It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure.

Objective: The main objective of this study was to detect the presence of 14 respiratory viruses and atypical bacteria (Mycoplasma pneumoniae, Chlamydia pneumoniae), via polymerase chain reaction in patients under 18 years old hospitalized due to community-acquired pneumonia (CAP) from Lima, Peru. Results: Atypical pathogens were detected in 40% (58/146); viral etiologies in 36% (52/146) and coinfections in 19% (27/146). The most common etiological agent was M. pneumoniae (n = 47), followed by C. pneumoniae (n = 11). The most frequent respiratory viruses detected were: respiratory syncytial virus A (n = 35), influenza virus C (n = 21) and parainfluenza virus (n = 10). Viral-bacterial and bacterium-bacterium coinfections were found in 27 cases. In our study population, atypical bacteria (40%) were detected as frequently as respiratory viruses (36%). The presence of M. pneumoniae and C. pneumoniae should not be underestimated as they can be commonly isolated in Peruvian children with CAP.

No abstract available. / Thesis (M.D.)-University of KwaZulu-Natal, 2004.

iv The present work describes the evaluation of the value of polymerase chain reaction in diagnosis of pneumonia caused by the most common three bacterial pathogens / Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis from sputum of patients with community acquired pneumonia admitted to The Department of Pulmonary Diseases of Gulhane Military Medical Academy. In this study, 107 sputa from 142 patients with suspected community acquired pneumonia were used to survey the causative agents. Identification of the pathogens was performed by sputum Gram stain and conventional microbiological methods. Polymerase chain reaction was performed to investigate the presence of S.pneumoniae, H.influenzae, and M.catarrhalis for the same sputum samples as well. PCR products were processed by electrophoresis on 2% agarose gels with visualization of the amplicon with ethidium bromide and UV illumination. The 33 of 107 samples were positive in cultures and 67 in PCR. S.pneumoniae (48.5%) was the most common etiologic agent as to PCR analysis. The incidences of H.influenzae and M.catarrhalis were determined as 18.6%, and 4.7% respectively. The incidence of S.pneumoniae in patients with CAP and control group individuals were almost the same. The sputum PCR positives were higher than those reported carriage rates for these three microorganisms. 9 of 107 patients with PCR-positive had evidence of infection with pathogens other than S.pneumoniae. The results indicated that some of the PCR results were false positive due to oropharyngeal contamination. PCR testing of sputum samples for diagnosing pneumococcal pneumonia is unable to distinguish colonization from infection in some circumstances. To distinguish the colonization from infection, sputum Gram stain should be applied to the sputum specimens. Because of being faster and easier, PCR looks like becoming more reliable technique by the using of valid specimens from patients with community-acquired pneumonia if supported by quantitative techniques.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2012-08-29T19:42:59Z No. of bitstreams: 1 Sara Lacerda Almeida Sant anna. Epidemiologia da pneumonia infantil em uma comunidade de SalvadorBA.pdf: 753919 bytes, checksum: 5aa3e2124780501390e8191fa658803e (MD5) / Made available in DSpace on 2012-08-29T19:42:59Z (GMT). No. of bitstreams: 1 Sara Lacerda Almeida Sant anna. Epidemiologia da pneumonia infantil em uma comunidade de SalvadorBA.pdf: 753919 bytes, checksum: 5aa3e2124780501390e8191fa658803e (MD5) Previous issue date: 2010 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, Brasil / As Infecções Respiratórias Agudas (IRA), principalmente a pneumonia, constituem um importante problema de saúde pública contribuindo com altas taxas de morbidade. e mortalidade no mundo principalmente nos países em desenvolvimento. O objetivo deste trabalho foi caracterizar a infecção do trato respiratório inferior e estimar a incidência de pneumonia em crianças menores de cinco anos atendidas na unidade de emergência de São Marcos, em Pau da Lima, Salvador-Bahia, bem como identificar os principais fatores de risco associados à aquisição desta doença. No período de Junho de 2008 a Maio de 2009, um total de 2.542 crianças foram incluídas no estudo. Cerca de 55,1% eram do sexo masculino; 58,8% eram menores de dois anos de idade; 64,7% eram mulatos. Raio-X de tórax foi realizado na maioria das crianças (93%). Pneumonia foi diagnosticada em 41,9% das crianças. Hospitalização ocorreu em 37,8% dos casos diagnosticados com pneumonia. Considerando apenas as crianças moradoras na área de estudo da coorte de Pau da Lima, pode-se calcular a taxa de incidência de pneumonia em crinças menores de 5 anos, a qual foi de 38,4 por 1.000 habitantes. Dentre os fatores de risco investigados para pneumonia, identificamos que as crianças que frequentam creche/escola, crianças que convivem com menores de 15 anos em