RESUMEN
This study aimed to reinforce the importance of the epidemiological surveillance of multidrug-resistant tuberculosis (MDR-TB) in Rio de Janeiro State (RJ). Here, we reviewed seven articles we published between 2018 and 2022. This study had two phases. The quantitative phase where frequency was used to describe patient characteristics and regressions were used to evaluate the relationship between treatment outcomes and covariates. The qualitative phase where content analysis of the narratives was performed. Secondary (electronic systems) and primary (semi-structured interviews) data were used. We analyzed 2,269 MDR-TB, 58.1% MDR-TB, and 18.6% extensively drug-resistant TB (XDR-TB) cases, of which 44.3% exhibited unfavorable outcomes. Among the 140 patients with XDR-TB, 29.3% had not undergone prior treatment for MDR-TB. The primary resistance rate in MDR-TB cases was 14.7%, revealing significant demographic and clinical disparities, particularly among women, Caucasians, and those with higher education levels. The number of cases increased from 7.69% in 2000 to 38.42% in 2018, showing an increasing trend (AAPC = 9.4; 95% CI 1.4-18.0, p < 0.001), with 25.4% underreporting. A qualitative study confirmed a high proportion of primary resistance (64.5%) and delayed diagnosis of MDR-TB. In RJ, the diagnostic and therapeutic cascade of MDR-TB must be improved using molecular tests to achieve an early diagnosis of resistance and immediate initiation of appropriate treatment, promote social protection for MDR/XDR-TB patients and their families, enhance TB contact tracing, establish and monitor hospital surveillance centers integrated with Primary Care, and unify various information systems through interoperability for better integration.
Asunto(s)
Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Brasil/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Femenino , Masculino , Adulto , Persona de Mediana Edad , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , Adulto Joven , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Adolescente , Monitoreo EpidemiológicoRESUMEN
BACKGROUND: The growing threat from pre-extensively drug-resistant tuberculosis (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) poses a major public health concern in Latin America and the Caribbean (LAC). Therefore, this study aimed to summarize the available evidence on the prevalence of pre-XDR-TB and XDR-TB among patients with multidrug-resistant tuberculosis in LAC. METHODS: A systematic review was conducted in the following databases on June 3, 2023: PubMed, Scopus, Ovid Medline, Web of Science, Scielo and LILACS. We estimated pooled proportions using a random effects model (Dersimonian and Laird). The 95% confidence intervals (95% CI) were calculated using the binomial exact method (Clopper-Pearson Method). Subgroup (by time period and country) and sensitivity analyses were performed. RESULTS: Twenty-nine studies were eligible for qualitative synthesis and 27 for meta-analysis (n = 15,565). The pooled prevalence of XDR-TB in the study participants was 5% (95% CI: 3%-6%), while that of pre-XDR-TB was 10% (95% CI 7%-14%). Cuba (6%, 95% CI 0%-17%) and Peru (6%, 95% CI 5%-7%) had the highest pooled prevalence of XDR-TB. Regarding pre-XDR-TB, Brazil (16%, 95% CI 11%-22%) and Peru (13%, 95% CI: 9%-16%) showed the highest prevalence. CONCLUSIONS: The pooled prevalence of pre-XDR-TB and XDR-TB in LAC was 10% and 5%, respectively. Governments should strengthen drug-resistance surveillance and TB programs.
Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Humanos , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Antituberculosos/uso terapéutico , Antituberculosos/farmacología , América Latina/epidemiología , Pruebas de Sensibilidad Microbiana , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Región del Caribe/epidemiologíaRESUMEN
INTRODUCCIÓN: La resistencia a fármacos antituberculosos está influenciada por las características personales y las condiciones de salud de países en vías de desarrollo. OBJETIVO: Determinar los factores asociados a TB-pre extensamente resistente (TB-PRE XDR) en pacientes del Hospital Nacional Dos de Mayo (HNDM) entre 2017 y 2019. PACIENTES Y MÉTODO: Se desarrolló un estudio caso control no pareado, definiendo como caso al paciente con TB- PRE XDR y como control al paciente con TB-S. Se recolectaron variables epidemiológicas, clínicas y radiológicas. RESULTADOS: Se analizaron 51 casos y 102 controles. El análisis bivariado determinó como factores con p 51 años (OR: 0,17, IC95%: 0,05-0,51), uso de drogas (OR:2,5, IC95%: 1,1-5,4), antecedente de TB (OR: 20, IC95%: 8,4-47), reclusión previa (OR: 8, IC95%: 2,7-23,8), infección por VIH (OR: 0,2, IC95%: 0,08-1) y uso previo de fármacos antituberculosos (OR: 21, IC95%: 8,8-50). El análisis de regresión logística identificó como factores asociados a TB-PRE XDR al contacto de TB, antecedente de TB, tiempo de enfermedad y uso previo de fármacos antituberculosos. CONCLUSIÓN: Las medidas para limitar el desarrollo de TB-PRE XDR en pacientes con TB-S deben incidir sobre el antecedente de TB, contacto con TB, tiempo de enfermedad y uso previo de anti-TB no controlados; sin embargo, existen resultados no concluyentes sobre el hábito nocivo y la comorbilidad, siendo necesario más estudios para determinar su influencia como factores asociados identificables.
