Resistencia a fármacos antituberculosos en Cuba, 2015-2017 / Resistance to tuberculosis drugs in Cuba, 2015-2017

Introducción: La tuberculosis persiste como un importante problema de salud mundial. En el 2016 se estimaron 600 000 casos de resistente a rifampicina, y entre estos 490 000 casos multidrogorresistentes. Objetivo: Describir el comportamiento de la resistencia de los aislados de M. tuberculosis de pacientes con tuberculosis pulmonar notificados en Cuba entre los años 2015-2017. Métodos: Se determinó la susceptibilidad a isoniacida y rifampicina mediante el método de la nitratasa. A los aislados resistentes a rifampicina/multidrogorresistentes se les determinó mediante el método proporcional la susceptibilidad a ofloxacina, kanamicina, amikacina y capreomicina. Resultados: El 93,2 por ciento de los aislados fueron sensibles a isoniacida y rifampicina. En 39 se identificó resistencia a isoniacida y 23 fueron resistente a rifampicina. Se identificaron 10 multidrogorresistentes. No se detectó resistencia a fármacos de segunda línea. Conclusiones: Los resultados alertan sobre la necesidad de investigar las causas que han conllevado al incremento de la tuberculosis resistente en Cuba(AU)

Introduction: Tuberculosis continues to be an important health problem worldwide. In the year 2016, as many as 600 000 cases of rifampicin resistance were estimated, among which 490 000 were multi-drug resistant. Objective: Describe the behavior of resistance to M. tuberculosis isolates in patients with pulmonary tuberculosis reported in Cuba in the period 2015-2017. Methods: Susceptibility to isoniazid and rifampicin was determined by the nitratase method. Susceptibility of rifampicin resistant / multi-drug resistant isolates to ofloxacin, kanamycin, amikacin and capreomycin was determined by the proportional method. Results: Of the isolates analyzed, 93.2 percent were sensitive to isoniazid and rifampicin. Isoniazid resistance was identified in 39 and 23 were rifampicin resistant. Ten multi-drug resistant isolates were identified. Resistance to second line drugs was not detected. Conclusions: Results warn about the need to study the factors leading to the increase in resistant tuberculosis in Cuba(AU)

Perfil de resistencia del Mycobacterium tuberculosis a fármacos antituberculosos de primera línea y sus combinaciones / Resistance profile of Mycobacterium tuberculosis to first-line antituberculosis drugs and their combinations

Introducción: En Colombia el control de la tuberculosis se ha visto amenazado por la resistencia a los fármacos antituberculosos y especialmente la tuberculosis multidrogorresistente. Objetivo: Determinar la resistencia global y perfiles de resistencia del Mycobacterium tuberculosis a fármacos antituberculosos de primera línea y combinaciones. Métodos: Estudio descriptivo, transversal, en el que se evaluaron 2 701 pacientes con tuberculosis en el Departamento del Atlántico (Colombia), durante los años 2011 a 2016. Se valoraron aspectos sociodemográficos, clínicos y condiciones de riesgo. Se realizó análisis de frecuencias relativas y absolutas, diferencia de proporciones ((2) y razón de prevalencias. Resultados: El 66,5 por ciento de los pacientes eran hombres, el 53 por ciento tenían entre 15 y 44 años de edad. El 47,34 por ciento con pérdida en el seguimiento y el 11,62 por ciento monorresistentes a isoniacida. La resistencia en casos nuevos fue 7,30 por ciento (IC95 por ciento: 6,3-8,5), para este grupo la multidrogorresistencia fue de 1,1 por ciento; mientras que en los previamente tratados la resistencia fue de 18,27 por ciento (IC95 por ciento: 15,6- 22,4) y la multidrogorresistencia de 5,7 por ciento. Los factores asociados a resistencia fueron presencia de VIH/TB (RP= 2,6; p= 0,000), otros factores inmunosupresores (RP= 3,5; p= 0,009), contacto de paciente con tuberculosis multidrogorresistente (RP= 16; p= 0,000) y caso previamente tratado (RP= 2,24; p= 0,00). Conclusiones: Se evidencia un descenso en la resistencia global a rifampicina e isoniacida, así como en la prevalencia multidrogorresistente tanto en casos nuevos como en previamente tratados en la población estudiada; lo que genera una línea base para la toma de decisiones que permita continuar mejorando la vigilancia y control de la resistencia del M. tuberculosis a fármacos de primera línea, debido a los nuevos retos que este microorganismo representa para la salud pública(AU)

