Tuberculosis in Brazil: one country, multiple realities / Tuberculose no Brasil: um país, múltiplas realidades

ABSTRACT Objective: To identify the determinants of tuberculosis-related variables in the various regions of Brazil and evaluate trends in those variables over the ten-year period preceding the end of the timeframe defined for the United Nations Millennium Development Goals (MDGs). Methods: This was an ecological analytical study in which we utilized eight national public databases to investigate the 716,971 new tuberculosis cases reported between 2006 and 2015. Results: Over the study period, there were slight reductions in the prevalence, incidence, and mortality associated with tuberculosis. Brazil did not reach the MDG for tuberculosis-related mortality. Among the performance indicators of tuberculosis control, there were improvements only in those related to treatment and treatment abandonment. In terms of the magnitude of tuberculosis, substantial regional differences were observed. The tuberculosis incidence rate was highest in the northern region, as were the annual mean temperature and relative air humidity. That region also had the second lowest human development index, primary health care (PHC) coverage, and number of hospitalizations for tuberculosis. The northeastern region had the highest PHC coverage, number of hospitalizations for primary care-sensitive conditions, and tuberculosis-related mortality rate. The southern region showed the smallest reductions in epidemiological indicators, together with the greatest increases in the frequency of treatment abandonment and retreatment. The central-west region showed the lowest overall magnitude of tuberculosis and better monitoring indicators. Conclusions: The situation related to tuberculosis differs among the five regions of Brazil. Those differences can make it difficult to control the disease in the country and could explain the fact that Brazil failed to reach the MDG for tuberculosis-related mortality. Tuberculosis control measures should be adapted to account for regional differences.

RESUMO Objetivo: Identificar os determinantes das variáveis da tuberculose nas diversas regiões do Brasil e avaliar as tendências dessas variáveis ao longo dos dez anos anteriores ao término do prazo definido para os Objetivos de Desenvolvimento do Milênio (ODM) das Nações Unidas. Métodos: Estudo analítico ecológico no qual utilizamos oito bancos de dados públicos nacionais para investigar os 716.971 casos novos de tuberculose notificados entre 2006 e 2015. Resultados: Durante o período estudado, houve ligeiras reduções na prevalência, incidência e mortalidade associadas à tuberculose. O Brasil não atingiu o ODM de mortalidade por tuberculose. Entre os indicadores de desempenho no controle da tuberculose, houve melhora apenas naqueles relacionados a tratamento e abandono de tratamento. Em termos da magnitude da tuberculose, foram observadas diferenças regionais substanciais. A taxa de incidência de tuberculose foi maior na região Norte, assim como a temperatura média anual e a umidade relativa do ar. Essa região também apresentou a segunda menor média do índice de desenvolvimento humano, a menor cobertura de atenção primária à saúde (APS) e o menor número de hospitalizações por tuberculose. A região Nordeste apresentou a maior cobertura de APS, o maior número de hospitalizações por condições sensíveis à atenção primária e a maior taxa de mortalidade por tuberculose. A região Sul apresentou as menores reduções nos indicadores epidemiológicos, juntamente com os maiores aumentos na frequência de abandono de tratamento e de retratamento. A região Centro-Oeste apresentou a menor magnitude geral de tuberculose e melhores indicadores de monitoramento. Conclusões: A situação da tuberculose difere entre as cinco regiões do Brasil. Essas diferenças podem dificultar o controle da doença no país e podem explicar o fato de o Brasil não ter atingido o ODM de mortalidade por tuberculose. As medidas de controle da tuberculose devem ser adaptadas para dar conta das diferenças regionais.

Evaluation of the impact that the changes in tuberculosis treatment implemented in Brazil in 2009 have had on disease control in the country / Avaliação do impacto das mudanças do tratamento da tuberculose implantadas em 2009 no controle da tuberculose pulmonar no Brasil

