Forty years of Tuberculous meningitis: The new face of an old enemy.

BACKGROUND: Tuberculous meningitis (TBM) occurs in 1-5% of cases of tuberculosis. Without early treatment, mortality and permanent disability rates are high. METHODS: A retrospective study performed at a tertiary hospital in Madrid (Spain) to describe clinical, diagnostic, and therapeutic aspects of TBM and analyze epidemiological trends over forty years, divided into two intervals (1979-1998 and 1999-2018). RESULTS: Overall, TBM was diagnosed in 65 patients (1.8% of new tuberculosis diagnoses), 48 in the first period and 17 in the second one. Median age at diagnosis increased from 38.5 to 77 years (p = 0.003). The proportion of non-HIV immunosuppressed patients increased (from 2.1% to 29.4%, p < 0.001), while the percentage of patients with a history of drug-abuse decreased (from 33.3% to 5.9%, p = 0.027). The median time between the onset of neurological symptoms and lumbar puncture increased from seven to 15 days (p = 0.040). The time between the onset of symptoms and the initiation of tuberculostatic treatment also increased from eleven to 18 days (p = 0.555). Results from image, biochemical, and microbiological tests showed no differences between both periods. A decreasing trend was observed in survival rates at 1-week (from 97.9% to 64.7%, p < 0.001), 1-month (from 91.7% to 58.8%, p = 0.002) and 1-year (from 85.4% to 47.1%, p = 0.002) after TBM diagnosis. CONCLUSIONS: The profile of patients diagnosed with TBM has changed from a young HIV-infected patient with a history of drug addiction to an elderly patient with non-HIV immunosuppression. Diagnosis and start of treatment both experienced a noticeable delay in the second period, which could help explain the increase in mortality observed across the two periods.

Extra-pulmonary tuberculosis: differential aspects and role of 16S-rRNA in urine.

BACKGROUND: Early diagnosis of extra-pulmonary tuberculosis (EPTB) is important for successful treatment. METHODS: All cases of EPTB diagnosed at Ramon y Cajal Hospital, Madrid, Spain, from 1997 to 2008 were analysed and compared with pulmonary tuberculosis (PTB) patients to identify differential parameters that could serve to predict the presence of EPTB at initial presentation. Different microbiological techniques were analysed, including amplification of 16S-rRNA in urine. RESULTS: During the study period, 814 cases of TB were diagnosed at our centre; 330 (40.5%) were EPTB. Concomitant PTB was detected in 45% of EPTB cases. The main clinical forms of EPTB were lymphadenitis (86, 26%), miliary TB (60, 18%), and multifocal TB (43, 13%). Variables independently associated with EPTB were human immunodeficiency virus (HIV) infection (OR 3.6, 95%CI 2.4-5.4), older age (>60 years) (OR 3.7, 95%CI 2.5-5.6) and mortality (OR 2.9, 95%CI 1.3-6.3). 16S-rRNA in urine was performed in 82 EPTB patients (25%), among whom a positive result was obtained in 70%; in the PTB group, a positive result was found in 5 of 28 patients (18%) (P <0.001). CONCLUSIONS: HIV infection and older age appear to be the main risk factors associated with EPTB. In this study, mortality was significantly higher in patients with EPTB. A positive 16S-rRNA test result in urine is a useful marker of EPTB.

Extra-pulmonary tuberculosis: a biomarker analysis.

INTRODUCTION: Studies on biomarkers in tuberculosis are focused on pulmonary forms of this disease (PTB), and only limited information is currently available on biomarkers of extra-pulmonary tuberculosis (EPTB). METHODS: Serum samples from 24 patients with PTB, 29 patients with EPTB and 27 healthy controls were obtained, and the levels of interferon-gamma, chemokine ligand 9, mannose-binding lectin (MBL), tumor marker Ca-125 and adenosine deaminase were determined. RESULTS: The circulating levels of all tested biomarkers in the serum were significantly higher in PTB and EPTB patients than in controls. However, there were no significant differences in the levels of the biomarkers between patients with PTB and EPTB, with the exception of serum levels of MBL which were significantly higher in patients with EPTB than in patients with PTB (p = 0.01). In patients with EPTB, no significant differences were observed in biomarker levels among patients with or without concomitant PTB involvement. Based on MBL serum levels, ROC curve analysis showed an AUC of 0.85 for EPTB versus non-EPTB. The optimal cut-off value of MBL serum levels for EPTB versus non-EPTB was 1,000 µg/ml, with a sensitivity and specificity of 79.3 and 78.0 %, respectively. CONCLUSIONS: Biomarkers usually present as acute phase reactants and do not enable pulmonary forms to be differentiated from more serious or extra-pulmonary forms. MBL may be an exception.

Peliosis hepatis due to disseminated tuberculosis in a patient with AIDS.

