Monitoring changes in anti-tuberculosis treatment: associated factors determined at the time of diagnosis.

OBJECTIVES: To determine predictive factors for changes in standard anti-tuberculosis chemotherapy at the time of diagnosis. METHODS: A prospective study was performed among tuberculosis (TB) patients treated at specialised centres during 2008-2009. Treatment outcome was monitored per standard guidelines. Treatment was considered successful if the patient was cured or completed treatment. Factors associated with treatment modification were analysed at the bivariate and multivariate levels using logistic regression. RESULTS: A total of 427 patients were included in the study. The initial standard treatment regimen was retained for 249 patients (58.3%), extended to 9 months for 36 (8.4%) and changed for 142 (33.3%). Factors associated with a change of regimen at the multivariate level were female sex, age ≥ 50 years, human immunodeficiency virus infection, comorbidities, alcoholism, hospitalisation and culture-positive sputum. Drug resistance and toxicity were analysed independently. Treatment outcome was successful in 97.2% of cases without a regimen change and in 87.3% of those with a changed regimen (P < 0.001). CONCLUSION: Factors associated with changes in the initial anti-tuberculosis regimen should be considered for rigorous follow-up. Results obtained through individualised treatment provided by specialists were good despite the complexity of the cases treated.

Evolución de las características epidemiológicas de la tuberculosis en el Área 15 de la Comunidad Valenciana en el período 1987-2001 / Tuberculosis epidemiology in Area 15 of the spanish autonomous Community of Valencia: evolution from 1987 through 2001

OBJETIVOS: Valorar la evolución de las características epidemiológicas de la enfermedad tuberculosa (TB) en el Área 15 de la Comunidad Valenciana. MATERIAL Y MÉTODOS: Mediante búsqueda activa se identificaron todos los casos de TB diagnosticados en el área desde enero de 1987 a diciembre de 2001. Se recogió información clínica y epidemiológica de la historia clínica y de la entrevista con el paciente. RESULTADOS: Se diagnosticaron 476 casos de micobacteriosis (459 TB, 16 atípicas y una mixta), de los cuales eran residentes en el área 423 casos de TB. La tasa media anual fue de 24,6/105, con un descenso del 41,5% desde 1990. Los factores de riesgo más frecuentes fueron: tabaquismo en el 38%, etilismo en el 20%, infección por el virus de la inmunodeficiencia humana (VIH) en el 18% y contacto con TB en el 14%. La localización fue sólo pulmonar en el 61% de los casos (bacilíferos en el 49%, con tendencia a disminuir, aunque no significativamente), extrapulmonar en el 26% y mixta en el 13%; los infiltrados (67%) constituyeron el patrón más frecuente, con tendencia al aumento de incidencia en los lóbulos inferiores. El diagnóstico fue bacteriológico en el 77% de los pacientes, clínico en el 16% e histológico en el 7%. Fueron resistentes a isoniacida el 1,5% de los casos y a rifampicina el 0,3%. El 79% ingresó para diagnóstico, con una estancia media de 18 días. CONCLUSIONES: La TB ha disminuido su tasa, pese a la pandemia del VIH. No hay cambios en los factores de riesgo, se ha mejorado el diagnóstico bacteriológico y hemos observado cambios en la localización de los infiltrados pulmonares. La inmigración no ha tenido por el momento influencia sobre la tasa de TB

OBJECTIVES: To describe the evolution of tuberculosis epidemiology in Area 15 of the Autonomous Community of Valencia. MATERIAL AND METHODS: Cases of tuberculosis were identified by active case finding in Area 15 from January 1987 through December 2001. Clinical and epidemiological data were extracted from case records and a patient interview. RESULTS: Four hundred seventy-six diagnosed cases of mycobacterial infection were identified (459 tuberculosis, 16 atypical, and 1 mixed); 423 tuberculosis patients were residents of Area 15. The mean annual incidence rate was 24.6/100 000 population, representing a rate decrease of 41.5% from 1990. The most frequent risk factors were smoking (38%), alcoholism (20%), human immunodeficiency virus (HIV) infection (18%), and contact with a tuberculosis patient (14%). The site of tuberculosis involvement was the lung in 61% (49% bacillus positive, with a nonsignificant trend to decrease over time), nonpulmonary in 26%, and mixed in 13%. The radiographic pattern observed most often was pulmonary infiltrates (67%), and lower lobe involvement tended to increase over time. Diagnosis was by acid-fact bacillus stain for 77%, clinical picture for 16%, and histological for 7%. Isoniazid resistance was detected in 1.5% and rifampicin resistance in 0.3%. Patients were hospitalized during diagnosis in 79% of cases; the mean stay was 18 days. CONCLUSIONS: The incidence of tuberculosis has decreased in spite of the HIV pandemic. Risk factors have not changed, bacteriological diagnosis has improved, and the location of pulmonary infiltrates has changed. No influence of immigration on the incidence rate of tuberculosis has been detected to date

[Primary prevention and treatment of latent tuberculosis infection with isoniazid: efficacy of a control program, 1997-2002]. / Prevención primaria y tratamiento de la infección tuberculosa latente con isoniacida: eficacia de un programa de control, 1997-2002.