Introduction: Tuberculosis control in Colombia has been hampered by resistance to antituberculosis drugs and particularly by multi-drug resistant tuberculosis. Objective: Determine the overall resistance and resistance profiles of Mycobacterium tuberculosis to first-line antituberculosis drugs and their combinations. Methods: A descriptive cross-sectional study was conducted of 2 701 tuberculosis patients from Atlántico Department in Colombia in the period 2011-2016. The evaluation included sociodemographic aspects, clinical characteristics and risk conditions. Data analysis was based on relative and absolute frequencies, proportion difference (x2) and prevalence ratio. Results: Of the total sample, 66.5 percent were men and 53 percent were aged 15-44 years. 47.34 percent were lost to follow-up and 11.62 percent were monoresistant to isoniazid. In new cases resistance was 7.30 percent (CI 95 percent: 6.3-8.5) and multi-drug resistance was 1.1 percent, whereas in previously treated cases resistance was 18.27 percent (CI 95 percent: 15.6-22.4) and multi-drug resistance was 5.7 percent. The factors associated to resistance were the presence of HIV/TB (AR= 2.6; p= 0.000), other immunosuppressive factors (AR= 3.5; p= 0.009), contact with multi-drug resistant tuberculosis patient (AR= 16; p= 0.000) and previously treated case (AR= 2.24; p= 0.00). Conclusions: A reduction is observed in overall resistance to rifampicin and isoniazid, as well as in the prevalence of multi-drug resistance, both in new cases and in previously treated cases, which creates a baseline for the taking of decisions aimed at the continuing improvement of the surveillance and control of M. tuberculosis resistance to first-line drugs, due to the new challenges posed by this microorganism to public health(AU)

La tuberculosis drogorresistente en Cuba: ¿qué estamos haciendo? / Drug-resistant tuberculosis in Cuba: what are we doing?

La tuberculosis drogorresistente (TBDR) es un problema emergente en la lucha contra la tuberculosis en todo el mundo y Cuba no está exenta de este. Es un fenómeno causado por el hombre, por el uso indiscriminado de antibióticos sin la adecuada supervisión microbiológica de las cepas de micobacterium tuberculosis durante el tratamiento con drogas específicas.1,2 Probablemente el mayor problema al que nos enfrentamos con la TBDR es que, a nivel mundial, incluso aplicando los métodos diagnósticos y terapéuticos más sofisticados, no se logran tasas de curación general mayores al 70 por ciento, salvo algunos estudios puntuales que logran tasas superiores al 80 por ciento, con costosas terapias.3 El Reporte Global de Tuberculosis de la Organización Mundial de la Salud (OMS) de 2018 reportó para el 2017: 558 000 casos de TBDR en el mundo y de ellos, solo 25 por ciento fueron notificados. Las regiones de mayor incidencia de TB drogorresistente (DR) en el mundo fueron: Sudeste asiático...(AU)

Directrices unificadas de la OMS sobre el tratamiento de la tuberculosis farmacorresistente / WHO consolidated guidelines on drug-resistant tuberculosis treatment

Las cepas del bacilo tuberculoso con farmacorresistencia (TB-DR) son más difíciles de tratar que las farmacosensibles y amenazan el progreso mundial hacia los objetivos establecidos por la Estrategia Fin de la TB, de la Organización Mundial de la Salud (OMS). Por lo tanto, existe una necesidad imperiosa de contar con recomendaciones de política basadas en la evidencia sobre el tratamiento y la atención a los pacientes con TB-DR, de acuerdo con la evidencia más reciente y completa disponible. A este respecto, las Directrices unificadas de la OMS sobre el tratamiento de la tuberculosis farmacorresistente cumplen el mandato de la OMS de informar a los profesionales de la salud de los Estados Miembros sobre cómo mejorar el tratamiento y la atención de los pacientes con TB-DR.

