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.

Drug-resistant tuberculosis in Colombia, 2013-2018: Case-control study

Abtract Introduction. Multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) is difficult to control, has high morbidity and mortality, and demands priority public health intervention. In Colombia, MDR/RR-TB has been becoming more widespread annually. Before the COVID-19 pandemic, over an 8-year period, the number of cases of multidrug-resistant tuberculosis in Colombia was close to a thousand cases. Timely identification of the different risk factors for MDR/RR-TB will contribute fundamentally to the systematic management. Objective. To determine which risk factors were associated with the presentation of MDR in Colombia between 2013 and 2018. Materials and methods. A retrospective case-control study was carried out, for which the data from the routine surveillance of MDR/events in the country were used. Results. The cases of multidrug-resistant tuberculosis were mainly in young people, Afrodescendants, and males. Of the clinical conditions, comorbidities such as malnutrition, diabetes, and HIV, presence of at least one factor, such as drug dependence, taking immunosuppressive medications, belonging to the black race, afro, and living in an area of high disease burden were risk factors. Conclusion. In addition to the diagnosis and timely provision of MDR-TB treatment, it is necessary that public health programs at the local level pay special attention to patients with the identified risk factors.

Introducción. La tuberculosis multirresistente-resistente a la rifampicina (TB-MDR/RR) es difícil de controlar, tiene una alta morbilidad y mortalidad y exige una intervención prioritaria en salud pública. En Colombia, la TB-MDR/RR se ha ido extendiendo cada año. Antes de la pandemia de COVID-19, en un periodo de 8 años, el número de casos de TB-MDR/RR en Colombia se acercaba a los mil. La identificación oportuna de los diferentes factores de riesgo de TB-MDR/RR contribuirá de manera fundamental al manejo sistemático de la enfermedad. Objetivo. Determinar los factores de riesgo que se asociaron a la presentación de la TB- MDR/RR en Colombia entre 2013 y 2018. Materiales y métodos. Se realizó un estudio retrospectivo de casos y controles, para el cual se utilizaron los datos de la vigilancia rutinaria de eventos de TB MDR/RR en el país. Resultados. Los casos de TB MDR se presentaron principalmente en jóvenes, afrodescendientes y varones. De las condiciones clínicas, fueron factores de riesgo las comorbilidades como la desnutrición, la diabetes y el VIH, y la presencia de, al menos, un factor como la farmacodependencia, el consumo de medicamentos inmunosupresores, el ser de raza negra o afro y el vivir en una zona del país de alta carga de tuberculosis. Conclusiones. Además del diagnóstico y la provisión oportuna del tratamiento de la TB MDR, es necesario que los programas de salud pública a nivel local presten especial atención a los pacientes con los factores de riesgo identificados.

Tuberculosis multirresistente en Colombia, 2013-2018: estudio de casos y controles / Drug-resistant tuberculosis in Colombia, 2013-2018: Case-control study

INTRODUCTION: Multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) is difficult to control, has high morbidity and mortality, and demands priority public health intervention. In Colombia, MDR/RR-TB has been becoming more widespread annually. Before the COVID-19 pandemic, over an 8-year period, the number of cases of multidrug-resistant tuberculosis in Colombia was close to a thousand cases. Timely identification of the different risk factors for MDR/RR-TB will contribute fundamentally to the systematic management. OBJECTIVE: To determine which risk factors were associated with the presentation of MDR in Colombia between 2013 and 2018. MATERIALS AND METHODS: A retrospective case-control study was carried out, for which the data from the routine surveillance of MDR/events in the country were used. RESULTS: The cases of multidrug-resistant tuberculosis were mainly in young people, Afrodescendants, and males. Of the clinical conditions, comorbidities such as malnutrition, diabetes, and HIV, presence of at least one factor, such as drug dependence, taking immunosuppressive medications, belonging to the black race, afro, and living in an area of high disease burden were risk factors. CONCLUSION: In addition to the diagnosis and timely provision of MDR-TB treatment, it is necessary that public health programs at the local level pay special attention to patients with the identified risk factors.

Introducción: La tuberculosis multirresistente-resistente a la rifampicina (TB-MDR/RR) es difícil de controlar, tiene una alta morbilidad y mortalidad y exige una intervención prioritaria en salud pública. En Colombia, la TB-MDR/RR se ha ido extendiendo cada año. Antes de la pandemia de COVID-19, en un periodo de 8 años, el número de casos de TB-MDR/RR en Colombia se acercaba a los mil. La identificación oportuna de los diferentes factores de riesgo de TB-MDR/RR contribuirá de manera fundamental al manejo sistemático de la enfermedad. Objetivo: Determinar los factores de riesgo que se asociaron a la presentación de la TBMDR/RR en Colombia entre 2013 y 2018. Materiales y métodos: Se realizó un estudio retrospectivo de casos y controles, para el cual se utilizaron los datos de la vigilancia rutinaria de eventos de TB MDR/RR en el país. Resultados: Los casos de TB MDR se presentaron principalmente en jóvenes, afrodescendientes y varones. De las condiciones clínicas, fueron factores de riesgo las comorbilidades como la desnutrición, la diabetes y el VIH, y la presencia de, al menos, un factor como la farmacodependencia, el consumo de medicamentos inmunosupresores, el ser de raza negra o afro y el vivir en una zona del país de alta carga de tuberculosis. Conclusiones: Además del diagnóstico y la provisión oportuna del tratamiento de la TB MDR, es necesario que los programas de salud pública a nivel local presten especial atención a los pacientes con los factores de riesgo identificados.

Infections in patients with adverse reactions to the use of unknown modeling substances for soft tissue enhancement in Cali, Colombia.

