The obligate intracellular bacterium Chlamydia trachomatis is the most common bacterial STD agent in the US. This bacterium has a unique biphasic developmental cycle in which the infectious elementary body (EB) infects a host mucosal epithelial cell and differentiates into the replicative form (the reticulate body or RB) within a modified vacuole called an inclusion. The RB later divides and develops back into an EB and is released, perpetuating the infectious cycle. When developing chlamydiae are exposed to unfavorable environmental conditions, they deviate from the normal developmental cycle into a non-infectious but viable state termed persistence. Previous data from our laboratory indicate that i) during C. trachomatis/HSV co-infection, the chlamydiae become persistent and ii) HSV gD interaction with host cell surface is sufficient to induce this response. During viral entry, HSV gD interacts with one of four host co-receptors, one of which is the host adhesion molecule nectin-1. Interestingly, Western blotting demonstrated that nectin-1 is significantly decreased in C. trachomatis-infected HeLa cells. Additional studies indicated that active C. trachomatis replication is required for nectin-1 down-regulation and nectin-1 is likely down-regulated post-translationally. CPAF, a chlamydia-secreted protease, is responsible for degrading several host proteins. Both in vivo experiments using CPAF-specific chemical inhibitors and cell-free cleavage assays using recombinant CPAF indicate that nectin-1 is degraded by CPAF in C. trachomatis-infected cells. Further studies suggest that nectin-1 is the most likely candidate involved in triggering HSV-induced chlamydial persistence. Co-infection experiments using nectin-1-specific HSV-1 mutants suggest that nectin-1 is, indeed, required for persistence induction. Additional studies in single co-receptor-expressing CHO cells demonstrate that, despite the fact that HSV-1 enters both HVEM- and nectin-1-expressing cells, viral co-infection reduces chlamydial infectivity only in the CHO-nectin-1 cell line. These data confirm that HSV/nectin-1 interaction is sufficient for chlamydial persistence induction. Although nectin-1 ligation is known to activate Cdc42, pull-down assays indicate that Cdc42 is not activated in co-infected HeLa cells. Taken together, these data suggest that: i) HSV gD-nectin-1 binding activates a novel host epithelial cell pathway that restricts chlamydial development and ii) the chlamydiae may degrade nectin-1 to evade this inhibitory host response.

The aim of this thesis was to track the impact of selected herpesviruses, polyomaviruses, Chlamydia trachomatis and methylation of tumor supressor genes at the development and progression of high grade- lesion in HPV - positive patients by means of molecular-genetic techniques. Confirmation of these markers presence in women with severe lesions of cervix would help to raise necessary specificity of molecular genetics HPV testing and recommend it as a primary screening test for cervical carcinoma prevention. HPV testing could thus replace currently prevailing cytology which has relatively low sensitivity and therefore the number of false negative results. The analyzed samples consisted of cytological cervical smears of 51 HPV positive women, with histologically confirmed presence of severe lesions, collected in liquid medium. Samplings from 51 women without infection were used as a control. The possible effect on disease progress was confirmed only in the case of gene promoters' methylation whose presence was detected in up to 26 patients. It is, however, very unlikely that cancer would develop in all these women. This marker could thus help to stratify patients at risk but only to some extent. Although the individual effect of remaining markers has not been established in the carcinogenesis of cervical...