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.

Evaluation of the impact that the changes in tuberculosis treatment implemented in Brazil in 2009 have had on disease control in the country.

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 (ß = 2.17; 95% CI: -3.80 to 8.14; p = 0.47) and in the number of new cases (ß = -0.97; 95% CI: -5.89 to 3.94; p = 0.70), as well as having no association with treatment abandonment rates (ß = 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 (ß = -4.14; 95% CI: -8.63 to 0.34; p = 0.07), as well as an association with increased mortality from pulmonary tuberculosis (ß = 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.

Clinical challenges in the era of multiple and extensively drug-resistant tuberculosis / Retos clínicos en la era de la tuberculosis multirresistente y extensamente resistente / Desafios clínicos na era da tuberculose com resistência ampla a múltiplos medicamentos

ABSTRACT In 2014, there were 480 000 new cases of multidrug-resistant tuberculosis (MDR-TB) around the world, but only 25% of them were diagnosed and reported. Drug resistance in TB is necessarily a laboratory diagnosis. An urgent priority in everyday practice is to diagnose tuberculosis and rule out drug resistance as quickly and as accurately as possible. However, worldwide, only 12% of new bacteriologically confirmed TB cases and 58% of previously treated TB cases were tested for drug resistance in 2014. New tools for diagnosis of TB and drug-resistant TB have been introduced for clinical practice during the past decade. Those new tools can detect and identify drug resistance to antituberculosis drugs in less than 24 hours, and they should be urgently integrated into clinical practice, especially in high-burden regions. Ongoing transmission of TB generates new infections, and this infected population is the inexhaustible source of new TB cases. If we are really determined to stop the global TB epidemic, we need to treat active cases and also halt the transmission of the infection. The only strategy for preventing the development of active disease in individuals with subclinical infection is to give treatment for this latent infection. Global control of TB requires a huge investment of funds to address current detection and treatment gaps. We must reconsider our current strategy and combine social components with biomedical interventions. This will require the development of alliances between government and civil society, as well as leadership and true political commitment at the highest level of government.

RESUMEN En el 2014 se presentaron 480 000 nuevos casos de tuberculosis multirresistente, pero solo se diagnosticó y notificó 25% de ellos. La farmacorresistencia en la tuberculosis se diagnostica necesariamente por medio de pruebas de laboratorio. En la práctica clínica diaria resulta urgente y prioritario poder diagnosticar la tuberculosis y descartar la farmacorresistencia con la mayor rapidez y exactitud posibles. Sin embargo, en todo el mundo, apenas 12% de los nuevos casos de tuberculosis bacteriológicamente confirmados y 58% de los casos ya tratados se sometieron a prueba de farmacorresistencia en el 2014. En los diez últimos años se han dado a conocer nuevas herramientas para el diagnóstico de la tuberculosis y la tuberculosis farmacorresistente en la práctica clínica. Esas herramientas nuevas permiten detectar e identificar la resistencia a medicamentos antituberculosos en menos de 24 horas, por lo que deberían integrarse urgentemente a la práctica clínica, especialmente en las regiones con una carga de enfermedad alta. La persistencia de la transmisión de la tuberculosis genera nuevas infecciones, y la población infectada es una fuente inagotable de nuevos casos de esta enfermedad. Si estamos realmente decididos a poner fin a la epidemia mundial de la tuberculosis, tenemos que tratar los casos activos y también detener la transmisión de la infección. La única estrategia para prevenir la aparición de la enfermedad activa en personas con infección subclínica es administrar tratamiento contra esta infección latente. El control mundial de la tuberculosis requiere una enorme inversión de fondos para cerrar las brechas existentes en la detección y el tratamiento. Debemos reconsiderar nuestra estrategia actual y combinar los componentes sociales con las intervenciones biomédicas. Esto obliga a conformar alianzas entre el gobierno y la sociedad civil, y requiere del liderazgo y de un verdadero compromiso político de las más altas instancias gubernamentales.

