The effect of primary health care on tuberculosis in a nationwide cohort of 7·3 million Brazilian people: a quasi-experimental study.

BACKGROUND: Universal health coverage is one of the WHO End TB Strategy priority interventions and could be achieved-particularly in low-income and middle-income countries-through the expansion of primary health care. We evaluated the effects of one of the largest primary health-care programmes in the world, the Brazilian Family Health Strategy (FHS), on tuberculosis morbidity and mortality using a nationwide cohort of 7·3 million individuals over a 10-year study period. METHODS: We analysed individuals who entered the 100 Million Brazilians Cohort during the period Jan 1, 2004, to Dec 31, 2013, and compared residents in municipalities with no FHS coverage with residents in municipalities with full FHS coverage. We used a cohort design with multivariable Poisson regressions, adjusted for all relevant demographic and socioeconomic variables and weighted with inverse probability of treatment weighting, to estimate the effect of FHS on tuberculosis incidence, mortality, cure, and case fatality. We also performed a range of stratifications and sensitivity analyses. FINDINGS: FHS exposure was associated with lower tuberculosis incidence (rate ratio [RR] 0·78, 95% CI 0·72-0·84) and mortality (0·72, 0·55-0·94), and was positively associated with tuberculosis cure rates (1·04, 1·00-1·08). FHS was also associated with a decrease in tuberculosis case-fatality rates, although this was not statistically significant (RR 0·84, 95% CI 0·55-1·30). FHS associations were stronger among the poorest individuals for all the tuberculosis indicators. INTERPRETATION: Community-based primary health care could strongly reduce tuberculosis morbidity and mortality and decrease the unequal distribution of the tuberculosis burden in the most vulnerable populations. During the current marked rise in global poverty due to the COVID-19 pandemic, investments in primary health care could help protect against the expected increases in tuberculosis incidence worldwide and contribute to the attainment of the End TB Strategy goals. FUNDING: TB Modelling and Analysis Consortium (Bill & Melinda Gates Foundation), Wellcome Trust, and Brazilian Ministry of Health. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Racial disparity in excess mortality in Brazil during COVID-19 times.

We evaluated the impact of the COVID-19 pandemic on excess mortality by race/skin colour in Brazil, between epidemiological weeks 12 and 50 of 2020. We compared the 2020 point estimate and the expected point estimate applying 2019 mortality rates to the 2020 population. There was an excess of 187 002 deaths (+20.2%) compared to the expected. Excess mortality was 26.3% (23.3-29.3%) among blacks/browns compared to 15.1% (14.1-16.1%) among whites (58.9% of excess among black/browns). Age-standardized rates increased from 377 to 419/100 000 among blacks/browns compared to 328 to 398/100 000 in whites, resulting in 9% relative risk. Excess mortality in Brazil depicts a considerable gap, with increased mortality in all age groups in the black/brown population.

The impact of a cash transfer programme on tuberculosis treatment success rate: a quasi-experimental study in Brazil.

BACKGROUND: Evidence suggests that social protection policies such as Brazil's Bolsa Família Programme (BFP), a governmental conditional cash transfer, may play a role in tuberculosis (TB) elimination. However, study limitations hamper conclusions. This paper uses a quasi-experimental approach to more rigorously evaluate the effect of BFP on TB treatment success rate. METHODS: Propensity scores were estimated from a complete-case logistic regression using covariates from a linked data set, including the Brazil's TB notification system (SINAN), linked to the national registry of those in poverty (CadUnico) and the BFP payroll. RESULTS: The average effect of treatment on the treated was estimated as the difference in TB treatment success rate between matched groups (ie, the control and exposed patients, n=2167). Patients with TB receiving BFP showed a treatment success rate of 10.58 percentage points higher (95% CI 4.39 to 16.77) than patients with TB not receiving BFP. This association was robust to sensitivity analyses. CONCLUSIONS: This study further confirms a positive relationship between the provision of conditional cash transfers and TB treatment success rate. Further research is needed to understand how to enhance access to social protection so to optimise public health impact.

Journey towards universal viral load monitoring in Maputo, Mozambique: many gaps, but encouraging signs.

Introduction: Viral load (VL) monitoring for people on antiretroviral therapy (ART) is extremely challenging in resource-limited settings. We assessed the VL testing scale-up in six Médecins Sans Frontières supported health centres in Maputo, Mozambique, during 2014-15. Methods: In a retrospective cohort study, routine programme data were used to describe VL testing uptake and results, and multi-variate logistical regression to estimate predictors of VL testing uptake and suppression. Results: Uptake of a first VL test was 40% (17 236/43 579). Uptake of a follow-up VL test for patients with a high first VL result was 35% (1095/3100). Factors associated with a higher uptake included: age below 15 years, longer time on ART and attending tailored service delivery platforms. Virological suppression was higher in pregnant/breastfeeding women and in community ART Group members. Patients with a high first VL result (18%; 3100/17 236) were mostly younger, had been on ART longer or had tuberculosis. Out of 1095 attending for a follow-up VL test, 678 (62%) had virological failure. Of those, less than one-third had started second line ART. Conclusion: This was the first study describing the uptake and results of VL testing scale-up in Mozambique. Identified gaps show patient and programmatic challenges. Where service delivery was customized to patient needs, VL monitoring was more successful.

