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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.

Important epidemiological changes and improvement of new diagnostic approaches, mainly molecular tools, might have impacted the management and outcome of tuberculosis (TB) in the last years in industrialized countries. In order to describe the epidemiological trends, and changes in clinical, diagnostic, and therapeutic aspects in patients with TB, an observational study was performed in a tertiary hospital in Western Europe (Madrid, Spain). All adult patients (>16 years) with a diagnosis of TB in the period 1995 to 2013 were included in the study. TB was diagnosed in 1284 patients, including 304 (24%) foreign-born and 298 (23.2%) human immunodeficiency virus (HIV)-infected patients. The proportion of foreign-born patients increased significantly, from 7.4% (1995) to 40.3% (2013), P

Introduccion La epidemiologia de los pacientes con tuberculosis ha cambiado en los hospitales europeos en los ultimos anos. Metodos Presentamos un estudio prospectivo en pacientes hospitalizados en nuestra institucion con tuberculosis confirmada por cultivo entre los anos 1997 y 2008. Resultados Se analizaron 661 pacientes con tuberculosis pulmonar. Durante el periodo de estudio se confirmo un incremento de la incidencia (p < 0,001). El porcentaje de pacientes con infeccion por VIH disminuyo desde el 26% en los anos 1997-2000 al 12% en los anos 2005-2008. Sin embargo, la proporcion de pacientes mayores de 40 anos e inmigrantes se incremento de forma significativa, desde el 37 al 59% y desde el 12 al 35% respectivamente. El analisis multivariante confirmo el tratamiento antituberculoso previo y la inmigracion como factores asociados a resistencia a isoniazida y a isoniazida-rifampicina. Despues del ano 2000 la mortalidad se asocio de forma independiente con la presencia de tuberculosis extrapulmonar (OR: 3,1; IC 95%: 1,4-7,2), infeccion por virus de la hepatitis C (OR: 6,0; IC 95%: 2,2-16,3), y diabetes (OR: 6,4; IC 95%: 2,4-16,8). Conclusion La inmigracion desde paises con elevadas incidencias de tuberculosis ha reemplazado a la infeccion por VIH como factor de riesgo de tuberculosis en nuestros pacientes. En los ultimos anos, el incremento de la edad y la presencia de otros factores de comorbilidad, especialmente hepatopatia cronica, pueden justificar una mayor morbi-mortalidad en estos pacientes

The training program of residents in microbiology and parasitology in Spain includes clinical skills, ranging from the diagnostic approach to the patient and adequate sample collection for diagnosis of infectious diseases to antimicrobial therapy and infection control measures. Training also includes new challenges in clinical microbiology that ensure residents' participation in infection control programs of health-care associated infections, training in the resolution of public health problems, and application of new molecular microbiology methods. Specialization in clinical microbiology may be undertaken by graduates in Medicine, Biology, Biochemistry and Chemistry. The training is performed in accredited microbiology laboratories at different hospitals (n = 61) across the country through 4-year residency programs. In the last few years, there has been a major imbalance between the number of intended residents (0.17 per 100,000 inhabitants) and those graduating as specialists in clinical microbiology (0.13 per 100,000 inhabitants), with wide variations across the country. The current tendency in Europe is to strengthen the role of clinical microbiologists as key figures in the diagnosis of infectious diseases and in public health microbiology. Training programs have been hampered by the practice of sending samples for microbiological tests to external, centralized multipurpose laboratories with few clinical microbiologists and without a core curriculum. Essential elements in the training of specialists in clinical microbiology are a close relationship between the laboratory and the clinical center and collaboration with other specialists.

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.

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), IS 6110 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.

PCR-based characterization techniques have been adopted in most laboratories for Mycobacterium bovis typing. We report a molecular characterization of human multidrug-resistant M. bovis isolates and three bovine isolates that share the spoligotyping profile. The analysis of the direct repeat region showed that both groups differed in the presence of spacers not included in the current membrane. They were also distinguished by two out of the nine mycobacterial interspersed repetitive unit variable-number tandem repeat loci tested, indicating that the human infection was not acquired from the cattle from which isolates were obtained. These results highlight that a combination of techniques is required for appropriate discrimination, even for those spoligotypes that have a low frequency.

