Submitted by Geandra Rodrigues (geandrar@gmail.com) on 2018-04-18T10:56:17Z No. of bitstreams: 1 rodrigodemartinalmeida.pdf: 1545092 bytes, checksum: 867683f208ae95160982b0697b1b73c3 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-04-20T12:47:44Z (GMT) No. of bitstreams: 1 rodrigodemartinalmeida.pdf: 1545092 bytes, checksum: 867683f208ae95160982b0697b1b73c3 (MD5) / Made available in DSpace on 2018-04-20T12:47:44Z (GMT). No. of bitstreams: 1 rodrigodemartinalmeida.pdf: 1545092 bytes, checksum: 867683f208ae95160982b0697b1b73c3 (MD5) Previous issue date: 2015-02-26 / A tuberculose (TB) é uma doença existente há milhares de anos e estima-se que um terço da humanidade esteja infectada pelo bacilo da doença, com mais de oito milhões de casos novos ao ano. O aumento do número de casos de TB se deve a fatores diversos, como as condições de moradia e outros Determinantes Sociais da Saúde, mas nada modificou tanto sua evolução como a pandemia do vírus da imunodeficiência humana (HIV). A associação desta co-infecção é sinérgica, interativa e recíproca, impactando no curso das duas patologias. A taxa média global de co-infeccção está entre 9 e 18%, embora encontrem-se taxas de até 80% na África. Percebe-se, todavia, baixa cobertura do exame anti-HIV no Brasil, entre outros fatores, porque o exame só é realizado mediante autorização do paciente. Este estudo transversal objetivou descrever a população de pacientes (n=231) com TB, no período de março de 2008 a fevereiro de 2010, atendidos em centros de referência em Juiz de Fora, município com a segunda maior prevalência de TB do estado de Minas Gerais, além de estimar a prevalência de HIV nesses pacientes, estratificando-os de acordo com 3 blocos de variáveis: uso de drogas, de comportamento sexual e socioeconômicas, avaliando os possíveis fatores associados à co-infecção e maior vulnerabilidade, através de dados de um questionário estruturado. Mais de dois terços dos pacientes do estudo eram do sexo masculino, a maior parte da amostra era negra ou parda e mais de 90% da amostra estava na faixa etária economicamente produtiva. A sorologia para HIV detectou 13,0% de co-infecção para o total do estudo e 18,1% quando se descartam os dados ignorados (28,1% dos pacientes sem resultado de HIV por diferentes motivos). As variáveis que mostraram associação com HIV positivo (p≤0,10) na análise bivariada foram o tipo de moradia, condição de ocupação, estado civil, número de parceiros sexuais ao longo da vida, orientação sexual, tabagismo, alcoolismo, uso de drogas ilícitas e uso de drogas injetáveis. Essas variáveis foram incluídas no modelo de regressão logística binária hierarquizado por blocos- uso de drogas, comportamento sexual e socioeconômicas, nessa ordem. No modelo final, mostraram-se significativas o uso de drogas injetáveis, o número de parceiros sexuais ao longo da vida e a condição de ocupação (p≤0,05). Pacientes que nunca trabalharam ou não estavam trabalhando apresentaram risco aumentado para HIV, (OR= 7,49 IC 95% 1,17- 47,9) em relação aos que trabalhavam. Pacientes que tiveram entre 4 e 9 parceiros apresentaram maiores riscos quando comparados aos que tiveram entre nenhum e 3 parceiros (OR= 26,7 IC95% 1,95 - 365,4), e, quanto ao uso de drogas injetáveis, os usuários apresentaram maiores riscos que os não usuários (OR= 26,0 IC95% 1,43- 472,4). O modelo final apresentou uma variável de cada bloco, reforçando a interconexão entre os fatores que geram a associação HIV/TB. Portanto, o processo de co-infecção deve e precisa ser visto de forma multifatorial e abranger ações sociais e políticas, especialmente quanto à realização da sorologia para HIV, tanto para evitar o crescimento das taxas de incidência e prevalência, quanto para o cuidado dos pacientes já co-infectados, trazendo melhorias à Saúde Coletiva. / Tuberculosis (TB) is a disease existing for thousands of years and it is estimated that one third of humanity is infected with the bacillus of the disease, with more than eight million new cases a year. The increase in the number of TB cases is due to several factors, such as quality of housing and other social determinants of health, but nothing changed its evolution as the pandemic of human immunodeficiency virus (HIV). The co-infection is synergic, interactive and has a reciprocal impact on the course of both diseases. The overall average rate of co-infection is between 9 and 18%, rates of up to 80% are found in Africa. It is well-known, however, the reality of low coverage of HIV testing in Brazil, among other factors, because the examination is carried out only after the authorization of the patient. This cross-sectional study aimed to describe the patient population (n = 231) with TB, from March 2008 to February 2010, seen at referral centers in Juiz de Fora, a city with the second highest prevalence of TB in the state of Minas Gerais, and estimate the prevalence of HIV in these patients, stratifying them according to three blocks of variables: drug use, sexual behavior and socioeconomic status, evaluating the possible factors associated with co-infection and increased vulnerability through data obtained from a structured questionnaire. More than two thirds of the study patients were male, the majority of the sample was black or brown and more than 90% of the sample was in the economically productive age group. The HIV test detected 13.0% of co-infection for the total study (28.1% of patients without the HIV test result, were considered) and 18.1% when missing data were discarded. The variables associated with HIV (p≤0,10) in the bivariate analysis were the type of housing, employment status, marital status, number of sexual partners over a lifetime, sexual orientation, smoking, alcoholism, illicit drug use and injection drug use. These variables were included in the regression model, a multiple covariates dichotomous logistic model with hierarchical blocks - by drug use, sexual behavior and socioeconomic status, in that order. In the final model, the following variables were significant: use of injectable drugs, the number of sexual partners over a lifetime and the occupation (p ≤ 0.05). Patients who have never worked or were not working presented an increased risk for HIV (OR = 7.49 95% CI 1.17- 47.9) than those who worked. Patients who had between 4 to 9 partners had higher risk compared to those who had none and between 3 partners (OR = 26.7 95% CI 1.95 to 365.4) and on the use of injectiable drug users had higher risk than nonusers (OR = 26.0 95% CI 1.43- 472.4). The final model showed a variable of each block, reinforcing the interconnection between the factors that generate the HIV / TB association. Therefore, the co-infection should and must be seen in a multidisciplinary way and address social and political actions, especially the performance of HIV serology, both to prevent the growth of the incidence and prevalence rates, as for patient care already co-infected, bringing improvements to Public Health.

