipos detectados e os diferentes perfis de suscetibilidade à penicilina. A reação de Quellung foi usada para tipar os sorotipos 6A, 6B e 18C e os isolados não tipados pelo multiplex PCR. Para a análise de múltiplas colônias de S. pneumoniae, utilizou-se 28 amostras positivas para pneumococo, das quais se recuperou 3 colônias de cada placa de ágar sangue, totalizando 84 colônias, que foram submetidas aos testes de tipagem fenotípica e caracterização capsular pela técnica de multiplex PCR. Resultados: Cento e setenta e sete sorotipos em duzentos e dezessete (177/217), totalizando 81,6% dos pneumococos foram tipados. Os sorotipos mais freqüentes foram 14, 6, 23F, 19F e 18. Foram identificadas múltiplas colônias em 13 amostras de nasofaringe. Foram observados 19 tipos MLST e dois novos tipos de seqüência (ST). Quarenta (18,4%) dos isolados não foram tipados pelo multiplex PCR e todos não tipados pela reação de Quellung. A análise de múltiplas colônias de S. pneumoniae pela técnica de multiplex PCR permitiu a detecção de mais de um tipo em 25% (7/28) das amostras. Conclusões: (i) O método de multiplex PCR mostrou-se seguro e simples na detecção de diferentes tipos capsulares incluídos na reação, além de mais barato; (ii) representou uma valiosa ferramenta em investigações de vigilância de pneumococos; (iii) Aplicação da técnica multiplex PCR permitiu o conhecimento da diversidade genética de pneumococos colonizadores da nasofaringe, detectando a dinâmica da colonização desta bactéria na população, incluindo a colonização por múltiplos sorotipos; a substituição ou mudança de sorotipo como resultado da vacinação; como também vigilância das doenças pneumocócicas invasivas.

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Lee, Lai-ka y 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.
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Master of Public Health

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19

Sandgren, Andreas. "Microbial factors and host responses affecting severity of pneumococcal disease and pneumococcal carriage /". Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-416-3/.

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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.

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Saukkoriipi, A. (Annika). "Detection of pneumococcus by PCR". Doctoral thesis, University of Oulu, 2003. http://urn.fi/urn:isbn:9514272110.

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Abstract New rapid methods for sensitive and specific detection of pneumococci are not only needed to improve the diagnosis of pneumococcal disease but are also essential for vaccine and carriage studies. The purpose of this study was to develop sensitive PCR methods for the detection and quantification of S. pneumoniae and to study the applicability of these methods to detecting pneumococci in clinical samples. A previously described PCR method was first developed further by introducing a Europium-labelled hybridisation probe for the detection of amplification products. The hybridisation method was easy to use and improved the specificity of the PCR assay. The developed PCR assay was established as a sensitive method for detecting pneumococcal DNA when the presence of pneumococcal DNA in over 2500 middle ear fluid (MEF) samples of children with acute otitis media (AOM) was studied by using the method. Pneumococcal findings increased by 76% when using PCR detection in addition to culture, compared to using culture alone. However, the PCR-positive, culture-negative AOM events represented a less severe type of disease compared to the culture-positive events. A positive PCR finding seems to indicate the presence of viable, although often non-culturable pneumococci within the middle ear cleft. To be able to rapidly detect and quantify the initial numbers of pneumococcal genome copies in clinical samples, a real-time PCR method for the detection and quantification of pneumococcal DNA was developed. In real-time PCR, amplification and detection of amplification products occur simultaneously, which makes it possible to monitor the phase of the reaction at a particular stage or continuously. The method developed here was applied to the analysis of MEF samples and to investigating the nasopharyngeal carriage of pneumococcus. The sensitivities of bacterial culture and real-time PCR in detecting pneumococci were also compared. The real-time PCR assay was found to be rapid and sensitive and to provide information about the differences between the numbers of bacteria in samples. However, the quantitative results were shown to be dependent on the DNA extraction method applied. The real-time PCR method developed appears to be a good aid in research where an accurate and sensitive pneumococcal diagnosis is needed.

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22

Carter, Michael. "Childhood pneumococcal pneumonia in Nepal". Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:9b80fee9-60f3-448c-9f8f-bda1148f01c7.