RESUMO Em 2014, houve 480 mil novos casos de tuberculose (TB) resistente a múltiplos medicamentos, porém apenas 25% foram diagnosticados e notificados. A resistência aos medicamentos na TB requer necessariamente que seja feito um diagnóstico laboratorial. É prioridade na prática clínica diária diagnosticar a TB e descartar a resistência aos medicamentos o mais rápido e com maior precisão possível. Porém, em 2014, o teste da resistência aos medicamentos foi realizado mundialmente em apenas 12% dos novos casos de TB com confirmação bacteriológica e em 58% dos casos de TB com tratamento anterior. Novas ferramentas para o diagnóstico de TB e TB resistente a múltiplos a medicamentos foram introduzidas na prática clínica na última década. São ferramentas com capacidade de detectar e identificar a resistência aos medicamentos antituberculose em menos de 24 horas e, portanto, é imprescindível que sejam integradas à prática clínica, sobretudo em regiões de elevada carga da doença. A transmissão contínua da TB causa novas infecções, sendo a população infectada uma fonte inesgotável de novos casos da doença. Se estivermos realmente determinados a conter a epidemia global de TB, é preciso tratar os casos ativos e interromper a transmissão da infecção. A única estratégia para prevenir o surgimento de doença ativa em indivíduos com infecção subclínica é o tratamento da infecção latente. O controle global da TB requer um enorme investimento financeiro para sanar as falhas atuais de detecção e tratamento da doença. A estratégia atual deve ser reexaminada e combinar componentes sociais e intervenções biomédicas. Faz-se necessário forjar alianças entre o governo e a sociedade civil bem como assumir a liderança e o firme compromisso no mais alto nível político.

Resistência às drogas antituberculose na fronteira do Brasil com Paraguai e Bolívia / Antituberculosis-drug resistance in the border of Brazil with Paraguay and Bolivia

RESUMO Objetivo Estimar as taxas de resistência às drogas entre casos de tuberculose pulmonar (TBP) para o estado de Mato Grosso do Sul, Brasil, e especificamente para a região da fronteira com Paraguai e Bolívia, além de identificar fatores de risco associados. Métodos O presente estudo epidemiológico, transversal, enfocou os casos de TBP registrados de janeiro de 2007 a dezembro de 2010 no Sistema de Informação de Agravos de Notificação da Secretaria de Estado de Saúde com resultados do teste de suscetibilidade a rifampicina, isoniazida, etambutol e estreptomicina. Definiram-se como variáveis dependentes o desenvolvimento de resistência a uma única droga e a qualquer combinação de drogas. As variáveis independentes foram ser caso novo ou tratado, residência em região de fronteira ou outra região, presença ou ausência de diabetes e história de alcoolismo. Resultados Foram identificados 789 casos de TBP com teste de suscetibilidade. As características associadas à resistência foram: caso tratado (P=0,0001), região de fronteira (P=0,0142), alcoolismo (P=0,0451) e diabetes (P=0,0708). As taxas de resistência combinada, primária e adquirida no estado foram de 16,3%, 10,6% e 39,0%, e na fronteira, de 22,3%, 19,2% e 37,5%. As taxas de resistência a múltiplas drogas combinada, primária e adquirida no estado foram de 1,8%, 0,6% e 6,3%, e na fronteira, de 3,1%, 1,2% e 12,5%. Conclusões O estado deve, na região de fronteira, realizar cultura em todos os sintomáticos respiratórios, investigar o padrão de resistência nos casos confirmados, adotar o tratamento diretamente observado nos casos de TBP e desencadear ações de saúde conjuntas com os países fronteiriços. Em todo o estado, é necessário monitorar os níveis de resistência adquirida, ampliar a investigação de resistência para todos os casos tratados e adotar o tratamento diretamente observado prioritariamente entre pacientes com alcoolismo e diabetes.

