Orientador: Maria Marluce dos Santos Vilela / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T01:20:12Z (GMT). No. of bitstreams: 1 Zorzeto_TatianeQueiroz_M.pdf: 1695884 bytes, checksum: 267f0534bc256440762ad9d78bc6402d (MD5) Previous issue date: 2008 / Resumo: A associação temporal de eventos adversos de variada gravidade à imunização com pertussis celular total (DTP) tem estimulado o desenvolvimento de vacinas antipertussis menos reatogênicas. Este ensaio clínico fase I visou à avaliação da imunogenicidade da vacina pertussis celular modificada pela extração do lipopolissacarídeo (DTPm) em comparação com a vacina convencional (DTP). Um total de 234 lactentes foi imunizado aos dois, quatro e seis meses de idade com DTPm ou DTP. Os títulos de anticorpos para os componentes pertussis, tétano, difteria e hepatite B foram determinados um mês após a terceira dose de vacina. A proliferação de células T CD3+ foi avaliada por citometria de fluxo após seis dias de cultivo de células mononucleares de sangue periférico estimuladas com células inativadas de B. pertussis ou com fitohemaglutinina (PHA). Células CD4+, CD8+ e TCR ?d+ foram identificadas no gate de blastos. Os níveis de IFN-?, TNF-a, IL-4 e IL-10 no sobrenadante de cultura foram quantificados por ensaio imunoenzimático (ELISA). A vacina modificada DTPm mostrou-se inferior à DTP quanto ao título de anticorpos antipertussis, mas não houve diferença de resposta aos outros componentes vacinais avaliados. A porcentagem líquida de blastos sob estímulo da B. pertussis foi menor no grupo que recebeu três doses de DTPm (mediana de 3,9% para DTPm e 6,2% para DTP, p=0,029), mas as freqüências de células CD4+, CD8+ e ?d+ em proliferação e as concentrações de citocinas não diferiram entre os grupos. A vacina DTPm não apresentou, portanto, imunogenicidade similar à da vacina DTP convencional nos ensaios laboratoriais / Abstract: Concerns about systemic reactions after immunization with whole-cell pertussis (wP) have stimulated efforts to produce less reactogenic vaccines. This phase I comparative trial aimed the efficacy evaluation of a cellular pertussis vaccine with low lipopolysaccharide (LPS) content (wPlow) in comparison to conventional wP vaccine. A total of 234 infants was vaccinated at 2, 4, and 6 months with conventional wP or wPlow. Serum antibody titers to pertussis, diphtheria, tetanus and hepatitis B were measured 1 month after the third dose of vaccine. Proliferation of CD3+ T cells was evaluated by flow cytometry after 6 days of peripheral blood mononuclear cells culture, with heat-killed B. pertussis or phytohemagglutinin (PHA) stimulation. CD4+, CD8+ and TCR ?d+ cells were identified in the gate of blast lymphocytes. IFN-?, TNF-a, IL-4 and IL-10 levels in supernatants were determined by ELISA. wPlow was inferior to wP in terms of anti-pertussis titers, but there was no diference in other serum antibody evaluations. Net percent blasts in cultures with B. pertussis was lower in the group vaccinated with wPlow (medians of 3.9% and for wPlow and 6.2% for wP; p=0.029), but the frequency of proliferating CD4+, CD8+ and ?d+ cells and the cytokine concentrations in supernatants were similar between vaccination groups. Therefore, wPlow wasn't as imunogenic as conventional wP in experimental evaluations / Mestrado / Saude da Criança e do Adolescente / Mestre em Saude da Criança e do Adolescente

