Die vorliegende Habilitationsschrift befasst sich schwerpunktmäßig vor allem mit der Klinik und Therapie der Hepatitis C. Evaluiert wurden: 1. verschiedene therapeutische Strategien, 2. die Ursachen der "Non-Response" auf eine anti-virale Therapie sowie 3. die klinische Relevanz der neu entdeckten Hepatitis-assoziierten Viren und 4. ihre Bedeutung bei Patienten mit akuter bzw. chronischer Lebererkrankung unklarer Ätiologie sowie bei Patienten vor und nach Lebertransplantation. Ad 1. Aus dem Vergleich verschiedener Therapie-Konzepte wie der Kurzzeit- Kombinationstherapie, Triple-Therapie, Hochdosis-Interferon?-Therapie und der Anwendung antiviraler Substanzen wie Ribavirin und Amantadin ergaben sich neue Erkenntnisse hinsichtlich relevanter prognostischer Parameter für die Therapieresponse. Ad 2. Analysiert wurden die möglichen molekularen Mechanismen der Therapieresponse bzw. Non-Response sowie der Stellenwert von Interaktionen bestimmter HCV-Proteine (NS5A, E2, sogenannte PKR-eIF2a Phosphorylisations-Homologie-Domäne [PePHD]) mit den Interferon? induzierten Effektorproteinen. Es konnte gezeigt werden, daß die Anzahl der Mutationen innerhalb des NS5A Proteins einen prognostischen Parameter darstellen hinsichtlich der Response auf eine Interferon?-Therapie. Dagegen spielen Mutationen innerhalb der PePHD-Region keine Rolle. Ad 3. Aus den Untersuchungen zur klinischen Relevanz der neu entdeckten Hepatitis-assoziierten Viren GB Virus-C/Hepatitis G Virus (GBV-C/HGV) und TT-Virus (TTV) ergaben sich keine Hinweise bzgl. eines Einflusses von GBV-C/HGV bzw. TTV-Infektionen auf den Verlauf der chronischen Hepatitis C. Die durchgeführten Verlaufsuntersuchungen bei koinfizierten Patienten sprechen dafür, daß es sich um Interferon-sensitive Viren handelt; jedenfalls beeinflussen sie nicht die IFN?-induzierte Response. Ad 4. Untersucht wurden ferner die Prävalenz, Transmission und Relevanz der GBV-C/HGV und TTV-Infektion im Hinblick auf ihre Hepatitis-induzierenden Eigenschaften. Die Ergebnisse belegen, dass beide Viren parenteral übertragen werden, und dass sie eine hohe Prävalenz bei Patienten mit parenteralen Risikofaktoren besitzen. Eine Hepatitis-induzierende Potenz dieser Viren konnten wir nicht beobachten; bei der Mehrzahl aller chronisch infizierter Personen ließen sich keine Zeichen einer chronischen Hepatitis finden. / The major goal of this thesis is the analysis of the clinical outcome of patients with Hepatitis C virus (HCV) infection and the response to therapy. Analysed were 1. different types of therapeutic strategies 2. causes responsible for ineffective antiviral therapy (non-response) 3. clinical relevance of the newly discovered hepatitis-associated viruses and 4. the role of these viruses in patients with acute or chronic hepatitis of unknown causes and in those receiving liver grafts. Ad 1. Compared were different therapeutic concepts such as short-term combination therapy, triple-therapy, high dose IFN?-therapy and the use of antiviral substances such as ribavirin and amantadine. It emerged that relevant prognostic parameters can be deduced with respect to the therapeutic response rate. Ad 2. Analysed were possible molecular mechanisms, which may interfere with response or non-response to antiviral therapy. In this respect, we focussed on the interaction of certain HCV-proteins as NS5A, E2, so-called PKR-eIF2a phosphorylisation-homology-domain (PePHD). with the interferon-?-induced effector proteins. There is evidence, that number of mutations within the NS5A proteins are of prognostic relevance with respect to the response to interferon?-therapy. In contrast, mutations within the PePHD-region do not play any role in this respect. Ad 3. We also studied the clinical relevance of the newly discovered viruses GBV-C/HGV and TTV, and found, that they have no impact concerning the course of chronic hepatitis C. These viruses are interferon-sensitive and do not influence the IFNa-response as it could be documented by following the course of co-infected patients. Ad 4. Our studies also focused on the prevalence, transmission and relevance of GBV-C/HGV and TTV infections with respect to their role as hepatitis-inducing agents. We can show that both virus types are parenterally transmitted. There is a high prevalence for both types in patients confronted with risk factors for parenteral factors. From analysis of many patients being chronically infected with these viruses it became quite clear that they lack any important potency to provoke chronic liver disease.