ABSTRACT Objective To estimate the rate of drug resistance among pulmonary tuberculosis (PTB) cases in the state of Mato Grosso do Sul, Brazil, and specifically in the border areas with Paraguay and Bolivia, as well as to identify associated risk factors. Method The present cross-sectional, epidemiological study focused on PTB cases recorded between January 2007 and December 2010 in the State Reportable Disease Information System with results of susceptibility tests to rifampicin, isoniazid, ethambutol, and streptomycin. Dependent variables were development of resistance to a single drug or any combination of drugs. Independent variables were being a new or treated case, living in border areas, presence/absence of diabetes, and history of alcoholism. Results There were 789 TBP cases with susceptibility testing. The following characteristics were associated with resistance: treated case (P = 0.0001), border region (P = 0.0142), alcoholism (P = 0.0451), and diabetes (P = 0.0708). The rates of combined, primary, and acquired resistance for the state were 16.3%, 10.6%, and 39.0%, vs. 22.3%, 19.2%, and 37.5% for the border region. The rates of combined, primary, and acquired multidrug resistance for the state were 1.8%, 0.6%, and 6.3%, vs. 3.1%, 1.2%, and 12.5% for the border region. Conclusions In the border region, the state should investigate drug resistance in all patients with respiratory symptoms, determine the pattern of resistance in confirmed cases, adopt directly observed treatment for cases of PTB, and develop health actions together with neighboring countries. Across the state, the levels of acquired resistance should be monitored, with investigation of resistance in all treated cases and implementation of directly observed treatment especially among patients with diabetes or alcoholism.

Impact of Infection Control Measures to Control an Outbreak of Multidrug-Resistant Tuberculosis in a Human Immunodeficiency Virus Ward, Peru.

Multidrug-resistant tuberculosis (MDRTB) rates in a human immunodeficiency virus (HIV) care facility increased by the year 2000-56% of TB cases, eight times the national MDRTB rate. We reported the effect of tuberculosis infection control measures that were introduced in 2001 and that consisted of 1) building a respiratory isolation ward with mechanical ventilation, 2) triage segregation of patients, 3) relocation of waiting room to outdoors, 4) rapid sputum smear microscopy, and 5) culture/drug-susceptibility testing with the microscopic-observation drug-susceptibility assay. Records pertaining to patients attending the study site between 1997 and 2004 were reviewed. Six hundred and fifty five HIV/TB-coinfected patients (mean age 33 years, 79% male) who attended the service during the study period were included. After the intervention, MDRTB rates declined to 20% of TB cases by the year 2004 (P = 0.01). Extremely limited access to antiretroviral therapy and specific MDRTB therapy did not change during this period, and concurrently, national MDRTB prevalence increased, implying that the infection control measures caused the fall in MDRTB rates. The infection control measures were estimated to have cost US$91,031 while preventing 97 MDRTB cases, potentially saving US$1,430,026. Thus, this intervention significantly reduced MDRTB within an HIV care facility in this resource-constrained setting and should be cost-effective.

Border Lookout: Enhancing Tuberculosis Control on the United States-Mexico Border.

We evaluated the use of federal public health intervention tools known as the Do Not Board and Border Lookout (BL) for detecting and referring infectious or potentially infectious land border travelers with tuberculosis (TB) back to treatment. We used data about the issuance of BL from April 2007 to September 2013 to examine demographics and TB laboratory results for persons on the list (N = 66) and time on the list before being located and achieving noninfectious status. The majority of case-patients were Hispanic and male, with a median age of 39 years. Most were citizens of the United States or Mexico, and 30.3% were undocumented migrants. One-fifth had multidrug-resistant TB. Nearly two-thirds of case-patients were located and treated as a result of being placed on the list. However, 25.8% of case-patients, primarily undocumented migrants, remain lost to follow-up and remain on the list. For this highly mobile patient population, the use of this novel federal travel intervention tool facilitated the detection and treatment of infectious TB cases that were lost to follow-up.

