Bedaquiline and linezolid MIC distributions and epidemiological cut-off values for Mycobacterium tuberculosis in the Latin American region.

Objectives: To describe the distributions of bedaquiline and linezolid MIC values for the Mycobacterium tuberculosis WT population and to define the corresponding epidemiological cut-offs (ECOFFs) in three Latin American countries. Methods: MICs of bedaquiline and linezolid were determined by the resazurin microtitre assay (REMA). In phase 1, interlaboratory reproducibility was assessed using a panel of 10 fully susceptible M. tuberculosis strains. Phase 2 involved MIC determination for 248 clinical isolates from Argentina (n = 58), Brazil (n = 100) and Peru (n = 90) from patients who were treatment-naive for bedaquiline and linezolid. We then determined the ECOFFs for bedaquiline and linezolid by the eyeball method and the ECOFFinder statistical calculator. Results: Phase 1: REMA MIC values in the three sites were either identical to each other or differed by one 2-fold dilution from the consensus value with the exception of a single value. Phase 2: the bedaquiline MIC range was 0.0039-0.25 mg/L for pan-susceptible and drug-resistant isolates combined. The linezolid MIC range was 0.062-0.5 mg/L for pan-susceptible isolates and 0.031-4 mg/L for drug-resistant isolates. ECOFFs were 0.125 mg/L for bedaquiline and 0.50 mg/L for linezolid. Conclusions: REMA is reproducible and robust for the determination of bedaquiline and linezolid MIC distributions and ECOFF values when applied in laboratories of medium/low-resource countries. We suggest that WT MIC distributions for both drugs should be used as a monitoring tool to control the possible rapid emergence of resistance.

Hospital-based tuberculosis control activities in five cities of Latin America / Actividades hospitalarias de control de la tuberculosis en cinco ciudades de América Latina / Atividades de controle da tuberculose em hospitais em cinco cidades da América Latina

Objective. To generate actionable insights for improving TB control in urban areas by describing the tuberculosis (TB) control activities of hospitals in five cities in Latin America. Methods. A descriptive study of hospital-based TB control activities was conducted in 2013–2015 using a cross-sectional survey designed by the Pan American Health Organization and administered in Guatemala City, Guatemala; Guarulhos, Brazil; Bogotá, Colombia; Lima, Peru; and Asunción, Paraguay. Data were analyzed using Chi-squared, Fisher exact tests, and the Mantel–Haenszel test for Risk Ratios, as necessary (P < 0.05). Results. While variation among cities existed, most hospitals (91.3%) conducted acid-fast bacilli smears for TB diagnosis and had a quality control process (94.0%), followed national TB guidelines (95%), and reported TB cases to the respective health authorities (96%). Additionally, TB treatment was offered free of charge almost universally (97.1%). However, only 74.2% of hospitals were supervised by the national or local TB programs; 52.8% followed up on the outcome of referrals; and 39.1% offered full ambulatory TB treatment, with 68.7% using Directly-Observed Therapy. Conclusion. The study underscored strengths and weaknesses in specific areas for TB control activities in hospitals and highlighted the importance and complexity of coordinating efforts among private and public hospitals and the various stakeholders. Local TB programs and health authorities should use these results to enhance the quality of TB-related actions in hospitals in similar settings.

Objetivo. Generar información utilizable para mejorar el control de la tuberculosis en las zonas urbanas describiendo las actividades hospitalarias de control de la tuberculosis de cinco ciudades de América Latina. Métodos. Se realizó un estudio descriptivo de las actividades hospitalarias de control de la tuberculosis mediante una encuesta transversal formulada por la Organización Panamericana de la Salud y administrada entre el 2013 y el 2015 en Ciudad de Guatemala (Guatemala), Guarulhos (Brasil), Bogotá (Colombia), Lima (Perú) y Asunción (Paraguay). Los datos fueron analizados con la prueba de la ji al cuadrado, la prueba exacta de Fisher y la prueba de asociación de Mantel-Haenszel de las razones de riesgos, según fuera necesario (P < 0,05). Resultados. Pese a la variación observada entre las ciudades, la mayor parte de los hospitales (91,3 %) realizan frotis de bacilos acidorresistentes para diagnosticar la tuberculosis y disponen de un proceso de control de la calidad (94,0 %), siguen las directrices nacionales respecto de la tuberculosis (95 %) y notifican los casos a las autoridades de salud respectivas (96 %). Además, casi todos ofrecen tratamiento antituberculoso gratuito (97,1 %). Sin embargo, solo el 74,2 % de los hospitales está supervisado por el programa nacional o local contra la tuberculosis; el 52,8 % hace el seguimiento de la evolución de los pacientes derivados; y el 39,1 % ofrece tratamiento antituberculoso plenamente ambulatorio a los pacientes, del cual el 68,7 % corresponde al tratamiento bajo observación directa. Conclusiones. En el estudio se ponen de relieve las fortalezas y las debilidades de aspectos específicos de las actividades hospitalarias de control de la tuberculosis, así como la importancia y la complejidad que reviste coordinar los esfuerzos entre los hospitales privados y públicos y los diversos interesados directos. Los programas locales contra la tuberculosis y las autoridades de salud deben aprovechar estos resultados para mejorar la calidad de las actividades hospitalarias relacionadas con la tuberculosis en entornos similares.