Introduction: Malgré des taux d’efficacité comparable du traitement antiviral de l’hépatite C (VHC) entre utilisateurs de drogues par injection (UDIs) et non-UDIs, il y a encore d’importantes barrières à l’accessibilité au traitement pour cette population vulnérable. La méfiance des UDIs à l’égard des autorités médicales, ainsi que leur mode de vie souvent désorganisé ont un impact sur l’initiation du traitement. L’objectif de cette étude est d’examiner les liens entre l’initiation du traitement du VHC et l’utilisation des services de santé chez les UDIs actifs. Methode: 758 UDIs actifs et séropositifs aux anticorps anti-VHC ont été interrogés durant la période de novembre 2004 à mars 2011, dans la région de Montréal. Des questionnaires administrés par des intervieweurs ont fourni des informations sur les caractéristiques socio-économiques, ainsi que sur les variables relatives à l’usage de drogues et à l’utilisation des services de santé. Des échantillons sanguins ont été prélevés et testés pour les anticorps anti-VHC. Une régression logistique multivariée a permis de générer des associations entre les facteurs relatifs aux services de santé et l’initiation du traitement contre le VHC. Resultats: Parmi les 758 sujets, 55 (7,3%) avaient initié un traitement du VHC avant leur inclusion dans l’étude. Selon les analyses multivariées, les variables significativement associées à l’initiation du traitement sont les suivantes: avoir vu un médecin de famille dans les derniers 6 mois (Ratio de Cote ajusté (RCa): 1,96; Intervalle de Confiance à 95% (IC): 1,04-3,69); plus de 2 ans sous traitement de la dépendance à vie, sans usage actuel de méthadone (RCa: 2,25; IC: 1,12-4,51); plus de 2 ans sous traitement de la dépendance à vie, avec usage actuel de méthadone (RCa: 3,78; IC: 1,85-7,71); et avoir déjà séjourné en prison (RCa: 0,44; IC: 0,22-0,87). Conclusion: L’exposition à des services d’aide à la dépendance et aux services médicaux est associée à l’initiation du traitement du VHC. Ces résultats suggèrent que ces services jouent leur rôle de point d’entrée au traitement. Alternativement, les UDIs ayant initié un traitement du VHC, auraient possiblement adopté une attitude proactive quant à l'amélioration de leur santé globale. D’autre part, l’incarcération ressort comme un obstacle à la gestion de l’infection au VHC. / Introduction: In spite of comparable hepatitis C virus (HCV) treatment efficacy between injection drug users (IDUs) and non-IDUs, there are still important barriers impeding antiviral treatment access in this vulnerable population. Mistrust between IDUs and health care providers, along with IDU disorganised lifestyle, affect HCV treatment uptake. The objective of this study is to examine the association between HCV treatment initiation and the use of healthcare services among active IDUs. Methodology: 758 active IDUs, seropositive for anti-HCV antibody, were surveyed from November 2004 to March 2011 in Montreal. Interviewer-administered questionnaires elicited information on socio-demographic factors, drug use related behaviors and health care service utilization. Blood samples were collected and tested for HCV antibodies. Multivariate logistic regression analysis was conducted to identify the health service correlates of HCV treatment initiation. Results: Among the 758 subjects, 55 (7.3%) had initiated an HCV treatment prior to enrolment. In multivariate analysis, variables independently associated with treatment initiation included: having seen a general practitioner in the last 6 months (adjusted Odds Ratio (aOR): 1,96; 95% Confidence Interval (CI): 1,04-3,69); more than 2 years of lifetime addiction treatment exposure without current methadone use (aOR: 2,25; CI: 1,12-4,51); more than 2 years of lifetime addiction treatment exposure with current methadone use (aOR: 3,78; CI: 1,85-7,71); and having spent time in prison (aOR: 0,44; CI: 0,22-0,87). Conclusion: Exposure to addiction and medical services is associated with HCV treatment initiation. These results suggest that such services efficiently play their role as entry points for HCV treatment. Alternatively, IDU who have initiated HCV treatment, regardless of the viral response outcome, may have adopted a proactive stance towards improving their overall health. Incarceration on the other hand seems to be an obstacle to HCV treatment uptake.

