The spotted fever group rickettsiae are emerging diseases. They cause damage in their hosts by invading the endothelium in small to medium-sized blood vessels, which results in vasculitis that can cause clinical manifestations from most organs. The present thesis describes the prevalence of Rickettsia helvetica in ticks, the incidence of rickettsial infection based on seroreactivity and seroconversion in humans and their symptoms, from different parts of Sweden and the Åland Islands in Finland. This was accomplished through serological analysis of both retrospective and prospective serum samples from confirmed and suspected tick-bitten individuals compared to individuals with no knowledge of tick exposure (blood donors). We found a comparable seroprevalence to Rickettsia spp. in different geographical areas where ticks are present; it was also comparable to the seroprevalence of Borrelia spp. Seroprevalence was also more common, as suspected, in the tick-exposed group compared to blood donors. In comparison with co-infections with other tick-borne infections (Anaplasma spp. and Borrelia spp.), we could conclude that co-infections do exist and that, based on clinical findings, it is difficult to distinguish which microorganism causes certain clinical manifestations. For reliable conclusions regarding the causative microorganism, the diagnosis should basically rely on diagnostic tests. In comparison with Borrelia spp., seroconversion to Rickettisa spp. was more common in the areas we investigated, indicating that rickettsiosis is a common tick-borne infection in Sweden and most likely underdiagnosed. When investigating patients with meningitis, we found R. felis in cerebrospinal fluid from two patients with subacute meningitis. This was the first report in which R. felis was found and diagnosed in patients in Sweden. The patients recovered without sequelae and without causal treatment. To provide guidelines on when to treat Rickettisa spp. infections, more investigations are needed. The present thesis shows that Rickettsia spp. are common in ticks and do infect humans. Rickettsial infection should be considered in both non-specific or specific symptoms after a tick bite. It was also shown in the thesis that flea-borne rickettsiosis (R. felis) occurs in Sweden and may cause invasive infections

Made available in DSpace on 2016-08-10T10:54:46Z (GMT). No. of bitstreams: 1 DENISE PICCOLI DE PAULA.pdf: 7499605 bytes, checksum: acd6b8560cb237be607f00ebc352a85c (MD5) Previous issue date: 2014-08-14 / Co-infection with Human T Lymphotropic (HTLV) in individuals infected by the human immunodeficiency virus (HIV) occurs because these viruses share similar routes of transmission is through sexual, parenteral or vertical route, besides infecting the same cell type, and can accelerate as much retard the development of diseases related to them. Rates of HIV (HTLV) coinfection vary according to the geographical region and the population studied. Objective: To determine the prevalence of co-infection in HIV seropositive patients with HTLV 1 and 2, attended two reference centers in Goiânia. Methods: This was a cross-sectional epidemiological study of descriptive type. Were selected to study the first 2 groups, with 86 patients who had at least one laboratory test in the Reference Center on Diagnosis and Therapy (CRDT) Cândido José Santiago de Moura, in Goiania, from march 14 to may 27, 2011. And the second, with 103 HIV seropositive patients treated at the Hospital of the Federal University of Goiás, from september 13, 2013 to february 5, 2014. Questionnaire was applied and held for identification of HTLV serology. Statistically we used the t test and the chi-square (X2) applying the confidence interval of 95% and significance level p<0,05. Results: Males comprised 83.1% and females 16.9%. The most prevalent age group was 26-33 years old, 27.5%. According to sexual behavior, homosexuality excelled with 43.39%. A male patient, showed positive reaction for HTLV 1, demonstrating that there was a prevalence of co-infection of 0.53%. Conclusion: Although prevalence has been found to HTLV-1 below the national average in individuals infected with HIV (6.3%), highlights the importance of research on this virus, allowing a better prognosis related to potential complications in clinical progression to AIDS. / A co-infecção pelo Vírus Linfotrópico de Células T Humana (HTLV) em indivíduos infectados pelo vírus da Imunodeficiência Humana (HIV) ocorre em virtude destes vírus compartilharem vias de transmissão similares, seja por via sexual, parenteral ou vertical, além de infectarem o mesmo tipo de célula, podendo tanto acelerar como retardar o desenvolvimento de doenças a eles relacionadas. As taxas de co-infecção