Contextualizing and optimizing novel strategies to improve the latent TB continuum of care: Insights from people living with HIV and health care providers in Brazil.

Tuberculosis (TB) causes 1 in 3 deaths among people living with HIV (PLHIV). Diagnosing and treating latent tuberculosis infection (LTBI) is critical to reducing TB incidence and mortality. Blood-based screening tests (e.g., QuantiFERON-TB Gold Plus (QFT+)) and shorter-course TB preventive therapy (TPT) regimens such as 3HP (3 months weekly isoniazid-rifapentine) hold significant promise to improve TB outcomes. We qualitatively explored barriers and solutions to optimizing QFT+ and 3HP among PLHIV in three cities in Brazil. We conducted 110 in-depth interviews with PLHIV, health care providers (HCP) and key informants (KI). Content analysis was conducted including the use of case summaries and comparison of themes across populations and contexts. LTBI screening and treatment practices were dependent on HCP's perceptions of whether they were critical to improving TB outcomes. Many HCP lacked a strong understanding of LTBI and perceived the current TPT regimen as complicated. HCP reported that LTBI screening and treatment were constrained by clinic staffing challenges. While PLHIV generally expressed willingness to consider any test or treatment that doctors recommended, they indicated HCP rarely discussed LTBI and TPT. TB testing and treatment requests were constrained by structural factors including financial and food insecurity, difficulties leaving work for appointments, stigma and family responsibilities. QFT+ and 3HP were viewed by all participants as tools that could significantly improve the LTBI cascade by avoiding complexities of TB skin tests and longer LTBI treatment courses. QFT+ and 3HP were perceived to have challenges, including the potential to increase workload on over-burdened health systems if not implemented alongside improved supply chains, staffing, and training, and follow-up initiatives. Multi-level interventions that increase understanding of the importance of LTBI and TPT among HCP, improve patient-provider communication, and streamline clinic-level operations related to QFT+ and 3HP are needed to optimize their impact among PLHIV and reduce TB mortality.

Mortality and survival of tuberculosis coinfected patients living with AIDS in São Paulo, Brazil: a 12-year cohort study.

BACKGROUND: TB is still one of the leading causes of death among HIV patients. This study evaluates the effect of TB on the mortality rate, survival time, and predictors of survival in patients with AIDS living in different areas in São Paulo State (SPS). METHODS: Retrospective cohort of adolescents and adults with AIDS, diagnosed between 2003 and 2007 and followed-up until 2014. Data were obtained from the Brazilian Ministry of Health. Mortality rates were estimated by person-years. Survival analysis used the date of diagnosis as the reference for the construction of Kaplan-Meier curves. The Cox model was used for the investigation of survival-associated factors. RESULTS: A total of 35,515 patients were included, of whom 63.0% were male; 64.7% at the age group of 30 to 49 years, 64.4% were white, 12.9% co-infected with TB, and 37.6% had CD4 count above 200 cells/mm3 at diagnosis of AIDS. The 12-year survival probabilities were 74.1% and 55.7% among patients without and with TB co-infection, respectively. After adjustment for sex, age and year of diagnosis, the following exposures were independently associated with lower survival: residing in municipalities of the Interior (Hazard ratio (HR) = 1.43) and Coastal Area (HR = 1.9); illiteracy (HR = 2.61); being co-infected with TB (HR = 1.70); CD4 count below 200 cells/mm3 at AIDS diagnosis (HR = 2.31); viral load above 500 copies/ml at AIDS diagnosis (HR = 1.99); HAART1 regimen (one non-nucleoside reverse transcriptase inhibitor or boosted old protease inhibitors) (HR = 1.94). CONCLUSION: The impact of TB on survival of AIDS was heterogeneous, and affected by age, years of formal education, early AIDS diagnosis, and proper ARV treatment. These factors may not fully explain the different survival outcomes in each of the four regions within the same state. These results may subsidize focused interventions and public health policies conveying specific needs in each of the areas.