BACKGROUND: Resistance to anti-TB drugs is influenced by personal characteristics and health conditions in developing countries. AIM: To determine the factors associated with pre-extensively drug-resistant tuberculosis (PRE XDR-TB) at Hospital Nacional Dos de Mayo (HNDM) in patients between the 2017 and 2019. METHODS: An unpaired case control study was developed; defining as case PRE XDR-TB patient and as control S-TB patient. Epidemiological, clinical and radiological variables were collected. RESULTS: We analyzed 51 cases and 102 controls. The bivariate analysis showed as factors with p 51 years (OR: 0.17, 95% CI: 0.05-0.51), drug use (OR: 2.5, 95% CI: 1.1-5.4), previous history of TB (OR: 20, 95% CI: 8.4-47), previous confinement (OR: 8, 95% CI: 2.7-23.8), HIV infection (OR: 0.2, 95% CI: 0.08-1) and previous use of antiTB drugs (OR: 21, 95% CI: 8.8-50). The logistic regression analysis identified as associated factors with PRE XDR-TB the previous contact with TB, a history of TB, length of illness and previous use of tuberculosis antibiotics. CONCLUSION: The measures to limit the development of TB-PRE XDR in patients with TB-S must include the previous history of TB, TB contact, length of illness and previous use of uncontrolled antibiotics against TB; however, there are inconclusive results about the harmful habits and comorbidity, requiring more studies to determine their influence as identifiable associated factors.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Perú/epidemiología , Estudios de Casos y Controles , Factores Epidemiológicos , Análisis Multivariante , Análisis de Regresión , Factores de Riesgo , Tuberculosis Extensivamente Resistente a Drogas/diagnóstico por imagen , Hospitales PúblicosRESUMEN
BACKGROUND: Surveillance of multidrug resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB) is essential to guide disease dissemination control measures. Brazil contributes to a significant fraction of tuberculosis (TB) cases worldwide, but only few reports addressed MDR/XDR-TB in the country. METHODS: This cross-sectional, laboratory-based study describes the phenotypic resistance profiles of isolates obtained between January 2008 and December 2011 in Bahia, Brazil, and sociodemographic, epidemiological, and clinical characteristics (obtained from mandatory national registries) of the corresponding 204 MDR/XDR-TB patients. We analyzed the mycobacterial spoligotyping and variable number of tandem repeats of mycobacterial interspersed repetitive units in 12-loci profiles obtained from Salvador. RESULTS: MDR/XDR-TB patients were predominantly male, had a median age of 43 years, belonged to black ethnicity, and failed treatment before MDR-TB diagnosis. Nearly one-third of the isolates had phenotypic resistance (evaluated by mycobacteria growth indicator tube assay) to second-line anti-TB drugs (64/204, 31%), of which 22% cases (14/64) were diagnosed as XDR-TB. Death was a frequent outcome among these individuals and was associated with resistance to second-line anti-TB drugs. Most isolates successfully genotyped belonged to the Latin-American Mediterranean (LAM) Family, with an unprecedented high proportion of LAM10-Cameroon subfamily bacilli. More than half of these isolates were assigned to a unique cluster by the genotyping methods performed. Large clusters of identical genotypes were also observed among LAM SIT42 and SIT376 strains. CONCLUSIONS: We highlight the need for strengthening local and national efforts to perform early detection of TB drug resistance and to prevent treatment discontinuation to limit the emergence of drug-resistant strains.
Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Adulto , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Brasil , Estudios Transversales , Resistencia a Medicamentos , Farmacorresistencia Bacteriana Múltiple/genética , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Femenino , Genotipo , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológicoRESUMEN
Human tuberculosis is still a major world health concern. In Uruguay, contrary to the world trend, an increase in cases has been observed since 2006. Although the incidence of MDR-resistant strains is low and no cases of XDR-TB were registered, an increase in the number of patients with severe tuberculosis requiring critical care admission was observed. As a first aim, we performed the analysis of the genetic structure of strains isolated from patients with severe tuberculosis admitted to an intensive care unit. We compared these results with those corresponding to the general population observing a statistically significant increase in the Haarlem genotypes among ICU patients (53.3% vs 34.7%; p;<;0.05). In addition, we investigated the association of clinical outcomes with the genotype observing a major incidence of hepatic dysfunctions among patients infected with the Haarlem strain (p;<;0.05). The cohort presented is one of the largest studied series of critically ill patients with tuberculosis.
La tuberculosis (TB) aún representa un problema mayor de salud pública. En Uruguay, contrariamente a la tendencia mundial, se ha observado un incremento en el número de casos desde 2006. Aunque la incidencia de casos de multidrogorresistencia (MDR) es baja y no se han reportados casos de resistencia a fármacos de primera y segunda línea de tratamiento (XDR), se ha observado un incremento en el número de casos con TB grave, que requieren internación en unidad de terapia intensiva (CTI). Como primer objetivo del presente trabajo, se analizó la estructura genética de cepas de Mycobacterium tuberculosis aisladas de pacientes internados en CTI. Comparamos estos resultados con los obtenidos con cepas circulantes en la comunidad. Observamos un incremento estadísticamente significativo del genotipo Haarlem en los pacientes internados en CTI (53,3 vs. 34,7%; p;<;0,05). Además, investigamos la asociación del desenlace clínico con el genotipo, y encontramos una mayor incidencia de disfunción hepática en los pacientes infectados con la cepa Haarlem (p;<;0,05). La cohorte presentada en este trabajo corresponde a una de las series con mayor número de pacientes con tuberculosis que requirieron internación en CTI.