INTRODUÇÃO: O vírus da hepatite G (GBV-C) foi descoberto simultaneamente por dois grupos de pesquisa que buscavam identificar um agente causador de hepatite pós-transfusional não-A, não-B e não-C. Trata-se de um vírus linfotrópico que replica primariamente em células mononucleares do sangue periférico (PBMC), baço e medula óssea, sendo a replicação hepática menos importante. Sabe-se que, após um período de viremia assintomática, a maioria dos carreadores virais clareia o vírus ao longo do tempo havendo surgimento do anticorpo contra a glicoproteína do envelope viral, anti-E2. Uma vez que, provavelmente, não exista nenhuma associação entre o GBV-C e qualquer doença identificada até o momento, o mesmo tem sido considerado um vírus humano não patogênico. Entretanto, alguns estudos demonstraram haver uma interação benéfica entre o GBV-C e HIV a ponto de retardar a progressão da infecção pelo HIV para aids. OBJETIVOS: Avaliar a prevalência da viremia e de anticorpos contra a glicoproteína anti-E2 e estudar o efeito da interação GBV-C e HIV ao longo do acompanhamento de pacientes femininas baseado em valores da média e mediana de linfócitos T CD4+ , da carga viral do HIV e da carga viral quantitativa do GBV-C RNA. MÉTODOS: Foram estudas 248 pacientes femininas portadoras da infecção pelo HIV acompanhadas por um período de cerca de 10 anos, tendo como término de estudo a data limite de 01/01/2008, ou a data da última consulta no ambulatório ou a data do óbito. RESULTADOS: Das 115 pacientes expostas, 57 eram GBV-C RNA positivas (23%) e 58 eram anti-E2 positivas (23%). Não houve achado da presença concomitante do GBV-C RNA e do anticorpo anti-E2 nas pacientes estudas. Com relação à contagem de linfócitos T CD4+ e de carga viral basal do HIV no início do estudo, não observamos diferença estatística entre os valores em relação aos grupos (GBV-C RNA-/anti-E2- , GBV-C RNA+/anti-E2 - e GBV-C RNA -/anti-E2+), sendo o p=0,36 e 0,713, respectivamente. O risco relativo de óbito para o grupo GBV-C+/anti-E2- foi 63% menor do que para o grupo GBV-C-/anti-E2-. CONCLUSÃO: A prevalência da viremia por GBV-C RNA e a do anticorpo anti-E2 foi de 23%, perfazendo uma frequência de exposição ao GBV-C de 46%. Em análise multivariada, apenas a carga viral do HIV, maior que 100.000 cópias/mL, e manifestação de doença oportunística ao longo do acompanhamento das pacientes estiveram associadas à melhora da sobrevida. Provavelmente, o uso da terapia antirretroviral para o HIV foi fator limitante na análise de efeito protetor do GBV-C RNA em nossa casuística / INTRODUCTION: GB virus C (GBV-C) was discovered by two research groups that aimed to identify a possible agent responsible for a non-A, non-B and non-C pos-transfusion hepatitis. There is remarkable evidence that GBV-C is a lymphotropic virus that primarily replicates in PBMCs, spleen and bone marrow. This virus does not appear to be hepatotropic and does not replicate effectively in hepatocytes. After an asymptomatic viremia period, most subjetcs clear the virus over time with the development of antibody against a viral envelope glycoptrotein (anti-E2). Since there is probably no association between GBV-C and any identify disease, this virus has been considered not pathogenic. However, according to some studies, GBV-C co-infection in HIV seropositive patients is associated with a slower disease progression and longer survival after AIDS development in HIV infected patients. Objective: To evaluate the prevalence of GBV-C viremia, anti- E2 antibody and assess the effect of the interaction of GBV-C and HIV in an exclusive female cohort, in a follow up period of up to 10 years. Methodos: Two hundred forty-eight HIV infected women were enrolled in the study. Follow-up sample was obtained from 248 patients. Laboratorial variables as mean and median of values of CD4, HIV and GBV-C quantitative viral load, and clinical parameters as HAART use, OIs influence on survival were investigated. Results: One hundred and fifteen subjects were exposed to GBV-C: 57 were GBV-C RNA positive (23%) and 58 were anti-E2 antibody positive (23%). Viral RNA with concomitant anti-E2 antibodies was not found in any patient. There was no statistical difference among three studied groups (GBV-C RNA-/anti-E2 - , GBV-C RNA+/anti-E2- and GBV-C RNA -/anti-E2+), regarding CD4+ and viral load baselines (p=0,360 and 0,713, respectively). Relative risk of death for GBV-C RNA+/anti-E2- group was 63% lower than the GBV-C-/anti-E2 group. Conclusion: Forty-six percent of the enrolled individuals were exposed to GBV-C virus. Multivariate analysis demonstrated that only HIV load higher than 100.000 copies/mL and opportunistic disease during the follow-up period were associated to longer survival after AIDS development. Probably, antiretroviral therapy for HIV in our study blurred the observation of a putative protective effect related to GBVC RNA

