Encuestas telefónicas para el estudio de costos catastróficos por tuberculosis en Colombia: una herramienta innovadora / Telephone surveys for the study of catastrophic costs due to tuberculosis in Colombia: a novel tool / Pesquisas telefônicas para um estudo de custos catastróficos da tuberculose na Colômbia: uma ferramenta inovadora

[RESUMEN]. El estudio de costos catastróficos que experimentan las personas afectadas por tuberculosis realizado en Colombia durante la pandemia de COVID-19 trajo consigo la oportunidad de implementar encuestas telefónicas como medio para la recopilación de información. Lo anterior se constituye como una innovación metodológica en los estándares establecidos por la Organización Mundial de la Salud (OMS) que, para este tipo de estudios, suelen tener base en el empleo de encuestas cara a cara con los pacientes que acuden a las instalaciones de salud. El diseño del estudio, sus objetivos y metodología fueron adaptados del manual práctico para la realización de encuestas de costos de la tuberculosis de la OMS. Se seleccionaron 1 065 personas afectadas por tuberculosis como participantes del estudio, a quienes se les administró de manera telefónica el cuestionario estándar adaptado al contexto colombiano. Fue posible obtener datos estructurados sobre los costos directos e indirectos que enfrentan los pacientes con tuberculosis y sus familias; de manera general, se observó que todas las variables de recopilación alcanzaron una completitud mayor a 80%, con un tiempo promedio de encuesta de 40 minutos y una tasa de rechazo de 8%. La metodología de encuestas telefónicas desarrollada para determinar la línea base del estudio de costos catastróficos en Colombia resultó innovadora por el formato telefónico, que mantiene los estándares de información requerida para permitir estimaciones comparables a nivel internacional, y es un medio útil en la generación de resultados estandarizados en eventos en los cuales existe limitación para la realización de encuestas cara a cara.

[ABSTRACT]. The study of catastrophic costs incurred by people affected by tuberculosis (TB), conducted in Colombia during the COVID-19 pandemic, provided the opportunity to implement telephone surveys for data collection. This constitutes a methodological innovation regarding the standards established by the World Health Organization (WHO) which, for this type of study, usually rely on face-to-face surveys of patients attending health facilities. The study design, objectives, and methodology were adapted from the WHO publication Tuberculosis patient cost surveys: a handbook. A total of 1065 people affected by tuberculosis were selected as study participants and, by telephone, were administered a standard questionnaire adapted to the Colombian context. This allowed the collection of structured data on the direct and indirect costs faced by TB patients and their families. Greater than 80% completeness was achieved for all variables of interest, with an average survey duration of 40 minutes and a rejection rate of 8%. The described survey method to determine the baseline for further study of catastrophic costs in Colombia was novel because of its telephone-based format, which adheres to the information standards required to allow internationally comparable estimates. It is a useful means of generating standardized results in contexts in which the ability to conduct face-to-face surveys is limited.

[RESUMO]. O estudo dos custos catastróficos incorridos pelas pessoas afetadas pela tuberculose realizado na Colômbia durante a pandemia de COVID-19 representou uma oportunidade de implementar pesquisas telefônicas como forma de coleta de dados. Constitui-se uma inovação metodológica dos padrões estabelecidos pela Organização Mundial da Saúde (OMS), que, para esse tipo de estudo, geralmente se baseiam no uso de pesquisas presenciais com os pacientes que frequentam estabelecimentos de saúde. O delineamento, os objetivos e a metodologia do estudo foram adaptados do manual prático da OMS para a realização de pesquisas de custos da tuberculose. Um total de 1065 pessoas afetadas pela tuberculose foram selecionadas para participar do estudo. O questionário padrão, adaptado ao contexto colombiano, foi aplicado pelo telefone. Foi possível obter dados estruturados sobre os custos diretos e indiretos enfrentados pelos pacientes com tuberculose e suas famílias. Em geral, observou-se que todas as variáveis de coleta atingiram uma completude de mais de 80%, com um tempo médio de pesquisa de 40 minutos e uma taxa de recusa de 8%. A metodologia de pesquisa telefônica desenvolvida para determinar a linha de base do estudo de custos catastróficos na Colômbia foi inovadora devido ao formato telefônico, que mantém os padrões de informação necessários para permitir estimativas comparáveis internacionalmente e é uma forma útil de gerar resultados padronizados em circunstâncias em que há limitações para a realização de pesquisas presenciais.

