Celecoxib is a COX-2 selective non-steroidal anti-inflammatory drug which has been shown to inhibit growth and induce apoptosis in various cancer cell lines. Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and an apoptosis detection kit, we demonstrated that celecoxib was able to induce growth inhibition and apoptosis in a dose-dependent manner in 3 NPC cell lines: HK-1, Hone-1, and C666-1. Afterwards, a proteomic approach was used to study the underlying mechanisms involved in celecoxib-mediated effects on two COX-2 positive NPC cell lines (HK-1 and C666-1). Results showed that a total of 18 protein spots were differentially expressed in the HK-1 and C666-1 cells. On the other hand, we also compared the proteomic expression profile between an NPC cell line (C666-1) and a normal nasopharynx cell line (NP69) in order to study whether those differentially expressed proteins after celecoxib treatment were also involved in NPC carcinogenesis. Proteomics results with confirmation using Western blotting discovered that HSP27 phosphorylated of serine 82 (HSP27-pSer82) protein was up-regulated in C666-1 cells when compared with that in NP69 cells. After treatment with celecoxib, expression of HSP27-pSer82 protein was down-regulated in both HK-1 and C666-1 cells. These findings suggest that down-regulation of HSP27-pSer82 protein expression may have mediated the growth-inhibitory effects of celecoxib in HK-1 and C666-1 cells. Finally, other differential expressed proteins identified from proteomics with confirmation by immunocytochemical staining in the 2 NPC cell lines and 40 NPC patient specimens showed that down-regulation of annexin 2 and beta2-tubulin may be important in NPC formation. / COX-2 over-expression has been found in various cancers such as colorectal cancer, liver cancer and lung cancer. In vivo studies have shown that mice overexpressing COX-2 developed breast cancer whereas COX-2 knockout mice had reduced rates of cancer formation in the intestines and skin. In the present study, COX-2 expression in NPC patient biopsies was examined and correlated with the clinicopathological data of the patients. Immunocytochemical staining showed that COX-2 protein was over-expressed in 84.6% (66/78) of non-metastatic NPC patients and was associated with an advanced nodal stage (P<0.05). All these data support an important role for COX-2 in NPC pathogenesis. / In summary, this study is the first to identify HSP27-pSer82 protein as a potential target of celecoxib in NPC cells. Detailed investigations of the functional role of molecular targets identified in this study would improve our understanding of the chemotherapeutic effects of celecoxib and, in the long run, may lead to a more effective chemotherapeutic treatment to this common cancer. / Nasopharyngeal carcinoma (NPC) is prevalent in southern China. Although early stage patients have a high rate of cure with radiotherapy alone, the prognosis for those with stage III or IV disease remains poor due to subsequent development of distant metastases. Therefore there is an urgent need to develop novel biologic agents to improve treatment outcomes. / Chan, Ming Lok. / Adviser: Anthony T.C. Chan. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3418. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 141-171). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

(1) MRI is shown to be an accurate test for detecting NPC and one which has the potential to be used in screening to (a) screen out normal patients who do not require endoscopie biopsy; and (b) identify small tumours that would be missed on endoscopy. / (2) At diagnosis staging NPC by MRI reveals that oropharyngeal and maxillary sinus invasion are markers of more advanced disease than reflected in current staging system. Tumour involvement of the preclival/prevertebral region, skull base and retropharyngeal nodes are more common than previously recognised by computed tomography, while parapharyngeal tumour invasion is less common. The latter resuits from the superior ability of MRI to differentiate primary tumours with true parapharyngeal invasion from those contained within the nasopharynx which are causing bowing of the wall or lie adjacent to a retropharyngeal node. / (3) Post treatment complications were detected by MRI in over 50% of patients. Neural damage, especially to the temporal lobes and 12th cranial nerves, was the most frequent complication (48%), followed by osteoradionecrosis (20%) involving the mandible, upper cervical spine and skull base, the latter including destruction of the roof of the nasopharynx. Malignant tumours and unusual benign masses (6%) showed radiological features useful in the differential diagnosis from NPC recurrence. Malignant tumours were mainly squamous cell carcinomas or sarcomas showing a predilection for the maxillary region, tongue and external auditory canal. The unusual benign masses were found in the nasopharynx/sphenoid sinus. / (4) Finally functional MRI using DWI and 1H-MRS are feasible in the technically challenging region of the head and neck. Choline ratios and ADC values of NPC are established. The successful demonstration of differences between the biomarkers of NPC and those of lymphoma and squamous cell carcinoma, show that functional MRI is a new tool for the evaluation of NPC, opening up the possibility that these biomarkers can be used for monitoring NPC treatment response in the future. / Magnetic resonance imaging (MRI) provides excellent anatomical detail and functional information about cancer. This thesis explores the role of MRI in the assessment of nasopharyngeal carcinoma (NPC) from detection through to the long term complications of radiotherapy treatment. / Ann D King. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3468. / Thesis (M.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 180-191). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English only. / School code: 1307.

