Th22 response induced by Mycobacterium tuberculosis strains is closely related to severity of pulmonary lesions and bacillary load in patients with multi-drug-resistant tuberculosis.

The role of interleukin-22 (IL-22) in the pathogenesis or tissue repair in human tuberculosis (TB) remains to be established. Here, we aimed to explore the ex-vivo and in-vitro T helper 22 (Th22) response in TB patients and healthy donors (HD) induced by different local multi-drug-resistant (MDR) Mvcobacterium tuberculosis (Mtb) strains. For this purpose, peripheral blood mononuclear cells from drug-susceptible (S-TB) MDR-TB patients and HD were stimulated with local MDR strains and the laboratory strain H37Rv. IL-22 and IL-17 expression and senescent status were assessed in CD4+ and CD8+ cells by flow cytometry, while IL-22 amount was measured in plasma and culture supernatants by enzyme-linked immunosorbent assay (ELISA). We found lower IL-22 amounts in plasma from TB patients than HD, together with a decrease in the number of circulating T cells expressing IL-22. In a similar manner, all Mtb strains enhanced IL-22 secretion and expanded IL-22+ cells within CD4+ and CD8+ subsets, being the highest levels detected in S-TB patients. In MDR-TB, low systemic and Mtb-induced Th22 responses associated with high sputum bacillary load and bilateralism of lung lesions, suggesting that Th22 response could be influencing the ability of MDR-TB patients to control bacillary growth and tissue damage. In addition, in MDR-TB patients we observed that the higher the percentage of IL-22+ cells, the lower the proportion of programmed cell death 1 (PD-1)+ or CD57+ T cells. Furthermore, the highest proportion of senescent T cells was associated with severe lung lesions and bacillary load. Thus, T cell senescence would markedly influence Th22 response mounted by MDR-TB patients.

The IL-17A rs2275913 single nucleotide polymorphism is associated with protection to tuberculosis but related to higher disease severity in Argentina.

Mycobacterium tuberculosis (Mtb) causes nearly 10 millions of new tuberculosis disease cases annually. However, most individuals exposed to Mtb do not develop tuberculosis, suggesting the influence of a human genetic component. Here, we investigated the association of the rs2275913 SNP (G → A) from IL-17A and tuberculosis in Argentina by a case-control study. Furthermore, we evaluated in vitro the functional relevance of this SNP during the immune response of the host against Mtb and analyzed its impact on clinical parameters of the disease. We found an association between the AA genotype and tuberculosis resistance. Additionally, within the healthy donors population, AA cells stimulated with a Mtb lysate (Mtb-Ag) produced the highest amounts of IL-17A and IFN-γ, which further support the genetic evidence found. In contrast, within the tuberculosis patients population, AA Mtb-Ag stimulated cells showed the lowest immunological parameters and we evidenced an association between the AA genotype and clinical parameters of disease severity, such as severe radiological lesions and higher bacilli burden in sputum. Overall, our findings demonstrated that the AA genotype from the IL-17A rs2275913 SNP is positively associated with protection to active tuberculosis but related to higher disease severity in the Argentinean population.

Mastitis por Mycobacterium fortuitum en una paciente HIV negativa / Mastitis due to Mycobacterium fortuitum in an HIV negative patient

A case of a 39 year old HIV negative female patient with a Mycobacterium fortuitum mastitis without previous pathogenic history is reported. She was treated on the bases of drug-susceptibility testing and bibliographic empirical evidence with kanamycin, doxicicline, ciprofloxacin and trimetoprim-sulfametoxazol. A complete remission of her lesions was obtained after 15 months of treatment. Lesions due to this rapidly growing mycobacterium, diagnosis and treatment are commented.