The infiltration of foreign materials not approved for medical purposes or of modeling substances used in soft tissue to modify the anatomical appearance for aesthetic purposes represents a serious health problem. These procedures lead to the development of delayed complications, including infections. The objective of this study was to characterize infections in patients with adverse reactions to the use of modeling substances in Cali, Colombia. A cross-sectional and descriptive study was used to determine the frequency of bacterial and fungal infections associated with complications from and adverse reactions to the use of modeling substances in 113 patients. We identified microorganisms in 22 patients and a frequency of 68.1% monomicrobial infections and 31.8% polymicrobial infections. The microorganisms identified in our study included Bacillus cereus, Mycobacterium fortuitum, and Pseudomonas stutzeri, among other microorganisms. The presence of adverse effects derived from the use of illegal modeling substances has been demonstrated; among these effects, infections occur with high frequency and place the health of the patient at risk and increase problems in health care.

Synthesis, Anticancer and Antitubercular Properties of New Chalcones and Their Nitrogen-Containing Five-Membered Heterocyclic Hybrids Bearing Sulfonamide Moiety.

A new series of sulfonamides, 8a-b, 10, 12, and 14a-b, were synthesized by N-sulfonation reaction with sulfonyl chlorides 6a-b. Five new series of chalcone-sulfonamide hybrids (16-20)a-f were prepared via Claisen-Schmidt condensation of the newly obtained sulfonamides with aromatic aldehydes 15a-f in basic medium. Chalcones substituted with chlorine at position 4 of each series were used as precursors for the generation of their five-membered heterocyclic pyrazoline (22-23)a-d, (24-25)a-b and carbothioamide 27a-f derivatives. The synthesized compounds were evaluated for their anticancer and antituberculosis activities. To determine their anticancer activity, compounds were screened against sixty human cancer cell lines at a single dose (10 µM). Compounds 17a-c were highly active against LOX IMVI (melanoma), with IC50 values of 0.34, 0.73 and 0.54 µM, respectively. Chalcone 18e showed remarkable results against the entire panel of leukemia cell lines with IC50 values between 0.99-2.52 µM. Moreover, compounds 20e and 20f displayed growth inhibition of Mycobacterium tuberculosis H37Rv at concentrations below 10 µM. Although they showed low selectivity in cytotoxicity tests against the Vero cell line, further optimization could advance the potential biological activity of the selected compounds.

QSAR Studies, Molecular Docking, Molecular Dynamics, Synthesis, and Biological Evaluation of Novel Quinolinone-Based Thiosemicarbazones against Mycobacterium tuberculosis.

In this study, a series of novel quinolinone-based thiosemicarbazones were designed in silico and their activities tested in vitro against Mycobacterium tuberculosis (M. tuberculosis). Quantitative structure-activity relationship (QSAR) studies were performed using quinolinone and thiosemicarbazide as pharmacophoric nuclei; the best model showed statistical parameters of R2 = 0.83; F = 47.96; s = 0.31, and was validated by several different methods. The van der Waals volume, electron density, and electronegativity model results suggested a pivotal role in antituberculosis (anti-TB) activity. Subsequently, from this model a new series of quinolinone-thiosemicarbazone 11a-e was designed and docked against two tuberculosis protein targets: enoyl-acyl carrier protein reductase (InhA) and decaprenylphosphoryl-ß-D-ribose-2'-oxidase (DprE1). Molecular dynamics simulation over 200 ns showed a binding energy of -71.3 to -12.7 Kcal/mol, suggesting likely inhibition. In vitro antimycobacterial activity of quinolinone-thiosemicarbazone for 11a-e was evaluated against M. bovis, M. tuberculosis H37Rv, and six different strains of drug-resistant M. tuberculosis. All compounds exhibited good to excellent activity against all the families of M. tuberculosis. Several of the here synthesized compounds were more effective than the standard drugs (isoniazid, oxafloxacin), 11d and 11e being the most active products. The results suggest that these compounds may contribute as lead compounds in the research of new potential antimycobacterial agents.

[National Network for Knowledge Management, Research, and Innovation in Tuberculosis in ColombiaRede Nacional de Gestão do Conhecimento, Pesquisa e Inovação em tuberculose na Colômbia]. / Red Nacional de Gestión de Conocimiento, Investigación e Innovación en Tuberculosis en Colombia.

In 2018, the Colombian Ministry of Health and Social Protection, in collaboration with the National Health Institute and the Pan American Health Organization, convened all actors associated with the National Tuberculosis Prevention and Control Program (PNPCT) and the National Science, Technology, and Innovation System to form a national network to coordinate operations research on tuberculosis (TB) in the country. Seven workshops were held and a consensus was reached to establish the National Network for Knowledge Management, Research, and Innovation in Tuberculosis in Colombia (TB Colombia Network). With more than 180 participants, a central node, and five regional nodes that bring together the country's 37 territorial entities, the TB Colombia Network conducted four days of training in operations research in 2019, defining 65 priority research topics aligned with the strategic lines in the PNPCT: prevention and comprehensive care, with a focus on people affected by TB (41 topics in three modules); and political commitment, social protection, and support systems (24 topics in four modules). The peer comparison method was used for prioritization. The TB Colombia Network remains active and contributes to knowledge management aimed at eliminating TB in Colombia. It has helped make progress in building plans and implementing local operations research projects that generate scientifically validated results to strengthen the PNPCT and improve the care of TB patients.