Percepções de pessoas com tuberculose/HIV em relação à adesão ao tratamento / Perceptions of people with tuberculosis/HIV regarding treatment adherence

Resumo Objetivo Analisar aspectos relacionados à adesão ao tratamento da tuberculose em pessoas que vivem com coinfecção tuberculose/vírus da imunodeficiência humana. Métodos Trata-se de um estudo exploratório, do tipo descritivo, com abordagem qualitativa sobre a adesão ao tratamento da tuberculose entre pessoas que apresentam a coinfecção tuberculose/vírus da imunodeficiência humana. O cenário do estudo foi um centro de referência para vírus da imunodeficiência humana/síndrome da imunodeficiência adquirida do estado de São Paulo, localizado na capital. O instrumento de coleta de dados continha questões relacionadas ao perfil sóciodemográfico e de saúde. Para a análise do material empírico foi utilizado o método de análise de discurso que permitiu a depreensão de frases temáticas. Resultados Foram entrevistadas 16 pessoas, sendo a maioria do sexo masculino, da cor parda, na faixa etária entre 30 a 39 anos, com 9 a 12 anos de estudo, que moravam sozinhos, solteiros e que se declararam homossexuais. Da análise dos depoimentos emergiram três categorias de análise: Processo saúde doença: o impacto do diagnóstico e os significados de viver a coinfecção; Tratamento medicamentoso: motivos para o seguimento, facilidades e dificuldades envolvidas; e Cuidado no serviço de saúde: acolhimento e redes de apoio que favorecem a adesão ao tratamento. Conclusão A adesão ao tratamento na coinfecção tuberculose/vírus da imunodeficiência humana mostrou-se relacionada à forma como a pessoa está inserida na sociedade, suas condições de vida e trabalho. Ressalta-se também que o cuidado nos serviços de saúde interfere na adesão, dada a importância do vínculo entre o profissional de saúde e o usuário.

Resumen Objetivo Analizar los aspectos relacionados con la adherencia al tratamiento de tuberculosis en personas que viven con la coinfección tuberculosis/virus de la inmunodeficiencia humana. Métodos Se trata de un estudio exploratorio, tipo descriptivo, con enfoque cualitativo, sobre la adherencia al tratamiento de tuberculosis en personas que presentan la coinfección tuberculosis/virus de la inmunodeficiencia humana. El escenario de estudio fue un centro de referencia del virus de la inmunodeficiencia humana/síndrome de inmunodeficiencia adquirida del estado de São Paulo, ubicado en la capital. El instrumento de recopilación de datos contenía preguntas relacionadas con el perfil sociodemográfico y de salud. Para analizar el material empírico se utilizó el método de análisis de discurso que permitió extraer frases temáticas. Resultados Se entrevistaron 16 personas, de las cuales la mayoría era de sexo masculino, de color pardo, del grupo de edad entre 30 y 39 años, con 9 a 12 años de estudios, que vivían solos, solteros y que se declararon homosexuales. Del análisis de los relatos surgieron tres categorías de análisis: Proceso de salud y enfermedad: el impacto del diagnóstico y los significados de vivir la coinfección; Tratamiento farmacológico: motivos para el acompañamiento, facilidades y dificultades relacionadas, y Cuidado en el servicio sanitario: contención y redes de apoyo que favorecen la adherencia al tratamiento. Conclusión La adherencia al tratamiento de la coinfección tuberculosis/virus de la inmunodeficiencia humana demostró estar relacionada con la forma como la persona está insertada en la sociedad, su condición de vida y trabajo. También se observó que el cuidado en los servicios de salud interfiere en la adherencia, debido a la importancia del vínculo entre los profesionales de la salud y los usuarios.

Abstract Objective To analyze aspects related to adherence to tuberculosis treatment in people living with tuberculosis/human immunodeficiency virus coinfection. Methods This is an exploratory, descriptive, qualitative study on adherence to tuberculosis treatment among people with tuberculosis/human immunodeficiency virus coinfection. The study setting was a reference center for human immunodeficiency virus/acquired immunodeficiency syndrome located in the capital of the state of São Paulo. The data collection instrument contained socio-demographic and health profile related questions. The discourse analysis method was used for the analysis of the empirical material, which allowed the comprehension of thematic phrases. Results Sixteen people were interviewed. Most were male, mixed race, in the age group of 30-39 years, with 9-12 years of study, living alone, single and declared themselves homosexuals. Three categories of analysis emerged from the analysis of testimonies: Health-disease process: the impact of the diagnosis and the meanings of living with coinfection; Drug treatment: reasons for follow-up, facilities and difficulties involved; and Care in the health service: embracement and support networks that favor treatment adherence. Conclusion Adherence to treatment in the tuberculosis/human immunodeficiency virus coinfection has shown a relation to the way people are inserted in society, their living and working conditions. The fact that care in health services interferes with adherence is also noteworthy, given the importance of the bond between the health professional and the user.