Les infections respiratoires et plus particulièrement la pneumonie représentent la première cause de mortalité infantile dans le monde. L’essor des technologies de diagnostic moléculaire a permis de mettre en évidence une étiologie très hétérogène des infections respiratoires ainsi qu’un taux élevé de co-infection virale et bactérienne dont l’impact clinique reste difficile à évaluer. La recherche translationnelle menée au cours de ce projet de thèse avait pour objectif de décrire l’étiologie des infections respiratoires ainsi que l’impact des co-infections sur la modulation de la réponse immunitaire innée. Nous avons développé un modèle d’étude in-vitro d’infection successive de cellules présentatrice d’antigènes (CPA) humaines par le virus Influenza (IAV) et Streptococcus pneumoniae (SP) et étudié la modulation de la réponse inflammatoire. Les résultats obtenus démontrent que la co-infection des CPA par ces deux pathogènes majeurs de la pneumonie impacte fortement sur leur viabilité et induit une dérégulation importante de la réponse inflammatoire. Au cours de la co-infection, la chémokine pro-inflammatoire IP-10 est exprimée de manière synergique suggérant un rôle jusqu’à présent non décrit de cette chémokine dans la pathogénèse de la pneumonie. Nous avons également démontré que les micro-ARNs (dont le miR-200a-3p) participent activement à la régulation de la réponse inflammatoire, en ciblant des régulateurs de la voie de signalisation JAK-STAT (SOCS-6) et indirectement la voie de synthèse d’IP-10. Récemment, nous avons évalué la réponse inflammatoire d’enfants âgés de moins de 5 ans hospitalisés pour une pneumonie, en partenariat avec les équipes médicales et scientifiques du Paraguay via le réseau GABRIEL. Ce volet d’étude confirme 1) une étiologie variée de la pneumonie chez l’enfant et 2) un taux d’IP-10 sérique significativement plus élevé chez les enfants co-infectés et présentant une pneumonie très sévère. / Respiratory infections, especially pneumonia are the leading cause of death among children under 5 years-old worldwide. Advances in molecular diagnostic have highlighted heterogeneous etiologies of respiratory infections with a high proportion of viral and bacterial co-infections whose clinical impact remain difficult to assess. The translational research conducted during this thesis aimed to describe the etiology of respiratory infections and the impact of viral and bacterial co-infections on the innate immunity.We have developed an in-vitro study model of sequential infection of antigen presenting cells (APC) by the human influenza virus and Streptococcus pneumoniae and studied the modulation of the inflammatory response. The results show that APC co-infection by those two major pathogens of pneumonia strongly impacts cells viability and induces a significant deregulation of the inflammatory response. During co-infection, pro-inflammatory chemokine IP-10 is synergistically expressed suggesting a role so far undescribed for this chemokine in the pathogenesis of pneumonia. We also demonstrated that micro-RNAs (including miR-200a-3p) actively participate in the regulation of the inflammatory response by targeting the signaling pathway regulators JAK-STAT (SOCS-6) and indirectly IP-10 signalling pathway.Recently, we evaluated the inflammatory response of children aged under 5 hospitalized for pneumonia, in partnership with medical and scientific teams of Paraguay involved in the GABRIEL network. This study confirmed 1) a varied etiology of childhood pneumonia and 2) a significant elevated IP-10 serum level among children with very severe pneumonia caused by mixed viral and bacterial co-infections.