casa e crianças que têm contato com fumantes no domicílio tiveram chance maior de desenvolver a doença (p<0,001). Os principais antibióticos utilizados no tratamento foram amoxicilina e penicilina. Nenhum óbito foi registrado durante este período. Nosso estudo indica que a pneumonia exerce um grande impacto na morbidade, sugerindo que a conduta diagnóstica e tratamento precoce são fundamentais e importantes no impacto da mortalidade por este agravo. Nossa investigação fornece uma linha de base para futuras avaliações sobre este agravo, bem como o impacto da vacina neste grupo populacional. / The Acute Respiratory Infections (ARI) especially pneumonia, are an important public health problem contributing to high rates of morbidity and mortality worldwide especially in developing countries. The aim of this study was to characterize the lower respiratory tract infection and estimate the incidence of pneumonia in children under five years of age at the emergency department of San Marcos in Pau da Lima, Salvador, Bahia, as well as identify risk factors associated with acquisition of this disease. In the period of June 2008 to May 2009, a total of 2542 children were included in the study. About 55.1 % were male, 58.8% were under two years old, 64.7% were mulatto. Chest X-ray was performed in most of children (93%). Pneumonia was diagnosed in 41.9%. Hospitalization occurred in 37.8% of patients diagnosed with pneumonia. Considering only children living in the area of a cohort study of Lima, was possible to calculate the incidence rate of pneumonia comprised children younger than 5 years, which was 38.4 per 1,000 inhabitants. Among the investigated risk factors for pneumonia, we identified that children who attend day care / school, live with other children under 15 years at home and have contact with smokers at home, had a chance of developing the disease (p <0.001). The main antibiotics used in treatment were amoxicillin and penicillin. No death was reported during this period. Our study indicates that pneumonia has a major impact on morbidity, suggesting that the diagnostic and early treatment are essential and important impact on mortality from this disease. Our research provides a baseline for future evaluations of this offense, and the impact of the vaccine in this population group.

京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第20288号 / 社医博第77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 川上 浩司, 教授 一山 智, 教授 伊達 洋至 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DGAM

Récemment, les microbiotes pulmonaires bactériens d’un nombre très limité de patients atteints de mucoviscidose et de pneumopathies acquises sous ventilation mécanique (PAVM) ont été étudiés en utilisant l'amplification du gène 16S rDNA bactérien suivie par la construction de librairies de clones et différentes approches de séquençage. Ces études ont montré que la population microbienne de patients atteints de maladies respiratoires était plus diversifiée que prévue. Dans l'étude actuelle, nous utilisons une approche comparable pour identifier exhaustivement les agents pathogènes (bactéries, virus, et champignons) composant le microbiote pulmonaire associé aux pneumopathies développées en unités de réanimation. L'étude a inclus des patients admis en réanimation et présentant des formes de pneumopathies acquises sous ventilation mécanique (n = 106), de pneumopathies communautaires (n = 32), de pneumopathies nosocomiales sans ventilation mécanique (n = 22) et de pneumopathies d’aspiration (n = 25). Une cohorte de 25 patients admis en réanimation et ne présentant pas de symptômes de pneumopathie a été étudiée comme contrôle. Cette première partie du travail amènera ainsi à réaliser un catalogue exhaustif des agents de pneumopathies nosocomiales ; à connaître la prévalence des agents identifiés et d’identifier les co-infections fréquemment observées, et surtout à vérifier si ces agents peuvent être identifiés ou pas dans les prélèvements respiratoires profonds de patients non symptomatiques. Pour réaliser cette partie du travail, des séries de prélèvements, incluant des prélèvements de lavage broncho-alvéolaire (LBA), des prélèvements de sang et d'urine ont été étudiés. Ces prélèvements ont été testés par des moyens d’identification moléculaire moderne basés sur l’amplification de gènes conservés (gènes16S rDNA des bactéries et gène 18S rDNA des champignons) suivie par clonage et séquençage à grande échelle. D’autres pathogènes atypiques sont ciblés par des tests de PCR avec utilisation d’amorces spécifiques. Nous avons également inclus la culture, la co-culture d’amibes, la détection sérologique d'anticorps dirigés contre des agents sélectionnés et des tests d'antigène urinaire, afin de comparer ces tests de routine aux approches moléculaires. Comme résultats, les tests moléculaires nous ont permis d’identifier un vaste répertoire de 160 espèces bactériennes dont 73 n'ont jamais été précédemment rapportées à l’étiologie des pneumopathies. En outre, nous avons trouvé 37 phylotypes bactériens