This thesis is concerned with quantifying the dynamical role of stochasticity in models of recurrent epidemics. Although the simulation of stochastic models can accurately capture the qualitative epidemic patterns of childhood diseases, there is still considerable discussion concerning the basic mechanisms generating these patterns. The novel aspect of this thesis is the use of analytic methods to quantify the results from simulations. All the models are formulated as continuous time Markov processes, the temporal evolutions of which is described by a master equation. This is expanded in the inverse system size, which decomposes the full stochastic dynamics into a macroscopic part, described by deterministic equations, plus a stochastic fluctuating part. The first part examines the inclusion of non-exponential latent and infectious periods into the the standard susceptible-infectious-recovered model. The method of stages is used to formulate the problem as a Markov process and thus derive a power spectrum for the stochastic oscillations. This model is used to understand the dynamics of whooping cough, which we show to be the mixture of an annual limit cycle plus resonant stochastic oscillations. This limit cycle is generated by the time-dependent external forcing, but we show that the spectrum is close to that predicted by the unforced model. It is demonstrated that adding distributed infectious periods only changes the frequency and amplitude of the stochastic oscillations---the basic mechanisms remain the same. In the final part of this thesis, the effect of seasonal forcing is studied with an analysis of the full time-dependent master equation. The comprehensive nature of this approach allows us to give a coherent picture of the dynamics which unifies past work, but which also provides a systematic method for predicting the periods of oscillations seen in measles epidemics. In the pre-vaccination regime the dynamics are dominated by a period doubling bifurcation, which leads to large biennial oscillations in the deterministic dynamics. Vaccination is shown to move the system away from the biennial limit cycle and into a region where there is an annual limit cycle and stochastic oscillations, similar to whooping cough. Finite size effects are investigated and found to be of considerable importance for measles dynamics, especially in the biennial regime.

No description available.

Background: Little is known about whether there are any longer-term adverse health effects in children following Tdap (tetanus, diphtheria, and acellular pertussis) vaccination during pregnancy. Objective: To assess the association between maternal Tdap vaccination during pregnancy and risk of the following early childhood adverse health outcomes: (1) infections (upper and lower respiratory tract infections, gastrointestinal infections, and otitis media), (2) pediatric asthma, (3) neoplasm, (4) vision or hearing loss, and (5) urgent and in-patient health services utilization. Methods: This retrospective cohort study used multiple linked health administrative databases in the province of Ontario, Canada containing vaccine information in mothers and information on health outcomes in their children up to age 6 years. Infants exposed to prenatal Tdap were matched 1:5 with unexposed infants and outcomes were compared using hazard ratios and incidence rate ratios. Results: No significant adverse associations between prenatal Tdap and our study outcomes were observed. Inverse associations were found with upper respiratory infections (adjusted incidence rate ratio [aIRR]: 0.96, 95% CI: 0.93-0.99), lower respiratory infections (aIRR: 0.93, 95% CI: 0.89-0.98), gastrointestinal infections (aIRR: 0.88, 95% CI: 0.82-0.94), and urgent and in-patient health service utilization (aIRR: 0.95, 95% CI: 0.94-0.97). Conclusions: Our findings support the long-term safety of Tdap administration in pregnancy.

Retroperitoneal liposarcoma is often asymptomatic but sometimes attention is drawn to the neoplasm due to clinical manifestations. These include fever, flu-like symptoms, nausea or vomiting due to pressure or hypoglycemia related to paraneoplastic disease. We present a rare case of a massive retroperitoneal liposarcoma presenting with refractory dry cough. The patient underwent resection of the mass with complete resolution of her cough. Histopathological examination of the mass demonstrated a well-differentiated tumor with myxomatous features. No evidence of metastatic disease to the lungs was observed. This case points to the need for a thorough and careful evaluation of unexplained cough.

