Mauro Niskier Sanchez

Socio-demographic and clinical differences in subjects with tuberculosis with and without diabetes mellitus in Brazil--a multivariate analysis.

Background Several studies have evaluated the relationship between diabetes mellitus (DM) and tuberculosis (TB), but the nature of this relationship is not fully understood. TB incidence may be influenced by immunosuppression from DM, but this association may be confounded by other clinical and socioeconomic factors. We aimed to assess socio-demographic and clinical differences in TB patients with and without DM. Methods Using the Brazilian national surveillance system (SINAN), we compared 1,797 subjects with TB and DM with 29,275 subjects diagnosed with TB only in 2009. We performed multivariate analysis to identify factors associated with the presence of DM among TB patients. Results Subjects with TB – DM were older; have initial positive sputum smear test (OR = 1.42, 95% CI 1.26–1.60), and were more likely to die from TB (OR = 1.44, 95% CI 1.03–2.01). They were less likely to have been institutionalized [in prison, shelter, orphanage, psychiatric hospital (OR = 0.74, 95% CI 0.60–0.93)]; developed extra pulmonary TB (OR = 0.62, 95% CI 0.51–0.75) and to return to TB treatment after abandonment (OR = 0.66, 95% CI 0.51–0.86). Conclusions Prevalence of NCD continues to rise in developing countries, especially with the rise of elderly population, the prevention and treatment of infectious diseases will be urgent. DM and TB represent a critical intersection between communicable and non-communicable diseases in these countries and the effect of DM on TB incidence and outcomes provide numerous opportunities for collaboration and management of these complex diseases in the national public health programs.

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.

Treatment Outcomes in Tuberculosis Patients with Diabetes: A Polytomous Analysis Using Brazilian Surveillance System

Background The impact of non-communicable diseases on tuberculosis incidence has received significant attention. It has been suggested that the risk of tuberculosis is higher among subjects with diabetes and these subjects also has poor TB treatment outcomes.This study was aimed at assessing the socio-demographic and clinical factors that may influence different outcome of TB in patients with DM (TB-DM) identified in the Brazilian national database from 2001 to 2011. Methods TB-DM cases reported in the Brazilian information system were identified and compared.Covariates associated with the outcomes of interest (cure, default, deaths, and development of TB MDR) were included in a hierarchical regression model. Results TB-DM cases increased from 380/100,000/year in 2001 to 6,150/100,000/year in 2011. Some of the main associations found are pointed. The odds of default was higher among those in the age group 20–39 years (OR = 2.07, 95%CI 1.32–3.24); alcoholics (OR = 2.17, 95%CI 1.86–2.54), and HIV/AIDS (OR = 2.16, 95%CI 1.70–2.74);positive monitoring smear (OR = 1.94, 95%CI 1.55–2.43); prior default (OR = 5.41, 95%CI 4.47–6.54), and unknown type of treatment (OR = 3.33, 95%CI 1.54–7.22). The odds of death was greater for subjects ≥60 years old (OR = 2.74, 95%CI 1.74–4.29); institutionalized in shelter (OR = 2.69, 95%CI 1.07–6.77); alcoholics (OR = 2.70, 95%CI 2.27–3.22); HIV/AIDS (OR = 2.87, 95%CI 2.13–3.86); pulmonary+extrapulmonary TB (OR = 2.49, 95%CI 1.79–3.46); with unknown type of treatment (OR = 14.12, 95%CI 7.04–28.32).Development of MDR TB was more related to relapse (OR = 9.60, 95%CI 6.07–15.14);previous default (OR = 17.13, 95%CI 9.58–30.63); and transfer of treatment center (OR = 7.87, 95%CI 4.74–13.07). Conclusions Older subjects and those with comorbidities and with a previous treatment of TB had poorest outcomes. TB control program in Brazil will need to expand efforts to focus on treatment of TB-DM patients to improve their cure rates in order to achieve the goals of tuberculosis elimination.

Brazilian Response to Global End TB Strategy : The National Tuberculosis Research Agenda.

Afranio Kritski[1],[2], Draurio Barreira[3], Ana Paula Junqueira-Kipnis[1],[4], Milton Ozorio Moraes[5], Maria Martha Campos[1],[6], Wim Mauritz Degrave[7], Silvana Spindola Miranda[1],[8], Marco Aurelio Krieger[1],[9], Erica Chimara[1],[10], Carlos Morel[11], Margareth Pretti Dalcolmo[1],[12], Ethel Leonor Noia Maciel[1],[13], Maria do Socorro Nantua Evangelista[3],[14], Teresa Scatena Villa[1],[15], Mauro Sanchez[1],[16], Fernanda Dockhorn Costa[3], Inacio Queiroz[17], Martha Maria Oliveira[1],[11], Ruy Souza Junior[3], Jose Roberto Lapa e Silva[1],[2] and Antonio Ruffi no-Netto[1],[18]