ABSTRACT Objective: To analyze the impact that the 2009 changes in tuberculosis treatment in Brazil had on the rates of cure, tuberculosis recurrence, mortality, treatment abandonment, and multidrug-resistant tuberculosis (MDR-TB). Methods: An ordinary least squares regression model was used in order to perform an interrupted time series analysis of secondary data collected from the Brazilian Tuberculosis Case Registry Database for the period between January of 2003 and December of 2014. Results: The 2009 changes in tuberculosis treatment in Brazil were found to have no association with reductions in the total number of cases (β = 2.17; 95% CI: −3.80 to 8.14; p = 0.47) and in the number of new cases (β = −0.97; 95% CI: −5.89 to 3.94; p = 0.70), as well as having no association with treatment abandonment rates (β = 0.40; 95% CI: −1.12 to 1.93; p = 0.60). The changes in tuberculosis treatment also showed a trend toward an association with decreased cure rates (β = −4.14; 95% CI: −8.63 to 0.34; p = 0.07), as well as an association with increased mortality from pulmonary tuberculosis (β = 0.77; 95% CI: 0.16 to 1.38; p = 0.01). Although there was a significant increase in MDR-TB before and after the changes (p < 0.0001), there was no association between the intervention (i.e., the changes in tuberculosis treatment) and the increase in MDR-TB cases. Conclusions: The changes in tuberculosis treatment were unable to contain the decrease in cure rates, the increase in treatment abandonment rates, and the increase in MDR-TB rates, being associated with increased mortality from pulmonary tuberculosis during the study period. Keywords: Tuberculosis, pulmonary/epidemiology; Tuberculosis, pulmonary/drug therapy; Tuberculosis, pulmonary/mortality; Interrupted time series analysis; Drug resistance, multiple; Drug compounding.

RESUMO Objetivo: Analisar o impacto das mudanças do tratamento da tuberculose implantadas no Brasil em 2009 no número de casos de cura, de recidiva, de óbitos, de abandono e de tuberculose multirresistente (TBMR). Métodos: Foi realizada uma análise de séries temporais interrompida utilizando o modelo de regressão pelo método dos mínimos quadrados ordinários a partir de dados secundários coletados do Sistema de Informação de Agravos de Notificação da Tuberculose entre janeiro de 2003 e dezembro de 2014. Resultados: A análise mostrou independência entre as mudanças do tratamento e a redução do número total de casos (β = 2,17; IC95%: −3,80 a 8,14; 189 p = 0,47), a redução do número de novos casos (β = −0,97; IC95%: −5,89 a 3,94; p =190 0,70) e do abandono do tratamento (β = 0,40; IC95%: 199 −1,12 a 1,93; p = 0,60). Demonstrou ainda tendência à associação com a diminuição da cura (β = −4,14; IC95%: −8,63 a 0,34; p = 0,07) e associação com aumento da mortalidade por tuberculose pulmonar (β = 0,77; IC95%: 0,16 a 1,38; p = 0,01). A TBMR aumentou significativamente tanto no período anterior quanto no período posterior às mudanças do tratamento (p < 0,0001), embora de forma independente da intervenção (β = 0,13; IC95%: −0,03 a 0,29; p = 0,12). Conclusões: As mudanças no tratamento não impediram nem a diminuição na taxa de cura e nem o aumento do abandono e da TBMR; por outro lado, se associaram ao aumento de óbitos por tuberculose pulmonar durante o período do estudo.

Treatment decisions and mortality in HIV-positive presumptive smear-negative TB in the Xpert™ MTB/RIF era: a cohort study.

BACKGROUND: The Xpert™ MTB/RIF (XP) has a higher sensitivity than sputum smear microscopy (70% versus 35%) for TB diagnosis and has been endorsed by the WHO for TB high burden countries to increase case finding among HIV co-infected presumptive TB patients. Its impact on the diagnosis of smear-negative TB in a routine care setting is unclear. We determined the change in diagnosis, treatment and mortality of smear-negative presumptive TB with routine use of Xpert MTB/RIF (XP). METHODS: Prospective cohort study of HIV-positive smear-negative presumptive TB patients during a 12-month period after XP implementation in a well-staffed and trained integrated TB/HIV clinic in Kampala, Uganda. Prior to testing clinicians were asked to decide whether they would treat empirically prior to Xpert result; actual treatment was decided upon receipt of the XP result. We compared empirical and XP-informed treatment decisions and all-cause mortality in the first year. RESULTS: Of 411 smear-negative presumptive TB patients, 175 (43%) received an XP; their baseline characteristics did not differ. XP positivity was similar in patients with a pre-XP empirical diagnosis and those without (9/29 [17%] versus 14/142 [10%], P = 0.23). Despite XP testing high levels of empirical treatment prevailed (18%), although XP results did change who ultimately was treated for TB. When adjusted for CD4 count, empirical treatment was not associated with higher mortality compared to no or microbiologically confirmed treatment. CONCLUSIONS: XP usage was lower than expected. The lower sensitivity of XP in smear-negative HIV-positive patients led experienced clinicians to use XP as a "rule-in" rather than "rule-out" test, with the majority of patients still treated empirically.

