Background: Antibiotics are prescribed frequently for upper respiratory tract infections (URTIs) despite the fact that most of them do not require antibiotics. This over-prescription contributes to antibiotic resistance which is a major health problem. Physicians perceive that patients’ expectations influence their antibiotic prescribing practice. Methods: As the first phase of the thesis, we conducted a systematic review to determine the effectiveness of patient-oriented interventions to reduce unnecessary use of antibiotics for URTIs. As the second phase, we conducted a qualitative descriptive study to explore patients’ views about URTIs and identify ways they manage them by using semi-structured interviews based on Common Sense-Self-Regulation Model (CS-SRM). Results: Our systematic review included 14 studies which based on their interventions were classified into two major categories: delayed prescriptions and patient/public information and education interventions. Our meta-analysis revealed that almost all studies with delayed prescription significantly reduced use of antibiotics for URTIs. Our subgroup analysis showed that prescriptions that were given at a later time and prescriptions that were given at the index consultation had similar effects regarding antibiotic use. The small number of included studies in the patient/public information and education group did not allow us to make a definite conclusion on their effectiveness. For the qualitative study, 15 individuals were interviewed. almost all participants mentioned that they only visited their doctor if their symptoms got progressively worse and they could no longer self-manage URTI symptoms. When visiting a doctor, most participants reported that they expected to receive an examination and an explanation for their symptoms. Discussion: Patient-oriented interventions (especially delayed prescriptions) may be effective in reducing antibiotic use or prescription for URTIs in patients. Further research is needed to investigate the costs and feasibilities of implementing these interventions as part of routine clinical practice. Our participants reported good knowledge regarding the likely lack of benefit from antibiotics for URTIs. The results suggest a discrepancy between our participants’ reported reasons for visiting doctors and doctors’ perceptions about patients’ reason for their visit identified in previous studies. Focusing on interventions that facilitate the communication between patients and doctors, instead of providing more education to public may help in reducing the use of unnecessary antibiotics.

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第20623号 / 社医博第81号 / 社新制||医||9(附属図書館) / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 木原 正博, 教授 中川 一路, 教授 平家 俊男 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

IV. ABSTRACT The human metapneumovirus is a novel paramyxovirus associated with acute respiratory infections in children, adults, elderly and immunocompromised individuals. It has a worldwide distribution and the prevalence range between 1.5% to 25% in individuals with respiratory infections. Based on phylogenetic analysis 2 distinct genetic groups (A and B) that are sub-divided into four subgroups (A1, A2, B1 and B2) have been shown to circulate. Until recently, there was no information on the molecular epidemiology and the clinical characteristics of the hMPV in Africa, including South Africa, a region with a high prevalence of paediatric human immunodeficiency virus type-1 (HIV) infection. The molecular epidemiology and clinical characteristics of the hMPV in South Africa was investigated over a three period (2000-2002) in children hospitalized with lower respiratory tract infection. The children were part of a cohort participating in a phase 3 clinical trial investigating the efficacy of a 9-valent-pneumocococcal protein-polysaccharide conjugate vaccine (PCV). The objectives of the study were: i. to investigate the molecular epidemiology of hMPV in South Africa; ii. characterize the burden of hMPV disease and determine the clinical features of hMPV-LRTI in children infected and not infected by HIV; iii. probe the role of Streptococcus pneumoniae in the pathogenesis of hMPV-LRTI. The overall prevalence of hMPV in children hospitalized with lower respiratory tract infections (LRTI) was 7.4%. The mean age of children with hMPV associated LRTI (hMPV-LRTI) in South Africa was 13.3 months (range 1.4-49.2 months), with HIV infected children being older than children not infected with HIV (mean [range] 17.6 [4.5-44.3] vs. 12.3 [1.4-49.2] months; P=0.007). The incidence