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

The aim of this prospective study was to compare a model based on clinical variables with the clinical judgment of infectious disease specialists to identify HIV-infected patients requiring isolation at admission in order to prevent the nosocomial transmission of tuberculosis. Clinical, epidemiological and radiological variables available at admission were recorded for 362 admissions of 274 HIV-infected patients. Using multiple logistic regression analysis, a model to identify patients with tuberculosis was developed based on four clinical variables (node enlargement, constitutional symptoms, intravenous drug use, history of previous correct therapy for tuberculosis) and a positive auramine sputum stain. This model was applied to each of the 362 admissions studied. The decision made by the infectious disease specialist at admission was also recorded. The results indicate that application of the model would have allowed physicians to correctly identify and isolate 24 of 27 patients with tuberculosis, while 5.4 patients without tuberculosis would have been unnecessarily isolated for every patient with tuberculosis. The results for the infectious disease specialists were slightly better, with 26 of 27 patients with tuberculosis being identified and isolated correctly and only 3.2 patients being isolated unnecessarily for every patient with tuberculosis. Thus, a simple model based on clinical variables may be useful in helping physicians identify tuberculosis carriers among HIV-infected patients, but infectious disease specialists are able to identify them more efficiently.

Isolates from the Mycobacterium tuberculosis complex cultured from caprine pathological tissue samples were biochemically and genetically characterized. The isolates were negative for nitrate reduction and niacin accumulation, they weakly hydrolysed Tween 80, were sensitive to pyrazinamide (50 micrograms ml-1) and were resistant to 1 and 2 micrograms tiophene-2-carboxylic acid hydrazide ml-1 but not to 5 or 10 micrograms tiophene-2-carboxylic acid hydrazide ml-1. Sequencing of the pncA gene revealed a polymorphism characteristic of M. tuberculosis, whereas oxyR, katG and gyrA sequences were characteristic of Mycobacterium bovis. The fingerprinting patterns obtained with IS6110, direct repeats and polymorphic G+C-rich sequence-associated RFLP and direct variable repeat-spacer oligonucelotide typing (spoligotyping) segregated these isolates from the other members of the complex. The results of this testing, together with the repeated association of this micro-organism with goats, suggest that a new member of this taxonomic complex not matching any of the classical species had been identified. This unusual mycobacterium may play a role in the epidemiology of animal and human tuberculosis in Spain. The name Mycobacterium tuberculosis subsp. caprae subsp. nov. is proposed for these isolates. The type strain of Mycobacterium tuberculosis subsp. caprae subsp. nov. is gM-1T (= CIP 105776T).

An allele-specific amplification method based on two genetic polymorphisms to differentiate Mycobacterium tuberculosis from Mycobacterium bovis was tested. Based on the differences found at position 169 in the pncA genes from M. tuberculosis and M. bovis , a PCR system which was able to differentiate most of the 237 M. tuberculosis complex isolates tested in one of the two species was developed. All 121 M. tuberculosis strains showed the expected base (cytosine) at position 169. Most of the M. bovis isolates had a guanine at the cited position. Nevertheless, 18 of the 116 M. bovis isolates, all of them goat isolates, showed the pncA polymorphism specific to M. tuberculosis . These results suggest that goat M. bovis may be the nicotinamidase-missing link at the origin of the M. tuberculosis species. Based on the polymorphism found at position 285 in the oxyR gene, the same system was used to differentiate M. tuberculosis from M. bovis . In this case, DNAs from all 121 M. tuberculosis isolates had the expected base (guanine) at this position. In addition, all 116 M. bovis isolates, including those from goats, showed the identical polymorphism (adenine). The oxyR allele-specific amplification method can differentiate M. bovis from M. tuberculosis , is rapid (results can be obtained in less than 3 h), and is easy to perform.