Asunto(s)
Humanos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Mycobacterium tuberculosis/genética , Enfermedad Crítica , Genotipo , AntituberculososRESUMEN
Human tuberculosis is still a major world health concern. In Uruguay, contrary to the world trend, an increase in cases has been observed since 2006. Although the incidence of MDR-resistant strains is low and no cases of XDR-TB were registered, an increase in the number of patients with severe tuberculosis requiring critical care admission was observed. As a first aim, we performed the analysis of the genetic structure of strains isolated from patients with severe tuberculosis admitted to an intensive care unit. We compared these results with those corresponding to the general population observing a statistically significant increase in the Haarlem genotypes among ICU patients (53.3% vs 34.7%; p<0.05). In addition, we investigated the association of clinical outcomes with the genotype observing a major incidence of hepatic dysfunctions among patients infected with the Haarlem strain (p<0.05). The cohort presented is one of the largest studied series of critically ill patients with tuberculosis.
Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas , Mycobacterium tuberculosis , Tuberculosis Resistente a Múltiples Medicamentos , Antituberculosos , Enfermedad Crítica , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Genotipo , Humanos , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológicoRESUMEN
Drug-resistant tuberculosis (DR-TB) is major problem in the fight against TB. Multidrug resistant (MDR) TB patients have a reduced treatment success rates and for, extensively drug-resistant (XDR) TB the cure rate does not exceed 25% in many countries. To evaluate the pre-XDR-TB and XDR-TB prevalence and transmission in Rio Grande do Sul State, in southern Brazil, we performed a retrospective WGS-based analysis of 87 MDR-TB cases, aiming to identify resistance-conferring mutations and its phylogenetic distinctiveness. Using a five SNP threshold for genomic clustering, 60 strains were genomically linked within 10 clusters, including 14 likely transmission events identified by retrospective conventional epidemiological investigation. Moreover, five likely transmission events involved 17 patients deprived of liberty in the same prison establishment. Mutations associated with isoniazid and rifampicin resistance were identified respectively in 97.70% and 98.85% of MDR M.tb strains, more frequently in katG and rpoB genes. In total, we identified eight (9.19%) pre-XDR and four (4.59%) XDR M.tb strains. Resistance to ofloxacin was observed in seven (8.04%) strains, all of them presenting resistance-conferring mutations. Phenotypic resistance from capreomycin and kanamycin was found in seven (8.04%) and four (4.59%) strains respectively, but no classic mutations associated with resistance to these drugs was identified. The results put in evidence a scenario involving multiple phylogenetically distinctive clades associated with pre-XDR and XDR-TB in the largest state of southern Brazil, while stressing the potential of using WGS to predict anti-TB drug resistance and need to halt MDR-TB transmission in the region.
Asunto(s)
Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Adulto , Antituberculosos/farmacología , Brasil/epidemiología , Farmacorresistencia Bacteriana Múltiple/genética , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Femenino , Variación Genética , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Repeticiones de Minisatélite , Mutación , Mycobacterium tuberculosis/aislamiento & purificación , Filogenia , Polimorfismo de Nucleótido Simple , Tuberculosis Resistente a Múltiples Medicamentos/transmisión , Secuenciación Completa del GenomaRESUMEN
Introducción. La tuberculosis extremadamente resistente a los medicamentos (TB-XDR) es el resultado de deficiencias en la administración del tratamiento y en la prevención de la transmisión de la enfermedad; además, es un reto para los programas nacionales de control de la tuberculosis. Objetivo. Describir las características clínicas y epidemiológicas de los casos de TB-XDR diagnosticados en Colombia. Materiales y métodos. Se trata de un estudio de serie de casos, de pacientes con diagnóstico de TB-XDR, de 2006 a 2016 en Colombia. Las fuentes de información fueron el formato único de vigilancia y la base de datos del Laboratorio Nacional de Referencia. Se analizaron las variables: entidad territorial de procedencia, sexo, edad, régimen de afiliación, forma de tuberculosis, coinfección tuberculosis-HIV, patrón de sensibilidad a los fármacos de segunda línea y resultado (vivo o muerto). Resultados. En el período de estudio, se diagnosticaron 51 casos de TB-XDR, 28 hombres y 23 mujeres, con un promedio anual de cinco casos. En los departamentos de Antioquia, Valle del Cauca y Atlántico, se presentaron 46 (90 %) de los casos. El rango de edad fue de 5 a 81 años y, la mediana, de 40 años. De los 51 pacientes, 32 (63 %) estaban afiliados al régimen subsidiado de salud y 46 (90 %) presentaron tuberculosis pulmonar; de los 22 a quienes se les practicó la prueba para HIV, en tres (13,6 %) había coinfección con HIV, y 29 (57 %) murieron. Los fármacos a los cuales hubo mayor resistencia, fueron ofloxacina en 45 (88 %) casos y amikacina en 43 (84 %). Conclusión. La TB-XDR se presentó principalmente en formas pulmonares, lo cual aumenta la probabilidad de transmisión en la comunidad y se refleja en la aparición de tuberculosis resistente en menores de 15 años. La población más afectada es la económicamente activa, con una gran mortalidad. El Programa Nacional de Prevención y Control de la Tuberculosis debe generar estrategias para evitar la propagación de cepas resistentes.