of hMPV-LRTI was 5.0 (95%C.I.3.3-7.5) fold greater in HIV infected children (incidence rate: 2 504 [95%C.I. 1 683-3 577] per 100 000) than in HIV uninfected children (incidence rate: 505 [95%C.I. 409-618] per 100 000, P<0.0001). Human metapneumovirus was identified less frequently than RSV but more commonly than other studied respiratory viruses. The double-blind PCV-9 vs. placebo controlled trial was used to probe the role of pneumococcal co-infections contributing to the pathogenesis of severe hMPV-LRTI. The incidence of hospitalization for hMPV-LRTI was reduced by 46% (95%, CI, 25-63; P=0.0002) in PCV-9 vaccinees compared to placebo recipients. This inferred that coinfection with Streptococcus pneumoniae was integral to the pathogenesis of hMPV-LRTI requiring hospitalization. Both groups of the hMPV circulated during the three year period including concurrent circulation of multiple subtypes of the virus. There was a transition from group B to group A subtype virus as the dominant circulating virus over sequential years. Sequence analysis of the two attachment glycoproteins (F and G), showed the F gene protein to be highly conserved, in contrast the attachment protein gene (G protein) was highly variable particularly in the extracellular domain between lineages. Repeat hMPV-LRTI by either homologous or heterologous strains within 3 months of each other suggested that natural infection did not confer complete immunity to hMPV. The present study demonstrated that hMPV is a leading pathogen associated with LRTI among children in Africa and indicated that occult pneumococcal co-infections’ were integral in the pathogenesis of hMPV-LRTI requiring hospitalization. Additionally, this is the first study to have characterized the molecular epidemiology of hMPV in Africa and provides insight as to issues that may exist regarding the design of an hMPV vaccine.

Thesis (Ph.D.(Microbiology)) -- University of Limpopo, 2022 / Respiratory tract infections (RTIs) are frequent ailments among humans and are a high burden to public health. One strategy for the development of new therapies against pathogenic bacteria such as Mycobacterium tuberculosis is to target essential biosynthetic pathways of its metabolism. The aim of this study was to evaluate and target the biosynthesis of aromatic amino acids (shikimate pathway) of Mycobacterial spp using medicinal plant extracts. The selection of the plants in this study was based on their ethnopharmacological use for the treatment of tuberculosis infections and related symptoms. The leaves were dried at ambient temperatures and ground to fine powder. The powdered material was extracted with hexane, dichloromethane, acetone, methanol and water. Phytochemical screening was done using standard protocols that tested for tannins, saponins, terpenoids, alkaloids, flavonoids, steroids, anthraquinones, phlobatannins, quinones, and betacynins. Phytochemical fingerprints were established using thin layer chromatography (TLC) where three mobile phases varying in polarity were used to develop the chromatograms. Total Phenolics, flavonoids, flavonols, tannins, alkaloids and proanthocyanidin contents were quantified using UV/Vis spectrometry. Spectrometric quantification of the free radical (DPPH) scavenging activity and ferric (potassium ferricyanide) reducing power were performed. The heat-dependent bovine serum albumin and egg albumin denaturation assays were used to evaluate anti-inflammatory activity. Antimycobacterial activity was screened using bioautography assay in qualitative analysis. Quantitatively, broth microdilution assay was used to determine the minimal inhibitory concentrations. The Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 interference genetic editing technique was used to evaluate and validate the essentiality of the aromatic amino acids in Mycobacteria to further determine the vulnerability and draggability of the transketolase (tkt) and DAHPs (aroG) genes. Plasmid, PLJR962, was used for the CRISPRi/dCas9 gene knockdown experiments. The integrating CRISPRi plasmid expressed both sgRNA with the targeting region (for tkt or aroG) and the dCas9 handle which is under control of the anhydrotetracycline (ATC) inducible promoters. The spot assay and growth curves were used to for phenotypic characterisation and gene knockdown experiments. RNA microarray (qPCR) was used to evaluate the level of expression inhibition of tkt gene . Mechanism of action of plants extracts bioactive components were predicted based on synergy between gene knockdown, shikimate inhibitors and the plant extracts. To evaluate whether the shikimate