Since 1990, several nosocomial outbreaks of multidrug-resistant (MDR) tuberculosis have occurred, none of which have involved Mycobacterium bovis. We describe an epidemic of nosocomial and primary MDR M bovis tuberculosis from December, 1993, to February, 1995, among HIV-1-infected patients in a district of Madrid.We undertook genetic characterisation of the M bovis strain and investigated its presence in a tuberculosis epidemic in a Madrid hospital in a case-controlled study. We assessed 19 cases diagnosed with MDR tuberculosis due to M bovis during the study period. For the control group, we randomly selected 33 patients with HIV-1 infection and isolation of a strain of M tuberculosis susceptible to isoniazid, rifampicin, or both, who were treated in Ramón y Cajal Hospital. Infection-control policies and practices were implemented.We detected 19 cases in HIV-1-infected patients of primary MDR tuberculosis produced by M bovis resistant to 11 antituberculosis drugs. We found phenotypic and genotypic similarities in the strains of M bovis. In the case group, the index case and two other cases had had previous contact with another hospital that had had an MDR tuberculosis outbreak. All patients died after a mean of 44 days (range 2-116), despite multidrug treatment with first-line and second-line antituberculosis drugs. The cases with M bovis MDR tuberculosis were significantly more likely than controls to have been admitted to a hospital ward at the same time as patients already infected with MDR tuberculosis during the 10 months before their diagnosis (adjusted odds ratio 94.6 [95% CI 9.4-956.3], p0.0001). Advanced HIV-1 immunosuppression was associated with the development of MDR tuberculosis. Implementation of control measures stopped the epidemic.An M bovis primary MDR tuberculosis epidemic that cannot be treated effectively and with high mortality has emerged in Europe and has been transmitted between hospitals.

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).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.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.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.

Tuberculosis characteristics and incidence were assessed among patients with concurrent human immunodeficiency virus infection and chronic hepatitis C virus infection who were receiving interferon-based therapy at 3 hospitals in Spain. Four of 570 patients (0.7 cases per 100 person-years; 95% confidence interval, 0.19–1.78 cases per 100 person-years) received a diagnosis of tuberculosis; all of them presented with a decrease in CD4 + cell count before diagnosis, and 3 of them received a delayed diagnosis. After tuberculosis treatment, all patients were cured.

Isolation of Mycobacterium avium complex (MAC) organisms from clinical samples may occur in patients without clinical disease, making the interpretation of results difficult. The clinical relevance of MAC isolates from different types of clinical samples ( n = 47) from 39 patients in different sections of a hospital was assessed by comparison with environmental isolates ( n = 17) from the hospital. Various methods for identification and typing (commercial probes, phenotypic characteristics, PCR for detection of IS 1245 and IS 901 , sequencing of the hsp65 gene, and pulsed-field gel electrophoresis) were evaluated. The same strain was found in all the environmental isolates, 21 out of 23 (91.3%) of the isolates cultured from urine samples, and 5 out of 19 (26.3%) isolates from respiratory specimens. This strain did not cause disease in the patients. Testing best characterized the strain as M. avium subsp. hominissuis , with the unusual feature that 81.4% of these isolates lacked the IS 1245 element. Contamination of certain clinical samples with an environmental strain was the most likely event; therefore, characterization of the environmental mycobacteria present in health care facilities should be performed to discard false-positive isolations in nonsterile samples, mainly urine samples. Molecular techniques applied in this study demonstrated their usefulness for this purpose.

Mycobacterium bovis is the etiological agent of tuberculosis in domestic and wild animals. Its involvement as a human pathogen has been highlighted again with the recent descriptions of transmission through dairy products (18), reactivation or primary infection in human immunodeficiency virus-infected patients (5), and association with meat industry workers, animal keepers, or hunters (3). Strains resistant to antituberculous drugs (M. bovis is naturally resistant to pyrazinamide) pose an additional risk (2). Several studies have demonstrated that mutations in target genes are associated with resistance to antituberculous drugs (4, 7, 10, 11, 16). However, most of them have been developed in Mycobacterium tuberculosis strains and limited data are available regarding M. bovis isolates. The aim of this study was to characterize by sequencing the main genes involved in antibiotic resistance in two multidrug-resistant (MDR) M. bovis isolates in a human outbreak detected in a hospital in Madrid that subsequently spread to several countries (5, 6, 15). The isolates were resistant to 11 drugs, but only their rpoB and katG genes have been analyzed so far (1, 14). We studied the first (93/R1) and last (95/R4) M. bovis isolates of this nosocomial outbreak, characterized by spoligotyping as SB0426 (hexacode 63-5F-5E-7F-FF-60 in the database at www.mbovis.org) (1, 13). Several genes involved in resistance to isoniazid (katG, ahpC, inhA, and the oxyR-ahpC intergenic region), rifampin (rpoB), streptomycin (rrs, rpsL), ethambutol (embB), and quinolones (gyrA) were studied. These genes, or fragments of genes, were amplified and sequenced as previously described (12). The sequence analysis revealed polymorphisms in five (ahpC, rpoB, rpsL, embB, and gyrA) out of nine analyzed genes (Table 1). Nucleotide substitutions in four genes cause a change in the encoded amino acid. Two additional synonymous mutations in ahpC and rpsL differentiated the first and last isolates from the outbreak.