Asunto(s)
Antituberculosos/uso terapéutico , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Coinfección/epidemiología , Colombia/epidemiología , Femenino , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Distribución por Sexo , Adulto JovenRESUMEN
SETTING: The State of Rio de Janeiro stands out as having the second highest incidence and the highest mortality rate due to TB in Brazil. This study aims at identifying the factors associated with the unfavourable treatment of MDR/XDR-TB patients in that State. METHOD: Data on 2269 MDR-TB cases reported in 2000-2016 in Rio de Janeiro State were collected from the Tuberculosis Surveillance System. Bivariate and multivariate logistic regressions were run to estimate the factors associated with unfavourable outcomes (failure, default, and death) and, specifically, default and death. RESULTS: The proportion of unfavourable outcomes was 41.9% among MDR-TB and 81.5% among XDR-TB. Having less than 8 years of schooling, and being an Afro-Brazilian, under 40 years old and drug user were associated with unfavourable outcome and default. Bilateral disease, HIV positive, and comorbidities were associated with death. XDR-TB cases had a 4.7-fold higher odds of an unfavourable outcome, with 29.3% of such cases being not treated for multidrug resistance in the past. CONCLUSION: About 30% of XDR-TB cases may have occurred by primary transmission. The high rates of failure and death in this category reflect the limitation of treatment options. This highlights the urgency to incorporate new drugs in the treatment.
Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antituberculosos/uso terapéutico , Brasil/epidemiología , Niño , Preescolar , Estudios de Cohortes , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/mortalidad , Femenino , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo , Insuficiencia del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/mortalidad , Adulto JovenRESUMEN
Two Mycobacterium tuberculosis strains-M (sublineage 4.1) and Ra (sublineage 4.3)-have long prevailed in Argentina among patients with multidrug-resistant tuberculosis (MDR-TB). Recently, budget constraints have hampered the surveillance of MDR-TB transmission. Based on whole-genome sequence analysis, we used M- and Ra-specific single nucleotide polymorphisms to tailor two multiplex allele-specific polymerase chain reactions (PCRs), which we applied to 252 stored isolates (95% of all newly diagnosed MDR-TB cases countrywide, 2015-2017). Compared with the latest data available (2007-2009), the M strain has receded (80/324 to 20/252, P < 0.0001), particularly among cross-border migrants (12/58 to 0/53, P = 0.0003) and HIV-infected people (30/97 to 7/74, P = 0.0007), but it still accounts for 4/12 new cases of extensively drug-resistant TB. Differently, the Ra strain remained stable in frequency (39/324 to 33/252) and contributed marginally to the extensive drug-resistance load (1/12). Our novel strategy disclosed recent trends of the two major MDR-TB strains, providing meaningful data to allocate control interventions more efficiently.
Asunto(s)
ADN Bacteriano/genética , Farmacorresistencia Bacteriana Múltiple , Epidemias/estadística & datos numéricos , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Mycobacterium tuberculosis/genética , Alelos , Antituberculosos/farmacología , Argentina/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Genotipo , Humanos , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/efectos de los fármacos , Polimorfismo de Nucleótido Simple , Secuenciación Completa del GenomaRESUMEN
Background: Argentina is considered a country with a middle tuberculosis (TB) incidence. However, according to the last national epidemiological report released in 2018, since 2013, the trends are steadily increasing. The aims of this study were to determine the drug-resistance (DR), multi-DR and extensively DR (MDR/XDR-TB), and rifampicin resistance (RIF-R) burden as a part of the local TB diagnosis (June 2010-August 2018); to detect the mutations associated to isoniazid (INH) and RIF-R and their geographical distribution; and to analyze the lineage relationship among the genetic patterns of the isolates circulating in the community. Methods: Respiratory and extrapulmonary specimens were processed by Ziehl-Neelsen stain and cultured on specific media. Drug-susceptibility testing of isolates was performed by the MGIT 960 and a colorimetric micro-method. Mutations conferring DR were detected by Genotype and DNA sequencing. Results: The study showed a DR-TB prevalence of approximately 20% of the isolated strains, while M/XDR-TB-and particularly RIF-R-affected more than 5.0% of the total amount of cases. DR geographical distribution revealed isolates carrying mutations in the inhA gene promoter region only constrained to three districts where it was also registered two same family relatives' cases with the infrequent rpoB S522 L/Q mutation. The fact that most DR/MDR-TB isolates were not grouped in genetic clusters suggested that these cases may mostly have occurred due to endogenous reactivation rather than recently transmission. Conclusion: According to the obtained results, it would be convenient, in highly MDR-TB suspected individuals, to confirm phenotypically, the INH and RIF susceptibility detected by molecular tests.