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Pneumonia is the greatest cause of childhood mortality outside the neonatal period, yet the pathogen-specific aetiology of childhood pneumonia remains poorly defined. Vaccine probe studies estimate that approximately one third of children <5 years of age with radiographic endpoint consolidation have pneumococcal pneumonia in settings prior to the introduction of pneumococcal conjugate vaccination (PCV), such as much of South Asia. 10-valent PCV was introduced to the Nepali infant immunisation schedule in August 2015. I investigated childhood pneumococcal pneumonia in Nepal. I aimed to describe the prevalence of pneumococcal infection in children with suspected invasive bacterial disease admitted to Patan Hospital, Kathmandu, Nepal; to assess the impact of 10- valent PCV on pneumococcal pneumonia; and to assess two potential diagnostic tests for pneumococcal pneumonia based on the childhood response to pneumococci - assay of antibodies from lymphocyte supernatant (ALS) and analysis of differential gene expression (transcriptomics) - in children with pneumonia at Patan Hospital. Pneumococci were the second-most most prevalent pathogen isolated from the blood of children between 2005 and 2016. Interrupted time series analyses of data from children admitted with pneumonia from March 2014 - December 2016, showed a small increase (approximately 4%) in the odds of admission with pneumonia in comparison to non-pneumonia admis- sions temporally associated with 10-valent PCV introduction. However, it was not possible to adjust these time series analyses for extreme events including earthquakes (April 2015) and clean fuel shortages/increased air pollution (winter 2015/2016). In contrast, the indirect cohort method (a case-control approach in vaccinated vs unvaccinated children) showed vaccine effectiveness of 84% on the odds of nasopharyngeal carriage of vaccine-type pneumococci, but no effectiveness on pneumonia in these early data. Assay of IgG ALS pneumococcal capsular polysaccharides was complicated by what appear to be non-specific binding to capsular polysaccharides (of both S. pneumoniae, particularly serotype 3, and H. influenzae). Assay of IgG ALS to the best-performing of five pneumococcal proteins assessed had a sensitivity of 88% and specificity of 71% for the discrimination of pneumococcal pneumonia from other bacterial pneumonia. A transcriptomic signature discriminated between pneumococcal pneumonia and other bacterial pneumonia with a sensitivity of 91% and specificity of 100%. This thesis therefore contributes to knowledge of the clinical epidemiology of pneumococcal disease in South Asia. These data may also contribute to public health policy-making in the region. In addition, the development of two diagnostic tests for the aetiology of childhood pneumonia may be useful for future studies of childhood pneumonia aetiology.

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Cornick, Jen. "Roadmap to resistance : antimicrobial resistance in Malawian pneumococci". Thesis, University of Liverpool, 2012. http://livrepository.liverpool.ac.uk/11173/.

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Multi-drug resistant (MDR) Streptococcus pneumoniae are a major public health concern worldwide. In Malawi a resource poor country, even the simplest antimicrobials remain a precious commodity. Given the limited number of antimicrobials available for the management of MDR invasive pneumococcal disease (IPD) measures need to be implemented to limit the spread of resistance. In order to design such measures it is essential that we gain a better understanding of the evolution of antimicrobial resistance in this setting. The purpose of this thesis was to assess the molecular basis and mode of dissemination of antimicrobial resistance in S. pneumoniae with the aim of identifying a biomarker of antimicrobial resistance that could be used to design a diagnostic PCR to assist epidemiological surveillance of antimicrobial resistance and inform treatment policy. Malawi introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in 2011. To provide baseline data to assess the impact of PCV13 all invasive pneumococci isolated from children admitted to Queen Elizabeth Central Hospital, Malawi 2004-2006 were serotyped and subjected to antimicrobial susceptibility testing. The data suggested PCV13 will not provide protection against 61% of penicillin resistant pneumococci and if serotype replacement occurs following the introduction of PCV13, the incidence of penicillin resistant IPD could therefore increase Over 130 resistant and susceptible pneumococcal isolates from carriage and invasive disease were subjected to whole genome sequencing. The employment of an in vitro and in silco analytical approach established that S. pneumoniae employs a diverse array of antimicrobial resistance mechanisms, the dissemination of which is likely to be driven by high antimicrobial consumption. A relatively high incidence of antimicrobial resistant was observed in serotype 1 pneumococci, the most common cause of IPD in Malawi. This serotype is not usually associated with resistance in other geographic locations, the short duration of serotype 1 carriage is assumed to limit the chance it has to acquire resistance mechanisms via recombination. Interestingly the resistance mechanisms employed by serotype 1 had been acquired through multiple recombination events. Recombination was evidenced to contribute to >90% of the variation in the serotype 1 genomes. To allow the identification of resistance biomarkers free from any preconceptions about which genes are involved in resistance, multiple antimicrobial resistant lineages were generated in vitro. Isolates were sequenced at several time points as resistance developed. Comparison of the resistant isolates to the wild type isolates identified single nucleotide polymorphisms in 46 genes, 40 of these genes have not previously been implicated in antimicrobial resistance. The role of these genes in resistance warrants further investigation. The analysis suggests that rather than a single biomarker future research needs to identify multiple biomarkers; the dynamic nature of this organism means that it can adopt one of many routes to antimicrobial resistance.