O Ministério da Saúde e Previdência Social da Colômbia, em cooperação com o Instituto Nacional de Saúde e a Organização Pan-Americana da Saúde (OPAS), convocou em 2018 todas as partes interessadas vinculadas ao Programa Nacional de Prevenção e Controle da Tuberculose (PNPCT) e ao Sistema Nacional de Ciência, Tecnologia e Inovação para formar uma rede nacional com o objetivo de coordenar a pesquisa operacional em tuberculose no país. Foram promovidos sete seminários e, deste processo, se chegou a um consenso para criar a Rede Nacional de Gestão do Conhecimento, Pesquisa e Inovação em Tuberculose na Colômbia (Rede TB Colômbia). A rede conta com mais de 180 participantes, organizados em um núcleo central e cinco núcleos regionais que congregam 37 entidades territoriais. Em 2019, a Rede TB Colômbia realizou quatro jornadas de capacitação em pesquisa operacional e definiu 65 áreas temáticas prioritárias de pesquisa harmonizadas com as linhas estratégicas estabelecidas pelo PNPCT: prevenção e atenção integral com enfoque nas pessoas com TB (41 áreas temáticas divididas em três módulos) e compromisso político, proteção social e sistemas de apoio (24 áreas temáticas divididas em quatro módulos). A priorização foi definida pelo método de comparação pareada. A Rede TB Colômbia continua ativa contribuindo para a gestão do conhecimento voltado à eliminação da tuberculose no país e possibilitando avançar na formulação de planos e execução de projetos locais de pesquisa operacional com a produção de resultados científicos validados para fortalecer o PNPCT e melhorar a atenção das pessoas com TB.

Red Nacional de Gestión de Conocimiento, Investigación e Innovación en Tuberculosis en Colombia

[RESUMEN]. El Ministerio de Salud y Protección Social de Colombia, en colaboración con el Instituto Nacional de Salud y la Organización Panamericana de la Salud, convocaron en 2018 a todos los actores asociados al Programa Nacional de Prevención y Control de la Tuberculosis (PNPCT) y el Sistema Nacional de Ciencia, Tecnología e Innovación a la conformación de una red nacional que coordinara la investigación operativa (IO) relacionada con la tuberculosis (TB) en el país. Se realizaron siete talleres en los que se llegó al consenso de establecer la Red Nacional de Gestión de Conocimiento, Investigación e Innovación en Tuberculosis en Colombia (Red TB Colombia). Con más de 180 participantes, organizados en un nodo central y cinco nodos regionales que agrupan a las 37 entidades territoriales, en 2019 la Red TB Colombia realizó cuatro jornadas de capacitación en IO y definió 65 temas priorizados de investigación, ajustados a las líneas estratégicas establecidas por el PNPCT: prevención y atención integral, con foco en los afectados por la TB (41 temas en tres módulos) y compromiso político, protección social y sistemas de apoyo (24 temas en cuatro módulos). La priorización se realizó por el método de comparación por pares. La Red TB Colombia sigue activa y contribuye a la gestión del conocimiento dirigido a eliminar la TB en el país y ha permitido avanzar en la construcción de planes y la ejecución de proyectos locales de IO que generan resultados científicamente validados para fortalecer el PNPCT y mejorar la atención de los pacientes con TB.

[ABSTRACT]. In 2018, the Colombian Ministry of Health and Social Protection, in collaboration with the National Health Institute and the Pan American Health Organization, convened all actors associated with the National Tuberculosis Prevention and Control Program (PNPCT) and the National Science, Technology, and Innovation System to form a national network to coordinate operations research on tuberculosis (TB) in the country. Seven workshops were held and a consensus was reached to establish the National Network for Knowledge Management, Research, and Innovation in Tuberculosis in Colombia (TB Colombia Network). With more than 180 participants, a central node, and five regional nodes that bring together the country's 37 territorial entities, the TB Colombia Network conducted four days of training in operations research in 2019, defining 65 priority research topics aligned with the strategic lines in the PNPCT: prevention and comprehensive care, with a focus on people affected by TB (41 topics in three modules); and political commitment, social protection, and support systems (24 topics in four modules). The peer comparison method was used for prioritization. The TB Colombia Network remains active and contributes to knowledge management aimed at eliminating TB in Colombia. It has helped make progress in building plans and implementing local operations research projects that generate scientifically validated results to strengthen the PNPCT and improve the care of TB patients.

[RESUMO]. O Ministério da Saúde e Previdência Social da Colômbia, em cooperação com o Instituto Nacional de Saúde e a Organização Pan-Americana da Saúde (OPAS), convocou em 2018 todas as partes interessadas vinculadas ao Programa Nacional de Prevenção e Controle da Tuberculose (PNPCT) e ao Sistema Nacional de Ciência, Tecnologia e Inovação para formar uma rede nacional com o objetivo de coordenar a pesquisa operacional em tuberculose no país. Foram promovidos sete seminários e, deste processo, se chegou a um consenso para criar a Rede Nacional de Gestão do Conhecimento, Pesquisa e Inovação em Tuberculose na Colômbia (Rede TB Colômbia). A rede conta com mais de 180 participantes, organizados em um núcleo central e cinco núcleos regionais que congregam 37 entidades territoriais. Em 2019, a Rede TB Colômbia realizou quatro jornadas de capacitação em pesquisa operacional e definiu 65 áreas temáticas prioritárias de pesquisa harmonizadas com as linhas estratégicas estabelecidas pelo PNPCT: prevenção e atenção integral com enfoque nas pessoas com TB (41 áreas temáticas divididas em três módulos) e compromisso político, proteção social e sistemas de apoio (24 áreas temáticas divididas em quatro módulos). A priorização foi definida pelo método de comparação pareada. A Rede TB Colômbia continua ativa contribuindo para a gestão do conhecimento voltado à eliminação da tuberculose no país e possibilitando avançar na formulação de planos e execução de projetos locais de pesquisa operacional com a produção de resultados científicos validados para fortalecer o PNPCT e melhorar a atenção das pessoas com TB.