Se presenta el caso de una paciente HIV negativa de 39 años con una mastitis por Mycobacterium fortuitum, sin antecedentes patogénicos previos. Fue tratada en base a las pruebas de susceptibilidad a antibióticos y quimioterápicos y a la evidencia empírica citada por la bibliografía, con kanamicina, doxiciclina, ciprofloxacina y trimetoprima-sulfametoxazol. Se obtuvo la remisión completa de sus lesiones luego de 15 meses de tratamiento. Se comenta la capacidad de producir lesiones de esta micobacteria de crecimiento rápido, su diagnóstico y tratamiento

Tratamiento antirretroviral en pacientes con sida y micobacteriosis / Anti-retroviral treatment in patients with AIDS and mycobacterial diseases

La tuberculosis y otras micobacteriosis constituyen asociaciones o coinfecciones frecuentes en pacientes con sida y se asocian con una elevada mortalidad. En esta revisión se actualizan los tratamientos de las principales enfermedades micobacterianas asociadas al sida (tuberculosis y micobacteriosis por Mycobacterium avium), con especial énfasis en las interacciones farmacológicas entre antimicobacterianos, principalmente rifampicina y claritromicina, y fármacos antirretrovirales. Se analizan los esquemas de tratamiento, su duración, la quimioprofilaxis primaria y secundaria y el momento óptimo de iniciación del tratamiento antirretroviral. Finalmente se describe el síndrome inflamatorio de reconstitución inmune y su tratamiento.

Tratamiento antirretroviral en pacientes con sida y micobacteriosis / Anti-retroviral treatment in patients with AIDS and mycobacterial diseases

La tuberculosis y otras micobacteriosis constituyen asociaciones o coinfecciones frecuentes en pacientes con sida y se asocian con una elevada mortalidad. En esta revisión se actualizan los tratamientos de las principales enfermedades micobacterianas asociadas al sida (tuberculosis y micobacteriosis por Mycobacterium avium), con especial énfasis en las interacciones farmacológicas entre antimicobacterianos, principalmente rifampicina y claritromicina, y fármacos antirretrovirales. Se analizan los esquemas de tratamiento, su duración, la quimioprofilaxis primaria y secundaria y el momento óptimo de iniciación del tratamiento antirretroviral. Finalmente se describe el síndrome inflamatorio de reconstitución inmune y su tratamiento. (AU)

Treatment and follow-up of HIV-negative multidrug-resistant tuberculosis patients in an infectious diseases reference hospital, Buenos Aires, Argentina.

SETTING: An Argentinean reference hospital specialising in infectious diseases. OBJECTIVE: To assess the outcomes of all human immunodeficiency virus (HIV) negative multidrug-resistant tuberculosis (MDR-TB) patients referred to or diagnosed at Hospital Muñiz. DESIGN: Clinical study for the period 1996-1999, with follow-up until June 2002. RESULTS: One hundred and forty-one adult patients (52.5% female) with resistance to two to seven drugs were studied. Fifty patients (35.5%) had not been treated previously. The most frequently used second-line drugs were 5-F-quinolones, cycloserine and ethionamide in susceptibility based individually tailored three- to five-drug regimens. Hospital admission was associated with treatment success. Forty-five episodes of severe toxicity occurred. Treatment was successful in 51.8% of cases, but follow-up of 73 patients yielded 11.9% relapse. The mortality rate was 19.1% and default was 19.9%. Logistic regression analysis was statistically significant for treatment success in relation to patient admission, residence and resistance pattern. CONCLUSION: The burden of MDR-TB in this setting--prolonged infection, treatment cost and difficulties, low rates of cure and treatment adherence and high rates of fatality and relapse--can be improved by strengthening TB control programme activities and fighting against poverty and HIV/AIDS.