A nutritional supplement containing lactoferrin stimulates the immune system, extends lifespan, and reduces amyloid ß peptide toxicity in Caenorhabditis elegans.

Lactoferrin is a highly multifunctional glycoprotein involved in many physiological functions, including regulation of iron absorption and immune responses. Moreover, there is increasing evidence for neuroprotective effects of lactoferrin. We used Caenorhabditis elegans as a model to test the protective effects, both on phenotype and transcriptome, of a nutraceutical product based on lactoferrin liposomes. In a dose-dependent manner, the lactoferrin-based product protected against acute oxidative stress and extended lifespan of C. elegans N2. Furthermore, Paralysis of the transgenic C. elegans strain CL4176, caused by Aß1-42 aggregates, was clearly ameliorated by treatment. Transcriptome analysis in treated nematodes indicated immune system stimulation, together with enhancement of processes involved in the oxidative stress response. The lactoferrin-based product also improved the protein homeostasis processes, cellular adhesion processes, and neurogenesis in the nematode. In summary, the tested product exerts protection against aging and neurodegeneration, modulating processes involved in oxidative stress response, protein homeostasis, synaptic function, and xenobiotic metabolism. This lactoferrin-based product is also able to stimulate the immune system, as well as improving reproductive status and energy metabolism. These findings suggest that oral supplementation with this lactoferrin-based product could improve the immune system and antioxidant capacity. Further studies to understand the molecular mechanisms related with neuronal function would be of interest.

HIV testing, antiretroviral therapy, and treatment outcomes in new cases of tuberculosis in Brazil, 2011.

Objective To assess the implementation of HIV-related interventions for patients with tuberculosis (TB), as well as TB treatment outcomes in patients coinfected with HIV in Brazil in 2011. Methods This was a cross-sectional, operational research study of HIV-related interventions among TB cases and the sociodemographic and clinical characteristics of TB-HIV coinfected patients. It also used a retrospective cohort design to determine the association between antiretroviral therapy (ART) and favorable TB treatment outcomes. The source of data was a linkage of 2011 administrative health databases used by the National TB and HIV/AIDS Programs. Results Of 73 741 new cases of TB reported, 63.6% (46 865 patients) were tested for HIV; 10.3% were positive. Of patients with HIV, 45.9% or 3 502 were on ART. TB favorable outcome was achieved in 63.1% or 2 205 coinfected patients on ART and in only 35.4% or 1 459 of those not on ART. On multivariate analysis, the relative risk for the association between ART and TB treatment success was 1.72 (95% Confidence Interval = 1.64-1.81). Conclusions The linkage between national TB and HIV datasets has created a convenient baseline for ongoing monitoring of HIV testing, ART use, and TB treatment outcomes among coinfected patients. The low rates of HIV screening and ART use in 2011 need to be improved. The association between ART and treatment success adds to the evidence supporting timely initiation of ART for all patients with TB-HIV coinfection.

Effectiveness of a conditional cash transfer programme on TB cure rate: a retrospective cohort study in Brazil.

BACKGROUND: Despite the efforts of the National Tuberculosis Programme, TB cure rates in Brazil are sub-optimal. The End TB Strategy for post-2015 identifies conditional cash transfer interventions as powerful tools to improve TB control indicators, including TB cure rate. This study aims to inform the new policy by evaluating the role of the Bolsa Familia Programme (BFP), one of the largest conditional cash transfer programmes in the world, on TB cure rates in Brazil. METHODS: We undertook a retrospective cohort study, based on an unprecedented record linkage of socioeconomic and health data, to compare cases of patients newly diagnosed with TB in 2010 receiving BFP cash benefits (n=5788) with those who did not (n=1467) during TB treatment. We used Poisson regression with robust variance to estimate the relative risks for TB cure adjusted for known confounders. RESULTS: The cure rate among patients exposed to BFP during TB treatment was 82.1% (4752/5788), 5.2% higher than among those not exposed. This was confirmed after controlling for TB type, diabetes mellitus, HIV status and other relevant clinical and socioeconomic covariates (RR=1.07, 95% CI 1.04 to 1.11 for cure rates among BFP beneficiaries). This association seemed higher for patients not under directly observed treatment (RR=1.11; 95% CI 1.05 to 1.16). CONCLUSIONS: Although further research is needed, this study suggests that conditional cash transfer programmes can contribute to improve TB cure rate in Brazil.