No description available.

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Etwa 3% der Weltbevölkerung sind von dem Hepatitis-C-Virus-Infektion betroffen. Phänotyp der HCV-induzierten Lebererkrankung variiert stark von einem Patienten zum anderen. Die Wahrnehmung der viralen doppelsträngigen RNA (dsRNA) und einzelsträngigen RNA (ssRNA) durch den Toll-like-Rezeptor 3 (TLR3) bzw. TLR7 scheinen an der Früherkennung der Pathogene und an der Wirtsantwort auf viraler Infektion beteiligt zu sein. Darüber hinaus ist die membran-assoziierte Form des Endotoxin-Rezeptor-Bestandteils CD14 (mCD14) mit TLR3 in Intrazellulärräumen kolokalisiert und erweitert die dsRNA-Erkennung und TLR3-Signalleitung. Die vorliegende Arbeit analysiert epidemiologische und klinische Daten von Patienten kaukasischer Abstammung mit einer chronischen Hepatitis C in Bezug auf bestimmte Einzellnukleotidpolymorphismen (SNPs) mit relevanten minor allele frequencies (MAFs) in Genen, die für obengenannte Rezeptoren kodieren. Es wurde keine Assoziation von dem TLR3-Promotor-Polymorphism rs5743305 (T/A) mit TLR3-Genexpression gefunden, weder in peripheren mononukleären Zellen des Blutes (PBMCs) noch in der Leber; keine weitere Korrelation mit epidemiologischen und klinischen Parametern der chronischen Erkrankung waren zu beobachten. Andererseits, T-homozygote Patienten am rs3775291-(C/T)-Polymorphismus (der in Exon 4 lokalisierter nicht-synonymer SNP) zeigen Tendenz zu einer höheren TLR3-Genexpression in der Leber. Außerdem, unter HCV-subtyp-1a-infizierten Patienten sind keine T-Homozygoten zu finden. Im Unterschied zur Lage bei alkoholischer Lebererkrankung wurde in chronischen Hepatitis-C-Patienten keine Assoziation zwischen den Fibrosegrad und CD14-Gen-C-159T-Polymorphismus gefunden. Bei T-homozygoten Patienten wurden jedoch häufiger portale lymphoide Aggregaten gefunden als bei C-Allele-Trägern. Außerdem das Vorhandensein von portalen lymphoiden Aggregaten korrelierte eng mit der Leberentzündung und mit Gallengangsläsionen. Am Ende wurde der funktionelle nicht-synonyme SNP in Exon 3 des X-gekoppelten TLR7 Gens, rs179008/Gln11Leu, untersucht. Die Analyse war auf homo- und hemizygoten Personen, die mittels Allelspezifischentranskriptquantifizierung (ASTQ) in heterozygoten weiblichen Personen eingeordnet wurden, eingeschränkt. Es zeigte sich dabei ein individueller verzerrter Mosaizismus in PBMCs. Das variante T-Allel war nur mit der Anwesenheit der portalen lymphoiden Aggregaten assoziiert. Hepatische Viruslast und Expression der Gene, die bekannterweise bei einer chronischer HCV-Infektion induziert sind, unterschieden sich zwischen Wildtyp- und Variantallelträger nicht. Jedoch eine signifikant niedrigere Expression der interleukin-29 (IL-29)/lambda1 interferon (IFN-λ1) und beider Untereinheiten seines Rezeptors (IL-10 Rβ and IL-28Rα) war bei T-homo- und hemizygoten Patienten zu beobachten. Diese Tatsache könnte eher eine Auswirkung auf die Ansprechbarkeit auf zukünftige IFN- λ-basierte Therapie haben, als auf eine Vorhersage des Ausgangs der gängigen IFN-α-basierten Therapie.