Objetivo. Originar insights proativos para melhorar o controle da tuberculose (TB) em áreas urbanas descrevendo as atividades de controle da TB em hospitais em cinco cidades na América Latina. Métodos. Estudo descritivo das atividades de controle da TB em hospitais realizado em 2013–2015 com base em pesquisa transversal concebida pela Organização Pan- Americana da Saúde e conduzida na Cidade da Guatemala (Guatemala), Guarulhos (Brasil), Bogotá (Colômbia), Lima (Peru) e Assunção (Paraguai). Os dados foram analisados com o uso do teste qui-quadrado, teste exato de Fisher e teste de Mantel– Haenszel para razões de risco, conforme necessário (P < 0,05). Resultados. Apesar de ter existido variação entre as cidades, a maioria dos hospitais (91,3%) realizou o teste de esfregaço de bacilos acidorresistentes para o diagnóstico de TB e dispunha de um processo de controle de qualidade (94,0%), seguiu os protocolos nacionais de TB (95%) e notificou casos de TB aos órgãos sanitários competentes (96%). Além disso, o tratamento de TB foi proporcionado gratuitamente quase como um todo (97,1%). Porém, somente 74,2% dos hospitais receberam supervisão dos programas locais ou nacionais de combate à TB; 52,8% acompanharam os desfechos dos encaminhamentos e 39,1% ofereceram tratamento de TB ambulatorial completo, sendo que 68,7% usaram o tratamento diretamente observado. Conclusões. O estudo destacou os pontos fortes e os pontos fracos em áreas específicas das atividades de controle da TB em hospitais e ressaltou a importância e a complexidade de coordenar esforços entre hospitais públicos e privados e as diversas partes envolvidas. Os programas locais de combate à TB e as autoridades sanitárias devem se basear nestes resultados para melhorar a qualidade das ações relacionadas à TB nos hospitais em condições semelhantes.

Hospital-based tuberculosis control activities in five cities of Latin America.

OBJECTIVE: To generate actionable insights for improving TB control in urban areas by describing the tuberculosis (TB) control activities of hospitals in five cities in Latin America. METHODS: A descriptive study of hospital-based TB control activities was conducted in 2013-2015 using a cross-sectional survey designed by the Pan American Health Organization and administered in Guatemala City, Guatemala; Guarulhos, Brazil; Bogotá, Colombia; Lima, Peru; and Asunción, Paraguay. Data were analyzed using Chi-squared, Fisher exact tests, and the Mantel-Haenszel test for Risk Ratios, as necessary (P < 0.05). RESULTS: While variation among cities existed, most hospitals (91.3%) conducted acid-fast bacilli smears for TB diagnosis and had a quality control process (94.0%), followed national TB guidelines (95%), and reported TB cases to the respective health authorities (96%). Additionally, TB treatment was offered free of charge almost universally (97.1%). However, only 74.2% of hospitals were supervised by the national or local TB programs; 52.8% followed up on the outcome of referrals; and 39.1% offered full ambulatory TB treatment, with 68.7% using Directly-Observed Therapy. CONCLUSION: The study underscored strengths and weaknesses in specific areas for TB control activities in hospitals and highlighted the importance and complexity of coordinating efforts among private and public hospitals and the various stakeholders. Local TB programs and health authorities should use these results to enhance the quality of TB-related actions in hospitals in similar settings.

[Burden of tuberculosis attributable to diabetes in the adult population of the AmericasCarga de tuberculose atribuível à diabetes em população adulta nas Américas]. / Carga de enfermedad tuberculosa atribuible a la diabetes en población adulta de las Américas.