[Telephone surveys for the study of catastrophic costs due to tuberculosis in Colombia: a novel toolPesquisas telefônicas para um estudo de custos catastróficos da tuberculose na Colômbia: uma ferramenta inovadora]. / Encuestas telefónicas para el estudio de costos catastróficos por tuberculosis en Colombia: una herramienta innovadora.

The study of catastrophic costs incurred by people affected by tuberculosis (TB), conducted in Colombia during the COVID-19 pandemic, provided the opportunity to implement telephone surveys for data collection. This constitutes a methodological innovation regarding the standards established by the World Health Organization (WHO) which, for this type of study, usually rely on face-to-face surveys of patients attending health facilities. The study design, objectives, and methodology were adapted from the WHO publication Tuberculosis patient cost surveys: a handbook. A total of 1065 people affected by tuberculosis were selected as study participants and, by telephone, were administered a standard questionnaire adapted to the Colombian context. This allowed the collection of structured data on the direct and indirect costs faced by TB patients and their families. Greater than 80% completeness was achieved for all variables of interest, with an average survey duration of 40 minutes and a rejection rate of 8%. The described survey method to determine the baseline for further study of catastrophic costs in Colombia was novel because of its telephone-based format, which adheres to the information standards required to allow internationally comparable estimates. It is a useful means of generating standardized results in contexts in which the ability to conduct face-to-face surveys is limited.

O estudo dos custos catastróficos incorridos pelas pessoas afetadas pela tuberculose realizado na Colômbia durante a pandemia de COVID-19 representou uma oportunidade de implementar pesquisas telefônicas como forma de coleta de dados. Constitui-se uma inovação metodológica dos padrões estabelecidos pela Organização Mundial da Saúde (OMS), que, para esse tipo de estudo, geralmente se baseiam no uso de pesquisas presenciais com os pacientes que frequentam estabelecimentos de saúde. O delineamento, os objetivos e a metodologia do estudo foram adaptados do manual prático da OMS para a realização de pesquisas de custos da tuberculose. Um total de 1065 pessoas afetadas pela tuberculose foram selecionadas para participar do estudo. O questionário padrão, adaptado ao contexto colombiano, foi aplicado pelo telefone. Foi possível obter dados estruturados sobre os custos diretos e indiretos enfrentados pelos pacientes com tuberculose e suas famílias. Em geral, observou-se que todas as variáveis de coleta atingiram uma completude de mais de 80%, com um tempo médio de pesquisa de 40 minutos e uma taxa de recusa de 8%. A metodologia de pesquisa telefônica desenvolvida para determinar a linha de base do estudo de custos catastróficos na Colômbia foi inovadora devido ao formato telefônico, que mantém os padrões de informação necessários para permitir estimativas comparáveis internacionalmente e é uma forma útil de gerar resultados padronizados em circunstâncias em que há limitações para a realização de pesquisas presenciais.

Tuberculosis patients face high treatment support costs in Colombia, 2021.

OBJECTIVE: To estimate the baseline to measure one of the three indicators of the World Health Organization (WHO) End TB strategy (2015-2035), measure the costs incurred by patients affected by tuberculosis (TB) during a treatment episode and estimate the proportion of households facing catastrophic costs (CC) and associated risk factors, in Colombia, 2021. MATERIAL AND METHODS: A nationally representative cross-sectional survey was conducted among participants on TB treatment in Colombia, using telephone interviews due to the exceptional context of the COVID-19 pandemic. The survey collected household costs (direct [medical and non-medical out-of-pocket expenses] and indirect) over an episode of TB, loss of time, coping measures, self-reported income, and asset ownership. Total costs were expressed as a proportion of annual household income and analyzed for risk factors of CC (defined as costs above 20% annual household income). RESULTS: The proportion of TB-affected households incurring in costs above 20% annual household income (CC) was 51.7% (95%CI: 45.4-58.0) overall, 51.3% (95%CI: 44.9-57.7) among patients with drug-sensitive (DS) TB, and 65.0% (95%CI: 48.0-82.0) among drug-resistant (DR). The average patient cost of a TB case in Colombia was $1,218 (95%CI 1,106-1,330) including $860.9 (95%CI 776.1-945.7) for non-medical costs, $339 (95%CI 257-421) for the indirect costs, and $18.1 (95%CI 11.9-24.4) for the medical costs. The factors that influenced the probability of facing CC were income quintile, job loss, DR-TB patient, and TB type. CONCLUSION: Main cost drivers for CC were non-medical out-of-pocket expenses and income loss (indirect costs). Current social protection programs ought to be expanded to mitigate the proportion of TB-affected households facing CC in Colombia, especially those with lower income levels.

