Tuberculosis multirresistentes en Argentina / Multidrug-resistant tuberculosis in Argentina

La Tuberculosis (TBC) es una enfermedad que ha sido y sigue siendo en Argentina y en el mundo, un problema de salud importante que produce inhabilitación y muerte en gran medida en una parte importante de la población. La carga de enfermedad en el mundo supera los 9 millones de casos y en Argentina alcanza los 10.000 casos anuales. Dentro de este marco, la emergencia de la Tuberculosis Multirresistente (TBC MDR) es un evento que ha venido a agravar la situación de la TBC a nivel mundial y también en Argentina, toda vez que representa una parte de los casos de TBC que no responden de manera adecuada a los tratamientos de primera línea y que tienen peor pronóstico con tratamientos además, más costosos y complejos. En Argentina se estima que el 4,4% de los casos de TBC que ocurren en el país son Multirresistentes, lo que equivale, según las estimaciones a más de400 casos. Existen factores de riesgo asociados al desarrollo de TBC MDR entre los que se destacan lacondición de VIH, la migración y, principalmente, los antecedentes de tratamiento anterior, entre otros. Conocer el comportamiento de estos factores de riesgo en nuestro medio ycuantificar la magnitud de la asociación con el desenlace en nuestro país es lo que se intentó realizar. El presente trabajo analizó, a partir de la información de registro de casos de TBC del país incluyendo la información sobre TBC MDR; la magnitud y tendencia del problema y los principales factores asociados con el desarrollo de TBC MDR y cuál es la fuerza de la asociación existente...

Elevation of CD56[bright]CD16[-] lymphocytes in MDR pulmonary tuberculosis

Protective immune responses induced in the majority of people infected with Mycobacterium tuberculosis enable them to control TB infection. The aim of this study was to investigate CD56 and CD16 positive peripheral blood mononuclear cells [PBMCs] and leukocyte subsets from multi-drug resistant pulmonary tuberculosis [MDR-TB], and compare them with nonresistant [NR] TB patients and healthy controls. 13 MDR-tuberculosis patients, 20 NR-TB individuals and 40 healthy subjects were included. Peripheral blood mononuclear cells were double stained with fluorochrome conjugated antibodies against CD56 and CD16 cell surface markers. The phenotype of positive cells was then analyzed by flow cytometry and the percentages of CD56[+] CD16[+], CD56[-] CD16[+], CD56[dim]CD16[ +/- ], and CD56[bright]CD16[ +/- ] subsets were calculated. There was a significant decline in the percentage of CD56[]+CD16[+] lymphocytes in both MDR and NR-TB patients compared with healthy controls. We also observed lower proportions of CD56[dim]/[bright]CD16[+] in addition to higher percentages of CD56dim/brightCD16-subsets in all TB patients [p

Progression of chronic pulmonary tuberculosis in mice intravenously infected with ethambutol resistant Mycobacterium tuberculosis.

Purpose: Ethambutol (EMB) is an important first line drug, however little information on its molecular mechanism of resistance and pathogenicity of resistant isolates is available. Present work was designed to study virulence of the EMB resistant M. tuberculosis strains and the host responses in-vivo on infection of EMB resistant M. tuberculosis using Balb/c mouse model of infection. Methods: Three groups of Balb/c mice (female, age 4-6 wk; 21 mice in each group) were infected intravenously with 106 CFU of M. tuberculosis H37Rv and two EMB resistant clinical isolates. Age and sex matched control animals were mock inoculated with Middlebrook 7H9 broth alone. At 10, 20, 30, 40, 50, 60, and 70 days post-infection three animals from each group were sacrificed by cervical dislocation and lung tissue was collected for further analysis. Results: Infection with EMB resistant M. tuberculosis led to progressive and chronic disease with significantly high bacillary load (p=0.02). Massive infiltration and exacerbated lung pathology with increased expression of IFN-gamma and TNF-alpha was observed in lungs of mice infected with EMB resistant strains. The present study suggests that infection with EMB resistant M. tuberculosis leads to chronic infection with subsequent loss of lung function, bacterial persistence with elevated expression of TNF-alpha resulting in increased lung pathology. Conclusion: These findings highlight that EMB resistant M. tuberculosis regulates host immune response differentially and its pathogenicity is different from drug sensitive strains of M. tuberculosis.