Philosophiae Doctor - PhD / 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. / South Africa

Magister Public Health - MPH / BACKGROUND: Namibia has generalised Human Immunodeficiency Virus (HIV) and tuberculosis (TB) epidemics. In response to the TB/HIV co-epidemics in Namibia, the Ministry of Health and Social Services approved a policy of TB/HIV collaborative activities at national level and the integration of TB/HIV services at the point of service delivery. The present study explored barriers and facilitators of integration of TB and HIV service delivery in Tsandi District Hospital, which lies in rural northern Namibia. It focused on understanding the perspectives of healthcare workers and service users on integration of TB and HIV services at the health facility. AIMS & OBJECTIVES: The study aimed to describe the barriers, facilitators, and opportunities of integrated TB/HIV service delivery in Tsandi District Hospital. The specific objectives were: to describe the staffing and support systems in place for the integration of TB/HIV care; to describe the perceptions and experiences of integrated TB/HIV care by the health care workers, management and co-infected clients; and to describe the factors that facilitate or hinder the integration of TB/HIV services in the district from the point of view of district hospital managers, health care workers and co-infected clients. METHODS: The study used a descriptive qualitative study design with semistructured key-informant interviews conducted with five healthcare managers and senior clinicians and focus group discussions with 14 healthcare workers and five TB/HIV co-infected patients, supplemented by non-participant observation in Tsandi district hospital over two weeks between May – June 2011. Sessions were audiorecorded, transcribed, and thematically analysed. RESULTS: Several factors influenced whether and to what degree Tsandi district hospital was able to achieve integration of TB and HIV services. These are: (1) model of care and nature of referral links; (2) the availability and use of human resources and workspace; (3) the system of rotating staff among departments in the hospital; (4) the supply and mode of providing medicines to patients; (5) information systems, recording and reporting arrangements; (6) and the amount of follow-up and supervision of the integrated services. The main suggested barrier factors are: (1) poor communication and weak referrals links between services; (2) inadequate infrastructure to encourage and deliver TB and HIV care; (3) staff shortages and high workload; (4) lack of training and skills among healthcare workers; (5) financial constraints and other socioeconomic challenges; and (6) fragmented recording and reporting systems with limited data use to improve service delivery. The four main facilitating factors are: (1) positive staff attitudes towards TB/HIV integration; (2) common pool of staff managing different programmes; (3) joint planning and review of TB and HIV activities at the ARV Committee; and (4) informal task sharing to alleviate healthcare worker shortages. CONCLUSIONS: This study recommends that the district build on the current facilitators of integration, while the inhibitors should be worked on in order to improve the delivery of TB/HIV services in the district. Simple and practical recommendations have been made to address the some of the barriers at district level. It is hoped that these will inform future planning and review of the current model of care by the District nagement Team.