Dans le monde, 58 millions de personnes sont chroniquement infectées par le virus de l'hépatite C (VHC). Depuis 2011, l'introduction des antiviraux à action directe a permis la guérison des infections chroniques chez la majorité des sujets traités (~95 %). Toutefois, les traitements sont coûteux et ne protègent pas contre les réinfections, d'où la nécessité de développer un vaccin prophylactique pour freiner efficacement l'épidémie du VHC. Environ 30% des primo-infections sont éliminées spontanément, représentant une occasion unique d'étudier les corrélats de l’immunité protectrice nécessaires pour le développement d’un vaccin efficace. Dans cette thèse, nous avons procédé à la définition des corrélats de l'immunité protectrice au cours des infections par le VHC primaires et subséquentes aux niveaux transcriptomique, clonotypique et fonctionnel à partir d’une cohorte d’utilisateurs de drogues par injection. Le premier objectif était de caractériser le répertoire de récepteurs des cellules T CD8 spécifique de l'épitope immunodominant et cross-réactif NS3 1073-1081 (CINGVCWTV) restreint par HLA-A2 au cours d’une primo-infection aiguë progressant vers une résolution spontanée ou une infection chronique. Nous avons identifié un ensemble de treize clonotypes publics, indépendamment de l'issue de l'infection. Plusieurs clonotypes publics avaient une longue durée de vie après résolution de l’infection et ont proliféré après réinfection par le VHC. En explorant les bases de données publiques, nous avons identifié plusieurs clonotypes partagés avec d'autres épitopes viraux restreints par HLA-A2, mais ils étaient de faible fréquence et de réactivité croisée limitée, suggérant un rôle limité des lymphocytes T CD8 cross-réactifs au cours de l'infection primaire par le VHC. Le deuxième objectif était de caractériser les signatures transcriptomiques longitudinales des cellules mononucléaires du sang périphérique totaux chez huit sujets ayant spontanément résolu deux infections consécutives par le VHC. Nous avons également comparé ces signatures avec un schéma vaccinal composé d'un vecteur à adénovirus de chimpanzé suivi d'un rappel utilisant la vaccine modifiée Ankara, exprimant tout deux les protéines non-structurales du VHC. Nous avons identifié une signature transcriptomique des plasmocytes au cours d'une réinfection aiguë, absente lors de l'infection primaire et après le rappel du vaccin. La résolution spontanée est associée à une expansion rapide des cellules B mémoires spécifiques de la glycoprotéine E2 chez 3 sujets et à une augmentation transitoire des anticorps neutralisants anti- E2 chez 6 sujets. Parallèlement, il y avait une augmentation de l'étendue et de l'ampleur des lymphocytes T spécifiques du VHC chez 7 sujets. En conclusion, nous avons identifié treize clonotypes publics uniques au VHC qui ont proliféré au cours des infections primaire et secondaire. La faible fréquence des clonotypes cross-réactifs suggère qu'ils ne sont pas des déterminants majeurs de l’issue de l’infection. De plus, nous avons observé une augmentation simultanée des réponses des lymphocytes B et T spécifiques du VHC au stade aiguë précoce, suggérant un rôle des deux bras de l’immunité adaptative dans la clairance de la réinfection du VHC. Nos résultats soutiennent l'idée de combiner deux stratégies vaccinales induisant à la fois une immunité à médiation cellulaire et une immunité humorale visant à prévenir les infections chroniques par le VHC. / Worldwide, 58 million individuals are chronically infected with hepatitis C virus (HCV). Since 2011, the introduction of direct acting antivirals enabled the cure of chronic HCV in the majority of treated subjects (~95%). However, direct-acting antivirals treatments are expensive and do not protect against reinfection, urging the need to develop a prophylactic vaccine to efficiently curb the HCV epidemic. Around 30% of acutely infected individuals will spontaneously clear the infection, representing a unique opportunity to study the correlates of immune protection needed to develop a potent vaccine. In this thesis, we proceeded to define the correlates of protective immunity during primary and sub-sequent HCV infections at the transcriptomic, clonotypic and functional levels using longitudinal peripheral blood mononuclear cells samples collected from a cohort of people