A coinfecção tuberculose/HIV com enfoque no cuidado e na qualidade de vida / Tuberculosis/HIV coinfection focused on care and quality of life

Resumo Objetivo Descrever e analisar as percepções de pessoas que vivenciam a coinfecção tuberculose/ vírus da imunodeficiência humana, quanto à qualidade de vida e ao cuidado em saúde. Métodos Estudo exploratório, descritivo, com abordagem qualitativa, realizado com dez pessoas que vivenciavam a coinfecção e que recebiam atendimento em um centro de referência do município de São Paulo. Para a coleta de dados, foi utilizado um questionário semiestruturado, composto por questões fechadas e questões norteadoras. A análise dos depoimentos baseou-se na teoria da determinação social do processo saúde-doença. Resultados Os participantes apontaram que as condições precárias de vida interferiam na qualidade de vida e referiram satisfação em relação ao cuidado ofertado e com a rede de atenção à saúde. Vivenciar a coinfecção tuberculose/vírus da imunodeficiência humana acarretou sofrimento, isolamento social e estigma, o que pode contribuir para ideação suicida e diminuição da qualidade de vida. Na percepção dos participantes, os profissionais de saúde contribuem para a manutenção da qualidade de vida, por meio do estabelecimento de vínculo e atenção humanizada. Conclusão Intervenções voltadas à redução das desigualdades sociais, que apoiem a diminuição de estigma e do preconceito e que incrementem a interação humanizada nos serviços de saúde, de forma a atender às necessidades de saúde dos usuários podem repercutir positivamente na percepção sobre a qualidade de vida e o cuidado em saúde daqueles que vivenciam a coinfecção tuberculose/vírus da imunodeficiência humana.

Resumen Objetivo Describir y analizar las percepciones de personas que presentan la coinfección tuberculosis/virus de la inmunodeficiencia humana con relación a la calidad de vida y al cuidado de la salud. Métodos Estudio exploratorio, descriptivo, con enfoque cualitativo realizado con diez personas que presentaron la coinfección y que recibían atención en un centro de referencia del municipio de São Paulo. Para la recopilación de datos se utilizó un cuestionario semiestructurado, compuesto por preguntas cerradas y preguntas orientadoras. El análisis de los relatos se basó en la teoría de la determinación social del proceso salud-enfermedad. Resultados Los participantes señalaron que las condiciones precarias de vida interferían en la calidad de vida y relataron satisfacción con relación al cuidado ofrecido y a la red de atención en salud. Tener la coinfección tuberculosis/virus de la inmunodeficiencia humana conlleva sufrimiento, aislamiento social y estigma, lo que puede contribuir con ideación suicida y reducción de la calidad de vida. Bajo la percepción de los participantes, los profesionales de la salud contribuyen para mantener la calidad de vida, mediante el establecimiento de vínculos y atención humanizada. Conclusión Intervenciones orientadas a la reducción de las desigualdades sociales, que apoyen la disminución del estigma y los prejuicios y que aumenten la interacción humanizada en los servicios de salud, a fin de atender las necesidades de salud de los usuarios, pueden repercutir positivamente en la percepción sobre la calidad de vida y el cuidado de la salud de aquellas personas que padecen la coinfección tuberculosis/virus de la inmunodeficiencia humana.

Abstract Objective To describe and analyze the perceptions of people who experience tuberculosis/human immunodeficiency virus coinfection in relation to quality of life and health care. Methods An exploratory, descriptive, qualitative study conducted with ten people experiencing coinfection who received care at a reference center in the city of São Paulo. A semi-structured questionnaire composed of closed questions and guiding questions was used for data collection. The analysis of testimonies was based on the Theory of Social Determination of the Health-Disease Process. Results Participants mentioned that precarious conditions of life interfered in the quality of life and reported satisfaction with the care provided and the health care network. Experiencing tuberculosis/human immunodeficiency virus coinfection caused suffering, social isolation and stigma, which can contribute to suicidal ideation and lower quality of life. In the perception of participants, health professionals contribute to maintain the quality of life by developing bonds and humanized care. Conclusion Interventions aimed at reducing social inequalities that support the reduction of stigma and prejudice and increase humanized interaction in health services in order to meet users' health needs can exert positive impact on the perception of quality of life and health care of those experiencing tuberculosis/human immunodeficiency virus coinfection.