HIV(HTLV) variam de acordo com a região geográfica e a população estudada. Objetivo: Determinar a prevalência da co-infecção em pacientes HIV soropositivos, com o HTLV 1 e 2, atendidos em dois centros de referência de Goiânia. Métodos: Trata-se de um estudo epidemiológico transversal de tipo descritivo. Foram selecionados para o estudo 2 grupos, o primeiro, com 86 pacientes que realizaram pelo menos um exame laboratorial no Centro de Referência em Diagnóstico e Terapêutica (CRDT) Cândido José Santiago de Moura, em Goiânia, de 14 de março a 27 de maio de 2011. E o segundo, com 103 pacientes HIV soropositivos atendidos no Hospital das Clínicas da Universidade Federal de Goiás, de 13 de setembro de 2013 a 5 de fevereiro de 2014. Foi aplicado questionário e realizada sorologia para identificação do HTLV. Estatisticamente foram utilizados o Teste T e o Qui-quadrado (X2) aplicando o intervalo de confiança de 95% e nível de significância estatística p < 0,05. Resultados: O sexo masculino correspondeu a 83,1% e o feminino 16,9%. A faixa etária que mais prevaleceu foi de 26 a 33 anos, 27%. De acordo com o comportamento sexual, sobressaiu o homossexualismo com 43,39%. Um paciente do sexo masculino, apresentou reação positiva para o HTLV 1, demonstrando que houve uma prevalência de co-infecção de 0,53%. Conclusão: Embora tenha sido encontrada prevalência para HTLV-1 inferior à média nacional em indivíduos infectados por HIV (6,3%), destaca-se a importância da investigação desta virose, permitindo um melhor prognóstico relacionado às potenciais complicações clínicas na progressão para AIDS.

Os papilomavírus constituem uma extensa família de vírus associados a lesões epiteliotrópicas, assim como acometem o tecido mucoso onde podem causar tumores benignos que podem evoluir para a malignização. A papilomatose bovina é uma doença economicamente relevante, já que há a desvalorização dos animais a serem comercializados devido à aparência e depreciação do couro. Em humanos, a identificação dos tipos de papilomavírus (HPV) envolvidos bem como o relato de co-infecções são bem estabelecidos. Já foram descritos na literatura mais de 200 tipos de HPVs, o que ainda é pouco explorado na área da Medicina Veterinária, em que somente 21 tipos de papilomavírus bovino (BPV) foram caracterizados até o momento. A presente dissertação visou investigar a diversidade de BPV presentes em um papiloma de um bovino oriundo do Estado de Rondônia. A partir do DNA extraído da lesão, foi realizada a rooling circle amplification (RCA) seguida do sequenciamento de última geração (Ilumina MiSeq). O emprego dessas metodologias culminou na identificação do BPV13, que atualmente é bem caracterizado, e de três prováveis novos tipos de BPVs que haviam sido descritos em um único estudo recente. Estes resultados confirmam a presença de co-infecção em lesões de papilomatose bovina e demonstram que estas técnicas possibilitaram a detecção de espécies que não são identificadas pelos métodos convencionais. Este conhecimento sobre a diversidade de BPV servirá de base para o melhor entendimento da biologia do vírus e para a geração de vacinas profiláticas ou terapêuticas eficazes. / Papillomaviruses are an extensive family of viruses associated with epitheliotropic lesions, as well as affecting mucosal tissue where they can cause benign tumors that may progress to malignancy. Bovine papillomatosis is an economically relevant disease, since there is a devaluation of the animals to be marketed due to the appearance and depreciation of the leather. In humans, the identification of the types of papillomavirus (HPV) involved as well as the reporting of co-infections is well established. More than 200 types of HPV have been described in the literature, which is still little explored in the area of Veterinary Medicine, in which only 21 types of bovine papillomavirus (BPV) have been characterized. This study aimed to investigate the diversity of BPV present in a papilloma of a bovine animal from the State of Rondônia. From the DNA extracted from the lesion, the rooling circle amplification (RCA) was performed followed by the last generation sequencing (Ilumina MiSeq). The use of these methodologies culminated in the identification of BPV13, which is currently well characterized, and of three putative new BPVs types that had been described in a single recent study. These results confirm the presence of co-infection in bovine papillomatosis lesions and demonstrate that these techniques enabled the detection of species that are not identified by conventional methods. This knowledge on BPV diversity will serve as a basis for a better understanding of the biology of the virus and for the generation of effective prophylactic or therapeutic vaccines.