who inject drugs (PWID). The first aim was to characterize the CD8 T cell receptor repertoire specific to the immunodominant and cross-reactive HLA-A2 restricted NS3 1073-1081 (CINGVCWTV) epitope during acute HCV in PWID progressing to either spontaneous resolution or chronic infection. We identified a set of thirteen public clonotypes in HCV-infected subjects irrespective of infection outcome. Several public clonotypes were long-lived in resolvers and expanded upon reinfection. By mining publicly available data, we identified several TCR clonotypes shared with other HLA-A2 restricted epitopes, but they were of low frequency and limited cross-reactivity, suggesting that they are not major determinants of infectious outcome. The second aim was to characterize longitudinal transcriptomic signatures using total peripheral blood mononuclear cells, as well as T and B cell recall responses in eight subjects who spontaneously resolved two successive episodes of HCV infection. Furthermore, we compared the transcriptomic signatures of primary and secondary resolving HCV infections, with an HCV nonstructural protein vaccine regimen of recombinant chimpanzee adenovirus 3 vector prime followed by modified vaccinia Ankara boost. We identified a plasma cell transcriptomic signature during early acute HCV reinfection that was absent in primary infection and following HCV vaccine boost. Spontaneous resolution of HCV reinfection was associated with rapid expansion of glycoprotein E2-specifc memory B cells in 3 subjects and transient increase in E2-specific neutralizing antibodies in 6 subjects. Concurrently, there was an increase in the breadth and magnitude of HCV-specific T cells in 7 subjects. In conclusion, we identified thirteen new public CD8+ TCR clonotypes unique to HCV that expanded during acute infection and reinfection. The low frequency of crossreactive TCRs suggests that they are not major determinants of infectious outcome. Moreover, we observed a concurrent increase of HCV-specific B and T cell responses early during acute HCV reinfection at the transcriptomic and functional levels, suggesting a role for both arms of the adaptive immune response in HCV reinfection clearance. Our results support the combined T and B cell-based vaccine strategy aimed at preventing chronic HCV infections.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Hepatitis C virus (HCV) is one of the leading causes of hepatocellular carcinoma worldwide. HCV-neutralizing antibody AP33 recognizes a linear, highly conserved epitope on the viral entry protein E2, disrupting the interaction with the cellular receptor CD81 that leads to viral entry. AP33-related anti-idiotypes (Ab₂s) have the potential to carry the internal image of the antigen E2, eliciting the production of AP33-like antibodies in humans. This study reports the mid-resolution structure of the Fab fragment of anti-idiotype A164.3 and the high-resolution structure of the Fab fragment of AP33 in complex with the Fv fragment of anti-idiotype B2.1A. Analysis of the structures and comparison with the previously published structure of AP33 in complex with a peptide corresponding to the E2 epitope, suggests that while A164.3 does not mimic the antigen E2, B2.1A is characterized by high surface complementarity with AP33 and functional antigen mimicry. Thus, B2.1A can be classified as an Ab₂-β, a subgroup of anti-idiotypes carrying the internal image of the antigen. Preliminary binding studies show that AP33 binds B2.1A with nanomolar affinity, supporting the role of B2.1A as an idiotypic vaccine candidate. Zaire ebola virus causes severe, often lethal hemorrhagic fever in humans. Ebola virus polymerase cofactor VP35 is a multifunctional protein involved in, among other functions, dsRNA binding and inhibition of the host's interferon pathways. VP35 contains an N-terminal oligomerization domain and a C-terminal dsRNA-binding domain (RBD). Preliminary results on the oligomerization domain of VP35 suggest that this region contains a coiled-coil motif, as previously reported. In order to validate a recently-discovered dsRNA end-capping pocket as a drug target, the structure of VP35 RBD I278A mutant was solved at high resolution, showing that even a small perturbation in the binding pocket can cause dramatic binding impairment due to loss of contacts with dsRNA.