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El-Turki, A. A. "Impact of seven-valent Pneumococcal Conjugate Vaccination (PCV7) on childhood pneumococcal diseases in the UK". Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1408821/.

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Streptococcus pneumoniae is the leading cause of infectious childhood conditions such as Otitis Media (OM) and Pneumonia. Amoxicillin is the recommended first-line treatment for these indications. But because of growing resistance to penicillin based and other antibiotics prevention via effective immunisation is a more desirable approach. PCV7 was introduced in the UK in 2006. Studies conducted in the USA and Europe have shown that the use of this vaccine successfully reduces the incidence of OM and pneumonia. Yet its impact on community antibiotic use in the UK has not to date been adequately described. This thesis presents the findings of two retrospective cohort studies that analysed the diagnosed incidence of OM and pneumonia and the associated antibiotic prescribing, using the IMS DA and THIN GP databases. The extensive data manipulation conducted shows that the overall number of (all cause) pneumonia episodes in children recorded by GPs declined by 14% between 2006 and 2010. Associated antibiotic prescribing fell by 10%. In addition, the research presented here identified a fall of more than a third in primary care recorded OM diagnoses and antibiotic prescribing for the treatment of OM in children between 2006 and 2010. These data represent new evidence that the introduction of the original conjugated PCV7 contributed to a decline in antibiotic prescribing by GPs. However, additional prescribing behaviour change drivers were involved and consumption by patients may have fallen faster than the available data sets suggest. The PCV7 has now been replaced by the PCV13. Against this background a range of additional policy questions are discussed. They include issues relating to bacterial serotype replacement trends and virulence shifts, and the implications of effective infant and child protection for the health of older adults at high risk of contracting pneumococcal infections.

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25

Ekdahl, Karl. "Immunological aspects on pneumococcal infections with special reference to bacteremic pneumococcal infections and recurrent pneumonia /". Lund : Dept. of Infectious Diseases, University of Lund, 1995. http://catalog.hathitrust.org/api/volumes/oclc/39177549.html.

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AUDRY, JEAN-MARC. "Bacteriologie des infections pneumococciques profondes au c. H. R. De reims : bilan sur 5 ans". Reims, 1989. http://www.theses.fr/1989REIMM017.

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Ahmed, Muhammad Shamsher. "Natural immunity to pneumococcal Pilus-1 RrgA and RrgB antigens, and its relationship with pneumococcal carriage". Thesis, University of Liverpool, 2013. http://livrepository.liverpool.ac.uk/16633/.