Influenza A virus (IAV) causes annual epidemics and sporadic pandemics of respiratory disease in humans. One of the main complications of primary IAV infection is increased susceptibility to secondary bacterial co-infection, with Staphylococcus aureus being the most common co-infecting species. Previous work identified secreted proteases from S. aureus as a pro-viral factor, leading to specific cleavage of the IAV surface hemagglutinin and increase in infectious viral titre. The aim of this study was to investigate the effect of bacterial proteases, and other secreted bacterial proteins, on IAV replication. Supernatants from the S. aureus community-associated epidemic clone USA300 were separated by size exclusion chromatography and each fraction was tested for an impact on IAV replication in primary chicken embryo fibroblast (CEF) cells. A fraction that increased viral titre by at least 10-fold was identified, but this effect was independent of known secreted proteases. Through the use of mass spectrometry fingerprinting and bacterial mutagenesis, a single protein, S. aureus lipase 1, was identified to be responsible for the pro-viral effect. Lipase 1 is expressed by an array of diverse S. aureus strains of distinct clonal origins. Both the native and recombinant form of lipase 1 were pro-viral only during the infection of primary cells, including primary human lung fibroblasts. Further validation of this interaction indicated lipase 1 was pro-viral in a concentration dependant manner and for a range of IAV strains. Investigation into the mechanism of action of lipase 1 revealed the protein acts during a single infectious cycle in a manner dependent on its active site. Time of addition studies and western blot analysis showed lipase 1 affects the later stages of virus replication, but there is no direct interaction with the virus particle; rather, the protein manipulates the cell, resulting in an increased number of infectious particles being produced. This work has identified and validated a single S. aureus protein, which affects IAV replication. Thus, it has elucidated some of the complex interactions that occur between the virus and bacteria during co-infection. It has also demonstrated a novel role for a bacterial enzyme in IAV replication, the study of which can further our understanding of both IAV and cell biology.

A pesquisa teve como objetivo analisar o Programa de Controle da Tuberculose (PCT) no município de Ribeirão Preto -São Paulo, no período de 1998 a 2006. Utilizou-se para este propósito indicadores epidemiológicos e de desempenho construídos a partir de dados das fichas de notificação de tuberculose (TB) armazenadas no sistema de informação o EPI-Tb, da Secretaria municipal de saúde deste município e os dados populacionais de estimativas do DATASUS, do período de estudo. Selecionaram-se para o estudo casos novos de TB notificados e residentes no município, por ano de diagnóstico, excluindo-se casos atendidos em outros municípios e presidiários. No período compreendido entre 1998 a 2006 foram notificados no EPI-Tb da SMS/Ribeirão Preto 1623 casos novos de tuberculose, sendo que houve queda no número absoluto de casos e no coeficiente de incidência de 47,8% (50,01- 26,08) dos casos no período ou 5,3% ao ano. O risco de ser um caso novo de TB foi 2,4 vezes maior para homens que para as mulheres. Apesar do número de casos notificados serem maiores na faixa etária de 15 a 49 anos, o risco de adoecer por TB foi maior na faixa etária acima de 50 anos, a partir de 2001. O percentual de co-infecção HIV/TB ficou em 27,1% (prevalência mínima), mas a prevalência máxima foi de 32,7%. A forma clínica mais freqüente para os casos novos foi a pulmonar com 85%, enquanto para os casos co-infectados esta forma esteve presente em 58,3% deles e a extra pulmonar em 27,8%. O local de descoberta dos casos de TB foi 51% em ambulatórios (públicos e privados), 39% em hospitais (universitários, público e privados) e 10% outras formas. Uma das fragilidades observadas foi a baixa detecção de casos de TB no município que nos últimos anos ficou próxima de 45% e que as unidades básicas de saúde e PCTs realizam apenas um quinto das baciloscopias de escarro para diagnóstico que deveriam realizar (segundo estimativas do MS). No entanto uma das fortalezas foi a implantação