Mastitis por Mycobacterium fortuitum en una paciente HIV negativa / Mastitis due to Mycobacterium fortuitum in an HIV negative patient

A case of a 39 year old HIV negative female patient with a Mycobacterium fortuitum mastitis without previous pathogenic history is reported. She was treated on the bases of drug-susceptibility testing and bibliographic empirical evidence with kanamycin, doxicicline, ciprofloxacin and trimetoprim-sulfametoxazol. A complete remission of her lesions was obtained after 15 months of treatment. Lesions due to this rapidly growing mycobacterium, diagnosis and treatment are commented.(AU)

Se presenta el caso de una paciente HIV negativa de 39 años con una mastitis por Mycobacterium fortuitum, sin antecedentes patogénicos previos. Fue tratada en base a las pruebas de susceptibilidad a antibióticos y quimioterápicos y a la evidencia empírica citada por la bibliografía, con kanamicina, doxiciclina, ciprofloxacina y trimetoprima-sulfametoxazol. Se obtuvo la remisión completa de sus lesiones luego de 15 meses de tratamiento. Se comenta la capacidad de producir lesiones de esta micobacteria de crecimiento rápido, su diagnóstico y tratamiento(AU)

[Improved prognosis in HIV/AIDS related multi-drug resistant tuberculosis patients treated with highly active antiretroviral therapy]. / Mejoria pronóstica de pacientes con tuberculosis multirresistente asociada a enfermedad por HIV/SIDA tratados con terapia antirretroviral de alta eficacia.

A prospective cohort study was carried out in patients assisted in the F. J. Muñiz Infectious Disease Hospital, with the aim of determining the effectiveness of highly active antiretroviral therapy (HAART) implemented as soon as the sputum smear microscopy became negative (1 to 3 months) in the survival improvement of HIV/AIDS related multidrug-resistant tuberculosis patients. The cohort was recruited from June 1997 to February 1999 and compared with a pre-HAART control group that consisted of 43 patients. The follow-up of the patients was terminated June 2000. A total of 48 patients who received HAART precociously were included. The mortality rate in this group was 31.2% and the survival time of deceased patients 15.8 +/- 8.5 months. The T lymphocytes CD4+ count was initially 40.1 +/- 30.2/microL, while at the end of the observation period it was 140.4 +/- 73.04/microL and 79.1% of these patients presented undetectable viral load. In the control group the overall mortality was 90.7% and the survival time of deceased patients 8.95 +/- 3.72 months. We conclude that the early anti-retroviral therapy, together with the treatment of the multidrug-resistant tuberculosis and of other AIDS associated diseases represent a useful approach to achieve a longer and better survival in these severely immunodepressed patients.

Mejoria pronóstica de pacientes con tuberculosis multirresistente asociada a enfermedad por HIV/SIDA tratados con terapia antirretroviral de alta eficacia. / [Improved prognosis in HIV/AIDS related multi-drug resistant tuberculosis patients treated with highly active antiretroviral therapy]

A prospective cohort study was carried out in patients assisted in the F. J. Muñiz Infectious Disease Hospital, with the aim of determining the effectiveness of highly active antiretroviral therapy (HAART) implemented as soon as the sputum smear microscopy became negative (1 to 3 months) in the survival improvement of HIV/AIDS related multidrug-resistant tuberculosis patients. The cohort was recruited from June 1997 to February 1999 and compared with a pre-HAART control group that consisted of 43 patients. The follow-up of the patients was terminated June 2000. A total of 48 patients who received HAART precociously were included. The mortality rate in this group was 31.2

and the survival time of deceased patients 15.8 +/- 8.5 months. The T lymphocytes CD4+ count was initially 40.1 +/- 30.2/microL, while at the end of the observation period it was 140.4 +/- 73.04/microL and 79.1

of these patients presented undetectable viral load. In the control group the overall mortality was 90.7

and the survival time of deceased patients 8.95 +/- 3.72 months. We conclude that the early anti-retroviral therapy, together with the treatment of the multidrug-resistant tuberculosis and of other AIDS associated diseases represent a useful approach to achieve a longer and better survival in these severely immunodepressed patients.

[Coxitis due to multidrug resistant Mycobacterium tuberculosis in a HIV negative patient]. / Coxitis por Mycobacterium tuberculosis multirresistente en un paciente HIV negativo.

A case of an HIV negative female patient with coxofemoral arthritis of tuberculous etiology, multidrug-resistant strain, and connective tissue disease associated to glucocorticoid therapy is reported. The patient was treated with cycloserine, ethambutol, p-aminosalicylic acid and ofloxacin, with improvement of the joint lesions. Previous publications on this subject are reviewed.