Red Nacional de Gestión de Conocimiento, Investigación e Innovación en Tuberculosis en Colombia / National Network for Knowledge Management, Research, and Innovation in Tuberculosis in Colombia / Rede Nacional de Gestão do Conhecimento, Pesquisa e Inovação em tuberculose na Colômbia

RESUMEN El Ministerio de Salud y Protección Social de Colombia, en colaboración con el Instituto Nacional de Salud y la Organización Panamericana de la Salud, convocaron en 2018 a todos los actores asociados al Programa Nacional de Prevención y Control de la Tuberculosis (PNPCT) y el Sistema Nacional de Ciencia, Tecnología e Innovación a la conformación de una red nacional que coordinara la investigación operativa (IO) relacionada con la tuberculosis (TB) en el país. Se realizaron siete talleres en los que se llegó al consenso de establecer la Red Nacional de Gestión de Conocimiento, Investigación e Innovación en Tuberculosis en Colombia (Red TB Colombia). Con más de 180 participantes, organizados en un nodo central y cinco nodos regionales que agrupan a las 37 entidades territoriales, en 2019 la Red TB Colombia realizó cuatro jornadas de capacitación en IO y definió 65 temas priorizados de investigación, ajustados a las líneas estratégicas establecidas por el PNPCT: prevención y atención integral, con foco en los afectados por la TB (41 temas en tres módulos) y compromiso político, protección social y sistemas de apoyo (24 temas en cuatro módulos). La priorización se realizó por el método de comparación por pares. La Red TB Colombia sigue activa y contribuye a la gestión del conocimiento dirigido a eliminar la TB en el país y ha permitido avanzar en la construcción de planes y la ejecución de proyectos locales de IO que generan resultados científicamente validados para fortalecer el PNPCT y mejorar la atención de los pacientes con TB.

ABSTRACT In 2018, the Colombian Ministry of Health and Social Protection, in collaboration with the National Health Institute and the Pan American Health Organization, convened all actors associated with the National Tuberculosis Prevention and Control Program (PNPCT) and the National Science, Technology, and Innovation System to form a national network to coordinate operations research on tuberculosis (TB) in the country. Seven workshops were held and a consensus was reached to establish the National Network for Knowledge Management, Research, and Innovation in Tuberculosis in Colombia (TB Colombia Network). With more than 180 participants, a central node, and five regional nodes that bring together the country's 37 territorial entities, the TB Colombia Network conducted four days of training in operations research in 2019, defining 65 priority research topics aligned with the strategic lines in the PNPCT: prevention and comprehensive care, with a focus on people affected by TB (41 topics in three modules); and political commitment, social protection, and support systems (24 topics in four modules). The peer comparison method was used for prioritization. The TB Colombia Network remains active and contributes to knowledge management aimed at eliminating TB in Colombia. It has helped make progress in building plans and implementing local operations research projects that generate scientifically validated results to strengthen the PNPCT and improve the care of TB patients.

RESUMO O Ministério da Saúde e Previdência Social da Colômbia, em cooperação com o Instituto Nacional de Saúde e a Organização Pan-Americana da Saúde (OPAS), convocou em 2018 todas as partes interessadas vinculadas ao Programa Nacional de Prevenção e Controle da Tuberculose (PNPCT) e ao Sistema Nacional de Ciência, Tecnologia e Inovação para formar uma rede nacional com o objetivo de coordenar a pesquisa operacional em tuberculose no país. Foram promovidos sete seminários e, deste processo, se chegou a um consenso para criar a Rede Nacional de Gestão do Conhecimento, Pesquisa e Inovação em Tuberculose na Colômbia (Rede TB Colômbia). A rede conta com mais de 180 participantes, organizados em um núcleo central e cinco núcleos regionais que congregam 37 entidades territoriais. Em 2019, a Rede TB Colômbia realizou quatro jornadas de capacitação em pesquisa operacional e definiu 65 áreas temáticas prioritárias de pesquisa harmonizadas com as linhas estratégicas estabelecidas pelo PNPCT: prevenção e atenção integral com enfoque nas pessoas com TB (41 áreas temáticas divididas em três módulos) e compromisso político, proteção social e sistemas de apoio (24 áreas temáticas divididas em quatro módulos). A priorização foi definida pelo método de comparação pareada. A Rede TB Colômbia continua ativa contribuindo para a gestão do conhecimento voltado à eliminação da tuberculose no país e possibilitando avançar na formulação de planos e execução de projetos locais de pesquisa operacional com a produção de resultados científicos validados para fortalecer o PNPCT e melhorar a atenção das pessoas com TB.

Evaluation of nine serological rapid tests for the detection of SARS-CoV-2

[ABSTRACT]. Objective. To evaluate the operative capacity of nine serological rapid tests to detect the IgM/IgG antibodies response in serum from patients with SARS-CoV-2 in different clinical stages. Methods. A cross-sectional study of serological rapid tests was designed to compare the performance of the evaluated immunochromatographic tests for the diagnosis of SARS-CoV-2. A total of 293 samples was used, including negatives, asymptomatic, and symptomatic serum samples. Results. The sensitivity of the evaluated tests was low and moderate in the groups of asymptomatic serum samples and the group of serums coming from patients with less than 11 days since the onset of the symptoms. The specificity for the anti-SARS-CoV-2 antibodies tests ranged between 86.5%-99% for IgM and 86.5%-99.5% for IgG. The sensitivity and the likelihood ratio were different according to the study groups. The usefulness of these tests is restricted to symptomatic patients and their sensitivity is greater than 85% after 11 days from the appearance of symptoms. Conclusions. Serological tests are not an adequate strategy for the identification of asymptomatic and pre-symptomatic patients. Serological rapid tests for the detection of specific anti-SARS-CoV-2 antibodies can be used as a diagnostic aid, but diagnosis must be confirmed by RT-PCR. Rapid tests should be reserved for patients with symptoms lasting more than 11 days.