intermediates may rescue gene depleted M. smegmatis hypomorphs, the cultures were grown in L-tryptophan, L-phenylalanine, L-tyrosine and shikimic acid and growth curves constructed. Cytotoxicity of the extracts was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on Vero cell lines and phorbol 12-myristate 13-acetate (PMA) differentiated THP-1 macrophages. Phytochemical analysis showed that the various extracts had various polar and non-polar compounds which belonged to phenolics, saponins, steroids, terpenoids, alkaloids, cardiac glycosides and resins. Numerous non-polar compounds from Gardernia volkensii, Senna petersiana, Ficus sur had antimycobacterial activity against M. smegmatis in bioautography. Remarkably, acetone extracts from S. petersiana, Acacia senegal, Carissa bispinosa, P. africanum and C. gratissimus that had moderate to low antimycobacterial activity against wild type M. smegmatis (mc2 155) demonstrated improved inhibitory activity against the tkt PAM1 M. smegmatis CRISPRi mutant. Only the acetone Clerodendrum glabrum, Croton gratissimus, Peltophorum africanum and Gardenia volkensii demonstrated activity against M. tuberculosis H37Rv. These results suggest that the employment of CRISPRi in M. tuberculosis to develop screening models may increase changes of obtaining bioactive chemical species because the tkt gene knockdown was showed to possess the ability to potentiate the antimycobacterial activity of the plant extracts. An added advantage of the plant extracts is their antioxidant and anti-inflammatory activities which may benefit the host immune system during treatment of infection by reducing free radicals and pro-inflammatory agents that perpetuate the infection. Non polar compounds were found to generally have higher anti-inflammatory activity than the polar counterpart for all the plant extracts. These results suggest that the non-polar compounds from the tested extracts may not only confer antimycobacterial effects, but also anti-inflammatory activities. A. senegal, G. volkensii, F. sur, S. petersiana and C. glabrum were found to be toxic to the Vero cell line. However, purification techniques may circumvent their toxic effects. This study demonstrated that the amino acid biosynthesis is a potential antimycobacterial drug target because it was found to be essential, vulnerable and druggable by medicinal plant extracts / University of Limpopo and National Research Foundation (NRF-DAAD In-Country Doctoral Scholarship Programme)

Background: Humanmilk oligosaccharides (HMOs) support and concurrently shape the neonatal immune system through various mechanisms. Thereby, they may contribute to lower incidence of infections in infants. However, there is limited evidence on the role of individual HMOs in the risk of otitis media (OM), as well as lower and upper respiratory tract infections (LRTI and URTI, respectively) in children up to 2 years. Objective: To investigate whether individual HMO concentrations measured at 6 weeks of lactation were associated with risk of OM, LRTI or URTI up to 2 years in breastfed infants. Associations with OM, LRTI and URTI were determined for the most prominent human milk oligosaccharides including 13 neutral, partly isomeric structures (trioses up to hexaoses), two acidic trioses, and lactose. Design: HMO measurements and physician reported data on infections were available from human milk samples collected at 6 weeks postpartum (n = 667). Associations of HMOs with infections were assessed in crude and adjusted models using modified Poisson regression. Results: Absolute concentrations (median [min, max], in g/L) of 2′-fucosyllactose (2′-FL) tended (p = 0.04) to be lower, while lacto-N-tetraose (LNT) was higher in the milk for infants with OM in the 1st year of life (p = 0.0046). In the milk of secretor mothers, LNT was significantly higher in the milk for infants with OM (RR [95% CI]: 0.98 [0.15, 2.60]) compared to infants without OM (RR [95% CI]: 0.76 [0.14, 2.90]) at 1 year (p = 0.0019). No statistically significant milk group differences and associations were observed for OM, LRTI, and URTI (p > 0.0031). Conclusion: Our findings suggest that neither prominent neutral individual HMOs (ranging from 2′-FL to LNDFHs) nor acidic human milk sialyllactoses or lactose are significantly associated with a reduced or increased risk of infections in infants up to 2 years of age. Further research is needed to determine whether specific HMOs could potentially reduce the incidence or alleviate the course of distinct infections in early life.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 5 uppsatser.