Asunto(s)
Antituberculosos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Argentina/epidemiología , Proteínas Bacterianas/genética , Monitoreo Epidemiológico , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Genotipo , Geografía , Hospitales , Humanos , Isoniazida/farmacología , Pruebas de Sensibilidad Microbiana , Mutación , Mycobacterium tuberculosis/aislamiento & purificación , Rifampin/farmacología , Análisis de Secuencia de ADN , Tuberculosis Resistente a Múltiples Medicamentos/epidemiologíaRESUMEN
OBJECTIVES: To describe the prevalence, associated factors, treatment outcomes and transmission of extensively drug-resistant (XDR) tuberculosis (TB) in the state of São Paulo, Brazil, for 2011 to 2013. METHODS: Drug susceptibility testing to first- and second-line drugs was performed by BACTEC MGIT 960 and molecular typing, by IS6110 restriction fragment length polymorphism. Clinical, epidemiologic and demographic data were obtained from surveillance information systems for TB. Patients were divided into three groups: multidrug resistant (MDR) TB (resistance to at least isoniazid and rifampicin), pre-XDR-TB (MDR-TB resistant to a fluoroquinolone or to at least one of the second-line injectable drugs) and XDR-TB (MDR-TB resistant to a fluoroquinolone and to at least one of the second-line injectables). RESULTS: Among the 313 MDR-TB patients identified, the prevalence of XDR-TB and pre-XDR-TB was 10.2% (n = 32) and 19.2% (n = 60), respectively. Compared to MDR-TB patients, XDR-TB patients were more likely to be female (odds ratio (OR) = 2.74, 95% confidence interval (CI), 1.29-5.83), have a history of TB (OR = 5.16; 95% CI, 1.52-17.51) and present higher death rates (OR= 3.74; 95% CI 1.70-8.25). XDR-TB transmission was observed in households, between neighbours and between a patient and a healthcare worker in a hospital. CONCLUSIONS: The prevalence of XDR-TB in the state of São Paulo is close to that estimated globally. Most of the XDR-TB patients were treated previously for TB and presented the lowest successful outcome rates. Because transmission of XDR-TB occurred, it is important that timely diagnosis of drug resistance is performed.
Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/transmisión , Mycobacterium tuberculosis , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Brasil/epidemiología , Estudios Transversales , Farmacorresistencia Bacteriana Múltiple , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Femenino , Humanos , Masculino , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Evaluación de Resultado en la Atención de Salud , Polimorfismo de Longitud del Fragmento de Restricción , Prevalencia , Vigilancia en Salud Pública , Factores de RiesgoRESUMEN
A Tuberculose Multirresistente (TBMR) é um dos grandes problemas de saúde enfrentados em países em desenvolvimento, apresentando-se como um grande desafio global para o controle da Tuberculose (TB). Destacamos ainda o surgimento de formas mais graves de resistência, como a Tuberculose Extensivamente Resistente (TB-XDR). No Brasil foram implantadas diversas estratégias e ações com o objetivo de garantir o controle da doença, sua erradicação e redução nos indices de abandono terapêutico. Porém, na cidade do Rio de Janeiro, o índice de incidência da doença permanece elevado e se destaca como um dos mais altos do Brasil. O presente estudo tem por objetivos, avaliar a frequência e o perfil epidemiológico de pacientes com TBMR e TB-XDR diagnosticados em um Hospital de referência no município do Rio de Janeiro, no período de 2016 a 2018, com a determinação de contribuir para a geração de dados epidemiológicos sobre a situação da doença na cidade do Rio de Janeiro, identificar o grupo de pessoas mais vulneráveis, ajudar a completar o quadro clínico da doença além de estimular outros estudos, sobre o conhecimento da TBMR e TB-XDR. Estudo foi descritivo transversal. Os dados foram secundários coletados através de informações disponíveis em prontuários de pacientes diagnosticados com TB que tiveram como desfecho de interesse a resistência às medicações. Para a obtenção dos dados foi utilizado um instrumento estruturado, que possibilitou a captura de informações referentes à frequencia, o perfil sociodemográfico, características clínico-epidemiológicas, dentre outros. Foi realizada análise das variáveis sociodemógraficas, epidemiológicas e história de tratamento anterior com os resultados coletados armazenados em um banco de dados específico, sendo as análises de frequências e de associações realizadas por meio do software estatístico SPSS. Foram coletados dados de 100 pacientes com TBMR, 44% deles abandonaram o tratamento anteriormente. Dos pacientes investigados 61.6% eram do sexo masculino e 38.4% do sexo feminino. A média de idade encontrada neste estudo foi de 37.9 anos, com a variação entre 18 e 77 anos, 45.3% se declararam pardos e 39.3% possuíam de 4-7 anos de estudo, 19% dos pacientes apresentaram coinfecção HIV/TBMR, foi verificada associação entre abandono de tratamento anterior e caso de TBMR. Podemos concluir que os pacientes que foram encaminhados para tratamento no hospital de estudo apresentaram uma taxa elevada de casos de abandono de tratamento de tuberculose, o que se faz necessário o incremento de ações de planejamento para a adesão ao tratamento da tuberculose.
