The familial aggregation of Major Depressive Disorder (MDD) has been repeatedly demonstrated. Several studies have investigated associations between various clinical characteristics of MDD in probands and overall rates of MDD in relatives. Few studies, however, have considered the familial aggregation of clinical characteristics of MDD. The aim of the present report is to examine mother–offspring associations of a variety of clinical characteristics of MDD in a general population sample. Data were derived from baseline and 4-year-follow-up data of 933 adolescents and their biological mothers of the Early Developmental Stages of Psychopathology (EDSP) study, a prospective-longitudinal community study. MDD and its characteristics were assessed with the Munich-Composite International Diagnostic Interview. We found that children of mothers who had a lifetime history of severe MDD and high number of symptoms, high impairment and/or melancholia, revealed elevated odds of MDD regarding the same characteristics as their mothers (ORs between 5.2 and 13.9). The observed associations did not differ by the children’s sex. DSM-IV melancholia and severity as well as impairment were found to aggregate within families. This finding can be interpreted as a validation of the DSM-IV MDD severity subtypes as well as of the melancholic specifier. Severe and melancholic MDD reveal a considerable high degree of familiar aggregation making the search for mechanisms involved in the familiar transmission of these forms of MDD particularly promising.

Made available in DSpace on 2016-08-10T10:54:36Z (GMT). No. of bitstreams: 1 ZILENE DO SOCORRO SANTA BRIGIDA DA SILVA.pdf: 2232247 bytes, checksum: ee0c9b1410c53051a738452561c262cb (MD5) Previous issue date: 2015-03-13 / Objective: To analyze the epidemiological, clinical and behavioral characteristics of patients with AIDS accompanied by the Hospital for Tropical Diseases in Tocantins, from 2007 to 2013. Methods: A descriptive, retrospective and cross. Data were collected from 592 reporting forms and records of adult AIDS cases and child, the period under study, through adapted SINAN record, according to the inclusion and exclusion criteria. We used the chi-square test to see if there were significant differences (p <0.05) between the observed and expected frequencies and in all analyzes, adopting a significance level of 0.05. Results: excelled males (57.4%); aged 20-59 years (93.9%); the brown skin color (82.4%); Singles (65%); with occupancy type employees, self-employed or retired (75.8%); studied the elementary school (44.6%); resided in Tocantins (71.05%). Except gender (p = 0.0001), the other variables showed significant differences (p <0.0001); the cases were reported by the criteria Rio de Janeiro - Caracas: cachexia (16.8%) and asthenia (16.5%), CDC adapted: CD4 T lymphocyte count (51.3%), toxoplasmosis (11.7%) and pneumonia (11%) and 2.4% for criterion death; were alive until the end of data collection (72.5%); AIDS was reported in less than 1 year of HIV diagnosis (80.7%); the year 2013 had a higher incidence of AIDS notifications; exposure to HIV through sexual contact occurred (92.9%); were diagnosed by conventional tests (62.7%); in the notification: CD4 <350 cells - mm3 (79.9%) and viral load> 40 viral copies (77.2%); and last record: CD4> 500 cells - mm3 (49.5%) and viral load <40 copies to undetectable (57.1%); examination performed genotyping (2.4%); visceral leishmaniasis (35%) and pulmonary tuberculosis (21%) were the most prevalent and co-infections, toxoplasmosis (23%) and pneumocystosis (22%) were the major opportunistic infections; in relations: regular - irregular attendance to health services versus coinfection - IO, 56.7% of patients without regularity developed coinfection - IO (p <0.0001); regular - irregular attendance to health services versus death, 85.9% died without those regularly employed (p <0.0001); hospitalization versus coinfection - IO, 63.5% had coinfection - IO but not hospitalized (p <0.0001); coinfection - IO versus death, 71.7% of patients died with some coinfection (p <0.0001); 57.6% of patients used ART with AZT + 3TC + EFV at baseline and at the final on 42.3% used other combinations; the behavior of patients, 41.1% of men reported using or have used any legal or illegal drug (p = 0.0006); 85.7% of men reported not use or never used condoms during sexual intercourse (p = 0.4574); on the type of sexual partner, 93.3% of women and 69.1% of men reported having heterosexual relationship. Conclusion: The analysis of all variables and their results corroborate to achieve the objectives proposed in