Orientadores: Emilio Carlos Elias Baracat, Clarice Weis Arns / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T23:20:49Z (GMT). No. of bitstreams: 1 Riccetto_AdrianaGutLopes_D.pdf: 18036035 bytes, checksum: 951a577babe97ac325d8f7e4a0ea459c (MD5) Previous issue date: 2006 / Resumo: Infecções respiratórias agudas são a causa mais comum de internação hospitalar em pediatria.O Vírus Sincicial Respiratório (VSR) é o principal agente destas infecções, com apresentação clínica de bronquiolite ou pneumonia. Os casos graves ocorrem principalmente em pacientes prematuros, com pneumopatias crônicas, cardiopatias e imunodeficiências. Uma proporção de pacientes internados necessita de ventilação pulmonar mecânica invasiva (VPMI). O acompanhamento após a fase aguda mostra frequentemente obstrução respiratória recorrente. Objetivos: Descrever as características epidemiológicas e clínicas de lactentes menores de 12 meses, hospitalizados com doença respiratória aguda baixa, determinando fatores associados à ventilação mecânica e à infecção pelo VSR, e as características evolutivas tardias desta população. Casuística e métodos: Estudo de corte prospectivo, realizado de 01 de abril a 30 de setembro de 2004, em dois hospitais universitários da região de Campinas, São Paulo, Brasil. Foram avaliados 152 lactentes de 0 a 12 meses internados com diagnóstico inicial de doença respiratória aguda baixa. Realizou-se avaliação clínica e pesquisa do VSR, por imunofluorescência direta (EFD), em secreção nasofaríngea Os pacientes foram divididos em dois grupos, de acordo com a necessidade de VPMI e presença do VSR, comparando-se os fatores prognósticos. Seis a 12 meses após a internação hospitalar, os pacientes com IFD positiva para VSR e os submetidos à VPMI foram convocados e avaliados quanto à presença de sibilância recorrente. A associação entre fatores de risco e desfecho estudado foi analisada por Risco Relativo (RR) e intervalos de confiança (IC95%). Para comparação de proporções foi utilizado o teste Qui-quadrado e teste Exato de Fischer. Para comparação das medidas contínuas entre dois grupos foi aplicado o teste de Mann-Whitney. O nível de significância adotado para os testes estatísticos foi de 5%. Resultados. A pesquisa de VSR foi realizada em 149 lactentes, com positividade de 17,4% (26 pacientes) Vinte e um pacientes (13,8%) foram submetidos à VPMI e os fatores significativamente associados ã VPMI foram: idade menor de 3 meses (RR=2,35, IC95%: 1,06-5,22) e tempo de aleitamento materno menor que um mês (RR=3,15, IC95%: 1,35-7,35). Na comparação dos grupos com e sem a presença de VSR os fatores associados à infecção foram: idade gestacional abaixo de 35 semanas (RR=4,17, IC95%:2,21-7,87), peso ao nascer menor de 2500g (RR=2,69, IC95%: 1,34-5,37) e escolaridade materna menor que 5 anos (RR=2,28, IC 95%: 1,13-4,59). Na evolução clínica em seguimento ambulatorial, 26 de 41 convocados compareceram (63,4%), destes 19,2% eram não sibilantes, 57,7% eram sibilantes intermitentes e 23,1% sibilantes persistentes. Na comparação entre os grupos não sibilantes e sibilantes intermitentes, ocorreu diferença significativa na variável hospitalização após a alta, ocorrendo apenas no segundo grupo de pacientes. Na comparação entre os grupos não sibilantes e sibilantes persistentes leves/moderados, não ocorreram diferenças significativas nas variáveis analisadas. Conclusões: A incidência do VSR foi de 17,5% entre os lactentes internados com doença respiratória aguda baixa. Os fatores associados à VPM1 foram: idade menor que 3 meses e tempo de aleitamento materno menor que 1 mês Os fatores associados à aquisição do VSR foram idade gestacional abaixo de 35 semanas, peso ao nascer menor de 2500g e escolaridade materna menor que 5 anos. Na evolução clínica tardia, os lactentes com pesquisa positiva para VSR e os lactentes submetidos à VPMI apresentaram-se como sibilantes intermitentes, sem necessidade de corticoterapia inalatória e com maior número de hospitalizações após a alta / Abstract: In pediatrics, acute respiratory infections are the most common cause of hospitalization. The Respiratory Syncytial Virus (RSV) is the main agent