do tratamento supervisionado no município, que iniciou efetivamente em 1998, e foi aumentando gradativamente, chegando em 2006 a supervisionar 76% dos casos. Houve melhora nas taxas de cura, ficando próximo à 72% e 50,5%, para os casos novos sem co-infecção e com co-infecção HIV/TB, respectivamente. A taxa de mortalidade por TB no município apresentou ligeira tendência de queda no período. Apesar da baixa letalidade no período, 50,8% dos óbitos por TB só foram diagnosticados e notificados após o óbito; indicando dificuldade de acesso ao diagnóstico e tratamento da TB nestes casos. Conclui-se que para melhorar a detecção de casos de TB no município serão necessárias mudanças na forma de acolher os indivíduos suspeitos de TB na atenção básica de saúde, facilitando seu acesso a essas unidades, além de investigar mais sintomáticos respiratórios na comunidade. Algumas ações de controle da doença poderiam ser descentralizas, como o tratamento supervisionado e controle de comunicantes. Para os pacientes co-infectados HIV/TB apenas o tratamento supervisionado não está sendo suficiente para alcançarem sucesso no tratamento. / The objective of the present investigation was to analyze the Program of Tuberculosis Control (PTC) in the municipality of Ribeirão Preto- São Paulo, during the period from 1998 to 2006. Epidemiological and performance indicators were used for this purpose, constructed from data of the charts of tuberculosis (TB) notification stored in the information system of EPI-Tb, of the municipal health Secretariat of this municipality and from estimate population data of DATASUS regarding the study period. New TB cases notified regarding patients residing in the municipality were selected according to year of diagnosis, with cases attended in other municipalities and prisoners being excluded. A total of 1623 new cases of TB were notified to EPI-Tb of the SMS/Ribeirão Preto during the period from 1998 to 2006, with a fall in the absolute number of cases and a 47.8% (50,01-26,08) reduction of the coefficient of incidence being observed during this period, corresponding to 5.3% per year. The risk of being a new TB case was 2.4 times higher for men than for women. Although the number of notified cases was higher for the 15 to 49 year age range, starting in 2001 the risk of becoming ill with TB was higher in the age range above 50 years. The percentage of HIV/TB co-infection was 27.1% (minimum prevalence), but the maximum prevalence was 32,7%. The most frequent clinical form for the new cases was the pulmonary one (85%), while this form was present in 58.3% of co-infected cases and the extrapulmonary form in 27.8%. The site of detection of TB cases was public and private outpatient clinics in 51% of cases, university, public and private hospitals in 38%, and other sites in 10%. One of the fragilities observed was the low detection of TB cases in the municipality, which remained close to 45% over the last few years and the fact that the basic health units and PTCs perform only one fifth of the sputum bacilloscopies they should perform for diagnosis (according to Health Ministry estimates). However, one of the strong points was the implantation of supervised treatment in the municipality, which was effectively started in 1998 and increased gradually, with 76% of cases being supervised in 2006. There was an improvement in cure rates, that reached 72% and 50.5% for non-co-infected new cases and HIV/TB co-infected cases, respectively. The TB mortality rate in the municipality showed a slight tendency to a fall during the period. Despite the low lethality observed, 50.8% of the TB deaths were only diagnosed and notified after death, indicating a difficulty in access to diagnosis and treatment of TB in these cases. We conclude that, in order to improve the detection of TB cases in the municipality, changes are needed in the reception of individuals suspected to have TB at basic health units, facilitating their access to these units, in addition to the investigation of more persons with respiratory symptoms in the community. Some actions for the control of the disease such as supervised treatment and the control of communicants could be decentralized. Supervised treatment alone is not sufficient for HIV/TB-co-infected patients to achieve successful treatment.