Serotype, mating type and ploidy of Cryptococcus neoformans strains isolated from patients in Brazil

Serotype, mating type and ploidy of 84 strains of Cryptococcus neoformans isolated from 61 AIDS and 23 non-AIDS patients admitted in a tertiary teaching hospital in Sõo Paulo, Brazil were examined. Among 61 strains isolated from AIDS patients, 60 strains were var. grubii (serotype A). Only one strain was var. gattii (serotype B). No var. neoformans (serotype D) was found. Among 23 strains isolated from non-AIDS patients, 15 were var. grubii (serotype A) and the remaining 8 were var. gattii, all of which were serotype B. Seventy-three of the 75 serotype A strains were the heterothallic alpha type (MATalpha) and the remaining 2 were untypable (asexual). Most of the MATalpha strains (69/73) were haploid and the remaining 4 strains were diploid. Similarly, both of the 2 asexual strains among the 75 serotype A strains were haploid. There were no alpha-mating type (MATalpha) strains among the 84 isolates. All of the 8 var. gattii strains were serotype B and haploid. Among a total of 84 strains tested, neither serotype AD nor serotype D were found. Neither triploid nor tetraploid were found. These results suggest that the serological, sexual and ploidy characteristics in C. neoformans strains isolated from AIDS patients in Sõo Paulo were rather simple, whereas strains isolated from non-AIDS patients presented serotype A and B with predominance of serotype A

Inhibitory role of the zona incerta in the pilocarpine model of epilepsy.

Recent experiments have suggested that the zona incerta might be regarded as a highly sensitive structure for seizure induction. This sensitivity has been linked to this structure's abundant expression of cholinergic receptors. Here we have decided to investigate the participation of the GABAergic system of the zona incerta, one of its major neurotransmitters with widespread projections to the neocortex, in the pilocarpine (Pilo) model of epilepsy. Stereotaxic administration of a GABA(A) agonist (muscimol), antagonist (bicuculline) or saline (controls) bilaterally into the zona incerta of adult male Wistar rats was performed 30 min prior to the systemic injection of pilocarpine. Animals were electroencephalographically and behaviorally monitored for seizure activity. Administration of muscimol had a pro-convulsant effect characterised by a higher percentage of animals developing SE with a shorter latency. Conversely, administration of bicuculline had a dose dependent anticonvulsant effect, with no animals displaying SE. Our results contribute to the further characterisation of the regulatory role of the zona incerta in seizure-related phenomena, suggesting that its modulation might be a relevant target for anticonvulsant strategies.

Serotype, mating type and ploidy of Cryptococcus neoformans strains isolated from patients in Brazil.

Serotype, mating type and ploidy of 84 strains of Cryptococcus neoformans isolated from 61 AIDS and 23 non-AIDS patients admitted in a tertiary teaching hospital in São Paulo, Brazil were examined. Among 61 strains isolated from AIDS patients, 60 strains were var. grubii (serotype A). Only one strain was var. gattii (serotype B). No var. neoformans (serotype D) was found. Among 23 strains isolated from non-AIDS patients, 15 were var. grubii (serotype A) and the remaining 8 were var. gattii, all of which were serotype B. Seventy-three of the 75 serotype A strains were the heterothallic alpha type (MATalpha) and the remaining 2 were untypable (asexual). Most of the MATalpha strains (69/73) were haploid and the remaining 4 strains were diploid. Similarly, both of the 2 asexual strains among the 75 serotype A strains were haploid. There were no alpha-mating type (MATalpha) strains among the 84 isolates. All of the 8 var. gattii strains were serotype B and haploid. Among a total of 84 strains tested, neither serotype AD nor serotype D were found. Neither triploid nor tetraploid were found. These results suggest that the serological, sexual and ploidy characteristics in C. neoformans strains isolated from AIDS patients in São Paulo were rather simple, whereas strains isolated from non-AIDS patients presented serotype A and B with predominance of serotype A.