Identification of Novel Potential Vaccine Candidates against Tuberculosis Based on Reverse Vaccinology.

Tuberculosis (TB) is a chronic infectious disease, considered as the second leading cause of death worldwide, caused by Mycobacterium tuberculosis. The limited efficacy of the bacillus Calmette-Guérin (BCG) vaccine against pulmonary TB and the emergence of multidrug-resistant TB warrants the need for more efficacious vaccines. Reverse vaccinology uses the entire proteome of a pathogen to select the best vaccine antigens by in silico approaches. M. tuberculosis H37Rv proteome was analyzed with NERVE (New Enhanced Reverse Vaccinology Environment) prediction software to identify potential vaccine targets; these 331 proteins were further analyzed with VaxiJen for the determination of their antigenicity value. Only candidates with values ≥0.5 of antigenicity and 50% of adhesin probability and without homology with human proteins or transmembrane regions were selected, resulting in 73 antigens. These proteins were grouped by families in seven groups and analyzed by amino acid sequence alignments, selecting 16 representative proteins. For each candidate, a search of the literature and protein analysis with different bioinformatics tools, as well as a simulation of the immune response, was conducted. Finally, we selected six novel vaccine candidates, EsxL, PE26, PPE65, PE_PGRS49, PBP1, and Erp, from M. tuberculosis that can be used to improve or design new TB vaccines.

Tuberculose multirresistente: integralidade da atenção à saúde na perspectiva discursiva / Multidrug-resistant tuberculosis: integral healthcare from the discourse analysis perspective

Objetivo: Analisar as vivências dos doentes de tuberculose multirresistente sob a perspectiva da integralidade. Métodos: Estudo analítico, qualitativo, realizado com doentes em tratamento. Foram realizadas entrevistas semiestruturadas, transcritas na íntegra, interpretadas sob o referencial da Análise do Discurso de matriz francesa. Resultados: Notaram-se movimentos de sensibilização dos profissionais na busca da integralidade, atendendo às necessidades emocionais dos doentes, porém distanciavam-se desta em outros momentos. Quanto à organização da rede de atenção, perceberam-se fragilidades: falta de vinculação e acolhimento do doente nos serviços de saúde; falta de articulação entre os níveis de assistência; responsabilização do doente para com o tratamento e diferentes contextos da organização da Atenção Básica interferindo no acompanhamento do tratamento. Conclusão: Há necessidade de repensar a assistência ao doente de tuberculose multirresistente, de modo a assisti-lo de maneira integral, tanto em suas peculiaridades individuais relacionadas ao seu contexto de vida e processo de adoecimento, quanto ao que tange à organização e coordenação da atenção. .

Nivel de conocimientos sobre la tuberculosis multidrogoresistente en población general del Centro de Salud Mirones Bajo / Level of knowledge about multidrug-resistant tuberculosis in the general population of the Health Center Mirones Bajo