An ecological study was conducted to estimate the burden of incident tuberculosis attributable to diabetes in the Region of the Americas.Population size, the prevalence of diabetes, and the incidence of tuberculosis (TB) in the adult population of each country in 2013 were used to estimate the percent population attributable risk.The estimated population attributable risk was 16.8% (CI 95%: 10.8-23.8%), which corresponds to 25,045 (16,050-35,741) incident cases of TB per year. Diabetes is an important determinant of the incidence of tuberculosis in the countries of the Region of the Americas and may account for up to 1 in 4 incident TB cases. For countries, the intersection of both epidemics poses the dual challenge of providing integrated are and control of comorbidity and its structural social determinants.

Estudo ecológico conduzido para estimar a carga de tuberculose incidente atribuível à diabetes na Região das Américas.O tamanho populacional, a prevalência da diabetes e a incidência de tuberculose na população adulta de cada país em 2013 foram usados para estimar o risco atribuível populacional proporcional.Estimou-se um risco atribuível populacional de 16,8% (IC95% 10,8%-23,8%), correspondente a 25.045 (16.050-35.741) casos incidentes de tuberculose ao ano.A diabetes é um importante determinante da incidência de tuberculose nos países da Região das Américas e pode estar associada a até 1 em 4 casos incidentes de tuberculose. A intersecção de ambas as epidemias faz com que os países tenham de enfrentar o duplo desafio da atenção e controle integrados da comorbidade e de seus determinantes sociais estruturais.

Hospital-based tuberculosis control activities in five cities of Latin America / Actividades hospitalarias de control de la tuberculosis en cinco ciudades de América Latina / Atividades de controle da tuberculose em hospitais em cinco cidades da América Latina

ABSTRACT Objective To generate actionable insights for improving TB control in urban areas by describing the tuberculosis (TB) control activities of hospitals in five cities in Latin America. Methods A descriptive study of hospital-based TB control activities was conducted in 2013-2015 using a cross-sectional survey designed by the Pan American Health Organization and administered in Guatemala City, Guatemala; Guarulhos, Brazil; Bogotá, Colombia; Lima, Peru; and Asunción, Paraguay. Data were analyzed using Chi-squared, Fisher exact tests, and the Mantel-Haenszel test for Risk Ratios, as necessary (P < 0.05). Results While variation among cities existed, most hospitals (91.3%) conducted acid-fast bacilli smears for TB diagnosis and had a quality control process (94.0%), followed national TB guidelines (95%), and reported TB cases to the respective health authorities (96%). Additionally, TB treatment was offered free of charge almost universally (97.1%). However, only 74.2% of hospitals were supervised by the national or local TB programs; 52.8% followed up on the outcome of referrals; and 39.1% offered full ambulatory TB treatment, with 68.7% using Directly-Observed Therapy. Conclusion The study underscored strengths and weaknesses in specific areas for TB control activities in hospitals and highlighted the importance and complexity of coordinating efforts among private and public hospitals and the various stakeholders. Local TB programs and health authorities should use these results to enhance the quality of TB-related actions in hospitals in similar settings.

RESUMEN Objetivo Generar información utilizable para mejorar el control de la tuberculosis en las zonas urbanas describiendo las actividades hospitalarias de control de la tuberculosis de cinco ciudades de América Latina. Métodos Se realizó un estudio descriptivo de las actividades hospitalarias de control de la tuberculosis mediante una encuesta transversal formulada por la Organización Panamericana de la Salud y administrada entre el 2013 y el 2015 en Ciudad de Guatemala (Guatemala), Guarulhos (Brasil), Bogotá (Colombia), Lima (Perú) y Asunción (Paraguay). Los datos fueron analizados con la prueba de la ji al cuadrado, la prueba exacta de Fisher y la prueba de asociación de Mantel-Haenszel de las razones de riesgos, según fuera necesario (P < 0,05). Resultados Pese a la variación observada entre las ciudades, la mayor parte de los hospitales (91,3 %) realizan frotis de bacilos acidorresistentes para diagnosticar la tuberculosis y disponen de un proceso de control de la calidad (94,0 %), siguen las directrices nacionales respecto de la tuberculosis (95 %) y notifican los casos a las autoridades de salud respectivas (96 %). Además, casi todos ofrecen tratamiento antituberculoso gratuito (97,1 %). Sin embargo, solo el 74,2 % de los hospitales está supervisado por el programa nacional o local contra la tuberculosis; el 52,8 % hace el seguimiento de la evolución de los pacientes derivados; y el 39,1 % ofrece tratamiento antituberculoso plenamente ambulatorio a los pacientes, del cual el 68,7 % corresponde al tratamiento bajo observación directa. Conclusiones En el estudio se ponen de relieve las fortalezas y las debilidades de aspectos específicos de las actividades hospitalarias de control de la tuberculosis, así como la importancia y la complejidad que reviste coordinar los esfuerzos entre los hospitales privados y públicos y los diversos interesados directos. Los programas locales contra la tuberculosis y las autoridades de salud deben aprovechar estos resultados para mejorar la calidad de las actividades hospitalarias relacionadas con la tuberculosis en entornos similares.