Advanced-stage nasopharyngeal carcinoma (NPC) presents very difficult scenarios for radiation therapy (RT) planning. The infiltration of tumor to the skull base and beyond means that the tumor is very close to critical normal organs (organs at risk, OARs). Despite the advent of intensity-modulated radiotherapy (IMRT) treatment technique---the state-of-art RT technique, conflicting requirements between organ protection and target dose conformity is still problematic. The objectives of the present research are (1) to investigate the dosimetry properties of IMRT treatment in advanced-stage NPC in respect of its dosimetric limitations and planning problems, (2) to develop new methods and tools to resolve such problems, in particular to improve the quality of treatment plans and efficiency of the dose planning and optimization process. A series of four inter-linked studies were conducted to address these issues. / In conclusion, the solutions to several major problems in IMRT planning for advanced-stage NPC were investigated and established. It has been demonstrated in this research that, by applying these methods and tools, significant improvement in the dosimetry and efficiency of IMRT treatment planning can be accomplished as compared with conventional IMRT planning techniques. It is expected that such would translate into an improvement in treatment throughput, better tumor control and reduction in normal tissues complications. The methods developed have potential to be applied to all stages of NPC and to other tumor sites. / The first study was to improve the efficacy in target coverage and organs sparing using an "organ-splitting" approach. The OARs which overlapped with targets were split into target-overlapping and non-overlapping segments and each segment was assigned with different constraints parameters to increase the degree of flexibility during optimization. As a result, a steep gradient in the dose distribution at the regions of interface between the targets and normal critical organs could be achieved and treatment quality was improved. In the second study, a thorough dosimetric comparison between conventional 2-dimensional (2D) RT and IMRT plans was conducted to determine, with reference to outcome of 2D treatments, the extended tolerance dose limits for the critical organs, especially that of the brainstem and spinal cord, and their planning organ at risk volume. Such data could then serve as reference in IMRT planning when the dose of critical organs need be exceeded in order to allow adequate dose to a very close by target. In the third study, the feasibility of using interpolated contours for segmentation of targets and OARs in IMRT planning was investigated. The result indicated that the use of interpolated contours in IMRT planning could significantly reduce the contouring time by about 50% without degrading the target coverage and OARS sparing. In the final study, an array of dose constraint templates that could accommodate different degrees of overlap between the targets and OARs, together with a template selection program, were developed to improve the efficiency of IMRT planning. By applying the methods and tools developed, IMRT treatment planning of advanced NPC could become more efficient and less dependent on planner's experience. / Chau, Ming Chun. / Adviser: Anthony Chan Tak Cheung. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0948. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 118-128). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / School code: 1307.