Introducción: La Tuberculosis, según la OMS, es la segunda causa de muerte en el mundo causada por un agente infeccioso, después del SIDA, más del 95 por ciento de estas muertes ocurren en países con ingresos bajos. En el Perú según la OMS y el MINSA, cada año se diagnostican 35,000 casos de Tuberculosis, una de las cifras más elevadas, de todos ellos el 10 por ciento contrae la tuberculosis multidrogo-resistente (TB MDR), producidas por las cepas resistentes a las drogas más efectivas para curar la TB como son la isoniacida y la rifampicina. Esta situación se considera a nivel mundial sólo el comienzo de un problema de consecuencias imprevisibles, ya que la población portadora de esta infección puede ser la fuente de una epidemia de TB incurable en el planeta. Objetivo: El presente trabajo tiene como objetivo evaluar el nivel de conocimientos sobre la Tuberculosis multidrogo-resistente en la población usuaria del Centro de Salud Mirones Bajo del Cercado de Lima, para lo cual toma en cuenta su edad, sexo, grado de instrucción, entre otros. Metodología: Este estudio se basa en una encuesta, que se aplicó del 1 de marzo al 1 de abril del 2014. El tipo de diseño es no experimental, descriptivo de corte transversal. Se obtuvo una muestra de 112 pobladores usuarios del Centro de Salud y durante la aplicación del instrumento se usó el criterio por conveniencia. Resultados y Conclusiones: Finalmente una de las conclusiones a la que se llega, es que la población joven, la que según diversos estudios es la más afectada por esta enfermedad, tiene un nivel de conocimientos entre medio y bajo en todas las áreas evaluadas, como signos y síntomas, factores de riesgo, prevención y tratamiento. Recomendaciones: Por ello las recomendaciones van dirigidas a proveer de conocimientos documentados, a la luz de lo que hoy se sabe de la enfermedad, tal como consta en las Normas Técnicas que rigen el trabajo de las instituciones del estado, lo que permitirá afrontar este problema...

Introduction: Tuberculosis, according to the who, is the second leading cause of death in the world, caused by an infectious agent, after AIDS, over 95 per cent of these deaths occur in low-income countries. In the Peru as MINSA, and who each year are diagnosed 35.000 cases of Tuberculosis, one of the highest figures, all of them 10 per cent contract multidrug-resistant tuberculosis (MDR TB), caused by strains resistant to the most effective drugs to cure TB such as isoniazid and rifampicin. This situation is considered globally only the beginning of a problem of unforeseeable consequences, since the population carrier of this infection can be the source of an epidemic of incurable TB on the planet. Objective: This study aims to assess the level of knowledge about multidrug-resistant Tuberculosis in the user population of low onlookers health of the Cercado of Lima Center, which takes into account your age, sex, degree of instruction, among others. Methodology: This study is based on a survey, which applied from March 1 to April 1, 2014. The type of design is not experimental, descriptive cross-sectional. A sample of 112 residents health center users was obtained and during the implementation of the instrument the criterion was used for convenience. Results and conclusions: finally one of the conclusions that can be reached, is that the young population, which, according to various studies, is the most affected by this disease, has a level of knowledge between medium and low in all areas evaluated, signs and symptoms, risk factors, prevention and treatment. Recommendations: Why recommendations are aimed at providing documented knowledge, in the light of what today is known about disease, as described in the technical standards governing the work of the institutions of the State, which will allow to face this health problem better.

Recursos humanos en salud para el control de la Tuberculosis multidrogoresistente en el primer nivel de atención de salud de Lima / Health manpower to control TB multidrug in the first level of health care Lima

Caracterizar la capacidad instalada de los recursos humanos en salud(RHUS) involucrados en acciones de control de Tuberculosis Multidrogoresistente (TBMDR) en servicios de salud del primer nivel de atención de Lima Metropolitana. Métodos: estudio descriptivo transversal exploratorio realizado en el 2013. En 18 establecimientos de salud (EESS) con diferentes capacidades resolutivas (categoría) y carga de TBMDR, se identificó los RHUS que participan en acciones de control deTBMDR. Un cuestionario auto administrado respecto a las características demográficas, laborales, de formación y capacitación, condiciones de trabajo, motivación y riesgos fueutilizado para recolectar datos en 102 profesionales (90.3 por cento del total de profesionales identificados). Los datos fueron analizados por análisis descriptivos. La aprobaciónética se obtuvo del Instituto Nacional de Salud (Instituto Nacional de Salud de Perú) en Lima Perú. (...). Estos resultados varían según categoría del EESS, carga de TBMDR y grupo profesional. Conclusiones: Inequidad e incongruencias en asignación y distribución de RHUS, con una débil fuerza laboral, con es casos RHUS capacitados para control de la TBMDR en el contexto de atención primaria de salud; laboran en condiciones limitadasy expuestos a riesgos laborales, que tendrán un importante impacto en el proceso saludtrabajo-enfermedad de los RHUS, la satisfacción laboral y en los resultados en elcontrol de la TBMDR...