[RESUMEN]. Objetivo. Evaluar la capacidad operativa de nueve pruebas serológicas rápidas para detectar la respuesta de anticuerpos IgM/IgG en el suero de pacientes con SARS-CoV-2 en diferentes etapas clínicas. Métodos. Se diseñó un estudio transversal de las pruebas serológicas rápidas para comparar su rendimiento respecto del diagnóstico del SARS-CoV-2. Se utilizaron en total 293 muestras, inclusive muestras de suero de pacientes negativos, asintomáticos y sintomáticos. Resultados. La sensibilidad de las pruebas evaluadas fue baja y moderada en las muestras de suero del grupo de pacientes asintomáticos y en el grupo de pacientes con menos de 11 días desde el inicio de los síntomas. La especificidad de las pruebas de anticuerpos anti-SARS-CoV-2 varió entre 86,5%-99% para la IgM y 86,5%-99,5% para la IgG. La sensibilidad y la razón de verosimilitud (likelihood ratio) fueron diferentes según los grupos de estudio. La utilidad de estas pruebas se limita a los pacientes sintomáticos y su sensibilidad es superior al 85% después de 11 días de la aparición de los síntomas. Conclusiones. Las pruebas serológicas no son una estrategia adecuada para la identificación de los pacientes asintomáticos y presintomáticos. Las pruebas serológicas rápidas para la detección de anticuerpos específicos anti-SARS-CoV-2 pueden ser utilizadas como ayuda diagnóstica, pero el diagnóstico debe ser confirmado por RT-PCR. Las pruebas rápidas deben reservarse para los pacientes con síntomas que duren más de 11 días.

Antimicrobial Activity of Quinoline-Based Hydroxyimidazolium Hybrids.

Eight quinoline-based hydroxyimidazolium hybrids 7a-h were prepared and evaluated in vitro against a panel of clinically important fungal and bacterial pathogens, including mycobacteria. Hybrid compounds 7c-d showed remarkable antifungal activity against Cryptococcus neoformans with a minimum inhibitory concentration (MIC) value of 15.6 µg/mL. Against other opportunistic fungi such as Candida spp. and Aspergillus spp., these hybrids showed MIC values of 62.5 µg/mL. Regarding their antibacterial activity, all the synthetic hybrids demonstrated little inhibition of Gram-negative bacteria (MIC ≥50 µg/mL), however, hybrid 7b displayed >50% inhibition against Klebsiella pneumoniae at 20 µg/mL and full inhibition at 50 µg/mL. Moreover, this hybrid was shown to be a potent anti-staphylococcal molecule, with a MIC value of 2 µg/mL (5 µM). In addition, hybrid 7h also demonstrated inhibition of Staphylococcus aureus at 20 µg/mL (47 µM). Hybrids 7a and 7b were the most potent against Mycobacterium tuberculosis H37Rv with MIC values of 20 and 10 µg/mL (46 and 24 µM), respectively. The 7b hybrid demonstrated high selectivity in killing S. aureus and M. tuberculosis H37Rv in comparison with mammalian cells (SI >20), and thus it can be considered a hit molecule for mechanism of action studies and the exploration of related chemical space.

Characterization of clinical isolates of Mycobacterium tuberculosis from indigenous peoples of Colombia / Caracterización de aislamientos clínicos de Mycobacterium tuberculosis de pueblos indígenas de Colombia

INTRODUCTION: Tuberculosis continues to be a public health priority. Indigenous peoples are vulnerable groups with cultural determinants that increase the risk of the disease. OBJECTIVE: To determine molecular epidemiology and phenotypical features and of Mycobacterium tuberculosis isolates from indigenous people in Colombia during the period from 2009 to 2014. MATERIALS AND METHODS: We conducted an analytical observational study; we analyzed 234 isolates to determine their patterns of sensitivity to antituberculosis drugs and their molecular structures by spoligotyping. RESULTS: The isolates came from 41 indigenous groups, predominantly the Wayúu (13.10%) and Emberá Chamí (11.35%). We found 102 spoligotypes distributed among seven genetic families (37.2% LAM, 15.8% Haarlem, 8.1% T, 3.4% U, 2.6% S, 2.1% X, and 0.9%, Beijing). The association analysis showed that the non-clustered isolates were related to prior treatment, relapse, orphan spoligotypes, and the Beijing family. The H family presented an association with the Arhuaco and Camëntsá indigenous groups, the U family was associated with the Wounaan group, and the T family was associated with the Motilón Barí group. CONCLUSIONS: This is the first national study on M. tuberculosis characterization in indigenous groups. The study evidenced that diagnosis in indigenous people is late. We described 53% of orphan patterns that could be typical of the Colombian indigenous population. The high percentage of grouping by spoligotyping (62%) could indicate cases of active transmission, a situation that should be corroborated using a second genotyping marker. A new Beijing spoligotype (Beijing-like SIT 406) was identified in Colombia.

Introducción. La tuberculosis es prioridad de salud pública. Los pueblos indígenas son vulnerables debido a los factores culturales determinantes que aumentan el riesgo de tuberculosis. Objetivo. Determinar la epidemiologia molecular y las características fenotípicas de los aislamientos de Mycobacterium tuberculosis de pueblos indígenas de Colombia entre 2009 y 2014. Materiales y métodos. Se hizo un estudio observacional analítico; se analizaron 234 aislamientos para determinar la sensibilidad a los fármacos antituberculosos y la estructura molecular usando spoligotyping. La información epidemiológica se recolectó utilizando el formato único de vigilancia de micobacterias. Resultados. Los aislamientos provenían de 41 grupos indígenas, principalmente los wayúu (13,10 %) y emberá chamí (11,35 %). Se encontraron 102 genotipos distribuidos en siete familias genéticas (37,2 %, LAM; 15,8 %, Haarlem; 8,1 %, T; 3,4 %, U; 2,6 %, S; 2,1 %, X, y 0,9%, Beijing). El análisis de asociación mostró que los aislamientos no agrupados se asociaron con el tratamiento previo, las recaídas, los genotipos huérfanos y la familia Beijing. La familia H presentó una asociación con los grupos indígenas arhuaco y camëntsá, la familia U se asoció con el grupo wounaan y la familia T con el grupo motilón barí. Conclusiones. Este es el primer estudio nacional de caracterización de M. tuberculosis en grupos indígenas. Se evidenció que el diagnóstico en indígenas es tardío, y que 53 % de los patrones huérfanos podrían ser típicos de la población indígena colombiana. El alto porcentaje de agrupamiento por spoligotyping (62%) podría indicar casos de transmisión activa, una situación que debe ser corroborada usando un segundo marcador de genotipificación. Se identificó un nuevo genotipo (Beijing-like SIT 406) en Colombia.