potentiellement nouveaux. Nous avons également identifié 24 espèces de champignons dont 6 n'ont pas été précédemment rapportées à l’étiologie des pneumopathies, 7 virus et étonnamment 6 espèces de plantes. De plus, certains agents pathogènes considérés comme typiques aux pneumopathies nosocomiales tels que Pseudomonas aeruginosa et des Streptococci ont été détectés chez les contrôles comme chez les patients. Cet étonnant résultat souligne l'existence d'un noyau de microbiote pulmonaire.Dans un deuxième travail, faisant suite aux travaux effectués dans notre laboratoire et qui ont pu mettre en évidence que 19% des pneumopathies nosocomiales étaient déterminées par des microorganismes associés aux amibes (MAAs) de l’eau préalablement ignorés ou négligés, nous avons utilisé un test d'immunofluorescence multiplexe pour tester la prévalence des anticorps contre les MAAs dans le sang de patients admis en réanimation et atteints de pneumopathies et la comparer à la prévalence au moment de l'admission. Comme résultat, nous démontrons que certains MAAs peuvent être plus fréquemment détectés après des épisodes de pneumopathies nosocomiales que lors de l’admission. En outre, la réponse immunitaire aux MAAs semble augmenter lorsque le séjour en réanimation est prolongé. Enfin, nous avons mis au point une stratégie de metagénomique pour tester les prélévements pour lesquels aucune étiologie n’a été retrouvée. [...] / Recently, bacterial microbiota from a limited number of patients with cystic fibrosis and ventilator-associated pneumonia (VAP) was studied using 16S rDNA gene amplification followed by clone libraries construction and sequencing. These studies have showed that the microbial population of patients with respiratory infections was more diverse than expected. In the current study, we use a similar approach to identify exhaustively the pathogens (bacteria, viruses, and fungi) comprising the microbiota associated with episodes of pneumonia developed in the intensive care units (ICU). Our study included patients admitted to ICUswith with episodes of ventilator-associated pneumonia (n = 106), community-acquired pneumonia (n = 32), nosocomial pneumonia without mechanical ventilation (n = 22) and aspiration pneumonia (n = 25). A cohort of 25 patients admitted to ICUs without symptoms of pneumonia were studied as controls. This first part of the work enables to prepare an exhaustive repertoire of nosocomial pneumonia pathogenes; to know the prevalence of the pathogens identified and to identify co-infections frequently observed, and especially to ascertain whether these agents can be identified or not in the respiratory samples of patients without symptoms of pneumonia. To perform this part of work, series of samples, including bronchoalveolar lavage (BAL) samples, blood samples and urine samples were collected. These samples were tested by means of modern molecular tools based on the amplification of conserved genes (bacterial 16S rDNA and fungal 18S rDNA genes), followed by highthroutput cloning and sequencing. The atypical pathogens are targeted by PCR tests using specific primers and probes. We also included culture, amoeba co-culture, serological detection of antibodies against selected agents and urinary antigen testing, to compare these routine tests to molecular approaches. Based on molecular testing, we identified a wide repertoire of 160 bacterial species of which 73 were never previously reported in pneumonia samples. Moreover, we found 37 putative new bacterial phylotypes. We also identified 24 fungal species of which 6 have not been previously reported in pneumonia, 7 viruses and surprisingly 6 plant species. Some pathogens considered being typical for ICU pneumonia such as Pseudomonas aeruginosa and Streptococcus species may be detected as commonly in controls as in pneumonia patients which strikingly highlight the existence of a core of pulmonary microbiota.In a second work, following previous works performed in our laboratory which were able to show that 19% of nosocomial pneumonia were determined by micro-organisms associated to amoebae (AAMs) previously ignored or neglected, we used a recent test based on multiplex serology to test for the prevalence of antibodies against the AAMs in the blood of patients admitted to ICU and developed episodes of pneumonia and compare it to the prevalence at the time of admission (controls). As a result, we demonstrate that some AAMs may be more frequently detected after episodes of nosocomial pneumonia than at the admission. In addition, the immune response to AAMS appears to increase when the ICU stay is prolonged.Finally, in order to explore samples for which no microbial aetiology was found, we have developed a subtractive hybridization metagenomic strategy and tested it on different clinical samples. The sensitivity of this strategy was also evaluated. We have demonstrated that our method, based on the detection of DNA and RNA of microorganisms in a single test, allows sensitive detection of different types of microorganisms.