this study and to understand how it presents the profile of the AIDS epidemic at the local level, contributing to the management in control measures for the spread of AIDS in state and the region. / Objetivo: analisar as características epidemiológicas, clínicas e comportamentais dos pacientes com AIDS acompanhados pelo Hospital de Doenças Tropicais no Tocantins, no período de 2007 a 2013. Métodos: estudo descritivo, retrospectivo e transversal. Foram coletados dados de 592 fichas de notificação e prontuários de casos de AIDS adultos e criança, do período em estudo, através de ficha adaptada do SINAN, obedecendo aos critérios de inclusão e de exclusão. Foi aplicado o teste do Quiquadrado para verificar se havia diferenças significativas (p < 0,05) entre as frequências observadas e esperadas e em todas as análises, sendo adotado um nível de significância igual a 0,05. Resultados: sobressaiu o gênero masculino (57,4%); faixa etária entre 20 a 59 anos (93,9%); a cor parda da pele (82,4%); solteiros (65%); com ocupação tipo empregados, autônomos ou aposentados (75,8%); estudaram o ensino fundamental incompleto (44,6%); residiam no Tocantins (71,05%). Com exceção ao gênero (p = 0,0001), as demais variáveis apresentaram diferenças significativas (p < 0,0001); os casos foram notificados pelos critérios Rio de Janeiro-Caracas: caquexia (16,8%) e astenia (16,5%), CDC adaptado: contagem de linfócitos T CD4 (51,3%), neurotoxoplasmose (11,7%) e pneumonia (11%) e 2,4% por critério óbito; encontravam-se vivos até o final da coleta de dados (72,5%); foi notificado AIDS com menos de 1 ano do diagnóstico de HIV (80,7%); o ano de 2013 teve maior ocorrência de notificações de Aids; a exposição ao HIV ocorreu por via sexual (92,9%); foram diagnosticados por exames convencionais (62,7%); na notificação: CD4 < 350 cels-mm3 (79,9%) e carga viral > 40 cópias virais (77,2%); e último registro: CD4 > 500 cels-mm3 (49,5%) e carga viral < 40 cópias à indetectável (57,1%); realizaram exame de genotipagem (2,4%); a leishmaniose visceral (35%) e a tuberculose pulmonar (21%) foram as coinfecções mais prevalentes e, a toxoplasmose (23%) e a pneumocistose (22%) foram as principais infecções oportunistas; nas relações: comparecimento regular-irregular ao serviço de saúde versus coinfecção-IO, 56,7% dos pacientes sem regularidade desenvolveram coinfecção-IO (p < 0,0001); comparecimento regular-irregular ao serviço de saúde versus óbito, 85,9% faleceram aqueles sem regularidade ao serviço (p < 0,0001); hospitalização versus coinfecção-IO, 63,5% tiveram coinfecção-IO mas não hospitalizaram (p < 0,0001); coinfecção-IO versus óbito, 71,7% dos pacientes faleceram com alguma coinfecção (p < 0,0001); 57,6% dos pacientes utilizaram a TARV com EFZ + AZT + 3TC no início do tratamento e, na última consulta 42,3% utilizou outras combinações; quanto ao comportamento dos pacientes, 41,1% dos homens referiu usar ou já ter usado alguma droga lícita ou ilícita (p = 0,0006); 85,7% dos homens referiu não usar ou nunca ter usado preservativo nas relações sexuais (p = 0,4574); sobre o tipo de parceria sexual, 93,3% das mulheres e 69,1% dos homens informaram ter relacionamento heterossexual. Conclusão: A análise do conjunto de variáveis e seus resultados corroboraram para o alcance dos objetivos propostos neste estudo e para compreender como se apresenta o perfil da epidemia de Aids em âmbito local, contribuindo com a gestão nas medidas de controle para o avanço da Aids no estado e na região.

Magister Public Health - MPH (Public Health) / The presence of highly effective medicines has made very little impact in reducing deaths as a result of tuberculosis (TB), a curable condition but when managed inappropriately, may result in Drug Resistant TB. TB accounts for about one in four deaths that occur in HIV positive people and HIV has been found to be a risk factor for complex unfavorable outcomes in MDR TB patients and a very strong predictor for death and default. The relationship between diabetes and TB has also been explored, with some authors identifying diabetes as a risk factor for TB, and with related poor clinical outcomes in both conditions when they co-exist. Exploring the clinical characteristics and treatment outcomes of MDR TB patients in the presence of these risk factors could present an opportunity to provide better care through increased case-detection activities, improved clinical management and better access to care for all these conditions. The aim of the study was to describe the clinical characteristics and treatment outcomes of MDR TB patients initiated on treatment at Nkqubela and Fort Grey Hospitals.

