Marta Ambroggi

Nosocomial Spread of Human Immunodeficiency Virus-Related Multidrug-Resistant Tuberculosis in Buenos Aires

A steep upsurge of human immunodeficiency virus (HIV)-associated multidrug-resistant tuberculosis (MDR-TB) was recently observed at a referral treatment center in Buenos Aires City. Between January 1994 and June 1995, TB isolates resistant to at least five drugs were recovered from 101 of 272 HIV-infected inpatients. Highly resistant isolates from 77 patients underwent restriction fragment length polymorphism study with IS6110. After cross-contamination was eliminated, a single TB strain was found to have caused disease in 68 patients with a history of on-site exposure. The frequency of smear-positive pulmonary disease was higher among these patients than among non-MDR-TB HIV-infected patients (50/68 vs. 60/148, P < .001), and the 1-year survival was dramatically reduced (5/68 vs. 92/148). The strain involved in the outbreak was traced back to patients hospitalized in 1992. Institutional infection control policies were and may still be inadequate to contain the spread of TB among immunodepressed subjects, as is the case in other large urban hospitals in Argentina.

Successful alternative treatment of extensively drug-resistant tuberculosis in Argentina with a combination of linezolid, moxifloxacin and thioridazine

OBJECTIVES Current drug choices to treat extensively drug-resistant (XDR) tuberculosis (TB) are scarce; therefore, information on the safety, tolerability and efficacy of alternative regimens is of utmost importance. The aim of this study was to describe the management, drug adverse effects and outcome of alternative combined treatment in a series of XDR-TB patients. PATIENTS AND METHODS A retrospective study was performed on 17 non-AIDS, pulmonary adult patients with XDR-TB admitted to a referral treatment centre for infectious diseases in Buenos Aires from 2002 through 2008. Drug susceptibility testing was performed under regular proficiency testing and confirmed at the national TB reference laboratory. RESULTS Linezolid was included in the drug regimens of all patients; moxifloxacin and/or thioridazine were included in the regimens of 14 patients. Clinically tractable drug adverse effects were observed in nine patients, the most frequent being haematological disorders and neurotoxicity. In two patients, thioridazine was discontinued. Negative culture conversion was achieved in 15 patients, 11 completed treatment meeting cure criteria, 4 are still on follow-up with good evolution, 1 defaulted treatment and 1 was lost to follow-up. CONCLUSIONS The combination of linezolid, moxifloxacin and thioridazine is recommended for compassionate use in specialized centres with expertise in the management of XDR-TB.

Outbreaks of mycobacterium tuberculosis MDR strains induce high IL-17 T-cell response in patients with MDR tuberculosis that is closely associated with high antigen load.

BACKGROUND The proinflammatory cytokine interleukin 17 (IL-17) plays an important role in immune responses but it is also associated with tissue-damaging inflammation. So, we evaluated the ability of Mycobacterium tuberculosis clinical isolates to induce IL-17 in tuberculosis (TB) patients and in healthy human tuberculin reactors (PPD(+)HD). METHODS IL-17, interferon γ (IFN-γ), and interleukin 23 (IL-23) receptor expression were evaluated ex vivo and cultured peripheral blood mononuclear cells from TB and PPD(+)HD stimulated with irradiated clinical isolates from multidrug resistant (MDR) outbreaks M (Haarlem family) and Ra (Latin American-Mediterranean family), as well as drug-susceptible isolates belonging to the same families and laboratory strain H37Rv for 48 hours in T-cell subsets by flow cytometry. RESULTS We observed that: (1) MDR strains M and Ra are stronger IL-17 inducers than drug-susceptible Mtb strains of the Haarlem and Latin American-Mediterranean families, (2) MDR-TB patients show the highest IL-17 expression that is independent on the strain, (3) IL-17 expression is dependent on CD4(+) and CD8(+) T cells associates with persistently high antigen load. CONCLUSIONS IL-17--producing T cells could play an immunopathological role in MDR-TB promoting severe tissue damage, which may be associated with the low effectiveness of the second-line drugs employed in the treatment.

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.

HIV Infection and Geographically Bound Transmission of Drug-Resistant Tuberculosis, Argentina

Disease trends are driven by HIV co-infection and transmission of a few strains within narrow geographic niches.

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.

Soft tissue abscess and lymphadenitis due to Mycobacterium avium Complex as an expression of immune reconstitution inflammatory syndrome after a second scheme of highly active antiretroviral therapy

Immune reconstitution inflammatory syndrome (IRIS) is an atypical and unexpected reaction related to highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) infected patients. IRIS includes an atypical response to an opportunistic pathogen (generally Mycobacterium tuberculosis, Mycobacterium avium complex, cytomegalovirus and herpes varicella-zoster), in patients responding to HAART with a reduction of plasma viral load and evidence of immune restoration based on increase of CD4+ T-cell count. We reported a case of a patient with AIDS which, after a first failure of HAART, developed a subcutaneous abscess and supraclavicular lymphadenitis as an expression of IRIS due to Mycobacterium avium complex after starting a second scheme of HAART.

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.