Submitted by Edisangela Bastos (edisangela@ufpa.br) on 2013-05-06T22:21:44Z No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_FebreTifoideExperiencia.pdf: 1402656 bytes, checksum: 7a17b4a720b4331aeaeaa8105af844d0 (MD5) / Approved for entry into archive by Ana Rosa Silva(arosa@ufpa.br) on 2013-05-08T14:07:15Z (GMT) No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_FebreTifoideExperiencia.pdf: 1402656 bytes, checksum: 7a17b4a720b4331aeaeaa8105af844d0 (MD5) / Made available in DSpace on 2013-05-08T14:07:15Z (GMT). No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_FebreTifoideExperiencia.pdf: 1402656 bytes, checksum: 7a17b4a720b4331aeaeaa8105af844d0 (MD5) Previous issue date: 2005 / A febre tifóide é doença infecciosa de distribuição mundial e, estando estreitamente relacionada com baixos níveis sócio-econômicos, ocorre com maior freqüência nos países em desenvolvimento. Neste trabalho é apresentada a experiência do Instituto Evandro Chagas (IEe) com essa doença desde 1987 até 2004, período no qual se construiu uma casuística de 443 casos, todos diagnosticados por meio do isolamento da Salmonella Typhi no sangue e/ou nas fezes, sendo alguns deles complementados com a reação soro lógica de Widal. Os casos foram procedentes de Belém e do interior do Estado, ora encaminhados ao IEC pelas respectivas unidades do Sistema Único de Saúde para esclarecimento diagnóstico de síndrome febril, a maioria de curso prolongado, aqui designados como "demanda espontânea", ora detectados por ocasião da investigação de surtos ocorridos em localidades do interior. Discutiram-se aspectos relacionados à apresentação clínica, com ênfase às manifestações atípicas; à distribuição por gênero e faixa etária; à sazonalidade; e à distribuição por área de procedência, identificando-se os municípios de maior prevalência, e a distribuição por bairros, em relação aos casos procedentes de Belém. Foram discutidos, também, aspectos relacionados ao diagnóstico laboratorial com ênfase à aplicação dos métodos de cultivo (coprocultura e hemocultura) comparando o rendimento delas em relação ao tempo de doença e a relação dessas provas com a reação de Widal, comparando o valor desta como método auxiliar ou complementar no diagnóstico da doença. As análises estatísticas foram realizadas por meio do programa Bio Estat versão 3.0, aplicando-se o teste do qui-quadrado e teste "G" e a significância estatística foi aceita ao nível de 95%. Os resultados nos permitiram tirar as seguintes conclusões: 1) em situações de normalidade epidemiológica a febre tifóide acomete mais a faixa etária do adulto jovem, enquanto que, nas situações epidêmicas, a faixa etária mais atingida é a infantil; 2) existem homogeneidade entre as amostras provenientes dos casos de surtos e da demanda espontânea quanto à distribuição dos gêneros, sendo que o masculino está mais exposta à febre tifóide; 3) no interior do Estado a doença se mostrou mais freqüente nas regiões onde se concentra maior número de populações ribeirinhas e, em relação à capital, ela mostra a maior prevalência no bairro do Jurunas; 4) a enfermidade tem um perfil sazonal, que mostra a maior ocorrência na segunda metade do ano, favorecida provavelmente por fatores geo-climáticos e culturais; 5) a febre tifóide constitui sério problema de saúde pública no Estado do Pará, confirmando sua estreita relação com os elevados níveis de pobreza; 6) a fórmula leucocitária revelou padrão normal ou leucocitose em maior percentual em relação à leucopenia; 7) na abordagem laboratorial não se deve prescindir dos ensaios que visam ao isolamento em detrimento do teste sorológico, e a coprocultura e a hemocultura devem ser solicitadas em todos os casos sem se levar em conta o tempo de evolução do quadro clínico; 8) em nossa região, nas áreas onde não há disponibilidade das provas de cultivo a reação de Widal pode ser uma alternativa de valor diagnóstico; 9) é enfermidade de curso clínico prolongado e com manifestações clínicas atípicas (pneumonias e hepatite colestática) cujos sinais/sintomas, quando presentes, devem suscitar a suspeita por parte do investigador; 10) nas regiões de elevada endemicidade, a febre tifóide pode causar um impacto negativo na economia tanto pelos custos gerados com exames laboratoriais, tratamento, hospitalizações e eventuais intervenções cirúrgicas, como por afastar o trabalhador do seu posto de trabalho por um período de tempo prolongado. / Typhoid fever is an infection disease of world occurrence, but as it is strictly related with low socioeconomic levels it occurs most frequently in developing countries. In this work we present the experience of Instituto Evandro Chagas (IEC) with that disease since 1987 up to 2004, period in which a number of 443 cases was accumulated, all diagnosed by Salmonella Typhi’s isolation from blood or feces, being some of them complemented with Widal serologic reaction. The case were proceeding from Belém and the municipal districts of Pará state conduced to IEC by the respective Units from Health System for etiologic diagnosis of fever syndrome, most of them of persistent course, here designated as “spontaneous” demand, at that time detected during outbreak investigations occurred in the municipal districts. We discussed aspects related to the clinical presentation, with emphasis to the atypical manifestations, the distribution according to sex and age