HMPV was first reported in Australia by Nissen et al in 2002 from a group of 200 nasopharyngeal aspirate (NPA) specimens collected throughout 2001 from children presenting to the Royal Children’s Hospital, Brisbane. These specimens, previously negative for all common viral pathogens, were screened for hMPV by a polymerase chain reaction (PCR) assay based on known sequences. Molecular diagnostic assays including conventional reverse transcriptase PCR assay (RT-PCR) and real-time RT-PCR assays were subsequently developed, and molecular characterisation studies in our laboratory identified four genetic groups of hMPV. At the start of this project, little information were available regarding the virological characteristics of hMPV such as the isolation and replication kinetics of the virus in eukaryotic cells, molecular assays capable of detecting all virus subtypes, quantitation of viral load, genotyping and molecular epidemiology, correlation between virus subtypes and disease severity, and clinical spectrum of the infection. This project was designed to elucidate the virological features of hMPV that had not been explained by earlier studies on this virus. The project was limited to retrospective studies utilising the sera and nucleic acids obtained from positive subjects presenting to our hospital. The project provided relevant data in these areas, which helped in the early detection of infection and treatment, and also provided information for future research on antibody profiles and vaccine development. The study examined specific areas related to clinical and virological characteristics of hMPV with the aim of applying the results in patient management. During the project, five areas of hMPV research were undertaken, addressing each through detailed studies. An outline of the project aims and the conclusions derived from those experimental chapters is described below: 1. Isolation of the virus from clinical specimens obtained from infected subjects An optimised tissue culture protocol was successfully developed for isolating hMPV from positive nasopharyngeal aspirates, using LLC-MK2 cell lines. Viral stocks were prepared and maintained at stable conditions for future experiments. The demonstration of virus infection in the eukaryotic cells and titration of the infectious virions were performed using immunological assays developed and optimised in our laboratory, during the course of this study. 2. The complete genome sequence of an Australian hMPV isolate In this study, we described the ‘13,333 base pair’ complete genome sequence of the Queensland hMPV type-A strain, designated as AUS-001. Phylogenetic analyses of individual genes were used to generate ‘topological trees’ for systematic comparison of our local hMPV strain to that of international sequences. 3. A quantitative PCR assay (q.PCR) for hMPV A quantitative real-time reverse transcription PCR assay (qrt.RT-PCR) was developed for the simultaneous detection and quantification of hMPV in clinical samples. Serial dilutions of a synthetic RNA control were amplified after determining the absolute RNA copy numbers, and a standard curve was derived based on the cycle thresholds (Ct) values of the respective dilutions. Quantification of the hMPV RNA in clinical specimens was performed by extrapolating this data with Ct values of specimen dilutions obtained from the real-time assay. The dynamic range of the assay for hMPV genotypes A and B was determined. Validation of the inter- and intra- assay variations was completed using negative and positive controls along with a second assay targeting a different gene. 4. Determine the molecular epidemiology of hMPV genotypes This component of the project was designed to determine the molecular epidemiology of Queensland hMPV strains, using a selected ‘specimen population of hMPV positives’ representing the period 2001 to 2004. An RT-PCR assay based on P gene regions of hMPV was developed for the molecular typing of the above panel. Analyses of nucleotide and predicted amino acid sequences confirmed the heterogeneity of hMPV strains. In our study group, two genotypes (A and B) further classified into four subtypes (A1, A2, B1 and B2), were found to co-circulate during this period. General epidemiological features of the hMPV infections including seasonality, co-infections, incidence and prevalence in different age groups and in general population were described. 5. Clinical characteristics of hMPV infections The aim of this analysis was to illustrate the clinical spectrum of hMPV infections in a Queensland study population. We described the hMPV incidence pattern in different age groups and investigated the clinical severity scores of hMPV genotypes based on reported clinical features. We also undertook to identify any correlations between disease severity and other factors, including genotype, co-infections and viral load. Summary On completion, this PhD study provided valuable data on the isolation, molecular detection, epidemiological pattern and clinical severity of hMPV infections in Queensland. Overall hMPV was determined to be a serious respiratory pathogen in Queensland children. Data from this thesis will contribute to improved patient management and reduce the burden of hMPV-related disease in Queensland. These studies also formed the basis of further research involving respiratory viral pathogens in our laboratory and nationally.