Coxitis por Mycobacterium tuberculosis multirresistente en un paciente HIV negativo. / [Coxitis due to multidrug resistant Mycobacterium tuberculosis in a HIV negative patient]

A case of an HIV negative female patient with coxofemoral arthritis of tuberculous etiology, multidrug-resistant strain, and connective tissue disease associated to glucocorticoid therapy is reported. The patient was treated with cycloserine, ethambutol, p-aminosalicylic acid and ofloxacin, with improvement of the joint lesions. Previous publications on this subject are reviewed.

Estudio prospectivo de pacientes tuberculosos pulmonares tratados en la Liga Argentina contra la Tuberculosis durante el quinquenio 1975-1979. / Prospective study of patients with pulmonary tuberculosis treated at the Union Argentina against Tuberculosis in 1975-1979

Se controle el estado de salud de 379 pacientes TBC pulmonares tratados en LALAT durante el quinquenio 1975-1979, a traves de citaciones y concurrencia espontanea.Se observaron 15 reinfecciones la mayoria sin haber utilizado RMP en su primer tratamiento. Es destacada la importancia del estudio bacteriologico de sintomaticos respiratorios ex-TBC, con alta proporcion de casos positivos

Comparacion de la reaccion intradermica de Mantoux efectuada con dos diferentes productos biologicos. / Comparison of Mantoux intradermal reaction using 2 different biological products

Se efectuo la lectura comparativa de las intradermorreacciones de Mantoux efectuadas con dos tuberculinas de distinto origen: PPD RT 23 provista por el Statens Serum Institut de Copenhagen, fraccionada y distribuida por el Instituto Malbran (Prueba tuberculinica estandar de las OMS) y el PPD que distribuye un laboratorio de plaza, de origen frances. Se testificaron 258 sujetos, contactos de pacientes tuberculosos atendidos en el Dispensario de Adultos de la Liga Argentina contra la Tuberculosis aplicandose simultaneamente ambas tuberculinas, una en cada antebrazo.Efectuado el analisis estadistico comparativo entre las lecturas efectuadas a doble ciego de ambas testificaciones, se arribo a la conclusion de que no existen diferencias significativas entre las respuestas cutaneas a ambos PPD

Estudio prospectivo de pacientes tuberculosos pulmonares tratados en la Liga Argentina contra la Tuberculosis durante el quinquenio 1975-1979. / Prospective study of patients with pulmonary tuberculosis treated at the Union Argentina against Tuberculosis in 1975-1979

Se controle el estado de salud de 379 pacientes TBC pulmonares tratados en LALAT durante el quinquenio 1975-1979, a traves de citaciones y concurrencia espontanea.Se observaron 15 reinfecciones la mayoria sin haber utilizado RMP en su primer tratamiento. Es destacada la importancia del estudio bacteriologico de sintomaticos respiratorios ex-TBC, con alta proporcion de casos positivos

Comparacion de la reaccion intradermica de Mantoux efectuada con dos diferentes productos biologicos. / Comparison of Mantoux intradermal reaction using 2 different biological products

Se efectuo la lectura comparativa de las intradermorreacciones de Mantoux efectuadas con dos tuberculinas de distinto origen: PPD RT 23 provista por el Statens Serum Institut de Copenhagen, fraccionada y distribuida por el Instituto Malbran (Prueba tuberculinica estandar de las OMS) y el PPD que distribuye un laboratorio de plaza, de origen frances. Se testificaron 258 sujetos, contactos de pacientes tuberculosos atendidos en el Dispensario de Adultos de la Liga Argentina contra la Tuberculosis aplicandose simultaneamente ambas tuberculinas, una en cada antebrazo.Efectuado el analisis estadistico comparativo entre las lecturas efectuadas a doble ciego de ambas testificaciones, se arribo a la conclusion de que no existen diferencias significativas entre las respuestas cutaneas a ambos PPD