Introdução: No mundo especula-se que 15 a 20 milhões tenham infecção crônica pelo HDV. No Brasil, a área endêmica de hepatite Delta corresponde aos estados da Amazônia Ocidental, incluindo Rondônia. Hepatite Delta é a mais grave e com mais rápida evolução para cirrose dentre as hepatites virais. Poucos estudos avaliaram os aspectos epidemiológicos, clínicos e laboratoriais de uma coorte de pacientes em nosso país e no mundo. Objetivos: Em uma coorte de pacientes acompanhados em um serviço de referência: 1. Avaliar as características demográficas, epidemiológicas e clínicas; 2. Avaliar a frequência de doença hepática avançada; 3. Avaliar as características da população atendida com idade <=18 anos; 4. Avaliar a acurácia de escores não invasivos (razão AST/ALT, APRI e FIB-4) na determinação dos diferentes graus de fibrose. Métodos: Trata-se de um estudo transversal, descritivo, de uma coorte de pacientes retrospectivamente identificadas no ambulatório especializado em hepatites virais, pertencente ao Centro de Pesquisa em Medicina Tropical do Estado de Rondônia (CEPEM), situado na cidade de Porto Velho, com diagnóstico de infecção pelo HDV. Foram incluídos todos os pacientes com diagnóstico dessa infecção por sorologia (ELISA) ou por biologia molecular (HDV-RNA reagente), matriculados e atendidos neste serviço entre novembro de 1996 a março de 2015. Resultados: Dentre 4.101 pacientes diagnosticado com HBV, 224 (5,5%) apresentavam coinfecção com o HDV, e 205 foram incluídos nas análises. Dentre eles, 132 (64,4%) eram do sexo masculino, com idade média de 35,1 anos. O contato familiar foi o fator de exposição para infecção pelo VHB/VHD mais frequente. A determinação do genótipo do HDV foi obtida em 78 pacientes, destes 74 (94,9%) eram genótipo III e 4 (5,1%) genótipo I. Noventa e dois (44,9%) pacientes apresentavam evidência de doença hepática avançada. Dentre os pacientes incluídos 22 (10,7%) tinham idade <= 18 anos, sendo que 6 (27,3%) apresentavam sinais e sintomas de doença hepática avançada ou fulminante à primeira consulta. Métodos não invasivos foram calculados e comparados à biópsia hepática em 50 pacientes. A razão AST/ALT não teve valor significativo para avaliar fibrose em nenhum dos estágios. APRI e FIB-4 tiveram melhor desempenho para avaliar fibrose significativa (>=F2), com acurácia de 86 e 80, respectivamente. Conclusões: 1. O HDV representa importante agravo de saúde pública em Rondônia com frequência expressiva entre pessoas do sexo masculino e população indígena; 2. A presença da infecção pelo HDV esteve associada a expressivo número de complicações hepáticas e foi frequente causa de óbito na população analisada, particularmente entre adultos jovens; 3. Entre pacientes com idade <= 18 anos a hepatite delta esteve associada a significante morbidade e mortalidade e a falta de adesão dessa população pareceu contribuir para esse tipo de desfecho; 4. A utilização dos métodos não invasivos (APRI e FIB-4) foi capaz de identificar pacientes com fibrose significativa entre indivíduos infectados com HDV na Amazônia brasileira, podendo, apesar de todas as limitações destes métodos servir como alternativa para avaliação de fibrose hepática significativa, na ausência de outros métodos mais efetivos / Introduction: In the world, it is speculated that 15 to 20 million people have chronic HDV infection. In Brazil, the endemic area of hepatitis Delta corresponds to the states of the Western Amazon, including Rondônia. Hepatitis Delta is the most serious and most rapidly evolving cirrhosis among viral hepatitis. Few studies have evaluated the epidemiological, clinical, and laboratory aspects of a cohort of patients in our country and around the world. Objectives: In a cohort of patients followed at a referral service: 1. Evaluate demographic, epidemiological and clinical characteristics; 2. Assess the frequency of advanced liver disease; 3. Evaluate the characteristics of the population served with age <=18 years; 4. To evaluate the accuracy of non-invasive scores (AST/ALT ratio, APRI and FIB-4) in determining the different degrees of fibrosis. Methods: This is a cross-sectional, descriptive study of a cohort of patients retrospectively identified in the ambulatory specialized in viral hepatitis, belonging to the Research Center of Tropical Medicine of Rondônia State (CEPEM), located in the city of Porto Velho. All patients diagnosed with this serological method (ELISA) or molecular biology (HDV-RNA), enrolled in this service between November 1996 and March 2015, were included. Results: Out of 4,101 patients diagnosed with infection by HBV, 224 (5.5%) had coinfection with the hepatitis delta virus, and 205 were included in the analyzes. Among them, 132 (64.4%) were males, with a mean age at the time of enrollment of 35.1 years. Family contact was the most frequent exposure factor for HBV/HDV infection. It was identified seventy-eight patients (94.9%) of genotype III and four (5.1%) of genotype I. Ninety-two (44.9%) patients