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.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 (P0.001). 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, P0.05). 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%).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.

Mycobacterium bovis and Mycobacterium caprae are zoonotic bacteria that cause tuberculosis with several clinical manifestations. We have evaluated the susceptibility to anti-tuberculosis drugs of a panel of Spanish isolates of animal origin. The analysis of the sequence of the main genes involved in resistance was performed in 41 M. bovis and five M. caprae. The katG, inhA, rpsL, embB and gyrA genes had single nucleotide polymorphisms, not previously described in other organisms of the complex. Thirty-two M. bovis and three M. caprae isolates were tested for susceptibility to isoniazid (INH), rifampin, streptomycin, ethambutol, and ofloxacin using the standard proportion method. The results revealed that the isolates were sensitive to the five drugs. However, interference caused by sodium pyruvate in the INH test was detected: 94.3% grew at 0.2 microg INH/ml and 68.6% grew at 1 microg INH/ml. In the medium without pyruvate, 34.3% of the isolates did not grow whereas growth of the others was poor and slow. Nine M. bovis isolates were also tested by ESP Culture System II test and were sensitive to INH. The susceptibility of M. bovis to INH cannot be reliably determined using the standard proportion method due to the M. bovis growth requirements and the interference of pyruvate with INH.

Limited data are available to predict the length of time required for a patient to achieve sputum culture conversion after starting therapy for pulmonary tuberculosis.Rates of sputum smear and culture conversion were determined at weeks 2, 4, 8 and 16 after initiating therapy in patients admitted to our Respiratory Isolation Unit from January 1997 to December 2003.For the 184 patients included in the analysis, the mean time from the initiation of appropriate therapy to sputum culture and smear conversion were 34 +/- 26 and 38 +/- 32 days (mean +/- SD) respectively. Only 53% of patients obtained negative sputum cultures within the first 4 weeks of therapy. Multivariate analysis showed that the persistence of positive cultures during the first 4 weeks of therapy was associated with high bacillary counts in sputum smears at diagnosis [OR: 2.86; 95% confidence interval (95% CI): 1.20-6.66], lung cavitations (OR: 4.0; 95% CI: 1.63-9.09) and a prolonged period of symptoms (OR: 3.57; 95% CI: 1.43-3.57). The only factor associated with the persistence of positive cultures after more than 16 weeks of therapy was infection with a multidrug-resistant strain.High initial sputum bacillary counts and drug resistance result in delayed culture conversion. This should be taken into account when decisions regarding the potential discontinuation of isolation are made. The early identification of drug resistance is important for effective infection control in hospitals.

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 0.5 mg/L; however, the former method yielded slightly lower MIC 50 values (MICs for 50% of the organisms) (0.25 mg/L) compared with the latter method (0.5 mg/L). No differences were observed between susceptible and resistant isolates, including multidrug-resistant M. bovis isolates, with a MIC range of 0.12–0.5 mg/L. The potential role of linezolid in tuberculosis patients requires further in vivo evaluation.

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.