A pesquisa teve como objetivo analisar o Programa de Controle da Tuberculose (PCT) no município de Ribeirão Preto -São Paulo, no período de 1998 a 2006. Utilizou-se para este propósito indicadores epidemiológicos e de desempenho construídos a partir de dados das fichas de notificação de tuberculose (TB) armazenadas no sistema de informação o EPI-Tb, da Secretaria municipal de saúde deste município e os dados populacionais de estimativas do DATASUS, do período de estudo. Selecionaram-se para o estudo casos novos de TB notificados e residentes no município, por ano de diagnóstico, excluindo-se casos atendidos em outros municípios e presidiários. No período compreendido entre 1998 a 2006 foram notificados no EPI-Tb da SMS/Ribeirão Preto 1623 casos novos de tuberculose, sendo que houve queda no número absoluto de casos e no coeficiente de incidência de 47,8% (50,01- 26,08) dos casos no período ou 5,3% ao ano. O risco de ser um caso novo de TB foi 2,4 vezes maior para homens que para as mulheres. Apesar do número de casos notificados serem maiores na faixa etária de 15 a 49 anos, o risco de adoecer por TB foi maior na faixa etária acima de 50 anos, a partir de 2001. O percentual de co-infecção HIV/TB ficou em 27,1% (prevalência mínima), mas a prevalência máxima foi de 32,7%. A forma clínica mais freqüente para os casos novos foi a pulmonar com 85%, enquanto para os casos co-infectados esta forma esteve presente em 58,3% deles e a extra pulmonar em 27,8%. O local de descoberta dos casos de TB foi 51% em ambulatórios (públicos e privados), 39% em hospitais (universitários, público e privados) e 10% outras formas. Uma das fragilidades observadas foi a baixa detecção de casos de TB no município que nos últimos anos ficou próxima de 45% e que as unidades básicas de saúde e PCTs realizam apenas um quinto das baciloscopias de escarro para diagnóstico que deveriam realizar (segundo estimativas do MS). No entanto uma das fortalezas foi a implantação do tratamento supervisionado no município, que iniciou efetivamente em 1998, e foi aumentando gradativamente, chegando em 2006 a supervisionar 76% dos casos. Houve melhora nas taxas de cura, ficando próximo à 72% e 50,5%, para os casos novos sem co-infecção e com co-infecção HIV/TB, respectivamente. A taxa de mortalidade por TB no município apresentou ligeira tendência de queda no período. Apesar da baixa letalidade no período, 50,8% dos óbitos por TB só foram diagnosticados e notificados após o óbito; indicando dificuldade de acesso ao diagnóstico e tratamento da TB nestes casos. Conclui-se que para melhorar a detecção de casos de TB no município serão necessárias mudanças na forma de acolher os indivíduos suspeitos de TB na atenção básica de saúde, facilitando seu acesso a essas unidades, além de investigar mais sintomáticos respiratórios na comunidade. Algumas ações de controle da doença poderiam ser descentralizas, como o tratamento supervisionado e controle de comunicantes. Para os pacientes co-infectados HIV/TB apenas o tratamento supervisionado não está sendo suficiente para alcançarem sucesso no tratamento. / The objective of the present investigation was to analyze the Program of Tuberculosis Control (PTC) in the municipality of Ribeirão Preto- São Paulo, during the period from 1998 to 2006. Epidemiological and performance indicators were used for this purpose, constructed from data of the charts of tuberculosis (TB) notification stored in the information system of EPI-Tb, of the municipal health Secretariat of this municipality and from estimate population data of DATASUS regarding the study period. New TB cases notified regarding patients residing in the municipality were selected according to year of diagnosis, with cases attended in other municipalities and prisoners being excluded. A total of 1623 new cases of TB were notified to EPI-Tb of the SMS/Ribeirão Preto during the period from 1998 to 2006, with a fall in the absolute number of cases and a 47.8% (50,01-26,08) reduction of the coefficient of incidence being observed during this period, corresponding to 5.3% per year. The risk of being a new TB case was 2.4 times higher for men than for women. Although the number of notified cases was higher for the 15 to 49 year age range, starting in 2001 the risk of becoming ill with TB was higher in the age range above 50 years. The percentage of HIV/TB co-infection was 27.1% (minimum prevalence), but the maximum prevalence was 32,7%. The most frequent clinical form for the new cases was the pulmonary one (85%), while this form was present in 58.3% of co-infected cases and the extrapulmonary form in 27.8%. The site of detection of TB cases