[Social determinants and the Sustainable Development Goals' tuberculosis target in the AmericasDeterminantes sociais e a meta para a tuberculose dos Objetivos de Desenvolvimento Sustentável nas Américas]. / Determinantes sociales y meta de tuberculosis en los Objetivos de Desarrollo Sostenible en las Américas.

OBJECTIVE: Determine patterns of tuberculosis (TB) incidence indicators and number of deaths from TB within the framework of target 3.3 of the Sustainable Development Goals (SDGs) and their correlation with social determinants. METHODS: Ecological study methodology was used, in which the population is the unit of analysis. Social determinants were analyzed using a negative binomial regression model and strength of association. RESULTS: In the Americas, there was an average annual reduction in the TB incidence rate of 0.3% from 2009 to 2018; however, from 2015 to 2018, the rate increased, from 27.6 to 28.8 per 100,000 population. With regard to social determinants, the groups of countries with the lowest human development index (HDI) and gross domestic product (GDP) have a higher incidence of TB. TB risk in the country with the lowest HDI is six times that of the country with the highest HDI. CONCLUSIONS: At the current rate of reduction in the incidence rate and number of deaths from TB, the Region of the Americas will not meet the targets in the SDGs and in the End TB Strategy. Rapid implementation and expansion of interventions for TB prevention and control are required to attain the targets. This involves, among other actions, reducing access barriers to diagnosis and treatment and strengthening initiatives to address social determinants.

OBJETIVO: Determinar o comportamento dos indicadores de incidência da tuberculose (TB) e o número de mortes por TB no quadro da meta 3.3 dos Objetivos de Desenvolvimento Sustentável (ODS) e sua correlação com os determinantes sociais. MÉTODOS: Utilizamos uma metodologia de estudo ecológico, na qual a unidade de análise é a população. Para a análise dos determinantes sociais, utilizamos o modelo de regressão binomial negativo e a avaliamos a força das associações. RESULTADOS: Nas Américas, observou-se uma redução anual média na taxa de incidência de TB de 0,3% entre 2009 e 2018; entretanto, de 2015 a 2018 houve um aumento, de 27,6 para 28,8 por 100.000 habitantes. Com relação aos determinantes sociais, os grupos de países com índice de desenvolvimento humano (IDH) e produto interno bruto (PIB) mais baixos apresentam uma maior incidência de TB. O risco de TB no país com o menor IDH é seis vezes maior que no país com o maior IDH. CONCLUSÕES: Se mantido o ritmo atual de redução na taxa de incidência e no número de mortes por TB, a Região das Américas não alcançará as metas propostas nos ODS e na Estratégia pelo Fim da Tuberculose. É necessária uma implementação e expansão mais rápida das intervenções de prevenção e controle da TB para alcançar este objetivo. Isto implica, entre outras ações, reduzir as barreiras de acesso ao diagnóstico e tratamento e fortalecer as iniciativas que abordam os determinantes sociais.

Determinantes sociales y meta de tuberculosis en los Objetivos de Desarrollo Sostenible en las Américas

[RESUMEN]. Objetivo. Determinar el comportamiento de los indicadores de incidencia de tuberculosis (TB) y número de muertes por TB en el marco de la meta 3.3 de los Objetivos de Desarrollo Sostenible (ODS) y su correlación con los determinantes sociales. Métodos. Se utilizó una metodología de estudio ecológico, en el cual la unidad de análisis es la población. Para el análisis de los determinantes sociales, se hizo uso del modelo de regresión binomial negativo y la fuerza de asociación. Resultados. En las Américas se ha presentado una disminución promedio anual en la tasa de incidencia de TB de 0,3% entre 2009 y 2018; sin embargo, de 2015 a 2018 ha habido un aumento, pasando de 27,6 a 28,8 por 100 000 habitantes. Con respecto a los determinantes sociales, los grupos de países con índice de desarrollo humano (IDH) y producto interno bruto (PIB) más bajos tienen una incidencia de TB más alta. El riesgo de TB en el país con IDH más bajo es seis veces mayor que en el país con IDH más alto. Conclusiones. Al ritmo de la disminución actual de la tasa de incidencia y del número de muertes por TB, la Región de las Américas no alcanzará las metas propuestas en los ODS y en la Estrategia Fin de la TB. Se requiere una implementación y expansión rápidas de las intervenciones en prevención y control de TB para lograrlo. Esto implica, entre otras acciones, reducir las barreras de acceso al diagnóstico y tratamiento y fortalecer las iniciativas para abordar los determinantes sociales.