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Streptococcus pneumoniae (pneumococcus) is a leading cause of childhood morbidity and mortality around the world. The available polysaccharide-based vaccines are limited by either low efficacy in young children or narrow serotype coverage. Recent research has focused on developing protein vaccines. Pneumococcal pilus-1 proteins play an important role in pneumococcal adherence to host respiratory epithelium and subsequent bacterial colonization or invasion; and may therefore be an effective vaccine candidate. This PhD project investigated natural immunity in humans to pneumococcal pilus-1 proteins and its association with nasopharyngeal carriage of pneumococcus. Nasopharyngeal carriage of pneumococcus was analysed by bacteriological culture of nasal swabs on blood agar. Pneumococci were identified based on their colony morphology and optochin sensitivity; and further confirmed by PCR detection of pneumolysin gene in the isolates. Pneumococcal carriage was found to be common in young children, which gradually decreased with advancing age. PCR detection of pilus islet 1 (PI-1) gene revealed that percentage of pilus-1 positivity was low among these carriage isolates. This low prevalence may be associated with the recent introduction of pneumococcal conjugate vaccination, which covers the common piliated serotypes. ELISA based measurement of serum and salivary antibodies to pilus-1 proteins detected significant antibody levels to both RrgA and RrgB, presumably developed as a part of natural immune response in children and adults. An age-dependent increase in serum antibody levels to both RrgA and RrgB was also observed, and anti-RrgA appeared to develop earlier in childhood than anti-RrgB. Moreover, higher levels of antibody, especially anti-RrgA were found in children who were culture-negative than in those who were culture-positive for pneumococcus. It suggests that these naturally developed antibodies may contribute to the protection against pneumococcal carriage in humans. Using an in vitro model of human NALT, the study revealed that adenotonsillar tissues are important induction sites for immune response to these antigens, by priming B cell memory. The induction of antibody secreting cells in NALT was enumerated by ELISpot assay; and the antibody production was measured by antigen-specific ELISA. In vitro stimulation with a wild type (TIGR4) pneumococcal culture supernatant (containing both RrgA and RrgB proteins) induced a significant memory B cell and antibody response in adenotonsillar cells. Current carriage in vivo enhanced the memory B cell response and antibody production. Flowcytometric analysis of CFSE labelled adenotonsillar MNC suggested that pneumococcal pilus-1 proteins RrgA and RrgB were capable of stimulating CD4+ T cell proliferative response in human NALT. Stimulation with pneumococcal CCS induced Th17 related cytokines production in both human adenotonsillar MNC and PBMC culture supernatant. Importantly, this in vitro production of Th17 cytokines after stimulation with TIGR4wt CCS was significantly higher than that of CCS derived from its isogenic RrgA-/- and RrgB-/- mutants, indicating a contribution from both of these proteins. The ability of these pilus-1 proteins to stimulate CD4+ T cell proliferation and Th17 response may contribute to the natural immunity to pneumococcus in humans. This study has revealed that both of these pilus-1 proteins, RrgA and RrgB are immunogenic and are capable of priming for memory B and T cell response in human NALT. These findings aid to our understanding on the naturally developed immune response to pilus-1 proteins, and may inform future vaccination strategy with intranasal immunisation containing protein antigens against pneumococcal infection.

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King, Samantha Jane. "Epidemiology and evolution of pneumococcal neuraminidases". Thesis, University of Warwick, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343126.

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Trück, Johannes. "B cell response to pneumococcal vaccines". Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:4bbccd8c-febd-4713-a97b-d6a8a08e3979.

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Streptococcus pneumoniae is a significant cause of mortality and morbidity in both children and older adults, with infection resulting in invasive disease, pneumonia and otitis media. The inclusion of pneumococcal conjugate vaccines in routine infant immunisation programmes has had a major impact on disease rates. Vaccine-induced protection against pneumococcal infection is thought to be mediated by the generation of persistent serotype-specific functional antibodies and antigen-specific memory B cells, the latter capable of generating a rapid secondary antibody response on re-exposure to antigen. Although many studies have investigated the immunogenicity of pneumococcal vaccines in different age groups by measuring serotype-specific antibodies, there is more limited information about the B cells underlying such an immune response. Important areas to investigate include the identity of the B cell subsets involved in antibody production and the potential link between memory B cells (B_MEM) and persistent antibody production by long-lived plasma cells. In this thesis I have investigated in detail the immune response to pneumococcal vaccines given to children and adults by a variety of different methods. By examining the variability of a B_MEM ELISpot method, it was shown that this assay is robust and reproducible and can be performed on fresh or frozen samples and in different laboratories. Using this technique, in a study of pre-school children, it was demonstrated for the first time that the level of pre-existing serotype 3-specific antibody is negatively correlated with, and may directly impair the B_MEM response to a booster dose of 13-valent pneumococcal conjugate vaccine (PCV-13) containing serotype 3 glycoconjugate. In the same study, it was shown that antibody persistence against most vaccine serotypes can be expected until the age of 3.5 years. A novel antigen-labelling technique was used in a detailed kinetics study of antigen-specific B cell subsets in response to either PCV-13 or 23-valent pneumococcal polysaccharide vaccine in adults. The results of this study revealed distinct B cell subset response patterns that were observed in all study participants indicating that IgM B_MEM seem to play a major role in the immune response to pneumococcal vaccines. In addition, in the same study, genome wide analysis of gene expression was performed and it was shown that vaccination with either a pneumococcal conjugate or polysaccharide vaccine results in a marked difference in numbers of differentially expressed genes 8 days following vaccination. A further tool likely to be of use in investigating B cell responses is the analysis of the antibody repertoire using next-generation sequencing techniques. In order to test the ability of these methods to detect vaccine responses, a large dataset of high-throughput B cell receptor sequences was analysed and revealed convergence of antigen-specific complementary-determining region (CDR)₃ amino acid (AA) sequences following vaccination and identified antigen-specific sequences. It was further demonstrated that for sequences directed against the H. influenzae type b (Hib) polysaccharide, diversity of immunoglobulin gene rearrangements is much greater than previously recognised. Frequencies of Hib-specific CDR₃ AA sequences were linked with anti-Hib avidity indices highlighting the potential of this method as an alternative (functional) measure of vaccine immunogenicity. These data suggest that studying the B cells and antibody repertoire post-vaccination can give novel insights into the biology that underlies the immune responses.