HMPV was first reported in Australia by Nissen et al in 2002 from a group of 200 nasopharyngeal aspirate (NPA) specimens collected throughout 2001 from children presenting to the Royal Children’s Hospital, Brisbane. These specimens, previously negative for all common viral pathogens, were screened for hMPV by a polymerase chain reaction (PCR) assay based on known sequences. Molecular diagnostic assays including conventional reverse transcriptase PCR assay (RT-PCR) and real-time RT-PCR assays were subsequently developed, and molecular characterisation studies in our laboratory identified four genetic groups of hMPV. At the start of this project, little information were available regarding the virological characteristics of hMPV such as the isolation and replication kinetics of the virus in eukaryotic cells, molecular assays capable of detecting all virus subtypes, quantitation of viral load, genotyping and molecular epidemiology, correlation between virus subtypes and disease severity, and clinical spectrum of the infection. This project was designed to elucidate the virological features of hMPV that had not been explained by earlier studies on this virus. The project was limited to retrospective studies utilising the sera and nucleic acids obtained from positive subjects presenting to our hospital. The project provided relevant data in these areas, which helped in the early detection of infection and treatment, and also provided information for future research on antibody profiles and vaccine development. The study examined specific areas related to clinical and virological characteristics of hMPV with the aim of applying the results in patient management. During the project, five areas of hMPV research were undertaken, addressing each through detailed studies. An outline of the project aims and the conclusions derived from those experimental chapters is described below: 1. Isolation of the virus from clinical specimens obtained from infected subjects An optimised tissue culture protocol was successfully developed for isolating hMPV from positive nasopharyngeal aspirates, using LLC-MK2 cell lines. Viral stocks were prepared and maintained at stable conditions for future experiments. The demonstration of virus infection in the eukaryotic cells and titration of the infectious virions were performed using immunological assays developed and optimised in our laboratory, during the course of this study. 2. The complete genome sequence of an Australian hMPV isolate In this study, we described the ‘13,333 base pair’ complete genome sequence of the Queensland hMPV type-A strain, designated as AUS-001. Phylogenetic analyses of individual genes were used to generate ‘topological trees’ for systematic comparison of our local hMPV strain to that of international sequences. 3. A quantitative PCR assay (q.PCR) for hMPV A quantitative real-time reverse transcription PCR assay (qrt.RT-PCR) was developed for the simultaneous detection and quantification of hMPV in clinical samples. Serial dilutions of a synthetic RNA control were amplified after determining the absolute RNA copy numbers, and a standard curve was derived based on the cycle thresholds (Ct) values of the respective dilutions. Quantification of the hMPV RNA in clinical specimens was performed by extrapolating this data with Ct values of specimen dilutions obtained from the real-time assay. The dynamic range of the assay for hMPV genotypes A and B was determined. Validation of the inter- and intra- assay variations was completed using negative and positive controls along with a second assay targeting a different gene. 4. Determine the molecular epidemiology of hMPV genotypes This component of the project was designed to determine the molecular epidemiology of Queensland hMPV strains, using a selected ‘specimen population of hMPV positives’ representing the period 2001 to 2004. An RT-PCR assay based on P gene regions of hMPV was developed for the molecular typing of the above panel. Analyses of nucleotide and predicted amino acid sequences confirmed the heterogeneity of hMPV strains. In our study group, two genotypes (A and B) further classified into four subtypes (A1, A2, B1 and B2), were found to co-circulate during this period. General epidemiological features of the hMPV infections including seasonality, co-infections, incidence and prevalence in different age groups and in general population were described. 5. Clinical characteristics of hMPV infections The aim of this analysis was to illustrate the clinical spectrum of hMPV infections in a Queensland study population. We described the hMPV incidence pattern in different age groups and investigated the clinical severity scores of hMPV genotypes based on reported clinical features. We also undertook to identify any correlations between disease severity and other factors, including genotype, co-infections and viral load. Summary On completion, this PhD study provided valuable data on the isolation, molecular detection, epidemiological pattern and clinical severity of hMPV infections in Queensland. Overall hMPV was determined to be a serious respiratory pathogen in Queensland children. Data from this thesis will contribute to improved patient management and reduce the burden of hMPV-related disease in Queensland. These studies also formed the basis of further research involving respiratory viral pathogens in our laboratory and nationally.

No description available.