Susana Poggi

Human Mycobacterium bovis infection in ten Latin American countries.

The aim of this work was to obtain the best possible estimate of the relevance of bovine tuberculosis (BTB) in humans in Argentina, Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, Peru, Uruguay and Venezuela. Sources of information were a questionnaire filled by the participant laboratories, and a search of published literature (1970-2007). Only four of these countries reported bacteriologically confirmed cases of BTB in humans. Most of these were diagnosed in Argentina, where the mean percentage of Mycobacterium bovis cases in relation to those due to Mycobacterium tuberculosis (2000-2006) ranged from 0.34% to 1.0%, according to the region. A slowly decreasing trend was observed in non HIV as well as in HIV/AIDS patients in Buenos Aires. In most of these countries, the low coverage of culture methods, especially of those including pyruvate-containing media, appropriate to isolate M. bovis, contributes to an underestimate of the problem. It was confirmed that BTB in humans exists, even though its relevance seems to be low. Milk pasteurization, sanitary controls to dairy products, and meat inspection at slaughterhouses contribute to the protection of human health. However, occupational aerogenous exposure to TB cattle and their carcasses remains a source of infection in the region.

Tuberculous meningitis in HIV-infected patients: drug susceptibility and clinical outcome.

The objective of this study was to identify prognostic factors of death in patients with tuberculous meningitis (TM) and show the impact of infection by multidrug-resistant strains on the outcome of this disease. We retrospectively analysed clinical charts of HIV-infected patients with culture-confirmed TM attending our institution during 1996–2004. The following variables were associated with death during hospitalization: neurological signs at admission, a CD4 T-cell count less than 50 cells/μl and infection by multidrug-resistant strains.

Mycobacteria in HIV-infected patients in Buenos Aires

SETTING F. J. Muñiz Hospital and Department of Phthisiopneumonology, in Buenos Aires. OBJECTIVE To analyze bacteriological findings concerning tuberculosis and other mycobacteriosis, in association with HIV infection and AIDS. DESIGN From June 1985 to December 1991, 2521 samples from 1259 HIV-seropositive and AIDS patients were analyzed: 1133 samples were of bronchopulmonary origin and the remaining 1388 of extrapulmonary origin. Drug susceptibility tests were performed using the proportions method. RESULTS Mycobacterial disease was confirmed by culture in 240 of the 1259 HIV/AIDS patients (19%). Mycobacterium tuberculosis was isolated in 223 of these cases (92.9%) and M. bovis in two, while M. avium-complex (MAC) strains were identified as the cause of disease in 14 patients (5.8%). In only one case was disease due to M. kansasii. Blood cultures were positive in 21.2% of these 240 cases. Resistance of M. tuberculosis to antituberculosis drugs was found in 9.4% of the 223 isolates. In only one case was multidrug resistance detected, in a patient who had received previous treatment. CONCLUSION Smear examination, although less sensitive than in HIV-negative patients, was still a simple and reliable tool for the rapid diagnosis of mycobacterial disease. Blood culture aided in the successful diagnosis of about half of the cases of disseminated tuberculosis and of all cases of MAC disease. An alarming spread of tuberculosis was detected among a group of HIV-positive prisoners, and the possible emergence of multidrug resistance should be anticipated.

Evaluación de las medidas de control adoptadas frente a la epidemia de tuberculosis multirresistente asociada al sida en un hospital hispanoamericano

Antecedentes Desde 1992 se detectaron pacientes con tuberculosis multirresistente (TBMR) asociada al sida internados en el Hospital Muniz (Buenos Aires). El objetivo del trabajo es evaluar la eficacia de las medidas adoptadas frente a la expansion nosocomial de la TBMR/sida, que afecto a 803 enfermos entre 1992-2002. Metodos Se aplico un plan de accion que incluyo: cribado baciloscopico de admision, habitaciones de aislamiento para TB/sida, sala de aislamiento para TBMR/sida, diagnostico de multirresistencia mediante metodo radiometrico; banco de farmacos de segunda linea y proteccion respiratoria del personal de salud. Resultados Entre 1995 y 2002, se observo una tendencia estadisticamente significativa en la disminucion de casos de TBMR/sida y de los internamientos por TB/sida (33,9% frente a 80,5%, respectivamente), asi como una disminucion significativa en la mortalidad de los primeros. El cribado baciloscopico permitio diagnosticar el 63,4% de los casos de TB/sida internados. Progresivamente fueron empleados los recursos de aislamiento respiratorio y tratamiento eficaz de los casos de TBMR diagnosticados por metodo radiometrico. Respecto de la poblacion susceptible, el ingreso de pacientes con sida al hospital no vario significativamente a lo largo del periodo estudiado, tampoco lo hizo el recuento de linfocitos T CD4+ de los pacientes que requirieron internamiento. Conclusion Se observo una disminucion significativa de la curva epidemica nosocomial de TBMR en pacientes con sida, pese a la persistencia de pacientes susceptibles con bajo nivel de linfocitos T CD4+. Se considera que esta evolucion decreciente de la TBMR/sida puede ser atribuida al impacto de las medidas de control implementadas.

Primera serie de pacientes con TB-XDR y pre-XDR tratados con esquemas que incluyeron meropenem-clavulanato en Argentina

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.

Molecular Epidemiology of Mycobacterium tuberculosis, Buenos Aires, Argentina

To analyze the molecular epidemiology of Mycobacterium tuberculosis strains at a hospital in Buenos Aires, Argentina, and mutations related to multidrug-resistant and extensively drug-resistant tuberculosis, we conducted a prospective case–control study. Our findings reinforce the value of incorporating already standardized molecular methods for rapidly detecting resistance.

Formation of Foamy Macrophages by Tuberculous Pleural Effusions Is Triggered by the Interleukin-10/Signal Transducer and Activator of Transcription 3 Axis through ACAT Upregulation

The ability of Mycobacterium tuberculosis (Mtb) to persist in its human host relies on numerous immune evasion strategies, such as the deregulation of the lipid metabolism leading to the formation of foamy macrophages (FM). Yet, the specific host factors leading to the foamy phenotype of Mtb-infected macrophages remain unknown. Herein, we aimed to address whether host cytokines contribute to FM formation in the context of Mtb infection. Our approach is based on the use of an acellular fraction of tuberculous pleural effusions (TB-PE) as a physiological source of local factors released during Mtb infection. We found that TB-PE induced FM differentiation as observed by the increase in lipid bodies, intracellular cholesterol, and expression of the scavenger receptor CD36, as well as the enzyme acyl CoA:cholesterol acyl transferase (ACAT). Importantly, interleukin-10 (IL-10) depletion from TB-PE prevented the augmentation of all these parameters. Moreover, we observed a positive correlation between the levels of IL-10 and the number of lipid-laden CD14+ cells among the pleural cells in TB patients, demonstrating that FM differentiation occurs within the pleural environment. Downstream of IL-10 signaling, we noticed that the transcription factor signal transducer and activator of transcription 3 was activated by TB-PE, and its chemical inhibition prevented the accumulation of lipid bodies and ACAT expression in macrophages. In terms of the host immune response, TB-PE-treated macrophages displayed immunosuppressive properties and bore higher bacillary loads. Finally, we confirmed our results using bone marrow-derived macrophage from IL-10−/− mice demonstrating that IL-10 deficiency partially prevented foamy phenotype induction after Mtb lipids exposure. In conclusion, our results evidence a role of IL-10 in promoting the differentiation of FM in the context of Mtb infection, contributing to our understanding of how alterations of the host metabolic factors may favor pathogen persistence.