Multidrug-resistant tuberculosis (MDR-TB) is one of the major health problems faced in developed and developing countries, presenting itself as a major global challenge for Tuberculosis (TB) control. We also highlight the emergence of more severe forms of resistance, such as Extensively Resistant Tuberculosis (TB-XDR). In Brazil several strategies and actions were implemented with the objective of guaranteeing the control of the disease, its eradication and reduction in the rates of therapeutic abandonment. However, in the city of Rio de Janeiro, the incidence rate of the disease remains high and stands out as the highest in Brazil. The present study aims to evaluate the prevalence and epidemiological profile of patients with MDR-TB and MDR-TB diagnosed in a reference hospital in the city of Rio de Janeiro, from 2016 to 2018, with the determination to contribute to the generation epidemiological data on the disease situation in the city of Rio de Janeiro, identifying the group of most vulnerable individuals, helping to complete the clinical picture of the disease, and stimulating other studies on the knowledge of MDR-TB and XDR-TB. The thesis is that patients with MDR-TB and XDR-TB reported in a referral hospital in the city of Rio de Janeiro had abandoned previous treatment. Descriptive cross-sectional study. The data were collected through information available in medical records of patients diagnosed with TB who had as an outcome of interest the resistance to medications. To obtain the data, a structured instrument was used, which enabled the capture of information regarding prevalence, sociodemographic profile, clinical and epidemiological characteristics, among others. An analysis of sociodemographic, epidemiological and previous treatment history was performed with the collected data stored in a specific database, and the frequency and association analyzes were performed using the SPSS statistical software. Data were collected from 100 patients with MDR-TB, 44% of whom had previously discontinued treatment. Of the patients investigated, 61.6% were male and 38.4% female. The mean age found in this study was 37.9 years, ranging from 18 to 77 years, 45.3% were declared pardos and 39.3% had 4-7 years of schooling, 19% of the patients had HIV / MDR coinfection, was verified association between early cessation of treatment and case of MDR-TB. We can conclude that the study hospital had a high rate of cases of abandonment of tuberculosis treatment, which necessitates an increase in planning actions for adherence to tuberculosis treatment.
La Tuberculosis Multirresistente (TBMR) es uno de los grandes problemas de salud enfrentados en los países desarrollados y en desarrollo, presentándose como un gran desafío global para el control de la Tuberculosis (TB). Estamos de acuerdo con el surgimiento de formas más graves de resistencia, la Tuberculosis Extensivamente Resistente (TB-XDR). En Brasil se implantaron diversas estrategias y acciones con el objetivo de garantizar el control de la enfermedad, su erradicación y reducción en las tasas de abandono terapéutico. Sin embargo, en la ciudad de Río de Janeiro, el índice de incidencia de la enfermedad permanece elevado y se destaca como el más alto de Brasil. El presente estudio tiene por objetivos, evaluar la prevalencia y el perfil epidemiológico de pacientes con TBMR y TB-XDR diagnosticados en un Hospital de referencia en el municipio de Río de Janeiro, en el período de 2016 a 2018, con la determinación de contribuir a la generación de datos epidemiológicos sobre la situación de la enfermedad en la ciudad de Río de Janeiro, identificar el grupo de personas más vulnerables, ayudar a completar el cuadro clínico de la enfermedad además de estimular otros estudios, sobre el conocimiento de la TBMR y TB-XDR. la tesis es que los pacientes de TBMR y TB-XDR notificados en un hospital de referencia en la ciudad de Río de Janeiro tuvieron abandono de tratamiento anterior. Estudio descriptivo transversal. Los datos fueron recolectados a través de informaciones disponibles en prontuarios de pacientes diagnosticados con TB que tuvieron como resultado de interés la resistencia a las medicaciones. Para la obtención de los datos se utilizó un instrumento estructurado, que posibilitó la captura de informaciones referentes a la prevalencia, el perfil sociodemográfico, características clínico-epidemiológicas, entre otros. Se realizaron análisis de las variables sociodemóficas, epidemiológicas e historia de tratamiento anterior con los resultados recogidos almacenados en un banco de datos específico, siendo los análisis de frecuencias y de asociaciones realizadas por medio del software estadístico SPSS. Se recogieron datos de 100 pacientes con TBMR, el 44% de ellos abandonaron el tratamiento anteriormente. De los pacientes investigados 61.6% eran del sexo masculino y 38.4% del sexo femenino. La media de edad encontrada en este estudio fue de 37.9 años, con la variación entre 18 y 77 años, el 45.3% se declaró pardos y el 39.3% poseía de 4-7 años de estudio, el 19% de los pacientes presentaron coinfección VIH / TBMR, fue verificada asociación entre el abandono del tratamiento anterior y el caso de TBMR. Podemos concluir que el hospital de estudio presentó una tasa elevada de casos de abandono de tratamiento de tuberculosis, lo que se hace necesario el incremento de acciones de planificación para la adhesión al tratamiento de la tuberculosis.