A comprehensive immunohistochemical study was carried out to investigate the phenotypes and prevalence of intraepithelial lymphocytes in NPC samples semi-quantitatively. CD25+/FOXP3+ T-cells were highly prevalent in primary NPCs, suggesting the presence of the immunosuppressive Tregs in tumor microenvironments. The low abundance of CD4+ T-cells, and the positive correlation between FOXP3 and CD8 staining in NPC samples imply that CD8+FOXP3+ Tregs may be present and play role in the suppression of anti-tumor immune response in NPC patients. The involvement of chemokine in the migration of tumor-infiltrating lymphocytes was studied. Chemokine ligand 20 (CCL20) was overexpressed in all EBV-positive NPC cell lines and xenografts compared to EBV-negative NPC, and immortalized normal nasopharynx epithelial cell lines. The presence of CCL20 was also found in primary tumors but not in normal epithelium. Furthermore, the ability of LMP1 to upregulate CCL20 expression in epithelial cells indicates that EBV may induce the production of chemokine involved in lymphocyte migration. / Epstein-Barr virus (EBV) is invariably associated with the development of nasopharyngeal carcinoma (NPC). Although the association of EBV and cancer has been reported for about four decades, it is still not clear how EBV latent infection contributes to the transformation of nasopharyngeal epithelial cells. The aims of this study are to identify EBV-regulated cellular genes and pathways and to determine the potential role of EBV in the modulation of anti-tumor immune responses in NPC. / In summary, EBV plays critical roles in the development of NPC by regulation of multiple cellular genes and pathways such as the Notch signaling cascade, and modulation of anti-tumor immune responses through the induction of chemokine important in migration of immune cells. / Notch signaling pathway functions in diverse cellular processes such as proliferation, apoptosis, adhesion, and epithelial to mesenchymal transition. In the current study, aberrant expression of activated Notch1 receptor (NICD), Notch ligand (Jagged1), negative regulator of Notch ( NUMB) and Notch downstream effector (HEY1) was detected in NPC cell lines and xenografts. Overexpression of NICD, Jagged1 and HEY1 proteins was also commonly found in primary tumors of NPC. / Transfection of Jagged1 to normal nasopharynx epithelial cells resulted in increased cell proliferation. Moreover, EBERs, which is abundantly expressed in EBV-positive NPC tumors, was capable of inducing the expression of Jagged1 in epithelial cells. The current data shows that Notch signaling pathway is aberrantly activated by the deregulated expression of multiple Notch components in NPC. The induction of Jagged1 by EBERs also implies the potential role of EBV in the activation of Notch signaling cascade in NPC. / Using high-density oligonucleotide microarray, expression profiles of EBV-infected NPC cell lines, HK1+EBV and HONE1+EBV, and their uninfected counterparts, HK1 and HONE, were generated. From the microarray results, six EBV-upregulated (JDP2, IL8, ATP6V0E2L, PLAP, PIK3C2B and AKR1B10 ) and three EBV-downregulated genes (BACE2, PADI3 and MMP1) were identified in both HK1 and HONE1 cells upon EBV latent infection. One hundred and thirty-eight and seventy-six genes were also found to be differentially modulated by EBV in HK1 and HONE1 cells, respectively. This study shows that cellular genes involved in wide range of biological processes and cellular functions are differentially regulated by EBV, which suggest that EBV modulates multiple pathways and processes during NPC tumorigenesis. / Hui, Wai Ying. / Adviser: Kw Lo. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0806. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (leaves 166-204). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese. / School code: 1307.

Cheung Mei-chun. / "January 2003." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 66-94). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