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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 PCV13
Two 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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Ojal, J. O. "Long-term population effects of pneumococcal vaccines on carriage of pneumococcal serotypes and subsequent disease in Kenya". Thesis, London School of Hygiene and Tropical Medicine (University of London), 2018. http://researchonline.lshtm.ac.uk/4647054/.

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Many African counties, like Kenya, have introduced pneumococcal conjugate vaccines (PCVs) with financial support from Gavi, the Vaccine Alliance. However, in the near future, they are expected to transition and take up the full costs. Kenya introduced the ten-valent PCV (PCV10) in 2011 and enters the accelerated transition phase in 2022. This work aimed to study the effects of PCV10 vaccination on pneumococcal carriage and disease in the pre- and the immediate post-vaccination period, predict the long-term vaccination impact on carriage of pneumococcus and subsequent invasive pneumococcal disease, evaluate immune factors that may influence that impact and, ultimately, investigate the cost-effectiveness of potential policy options in order to guide Kenya’s decision-making. A dynamic transmission model was fitted to pre-vaccination carriage data and its predictions were validated against post-vaccination carriage data. In order to evaluate immune factors that may influence vaccination impact and thus warrant consideration in the mathematical model, statistical modelling of the association between pre-existing pneumococcal carriage and vaccine responsiveness, and between maternally-derived anti-protein and anti-capsular antibodies and the rate pneumococcal acquisition in newborns, was undertaken. A cost-effectiveness analysis was done based on the disease incidence predictions from the transmission model. The dynamic transmission model was shown be useful as it closely predicted the observed magnitude and timing of serotype replacement. Maternal anti-capsular antibodies were estimated to have a limited role while impaired immune responses were observed among vaccine serotype carriers at the point of vaccination. These two immune factors were evaluated within the decision making structure and considered to have negligible impact on the performance of the model. In the conclusion, I estimated that sustaining PCV10 vaccination in Kenya will be cost-effective but will present a significant challenge to affordability by the Kenyan Government.

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32

Heinsbroek, E. "Pneumococcal carriage and transmission in Karonga district, Malawi, before and after introduction of 13-valent pneumococcal conjugate vaccination". Thesis, University of Liverpool, 2016. http://livrepository.liverpool.ac.uk/3003529/.

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Streptococcus pneumoniae (pneumococcus) is a leading cause of childhood morbidity and mortality worldwide. Thirteen-valent pneumococcal conjugate vaccine (PCV-13) was introduced in the Malawian infant immunisation programme in November 2011. PCV-13 is currently given at a “3+0” schedule: doses are given at 6, 10 and 14 weeks and no booster dose is currently implemented. The aim of this thesis was to study pneumococcal carriage and transmission in Karonga District, Malawi, before and after introduction of PCV-13, in order to review the effect of the current pneumococcal vaccination programme on carriage, and to give recommendations on the implementation of different vaccination strategies in Malawi. Pneumococcal carriage studies were conducted in Karonga between 2008 and 2014, with a focus on infants born to an HIV-positive mother, and HIV-positive adults, both of whom are at high risk of invasive pneumococcal disease. We found no difference in pneumococcal acquisition in infants by maternal HIV-status. A greater proportion of infant pneumococcal acquisition was attributable to carriage in other children < 5 years in the household than to maternal carriage. Pneumococcal carriage in HIV-positive adults in Malawi remained high despite up to two years of antiretroviral treatment, indicating a failure of reconstitution of respiratory mucosal immune response. An analysis on the uptake and timeliness of PCV-13 vaccination showed that despite high vaccination coverage in this setting, delays in vaccination were common. Infants born to lower educated or farming mothers and those living more remotely were at greater risk of being not fully vaccinated and being vaccinated late. Carriage studies conducted in 2014, two years post PCV-13 introduction, showed that carriage of vaccine type (VT) pneumococci had decreased in vaccinated children and unvaccinated older age groups, but that a reservoir of VT carriage was still present. VT carriage had not decreased in unvaccinated children < 5 years. Carriage of non-vaccine type pneumococci (NVT) had increased in vaccinated children. Our results suggest that a herd immunity effect is taking place albeit slowly in comparison to other countries. Waning immunity seemed to occur in vaccinated children 1-4 years. Our mathematical modelling studies provided further evidence for waning immunity. An immunity half-life between 6 months and 1 year was found to fit best with the observed post-vaccination carriage prevalence. If the immunity half-life were to be increased to 2 years, this would have a large impact on VT carriage decline in vaccinated and unvaccinated age groups. In the stochastic individual-based transmission models, which included explicit household transmission, an indirect vaccine effect was observed immediately after introduction of PCV-13. Adding a booster dose to the current three-dose schedule (3+1 schedule) would be beneficial for vaccinated and unvaccinated groups. Replacing the current 3+0 schedule with a 2+1 schedule (booster dose at 9 months) initially resulted in slower VT decline, but seemed to be associated with a longer-term gain in lower VT carriage in 1-4 year olds. Maternal vaccination did not result in additional VT carriage reduction in the infant. Ongoing surveillance is required to assess VT carriage in this population and monitor waning immunity and serotype replacement in vaccination individuals. A review of the vaccination schedule may be required to optimise total population impact in this high carriage setting. There is need for cheaper, more effective, serotype-independent pneumococcal vaccines. Potentially cheaper PCVs produced in India are in the pipeline, as well as a couple of new generation vaccines that are currently in phase 2 clinical trials. The next decade is promising to be an exciting time for pneumococcal researchers and policy makers worldwide, as new vaccines will pose interesting possibilities to further decrease pneumococcal carriage and disease worldwide.