Tuberculosis multirresistente en pacientes con SIDA a comienzos del milenio / Multidrug-resistant tuberculosis in AIDS patients at the beginning of the millennium

La tuberculosis multirresistente (TBMR) asociada al sida emergió durante los años 90 en varios países del mundo. En Argentina, el brote más importante se originó en el Hospital Muñiz y susconsecuencias persisten hasta ahora. Con el objeto de evaluar la situación de la TBMR en este hospital, analizamoslas características clínico-demográfico-epidemiológicas de los 53 pacientes masculinos con TBMR/sida internados por primera vez en el trienio 2001-2003 con relación al genotipo del polimorfismo de longitud de fragmentos de restricción (RFLP) IS6110 de los aislamientos. La edad promedio de los pacientes fue 32 años, 37 (70%) residían en el conurbano bonaerense, 36 (68%) eran usuarios de drogas ilícitas y 14 (26.4%) tenían antecedentes carcelarios. El 88% presentó grave inmunodepresión (CD4+<100/μl) y el 58.5% falleció. La mortalidadse asoció a baja adherencia al tratamiento y a comorbilidades, pero no a enfermedad por Mycobacteriumtuberculosis cepa “M”, causante del brote original. De los 40 casos analizados por RFLP, 29 (72.5%) conformaron clusters y 24 presentaban el genotipo “M”. La resistencia a 5 o 6 drogas resultó un indicador de enfermedad por esa cepa. El genotipo “M” se asoció significativamente a internaciones previas en el Hospital Muñiz oencarcelamiento. En síntesis, 14 años después de ocurrido el primer caso de TBMR/sida, se constata la persistenciay predominancia en el hospital de la cepa responsable del brote. Se requiere una intensificación de las medidas de control de la diseminación institucional de la tuberculosis para consolidar la tendencia decrecientede la TBMR observada en el país en la última década

Aids-related multidrug-resistant tuberculosis (MDRTB) emerged during the 90s in several countries aroundthe world. In Argentina, the most notorious outbreak was documented in the Hospital Muñiz, which is still undergoing its aftermaths. In order to evaluate the situation in this hospital regarding MDRTB, we analysed clinical,demographic and epidemiological traits of the 53 male MDRTB-aids patients admitted during 2001-2003 at award especially dedicated to their isolation. Patients’ mean age was 32 years, 70% lived in Buenos Aires suburbs. A history of illicit drug users or imprisonment was recorded in 68% and 26% of the patients, respectively.Severe immunodepression (CD4+ count <100/μl) was found in 88% of the patients and 58% died. Mortality wasassociated with non-adherence to treatment and co-morbidity, but not with the genotype of the “M” strain, responsible for the original outbreak. Of 40 cases available for restriction fragment length polymorphism (RFLP),29 (72.5%) resulted in cluster. RFLP patterns of 24 matched the “M” genotype. In this study, resistance to 5 or 6 drugs was found to be an indicator of disease due to the “M” strain. The “M” genotype associated significantlyto previous admission at the Hospital Muñiz or imprisonment. In brief, 14 years after the detection of the firstMDRTB-aids case, we report here the persistence and predominance of the original outbreak strain at the hospital.Stronger TB infection control measures are urgently needed in hospitals and jails in order to strengthenthe declining trend of the MDRTB observed in our country towards the end of the last decade

Mycobacterium vaccae immunotherapy in the treatment of multi-drug-resistant tuberculosis: a preliminary report

Multiple drug resistance [MDR] of tubercle bacilli to chemotherapy is becoming a problem of major concern. In this study 41 patients infected with resistant strains of tubercle bacilli received immunotherapy with killed Mycobacterium vaccae as an adjunct to continuing chemotherapy. Eleven of the 41 patients were cured and became sputum negative. The combined therapy was particularly effective in male patients with short histories of previous chemotherapy. We conclude that immunotherapy with M. vaccae may be helpful in the treatment of multiple drug resistant tuberculosis