responsible for these infections that are clinically manifested as bronchiolitis or pneumonia Severe cases occur mostly in premature patients who have chronic pneumopathies, cardiopathies and immunodeficiencies. Some of the hospitalized patients require invasive mechanical ventilation (IMV) Follow up after the acute phase often demonstrates recurring respiratory obstruction. Objectives: to describe the epidemiological and clinical characteristics of infants under the age of 12 months hospitalized with acute lower respiratory tract infections, determine factors related to mechanical ventilation and RSV as well as delayed evolutional characteristics of this population. Methods and Cases: This was a prospective cohort study conducted from 2001 April to 2001 September at two university hospitals in the region of Campinas, Sao Paulo. An evaluation was performed of 152 infants aged 0 to 12 months, hospitalized with an initial diagnosis of acute lower respiratory tract diseases Direct Immunofluorescence Assay (DFA) was used to perform a clinical research and assess RSV in the nasopharyngeal secretion. The patients were divided into two groups according to the need for IMV as well as the presence of RSV and their prognostic factors were compared. Six to twelve months after hospitalization, patients with DFA positive for RSV as well as patients who were subjected to IMV were recalled and checked for the presence of recurrent wheezing. The relation between risk factors and outcome was analyzed by applying Relative Risk (RR) and Confidence Intervals (CI 95%). The chi-square test and the Fisher Exact test were used for comparing proportions. Continuous measures were compared using the Mann Whitney test. The significance level adopted for statistical tests was 5%. Results: RSV research was conducted on 149 infants, revealing 17.4% positivity (26 patients). Twenty-one patients (13 8%) were subjected to IMV' and factors significantly associated were age below three months (RR=2.35, IC 95%: 1.06-5.22) and breastfeeding period less than one month (RR=3.15; IC95%: 1.35-7.35). When both groups were compared with and without the presence of RSV, the factors associated with infection were: gestational age less than 35 weeks (RR=4 17, IC95%: 2.21-7.87), birth weight less than 2,500g (RR=2.69, 1C95%: 1.34 -5.37) and maternal education less than five years (RR=2 28, IC 95%: 1 13-4.59). Only 26 (63.4%) out of 41 patients reported for follow up of clinical evolution. Of these, 19.2% were non-sibilants, 57.7% were intermittent sibilants and 23.1% were persistent sibilants When the non-sibilant groups were compared with the intermittent sibilants, a significant difference was observed in relation to the variable - hospitalization after discharge, which only occurred in the second group. No significant difference was observed regarding the variables analyzed when non-sibilant groups were compared with moderate/mild persistent sibilants. Conclusions: The incidence of RSV was 17.5% in infants hospitalized with acute lower respiratory tract infections. Factors associated with IMV were age below three months and breastfeeding period less than one month Factors associated with acquisition of RSV were: gestational age less than 35 weeks, birth weight below 2,500 gm; maternal education level less than five years. Delayed clinical evolution revealed that infants who were positive for RSV and infants subjected to IMV demonstrated intermittent wheezing with no need for inhalation corticotherapy and also a higher number of hospitalizations after discharge / Doutorado / Saude da Criança e do Adolescente / Doutor em Saude da Criança e do Adolescente