had evidence of advanced liver disease. Among the patients included, 22 (10.7%) were aged <= 18 years, and 6 (27.3%) had signs and symptoms of advanced or fulminant liver disease at the first visit. Noninvasive methods were calculated and compared to liver biopsy in 50 patients. The AST/ALT ratio had no significant value for evaluating fibrosis in any of the stages. APRI and FIB-4 had better performance to evaluate significant fibrosis (>=F2), with the accuracy of 86 and 80 respectively. Conclusions: 1. The hepatitis delta virus represents an important public health problem in the State of Rondônia, affecting both adults and children, with significant frequency among males and the indigenous population; 2. The presence of HDV infection was associated with a significant number of hepatic complications and was a frequent cause of death in the analyzed population, particularly among young adults; 3. Among patients aged <= 18 years, delta hepatitis was associated with significant morbidity and mortality and the lack of adherence of this population to follow-up seemed to contribute to this type of outcome; 4. The use of the non-invasive APRI and FIB-4 methods were able to identify patients with significant fibrosis among individuals infected with HDV in the Brazilian Amazon, although all limitations of these methods may serve as an alternative for the evaluation of significant hepatic fibrosis in the absence of other more effective methods

Die ökologische Rolle der meisten Wildtier-Pathogene in Bezug zur langfristigen Populationsdynamik ihrer Wirte ist nur ansatzweise erforscht und wird deshalb nur unzureichend verstanden. Stattdessen ist die Erforschung von Infektionen mit Pathogenen oft beschränkt auf einzelne Fallstudien oder auf Perioden mit deutlich erhöhten Mortalitätsraten innerhalb der Wirtspopulation. Pathogene mit geringer Virulenz können jedoch durch synergistisches Auftreten verheerende Auswirkungen auf die Fitness ihrer Wirte haben oder sich auf wichtige individuelle lebensgeschichtliche Merkmale, wie zum Beispiel Lebensdauer oder Reproduktionserfolg, auswirken. Des Weiteren sind die Auswirkungen von Krankheitserregern auf die Populationsdynamik der Wildtiere schwer abzuschätzen, zum Beispiel wenn sie die Überlebenschancen von selten zu beobachtenden Jungtieren beeinträchtigen. Bis heute sind Untersuchungen von Infektionen mit Pathogenen und deren Auswirkungen auf Lebensgeschichten meist auf Laborstudien beschränkt, in denen Tiere unter streng definierten Bedingungen gezüchtet und gehalten werden, bzw. auf Studien an kleinen, kurzlebigen Arten wie Nagern, Vögeln und Insekten oder auf Studien an der Humanpopulation. Ziel dieser Arbeit war, die Auswirkungen von Einzel- oder Koinfektionen auf individuelle lebensgeschichtliche Schlüsselparameter sowie die Einflüsse bestimmter lebensgeschichtlicher Merkmale auf den Infektionsstatus anhand einer frei lebenden sozialen Karnivorenart, der Tüpfelhyäne Crocuta crocuta, zu untersuchen. Diese Arbeit war in eine Langzeitstudie integriert und wurde an mehreren Gruppen von Tüpfelhyänen zweier Subpopulationen durchgeführt, die im Serengeti Nationalpark sowie in dem angrenzenden Ngorongoro Krater in Tansania in Ostafrika lebten. Daten über wichtige lebensgeschichtliche Merkmale von mehreren hundert individuell bekannten Tieren in Kombination mit Daten über die wechselhafte Beuteverfügbarkeit in den Territorien der Gruppen standen hierfür zur Verfügung. Ich etablierte molekularbiologische Methoden (Polymerase Kettenreaktionen (PCRs) und Reverse Transkriptions PCRs), um eine Vielzahl an Kot-, Blut- und Gewebeproben individueller Tüpfelhyänen und sympatrisch lebender Karnivoren auf das Vorkommen von Coronaviren, Caliciviren, Hundestaupe-Viren, Parvoviren sowie eines von Zecken übertragenen Blutparasiten, Hepatozoon sp., zu untersuchen. 1 / The ecological role of most wildlife pathogens is poorly understood because pathogens are rarely studied in relation to the long-term population dynamics of wildlife hosts. Instead, pathogen infections are reported on a case basis or studies are focused on periods when pathogens cause noticeable mortality in their hosts. However, pathogens that appear to be of low virulence may also have an important effect if they operate in a synergistic fashion or affect life history parameters such as longevity or reproductive success. Furthermore, the effect of pathogens on population dynamics may be difficult to detect in wildlife, for example if they reduce the survival of young age classes that are rarely observed. Until now, research on the life history consequences of pathogen infection has mainly been confined to laboratory studies where animals are raised and kept under strictly defined conditions, or to small, short lived species such as rodents, birds or insects, as well as to human populations. The aim of this thesis was to address these problems by assessing the impact of single infections and