HIV testing, antiretroviral therapy, and treatment outcomes in new cases of tuberculosis in Brazil, 2011 / Pruebas de detección del VIH, tratamiento antirretrovírico y resultados del tratamiento en casos nuevos de tuberculosis en Brasil en 2011

ABSTRACT Objective To assess the implementation of HIV-related interventions for patients with tuberculosis (TB), as well as TB treatment outcomes in patients coinfected with HIV in Brazil in 2011. Methods This was a cross-sectional, operational research study of HIV-related interventions among TB cases and the sociodemographic and clinical characteristics of TB-HIV coinfected patients. It also used a retrospective cohort design to determine the association between antiretroviral therapy (ART) and favorable TB treatment outcomes. The source of data was a linkage of 2011 administrative health databases used by the National TB and HIV/AIDS Programs. Results Of 73 741 new cases of TB reported, 63.6% (46 865 patients) were tested for HIV; 10.3% were positive. Of patients with HIV, 45.9% or 3 502 were on ART. TB favorable outcome was achieved in 63.1% or 2 205 coinfected patients on ART and in only 35.4% or 1 459 of those not on ART. On multivariate analysis, the relative risk for the association between ART and TB treatment success was 1.72 (95% Confidence Interval = 1.64–1.81). Conclusions The linkage between national TB and HIV datasets has created a convenient baseline for ongoing monitoring of HIV testing, ART use, and TB treatment outcomes among coinfected patients. The low rates of HIV screening and ART use in 2011 need to be improved. The association between ART and treatment success adds to the evidence supporting timely initiation of ART for all patients with TB-HIV coinfection.

RESUMEN Objetivo Evaluar la ejecución de las intervenciones relacionadas con el virus de la inmunodeficiencia humana (VIH) en los pacientes con diagnóstico de tuberculosis y examinar los desenlaces del tratamiento antituberculoso en los pacientes coinfectados por el VIH en Brasil en 2011. Métodos Estudio de investigación operativa. Mediante un diseño transversal se evaluaron las intervenciones relacionadas con el VIH en los casos de tuberculosis y se describieron las características sociodemográficas y clínicas de los pacientes coinfectados por el VIH y la tuberculosis; con un diseño retrospectivo de cohortes se determinó la asociación entre el tratamiento antirretrovírico y los desenlaces favorables del tratamiento antituberculoso. Los datos se obtuvieron mediante un enlace administrativo de las bases de datos de salud del 2011 que utilizaron el Programa Nacional contra la Tuberculosis y el Programa contra el VIH/sida. Resultados De los 73 741 casos nuevos de tuberculosis notificados, se practicó detección del VIH en 63,6% (46 865 pacientes) y los resultados fueron positivos en 10,3%. De los pacientes coinfectados por el VIH, 45,9% o 3 502 pacientes, recibían tratamiento antirretrovírico. Se alcanzó un desenlace favorable de la tuberculosis en 63,1% (2 205) de los pacientes coinfectados que recibían tratamiento antirretrovírico, y en solo 35,4% (1 459) de los pacientes coinfectados que no recibían este tratamiento. Según el análisis multivariante, el riesgo relativo de asociación entre el tratamiento antirretrovírico y el éxito del tratamiento antituberculoso fue 1,72 (intervalo de confianza de 95%: de 1,64 a 1,81). Conclusiones El enlace de los registros nacionales sobre la tuberculosis y la infección por el VIH creó una referencia de base útil para el seguimiento continuo de la utilización de las pruebas de detección del VIH, la administración del tratamiento antirretrovírico y los desenlaces del tratamiento antituberculoso en los pacientes coinfectados. Es necesario mejorar las bajas tasas de detección sistemática del VIH y de administración del tratamiento antirretrovírico que se observaron en el 2011. Esta correlación entre el tratamiento antirretrovírico y el éxito del tratamiento antituberculoso avala la evidencia que respalda la iniciación oportuna del tratamiento antirretrovírico en todos los pacientes que presentan coinfección por el VIH y la tuberculosis.

Microneedling dilates the follicular infundibulum and increases transfollicular absorption of liposomal sepia melanin.