Peliosis hepatis is a rare histopathological entity of unknown etiology. We present a case of peliosis hepatis in a 44-year-old man with disseminated tuberculosis and acquired immunodeficiency syndrome. The diagnosis of peliosis hepatis was based on liver biopsy results which were suggestive of tuberculous etiology. Diagnosis of tuberculosis was confirmed by auramine stain, rRNA amplification and culture of Mycobacterium tuberculosis from synovial fluid of the elbow joint. The patient responded favourably to tuberculostatic treatment with four drugs and the early initiation of highly active antiretroviral therapy. Histopathological evidence of peliosis hepatis, without an obvious cause, makes it necessary to rule out tuberculosis, especially in the context of immunodeficiency diseases and immigrants from endemic areas.

Ca-125: a useful marker to distinguish pulmonary tuberculosis from other pulmonary infections.

INTRODUCTION: Ca-125 is secreted by different celomic epitheliums. Serum levels may be increased in malignant diseases, like ovarian cancer but also in other medical conditions, such as pulmonary and extrapulmonary tuberculosis. METHODS: From Jan-04 to Dec-06 a retrospective study analyzing Ca-125 levels in serum samples from patients with a diagnosis of pulmonary TB, was performed. These results were compared with those samples obtained from patients with non-TB pulmonary infections. RESULTS: Eighty-nine patients were included in the study, thirty-five with pulmonary TB and 54 with other respiratory infections. In patients with TB, the mean Ca-125 value was 104.9 IU/ml (SD: +/- 136.1). In the control group, mean value was 27.1 IU/ml (SD: +/-19.7). The optimal cut-off for pulmonary tuberculosis was 32.5 IU/ml (sensitivity: 68.6%, specificity: 77.8%). Pulmonary TB was the only factor associated with a Ca-125 level >32.5. In 10 patients with TB, Ca-125 levels were available >/= 2 months after starting TB therapy and a decrease during treatment was shown. CONCLUSIONS: Ca-125 values increase in patients with pulmonary TB and decline to normal values during treatment. Determination of Ca 125 may be usedin patients with a negative sputum AFB stain.

Transmission permeability of tuberculosis involving immigrants, revealed by a multicentre analysis of clusters.

In recent years, the number of cases of tuberculosis (TB) among immigrants in Spain has increased markedly, and led to this analysis of the recent transmission patterns of TB in the immigrant population in Madrid. The countries from which the highest number of immigrant cases have been reported were Ecuador (21%), Romania (16%), Morocco (12%), Peru (11%) and Bolivia (9%). Fifty-one per cent of the cases were from South America. In a multicentre study (2004-2006), IS6110 restriction fragment length polymorphism and spoligotyping were used to genotype the Mycobacterium tuberculosis isolates from 632 immigrant cases from 47 countries. A total of 183 cases (29%) were grouped into 59 clusters, which are markers of potential transmission events. Most of the clusters (81%) included patients living in different healthcare districts, and 54% of the clusters were multinational. When a sample of 478 autochthonous cases was included, 53% of the clusters involving immigrants also included autochthonous cases. This study revealed marked transmission permeability among nationalities and between the immigrant and the autochthonous populations.

Lesiones cutáneas múltiples pormycobacterium chelonae en huésped inmunocompetente / Multiple cutaneous lesions by mycobacterium chelonae in an immunocompetent host

Mycobacterium chelonae es una micobacteria no tuberculosa (MNTB) de rápido crecimiento, que en el huésped inmunocompetente puede producirlesiones cutáneas localizadas relacionadas con traumatismos.Presentamos dos casos de infección cutánea en hermanas inmunocompetentes quienes desarrollaron lesiones múltiples en muslos y piernas relacionadascon el uso de cera depilatoria. Del cultivo de la lesión se aisló M. chelonae sensible a eritromicina. Se trataron con claritromicina durante 3 mesescon respuesta clínica favorable (AU)

Mycobacterium chelonae is a rapidly growing mycobacterium. In inmunocompetent host cutaneous infection is ussualy isolated, localized and associated with trauma.Two inmunocompetent sisters who consulted because of multiple skin lesion localized in legs and thigs associated to depilation are reported. The cultureof skin lesion showed M. chelonae (AU)

Epidemiology and clinical features of tuberculosis in immigrants at an infectious diseases department in Madrid.