To characterize the installed capacity of human resources for health (HRH)are involved in control actions of Multidrug Resistant Tuberculosis (MDRTB) atservices of primary health care in Metropolitan Lima, Peru. Methods: An descriptivetransversal exploratory study was conducted in 2013. HRH involved in control actionsof Multidrug Resistant Tuberculosis (MDRTB) were identified in 18 health carefacilities (HCF) with different resolution capabilities (category) and MDRTB burden. Aself-administered questionnaire regarding demographic characteristics, employmentcondition, educational and training situation, working conditions, job motivation andrisks was utilized for collecting data of 102 health care professionals (90.3 percent ofprofessionals identified). Data were analyzed by descriptive analyzes. Ethical approvalwas obtained from the Instituto Nacional de Salud (Peruvian National Institute ofHealth) in Lima Peru. (...) These results vary by HCF category, burdenMDRTB and professional group. Conclusions: There are inequality and inconsistenciesin allocation and distribution of HRH, weak workforce and a few trained RHR for theMDR-TB control in the context of primary health care. Those health care professionalsare working in adverse conditions and are exposed to occupational risks which in turnmay lead to important repercussions on health - work- disease process of HRH, theirjob satisfaction and results in the control of MDR-TB...

Universal access to care for multidrug-resistant tuberculosis: an analysis of surveillance data.

BACKGROUND: The prospects for global tuberculosis control in the near future will be determined by the effectiveness of the response of countries to their burden of multidrug-resistant (MDR; resistance to, at least, isoniazid and rifampicin) tuberculosis. During the 2009 World Health Assembly, countries committed to achieve universal access to MDR-tuberculosis care by 2015. We assessed the progress towards the 2015 targets achieved by countries accounting for 90% of the estimated MDR-tuberculosis cases in the world in 2011. METHODS: We analysed data reported to WHO by 30 countries expected to have more than 1000 MDR-tuberculosis cases among notified patients with pulmonary tuberculosis in 2011. FINDINGS: In the 30 countries, 18% of the estimated MDR-tuberculosis cases were enrolled on treatment in 2011. Belarus, Brazil, Kazakhstan, Peru, South Africa, and Ukraine each detected and enrolled on treatment more than 50% of their estimated cases of MDR-tuberculosis. In Ethiopia, India, Indonesia, the Philippines, and Russia, enrolments increased steadily between 2009 and 2011 with a mean yearly change greater than 50%: however, in these countries enrolment in 2011 was low, ranging from 4% to 43% of the estimated cases. In the remaining countries (Afghanistan, Angola, Azerbaijan, Bangladesh, China, Democratic Republic of the Congo, Kenya, Kyrgyzstan, Moldova, Mozambique, Burma, Nepal, Nigeria, North Korea, Pakistan, South Korea, Thailand, Uzbekistan, and Vietnam) progress in detection and enrolment was slower. In 23 countries, a median of 53% (IQR 41-71) patients with MDR-tuberculosis successfully completed their treatment after starting it in 2008-09. INTERPRETATION: Six countries (Belarus, Brazil, Kazakhstan, Peru, South Africa, and Ukraine) can achieve universal access to MDR-tuberculosis care by 2015 should they sustain their current pace of progress. In other countries a radical scale-up will be needed for them to have an effect on their MDR-tuberculosis burden. Unless barriers to diagnosis and successful treatment are urgently overcome, and new technologies in diagnostics and treatment effectively implemented, the global targets for 2015 are unlikely be achieved. FUNDING: WHO.

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.