RESUMO Objetivo Originar insights proativos para melhorar o controle da tuberculose (TB) em áreas urbanas descrevendo as atividades de controle da TB em hospitais em cinco cidades na América Latina. Métodos Estudo descritivo das atividades de controle da TB em hospitais realizado em 2013-2015 com base em pesquisa transversal concebida pela Organização Pan-Americana da Saúde e conduzida na Cidade da Guatemala (Guatemala), Guarulhos (Brasil), Bogotá (Colômbia), Lima (Peru) e Assunção (Paraguai). Os dados foram analisados com o uso do teste qui-quadrado, teste exato de Fisher e teste de Mantel-Haenszel para razões de risco, conforme necessário (P < 0,05). Resultados Apesar de ter existido variação entre as cidades, a maioria dos hospitais (91,3%) realizou o teste de esfregaço de bacilos acidorresistentes para o diagnóstico de TB e dispunha de um processo de controle de qualidade (94,0%), seguiu os protocolos nacionais de TB (95%) e notificou casos de TB aos órgãos sanitários competentes (96%). Além disso, o tratamento de TB foi proporcionado gratuitamente quase como um todo (97,1%). Porém, somente 74,2% dos hospitais receberam supervisão dos programas locais ou nacionais de combate à TB; 52,8% acompanharam os desfechos dos encaminhamentos e 39,1% ofereceram tratamento de TB ambulatorial completo, sendo que 68,7% usaram o tratamento diretamente observado. Conclusões O estudo destacou os pontos fortes e os pontos fracos em áreas específicas das atividades de controle da TB em hospitais e ressaltou a importância e a complexidade de coordenar esforços entre hospitais públicos e privados e as diversas partes envolvidas. Os programas locais de combate à TB e as autoridades sanitárias devem se basear nestes resultados para melhorar a qualidade das ações relacionadas à TB nos hospitais em condições semelhantes.

Social determinants and inequalities in tuberculosis incidence in Latin America and the Caribbean / Determinantes sociales y desigualdades en la incidencia de tuberculosis en América Latina y el Caribe

Objective. To identify key social determinants of tuberculosis (TB) incidence among countries in Latin America and the Caribbean (LAC), a geographic area regarded as one of the most socioeconomically unequal in the world. Methods. An ecological study was conducted at the country level. Data were obtained from several institutional-based sources. Random-effects regression modeling was used to explore the relationship between several social determinants indicators and TB incidence rates in 20 LAC countries in 1995–2012. Standard gap and gradient metrics of social inequality in TB incidence among countries in 2000, 2005, and 2010 were then calculated. Results. TB incidence rate trends were significantly associated with health expenditure per capita and access to improved sanitation facilities, as well as with life expectancy at birth and TB detection rate, after adjusting for other socioeconomic, demographic, and health services variables. Absolute and relative inequality in TB incidence remained mostly unchanged: countries at the bottom 20% of both health expenditure and sanitation coverage distributions concentrated up to 40% of all TB incident cases, despite a considerable decline in the overall TB incidence mean rate during the period assessed. Conclusions. Along with the intensity of TB control (reflected by TB detection rate), both access to sanitation (as a proxy of quality of living conditions) and health expenditure per capita (either as an indicator of the level of resources and/or commitment to health care) appear to be key determinants of TB incidence trends in LAC countries. Inequalities in both health expenditure per capita and access to sanitation seem to define profound and persistent inverse gradients in TB incidence among LAC countries.