OBJECTIVE: To perform a comparative analysis of tuberculous immigrants and native-born subjects at a tertiary centre in Madrid, Spain, from January 1990 to December 2002. RESULTS: The annual incidence of tuberculosis (TB) decreased from 141 in 1990 to 73 in 2002 despite an increase among immigrants (from 1% in 1990 to 27% in 2002), with 98 cases of TB among 1353 immigrants (overall rate 7.2%). The mean age was 30 years (6-77) and 54% were male. Most patients were from Latin America (55%) and Africa (37%). TB was diagnosed within 2 years of arrival in 69%. When performed, purified protein derivative test was positive in 88%. Human immunodeficiency virus co-infection was present in 6% vs. 37% among the native-born (P < 0.001). Pulmonary TB was the most frequent form in both groups (79% and 80%), with no differences in rates of sputum positivity (70% vs. 75%). Primary drug resistance was significantly higher among immigrants (13% vs. <6% among the native-born, P < 0.05). Initial four-drug regimens were followed by all immigrants. Overall, 82% of the patients were cured, one died due to disseminated disease (1%), and follow-up data were incomplete in 17 (17%). CONCLUSION: TB among immigrants was clinically similar, but was not related to the common risk factors observed in native-born subjects. Given the higher prevalence of primary resistance in this population, initial four-drug regimens should be prescribed until susceptibility results are available.

In vitro activity of linezolid against Mycobacterium tuberculosis complex, including multidrug-resistant Mycobacterium bovis isolates.

The activity of linezolid was studied against 55 Mycobacterium tuberculosis (42 susceptible, 3 isoniazid resistant and 10 isoniazid and rifampicin resistant), one Mycobacterium bovis and two multidrug-resistant M. bovis isolates using the standard 7H10 agar proportion and the ESP Culture System II methods. Both methods displayed similar MIC(90) values (minimum inhibitory concentrations for 90% of the organisms) of 0.5mg/L; however, the former method yielded slightly lower MIC(50) values (MICs for 50% of the organisms) (0.25mg/L) compared with the latter method (0.5mg/L). No differences were observed between susceptible and resistant isolates, including multidrug-resistant M. bovis isolates, with a MIC range of 0.12-0.5mg/L. The potential role of linezolid in tuberculosis patients requires further in vivo evaluation.

[Infection for papillomavirus in the man. Current state]. / Infección por papillomavirus en el hombre. Estado actual.

The Virus of the Human Papiloma (HPV), classically he/she has been related with infections of sexual transmission and processes wicked oncologists of the feminine genital apparatus and with less frequency of the masculine one. The new technical diagnostics, based on molecular biology (by means of polymerase chain reaction), they help to a better epidemic approach, an improvement in the I diagnose viral, and a correct therapeutic focus. The object of this work is to revise the current state of the HPV from the points of view etiopathogenics, epidemic, clinical, diagnosis, therapeutic and preservative.

Infección por Papillomavirus en el hombre. Estado actual / Infection for papillomavirus in the man. Current state

El Virus del Papiloma Humano (VPH), clásicamente se ha relacionado con infecciones de transmisión sexual y procesos oncológicos malignos del aparato genital femenino y con menos frecuencia del masculino. Las nuevas técnicas diagnósticas, basadas en biología molecular (mediante reacción en cadena de la polimerasa), ayudan a una mejor aproximación epidemiológica, una mejora en el diagnostico viral, y un correcto enfoque terapéutico. El objeto de este trabajo es revisar el estado actual del VPH desde los puntos de vista etiopatogénico, epidemiológico, clínico, diagnóstico, terapéutico y profiláctico (AU)

The Virus of the Human Papiloma (HPV), classically he/she has been related with infections of sexual transmission and processes wicked oncologists of the feminine genital apparatus and with less frequency of the masculine one. The new technical diagnostics, based on molecular biology (by means of polymerase chain reaction), they help to a better epidemic approach, an improvement in the diagnose viral, and a correct therapeutic focus. The object of this work is to revise the current state of the VPH from the points of view etiopatogenics, epidemic, clinical, diagnosis, therapeutic and preservative (AU)

Nocardial infection in patients infected with the human immunodeficiency virus.

During the period 1981-2000, we diagnosed eight cases of HIV-Nocardia co-infection (0.38% of AIDS cases). Six were males, and the mean age was 28.6 years. The most common risk factor for HIV infection was intravenous drug abuse. Most patients were severely immunodepressed at the time of diagnosis (mean CD4+ count, 35 cells/ micro L). The clinical forms of nocardiosis seen were pulmonary infection in three, skin or soft tissue infection in three, disseminated in one, and pulmonary colonization in one. Most patients were given sulfonamides, and a clinical response was observed in six of seven treated patients. However, two patients with pulmonary disease died from progressive infection. Although its incidence is very low among AIDS patients, nocardiosis is associated with high morbidity and mortality among HIV-infected individuals.

Infection with Nocardia species: clinical spectrum of disease and species distribution in Madrid, Spain, 1978-2001.