[ABSTRACT]. Objective. Determine patterns of tuberculosis (TB) incidence indicators and number of deaths from TB within the framework of target 3.3 of the Sustainable Development Goals (SDGs) and their correlation with social determinants. Methods. Ecological study methodology was used, in which the population is the unit of analysis. Social determinants were analyzed using a negative binomial regression model and strength of association. Results. In the Americas, there was an average annual reduction in the TB incidence rate of 0.3% from 2009 to 2018; however, from 2015 to 2018, the rate increased, from 27.6 to 28.8 per 100,000 population. With regard to social determinants, the groups of countries with the lowest human development index (HDI) and gross domestic product (GDP) have a higher incidence of TB. TB risk in the country with the lowest HDI is six times that of the country with the highest HDI. Conclusions. At the current rate of reduction in the incidence rate and number of deaths from TB, the Region of the Americas will not meet the targets in the SDGs and in the End TB Strategy. Rapid implementation and expansion of interventions for TB prevention and control are required to attain the targets. This involves, among other actions, reducing access barriers to diagnosis and treatment and strengthening initiatives to address social determinants.

[RESUMO]. Objetivo. Determinar o comportamento dos indicadores de incidência da tuberculose (TB) e o número de mortes por TB no quadro da meta 3.3 dos Objetivos de Desenvolvimento Sustentável (ODS) e sua correlação com os determinantes sociais. Métodos. Utilizamos uma metodologia de estudo ecológico, na qual a unidade de análise é a população. Para a análise dos determinantes sociais, utilizamos o modelo de regressão binomial negativo e a avaliamos a força das associações. Resultados. Nas Américas, observou-se uma redução anual média na taxa de incidência de TB de 0,3% entre 2009 e 2018; entretanto, de 2015 a 2018 houve um aumento, de 27,6 para 28,8 por 100.000 habitantes. Com relação aos determinantes sociais, os grupos de países com índice de desenvolvimento humano (IDH) e produto interno bruto (PIB) mais baixos apresentam uma maior incidência de TB. O risco de TB no país com o menor IDH é seis vezes maior que no país com o maior IDH. Conclusões. Se mantido o ritmo atual de redução na taxa de incidência e no número de mortes por TB, a Região das Américas não alcançará as metas propostas nos ODS e na Estratégia pelo Fim da Tuberculose. É necessária uma implementação e expansão mais rápida das intervenções de prevenção e controle da TB para alcançar este objetivo. Isto implica, entre outras ações, reduzir as barreiras de acesso ao diagnóstico e tratamento e fortalecer as iniciativas que abordam os determinantes sociais.

Analisis de situación de los sistemas de información de los laboratorios supranacionales, laboratorios de referencia nacional y las redes nacionales de laboratorios de TB / Situation analysis of information systems of supranational laboratories, national reference laboratories and national networks of TB laboratories

El presente estudio tiene el objetivo de tener un análisis de la situación de los sistemas de información de los Laboratorios Supranacionales-LSN, Laboratorios de Referencia Nacional -LRN, y las Redes Nacionales de Laboratorios- RNL de los 20 países que hacen parte del Programa "Fortalecimiento de la Red de Laboratorios de Tuberculosis de la Región de las Américas" a fin de generar propuestas para el fortalecimiento de los sistemas de información. Para el levantamiento de la información, se realizó la construcción de una encuesta con variables que permitieron identificar la situación actual de los sistemas de información de los LSN, LRN y las RNL de los países participantes del Programa; ésta fue validada por grupos de expertos y aplicada a los coordinadores de los LRN y los LSN durante el mes de agosto de 2017; se realizó la socialización y retroalimentación de los resultados preliminares de la encuesta en una presentación realizada en el mes de septiembre, en ocasión de la Reunión Técnica Regional de Tuberculosis realizada en Lima,-Perú

Estructura y funcionamiento de las redes nacionales de laboratorios de tuberculosis en la Región de las Américas / Structure and Functioning of National Tuberculosis Laboratory Networks in the Region of the Americas

El presente estudio pretende identificar necesidades y brechas de acceso al diagnóstico de calidad. Se desarrolló un cuestionario que fue remitido a los laboratorios nacionales de referencia (LNR) de 20 países de la región (Argentina, Belice, Bolivia, Chile, Colombia, Costa Rica, Cuba, Ecuador, El Salvador, Guatemala, Guyana, Honduras, México, Nicaragua, Panamá, Paraguay, Perú, República Dominicana, Uruguay y Venezuela) durante el año 2017. El análisis de los resultados de este estudio, que describe la estructura y actividades de las 20 redes nacionales de laboratorio de TB (RNLTB) durante 2016, permitió realizar diversas observaciones y recomendaciones, según se citan.