OBJECTIVE: To analyze the efficacy of a specific program for the study and follow up of tuberculosis contacts. To study factors related to low adherence to treatment and to the development of liver toxicity caused by isoniazid. PATIENTS AND METHODS: Between December 1996 and December 2002, we found 458 contacts of 79 cases of pulmonary tuberculosis in patients uninfected by human immunodeficiency virus. The contacts were screened for tuberculosis infection and chemoprophylaxis was prescribed according to the recommendations of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR). RESULTS: We identified 3 cases of tuberculosis among the contacts (prevalence 0.8%). Chemoprophylaxis with isoniazid was prescribed for 215 contacts. One hundred sixty-nine (79%) completed the prophylaxis protocol. The rate of adherence to treatment was lower in immigrants than in nonimmigrants (odds ratio, 3.42; 95% confidence interval, 1.03-11.04; P=.02). Forty-three patients (22%) developed liver toxicity during treatment, which had to be suspended in 3 cases. Duration of chemoprophylaxis was the only independent variable associated with liver toxicity (odds ratio, 3.80; 95% confidence interval, 1.10-13.13; P=.03). CONCLUSIONS: Our study demonstrates the effectiveness of a specific program of study and follow up of tuberculosis contacts. Immigrants require tailored strategies to improve their adherence to the program. The duration of chemo-prophylaxis plays an important role in the development of liver toxicity.

Prevención primaria y tratamiento de la infección tuberculosa latente con isoniacida: eficacia de un programa de control, 1997-2002 / Primary prevention and treatment of latent tuberculosis infection with isoniazid: efficacy of a control program, 1997-2002

OBJETIVO: Analizar la eficacia de un programa específico para el estudio y seguimiento de los contactos de los pacientes con tuberculosis. Evaluar los factores relacionados con una baja adherencia al tratamiento y con el desarrollo de toxicidad hepática por isoniacida. PACIENTES Y MÉTODOS: Entre diciembre de 1996 y diciembre de 2002 se censaron 458 contactos de 79 casos de tuberculosis pulmonar en pacientes sin infección por el virus de la inmunodeficiencia humana. Se realizó cribado de infección tuberculosa y se indicó quimioprofilaxis según la normativa vigente de la Sociedad Española de Neumología y Cirugía Torácica. RESULTADOS: Encontramos 3 casos de tuberculosis entre los contactos (prevalencia del 0,8%). Se indicó quimioprofilaxis con isoniacida en 215 casos. Un total de 169 (79%) completaron el protocolo de quimioprofilaxis. Los inmigrantes mostraron baja adherencia al tratamiento frente a los que no lo eran (odds ratio = 3,42; intervalo de confianza del 95%, 1,03-11,04; p = 0,02). Cuarenta y tres (22%) pacientes presentaron toxicidad hepática durante el tratamiento y en 3 de los casos tuvo que suspenderse. Sólo la duración de la quimioprofilaxis se asoció de forma independiente con el desarrollo de hepatotoxicidad (odds ratio = 3,80; intervalo de confianza del 95%, 1,10-13,13; p = 0,03). CONCLUSIONES: Nuestro estudio demuestra la efectividad de un programa específico de estudio y seguimiento de los contactos de pacientes con tuberculosis. Los inmigrantes requieren estrategias individuales para mejorar su adherencia al programa. La duración de la quimioprofilaxis es un factor importante en el desarrollo de hepatotoxicidad

OBJECTIVE: To analyze the efficacy of a specific program for the study and follow up of tuberculosis contacts. To study factors related to low adherence to treatment and to the development of liver toxicity caused by isoniazid. PATIENTS AND METHODS: Between December 1996 and December 2002, we found 458 contacts of 79 cases of pulmonary tuberculosis in patients uninfected by human immunodeficiency virus. The contacts were screened for tuberculosis infection and chemoprophylaxis was prescribed according to the recommendations of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR). RESULTS: We identified 3 cases of tuberculosis among the contacts (prevalence 0.8%). Chemoprophylaxis with isoniazid was prescribed for 215 contacts. One hundred sixty-nine (79%) completed the prophylaxis protocol. The rate of adherence to treatment was lower in immigrants than in nonimmigrants (odds ratio, 3.42; 95% confidence interval, 1.03-11.04; P=.02). Forty-three patients (22%) developed liver toxicity during treatment, which had to be suspended in 3 cases. Duration of chemoprophylaxis was the only independent variable associated with liver toxicity (odds ratio, 3.80; 95% confidence interval, 1.10-13.13; P=.03). CONCLUSIONS: Our study demonstrates the effectiveness of a specific program of study and follow up of tuberculosis contacts. Immigrants require tailored strategies to improve their adherence to the program. The duration of chemoprophylaxis plays an important role in the development of liver toxicity