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33

Goulart, Cibelly. "Vacinas pneumocócicas proteicas, avaliação da resposta imune sob diferentes apresentações". Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/87/87131/tde-03092015-124655/.

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Diversas proteínas pneumocócicas têm sido estudadas como candidatos vacinais. Entre elas, PspA e Ply induzem anticorpos essenciais para a proteção contra sepse, enquanto, SP 0148 e SP 2108 induzem IL-17 e protegem camundongos contra a colonização. Esse trabalho teve como objetivo principal desenvolver vacinas pneumocócicas baseadas em proteínas. Primeiramente, foi selecionada uma molécula de PspA com ampla reatividade cruzada. Em seguida, esta PspA foi fusionada com PdT, um pneumolisóide derivado da Ply. Essa proteína de fusão mostrou-se capaz de induzir resposta imunológica humoral e celular e protegeu camundongos contra desafio letal. Vacinas baseadas em BCG, que possui diversas propriedades adjuvantes, foram desenvolvidas expressando as proteínas pneumocócicas rPspA-PdT, SP 0148 e SP 2108. A imunização com o rBCG 0148/rSP 0148 induziu IL-17 e levou a proteção contra colonização. A combinação das três vacinas de rBCG mostrou-se mais eficiente na proteção contra desafio de colonização. Esses resultados sugerem um uso promissor do rBCG como vacina pneumocócica.
Several pneumococcal proteins have been proposed as vaccine candidates. PspA and Ply induce protective antibodies against sepse, while SP 0148 and SP 2108, induce IL-17 and protect mice against pneumococcal colonization. The major aim of this study was to produce pneumococcal vaccines based on proteins. First, we selected one PspA molecule able to induce broad-ranging cross-reactivity. Second, we constructed a hybrid protein containing a PspA fused to PdT, a detoxified form of Ply. The hybrid protein was able to induce humoral and cellular responses and protected mice against lethal challenge. Finally, due the adjuvant properties of BCG, we constructed recombinant BCG strains expressing PspA-PdT, SP 0148 and SP 2108. The immunization with rBCG-0148/rSP 0148 induced IL-17 and IFN-, and pneumococcal colonization in mice. Interestingly, the combination of all rBCG vaccines was more efficient in protecting mice against pneumococcal colonization. These results suggesting a promising use of rBCG as pneumococcal vaccine.

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34

Wu, Yunyan y 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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35

Fan, Hiu-yan y 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.
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36

Wong, Kwan-ting y 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.
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37

Segal, Shelley. "Host genetic susceptibility factors in pneumococcal disease". Thesis, Open University, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275104.

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38

SIME, FONGA-DJIMI HORTENSE. "Infections graves a pneumocoque en pediatrie : etude retrospective de 1989-1991 a la polyclinique pediatrique de calmette". Lille 2, 1992. http://www.theses.fr/1992LIL2M249.

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39

Wisby, Laura. "The genetics of susceptibility to pneumococcal infection". Thesis, Oxford Brookes University, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.543822.

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40

Shepherd, Jennifer. "Characterisation of pneumococcal peptidoglycan cross-linking enzymology". Thesis, University of Warwick, 2011. http://wrap.warwick.ac.uk/49184/.