Antecedentes: La neumonía es una infección grave común en la infancia y principal causa de muerte en niños menores de 5 años. Se sabe poco sobre escalas que evalúen el riesgo de muerte por neumonía. Objetivos: Establecer qué escala tiene mejor desempeño como predictor de muerte por neumonía adquirida en la comunidad (NAC) en niños menores de cinco años. Métodos: Se realizo un estudio observacional, retrospectivo, analítico con un diseño de precisión diagnóstica en una cohorte de registros clínicos de pacientes con NAC entre 2013 y 2015 en las primeras 24 horas de ingreso al hospital. El desempeño de las tres escalas se evaluó comparando el área bajo la curva (ABC) como medida de capacidad discriminativa. Resultados: La escala PIRO modificada (Predisposition, Insult, Response and Organic dysfunction) tiene mayor capacidad discriminatoria con un ABC de 0,93 (IC del 95%: 0,89 a 0,96), siendo la mejor de las tres escalas evaluados. En segundo lugar, la escala RISC (Respiratory Index of Severity in Children) con ABC 0,83 (IC 95%: 0.79-0.87) y, finalmente, la escala PRESS (Pediatric Respiratory Severity Score) ABC 0.67 (IC 95% 0.61 - 0.74). Conclusión: Las escalas PIROm y RISC son buenos predictores de muerte en niños menores de 59 meses, basados en criterios clínicos, radiológicos y laboratoriales. La primera escala podría ser utilizada en centros de salud de mayor complejidad. La segunda escala netamente clínica podría ser utilizada en centros de atención primaria de salud. Se sugiere realizar más estudios en poblaciones con diversas características clínicas, demográficas y ambientales. / Background: Pneumonia is a common serious infection in childhood, being the major cause of death in children under 5 years. Little is kwon about clinical scales predicting risk of death owing to pneumonia Objectives: Establish which scale has better performance as a predictor of death due to community-acquired pneumonia (CAP) in children under five years. Methods: An observational, retrospective, analytical study with a diagnostic precision design was conducted in a cohort of clinical records of patients with CAP between 2013 and 2015 that were review in the first 24 hours of admission to the hospital. The performance of the three scales were evaluated by the comparison of the area under the curve (AUC) as a measure of discriminative capacity. Results: The PIRO modified scale (Predisposition, Insult, Response and Organic dysfunction) has greater discrimination capacity AUC of 0.93 (95% CI 0.89 - 0.96) being the best of the three evaluated. Secondly, the RISC scale (Respiratory Severity Index in children) with AUC 0.83 (95% CI: 0.79-0.87) and, finally, the PRESS scale (Pediatric Respiratory Severity Score) AUC 0.67 (95% CI 0.61 - 0.74). Conclusion: The PIROm and RISC scales are good predictors of death in children under 59 months, based on clinical, radiological and laboratory criteria. The first scale could be used in healthcare centers of higher complexity. The second scale purely clinical could be used in centers of primary health care attention. It is suggested to carry out more studies in diverse populations with different clinical, demographical and environmental characteristics. / Tesis

The transcription factor Krueppel-like factor (KLF) 4 fosters the pro-inflammatory immune response in macrophages and polymorphonuclear neutrophils (PMNs) when stimulated with Streptococcus pneumoniae, the main causative pathogen of community-acquired pneumonia (CAP). Here, we investigated the impact of KLF4 expression in myeloid cells such as macrophages and PMNs on inflammatory response and disease severity in a pneumococcal pneumonia mouse model and in patients admitted to hospital with CAP. We found that mice with a myeloid-specific knockout of KLF4 mount an insufficient early immune response with reduced levels of pro-inflammatory cytokines and increased levels of the anti-inflammatory cytokine interleukin (IL) 10 in bronchoalveolar lavage fluid and plasma and an impaired bacterial clearance from the lungs 24 hours after infection with S. pneumoniae. This results in higher rates of bacteremia, increased lung tissue damage, more severe symptoms of infection and reduced survival. Higher KLF4 gene expression levels in the peripheral blood of patients with CAP at hospital admission correlate with a favourable clinical presentation (lower sequential organ failure assessment (SOFA) score), lower serum levels of IL-10 at admission, shorter hospital stay and lower mortality or requirement of intensive care unit treatment within 28 days after admission. Thus, KLF4 in myeloid cells such as macrophages and PMNs is an important regulator of the early proinflammatory immune response and, therefore, a potentially interesting target for therapeutic interventions in pneumococcal pneumonia.