BACKGROUND: Clinical experience with nocardiosis is very limited in European countries. We describe 34 cases of nocardial infection seen at one Spanish teaching hospital. PATIENTS AND METHODS: A retrospective review of the clinical features and outcome of nocardial infections was conducted during a 24-year period (1978-2001). All cases were confirmed by culture. RESULTS: Predisposing factors included immunosuppression and/or pulmonary disease in 85% of patients; eight cases were related to HIV infection. Most isolates were initially identified as Nocardia asteroides complex (97%). The most common clinical form was pulmonary disease (41%), followed by disseminated (15%), cutaneous (12%), cerebral (9%) and articular disease (3%). A high proportion of patients (20%) had pulmonary colonization. Therapy with sulfonamides, imipenem or amikacin was given to 26 patients and a clinical response was observed in 65%. Overall mortality among patients with nocardial disease was 48% (13/27) but only seven patients (26%) died from nocardiosis. CONCLUSION: Nocardiosis remains a rare opportunistic infection that appears in immunosuppressed patients. HIV infection has become a common predisposing condition. The species distribution and disease spectrum are similar to those described in other European countries. Although most patients develop active disease, pulmonary colonization might not be as rare as has generally been assumed. Treatment with sulfonamides is usually effective and many patients may remain free of nocardial disease for a prolonged period.

Laboratorio de Microbiología y tuberculosis / The microbiology laboratory and tuberculosis

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Tuberculosis pulmonar en un paciente con fibrosis quística / Pulmonary tuberculosis in a patient cystic fibrosis

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Risk factors for nosocomial transmission of multidrug-resistant tuberculosis due to Mycobacterium bovis among HIV-infected patients.

OBJECTIVE: To identify risk factors for transmission of multidrug-resistant tuberculosis (MDR-TB) among hospitalized human immunodeficiency virus (HIV) infected patients exposed during a nosocomial outbreak. DESIGN: Case control study. Cases were HIV-infected patients with MDR-TB due to Mycobacterium bovis (MDR-TBMb) who acquired the disease after exposure to an MDR-TBMb patient in an hospital ward. Controls were HIV-infected patients exposed to a case of MDR-TBMb in an hospital ward but who did not develop MDR-TBMb during the follow-up. RESULTS: Nineteen cases and 31 controls were included. CD4 cell counts were significantly lower among cases. Exposure in the infectious diseases ward or exposure to the index patient were associated with development of MDR-TBMb, while exposure during a single-room hospital stay and exposure in the respiratory isolation ward were associated with non-development of MDR-TBMb. A multiple regression logistic model showed that only a CD4 cell count below 50/microL and exposure to the index patient increased the risk of developing MDR-TBMb (P < 0.05). Hospitalization in a single room seemed to protect HIV-infected patients from developing nosocomial MDR-TBMb (P = 0.052). CONCLUSIONS: Over classic risk factors, such as length of exposure or sharing a room with a case, severe immunosuppression independently increases the risk of MDR-TB transmission in the context of a nosocomial MDR-TB outbreak among HIV-infected patients. This information must be considered in the management of tuberculosis outbreaks. Patients with CD4 cell counts below 50/microL should be the principal group targeted for prevention strategies in nosocomial outbreaks.

Nontuberculous mycobacteria in patients with cystic fibrosis.

The prevalence and clinical implications of colonization with nontuberculous mycobacteria were prospectively studied in 37 patients who had cystic fibrosis. Sputum samples were cultured on Coletsos and Löwenstein-Jensen selective media after decontamination with sodium hydroxide and oxalic acid. Oxalic acid-decontaminated fractions were also cultured in selective liquid medium. Nontuberculous mycobacteria were isolated from 6 patients (16.1%). Mycobacterium chelonae and Mycobacterium avium-intracellulare complex were the most common species. Three patients with positive results of culture had at least 1 positive result by acid-fast smear. Oxalic acid decontamination and culture in liquid medium had the lowest contamination rate (6.7%). Colonization with nontuberculous mycobacteria was associated with humoral response to mycobacteria (immunoglobulin G titers against antigen A60) in patients with samples that tested positive by acid-fast smear. An improvement in pulmonary function was observed in 2 patients after they received a course of antimycobacterial therapy. Screening for nontuberculous mycobacteria in patients with cystic fibrosis will contribute to understanding the relevance of these pathogens with regard to deterioration of pulmonary function in patients with cystic fibrosis.

Mycobacterium kansasii pericarditis as a presentation of AIDS.

Mycobacterium kansasii infection is a recognized complication of AIDS and a broad spectrum of extrapulmonary manifestations has been reported. However, AIDS-related M. kansasii pericarditis is an extremely rare disease. We report the first European case of this infection, that presented some different clinical findings to those previously described in HIV-infected individuals. M. kansasii pericarditis was the first AIDS-defining illness presented by the patient. The stained smears of pericardial fluid were negative for acid-fast bacilli and an increased level of adenosine deaminase was observed in pericardial fluid. A short course of prednisone therapy was added to antituberculous treatment, with a good clinical response.