S.pneumoniae yra vienas dažniausiai sutinkamų bakterinių patogenų, sukeliančių ligas mažiems vaikams. S.pneumoniae, ypatingai atskirų jo serotipų, paplitimas, jautrumas antibakteriniams preparatams yra skirtingas įvairiose šalyse ir nuolat kinta. Pagrindinis S.pneumoniae infekcijos šaltinis – sveiki ikimokyklinio amžiaus vaikai, nešiojantys pneumokoką nosiaryklėje. Šio tyrimo tikslas – išanalizuoti S.pneumoniae nešiojimo nosiaryklėje dažnumą tarp sveikų ir dažnai sergančių kvėpavimo takų ligomis vaikų Vilniuje, nustatyti vyraujančius S.pneumoniae serotipus ir jų jautrumą antibakteriniams preparatams. Taip pat nustatyti dažno antibakterinių preparatų vartojimo įtaką pneumokokų nešiojimui nosiaryklėje, atskirų serotipų paplitimui, jautrumui antibakteriniams preparatams. Įvertinti gleivinių imuninį atsaką į pneumokokinę infekciją, pagal seilėse esančius imunoglobulinus. Išvados: 1. Nustatytas dažnas - apie 40% S.pneumoniae nešiojimas tirtų vaikų nosiaryklėse, vyrauja invazines ligas sukeliantys S.pneumoniae serotipai. 2. Jautrumas penicilino grupės antibakteriniams preparatams išlieka nekintantis ir sudaro 90% visų tirtų S.pneumoniae padermių. Jautrumas makrolidų grupės antibakteriniams preparatams palaipsniui mažėja, nuo 96% iki 82 %; tai susiję su dažnėjančiu naujos kartos makrolidų vartojimu. 3. Daugkartinis antibakterinių preparatų vartojimas neapsaugo nuo S.pneumoniae nešiojimo nosiaryklėje. 4. Vaikų gleivinių imuninis atsakas skirtingas atskiriems S.pneumoniae serotipams... [toliau žr. visą tekstą] / Streptococcus pneumoniae, or pneumococcus, is Gram-positive, alpha-hemolytic, bile soluble diplococcus aerotolerant anaerobe and a member of the genus Streptococcus (phylum Firmicutes). Streptococcus pneumoniae (S.pneumoniae) is known in medical microbiology as the pneumococcus. It has a polysaccharide capsule that acts as a virulence factor for the organism; more than 90 different serotypes are known, and these types differ in virulence, prevalence, and extent of drug resistance. Streptococcus pneumoniae is a normal inhabitant of the human upper respiratory tract. The serotype distribution among nasopharyngeal carriage isolates varies by country, age-group, origin, type of cohort. Pneumococcal disease will not occur without preceding nasopharyngeal colonization with the homologous strain. In addition, pneumococcal carriage is believed to be an important source of horizontal spread this pathogen within the community. Because the highest frequency of the pneumococcal colonization and the highest crowding index are found in young children, this risk group is thought to be the most important vector for horizontal dissemination of pneumococcal strains within the community. In Europe asymptomatic nasopharyngeal carriage of pneumococcal infection is 30% -60% and in Asia or Africa it is up to 98%. Carriage rate of different serotypes in the same population changes during the time. S.pneumoniae is a common bacterial agent that causes a wide variety of infections including mucosal... [to full text]

Streptococcus pneumoniae, or pneumococcus, is Gram-positive, alpha-hemolytic, bile soluble diplococcus aerotolerant anaerobe and a member of the genus Streptococcus (phylum Firmicutes). Streptococcus pneumoniae (S.pneumoniae) is known in medical microbiology as the pneumococcus. It has a polysaccharide capsule that acts as a virulence factor for the organism; more than 90 different serotypes are known, and these types differ in virulence, prevalence, and extent of drug resistance. Streptococcus pneumoniae is a normal inhabitant of the human upper respiratory tract. The serotype distribution among nasopharyngeal carriage isolates varies by country, age-group, origin, type of cohort. Pneumococcal disease will not occur without preceding nasopharyngeal colonization with the homologous strain. In addition, pneumococcal carriage is believed to be an important source of horizontal spread this pathogen within the community. Because the highest frequency of the pneumococcal colonization and the highest crowding index are found in young children, this risk group is thought to be the most important vector for horizontal dissemination of pneumococcal strains within the community. In Europe asymptomatic nasopharyngeal carriage of pneumococcal infection is 30% -60% and in Asia or Africa it is up to 98%. Carriage rate of different serotypes in the same population changes during the time. S.pneumoniae is a common bacterial agent that causes a wide variety of infections including mucosal... [to full text] / S.pneumoniae yra vienas dažniausiai sutinkamų bakterinių patogenų, sukeliančių ligas mažiems vaikams. S.pneumoniae, ypatingai