Encapsulation of chemicals in liposomes and microneedling are currently used techniques to enhance the penetration of several substances through skin and hair. In this study, we apply a liposomal melanin-fluorescein compound to an ex vivo model of human skin, using a new electrical microneedling device (Nanopore turbo roller). The product was applied by hand massage (A) or with the assistance of the electrical roller for 2 minutes (B). An additional test was performed free of product and with only the E-roller (C). Histological changes and product absorption were evaluated by optical and fluorescent microscopy 60 and 90 minutes after the treatment. Site B showed larger deposits of melanin-fluorescein at superficial and deep levels of hair structures in comparison to site A. Light, epidermal deposits of the melanin-fluorescein complex were also observed. Sites B and C showed a significant widening (47%) of the follicular infundibulum which could explain the increased penetration of the formulation. Microneedling also removed the scales and sebum residues in the neighborhood of the infundibulum. Targeting hair follicles with melanin may be useful to dye poorly pigmented hairs, improving laser hair removal. The procedure accelerates the delivery of melanin into hair structures allowing an even absorption, larger pigment deposits, and deeper penetration of the formulation into the hair.

Phosphatidylcholine liposomes as carriers to improve topical ascorbic acid treatment of skin disorders.

Liposomes have been intensively investigated as carriers for different applications in dermatology and cosmetics. Ascorbic acid has potent antioxidant and anti-inflammatory properties preventing photodamage of keratinocytes; however, due to its instability and low skin penetration, an appropriate carrier is mandatory to obtain desirable efficacy. The present work investigates the ability of a specific ascorbate phosphatidylcholine (PC) liposome to overcome the barrier of the stratum corneum and deliver the active agent into the dermis to prevent photodamage. Abdominal skin from ten patients was used. Penetration of PC liposomes was tested ex vivo in whole skin, epidermis, and dermis by means of fluorescein and sodium ascorbate. Histology and Franz diffusion cells were used to monitor the percutaneous absorption. Ultraviolet (UV)-high performance liquid chromatography was used to analyze diffusion of sodium ascorbate through the different skin layers, while spectrofluorimetry and fluorescent microscopy were used for fluorescein monitoring. UVA/UVB irradiation of whole skin was applied to analyze the antioxidant capacity by Trolox assay and anti-inflammatory effects by tumor necrosis factor alpha and interleukin 1 beta enzyme-linked immunoassay. PC liposomal formulation improved skin penetration of fluorescein and ascorbate. Fluorescein PC liposomes showed better diffusion through epidermis than dermis while ascorbate liposomes showed better diffusion through the dermis than the epidermis. Ascorbate PC liposomes showed preventive antioxidant and anti-inflammatory properties on whole human skin irradiated with UVA/UVB. In summary, ascorbate PC liposomes penetrate through the epidermis and allow nonstable hydrophilic active ingredients reach epidermis and dermis preventing skin photodamage.

Tuberculosis in Brazil: last ten years analysis - 2001-2010

OBJECTIVE: To describe tuberculosis epidemiological situation in Brazil, as well as program performance indicators in 2001-2010 period, and discuss the relationship between changes observed and control measures implemented in this century first decade. METHODS: It is a descriptive study, data source was the Information System for Notifiable Diseases (Sinan), Mortality Information System (SIM), Unified Health System Hospital Information System (SIH/SUS) and TB Multidrug-resistant Surveillance System (MDR-TB/SS). Indicators analyzed were organized into four major groups: TB control program (TCP) coverage and case detection; morbidity; treatment and TCP performance; and mortality. RESULTS: In the years analyzed there was a decrease in the number of new cases and incidence rate, mortality reduction (relative and absolute), and improvement in TB detection and diagnosis, as well in TB/HIV coinfection and drug resistance. However, little progress was found in contact investigation, diagnosis in primary care and TB cure rate. DISCUSSION: Results showed many advances in tuberculosis control in the 10 years analyzed, but it also points to serious obstacles that need to be solved so Brazil can eliminate tuberculosis as a public health problem.

Tuberculosis in Brazil: last ten years analysis - 2001-2010.

OBJECTIVE: To describe tuberculosis epidemiological situation in Brazil, as well as program performance indicators in 2001-2010 period, and discuss the relationship between changes observed and control measures implemented in this century first decade. METHODS: It is a descriptive study, data source was the Information System for Notifiable Diseases (Sinan), Mortality Information System (SIM), Unified Health System Hospital Information System (SIH/SUS) and TB Multidrug-resistant Surveillance System (MDR-TB/SS). Indicators analyzed were organized into four major groups: TB control program (TCP) coverage and case detection; morbidity; treatment and TCP performance; and mortality. RESULTS: In the years analyzed there was a decrease in the number of new cases and incidence rate, mortality reduction (relative and absolute), and improvement in TB detection and diagnosis, as well in TB/HIV coinfection and drug resistance. However, little progress was found in contact investigation, diagnosis in primary care and TB cure rate. DISCUSSION: Results showed many advances in tuberculosis control in the 10 years analyzed, but it also points to serious obstacles that need to be solved so Brazil can eliminate tuberculosis as a public health problem.