Retroperitoneal liposarcoma is often asymptomatic but sometimes attention is drawn to the neoplasm due to clinical manifestations. These include fever, flu-like symptoms, nausea or vomiting due to pressure or hypoglycemia related to paraneoplastic disease. We present a rare case of a massive retroperitoneal liposarcoma presenting with refractory dry cough. The patient underwent resection of the mass with complete resolution of her cough. Histopathological examination of the mass demonstrated a well-differentiated tumor with myxomatous features. No evidence of metastatic disease to the lungs was observed. This case points to the need for a thorough and careful evaluation of unexplained cough.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19589号 / 医博第4096号 / 新制||医||1014(附属図書館) / 32625 / 京都大学大学院医学研究科医学専攻 / (主査)教授 大森 孝一, 教授 木村 剛, 教授 福田 和彦 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Vaccine-preventable infectious diseases are still prevalent today. Hence, accurate data and techniques such as mathematical modelling are required to better understand their impact on a population level. This is especially the case for measles, as it has been identified to cause immune amnesia (IA): the loss of pre-existing immunological memory for other diseases after a measles infection. First, spectral analysis was used to describe the recurrent patterns of measles and whooping cough (WC) using weekly London mortality data between 1750–1900. Then, stochastic simulations of a model incorporating IA were performed to understand the effect of IA on the recurrent patterns of WC. The periodograms of the simulated model revealed that increasing IA strength and duration caused the longer periodicities of WC to resemble those of measles. This shift was seen for different population sizes, seasonal forcing amplitudes, and mean transmission rates, suggesting this trend can be observed in different ecological or social contexts. When the birth and death rates of London were used in the model with IA duration of less than a year, the WC periodogram of the simulations resembled that of the London mortality data between 1842–1900. Overall, the simulations demonstrate that IA may have contributed to the longer period spectral structure of WC that was found in the real data. Additionally, the mortality, birth rate, and death rate data presented in this thesis provide new tools for future studies in mathematical epidemiology. / Thesis / Master of Science (MSc) / This thesis presents the weekly mortality time series of measles and whooping cough between 1750 and 1900, and describes their epidemic patterns over time. We also model the phenomenon of measles-induced immune amnesia (reduced pre-existing immunity after a measles infection), and examine how it alters the recurrent patterns of whooping cough at a population level. Additionally, we construct a plausible time series of the birth and all-cause mortality rate over the same 150 years. Overall, our analysis suggests immune amnesia alters the longer periodicities of whooping cough to resemble that of measles. Furthermore, we show that this longer periodic structure is similar to that of whooping cough in the late 19th century. Finally, the given mortality, birth rate, and all-cause mortality rate time series can serve as tools for other epidemiological studies, such as predicting long-term epidemic patterns of other diseases.

Background: Persistent cough following an acute respiratory tract infection is a challenging and frequently encountered problem in primary care. Mycoplasma pneumoniae (M. pneumoniae) and Bordetella pertussis (pertussis) particularly predispose patients to persistent cough. Whilst the incidence of M. pneumoniae is highest in children, pertussis may also occur in adults. Method: Four studies were conducted for this thesis. First, a systematic review to assess the diagnostic accuracy of symptoms and signs in the clinical recognition of M. pneumoniae. Second, a retrospective analysis of a cohort of children with persistent cough to assess the prognostic value of diagnosing M. pneumoniae. Third, a prospective cohort study to estimate the prevalence of M. pneumoniae and pertussis in children with persistent cough following recent changes in vaccination policy. Fourth, a double-blind randomised placebo-controlled trial to determine the effectiveness of montelukast in the treatment of persistent cough and pertussis-induced cough in adults. Results: M. pneumoniae and pertussis can each be found in one-sixth of children who present in primary care with persistent cough. Although coverage with the preschool pertussis booster vaccine is high, its efficacy wanes rapidly, with the likelihood of pertussis increasing by 30% per year after vaccination. Montelukast is not an effective treatment for persistent cough, but may be an effective treatment for pertussis-induced cough. Median duration of cough in children with M. pneumoniae is only one-third of that in children with pertussis (39 days versus 118 days). However, the diagnostic accuracy of symptoms and signs in the clinical recognition of M. pneumoniae is limited. Since M. pneumoniae occurs in cyclical epidemics, clinicians should consider current prevalence of M. pneumoniae when making a clinical diagnosis. Conclusions: Diagnosing M. pneumoniae and pertussis can help clinicians give patients an explanation for their cough and inform them about its likely prognosis. At the moment, clinicians should adopt a conservative approach to managing postinfectious persistent cough. A further trial is needed to assess the efficacy of montelukast for the treatment of pertussis-induced cough.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.