was public and private outpatient clinics in 51% of cases, university, public and private hospitals in 38%, and other sites in 10%. One of the fragilities observed was the low detection of TB cases in the municipality, which remained close to 45% over the last few years and the fact that the basic health units and PTCs perform only one fifth of the sputum bacilloscopies they should perform for diagnosis (according to Health Ministry estimates). However, one of the strong points was the implantation of supervised treatment in the municipality, which was effectively started in 1998 and increased gradually, with 76% of cases being supervised in 2006. There was an improvement in cure rates, that reached 72% and 50.5% for non-co-infected new cases and HIV/TB co-infected cases, respectively. The TB mortality rate in the municipality showed a slight tendency to a fall during the period. Despite the low lethality observed, 50.8% of the TB deaths were only diagnosed and notified after death, indicating a difficulty in access to diagnosis and treatment of TB in these cases. We conclude that, in order to improve the detection of TB cases in the municipality, changes are needed in the reception of individuals suspected to have TB at basic health units, facilitating their access to these units, in addition to the investigation of more persons with respiratory symptoms in the community. Some actions for the control of the disease such as supervised treatment and the control of communicants could be decentralized. Supervised treatment alone is not sufficient for HIV/TB-co-infected patients to achieve successful treatment.

<p>The study was conducted among TB patients aged 18 years and older who were registered from January to June 2010. The findings showed a high level of knowledge on TB/HIV prevention and a low level of knowledge on TB/HIV treatment and care. The study also showed that respondents who did not know their HIV status had a positive attitude towards VCT services, while those who knew their status had a positive attitude towards HIV/TB prevention and care programmes. Finally, the findings also showed that most respondents trusted conventional medicine more than traditional medicine. All these findings suggested that respondents had good knowledge of HIV and TB co-infection, had a positive attitude and practiced favourable behaviour towards programmes related to the prevention and care of this co-infection.</p>

En 1998, le traitement de la co-infection VHC rarement discuté avant l'ère des HAART, compte tenu d'une réponse médiocre à la monothérapie par IFNα et d'un pronostic de vie lié au VIH estimé en moyenne à 10 ans, fût reconsidéré. C'est ainsi que débuta en 2000, l'essai RIBAVIC HC02, essai randomisé et multicentrique comparant l'association de la ribavirine 800 mg/j à l'Interféron 3 MUI x3/semaine ou au PEG-α-2b Interféron 1,5 μg/kg/semaine pendant 48 semaines. Une cohorte des patients inclus dans l'essai RIBAVIC (cohorte RIBAVIC EP10) débuta en 2001 pour évaluer le devenir à long terme de ces patients. L'essai RIBAVIC et la cohorte RIBAVIC ont apporté les enseignements suivants : - la cinétique de la charge virale VHC peut différer selon la nature du traitement antirétroviral. - la prévalence et les facteurs de risque de la stéatose sont similaires à ceux observés dans la population mono-infectée VHC - le taux de réponse virologique soutenue est inférieur chez les patients co-infectés (27%) comparé aux patients mono-infectés VHC (50%) - le taux de non réponse virologique (diminution de la charge virale VHC inférieure à 2 log à S12) sous traitement par pegIFN plus ribavirine est plus élevé (33%) comparé aux patients monoinfectés VHC (14%). L'interaction entre la ribavirine et l'abacavir pourrait être un facteur de risque. - l'indétectabilité de l'ARN VHC dès S4 est prédictive de la réponse à long terme (valeur prédictive positive 97%) et la décroissance de la charge virale VHC est significativement plus lente chez les patients rechuteurs comparée aux patients répondeurs long terme à S2 et à S4 - Au cours du traitement anti-VHC :1- le risque d'anémie est élevé et majoré par la coprescription de zidovudine et de ribavirine ; 2- l'amaigrissement est fréquent et sévère et peut être révélateur d'une toxicité mitochondriale ; 3- le risque bactérien n'est pas lié au taux des polynucléaires neutrophiles mais à la fibrose hépatique ; 4- le risque de toxicité mitochondriale, d'aggravation de la fibrose et de décompensation hépatique est majoré par l'interaction entre la didanosine et la ribavirine - une réponse virologique soutenue est associée à un bénéfice histologique et clinique.