atskirų jo serotipų, paplitimas, jautrumas antibakteriniams preparatams yra skirtingas įvairiose šalyse ir nuolat kinta. Pagrindinis S.pneumoniae infekcijos šaltinis – sveiki ikimokyklinio amžiaus vaikai, nešiojantys pneumokoką nosiaryklėje. Šio tyrimo tikslas – išanalizuoti S.pneumoniae nešiojimo nosiaryklėje dažnumą tarp sveikų ir dažnai sergančių kvėpavimo takų ligomis vaikų Vilniuje, nustatyti vyraujančius S.pneumoniae serotipus ir jų jautrumą antibakteriniams preparatams. Taip pat nustatyti dažno antibakterinių preparatų vartojimo įtaką pneumokokų nešiojimui nosiaryklėje, atskirų serotipų paplitimui, jautrumui antibakteriniams preparatams. Įvertinti gleivinių imuninį atsaką į pneumokokinę infekciją, pagal seilėse esančius imunoglobulinus. Išvados: 1. Nustatytas dažnas - apie 40% S.pneumoniae nešiojimas tirtų vaikų nosiaryklėse, vyrauja invazines ligas sukeliantys S.pneumoniae serotipai. 2. Jautrumas penicilino grupės antibakteriniams preparatams išlieka nekintantis ir sudaro 90% visų tirtų S.pneumoniae padermių. Jautrumas makrolidų grupės antibakteriniams preparatams palaipsniui mažėja, nuo 96% iki 82 %; tai susiję su dažnėjančiu naujos kartos makrolidų vartojimu. 3. Daugkartinis antibakterinių preparatų vartojimas neapsaugo nuo S.pneumoniae nešiojimo nosiaryklėje. 4. Vaikų gleivinių imuninis atsakas skirtingas atskiriems S.pneumoniae serotipams... [toliau žr. visą tekstą]

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-07-19T21:35:50Z No. of bitstreams: 1 Jailton de Azevedo Silva Junior Estudo da colonização....pdf: 1101716 bytes, checksum: 049972199c76bb97406fc006c2ba9c27 (MD5) / Made available in DSpace on 2012-07-19T21:35:50Z (GMT). No. of bitstreams: 1 Jailton de Azevedo Silva Junior Estudo da colonização....pdf: 1101716 bytes, checksum: 049972199c76bb97406fc006c2ba9c27 (MD5) Previous issue date: 2011 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / Streptococcus pneumoniae constitui um dos mais importantes patógenos bacterianos do trato respiratório, podendo causar infecções invasivas e não invasivas, levando a altas taxas de morbi-mortalidade, particularmente em crianças menores de cinco anos de idade. A bactéria ganha acesso ao hospedeiro através da colonização da nasofaringe, que representa um importante reservatório para a transmissão deste patógeno na comunidade, contribuindo para a disseminação horizontal de S. pneumoniae entre os indivíduos de uma população. No presente estudo, procuramos caracterizar o perfil de colonização nasofaringeana por S. pneumoniae em pacientes menores de cinco anos de idade com suspeita clínica de pneumonia, atendidos na Unidade de Saúde de São Marcos, Bairro de Pau da Lima, Salvador, no ano de 2009. Um total de 205 swabs foram coletados entre as crianças consideradas elegíveis para o estudo. Os isolados de S. pneumoniae foram identificados através de métodos microbiológicos clássicos e a determinação do sorogrupo/sorotipo foi realizada empregando-se a técnica de Multiplex-PCR. A sensibilidade a sete antimicrobianos foi testada através da técnica de microdiluição em caldo, sendo que os isolados com CIM para penicilina ≥ 0,125 μg/mL foram considerados não-susceptíveis. A técnica de PFGE foi realizada para 26 isolados correspondentes aos sorotipos mais frequentes e associados a não-sensibilidade à penicilina (sorotipos 14, 19F e 23F). Um total de 72 (35,1%) crianças foram diagnosticadas com pneumonia, sendo 39 (54,2%) menores de dois anos de idade. A taxa de colonização geral foi de 50,2%, não havendo diferença entre essas taxas quando se considerou o grupo de crianças confirmadas e suspeitas para pneumonia. Crianças na faixa etária de 36 a 47 meses formaram o grupo com maior risco de ter pneumonia bacteriana (OR: 3.17 [1.29-7.88]). Entre os sorotipos encontrados, o sorogrupo 6 (6A/6B) (17,3%) foi predominante, seguido dos sorotipos 14 (15,4%), 19F (10,6%), sorogrupo 15 (15B/15C) (9,6%), 23F (6,7%) e o sorotipo 19A (6,7%). Os demais sorotipos e sorogrupos compreenderam 33,7%. O padrão de sorotipos foi semelhante aqueles encontrados nos casos de meningite pneumocócica na cidade de Salvador. Um total de 41 isolados (39,8%) apresentaram CIM ≥ 0,125 μg/mL para penicilina e a resistência a SMX-TMP foi identificada em 69,2% dois isolados. A tipagem por PFGE identificou 11 padrões eletroforéticos, sendo que a maioria