Objetivo. Establecer los determinantes sociales clave de la incidencia de tuberculosis (TB) en los países de América Latina y el Caribe (ALC), una zona geográfica consideraba como una de las más afectadas por las desigualdades socioeconómicas en el mundo. Métodos. Se llevó a cabo un estudio ecológico a nivel de país. Los datos se obtuvieron de diversas fuentes institucionales. Mediante un modelo de regresión de efectos aleatorios se exploró la relación entre varios indicadores de determinantes sociales y las tasas de incidencia de TB en 20 países de ALC durante el periodo de 1995 al 2012. A continuación, se calcularon los valores ordinarios de la brecha y el gradiente de desigualdad social en la incidencia de TB entre países en el 2000, el 2005 y el 2010. Resultados. Las tendencias en la tasa de incidencia de TB se asociaban significativamente con el gasto per cápita en salud y el acceso a mejores instalaciones de saneamiento, así como con la esperanza de vida al nacer y la tasa de detección de la TB, tras ajustar para otras variables socioeconómicas, demográficas y de servicios de salud. La desigualdad absoluta y relativa en la incidencia de TB se mantuvo prácticamente inalterada: los países que se distribuían en el 20% inferior del gasto en salud y la cobertura de saneamiento aglutinaban hasta un 40% de todos los casos nuevos de TB, a pesar de una considerable disminución de la tasa general media de incidencia de TB durante el período evaluado. Conclusiones. Junto con la intensidad de las actividades de control de la TB (reflejada por la tasa de detección de la TB), tanto el acceso al saneamiento (reflejo de la calidad de las condiciones de vida) como el gasto per cápita en salud (ya sea como indicador del nivel de recursos o del compromiso con la atención de salud) parecen ser determinantes clave de las tendencias en la incidencia de TB en los países de ALC. Las desigualdades tanto en el gasto per cápita en salud como en el acceso al saneamiento parecen definir los gradientes inversos profundos y persistentes en la incidencia de TB entre los países de ALC.

Towards tuberculosis elimination: an action framework for low-incidence countries.

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.

Social determinants and inequalities in tuberculosis incidence in Latin America and the Caribbean.

OBJECTIVE: To identify key social determinants of tuberculosis (TB) incidence among countries in Latin America and the Caribbean (LAC), a geographic area regarded as one of the most socioeconomically unequal in the world METHODS: An ecological study was conducted at the country level. Data were obtained from several institutional-based sources. Random-effects regression modeling was used to explore the relationship between several social determinants indicators and TB incidence rates in 20 LAC countries in 1995-2012. Standard gap and gradient metrics of social inequality in TB incidence among countries in 2000, 2005, and 2010 were then calculated. RESULTS: TB incidence rate trends were significantly associated with health expenditure per capita and access to improved sanitation facilities, as well as with life expectancy at birth and TB detection rate, after adjusting for other socioeconomic, demographic, and health services variables. Absolute and relative inequality in TB incidence remained mostly unchanged: countries at the bottom 20% of both health expenditure and sanitation coverage distributions concentrated up to 40% of all TB incident cases, despite a considerable decline in the overall TB incidence mean rate during the period assessed. CONCLUSIONS: Along with the intensity of TB control (reflected by TB detection rate), both access to sanitation (as a proxy of quality of living conditions) and health expenditure per capita (either as an indicator of the level of resources and/or commitment to health care) appear to be key determinants of TB incidence trends in LAC countries. Inequalities in both health expenditure per capita and access to sanitation seem to define profound and persistent inverse gradients in TB incidence among LAC countries.

Influence of multidrug resistance on tuberculosis treatment outcomes with standardized regimens.

RATIONALE: Multidrug-resistant tuberculosis (TB) poses a major challenge to global TB control. We analyzed the association between estimated prevalence of initial or acquired MDR-TB, and treatment outcomes reported nationally. OBJECTIVES: We analyzed the estimated prevalence of initial or acquired MDR-TB and treatment outcomes reported nationally. METHODS: Countries were analyzed if multidrug resistance prevalence estimates were available, and if they reported outcomes for more than 250 cases treated using standardized regimens in 2003 and/or 2004. Data sources were the World Health Organization for treatment regimens, prevalence of initial multidrug resistance, and reported cases and treatment outcomes in 2003 and 2004; the Joint United Nations Programme on HIV/AIDS for HIV seroprevalence; and the World Bank for income per capita. The adjusted impact of initial multidrug resistance on initial and retreatment outcomes was estimated with weighted multivariate linear regression. MEASUREMENTS AND MAIN RESULTS: Among countries using one of two standardized initial regimens, failure rates averaged 5.0%, and relapse rates averaged 12.8% in the 20 countries where prevalence of initial multidrug resistance exceeded 3%, compared with an average of 1.6% (P < 0.0001) and 8.1% (P = 0.0002), respectively, in 83 countries where initial multidrug resistance prevalence was less than 3%. In 92 countries using one standardized retreatment regimen, failure rates were 2.7%, 3.8%, 6.2%, and 8.1% in quartiles of increasing prevalence of acquired multidrug resistance (P < 0.0001). When stratified by initial multidrug resistance prevalence, initial and retreatment outcomes in the 79 countries using the 6-month rifampin initial regimen were not significantly different from the 24 countries using the 2-month rifampin initial regimen. CONCLUSIONS: Currently recommended standardized TB initial and retreatment regimens should be reevaluated in countries where prevalence of initial multidrug resistance exceeds 3%, in view of poor treatment outcomes.