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Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Adulto , Persona de Mediana Edad , Perfil de Salud , Infecciones por VIH , Cooperación del Paciente , Tuberculosis Extensivamente Resistente a Drogas/diagnóstico , Hospitales Universitarios , Pacientes , Condiciones Sociales/estadística & datos numéricos , Factores Socioeconómicos , Comorbilidad , Estudios Transversales , Tuberculosis Extensivamente Resistente a Drogas/prevención & control , Tuberculosis Extensivamente Resistente a Drogas/transmisión , Tuberculosis Extensivamente Resistente a Drogas/epidemiologíaRESUMEN
INTRODUCTION Systematic surveillance of antituberculosis drug resistance allows identification of multidrug-resistant and extensively drug-resistant isolates of Mycobacterium tuberculosis. Surveillance studies of antituberculosis drug resistance systematically conducted in Cuba for over 15 years have revealed low circulation of multidrug-resistant tuberculosis, under 1% in new cases. OBJECTIVE Characterize antituberculosis drug resistance in isolates of M. tuberculosis recovered from patients with pulmonary tuberculosis in Cuba in 2012-2014. METHODS The nitrate reductase assay was used to test 997 isolates of M. tuberculosis for sensitivity to isoniazid and rifampicin. Isolates identified as multidrug resistant were tested for sensitivity to isoniazid, rifampicin, streptomycin, ethambutol, ofloxacin, amikacin, kanamycin and capreomycin by the proportion method, as well as genetic resistance mutations in rpoB, katG, inhA, gyrA, rrs and embB genes, using GenoType MTBDRplus and MTBDRsl commercial kits. RESULTS Some 95.6% of isolates from new cases and 89.6% of isolates from previously treated patients were sensitive to isoniazid and rifampicin. Multidrug resistance was found in 0.8% of new and 5.2% of previously treated patients, a statistically significant difference. One extensively drug-resistant isolate was detected among previously treated cases. All isolates examined with the molecular method had mutations in the rpoB gene, which is associated with resistance to rifampicin; only seven showed mutations in the katG gene and one in the inhA gene associated with isoniazid resistance. In one isolate, we found mutations in both gyrA and rrs genes, which are associated with resistance to fluoroquinolones and second-line injectable drugs and therefore, extensive resistance. CONCLUSIONS Results corroborate the low frequency of multidrug-resistant and extensively resistant M. tuberculosis strains in Cuba and highlight the need for continuous improvement of surveillance of antituberculosis drug resistance in Cuba. KEYWORDS Mycobacterium tuberculosis, multidrug resistance, extensively drug-resistant tuberculosis, Cuba.
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Antituberculosos/uso terapéutico , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Estudios Transversales , Farmacorresistencia Microbiana/genética , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiologíaRESUMEN
INTRODUCTION: Diabetes mellitus (DM), a very common disease in Mexico, is a well-known risk factor for tuberculosis (TB). However, it is not known by which extent DM predisposes to adverse events (AE) to anti-TB drugs and/or to worse outcomes in patients with multidrug-resistant (MDR-TB) and extensively drug-resistant TB (XDR-TB). The main objective of this study was to describe the outcomes of TB treatment, the impact of DM and the prevalence of AE in a cohort of patients with MDR-/XDR pulmonary TB treated at the national TB referral centre in Mexico City. RESULTS: Ninety patients were enrolled between 2010 and 2015: 73 with MDR-TB (81.1%), 11 with pre-XDR-TB (12.2%) and 6 (6.7%) with XDR-TB, including 49 (54.4%) with DM, and 3 with Human Immunodeficiency Virus (HIV) co-infection (3.3%). In 98% of patients, diagnosis was made by culture and drug susceptibility testing, while in a single case the diagnosis was made by a molecular test. The presence of DM was associated with an increased risk of serious drug-related AEs, such as nephrotoxicity (Odds Ratio [OR]=6.5; 95% Confidence Interval [95% CI]: 1.9-21.8) and hypothyroidism (OR=8.8; 95% CI: 1.8-54.2), but not for a worse outcome. CONCLUSIONS: Our data suggest that DM does not impact second-line TB treatment outcomes, but patients with DM have a higher risk of developing serious AEs to drug-resistant TB treatment, such as nephrotoxicity and hypothyroidism.
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Antituberculosos/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/etiología , Comorbilidad , Susceptibilidad a Enfermedades , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Femenino , Infecciones por VIH/epidemiología , Pérdida Auditiva/inducido químicamente , Pérdida Auditiva/epidemiología , Humanos , Hipertensión/epidemiología , Hipotiroidismo/inducido químicamente , Hipotiroidismo/epidemiología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/epidemiología , Masculino , México/epidemiología , Persona de Mediana Edad , Náusea/inducido químicamente , Náusea/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Pulmonar/epidemiología , Adulto JovenRESUMEN
Mexico is one of the most important contributors of multidrug resistance tuberculosis (MDR-TB) in Latin-America, however little is known about the molecular characteristics of these strains. For this reason, the objective of this work was to determine the genotype and characterize polymorphisms in genes associated with resistance to rifampicin, isoniazid, and second-line drugs in isolates from two regions of Mexico with high prevalence of drug resistant tuberculosis. Clinical isolates from individuals with confirmed MDR-TB were genotyped using MIRU-VNTR 12 loci. To characterize the polymorphisms in genes associated with resistance to rifampicin, isoniazid and second-line drugs; rpoB, katG, inhA, rrs, eis, gyrA, gyrB and tlyA were sequenced. 22 (41%) of the 54 MDR-TB isolates recovered were from the state of Baja California, while 32 (59%) were from Veracruz. The results show the katGS315T mutation was observed in 20% (11/54) of the isolates, while rpoBS315L was present in 33% (18/54). rrs had three polymorphisms (T1239C, ntA1401C and ntA1401G), gyrB presented no modifications, whereas gyrA showed five (S95T, F60Y, A90V, S91P and P124A), eis two (G-10A and A431G) and tlyA one (insertion at codon 67). Only 20% (11/54) of isolates were confirmed as MDR-TB by sequencing, and no mutations at any of the genes sequenced were observed in 43% (23/54) of the strains. Two isolates were recognized with the proper set of mutations like pre-XDR and one was XDR-TB. Eighteen isolates were classified as orphans and the remaining thirty-six were distributed in fourteen lineages, the most frequent were S (11%), Haarlem (9%), Ghana (9%) and LAM (7%). Out of the fourteen clusters identified, seven included unknown genotypes and nine had lineages. This is one of the most detailed analyses of genotypic characteristics and mutations associated with drug resistance to first and second-line drugs in MDR-TB isolates from Mexico. An important genetic variability and significant discrepancy between phenotypic tests and polymorphisms was observed. Our results set the need to screen additional loci as well as implement a molecular epidemiological surveillance system of MDR-TB in the country.