O Streptococcus pneumoniae (pneumococo) constitui um dos mais importantes patógenos bacterianos do trato respiratório, podendo causar infecções invasivas e não invasivas, levando a altas taxas de morbimortalidade, 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 pneumococo entre os indivíduos de uma população. As doenças respiratórias causadas por pneumococo constituem em uma das prioridades atuais em Saúde Pública, recebendo atenção destacada das organizações internacionais da área da saúde, como a Organização Mundial da Saúde. No presente trabalho procura-se conhecer e avaliar a ocorrência da pneumonia adquirida na comunidade (PAC) antes e após a implantação no Calendário Vacinal da Vacina Pneumocócica-10 Valente Conjugada em 2010, na área de abrangência da Superintendência Regional de Saúde (SRS) de Alfenas/MG. Foi realizado um estudo ecológico com componente temporal que incluiu registros de crianças menores que um ano de idade, vacinadas e não vacinadas com a vacina antipneumocócica 10-valente conjugada, no período pré e pós inclusão da vacina no PNI nos municípios da Superintendência Regional de Saúde (SRS) de Alfenas/MG, sendo a vacinação o fator de exposição e a ocorrência de PAC o desfecho, utilizando dados anuais secundários por município para cálculo da cobertura vacinal e das taxas de morbidade por pneumonia em menores de um ano no período de 2007 a 2013. Considerando se os 26 municípios da SRS de Alfenas, houve redução significativa do número de casos de PAC em crianças abaixo de um ano de idade, cuja Razão de Prevalência foi de 0,81 (IC95%: 0,74 0,89; p<0,05). Mesmo com um tempo reduzido de uso, a vacina pneumocócica conjugada 10 valente apresentou um impacto relevante na redução de PAC em crianças, ajustada por cobertura vacinal no período pós vacinação (2011-2013), sendo estatisticamente significativa na maioria dos municípios, o que sugere a efetividade da vacina PCV-10 na prevenção de casos da doença em crianças menores de um ano de idade. / The Streptococcus pneumoniae (pneumococcus) is one of the most important bacterial pathogens of the respiratory tract, may cause invasive and non-invasive infections, leading to high morbidity and mortality rates, particularly in children under five years of age. The bacteria gain access to the host through the nasopharyngeal colonization, which is an important reservoir for the transmission of this pathogen in the community, contributing to the horizontal spread among individuals in a population. Respiratory diseases caused by pneumococcus are in one of the current priorities in Public Health, receiving outstanding attention of international organizations in the health field, such as the World Health Organization. In the present study we aimed to understand and evaluate the occurrence of community acquired pneumonia (CAP) before and after implantation in 10- valent pneumococcal conjugate vaccine in 2010, on the coverage area of the Regional Health Service (SRS) of Alfenas / MG. An ecological study with temporal component was conducted which included records of children under one year old, vaccinated and not vaccinated with 10-valent pneumococcal conjugate vaccine, before and after period inclusion of the vaccine in PNI, in the municipalities of SRS of Alfenas / MG, with vaccination the exposure factor and the occurrence of CAP the outcome, using annual data side by municipality to calculate vaccination coverage and pneumonia morbidity in children under one year old, in the period 2007 to 2013. Considering the 26 municipalities of SRS Alfenas, there was a significant reduction in the number of CAP cases in children under one year old. The prevalence ratio was 0.81 (95%CI: 0.74 - 0.89; p<0.05). Even with a short period of use, the 10-valent pneumococcal conjugate vaccine had a significant impact on the reduction of CAP in children, adjusted for immunization coverage in the post vaccination period (2011-2013) and was statistically significant in most municipalities, which suggests the effectiveness of PCV-10 vaccine in preventing cases of the disease in children under one year of age.