Submitted by Cleide Dantas (cleidedantas@ufpa.br) on 2014-02-07T15:44:34Z No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_AvaliacaoFatoresRiscoInfeccao.pdf: 590365 bytes, checksum: f672712219ca8ab37153dddf238154ab (MD5) / Approved for entry into archive by Ana Rosa Silva (arosa@ufpa.br) on 2014-04-03T14:47:17Z (GMT) No. of bitstreams: 2 Dissertacao_AvaliacaoFatoresRiscoInfeccao.pdf: 590365 bytes, checksum: f672712219ca8ab37153dddf238154ab (MD5) license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) / Made available in DSpace on 2014-04-03T14:47:17Z (GMT). No. of bitstreams: 2 Dissertacao_AvaliacaoFatoresRiscoInfeccao.pdf: 590365 bytes, checksum: f672712219ca8ab37153dddf238154ab (MD5) license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Previous issue date: 2009 / As hepatites virais constituem um dos mais importantes assuntos de saúde pública, podendo ser causadas por diferentes agentes etiológicos. Dentre estes, encontra-se o Vírus da hepatite C (HCV), que segundo a Organização Mundial da Saúde (OMS) afeta mundialmente cerca de 123 milhões de pessoas, com uma prevalência de 2%. A principal forma de transmissão do HCV é a exposição ao sangue contaminado. O HCV pertence à família Flaviviridae, gênero Hepacivirus, possui 6 genótipos e múltiplos subtipos. No Brasil, o genótipo 1 é observado em 70% dos pacientes infectados, seguido pelo genótipo 3 (25%) e o genótipo 2 (5%). Alguns fatores de risco são fortemente associados à transmissão do HCV, dentre eles: o uso de seringa de vidro esterilizada em domicílio; o compartilhamento de utensílios de higiene pessoal como a lâmina de barbear, escova de dente, alicates de manicure e cortadores de unhas e também a transfusão de sangue antes de 1993. O presente estudo teve como objetivo executar um inquérito epidemiológico sobre fatores de risco relacionados à infecção pelo HCV e, determinar a soroprevalência de anti-HCV em candidatos a doação de sangue, no Estado do Pará. Foram analisados os seguintes fatores de risco: o uso de agulhas e seringas esterilizadas em domicílio; o uso de material próprio de manicure e pedicure; o uso de lâminas descartáveis em ambiente público; o uso compartilhado de lâminas em ambiente domiciliar; a realização de tratamento dentário invasivo e; o recebimento de transfusão antes de 1993. Foram alocados ao acaso, 11.916 candidatos ao processo de doação sanguínea da Fundação HEMOPA, no período de fevereiro de 2008 a março de 2009, posteriormente divididos em dois grupos: (1) aqueles com sorologia positiva para anti-HCV e; (2) aqueles com sorologia negativa para anti-HCV. O primeiro grupo foi constituído de 53 candidatos com sorologia positiva (0,4%) e o segundo grupo de 11.863 candidatos com sorologia negativa (99,6%). A análise dos dados mostrou que a mediana de idade entre os indivíduos anti-HCV positivos foi de 35 anos. Observou-se que dentre os indivíduos com sorologia positiva, 36 eram do sexo masculino (68%) e 17 do sexo feminino (32%). Já entre os candidatos com sorologia negativa, 9.250 pertenciam ao sexo masculino (78%) e 2.613 ao sexo feminino (22%). A análise dos fatores de risco estudados demonstrou que o uso de seringa de vidro em domicílio, a utilização de material não-próprio de manicure e pedicure e o recebimento de transfusão antes de 1993, foram fatores significativos para a transmissão do HCV na população de candidatos à doação de sangue, no Estado do Pará. Estes achados poderão propiciar estratégias de redução da hepatite C transfusional. / The viral hepatitis are the most important subject of public health, being caused by differents etiologic agents. Amongst these, we find the hepatitis C virus (HCV) that according to the World Health Organization (WHO) its affects about 123 millions of people world-wide, a prevalence of 2%. The main form of transmission is the exposition to infected blood. The HCV is part of Flaviviridae family, Hepacivirus genus, its possess 6 genotypes and