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Despite the introduction of penicillin, infections caused by Streptococcus pneumoniae are associated with significant morbidity and mortality. As a result, there is an urgent need for successful identification of new drug targets within the organism. This thesis focuses on characterisation of MurM, which initiates the synthesis of branched muropeptides within pneumococcal peptidoglycan. MurM and MurN generate either alanyl-alanine or seryl-alanine appendages on the stem peptide lysine of Lipid II, ultimately resulting in indirect cross-linkage of the cell wall. Inactivation of murMN causes a reversion to penicillin sensitivity in penicillinresistant strains. However, elucidation of the relationship between MurM activity and penicillin-resistance is complicated by some penicillin-sensitive strains, including R6, having an unusually high proportion of indirect cross-linkage in their cell wall. Therefore, MurMR6 has been kinetically characterised with Lipid II, AlatRNAAla and Ser-tRNASer for comparison to MurMPn16 (penicillin-sensitive) and MurM159 (penicillin-resistant). These results confirmed that MurM159 is more catalytically active than MurMPn16. However, in the presence of Ser-tRNASer, the catalytic activity of MurMR6 approaches that of MurM159. Stimulation of MurM by cardiolipin indicates the potential role of pneumococcal membrane phospholipid composition in the regulation of this enzyme. Assessment of MurM substrate specificity was made using misaminoacylated SertRNAAla. Results indicate that Ser-tRNAAla is used more efficiently by MurM providing a link between peptidoglycan biosynthesis and the fidelity of protein synthesis in S. pneumoniae. A 2’-amino minihelix analogue of Ala-tRNAAla inhibits MurM with an IC50 of 0.5 μM demonstrating specific acceptance of the amino acid from the 2’ hydroxyl of the terminal adenine of the tRNA substrate. Crystallisation of MurM in the presence of zinc and subsequent characterisation of its metal-ion binding properties by kinetic analysis, isothermal titration calorimetry and bioinformatics-informed site-directed mutagenesis have identified that this enzyme is zinc-dependent. In combination, these findings have far-reaching implications for future drug design.

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41

Philippe, Jules. "Pneumococcus morphogenesis and resistance to beta-lactams". Thesis, Grenoble, 2014. http://www.theses.fr/2014GRENV018/document.

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Streptococcus pneumoniae, le pneumocoque, est une bactérie pathogène qui entraîne le décès de plus d'un million et demi de personnes dans le monde chaque année. Les β-lactamines sont très utilisées pour traiter les infections à pneumocoques. Ces antibiotiques inhibent la synthèse du peptidoglycane, une molécule géante constituant un réseau de chaînes glycopeptidiques qui englobe la cellule, lui confère sa forme et lui permet de maintenir son intégrité face à la pression osmotique. Le mécanisme d'action des β-lactamines est bien connud'un point de vue biochimique. En revanche, la réponse physiologique empêchant la multiplication des bactéries traitées est mal connue. Au cours de ma thèse, j'ai étudié les mécanismes moléculaires de la morphogenèse du pneumocoque par des approches de biochimie et de microbiologie. Un modèle de morphogenèse est proposé intégrant mes résultats à la littérature et permettant de formuler des hypothèses sur la réponse physiologique de S. pneumoniae aux β-lactamines
Streptococcus pneumoniae, the pneumococcus, is a bacterial pathogen that causes more than 1.5 million deaths each year in the world. β-Lactams are widely used to treat patients with pneumococcal infections. These antibiotics inhibit the synthesis of the peptidoglycan, a giant molecule constituting a mesh of aminosugar strands encasing the cell. This main constituent of the cell wall allows cells to maintain their integrity under the turgor pressure, and endows bacteria with their shape. The action of β-lactams is well understood from a biochemical point of view. However, a complete understanding of the physiological response of treated bacteria remains elusive. In this thesis, I investigated the molecular mechanisms of the morphogenesis of S. pneumoniae using methods of biochemistry and microbiology. A morphogenesis model is built based on my results and the literature, which permits to emit hypotheses concerning the response of the pneumococcus to β-lactams

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42

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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43

Högberg, Liselotte. "Penicillin-resistant pneumococci in Sweden - epidemiology and public health response /". Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-526-7/.

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44

Sheppard, Carmen Lucia. "The detection and characterisation of pneumococci in culture negative infections". Thesis, Queen Mary, University of London, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435185.

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45

Sleeman, Karen. "Characterising pneumococcal carriage and the role of maternally derived pneumococcal antibodies in infants less than 6 months of age". Thesis, University of Oxford, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393978.