<p>The study was conducted among TB patients aged 18 years and older who were registered from January to June 2010. The findings showed a high level of knowledge on TB/HIV prevention and a low level of knowledge on TB/HIV treatment and care. The study also showed that respondents who did not know their HIV status had a positive attitude towards VCT services, while those who knew their status had a positive attitude towards HIV/TB prevention and care programmes. Finally, the findings also showed that most respondents trusted conventional medicine more than traditional medicine. All these findings suggested that respondents had good knowledge of HIV and TB co-infection, had a positive attitude and practiced favourable behaviour towards programmes related to the prevention and care of this co-infection.</p>

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2016-02-04T16:10:12Z No. of bitstreams: 1 Luana Leandro Gois Perfil... 2015.pdf: 11133579 bytes, checksum: 84c1592269b916a72d1e76ba863403c7 (MD5) / Approved for entry into archive by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2016-02-04T16:10:24Z (GMT) No. of bitstreams: 1 Luana Leandro Gois Perfil... 2015.pdf: 11133579 bytes, checksum: 84c1592269b916a72d1e76ba863403c7 (MD5) / Made available in DSpace on 2016-02-04T16:10:24Z (GMT). No. of bitstreams: 1 Luana Leandro Gois Perfil... 2015.pdf: 11133579 bytes, checksum: 84c1592269b916a72d1e76ba863403c7 (MD5) Previous issue date: 2015 / Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / A infecção pelo HIV promove a redução do número de linfócitos T CD4+ e, consequentemente, o surgimento de doenças oportunistas. A leishmaniose visceral e a tuberculose são comumente reconhecidas como doenças oportunistas importantes e associadas ao óbito de indivíduos infectados por HIV. Ambos os patógenos, Leishmania e Mycobacterium tuberculosis (Mtb) infectam cronicamente macrófagos. A imunidade protetora associada a estas infecções envolve linfócitos Th1 produtores de IFN-g. O prejuízo na resposta imune celular causado pelo HIV perturba a resposta imune contra estes patógenos. Não são bem determinadas quais alterações imunológicas causadas pelo HIV promovem o prejuízo na resposta imune específica contra a Leishmania spp. e Mtb, induzindo o desenvolvimento de formas atípicas e graves destas infecções. Deste modo, esta tese teve como objetivo descrever o perfil da resposta imune celular aos antígenos de Leishmania spp. ou Mtb em pacientes infectados com HIV. Para tal., foram recrutados pacientes infectados por HIV e com diagnóstico de leishmaniose (HIV/LV) e tuberculose (HIV/TB). Indivíduos não infectados por HIV e diagnóstico de leishmaniose (LV) ou tuberculose (TB) forma incluídos como controles. Foram avaliadas a linfoproliferação e a frequência das subpopulações de memória dos linfócitos T CD4+ em resposta aos antígenos solúveis de Leishmania spp. (SLA). Igualmente, foram avaliadas a linfoproliferação, a frequência das subpopulações de memória dos linfócitos T CD4+ e CD8+, o perfil de funcional de linfócitos T CD4+ e CD8+ produtores de citocinas e a atividade citotóxica de linfócitos T CD8+ e células NK em resposta ao purificado protéico derivado (PPD) do M. bovis. Duas revisões sistemáticas da literatura que abordam a associação entre estas infecções e a síndrome inflamatória de reconstituição imune em indivíduos infectados por HIV após terapia antiretroviral foram realizadas. Os linfócitos T CD4+ e CD8+ dos pacientes HIV-LV não apresentavam resposta proliferativa ao SLA e houve redução na frequência de subpopulações de linfócitos