multiples subtypes. In Brazil, the genotype 1 is observed in 70% of infected patients, followed by genotype 3 (25%) and genotype 2 (5%). Some risk factors are strongly related with the HCV transmission, amongst them: the utilization of sterilized glass syringe at home; the sharing of utensils of personal hygiene as shavers, tooth brush, pliers of manicure and cutting nails and; blood transfusion before 1993. The present study aimed to execute an epidemiologic inquiry about risk factors related with the HCV infection and determinate the anti-HCV seroprevalence in candidates of blood donation, in the State of Pará. The following risk factors were analyzed: the use of sterilized needles and syringes at home; the use of proper material of manicure and pedicure; the use of disposable blades in public environment; the accomplishment of invasive dental treatment and; the act of receiving blood transfusion before 1993. At the period of february/2008 to march/2009, 11.916 candidates to the blood donation process at HEMOPA Foundation were random placed, later divided in two groups: (1) with anti-HCV positive serology and; (2) with anti-HCV negative serology. The first group was constituted of 53 candidates with positive serology (0,4%) and the second of 11.863 candidates with negative serology (99,6%). The data analyses showed that the median age of the anti-HCV positive individuals were 35 years. It was observed that amongst individuals with positive serology, 36 were male (68%) and 17 were female (32%). Between candidates with negative serology, 9.250 were male (78%) and 2.613 were female (22%). The analyses of the studied risk factors showed that the use of glass syringe at home, the use of non-proper material of manicure and pedicure and the act of receiving blood transfusion before 1993 are significant factors to the HCV transmission into the population of candidates to blood donation, in the State of Pará. These findings will propitiate strategies to the reduction of transfusional hepatitis C.

Submitted by Edisangela Bastos (edisangela@ufpa.br) on 2015-07-02T16:17:38Z No. of bitstreams: 2 license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) Dissertacao_SoroepidemiologiaHCVDoadores.pdf: 1087496 bytes, checksum: d9256a5068e7e690412f5245c8574338 (MD5) / Approved for entry into archive by Albirene Aires (albireneufpa@gmail.com) on 2015-07-09T14:15:05Z (GMT) No. of bitstreams: 2 license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) Dissertacao_SoroepidemiologiaHCVDoadores.pdf: 1087496 bytes, checksum: d9256a5068e7e690412f5245c8574338 (MD5) / Made available in DSpace on 2015-07-09T14:15:05Z (GMT). No. of bitstreams: 2 license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) Dissertacao_SoroepidemiologiaHCVDoadores.pdf: 1087496 bytes, checksum: d9256a5068e7e690412f5245c8574338 (MD5) Previous issue date: 2012 / Devido à alta mortalidade e, principalmente, a morbidade, as hepatites são um dos mais graves problemas de Saúde Pública, no País e no mundo. Entre elas destacamos a infecção da hepatite C. O número de pessoas que desconhecem que são portadoras do vírus HCV é relevante. Como atualmente a transmissão do HCV por transfusão sanguínea e hemoderivados é rara entre os doadores de sangue, depois da introdução do método de triagem nos centros hemoterápicos, fundamental para detectar a existência de uma possível infecção neste doador. A realidade epidemiológica da hepatite C em Imperatriz necessita de maior conhecimento e planejamento das estratégias de prevenção e assistência aos portadores de HCV, uma vez que não existe uma rede de serviço consolidada para o tratamento, a burocracia é grande para se chegar ao diagnóstico da doença e a sub-notificação dos casos é elevada. Tem como objetivo avaliar a soroprevalência do HCV em candidatos à doação de sangue no município de Imperatriz – MA; assim como analisar o perfil dos candidatos considerados inaptos a doação de sangue no HEMOMAR, nesta