O Programa Mais Médicos: provimento de médicos em municípios brasileiros prioritários entre 2013 e 2014

The inadequate placement and distribution of health professionals are problems that occur in various countries. The scope of the “Programa Mais Medicos” (More Doctors Program) was to reduce the shortfall of physicians and diminish regional inequalities in health. A descriptive study on the placement of physicians between 2013 and 2014 using the Ministry of Health database is presented. There was an allocation of 14,168 physicians to the 3,785 municipalities that signed up to the program: 2,377 met the priority and/or vulnerability criteria and received 77.7% of the physicians; 1,408 received 22.3% of the physicians, but did not meet the established priorities. This study reveals the reduction in the lack of physicians, mainly in the North and Northeast. These regions account for 36% of the Brazilian population and 46.3% of the physicians were allocated there. However, the introduction of an eligibility profile, which allocated 3,166 physicians in 1,408 non-priority municipalities is questionable. The conclusion drawn is that this may have hindered the ability of the Mais Medicos Program to fully achieve its objectives as a public policy aimed at reducing regional inequalities of access to primary healthcare. Further studies are necessary to evaluate the impact of the Mais Medicos Program.

Prevention of neural tube defects by the fortification of flour with folic acid: a population-based retrospective study in Brazil.

Abstract Objective To determine if the fortification of wheat and maize flours with iron and folic acid – which became mandatory in Brazil from June 2004 – is effective in the prevention of neural tube defects. Methods Using data from national information systems on births in central, south-eastern and southern Brazil, we determined the prevalence of neural tube defects among live births and stillbirths in a pre-fortification period – i.e. 2001–2004 – and in a post-fortification period – i.e. 2005–2014. We distinguished between anencephaly, encephalocele, meningocele, myelomeningocele and other forms of spina bifida. Findings There were 8554 neural tube defects for 17 925 729 live births notified between 2001 and 2014. For the same period, 2673 neural tube defects were reported for 194 858 stillbirths. The overall prevalence of neural tube defects fell from 0.79 per 1000 pre-fortification to 0.55 per 1000 post-fortification (prevalence ratio, PR: 1.43; 95% confidence interval, CI: 1.38–1.50). For stillbirths, prevalence fell from 17.74 per 1000 stillbirths pre-fortification to 11.70 per 1000 stillbirths post-fortification. The corresponding values among live births were 0.57 and 0.44, respectively. Conclusion The introduction of the mandatory fortification of flour with iron and folic acid in Brazil was followed by a significant reduction in the prevalence of neural tube defects in our study area.

Rifapentine for latent tuberculosis infection treatment in the general population and human immunodeficiency virus-positive patients: summary of evidence

Latent tuberculosis infection (LTBI) and human immunodeficiency virus (HIV)-coinfection are challenges in the control of tuberculosis transmission. We aimed to assess and summarize evidence available in the literature regarding the treatment of LTBI in both the general and HIV-positive population, in order to support decision making by the Brazilian Tuberculosis Control Program for LTBI chemoprophylaxis. We searched MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, Embase, LILACS, SciELO, Trip database, National Guideline Clearinghouse, and the Brazilian Theses Repository to identify systematic reviews, randomized clinical trials, clinical guidelines, evidence-based synopses, reports of health technology assessment agencies, and theses that investigated rifapentine and isoniazid combination compared to isoniazid monotherapy. We assessed the quality of evidence from randomized clinical trials using the Jadad Scale and recommendations from other evidence sources using the Grading of Recommendations, Assessment, Development, and Evaluations approach. The available evidence suggests that there are no differences between rifapentine + isoniazid short-course treatment and the standard 6-month isoniazid therapy in reducing active tuberculosis incidence or death. Adherence was better with directly observed rifapentine therapy compared to self-administered isoniazid. The quality of evidence obtained was moderate, and on the basis of this evidence, rifapentine is recommended by one guideline. Available evidence assessment considering the perspective of higher adherence rates, lower costs, and local peculiarity context might support rifapentine use for LTBI in the general or HIV-positive populations. Since novel trials are ongoing, further studies should include patients on antiretroviral therapy.