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Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Antituberculosos/farmacología , Proteínas Bacterianas/genética , Análisis por Conglomerados , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Variación Genética , Genotipo , Humanos , México/epidemiología , Pruebas de Sensibilidad Microbiana , Repeticiones de Minisatélite , Tipificación de Secuencias Multilocus , Mutación , PrevalenciaRESUMEN
XDR (extensively drug-resistant) and pre-XDR tuberculosis (TB) seriously compromise prognosis and treatment possibilities, and inevitably require the use of group V drugs (World Health Organization). The progress of all patients with XDR and pre-XDR TB seen in a specialized unit during 2012 and 2013 and treated with regimens that included at least 6 months of meropenem-clavulanate (MPC), capreomycin, moxifloxacin, linezolid, clofazimine, high-dose isoniazid, PAS, and bedaquiline in 1 case, were retrospectively analysed. Ten patients were treated, 9 with an extensive pattern of resistance to at least 6 drugs, and 1 because of adverse reactions and drug interactions leading to a similar situation. Eight of the 10 patients treated achieved bacteriological sputum conversion (2 consecutive negative monthly cultures) over a period of 2-7 months, while 2 died. No adverse reactions attributable to prolonged administration of MPC were observed.
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Antituberculosos/uso terapéutico , Ácido Clavulánico/uso terapéutico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tienamicinas/uso terapéutico , Adulto , Antituberculosos/clasificación , Antituberculosos/farmacología , Argentina/epidemiología , Ácido Clavulánico/farmacología , Quimioterapia Combinada , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Femenino , Humanos , Masculino , Meropenem , Persona de Mediana Edad , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/aislamiento & purificación , Perú/etnología , Estudios Retrospectivos , Esputo/microbiología , Tienamicinas/farmacología , Resultado del Tratamiento , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Uruguay/etnología , Adulto JovenRESUMEN
Mycobacterial species have practically evolved along humankind, sometimes provoking serious diseases. Among them, tuberculosis (TB), produced by M. tuberculosiscomplex bacteria, is historically the single most devastating infectious agent. Like many other microorganisms, M. tuberculosis resistant to antibiotics have risen as a consequence of selective pressure for mutants able to persist despite being attacked with drugs that would otherwise erradicate them from the infected person. Given the current long-term (6-9 months) therapy with multiple antibiotics, many people abandon their treatments, therefore promoting that bacteria that were not eliminated during therapy get exposed to suboptimal antibiotic concentrations, probably leading to mutations and drug resistance. In this scenario, extremely-drug resistant (XDR) TB was recognized not more than a decade ago, prompting concerns for a more complicated drug regimen with few available molecules. In recent years, either old antibiotics have been rediscovered as good measures to control XDR-TB, or new ones have emerged as alternatives to cure patients of this type of infection. In this work we aim to provide the medical community in Mexico with information of such drug regimens that have succesfully worked, in order to get their consideration for use in our country.
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Antituberculosos/uso terapéutico , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Antituberculosos/clasificación , Antituberculosos/economía , Ensayos Clínicos como Asunto , Costos de los Medicamentos , Farmacorresistencia Bacteriana Múltiple , Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Salud Global , Humanos , Mycobacterium tuberculosis/efectos de los fármacosRESUMEN
SETTING: Dr Cetrángolo Hospital, Buenos Aires, Argentina. OBJECTIVES: To characterise drug-resistant (DR), multidrug-resistant (MDR-) and extensively drug-resistant (XDR-) Mycobacterium tuberculosis isolates, and identify their genetic profiles, drug resistance levels and resistance-conferring mutations. DESIGN: Phenotypic drug susceptibility testing methods were used to determine drug resistance profiles. Minimal inhibitory concentrations (MICs) of isoniazid (INH), rifampicin (RMP) and levofloxacin (LVX) from 169 DR tuberculosis (TB) isolates, 78 of them monoresistant to INH, 13 to RMP, 7 to LVX, and 71 MDR-TB, were determined. Multiplex allele-specific polymerase chain reaction and DNA sequencing were used to detect mutations in katG, rpoB and gyrA/B genes. Genotyping was performed using spoligotyping and insertion sequence 6110 restriction fragment length polymorphism. RESULTS: In total, 38.9% of the INH-resistant (INH(R)) isolates had an MIC ≥ 32 g/ml; 61.3% of RMP-resistant (RMP(R)) isolates had an MIC ≥ 64 g/ml and 55.6% of the LVX-resistant (LVX(R)) isolates had an MIC 4 ≥ 16 g/ml. The main mutations found in INH(R) isolates were katG315 (53.7%) and inhAP-15 (25.5%), whereas in RMP(R) isolates the main mutations were rpoB531 (61.9%), followed by rpoB526 (16.7%). LVX(R) isolates showed mutations in gyrA94/90. Haarlem, LAM and T were the main spoligotyping families found. katG315 was mainly associated with Haarlem and LAM, whereas inhAP-15 was associated with T. CONCLUSIONS: Several isolates showed an association between high INH(R) levels and katG mutation; others from the Haarlem family were prone to becoming MDR-TB and continue to circulate in the community.