co-infections by pathogens on key life history parameters and the influence of life history traits on infection status in a free-ranging social carnivore species, the spotted hyena Crocuta crocuta. The study was embedded in a long-term study on several clans of spotted hyenas from two subpopulations inhabiting the Serengeti National Park and the adjacent Ngorongoro Crater in Tanzania, East Africa. Data on key life history parameters were available for several hundred individually known animals as was information on changing levels of prey availability. I established molecular biological methods (polymerase chain reactions (PCRs) and reverse transcription PCRs) to screen an extensive set of faecal, blood and tissue samples from individually known spotted hyenas and sympatric carnivores for the presence of coronavirus, calicivirus, canine distemper virus, canine parvovirus and the tick-borne blood parasite Hepatozoon sp. to determine the prevalence of the pathogens. 1

Made available in DSpace on 2016-08-19T18:15:59Z (GMT). No. of bitstreams: 1 FLAVIA LOPES CARVALHO.pdf: 442162 bytes, checksum: b9d2b399e741a894bb9550e5094975a0 (MD5) Previous issue date: 2009-11-18 / Co-infection Leishmania-HIV/Aids is a serious public health problem in almost of the world. The visceral leishmaniasis is the clinical form of leishmaniosis hat is most associated with HIV/Aids cases being the co-infection understated, since the leishmaniasis is not AIDS-defining illness. This was a descriptive cross sectional study from March 2006 to December 2008, aiming to investigate the occurrence of co-infection Leishmania-HIV in individuals living with HIV/Aids in a Reference Center in São Luís-MA. The population studied was composed of 287 individuals. It was used a questionnaire to collect demographic, epidemiological and socioeconomic data. The physical examination was performed and biological material for detection of infection by Leishmania chagasi was collected by indirect immunofluorescence technique (IIFT), and laboratory tests (blood count, CD4 and CD8, viral load, myelography) were found in charts. We used the chi-square test to assess association of demographic, socioeconomic and epidemiological variables between women and men, whereas p ≥ 0.05 for significance. Women and men had a statistically significant difference in color, destination of waste, occupation and family income. The presence of pen and near the residence showed statistically significant differences when comparing men and women. The prevalence of infection with Leishmania sp, detected by Montenegro Skin Test (MST) was 1,4%. All co-infected showed RIFI and as well as the bone marrow aspirate (myelogram) positives. This study helped identify the magnitude of the prevalence of co-infection Leishmania/HIV. Thus, we suggest that the anti-Leishmania has to be part of the differential diagnosis of individuals with HIV / AIDS and those public policies are increased for this problem. / A co-infecção Leishmania-HIV/Aids é um sério problema de saúde pública em quase todo o mundo. A Leishmaniose Visceral é a forma clínica das leishmanioses que está mais associada ao HIV/Aids, sendo os casos de co-infecção considerados subestimados, uma vez que, a leishmaniose não se constitui doença definidora de Aids. Foi realizado um estudo descritivo transversal de março de 2006 a dezembro de 2008, com o objetivo de investigar a ocorrência de co-infecção Leishmania-HIV em indivíduos convivendo com HIV/Aids, atendidas em um Centro de Referência em São Luís-MA. A população do estudo foi constituída por 287 indivíduos. A coleta de dados foi feita por meio de um questionário para a obtenção de dados demográficos, socioeconômicos e epidemiológicos, bem como foi realizado exame físico e coleta de material biológico para detecção da infecção por Leishmania sp , por meio da Intradermorreação de Montenegro (IDRM), Reação de Imunofluorescência Indireta (RIFI) e os exames laboratoriais (hemograma, contagem de CD4 e CD8, carga viral, mielograma) foram consultados nos prontuários. Através do teste qui-quadrado foi avaliado as variáveis demográficos, socioeconômicas e epidemiológicas entre mulheres e homens convivendo com HIV/Aids, considerando p ≥ 0,05 de significância. Houve diferença estatística significante na cor da pele, no destino dos dejetos, na ocupação e na renda familiar; como também na presença de chiqueiro em local próximo à residência. A prevalência da infecção por Leishmania sp detectada pela Intradermorreação de Montenegro (IDRM) foi de 1,4% e a prevalência da co-infecção Leishmania-HIV/Aids foi de 4,2%. Todos os co-infectados apresentaram RIFI e o aspirado de medula óssea (mielograma) positivos. Este estudo permitiu conhecer a magnitude da prevalência da co-infecção Leishmania/HIV. Assim, sugerimos que o teste anti-Leishmania seja realizado em todos os indivíduos com HIV/Aids, e que sejam incrementadas políticas públicas voltadas para essa problemática.