Treatment outcomes of MDR-tuberculosis patients in Brazil: a retrospective cohort analysis

BackgroundMultidrug-resistant tuberculosis (MDR-TB) is a threat for the global TB epidemic control. Despite existing evidence that individualized treatment of MDR-TB is superior to standardized regimens, the latter are recommended in Brazil, mainly because drug-susceptibility tests (DST) are often restricted to first-line drugs in public laboratories. We compared treatment outcomes of MDR-TB patients using standardized versus individualized regimens in Brazil, a high TB-burden, low resistance setting.MethodsThe 2007–2013 cohort of the national electronic database (SITE-TB), which records all special treatments including drug-resistance, was analysed. Patients classified as MDR-TB in SITE-TB were eligible. Treatment outcomes were classified as successful (cure/treatment completed) or unsuccessful (failure/relapse/death/loss to follow-up). The odds for successful treatment according to type of regimen were controlled for demographic and clinical variables.ResultsOut of 4029 registered patients, we included 1972 recorded from 2010 to 2012, who had more complete outcome data. The overall success proportion was 60%. Success was more likely in non-HIV patients, sputum-negative at baseline, with unilateral disease and without prior DR-TB. Adjusted for these variables, those receiving standardized regimens had 2.7-fold odds of success compared to those receiving individualized treatments when failure/relapse were considered, and 1.4-fold odds of success when death was included as an unsuccessful outcome. When loss to follow-up was added, no difference between types of treatment was observed. Patients who used levofloxacin instead of ofloxacin had 1.5-fold odds of success.ConclusionIn this large cohort of MDR-TB patients with a low proportion of successful outcomes, standardized regimens had superior efficacy than individualized regimens, when adjusted for relevant variables. In addition to the limitations of any retrospective observational study, database quality hampered the analyses. Also, decision on the use of standard or individualized regimens was possibly not random, and may have introduced bias. Efforts were made to reduce classification bias and confounding. Until higher-quality evidence is produced, and DST becomes widely available in the country, our findings support the Brazilian recommendation for the use of standardized instead of individualized regimens for MDR-TB, preferably containing levofloxacin. Better quality surveillance data and DST availability across the country are necessary to improve MDR-TB control in Brazil.

Modelling the impact of social protection on tuberculosis: the S-PROTECT project

BackgroundTackling the social determinants of Tuberculosis (TB) through social protection is a key element of the post-2015 End TB Strategy. However, evidence informing policies are still scarce. Mathematical modelling has the potential to contribute to fill this knowledge gap, but existing models are inadequate. The S-PROTECT consortium aimed to develop an innovative mathematical modelling approach to better understand the role of social protection to improve TB care, prevention and control.MethodsS-PROTECT used a three-steps approach: 1) the development of a conceptual framework; 2) the extraction from this framework of three high-priority mechanistic pathways amenable for modelling; 3) the development of a revised version of a standard TB transmission model able to capture the structure of these pathways. As a test case we used the Bolsa Familia Programme (BFP), the Brazilian conditional cash transfer scheme.ResultsAssessing one of these pathways, we estimated that BFP can reduce TB prevalence by 4% by improving households income and thus their nutritional status. When looking at the direct impact via malnutrition (not income mediated) the impact was 33%. This variation was due to limited data availability, uncertainties on data transformation and the pathway approach taken. These results are preliminary and only aim to serve as illustrative example of the methodological challenges encountered in this first modelling attempt, nonetheless they suggest the potential added value of integrating TB standard of care with social protection strategies.ConclusionsResults are to be confirmed with further analysis. However, by developing a generalizable modelling framework, S-PROTECT proved that the modelling of social protection is complex, but doable and allowed to draw the research road map for the future in this field.

The impact of a governmental cash transfer programme on tuberculosis cure rate in Brazil: A quasi-experimental approach

Background Social vulnerability is strongly associated with tuberculosis (TB) indicators like cure rate. By addressing key social determinants, social protection policies such as Brazil’s Bolsa Família Programme (BFP), a governmental conditional cash transfer, may play a role in TB control. Evidence is consolidating around a positive effect of social protection on TB outcomes, however methodological limitations prevent strong conclusions. This paper uses a quasi-experimental approach to more rigorously evaluate the effect of BFP on TB cure rate. Methods & Findings The data source was Brazil’s TB notification system (SINAN), linked to the national registry of those in poverty (CadUnico) and the BFP payroll. Propensity scores (PSs) were estimated from a complete-case logistic regression using covariates from this linked dataset, informed by a directed acyclic graph. Control patients were matched to exposed patients on the PS and the average effect of treatment on the treated (ATT) was estimated as the difference in TB cure rate between matched groups (n = 2167). The ATT was estimated as 10·58 (95% CIs: 4·39, 16·77). This suggests that 10·58% of the TB patients receiving BFP who were cured would not have been cured had they not received BFP. The direction of this effect was robust to sensitivity analyses performed and the PS matching broadly improved balance, although missing data limited the sample size. Conclusions This work is the first quasi-experimental evaluation of social protection in wide-scale practice on TB outcomes. It demonstrates a positive effect of conditional cash transfers on TB cure rate consistent with existing work, suggesting changes to policy and future research on increasing access to social protection for TB patients who remain uncovered by the programme.