New chalcone-sulfonamide hybrids exhibiting anticancer and antituberculosis activity.

New sulfonamides 5/6 derived from 4-methoxyacetophenone 1 were synthesized by N-sulfonation reaction of ammonia (3) and aminopyrimidinone (4) with its sulfonyl chloride derivative 2. Sulfonamides 5 and 6 were used as precursors of two new series of chalcones 8a-f and 9a-f, which were obtained through Claisen-Schmidt condensation with aromatic aldehydes 7a-f. Compounds 5/6, 8a-d, 8f, 9a-d, and 9f were screened by the US National Cancer Institute (NCI) at 10 µM against sixty different human cancer cell lines (one-dose trial). Chalcones 8b and 9b satisfied the pre-determined threshold inhibition criteria and were selected for screening at five different concentrations (100, 10, 1.0, 0.1, and 0.01 µM). Compound 8b exhibited remarkable GI50 values ranging from 0.57 to 12.4 µM, with cytotoxic effects being observed in almost all cases, especially against the cell lines K-562 of Leukemia and LOX IMVI of Melanoma with GI50 = 0.57 and 1.28 µM, respectively. Moreover, all compounds were screened against Mycobacterium tuberculosis H37Rv, chalcones 8a-c and 9a-c were the most active showing MIC values between 14 and 42 µM, and interestingly they were devoid of antibacterial activity against Mycobacterium smegmatis and Staphylococcus aureus. These antituberculosis hits showed however low selectivity, being equally inhibitory to M. tuberculosis and mammalian T3T cells. The chalcone-sulfonamide hybrids 8a-f and 9a-f resulted to be appealing cytotoxic agents with significant antituberculosis activity.

Diarylethenes Display In Vitro Anti-TB Activity and Are Efficient Hits Targeting the Mycobacterium tuberculosis HU Protein.

Tuberculosis continues to be a great source of concern in global health because of the large reservoir of humans infected with the bacilli and the appearance of clinical isolates resistant to a wide array of anti-tuberculosis drugs. New drugs with novel mechanisms of action on new targets are urgently required to reduce global tuberculosis burden. Mycobacterium tuberculosis nucleoid associated protein (NAP) HU has been shown to be druggable and essential for the organism's survival. In this study, four diarylethenes were synthesized using a one-pot decarboxylated Heck-coupling of coumaric acids with iodoanisoles. The prepared compounds 1-4 were tested for their in vitro growth inhibition of M. tuberculosis H37Rv using the spot culture growth inhibition assay, displaying minimum inhibitory concentrations between 9 and 22 µM. Their cytotoxicity against BHK-21 cell line showed half inhibition at concentrations between 98 and 729 µM. The most selective hit (SI = 81), demonstrated inhibition of M. tuberculosis HU protein involved in maintaining bacterial genome architecture.

[Characterization of clinical isolates of Mycobacterium tuberculosis from HIV positive individuals in Colombia, 2012].

INTRODUCTION: One third of the increase in tuberculosis cases is attributed to the spread of HIV. In 2012, 1,397 HIV-associated tuberculosis cases were reported in Colombia, i.e., 11.8% of the total cases. Molecular epidemiology tools help to understand the transmission of tuberculosis. OBJECTIVE: To characterize clinical isolates of Mycobacterium tuberculosis derived from HIV-infected individuals, received at the Laboratorio Nacional de Referencia in the Instituto Nacional de Salud. MATERIALS AND METHODS: This was a descriptive observational study. We analyzed 63 isolates of M. tuberculosis from HIV-infected individuals. Identification, drug susceptibility and genotyping assays were performed. RESULTS: Of the new cases evaluated, three (5.0%) were resistant to isoniazid combined with streptomycin; two (3.3%) to rifampicin, and one (1.6%) to isoniazid. Previously treated cases were sensitive. No multidrug resistance was evident. Among the predominant genotypes, 20 isolates were (31.7%) LAM9, eight (12.7%), H1, and seven (11.1%), T1. Nineteen isolates corresponded to orphan patterns. One single grouping was observed among tested isolates. We found no statistically significantdifference between the proportions of the antituberculous drug resistance and genotypes. CONCLUSION: We found resistant isolates to the most powerful drugs, rifampicin and isoniazid, among new cases, showing the transmission of resistant strains. Genetic families of M. tuberculosis LAM9, T1 and H1 correspond to those described in the general population. We detected no active transmission among studied isolates. More comprehensive studies are needed to assess the real situation of HIV associated tuberculosis in the country regarding sensitivity and transmission.