Immunogenicity and protection conferred by Mycobacterium habana in a murine model of pulmonary tuberculosis.

Mycobacterium habana was isolated in Cuba in 1971. Later, was demonstrated its protection capacity in mycobacterial infection. Here we determined the level of virulence, immunogenicity and the efficacy of three different M. habana strains as attenuated live vaccines. Intratracheal infection of BALB/c mice with high dose M. habana TMC 5135 or IPK-337 strains permitted 100% survival and limited tissue damage. Mice infected with M. habana IPK-220 showed lower attenuation, so it was discarded for the vaccination experiments. Strains IPK-337 and TMC 5135 were used as subcutaneous vaccine and compared with BCG. Nude mice vaccinated with strain 5135 showed longer but non-significant survival than BCG vaccinated animals. Cell suspensions from M. habana vaccinated mice produced higher IFNγ after stimulation with mycobacterial antigens than BCG recipients. After four months of challenge with Mycobacterium tuberculosis strain H37Rv, mice vaccinated with BCG substrain Phipps or strain TMC 5135 showed total survival, while 60% survival was exhibited by animals vaccinated with M. habana IPK-337. Both M. habana strains do not prevent the infection with M. tuberculosis but avoided the progression of the experimental disease; strain TMC 5135 showed similar level of protection than BCG.

Association between embB mutations and ethambutol resistance in Mycobacterium tuberculosis isolates from Cuba and the Dominican Republic: reproducible patterns and problems.

The relation of ethambutol resistance to embB mutations remains unclear, and there are no reports on ethambutol resistance from the caribbean. We examined the sequence of embB in 57 distinct Multi-Drug Resistant (MDR) and non-MDR strains of Mycobacterium tuberculosis, mostly from Cuba and the Dominican Republic. embB306 codon mutations were found exclusively in MDR-TB, but in both ethambutol sensitive and resistant strains. Valine substitutions predominated in ethambutol resistant strains, while isoleucine replacements were more common in sensitive strains. Three ethambutol resistant MDR strains without embB306 substitutions had replacements in embB406 or embB497, but these were also found in ethambutol sensitive MDR strains. The results confirm previous findings that amino acid substitutions in EmbB306, EmbB406 and EmbB497 are found only in MDR-TB strains but in both phenotypically resistant and sensitive strains. One ethambutol resistant non-MDR strain did not have any embB mutation suggesting that other undefined mutations can also confer ethambutol resistance.

Association between embB mutations and ethambutol resistance in Mycobacterium tuberculosis isolates from Cuba and the Dominican Republic: reproducible patterns and problems / Association between embB mutations and ethambutol resistance in Mycobacterium tuberculosis isolates from Cuba and the Dominican Republic: reproducible patterns and problems.

The relation of ethambutol resistance to embB mutations remains unclear, and there are no reports on ethambutol resistance from the caribbean. We examined the sequence of embB in 57 distinct Multi-Drug Resistant (MDR) and non-MDR strains of Mycobacterium tuberculosis, mostly from Cuba and the Dominican Republic. embB306 codon mutations were found exclusively in MDR-TB, but in both ethambutol sensitive and resistant strains. Valine substitutions predominated in ethambutol resistant strains, while isoleucine replacements were more common in sensitive strains. Three ethambutol resistant MDR strains without embB306 substitutions had replacements in embB406 or embB497, but these were also found in ethambutol sensitive MDR strains. The results confirm previous findings that amino acid substitutions in EmbB306, EmbB406 and EmbB497 are found only in MDR-TB strains but in both phenotypically resistant and sensitive strains. One ethambutol resistant non-MDR strain did not have any embB mutation suggesting that other undefined mutations can also confer ethambutol resistance.

Association between embB mutations and ethambutol resistance in Mycobacterium tuberculosis isolates from Cuba and the Dominican Republic: reproducible patterns and problems. / Association between embB mutations and ethambutol resistance in Mycobacterium tuberculosis isolates from Cuba and the Dominican Republic: reproducible patterns and problems.