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46

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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47

Mezones, Holguín Edward, Díaz Rafael Bolaños, Víctor Fiestas, César Sanabria, Aguado Alfonso Gutiérrez, Fabián Fiestas, Víctor J. Suárez, Morales Alfonso J. Rodríguez y Adrian V. Hernández. "Cost-effectiveness analysis of pneumococcal conjugate vaccines in preventing pneumonia in Peruvian children". The Journal of Infection in Developing Countries, 2015. http://hdl.handle.net/10757/337985.

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emezones@gmail.com
Introduction: Pneumococcal pneumonia (PP) has a high burden of morbimortality in children. Use of pneumococcal conjugate vaccines (PCVs) is an effective preventive measure. After PCV 7-valent (PCV7) withdrawal, PCV 10-valent (PCV10) and PCV 13-valent (PCV13) are the alternatives in Peru. This study aimed to evaluate cost effectiveness of these vaccines in preventing PP in Peruvian children <5 yearsold. Methodology: A cost-effectiveness analysis was developed in three phases: a systematic evidence search for calculating effectiveness; a cost analysis for vaccine strategies and outcome management; and an economic model based on decision tree analysis, including deterministic and probabilistic sensitivity analysis using acceptability curves, tornado diagram, and Monte Carlo simulation. A hypothetic 100 vaccinated children/vaccine cohort was built. An incremental cost-effectiveness ratio (ICER) was calculated. Results: The isolation probability for all serotypes in each vaccine was estimated: 38% for PCV7, 41% PCV10, and 17% PCV13. Avoided hospitalization was found to be the best effectiveness model measure. Estimated costs for PCV7, PCV10, and PCV13 cohorts were USD13,761, 11,895, and 12,499, respectively. Costs per avoided hospitalization were USD718 for PCV7, USD333 for PCV10, andUSD 162 for PCV13. At ICER, PCV7 was dominated by the other PCVs. Eliminating PCV7, PCV13 was more cost effective than PCV10 (confirmed in sensitivity analysis). Conclusions: PCV10 and PCV13 are more cost effective than PCV7 in prevention of pneumonia in children <5 years-old in Peru. PCV13 prevents more hospitalizations and is more cost-effective than PCV10. These results should be considered when making decisions about the Peruvian National Inmunizations Schedule.
This study was funded by Instituto Nacional de Salud, Lima, Peru
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48

Sjöström, Karin. "Molecular epidemiology of pneumococcal carriage and invasive disease /". Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-094-7/.

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49

Fernebro, Jenny. "Genetic approaches towards understanding pneumococcal virulence and biology /". Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-403-7/.

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50

Stanford, Elaine Yvonne. "Humoral immune responses to pneumococcal disease and vaccination". Thesis, Manchester Metropolitan University, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.582746.

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Background: Streptococcus pneumoniae causes infections in children, older adults and the immunocompromised. This thesis investigates humoral immune responses to pneumococcal vaccination in asplenic adults, and responses to infection and vaccination in children with invasive pneumococcal disease (IPD). Methods: Pneumococal serotype-specific antibody was measured using IgG enzyme-linked immunosorbent assay (asplenic adults), multiplexed bead assays (lgG and IgA) and opsonophagocytic assay (children with IPD), and total IgG was measured using nephelometry. Results: Seven-valent pneumococcal conjugate vaccine (PCV7) elicited significant increases (p <0.01) in vaccine-serotype specific IgG from levels pre-to 3-6 weeks post-vaccination in III asplenic adults. Although 97% (108/111) previously had ~ 1 dose(s) of pneumococcal polysaccharide vaccine, compliance with other UK guidelines for prevention of post-splenectomy infection (meningococcal vaccines and antibiotic prophylaxis) was poor. PCV7 in children with IPD was immunogenic for vaccine serotypes, with IgG GMCs higher in the group immunised under the original licensed schedule than those under a reduced schedule for serotypes 4, 14, 19F and 23F (p <0.05). Thirteen children with age-appropriate vaccination, however, failed to respond to their infecting serotype following additional PCV7 vaccination; this immunological unresponsiveness persisted despite up to 2 further doses. This was the first reported observation of this phenomenon, which has since been seen in association with asymptomatic carriage of vaccine-serotype pneumococci. Conclusion: Although PCV7 was immunogenic in children with IPD and adults with asplenia, protection should not be assumed for individuals colonised by, or infected with, a vaccine serotype when vaccinated. Further work is required to investigate causes of immunological unresponsiveness.

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