group, the seasoning, the distribution by origin area, identifying the municipal districts of larger prevalence, and the distribution by districts, in relation to the cases coming from Belém. We also discussed aspects related to the laboratorial diagnosis emphasizing the application of the cultivation methods (coproculture and hemoculture) comparing their performance concerning the time of disease and the relationship of those tests with Widal reaction, by measuring the value of these as auxiliary or complementary method in the diagnosis of the disease. Clinical, epidemiological and laboratorial analyses were made, using Bio Estat version 3.0 program by applying qui-square and G test and the statistic significance was accepted at 95% level. The results allowed us to have the following conclusions: 1) in situations of epidemic normality the typhoid fever affects more the young adult group, while, in the epidemic situations, the affected age group is the infantile; 2) there is homogeneity among the samples from cases of outbreaks and the spontaneous demand according to the gender distribution, but males are more exposed to typhoid fever; 3) in municipal districts of the State the disease was shown to be more frequent in the areas where it concentrates larger number of populations who live near rivers and, in relation to the capital, it showed larger prevalence in jurunas district; 4) the illness has a seasonal profile, which shows the largest occurrence in the second half of the year, probably favored by geo-climatic and cultural factors; 5) the typhoid fever constitutes serious problem of public health en the State do Pará, confirming its narrow relationship with the high poverty levels; 6) the leukocytic formula revealed normal pattern or leucocytosis compared to leucopenia; 7) in the laboratorial approach it should not dispense the assays that seek to the isolation in detriment of the serological test, and the coproculture and the hemoculture should be requested in all the cases without considering the time of evolution of the clinical situation; 8) in our area, where there is not availability of cultivation tests, Widal reaction can be an alternative of value diagnosis; 9) it is illness of persistent clinical course and with atypical clinical manifestations (pneumonias and cholestatic hepatitis) whose sings/symptoms, when presented, should raise the suspicion by the investigator; 10) in the areas high endemicity, the typhoid fever can cause a negative impact in the economy not only for the costs generated with laboratorial exams, treatment, hospitalizations and eventual surgical interventions, but also because it can let the worker to be away from work for a prolonged period of time.

Typhoid disease, caused by infection with S. Typhi, is a significant cause of mortality and morbidity in resource–poor countries. Efforts have been made to generate a new generation of vaccines that are efficacious and can be given to infants, but have been hindered by a poor understanding of the protective immune response to S. Typhi infection, and in particular by the absence of a correlate of protection. Controlled human infection studies (‘challenge studies’) provide a model for investigating infectious diseases and appraising novel vaccines, including in typhoid disease. This DPhil described the development of a human challenge model of typhoid fever using <en>S. Typhi Quailes strain administered to healthy adults in a sodium bicarbonate buffer. The careful characterisation and manufactured of the strain is described. Following ingestion of 10³ CFU of S. Typhi 55% of participants developed typhoid disease, whilst ingestion of 10⁴ CFU gave a higher attack rate of 65%. At this attack rate vaccine efficacy against human challenge should be demonstrable with a modest sample size. Validity of the model in the appraisal of vaccines was demonstrated using Ty21a, a live, oral, attenuated vaccine. Protective efficacy of Ty21a compared to placebo against challenge was 35%, comparable to that observed in some endemic settings, and the estimated protection in the first year after vaccination in Cochrane meta-analysis. Clinical, microbiological and humoral immune responses were investigated in participants challenged during model development. Typhoid disease was associated with a high fever in most, but not all participants, and a range of symptoms. Severity of disease was variable, and included asymptomatic bacteraemia, as well as fever and symptoms in participants in whom bacteraemia could not be demonstrated. Typhoid disease was associated with a strong humoral immune response to the flagellin and lipopolysaccharide antigens of S. Typhi but not the Vi polysaccharide capsule. Humoral immune responses were not demonstrated in participants without typhoid fever. There was a dose-response relationship to the clinical, microbiological and humoral responses with participants challenged with 10⁴ CFU having more marked responses than those challenged with 10³ CFU. Future success of challenge studies relies on the willing participation of healthy adult volunteers. The motivations for participation, and experiences of participants, were appraised by questionnaire. Whilst financial compensation was an important motivator, it was not the sole motivator. Participants were positive about their experiences, and most would participate again.