The relation of ethambutol resistance to embB mutations remains unclear, and there are no reports on ethambutol resistance from the caribbean. We examined the sequence of embB in 57 distinct Multi-Drug Resistant (MDR) and non-MDR strains of Mycobacterium tuberculosis, mostly from Cuba and the Dominican Republic. embB306 codon mutations were found exclusively in MDR-TB, but in both ethambutol sensitive and resistant strains. Valine substitutions predominated in ethambutol resistant strains, while isoleucine replacements were more common in sensitive strains. Three ethambutol resistant MDR strains without embB306 substitutions had replacements in embB406 or embB497, but these were also found in ethambutol sensitive MDR strains. The results confirm previous findings that amino acid substitutions in EmbB306, EmbB406 and EmbB497 are found only in MDR-TB strains but in both phenotypically resistant and sensitive strains. One ethambutol resistant non-MDR strain did not have any embB mutation suggesting that other undefined mutations can also confer ethambutol resistance.

Vigilancia de la resistencia a los fármacos antituberculosos en Cuba, 2000–2009 / Surveillance of resistance to antitubercular drugs in Cuba, 2000–2009

Objetivo. Determinar la prevalencia de la resistencia a los fármacos antituberculosos en Cuba en el decenio 2000–2009. Métodos. Se realizó un estudio prospectivo longitudinal. El universo de trabajo estuvo constituido por un total de 2 285 aislamientos de Mycobacterium tuberculosis obtenidos de todo el país en el período comprendido entre el 1 de enero de 2000 y el 31 de diciembre de 2009. Se empleó el método de las proporciones en medio Löwenstein-Jensen con los fármacos de primera línea: isoniazida, estreptomicina, etambutol y rifampicina. Resultados. La resistencia entre los casos nuevos y los pacientes con antecedente de tratamiento previo fue de 8,5% y 37,0%, respectivamente; para estas mismas categorías de caso, la multirresistencia fue de 0,4% y 8,8%, respectivamente. Conclusiones. El presente estudio muestra baja prevalencia de cepas multirresistentes en Cuba. Estos resultados reflejan los avances logrados por el programa nacional de control, que trabaja en la actualidad hacia la eliminación de la tuberculosis como problema de salud pública en el país.

Objective. Determine the prevalence of resistance to antitubercular drugs in Cuba in the 2000–2009 decade. Methods. A prospective longitudinal study was conducted. The sample group consisted of 2 285 Mycobacterium tuberculosis isolates obtained from throughout the country in the period from 1 January 2000 to 31 December 2009. The proportion method was used in Löwenstein-Jensen media with the first-line drugs: isoniazid, streptomycin, ethambutol, and rifampicin. Results. In the new cases and patients with a history of previous treatment, resistance was 8.5% and 37.0%, respectively. In these case categories, multidrug resistance was 0.4% and 8.8%, respectively. Conclusions. This study shows low prevalence of multidrug-resistant strains in Cuba. The results reflect the progress made by the national control program, which is currently working on the elimination of tuberculosis as a public health problem in the country.

[Surveillance of resistance to antitubercular drugs in Cuba, 2000-2009]. / Vigilancia de la resistencia a los fármacos antituberculosos en Cuba, 2000-2009.

OBJECTIVE: Determine the prevalence of resistance to antitubercular drugs in Cuba in the 2000-2009 decade. METHODS: A prospective longitudinal study was conducted. The sample group consisted of 2,285 Mycobacterium tuberculosis isolates obtained from throughout the country in the period from 1 January 2000 to 31 December 2009. The proportion method was used in Löwenstein-Jensen media with the first-line drugs: isoniazid, streptomycin, ethambutol, and rifampicin. RESULTS: In the new cases and patients with a history of previous treatment, resistance was 8.5% and 37.0%, respectively. In these case categories, multidrug resistance was 0.4% and 8.8%, respectively. CONCLUSIONS: This study shows low prevalence of multidrug-resistant strains in Cuba. The results reflect the progress made by the national control program, which is currently working on the elimination of tuberculosis as a public health problem in the country.

Structural studies of cord factors from Mycobacterium simiae related to the capacity for tumour necrosis factor alpha (α-TNF) induction.