cidade; determinar a soroprevalência do Vírus da Hepatite C entre os doadores de sangue no período de 2005 a 2010; realizar o levantamento dos dados epidemiológicos, destacando o gênero e a faixa etária de maior prevalência do vírus da hepatite C; comparar os dados epidemiológicos identificando a procedência dos candidatos soropositivos para o vírus da hepatite C. o estudo é de caráter descritivo transversal, envolvendo doadores de sangue do Centro de Hematologia e Hemoterapia do Estado do Maranhão de Imperatriz - MA. Na distribuição dos doadores de sangue do HEMOMAR, regional de Imperatriz -MA quanto ao sexo, constata-se que, nos anos de 2005 à 2011 o fluxo de doadores caracterizou-se por indivíduos de ambos os sexos,com predominância do masculino (75,01%), quando analisamos o perfil dos candidatos a doadores com sorologia positiva para HCV, observamos que estes também eram a maioria. A faixa etária dos doadores de sangue do HEMOMAR predominante era de 18-29. Os candidatos a doação com sorologia positiva para HCV, foram encontrados 79,17% na situação de casados/união estável. Entre os doadores que foram considerados inaptos a doação, 0,21% apresentou sorologia positiva para HCV. A maioria dos candidatos a doadores com soropositividade para HCV pertencia ao município de Imperatriz. Concluiu-se que é importante lembrar que o processo de triagem clínica e laboratorial diminui riscos de contaminação no processo de transfusão sanguínea. A figura do doador de sangue deve ser sempre valorizada e parabenizada por todos. / Due to high mortality and especially morbidity, hepatitis is one of the most serious public health problems in the country and the world. Among them we highlight the infection of hepatitis C. The number of people who are unaware they are infected with HCV is relevant. As currently HCV transmission by blood transfusion and blood products is rare among blood donors, after the introduction of screening method in centers haemotherapic, crucial to detect the existence of a possible infection in the donor. The epidemiological reality of hepatitis C in Empress needs more knowledge and planning prevention strategies and assistance to individuals with HCV, since there is no network service for consolidated treatment, bureaucracy is great to reach the diagnosis of disease and under-reporting of cases is high. Aims to evaluate the prevalence of HCV in blood donation candidates in the municipality of Imperatriz - MA, so as to analyze the profile of the candidates considered unfit to donate blood in HEMOMAR, this city; determine the seroprevalence of Hepatitis C Virus among blood donors in the period from 2005 to 2010; conduct the survey of epidemiological data, highlighting the gender and age group with the highest prevalence of hepatitis C; comparing epidemiological data identifying the merits of the candidates seropositive for hepatitis C. the study is cross-sectional in nature, involving blood donors of the Center for Hematology of Maranhão Imperatriz - MA. In the distribution of blood donors HEMOMAR, regional Imperatriz-MA for sex, it appears that, in the years 2005 to 2011 the flow of donors was characterized by individuals of both sexes, with male predominance (75, 01%), when analyzing the profile of prospective donors with positive serology for HCV, we found that these were also the majority. The age of the blood donors was the predominant HEMOMAR 18-29. Candidates donation with positive serology for HCV, 79.17% were found in the situation of married / stable. Among the donors who were considered unfit to donate, 0.21% were seropositive for HCV. Most prospective donors with HCV seropositivity belonged to the municipality of Imperatriz. It was concluded that it's important to remember that the screening process clinical and laboratory reduces contamination risks in the process of blood transfusion. The figure of the donor blood should always be appreciated and congratulated by all.