Le développement de maladies d'origine tellurique relève de mécanismes épidémiologiques particuliers, propres au cycle biologique et aux traits d'histoire de vie des agents pathogènes incriminés. La caractérisation des processus qui déterminent le développement des épidémies est une étape clé dans la conception et l'optimisation de méthodes de protection contre ces maladies. Les cultures légumières de plein champ constituent des agrosystèmes particulièrement sensibles aux attaques parasitaires. Les Pythium sont responsables du cavity spot de la carotte, une maladie racinaire qui affecte la qualité des récoltes dans plusieurs bassins de production en France et dans le monde. L'objectif des recherches présentées ici est d'identifier, comprendre et hiérarchiser les processus déterminant la dynamique spatio-temporelle de cette maladie, essentiellement due à Pythium violae, en association avec d'autres espèces du complexe parasitaire. L'analyse de la composition d'un de ces complexes, complétée par la caractérisation biologique des principales espèces pathogènes, suggère que par souci de simplification, il est raisonnable de négliger les interactions entre espèces au cours de la phase infectieuse. L'existence d'infections secondaires (auto- et allo-infections) chez P. violae, et donc la nature polycyclique d'une épidémie de cavity spot, sont démontrées expérimentalement. Cette hypothèse est initialement étayée par deux étapes de l'analyse, l'une portant sur l'examen de relations pathométriques, et l'autre sur les ajustements de modèles aux données illustrant des cinétiques de la maladie. L'ensemble des résultats obtenus permet de concevoir un modèle épidémiologique exploratoire, basé sur l'occurrence des infections primaires et secondaires. Les effets de différents facteurs sur ces processus, comme l'application d'un fongicide, l'humidité du sol et la densité de semis, sont testés expérimentalement et discutés. Ils permettent d'envisager l'association de moyens de lutte complémentaires dans le cadre de stratégies de protection intégrée.

<p><font face="Times New Roman" size="3"><font face="Times New Roman" size="3"> <p align="left">The aim of the study is to explore the barriers associated with low VCT uptake by the TB patients attending primary health care clinics within the Buffalo City municipality. <font face="Times New Roman" size="3"><font face="Times New Roman" size="3">The study population was drawn from TB patients attending the primary health care facilities in Buffalo city municipality in the Eastern Cape Province. Eight participants were purposively selected to include those who had accepted VCT as well as those who did not.</font></font></p> </font></font></p>

There is a growing interest in the dynamics of the co-infection of these two diseases. In this thesis, firstly we focus on studying the effect of a distributed delay representing the incubation period for the malaria parasite in the mosquito vector to possibly reduce the initial transmission and prevalence of malaria. This model can be regarded as a generalization of SEI models (with a class for the latently infected mosquitoes) and SI models with a discrete delay for the incubation period in mosquitoes. We study the possibility of occurrence of backward bifurcation. We then extend these ideas to study a full model of HIV and malaria co-infection. To get further inside into the dynamics of the model, we use the geometric singular perturbation theory to couple the fast and slow models from the full model. Finally, since the governing models are very complex, they cannot be solved analytically and hence we develop and analyze a special class of numerical methods to solve them.

In this thesis, we study these models and design and analyze robust numerical methods to solve them. To proceed in this direction, first we study the sub-models and then the full model. The first sub-model describes the transmission dynamics of HIV that accounts for behavior change. The impact of HIV educational campaigns is also studied. Further, we explore the effects of behavior change and different responses of individuals to educational campaigns in a situation where individuals may not react immediately to these campaigns. This is done by considering a distributed time delay in the HIV sub-model. This leads to Hopf bifurcations around the endemic equilibria of the model. These bifurcations correspond to the existence of periodic solutions that oscillate around the equilibria at given thresholds. Further, we show how the delay can result in more HIV infections causing more increase in the HIV prevalence. Part of this study is then extended to study a co-infection model of HIV-TB. A thorough bifurcation analysis is carried out for this model. Robust numerical methods are then designed and analyzed for these models. Comparative numerical results are also provided for each model.