Caracterización de aislamientos clínicos de Mycobacterium tuberculosis obtenidos de individuos positivos para HIV en Colombia, 2012 / Characterization of clinical isolates of Mycobacterium tuberculosis from HIV positive individuals in Colombia, 2012

Resumen Introducción: Una tercera parte de los casos nuevos de tuberculosis se atribuye a la propagación del HIV. En 2012, se presentaron en Colombia 1.397 casos de tuberculosis concomitante con la infección por HIV, es decir, 11,8 % del total de notificados. El uso de las herramientas de epidemiología molecular contribuye a una mejor comprensión de la transmisión de la enfermedad. Objetivo: Caracterizar los aislamientos clínicos de Mycobacterium tuberculosis de individuos positivos para HIV recibidos en el Laboratorio Nacional de Referencia del Instituto Nacional de Salud. Materiales y métodos: Se hizo un estudio observacional descriptivo. Se estudiaron 63 aislamientos de individuos con tuberculosis e infección por HIV mediante pruebas de identificación, sensibilidad y genotipificación. Resultados: Dos de los casos nuevos (3,3 %) eran resistentes a rifampicina y uno (1,6 %) a isoniacida, en tanto que tres (5,0 %) lo eran a la isoniacida combinada con estreptomicina. Los casos previamente tratados fueron sensibles. No se evidenció multirresistencia. Hubo 20 (31,7 %) aislamientos de la familia genética LAM9, 8 (12,7 %) de la H1 y 7 (11,1 %) de la T1 . Diecinueve aislamientos correspondieron a patrones huérfanos. Se observó un único agrupamiento entre los aislamientos analizados. No se encontraron diferencias estadísticamente significativas entre la resistencia a fármacos y las familias genéticas. Conclusión: La resistencia encontrada demostró la transmisión de cepas resistentes a rifampicina e isoniacida. Las familias genéticas LAM9, T1 y H1 corresponden a las descritas en la población general. No se evidenció transmisión activa en los aislamientos estudiados. Se necesitan estudios más completos para conocer la situación real de la infección concomitante de tuberculosis y HIV en el país.

Abstract Introduction: One third of the increase in tuberculosis cases is attributed to the spread of HIV. In 2012, 1,397 HIV-associated tuberculosis cases were reported in Colombia, i.e., 11.8% of the total cases. Molecular epidemiology tools help to understand the transmission of tuberculosis. Objective: To characterize clinical isolates of Mycobacterium tuberculosis derived from HIV-infected individuals, received at the Laboratorio Nacional de Referencia in the Instituto Nacional de Salud. Materials and methods: This was a descriptive observational study. We analyzed 63 isolates of M. tuberculosis from HIV-infected individuals. Identification, drug susceptibility and genotyping assays were performed. Results: Of the new cases evaluated, three (5.0%) were resistant to isoniazid combined with streptomycin; two (3.3%) to rifampicin, and one (1.6%) to isoniazid. Previously treated cases were sensitive. No multidrug resistance was evident. Among the predominant genotypes, 20 isolates were (31.7%) LAM9, eight (12.7%), H1, and seven (11.1%), T1. Nineteen isolates corresponded to orphan patterns. One single grouping was observed among tested isolates. We found no statistically significant difference between the proportions of the antituberculous drug resistance and genotypes. Conclusion: We found resistant isolates to the most powerful drugs, rifampicin and isoniazid, among new cases, showing the transmission of resistant strains. Genetic families of M. tuberculosis LAM9, T1 and H1 correspond to those described in the general population. We detected no active transmission among studied isolates. More comprehensive studies are needed to assess the real situation of HIV associated tuberculosis in the country regarding sensitivity and transmission.

Mycobacterium tuberculosis Genotypes Determined by Spoligotyping to Be Circulating in Colombia between 1999 and 2012 and Their Possible Associations with Transmission and Susceptibility to First-Line Drugs.

INTRODUCTION: Tuberculosis (TB) remains a primary public health problem worldwide. The number of multidrug-resistant tuberculosis (MDR TB) cases has increased in recent years in Colombia. Knowledge of M. tuberculosis genotypes defined by spoligotyping can help determine the circulation of genotypes that must be controlled to prevent the spread of TB. OBJECTIVE: To describe the genotypes of M. tuberculosis using spoligotyping in resistant and drug-sensitive isolates and their possible associations with susceptibility to first-line drugs. METHODS: An analytical observational study was conducted that included 741 isolates of M. tuberculosis from patients. The isolates originated from 31 departments and were obtained by systematic surveillance between 1999 and 2012. RESULTS: In total 61.94% of the isolates were resistant to 1 or more drugs, and 147 isolates were MDR. In total, 170 genotypes were found in the population structure of Colombian M. tuberculosis isolates. The isolates were mainly represented by four families: LAM (39.9%), Haarlem (19%), Orphan (17%) and T (9%). The SIT42 (LAM 9) was the most common genotype and contained 24.7% of the isolates, followed by the genotypes SIT62 (Haarlem1), SIT53 (T1), and SIT50 (H3). A high clustering of isolates was evident with 79.8% of the isolates classified into 32 groups. The Beijing family was associated with resistant isolates, whereas the Haarlem and T families were associated with sensitive isolates. The Haarlem family was also associated with grouped isolates (p = 0.031). CONCLUSIONS: A high proportion (approximately 80%) of isolates was found in clusters; these clusters were not associated with resistance to first-line drugs. The Beijing family was associated with drug resistance, whereas the T and Haarlem families were associated with susceptibility in the Colombian isolates studied.

Population structure among mycobacterium tuberculosis isolates from pulmonary tuberculosis patients in Colombia.