The structure of cord factor was studied in several strains of Mycobacterium simiae, including 'habana' TMC 5135, considered as highly immunogenic in experimental tuberculosis and leprosy. The mycolic acids liberated from cord factor were identified in all cases as α'-, α- and keto-mycolates. According to the general NMR and MS data, α'-mycolates were mono-unsaturated and contained from 64 to 68 carbon atoms, whereas α-mycolates mainly presented two 2,3-disubstituted cyclopropane rings and a chain length of 80-91 carbon atoms; keto-mycolates mostly contained one cyclopropane ring and 85-91 carbon atoms. Taking into account the (1)H-NMR results, strains varied in the ratio of the different mycolates, and the high levels of keto-mycolates found in the cord factors of TMC 5135 and ATCC 25275(T) stood out. Notably, MS revealed that the odd carbon number series of α-mycolates (C87-C89) predominated in the cord factor of TMC 5135, in contrast to the remaining studied strains, in which the even (C84-C86) and odd carbon number series appeared more equal. The fine structural differences detected among the cord factors studied did not seem to be relevant to the general capacity of these molecules to induce the secretion of tumour necrosis factor alpha, as the cord factors from several strains of M. simiae (TMC 5135, IPK-342 and ATCC 25275(T)) induced similar amounts of this cytokine in RAW 264.7 cells.

Evaluation of colorimetric methods using nicotinamide for rapid detection of pyrazinamide resistance in Mycobacterium tuberculosis.

The direct detection of pyrazinamide resistance in Mycobacterium tuberculosis is sufficiently difficult that many laboratories do not attempt it. Most pyrazinamide resistance is caused by mutations that inactivate the pyrazinamidase enzyme needed to convert the prodrug pyrazinamide to its active form. We evaluated two newer and simpler methods to assess pyrazinamidase activity, the nitrate reductase and malachite green microtube assays, using nicotinamide in place of pyrazinamide. A total of 102 strains were tested by these methods and the results compared with those obtained by the classic Wayne assay. Mutations in the pncA gene were identified by sequencing the pncA genes from all isolates in which pyrazinamide resistance was detected by any of the three methods. Both the nitrate reductase and malachite green microtube assays showed sensitivities of 93.75% and specificities of 97.67%. Mutations in the pncA gene were found in 14 of 16 strains that were pyrazinamide resistant and in 1 of 4 strains that were sensitive by the Wayne assay. Both of these simple methods, used with nicotinamide, are promising and inexpensive alternatives for the rapid detection of pyrazinamide resistance in limited-resource countries.

Obtención y caracterización parcial de un extracto lipídico de la membrana externa de Mycobacterium smegmatis / Obtainment and partial characterization of a lipidic fragment of the outer membrane of Mycobacterium smegmatis

En la actualidad, los antígenos lipídicos de las micobacterias constituyen blancos atractivos para el desarrollo de nuevas formulaciones vacunales contra la tuberculosis. En nuestro trabajo se realizó la caracterización parcial de un extracto lipídico de pared celular de Mycobacterium smegmatis mediante cromatografía de capa delgada y Dot blot frente a gammaglobulina humana. Se identificó, fundamentalmente, la presencia de fosfolípidos y ßcidos micólicos en el extracto lipídico y se observó un elevado reconocimiento de los mismos por la gammaglobulina humana, lo cual indica la importancia de continuar los estudios de inmunoprotección empleando antígenos lipídicos de micobacterias(AU)

Currently, lipid antigens of mycobacteria are attractive targets for the development of new tuberculosis vaccinal formulations. A lipid extract of Mycobacterium smegmatis cell wall was characterized using a Thin Layer Chromatography and Dot blot with human gammaglobulin. Mainly we identified the presence of phospholipids and micolic acids in the lipid extract showing a high recognition by human gammaglobulin. These results indicate the relevance of continuing immunoprotection studies with mycobacterial lipid antigens(AU)

Diagnóstico de mycobacterium tuberculosis en pacientes sintomáticos incluyendo los infectados con el síndrome de inmunodeficiencia adquirida (SIDA) / Diagnosis of mycobacterium tuberculosis in symptomatic patients including those infected with the acquired immunodeficiency syndrome (AIDS)

Con la aparición del Virus de Inmunodeficiencia Humana (VIH), la tuberculosis ha tenido un significativo aumento, se ha planteado que esta coinfección es denominada como el "dúo mortal": uno acelera el avance de la otra y viceversa, por lo que cada día su temprano diagnóstico se hace más necesario. El objetivo de nuestro trabajo fue analizar, en el periodo de enero 2000 a diciembre 2006, la positividad en el diagnóstico bacteriológico de Mycobacterium tuberculosis en pacientes sintomáticos, incluyendo los pacientes VIH+/SIDA tratados en nuestra Institución Hospitalaria. Las muestras estudiadas fueron procesadas por las técnicas establecidas para el diagnóstico convencional; examen directo, examen de cultivo, e identificación. Mycobacterium tuberculosis solamente fue aislado de un total de 8151 muestras analizadas, en 205 muestras para un 2.5 por ciento de positividad; conjuntamente a las cepas identificadas se les realizó estudios de resistencia y/o sensibilidad por el método de Canetti, donde no se encontró cepas resistentes a ninguna de las drogas antibacilares empleadas, por lo que afirmamos que estudios como éste son imprescindibles para la vigilancia epidemiológica de esta enfermedad. Los resultados obtenidos muestran que la asociación VIH/SIDA/TB en nuestro país ha evolucionado en forma lenta, el incremento no es comparable con los reportados en la literatura internacional, demostrando la eficiencia de los Programas Nacionales de Control establecidos para estas dos enfermedades.