Chaque année, deux à trois millions de musulmans de plus de 180 pays à travers le monde affluent vers l'Arabie Saoudite pour l'accomplissement du grand pèlerinage à la Mecque, appelé communément le "Hajj". Les virus, et particulièrement celui de la grippe, sont les causes les plus fréquentes d'infections respiratoires aiguës chez les pèlerins.Nous avons décidé de réaliser une étude bibliographique afin de rechercher des preuves de l'efficacité des mesures non pharmaceutiques de prévention des infections respiratoires pendant le Hajj. En résumé, bien que le lavage des mains soit fréquent parmi les pèlerins, le port du masque reste un défi majeur et la distanciation sociale, visant à réduire les contacts avec les personnes infectées, difficilement réalisable pendant le séjour en Arabie Saoudite. Les données sur l'efficacité de ces mesures non pharmaceutiques dans le contexte du Hajj sont limitées et les résultats sont contradictoires, soulignant la nécessité d'études supplémentaires.En 2012 et 2013, nous avons conduit une étude prospective afin d'évaluer sur la même cohorte de pèlerins la prévalence de virus et de bactéries pouvant être responsables d'infections respiratoires aiguës, avant le départ de France pour le Hajj et au retour d'Arabie Saoudite. Nous avons ainsi démontré l'acquisition par les pèlerins de virus respiratoires, principalement rhinovirus, coronavirus (non MERS-CoV) et les virus grippaux, pendant leur séjour en Arabie Saoudite. Aucun n'a été testé positif pour le MERS-CoV. Aussi, une proportion importante de pèlerins a été infectée par Streptococcus pneumoniae, alors que leur couverture vaccinale contre le pneumocoque est faible. / Annually, over two million Muslims from more than 180 countries gather in the Kingdom of Saudi Arabia to perform the pilgrimage to Mecca, also known as the "Hajj". Respiratory viruses, and especially influenza virus, are the most common cause of acute respiratory infection among pilgrims.We conducted a review to summarize the evidence related to the effectiveness of non-pharmaceutical interventions in preventing the spread of respiratory infectious diseases during the Hajj. Overall, although hand hygiene compliance is high among pilgrims, face mask use and social distancing remain difficult challenges. Data about the effectiveness of these measures at the Hajj are limited, and results are contradictory, highlighting the need for future large-scale studies.In 2012 and 2013, we conducted for the first time a prospective longitudinal study of pilgrims, to determine the prevalence of viruses and bacteria potentially responsible for acute respiratory symptoms, before departing from France for the Hajj and before leaving Saudi Arabia. We thus demonstrated the acquisition of respiratory viruses, most notably rhinovirus, coronaviruses (other than MERS-CoV), and influenza viruses, by pilgrims during their stay in Saudi Arabia. None of the pilgrims was positive for MERS-CoV. Also, while vaccination coverage against pneumococcal infection is low among pilgrims, many of them have acquired Streptococcus pneumoniae.

Submitted by PPG Pediatria e Sa?de da Crian?a (pediatria-pg@pucrs.br) on 2018-07-12T11:24:06Z No. of bitstreams: 1 Disserta??oLu SteffenVers?oFinal.pdf: 1086203 bytes, checksum: 9b8f206613da0e87460cd6110bcec5ac (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-07-17T11:24:05Z (GMT) No. of bitstreams: 1 Disserta??oLu SteffenVers?oFinal.pdf: 1086203 bytes, checksum: 9b8f206613da0e87460cd6110bcec5ac (MD5) / Made available in DSpace on 2018-07-17T11:32:31Z (GMT). No. of bitstreams: 1 Disserta??oLu SteffenVers?oFinal.pdf: 1086203 bytes, checksum: 9b8f206613da0e87460cd6110bcec5ac (MD5) Previous issue date: 2017-03-22 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Introduction: Cystic Fibrosis is a disease characterized by recurrent infections and chronic inflammation of the respiratory system that lead to irreversible pulmonary complications. Infections are mainly caused by Staphilococcus aureos(SA) and Pseudomonas aeruginosa (PA). Early diagnosis for identification of colonizing germs is an important challenge. Guidelines suggest the use of swab cultures of the oropharynx or sputum. However, studies on molecular testing, or alternative methods of collection are still unconclusive. The involvement of the upper airway (nasopharynx and paranasal sinuses) has been cited as the primary source of infection. The present study aims to describe and compare the most frequent findings and pathogens in the nasal tract in patients with cystic fibrosis and to correlate findings with markers of severity and progression of lung disease. Methods: This is a retrospective study, which included patients with a diagnosis of Cystic Fibrosis (CF) who are followed up at the Multidisciplinary Outpatient Clinic of the Pediatric Pulmonology Unit of the Hospital S?o Lucas (Pontifical Catholic University of Rio Grande do Sul - PUCRS). Patients who have performed otorhinolaryngological evaluation (ENT) in the last two years (2015-2016) were included. The video naso endoscopy and nasal swab collection were part of the ENT evaluation. Results: 48 patients with CF were included, of which 30 (62.5%) were male. The mean age was 12.15 years ?6.60, and the mean predicted forced expiratory volume in the first second (FEV1%) was 83.36 ?30.04. When evaluating the presence and characteristic of nasal secretion, only 9 patients (18.7%) presented purulent secretion. Twenty-six patients (54.2%) presented grade 1 tonsils and 12 (25%) grade 2 or 3 patients. Nasal swab bacteriology was positive in 26 (54.1%) patients, from which 22 presented Staphylococcus aureos, 2 Pseudomonas aeruginosa, 1 Pseudomonas cepacea and 1 Stenotrophomonas maltophila (SM). In 22 patients (45.8%) the result of the culture was negative. In this study, patients who presented positive colonization by the traditional method (oropharynx / sputum) had a statistically significant chance of being identified also by nasal cavity culture (p<0.001). However, the association was not perfect, and showed a low correlation for the detection of gram negative germs. Nasal polyps were observed in 9 participants. When polyp is used as a marker of disease in nasal endoscopy, a strong association is observed between the presence of polyps and lower Shwachman-Kulczycki clinical score (p <0.001). Conclusions: the results of the culture obtained by collection of the nasal cavity were similar to those found by the standardized collection methods as markers of colonization of the inferior airway. In addition, nasal swabs is characterized as a non-invasive technique and showed to be sensitive to the identification of relevant pathogens in CF, especially SA. In addition, the presence of the polyp in the nasal cavity was shown to be associated with prognostic markers as Shwachman-Kulczycki clinical score. / Introdu??o: a fibrose c?stica ? uma patologia caracterizada por infec??es recorrentes e inflama??o cr?nica do sistema respirat?rio que levam a complica??es pulmonares, por vezes, irrevers?veis. As infec??es s?o causadas, principalmente pelos microorganismos Staphilococcusaureos(SA) e Pseudomonas aeruginosa(PA). O diagn?stico precoce para identifica??o dos germes colonizadores ? ainda um desafio. Consensos sugerem o uso de culturas de swab da orofaringe ou escarro. No entanto, pesquisa por testes moleculares como op??o, ou formas alternativas de coleta ainda s?o inconclusivos. O comprometimento da via a?rea superior (nasofaringe e seios paranasais) tem sido citada como fonte prim?ria de infec??o. O presente estudo tem por objetivo descrever e comparar as altera??es e os pat?genos mais frequentes no trato nasal em pacientes com fibrose c?stica e correlacionar os achados com marcadores de gravidade e progress?o da doen?a pulmonar. M?todos: este ? um estudo retrospectivo, que incluiu pacientes com diagn?stico de Fibrose C?stica (FC) que s?o acompanhados no Ambulat?rio Multidisciplinar de FC do Servi?o de Pneumologia Pedi?trica do Hospital S?o Lucas da Pontif?cia Universidade Cat?lica do Rio Grande do Sul (PUCRS), e que tenham realizado avalia??o otorrinolarigol?gica (ORL) entre os anos de 2015 e 2016. A videonasoendoscopia e a coleta de material da fossa nasal com o uso do swab fizeram parte da avalia??o ORL. Os marcadores de gravidade e progress?o da doen?a foram: ?ndice de massa corporal (IMC), volume expirat?rio for?ado no primeiro segundo(VEF1%) e o escore cl?nico de Shwachman-Kulczycki(S-K). Resultados: foram inclu?dos 48 pacientes com FC, sendo 30 (62,5%) do g?nero masculino. A m?dia de idade foi 12,15 anos ? 6,60, e a m?dia do percentual do valor previsto de volume expirat?rio for?ado no primeiro segundo (VEF1%) foi de 83,36 ? 