dos isolados do sorotipo 14 estavam relacionados a clones amplamente disseminados entre os casos de doença pneumocócica (“A” e “GK”). Um total de 50,5% dos isolados foram de sorotipos inclusos na vacina decavalente (PCV10) e considerando os isolados não-susceptíveis à penicilina, esta representatividade foi de 90,2%. O estudo ressalta a importância de um contínuo monitoramento do perfil de sorotipos na colonização nasofaringeana por S. pneumoniae, no período pós-vacina e da necessidade de busca de novos métodos de diagnóstico que otimizem a definição da pneumonia. / Streptococcus pneumoniae is one of the most important bacterial pathogens of the respiratory tract, causing invasive and noninvasive infections, leading to high rates of morbidity and mortality, particularly among children under five years old. The bacterium gains access to the host by colonizing the nasopharynx, which represents an important reservoir for transmission of this pathogen in the community, contributing to the horizontal spread of S. pneumoniae among individuals in a population. In this study, we sought to characterize the profile of nasopharyngeal colonization by S. pneumoniae in patients under five years of age with clinical suspicion of pneumonia seeking medical care at the Unidade de Saúde de São Marcos, District of Pau da Lima, Salvador, in 2009. A total of 205 swabs were collected from children eligible for the study. The isolates of S. pneumoniae were identified by classical methods and the determination of the serogroup / serotype was performed using the technique of multiplex-PCR. The sensitivity to seven antibiotics was tested by the microdilution broth method, and strains with MIC for penici≥lli n 0.125 mg/mL were considered non-susceptible. The PFGE technique was performed for 26 strains corresponding to serotypes more frequent and associated with nonsusceptibility to penicillin (serotypes 14, 19F and 23F). A total of 72 (35.1%) children were diagnosed with pneumonia, 39 (54.2%) less than two years old. The overall colonization rate was 50.2%, with no difference between those rates when considering the children's group confirmed and suspected to pneumonia. Children aged 36 to 47 months formed the group with higher risk for bacterial pneumonia (OR: 3.17 [1.29-7.88]). Among the serotypes, serogroup 6 (6A/6B) (17.3%) predominated, followed by serotypes 14 (15.4%), 19F (10.6%), serogroup 15 (15B/15C) (9.6%), 23F (6.7%) and serotype 19A (6.7%). The other serotypes and serogroups comprised 33.7%. The pattern of serotypes was similar to those found in cases of pneumococcal meningitis in Salvador. A total of 41 isolates (39.8%) had MIC ≥ 0.125 mg / mL and resistance to TMP-SMX was identified in 69.2% of isolates. Molecular typing identified 11 electrophoretic patterns, whereas most isolates of serotype 14 was associated with widespread clones among cases of pneumococcal disease ("A" and "GK"). The 10-valent conjugate vaccine (PCV10) implemented in Brazil shows a coverage of 50.5% from serotypes in the population and 90.2% for isolates not susceptible to penicillin. The study underscores the importance of continued monitoring of the prevalence of serotypes in nasopharyngeal colonization by S. pneumoniae, in the post-vaccine era, and the need to search for new methods for diagnosing pneumonia.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2014-11-24T17:17:11Z No. of bitstreams: 1 Ana Paula Menezes.Colonização...pdf: 2951203 bytes, checksum: 9bb7bf3f9b13f1072a22b34565226bf2 (MD5) / Made available in DSpace on 2014-11-24T17:17:11Z (GMT). No. of bitstreams: 1 Ana Paula Menezes.Colonização...pdf: 2951203 bytes, checksum: 9bb7bf3f9b13f1072a22b34565226bf2 (MD5) Previous issue date: 2014 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Streptococcus pneumoniae é um dos agentes etiológicos mais importantes em infecções adquiridas na comunidade. Este patógeno coloniza o trato respiratório de indivíduos saudáveis, apresentando maior prevalência entre 1 e 2 anos de idade (aproximadamente 50%) e depois diminui com a idade adulta (aproximadamente 10%). A alta incidência das doenças pneumocócicas e a crescente resistência aos antimicrobianos, favoreceu a introdução das vacinas conjugadas (ano de 2000). Após a introdução das vacinas conjugadas foi observado à queda na incidência da doença pneumocócica e