Consideraciones sobre la implementación de nuevas herramientas diagnósticas en las redes de laboratorios de tuberculosis de Latinoamérica / New diagnosis tools for tuberculosis laboratory network in Latin America

Se analizó la factibilidad de utilizar métodos de diagnósticos rápidos que sean sustentables en Latinoamérica, los cuales brindan resultados oportunos y útiles para orientar el control clínico de pacientes con tuberculosis. La introducción de estos métodos en los laboratorios de los países en vías de desarrollo requiere una política racional que guíe la incorporación y aplicación de esta tecnología. En los últimos años, se han reportado sistemas automatizados para los cultivos y métodos moleculares para el diagnóstico de tuberculosis que han aportado precisión y rapidez. Sin embargo, su implementación está limitada porque dependen de costosos recursos, equipos e infraestructura de laboratorio. Recién se han desarrollado diferentes técnicas que han demostrado ser económicamente factibles de aplicar en laboratorios de escasos recursos. La detección de la enzima adenosina-desaminasa (ADA) en líquido pleural tiene un bajo costo y permite realizar el diagnóstico de tuberculosis. Por su parte, la detección microscópica de Mycobacterium tuberculosis mediante el método de agar en placa delgada tiene un costo moderado y constituye un método alternativo. El método de nitrato reductasa para la detección de resistencia a las drogas antituberculosas, acelera la obtención de resultados en los laboratorios que utilizan técnicas convencionales para el diagnóstico de tuberculosis(AU)

Feasibility of rapid and sustainable diagnostic methods that provide useful and timely results to guide the clinical control of tuberculosis patients was analyzed. However, policies guiding the insertion of new diagnostics in the laboratory services that support the tuberculosis control are lacking in developing countries. The introduction of these methods in developing countries laboratories requires rational policies guiding the application of these technologies. In the last few years, some automated systems for culture and molecular testing in laboratory services for tuberculosis diagnosis, which offered accuracy and speed, have been reported. However, their implementation is restricted because of costly resources, logistics and infrastructure. Recently, various economically feasible tests have demonstrated to be applicable in poor-resource labs. The detection of adenosine desaminase (ADA) in pleural fluid is a valuable low-cost approach to the diagnosis of tuberculosis. On the other hand, the microscopic detection of Mycobacterium tuberculosis using thin layer agar is a moderate cost alternative method. Drug susceptibility testing to antituberculous drugs can be expedited by the nitrate reduction assay in tuberculosis laboratories using routine procedures for tuberculosis diagnosis(AU)

[New diagnosis tools for tuberculosis laboratory network in Latin America]. / Consideraciones sobre la implementación de nuevas herramientas diagnósticas en las redes de laboratorios de tuberculosis de Latinoamérica.

Feasibility of rapid and sustainable diagnostic methods that provide useful and timely results to guide the clinical control of tuberculosis patients was analyzed. However, policies guiding the insertion of new diagnostics in the laboratory services that support the tuberculosis control are lacking in developing countries. The introduction of these methods in developing countries laboratories requires rational policies guiding the application of these technologies. In the last few years, some automated systems for culture and molecular testing in laboratory services for tuberculosis diagnosis, which offered accuracy and speed, have been reported. However, their implementation is restricted because of costly resources, logistics and infrastructure. Recently, various economically feasible tests have demonstrated to be applicable in poor-resource labs. The detection of adenosine desaminase (ADA) in pleural fluid is a valuable low-cost approach to the diagnosis of tuberculosis. On the other hand, the microscopic detection of Mycobacterium tuberculosis using thin layer agar is a moderate cost alternative method. Drug susceptibility testing to antituberculous drugs can be expedited by the nitrate reduction assay in tuberculosis laboratories using routine procedures for tuberculosis diagnosis.