30,04. Ao avaliar a presen?a e caracter?stica da secre??o nasal, apenas 9 pacientes (18,7%) apresentavam secre??o purulenta. Com rela??o as tonsilas far?ngeas, 26 pacientes (54,2%) apresentavam tonsilas grau 1 e 12 pacientes (25%) grau 2 ou 3. A bacteriologia do swab nasal foi positiva em 26 (54,1%) pacientes, onde 22 apresentavam Staphylococcus aureos, 2 Pseudomonas aeruginosa, 1 Pseudomonas cepacea e 1 Stenotrophomonas maltophila(SM). Em 22 pacientes (45,8%) o resultado da cultura foi negativo. Neste estudo, os pacientes que apresentavam coloniza??o positiva pelo m?todo tradicional (orofaringe/escarro), tinham uma chance estatisticamente significativa de serem identificados tamb?m pela cultura da cavidade nasal (p<0,001). Por?m a associa??o n?o ? perfeita, e demonstrou baixa correla??o para detec??o de germes gram negativos. Foram observados p?lipos nasais em 9 participantes. Quando utilizada a presen?a de p?lipo como marcador de doen?a na endoscopia nasal, observa-se uma forte associa??o entre a presen?a de p?lipos e o redu??o dos valores no escore cl?nico de Shwachman-Kulczycki (p<0,001). Conclus?es: os resultados da cultura obtidos pela coleta da fossa nasal foram semelhantes aos encontrados pelos m?todos de coleta padronizados como marcadores de coloniza??o da via a?rea inferior. Al?m de caracterizar-se como uma t?cnica pouco invasiva, o swab nasal mostra-se sens?vel ? identifica??o de pat?genos relevantes na FC, especialmente SA. Al?m disso, a presen?a do p?lipo na cavidade nasal mostrou ser um dado associado a marcadores de progn?stico medido pelo escore cl?nico de Shwachman-Kulczycki.

A reação em cadeia por polimerase (PCR) e suas variantes tem sido, desde o isolamento do metapneumovírus humano (hMPV), a técnica mais utilizada para a detecção do vírus em secreções respiratórias de diferentes grupos de pacientes. Entretanto, a interpretação de estudos abordando aspectos epidemiológicos e patogenéticos da infecção pelo hMPV tem sido dificultada pelo uso de uma grande variedade de técnicas de PCR \"in house\" na ausência de uma técnica \"padrão ouro\" claramente definida. A avaliação da sensibilidade, especificidade e reprodutibilidade de qualquer técnica molecular \"in house\" é um passo crucial para podermos comparar estudos realizados por diferentes grupos de pesquisa e diferentes grupos de pacientes. Este estudo teve como objetivos a padronização de duas técnicas de PCR - convencional e em tempo real - para a detecção do hMPV em secreções respiratórias e a avaliação da concordância existente entre as técnicas. Entre 228 amostras de lavado de nasofaringe coletadas de receptores de transplante de células tronco hematopoiéticas com sintomas de infecção respiratória aguda, 10 (4,4%) foram positivas para a presença do hMPV pela técnica de PCR convencional enquanto que 11 (4,8%) foram positivas pela técnica de PCR em tempo real. A concordância entre as técnicas, medida pelo índice Kappa para um intervalo de confiança de 95%, foi de 0,95, ou seja, quase perfeita. / The polymerase chain reaction (PCR) has been, since the isolation of the virus in 2001, the most used technique for detection of human metapneumovirus (hMPV) in respiratory specimens of several groups of patients. However, the interpretation of studies regarding the epidemiology and pathogenesis of hMPV infection has been hindered by the use of a great variety of PCRs techniques for hMPV detection, in the absence of a clearly defined \"gold standard\". The assessment of the sensitivity, specificity and reproducibility of any in-house molecular technique is a crucial step to allow the comparison of studies conducted in different settings and different groups of patients. The aim of the present study was to standardize two in-house PCR assays a conventional PCR and a real-time PCR for detecting hMPV in nasopharyngeal aspirates and to evaluate the agreement between the two assays. Of 228 samples of nasopharyngeal aspirates obtained from hematopoietic stem cell transplant recipients with acute respiratory symptoms, 10 (4.4%) were positive for hMPV by conventional PCR whereas 11 (4.8%) were positive by real-Time PCR. The agreement of both assays, measured by Kappa Index, was almost perfect (0.95, 95% confidence interval).