BACKGROUND: Phylogeographic composition of M. tuberculosis populations reveals associations between lineages and human populations that might have implications for the development of strategies to control the disease. In Latin America, lineage 4 or the Euro-American, is predominant with considerable variations among and within countries. In Colombia, although few studies from specific localities have revealed differences in M. tuberculosis populations, there are still areas of the country where this information is lacking, as is a comparison of Colombian isolates with those from the rest of the world. PRINCIPAL FINDINGS: A total of 414 M. tuberculosis isolates from adult pulmonary tuberculosis cases from three Colombian states were studied. Isolates were genotyped using IS6110-restriction fragment length polymorphism (RFLP), spoligotyping, and 24-locus Mycobacterial interspersed repetitive units variable number tandem repeats (MIRU-VNTRs). SIT42 (LAM9) and SIT62 (H1) represented 53.3% of isolates, followed by 8.21% SIT50 (H3), 5.07% SIT53 (T1), and 3.14% SIT727 (H1). Composite spoligotyping and 24-locus MIRU- VNTR minimum spanning tree analysis suggest a recent expansion of SIT42 and SIT62 evolved originally from SIT53 (T1). The proportion of Haarlem sublineage (44.3%) was significantly higher than that in neighboring countries. Associations were found between M. tuberculosis MDR and SIT45 (H1), as well as HIV-positive serology with SIT727 (H1) and SIT53 (T1). CONCLUSIONS: This study showed the population structure of M. tuberculosis in several regions from Colombia with a dominance of the LAM and Haarlem sublineages, particularly in two major urban settings (Medellín and Cali). Dominant spoligotypes were LAM9 (SIT 42) and Haarlem (SIT62). The proportion of the Haarlem sublineage was higher in Colombia compared to that in neighboring countries, suggesting particular conditions of co-evolution with the corresponding human population that favor the success of this sublineage.

Tuberculosis cutánea por mesoterapia, estudio de seis casos / Cutaneous tuberculosis after mesotherapy: report of six cases

Introducción. La tuberculosis cutánea secundaria a la inyección con agujas es rara; se presenta en personal médico y de laboratorio, y en pacientes que reciben tratamientos percutáneos.Objetivo. Presentar seis pacientes con tuberculosis cutánea secundaria a tratamiento por mesoterapia.Materiales y métodos. Entre 1 y 4 meses después de la inyección en la piel glútea y abdominal de material no precisado, como tratamiento para la obesidad y la celulitis, cinco mujeres y un hombre desarrollaron pápulas, nódulos y senos de drenaje de material seroso en los sitios de inoculación, interpretados clínicamente como infección por micobacterias no tuberculosas. Se practicaron cultivos de las secreciones y de las biopsias de piel para la identificación fenotípica y estudio de histopatología. Con los resultados iniciales se realizaron pruebas moleculares de PRA (PCR-restriction pattern analysis) en las biopsias de piel y estudio ampliado de los pacientes.Resultados. Se demostró Mycobacterium tuberculosis en los cultivos, hallazgo confirmado por la técnica de PRA en las biopsias incluidas en parafina. Los pacientes no habían padecido tuberculosis. Las placas de tórax fueron normales y la tuberculina midió entre 17 y 20 mm. Cinco curaron con terapia antituberculosa y otro curó espontáneamente luego de la resección-biopsia de la lesión más grande. No se encontraron adenopatías satélites ni recurrencias. Conclusiones. Se demostró una nueva forma de adquirir la tuberculosis cutánea. Esta es la segunda demostración de tuberculosis cutánea por mesoterapia en Colombia. El estudio de las lesiones de la piel en el sitio de la inyección cutánea debe incluir pruebas para detectar micobacterias, entre ellas M. tuberculosis. Las autoridades sanitarias deben prestar atención y prevenir esta modalidad de adquirir la tuberculosis.

Introduction. Cutaneous tuberculosis as a result of a needle injection is a rare event; it generally occurs among medical and laboratory personnel and among patients receiving percutaneous treatment. Objective. Six patients are presented who developed cutaneous tuberculosis after mesotherapy cosmetic treatment. Material and methods. One to four months after injection of an unknown product as treatment for obesity and cellulites, five women and a man developed papules, nodules and drainage of wax like material at the inoculated sites; this was interpreted clinically as a non tuberculous mycobacterium infection. Skin biopsies were taken for a histopathologic study; the biopsy and exudates were cultured to make a phenotypic identification. Polymerase chain reaction and restriction enzyme pattern analyses (PCR-restriction pattern analysis)) procedures were applied to the skin biopsies. Results. Mycobacterium tuberculosis was confirmed in the culture and by PRA analysis in the paraffin-embedded biopsies. The patients had never had tuberculosis. Their thoracic X rays were normal and the size of the tuberculin reaction was 17 to 20 mm. Five patients recovered with antituberculosis treatment and the sixth spontaneously healed after the removal of the largest cutaneous module. No satellite adenopathy or recurrences were observed. Conclusions. A previously undescribed mode of acquisition cutaneous tuberculosis was described. This was the second incident of a demonstrated cutaneous tuberculosis following mesotherapy in Colombia. Skin lesions induced by injections must be tested to detect mycobacterias to include M. tuberculosis.

Cutaneous tuberculosis after mesotherapy: report of six cases.

INTRODUCTION: Cutaneous tuberculosis as a result of a needle injection is a rare event; it generally occurs among medical and laboratory personnel and among patients receiving percutaneous treatment. OBJECTIVE: Six patients are presented who developed cutaneous tuberculosis after mesotherapy cosmetic treatment. MATERIAL AND METHODS: One to four months after injection of an unknown product as treatment for obesity and cellulites, five women and a man developed papules, nodules and drainage of wax like material at the inoculated sites; this was interpreted clinically as a non tuberculous mycobacterium infection. Skin biopsies were taken for a histopathologic study; the biopsy and exudates were cultured to make a phenotypic identification. Polymerase chain reaction and restriction enzyme pattern analyses (PCR-restriction pattern analysis)) procedures were applied to the skin biopsies. RESULTS: Mycobacterium tuberculosis was confirmed in the culture and by PRA analysis in the paraffin-embedded biopsies. The patients had never had tuberculosis. Their thoracic X rays were normal and the size of the tuberculin reaction was 17 to 20 mm. Five patients recovered with antituberculosis treatment and the sixth spontaneously healed after the removal of the largest cutaneous module. No satellite adenopathy or recurrences were observed. CONCLUSIONS: A previously undescribed mode of acquisition cutaneous tuberculosis was described. This was the second incident of a demonstrated cutaneous tuberculosis following mesotherapy in Colombia. Skin lesions induced by injections must be tested to detect mycobacterias to include M. tuberculosis.