diminuição da prevalência de colonização por sorotipos vacinais. Em contrapartida vem sendo notado o aumento de casos de doença sorotipos não vacinais. Por isso a importância de verificar a dinâmica da colonização nasofaringeana por pneumococos em crianças < 5 anos de idade antes da introdução da vacina. Foram selecionadas radomicamente 203 crianças residentes da comunidade de Pau da Lima, Salvador, Bahia, das quais foi colhido a amostra nasofaringeana em quatro períodos durante um ano com intervalo de três a quatro meses entre cada coleta. No período de janeiro de 2008 a janeiro de 2009 foram colhidos um total de 721 swabs, sendo 398 positivos para pneumococos (56%). Os fatores de risco associados a colonização foram: aglomeração, contato com crianças menores de 2 anos de idade e presença de ITRS. Os sorotipos vacinais mais prevalentes foram o 6A/B, 19F, 14, 23F e 18. O sorotipo 19F foi o segundo mais prevalente e associado com a não susceptibilidade à penicilina. Dezesseis isolados do sorotipo 19F foram não tipáveis (NT) pelo método de multiplex PCR; sendo identificados apenas quando submetidos a reação de Quellung. Por isso, foi desenvolvido um novo primer para identificação deste sorotipo. Entre os sorotipos não vacinais os mais prevalentes foram o 16F, 15B/C, 6C e 34. A não susceptibilidade a penicilina e TMP/SMX foi de 38,5% e 58,0%, respectivamente. Pode-se observar que 91% dessas crianças estiveram colonizadas pelo menos uma vez durante o seguimento e que sorotipos não vacinais (34 e 15B/C) persistiram colonizando a mesma criança em mais de uma coleta. Ao longo do estudo, clones internacionais foram identificados na comunidade como o “Spain9V-3” (ST 156) e “Portugal 19F-21” (ST 177), relacionados com a não susceptibilidade a penicilina. O monitoramento da dinâmica da colonização pós-vacina é importante para a adequação da prevenção na era das vacinas conjugadas com limitado número de sorotipos. / Streptococcus pneumoniae is one of the most important etiologic agents in community-acquired infections. This pathogen colonizes the respiratory tract of healthy individuals shortly after birth, with higher prevalence of between 1 and 2 years of age (approximately 50%) and then decreases with age reaching adult rates below 10%. The high incidence and increasing antimicrobial resistance, favored the introduction of conjugate vaccines in 2000. After the introduction of conjugate vaccines a decreasing incidence of pneumococcal disease and carriage rates by vaccine serotypes was observed. In contrast we observe an increase in number of cases of disease and carriage by non-vaccine serotypes. Thus, this study aims to determine the dynamics of nasopharyngeal colonization by pneumococci in children <5 years of age after introduced the conjugate vaccine. A total of 203 children were random selected at the community of Pau da Lima in Salvador, Bahia, of whom the nasopharyngeal swab was collected in four periods with interval of 3 to 4 months between each collection. A total of 721 swabs were collected from January 2008 to January 2009, with 398 positive for pneumococci (56%). Risk factors associated with colonization were: crowding, contact with children lower than 2 years old and the presence of URTI. and The most prevalent vaccine serotype were 6A / B, 19F, 14; 23F and 18. The serotype 19F was the second most prevalent and associated with non-susceptibility to penicillin. Sixteen isolates of serotype 19F were nontypeable (NT) by the method of multiplex PCR; being identified only when submitted to Quellung reaction. Therefore, we developed a new primer to identify this serotype. The most prevalent non-vaccine serotypes were 16F, 15B / C, 6C and 34. The non-susceptibility to penicillin and TMP / SMX was 38.5% and 58.0%, respectively. It can be seen that 91% of the children were colonized at least once during follow-up and non-vaccine serotypes (34 and 15B / C) persisted colonizing the same child on more the one collection. Throughout the study, international clones were identified circulating at this community as the Spain9V-3 (ST 156) and Portugal 19F-21 (ST 177), all related with non-susceptibility to penicillin. The monitoring of the dynamics of post-vaccine colonization is important for the adequacy of prevention in the era of conjugated vaccines with limited repertoire of serotypes.