Das 1995 entdeckte GB-Virus C (GBV-C) gehört als Pegivirus zur Familie der Flaviviridae und ist nichtpathogen. In Industrieländern sind 2 bis 12,5 % der gesunden Bevölkerung und bis zu 45 % der Personen aus Risikokollektiven, z.B. Patienten mit Infektionen mit dem humanen Immundefizienzvirus Typ 1 (HIV-1) oder dem Hepatitis-C-Virus (HCV), virämisch. Die Mehrzahl der klinischen Studien und Metaanalysen zu GBV-C/HIV-1-Koinfektionen zeigten, dass GBV-C mit einem verlangsamten Krankheitsverlauf und einer erhöhten Überlebenswahrscheinlichkeit von GBV-C/HIV-1-koinfizierten Patienten korreliert. In der Hemophilia Growth and Development Study konnte dieser Effekt bei GBV-C/HCV-/HIV-1-infizierten Kindern und Jugendlichen jedoch nur bedingt nachgewiesen werden. Dafür wurde ein Zusammenhang zwischen einer GBV-C/HCV-Koinfektion und dem Ausheilen der HCV-Infektion beobachtet und in einer weiteren Patientenkohorte aus der Anti-D-Studie bestätigt. GBV-C/HCV-koinfizierte Patienten haben schlechtere Chancen, die HCV-Infektion auszuheilen. Der Einfluss von GBV-C auf die HIV-1-Replikation wurde in Zellkulturexperimenten untersucht. Es zeigte sich, dass sich die verschiedenen GBV-C-Isolate hinsichtlich ihrer inhibitorischen Kompetenz unterschieden. Folgende mögliche Ursachen wurden untersucht: 1.) die IRES-Aktivität als Indikator für die Translationseffizienz, 2.) die NS5A-Sequenz des in der Literatur beschriebenen HIV-1-inhibitorisch aktiven 16mer-Peptids sowie 3.) die E2-Sequenz und die HIV-1-inhibitorische Wirkung von 18mer-E2-Peptiden. Es konnten weder Unterschiede in der IRES-Aktivität noch in der NS5A-Sequenz zwischen den unterschiedlich inhibitorisch-kompetenten GBV-C-Isolaten nachgewiesen werden. Im E2-Protein hingegen wurden zwei für alle HIV-1-nichtinhibitorischen GBV-C-Isolate einheitliche Mutationen, E143K/H und T204A, identifiziert. Diese könnten eine Ursache für die Varianz in der Fähigkeit, HIV-1 zu inhibieren, darstellen. Die Mutation an Position E143 ist an der Oberfläche des nativen E2-Proteins exponiert und spielt möglicherweise im Hemmmechanismus eine wichtige Rolle. Hinweise darauf gaben die Untersuchungen mit synthetischen 18mer-Peptiden, von denen das Peptid mit dem größten inhibitorischen Potenzial die Aminosäure an Position 143 beinhaltete. Eine mögliche Theorie des Wirkmechanismus des E2-Proteins wäre wie folgt denkbar: Das E2-Protein interagiert über eine Domäne um die Aminosäure E143 mit dem gp41 des HIV-1, verhindert somit die Fusion von Virus- und Zellmembran und in der Folge den Eintritt des HIV-1 in die Zielzelle.

For several decades amphibian populations have been declining. Historically, the bacterium A. hydrophila (Ah) was hypothesized to be the causal factor in amphibian disease and population declines. However, with the discovery of a chytrid fungus, Batrachochytrium dendrobatidis (Bd) in 1998, which was identified on the skin of amphibians during documented mortality events, Ah research became of minor interest as focus shifted to Bd. Recent studies into the immunocompromising abilities of Bd, however, have opened new questions about its relationship with Ah and their combined effects on a host. In this study, I explore the relationship between infection with these two pathogens, Bd and Ah, in two amphibian species from distinct regions of the United States. I developed a novel qPCR assay to measure the microbial load of Ah on the skin of two anuran species, Lithobates yavapaiensis (N=232) and Pseudacris ornata (N=169), which have confirmed Bd infections. I use a logistic regression model to identify whether significant relationships exist between these two pathogens, disease, and death. I find that even amongst the most severely infected frogs, Ah is not detectable on the skin and only appears post-mortem. I therefore conclude that Ah is an opportunistic bacterial pathogen, scavenging on anurans only after mortality events. This research is the first known study to quantitatively assess Ah in amphibians in conjunction with Bd. While there is no causal relationship between these pathogens, future work will examine potential Ah infections in other organs to more fully understand the relationship between Bd and Ah.