OBJECTIVES In vitro studies have shown good activity of linezolid against Mycobacterium tuberculosis, including multidrug-resistant strains. However, clinical experience with linezolid in tuberculosis is scarce. METHODS We report our clinical experience with five consecutive patients with multidrug-resistant tuberculosis infection treated with combination regimens that included linezolid. RESULTS Two patients had multidrug-resistant Mycobacterium bovis infection, with resistance to 12 antituberculous agents (one of them with HIV co-infection and

Resumen El Virus del Papiloma Humano (VPH), clasicamente se ha relacionado con infecciones de transmision sexual y procesos oncologicos malignos del aparato genital femenino y con menos frecuencia del masculino. Las nuevas tecnicas diagnosticas, basadas en biologia molecular (mediante reaccion en cadena de la polimerasa), ayudan a una mejor aproximacion epidemiologica, una mejora en el diagnostico viral, y un correcto enfoque terapeutico. El objeto de este trabajo es revisar el estado actual del VPH desde los puntos de vista etiopatogenico, epidemiologico, clinico, diagnostico, terapeutico y profilactico.

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.

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 efffective and many patients may remain free of nocardial disease for a prolonged period.

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.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.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 (P0.05). Hospitalization in a single room seemed to protect HIV-infected patients from developing nosocomial MDR-TBMb (P = 0.052).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.

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.

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 Lowenstein-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.

To investigate the clinical and radiographic features and the response to therapy of Mycobacterium kansasii infection in human immunodeficiency virus-infected patients, the clinical charts of 19 cases diagnosed during a 15-year period were reviewed retrospectively. Most patients were male intravenous drug abusers. Mycobacterium kansasii infection occurred late in the course of HIV disease and was associated with advanced immunosuppression. Thirteen patients had pulmonary disease, three extrapulmonary disease (2 with pulmonary involvement), and three pulmonary colonization. Most of them had fever and nonspecific respiratory symptoms; interstitial and alveolar infiltrates were the most common radiographic findings. Fourteen patients were given antituberculous treatment; among these, a clinical response was observed in 85%. Overall mortality was 63%, but only four patients died from active Mycobacterium kansasii disease. HIV infection has become the most important risk factor for Mycobacterium kansasii disease in our setting. Pulmonary infection is the most frequent form of disease and is usually responsive to antituberculous therapy.

The low current prevalence of leprosy in Spain together with the diversity of its clinical expression make the detection of this disease difficult. Three native and three imported cases are here reported. Different specialists mistook this disease for other entities: familial polyneuropathy, autoimmune disease, tuberculosis, cutaneous mycosis, and cutaneous sarcoidosis. Lepra is a very polymorphic disease and its diagnosis is based on finding cutaneous hypoesthesic lesions, neural thickening and presence of acid-fast bacilli (in cutaneous specimens or nasal exudates).

Clinical presentation of disseminated tuberculosis and visceral leishmaniosis can be very similar, mainly in those infected with HIV, being serology a useful tool in making a differential diagnosis. Cross-reactions of IFAT serodiagnosis of visceral leishmaniosis with other diseases are well known, but few data is available with tuberculosis.Detection of serum antibodies against Leishmania, using a commercial IFAT kit, was attempted in sera of 51 patients with active pulmonar and/or extrapulmonar tuberculosis (25 HIV+ and 26 HIV-). Overall cross-reactions was found in 19.6% patients without significative differences in between 2 groups, but differences in positive serum titres was observed: one at 1/256, three at 1/160, and one at 1/80 dilution, in the HIV+ group, whereas all 5 patients in HIV- group cross-reacted at 1/80 dilution. Recognition of specific leishmanial antigenic bands by serum antibodies of patients with tuberculosis were not clearly defined by Western-blot.IFAT technique for leishmaniosis cross-react in 20% of patients with tuberculosis.