Sputum is a surrogate for bronchoalveolar lavage for monitoring Mycobacterium tuberculosis transcriptional profiles in TB patients.

Pathogen-targeted transcriptional profiling in human sputum may elucidate the physiologic state of Mycobacterium tuberculosis (M. tuberculosis) during infection and treatment. However, whether M. tuberculosis transcription in sputum recapitulates transcription in the lung is uncertain. We therefore compared M. tuberculosis transcription in human sputum and bronchoalveolar lavage (BAL) samples from 11 HIV-negative South African patients with pulmonary tuberculosis. We additionally compared these clinical samples with in vitro log phase aerobic growth and hypoxic non-replicating persistence (NRP-2). Of 2179 M. tuberculosis transcripts assayed in sputum and BAL via multiplex RT-PCR, 194 (8.9%) had a p-value <0.05, but none were significant after correction for multiple testing. Categorical enrichment analysis indicated that expression of the hypoxia-responsive DosR regulon was higher in BAL than in sputum. M. tuberculosis transcription in BAL and sputum was distinct from both aerobic growth and NRP-2, with a range of 396-1020 transcripts significantly differentially expressed after multiple testing correction. Collectively, our results indicate that M. tuberculosis transcription in sputum approximates M. tuberculosis transcription in the lung. Minor differences between M. tuberculosis transcription in BAL and sputum suggested lower oxygen concentrations or higher nitric oxide concentrations in BAL. M. tuberculosis-targeted transcriptional profiling of sputa may be a powerful tool for understanding M. tuberculosis pathogenesis and monitoring treatment responses in vivo.

Prevalência de coinfecção tuberculose/HIV em pacientes do Centro de Saúde Modelo de Porto Alegre, Rio Grande do Sul / Prevalence of tuberculosis/HIV coinfection in patients from Model Health Centre in Porto Alegre, Rio Grande do Sul

Objetivos: o estudo teve como propósito estimar a prevalência da infecção pelo Vírus da Imunodeficiência Humana (HIV) nos pacientes em tratamento para tuberculose, no Centro de Saúde Modelo de Porto Alegre, RS.Métodos: foi realizada uma investigação transversal cuja população constituiu-se na totalidade dos pacientes em tratamento para tuberculose no Centro de Saúde Modelo de Porto Alegre, RS, entre 2004 e 2007. Para análise estatística foram utilizados o teste qui-quadrado e análise multivariada pelo método forward likelihood ratio. Resultados: no período em estudo foram diagnosticados 1537 casos de tuberculose, sendo que 449 apresentaram sorologia positiva para o HIV, o que representou uma taxa de coinfecção de 29,2%. Nesse grupo houve predominância do sexo masculino (73,9%) e da faixa etária de 30 a 39 anos (40,8%). No diagnóstico dos coinfectados com HIV/tuberculose a forma clínica prevalente foi a extrapulmonar (49%). Na baciloscopia, a forma negativa prevaleceu (29,8%) e a radiologia sugestiva (74,9%) também predominou nesse grupo. O esquema medicamentoso rifampicina, isoniazida e pirazinamida foi o tipo de tratamento mais usado (87,5%) e a alta por cura nos pacientes com sorologia positiva para o HIV em tratamento para tuberculose foi de 43,7%.Conclusões: os resultados ressaltam a importância da realização do teste sorológico para HIV quando se diagnostica a tuberculose.

Aims: The study aimed to estimate the prevalence of Human Immunodeficiency Virus (HIV) infection in patients undergoing treatment for tuberculosis, at the Model Health Center in Porto Alegre, RS.Methods: This was a cross-sectional study in which the studied population consisted of all patients undergoing treatment for tuberculosis in the Model Health Center in Porto Alegre, RS, from 2004 to 2007. Statistical analysis was made by the chi-square test and by multivariate analysis by the forward likelihood ratio method. Results: In the studied period, 1537 patients were diagnosed with tuberculosis, of whom 449 presented positive serology for HIV, resulting in a rate of coinfection of 29.2%. This group was predominantly male (73.9%), aging 30 to 39 years (40.8%). In cases of HIV/tuberculosis coinfection, the most prevalent clinical form was the extra pulmonary (49%). In bacilloscopy, the negative form prevailed (29.8%), and suggestive radiology (74.9%) also predominated in this group. The therapeutic schedule rifampin, isoniazid and pyrazinamide was the most used (87.5%), and the discharge by cure of treated tuberculosis of patients with positive serology for HIV was 43.7%.Conclusion: The results have emphasized the importance of the serological test for HIV when tuberculosis is diagnosed.