The purpose of this study was to determine and compare the outcomes of tuberculosis (TB) treatment among Human Immunodeficiency Virus (HIV) co-infected TB patients, and identify factors associated with these outcomes. A quantitative cross-sectional analytic design was used. Patient level secondary data was collected and analysed for the study. A total of 575 TB patients, including 360 non-HIV infected, 169 HIV co-infected and 46 without a documented HIV status, were enrolled. The overall treatment success rate was 91.5%, and HIV co-infected TB patients had a high rate (11.8%) of unfavourable outcomes. The cure rate was significantly lower (10.1% versus 24.2%) and the death rate higher in HIV co-infected patients (8.3% versus 2.5%). Age and TB classification were significantly associated with treatment outcome. No association was found with starting ART, Cotrimoxazole prophylactic treatment or enrolment in HIV care, but 22% of HIV co-infected TB patients were taking ART when they developed TB disease / Health Studies / M.A. (Public Health)

Purpose: The purpose of this study is to assess risk factors associated with TB co-infection in HIV/AIDS patients taking antiretroviral therapy (ART). Methodology: An observational, analytic, case-control and quantitative study was conducted on a randomly selected 367 HIV and AIDS patients of whom 92 of them were TB co-infected. Data collection was done by using self-structured questionnaire. Result: In this study, educational status, waste disposal system, monthly income, contact history with a patient of active tuberculosis or presence of a family member with active tuberculosis, drug adherence, knowledge on tuberculosis prevention and history of exposure to substance were factors independently associated with the occurrence of active tuberculosis among HIV and Aids patients taking ART. Conclusion: The findings highlight the need for on-going educational, informational and other interventions to address the risk factors of tuberculosis in HIV and Aids patients in order to decrease the rate of TB co-infection / Health Studies / M.A. Public Health

Immunodeficient honey bee (Apis mellifera) colonies suffer from broad range of parasites including eukaryotic protozoa. Despite this fact, the eukaryotic parasites are still poorly documented in the Czech Republic. The presence of eukaryotic parasites (Nosema ceranae, Nosema apis, Crithidia mellificae and Apicystis bombi) was observed in different apiaries in the Czech Republic. The samples were taken in 9 apiaries in 53 beehives during the 2014/2015 season. From each beehive, 10 adult of honey bees were taken from the peripheral comb in triplicate. DNA was isolated from every sample of honey bees. The parasites were detected by polymerase chain reaction (PCR) with specific primers. The treatment fall of parasitic mite Varroa destructor was obtained from beekeepers for season of 2014. Crithidia mellificae was detected by 5 types of specific primers (SEF, SER; SSU, SSU rRNA, Cyt b, Tryp cyt b) and positive amplicons were cloned and sequenced. The obtained sequences were compared with GeneBank and showed similarity from 98-100% to sequences of Lotmaria passim (Trypanosomatid). Crithidia mellificae was not detected. L. passim had prevalence of 79,2% and is reported in the Czech Republic for the first time. Primer Tryp-cyt b is recommended for the routine detection of L. passim. Nosema ceranae was...

The purpose of this study was to determine and compare the outcomes of tuberculosis (TB) treatment among Human Immunodeficiency Virus (HIV) co-infected TB patients, and identify factors associated with these outcomes. A quantitative cross-sectional analytic design was used. Patient level secondary data was collected and analysed for the study. A total of 575 TB patients, including 360 non-HIV infected, 169 HIV co-infected and 46 without a documented HIV status, were enrolled. The overall treatment success rate was 91.5%, and HIV co-infected TB patients had a high rate (11.8%) of unfavourable outcomes. The cure rate was significantly lower (10.1% versus 24.2%) and the death rate higher in HIV co-infected patients (8.3% versus 2.5%). Age and TB classification were significantly associated with treatment outcome. No association was found with starting ART, Cotrimoxazole prophylactic treatment or enrolment in HIV care, but 22% of HIV co-infected TB patients were taking ART when they developed TB disease / Health Studies / M.A. (Public Health)