T CD4+, a qual foi restaurada após o tratamento para leishmaniose visceral. Nos pacientes HIV-TB foi igualmente observada ausência de resposta proliferativa de linfócitos T CD4+ e CD8+ e de células produtoras de IFN-g em resposta ao PPD. Além disso, o HIV promoveu a redução da atividade degranulativa de células NK, o que contribui para o descontrole da infecção e desenvolvimento de TB ativa. Nos pacientes HIV-TB, HAART foi capaz de induzir uma recuperação parcial de células específicas produtoras de IFN-g, bem como da proliferação em resposta ao PPD. Em conjunto, os resultados desta tese sugerem que a infecção pelo HIV induz alterações na resposta celular de memória central e efetora contra patógenos intracelulares oportunistas. Essas alterações são parcialmente restauradas no curso da HAART. / The HIV-infection promotes reduced number of CD4+ T-lymphocytes and manifestation of opportunistic diseases. Visceral leishmaniasis and tuberculosis are commonly known as main opportunistic infections and are associated with mortality in HIV-infected individuals. Both pathogens, Leishmania and Mycobacterium tuberculosis (Mtb), infect macrophages. The protect immune response involve T-lymphocytes help 1 (Th1) and producing of IFN-g. The impairment of cellular immune response caused by HIV disrupts the immune response against these pathogens. It is unclear which immunological alterations caused by HIV infection promote the damage in specific cellular immune response against Leishmania and Mtb and induces the development of atypical and severe forms. Thus, this thesis aimed to describe the profile of the cellular immune response to Leishmania antigens or Mtb in HIV infected patients. To this end, were recruited HIV infected patients with visceral leishmaniasis (HIV/VL) and HIV infected patients with active tuberculosis (HIV/TB). Moreover, HIV uninfected individuals with VL or TB were also included as controls. Lymphoproliferation and frequency of memory CD4+ T-lymphocyte subsets in response to soluble Leishmania antigen (SLA) were evaluated. Also were evaluated lymphoproliferation, frequency of memory CD4+ and CD8+ T-lymphocyte subsets, functional profile of cytokines producing CD4+ and CD8+ T-lymphocytes and cytotoxic activity of CD8+ Tlymphocytes and NK cells in response to purified protein derivative (PPD) of M. bovis. Two systematic reviews of the literature concerning the association between leishmaniasis and tuberculosis with the inflammatory immune reconstitution syndrome (IRIS) in HIV-infected individuals after antiretroviral therapy were done. The absence of proliferative response to SLA of CD4+ and CD8+ T-lymphocytes and the reduced frequency of memory CD4+ T-lymphocyte subsets were observed in HIV/VL patients. The frequency of memory CD4+ T-lymphocyte subset was restored after treatment for visceral leishmaniasis. In HIV/TB patients was also observed absence of proliferative response to PPD of CD4+ and CD8+ T-lymphocytes and of PPD-specific IFN-g producing cells. In addition, HIV infection promotes the reduction in degranulative activity of NK cells which contributes to the survival of Mtb into macrophages and development of active TB. In HIV/TB patients, HAART was able to induce a partial recovery of PPD-specific IFN-g producing cells and of lymphoproliferation in response to PPD. Taken together, the results suggest HIV infection induces changes in cellular immune response of central and effector memory against opportunistic intracellular pathogens. These alterations are partially restored in the after HAART. Keywords: HIV,