The aim of the study was to assess all patients with ENT symptoms whose histologic and/or microbiologic diagnosis confirmed tuberculosis.All the anatomopathologic studies performed in the ENT unit in the authors' hospital in which the presence of acid-alcohol resistant bacilli were observed. All cases of cervical adenitis were not included.Eighteen patients with the following localizations were studied: 14 laryngeal tuberculosis and 4 extra-laryngeal tuberculosis (2 oropharyngeal, 1 otic and 1 sinusal). In the laryngeal forms, all patients were male except for one, and all were smokers. The duration of the symptoms was greater than 3 months in all the cases. Unilateral cord involvement was most commonly found, and in 2 cases this was associated with carcinoma of the vocal cord. Twenty-nine percent did not present with coincident pulmonary tuberculosis. None of the extra-laryngeal forms showed pulmonary involvement. All the patients were women and only 1 was smoker, the symptomatology was greater than 3 months in all cases and all required biopsy for achieving diagnosis. The evolution with medical treatment was favorable in all cases. During the same time period, 2300 cases of pulmonary tuberculosis were diagnosed in the authors' hospital.Tuberculosis of the upper respiratory tract is infrequent. Pulmonary involvement is common, although in this series this was only found in 71% of all laryngeal forms. Diagnosis is difficult, except in cases of coinciding pulmonary involvement and usually requires surgery for biopsy. Response to medical treatment is usually good.

Tuberculosis in HIV infected patients does not carry a worse therapeutic response rate. Treatment failure is usually due to incomplete schedule, with development of acquired resistance. Two patients with HIV infection and disseminated tuberculosis who developed fatal meningitis are presented.In vitro studies of sensitivity to anti-tuberculous drugs were carried out, using the proportions method.Following a good initial evolution, both patients were readmitted with tuberculous meningitis resistant to isoniazide in both and to rifampicin in one of the patients. In one patient, the original strain (which was sensitive) was available. In this patient, changes in the treatment were performed in the initial phase.The importance of anti-tuberculous multiple therapy, particularly in the initial phases, for HIV positive patients is crucial. The lengthen of admission when good patient's compliance is in question, but also to avoid, whenever possible, changes in treatment are important measures in this stage. Meningitis may occur as a form of therapeutic failure and its cure may be difficult if the strains are resistant.

A total of 763 immigrants (both symptomatic and asymptomatic for TB) were included in a retrospective study that included every immigrant that was referred to the Tropical Medicine Unit at the Ramon y Cajal Hospital (Madrid, Spain) between January 1990 and January 1999. A diagnostic test protocol for TB was followed, including serological investigation for HIV infection, a tuberculin skin test (5 TU of purified protein derivative; considered positive if induration was 110 mm), and a chest radiograph. Detection of acidfast bacilli and culture of sputum and urine samples for Mycobacterium (using Colestos medium) were attempted in every patient with an abnormal chest radiograph and a positive skin test. Isolation and identification of Mycobacterium strains and in vitro susceptibility tests were performed according to standard procedures. The TB World Health Organisation (WHO) criteria for case definition, classification of resistance, drug regimens, and follow-up were used [4]. Patients were monitored for 6–36 months after treatment was completed.

Summary Alveolar proteinosis is a relatively rare disease of unclear pathogenesis associated with opportunistic-infections. Although nocardiosis is the most frequent one, only 22 cases have been reported previously and are reviewed here. We present a patient with alveolar proteinosis with nocardiosis treated as an emergency with bilateral bronchopulmonary lavage and antibiotics. No previous cases of this association have been successfully managed in this way.

A 40-year-old woman on chronic hemodialysis had been diagnosed as having lepromatous leprosy at the age of 17 and treated for 15 years with sulfones. She remained clinically free of leprosy during 19 months of hemodialysis and then underwent successful renal transplantation. Fourteen months after surgery, recurrence of leprosy was observed. In spite of immunosuppression, the skin lesions healed with sulfone treatment. Renal transplantation is a useful treatment in patients with leprosy and chronic renal failure.

The presence of Listeria monocytogenes is studied in 1112 women belonging to four different groups: healthy women with no pathological obstetric antecedents, women with pathological obstetric antecedents, sterile women, and women with neonates suffering from listeriosis. Investigation on Listeria monocytogenes was achieved in 512 cases from the endocervical cavity and in all cases from the vaginal exudate. We have obtained a total of 2.3% of positive results. The 25 isolations of Listeria monocytogenes correspond to women with macerated fetuses, dead during the birth or after the birth, or to women whose neonatus was diagnosed to have listeriosis. We have not obtained positive results in women with abortions or malformed fetuses. In the same way we have not objectified the relation between listeriosis and female sterility. The endocervical exudate provides 33% more isolations than the vaginal. The higher percentage of isolations is obtained within the first 10 days after birth.