Impact of the human immunodeficiency virus on the epidemiology of tuberculosis in area 15 of the Valencian community in Spain.

SETTING: Area 15 in Valencia. OBJECTIVES: To describe the epidemiology (1987-2001) of tuberculosis (TB) in human immunodeficiency virus (HIV) patients. METHODS: Study of annual incidence, age distribution, excess cases attributed to HIV, etiological risk fraction (ERF), population attributable fraction (PAF) and f factor. RESULTS: Of 476 cases diagnosed, 459 were TB, 16 environmental and one mixed; 76% of environmental cases were HIV-positive (P < 0.001). There was a mean annual TB incidence of 24.6/100000, with an annual reduction of 4%. Seventy-three patients were HIV coinfected (16%) (mean incidence 3834/100 000 seropositives). The principal risk factor was drug use (59%) for HIV+ and contact with TB for HIV-. We found no difference in pulmonary or extra-pulmonary location between groups, contrary to mixed cases (P < 0.001). In HIV+ there was a lower frequency of infiltrates (P < 0.001) and cavitation (P < 0.01), and a higher frequency of adenitis (P < 0.001), miliary or nodular pattern and normal X-ray (P < 0.001). Seropositives had a 174 times higher probability of developing TB. The mean ERF attributed to HIV was 99%, the PAF was 16% and the f factor was 1.19. Highly active antiretroviral therapy (HAART) reduced the risk of TB in HIV+ by 80%. CONCLUSIONS: TB has continued its decline, although HIV generated an excess of cases in the 1990s. HAART has reduced the TB risk in HIV+ and possibly the overall rate of TB.

[Tuberculosis notification from 1987 to 1999 for the public health area of the community of Valencia (Spain)]. / Evolución de la declaración de la tuberculosis en un área sanitaria de la Comunidad Valenciana desde 1987 hasta 1999.

OBJECTIVE: Under notification of tuberculosis (TB) is common worldwide but has hardly been studied in Spain. The objective of this study was to determine how many cases of TB are reported in our health care area. MATERIAL AND METHOD: Between 1987 and 1999 we carried out a direct study of the incidence and reporting of TB cases in our area (106,632 inhabitants on the census). Cases were taken from mandatory notification, pathology and bacteriology files and were then reviewed. RESULTS: Of the 410 TB cases diagnosed, 378 were residents of the area (annual incidence: 27/100,000 inhabitants), 223 of whom were reported (54%). Forty-eight patients were under 15 years of age. Sixty-seven percent of the pediatric cases and 53% of the adult cases were reported (n.s.). Of the 78 cases with HIV co-infection, only 32% were reported, in contrast with 60% of HIV-negative cases (p < 0.001). Of the 300 cases with pulmonary involvement, 56% were reported, versus 50% of those with exclusively extrapulmonary involvement (n.s.). For the 149 with positive Ziehl-Neelsen stain, 61% were reported, in contrast with 51% of those who were smear negative (n.s.). Diagnosis was based on clinical signs in 65 cases (16%), 51% of which were reported, versus 55% of those in which diagnosis was based on bacteriology or histology consistent with TB (n.s.). Overall under notification tended to decrease during the study period (r = 0.73, p < 0.005). Under notification also tended to decrease for patients with pulmonary involvement (r = 0.83, p < 0.0001) and for those with positive Ziehl-Neelsen staining of sputum (r = 0.79, p< 0.001). Likewise, under notification also decreased for HIV negative patients (r = 0.74, p < 0.02) but not significantly so for HIV positive patients r = 0.44, n.s.). CONCLUSIONS: Direct quantification of cases revealed a significant degree of under notification that is tending to decrease. Under notification is greatest for HIV-positive patients and is not changing. No differences were seen for smear positive and smear negative patients, by pulmonary or extra-pulmonary involvement, for clinical versus laboratory diagnosis, or for patients who were younger or older than 15 years of age. Reporting should be improved so that measures to decrease the incidence of TB can be taken.

Evolución de la declaración de la tuberculosis en un área sanitaria de la Comunidad Valenciana desde 1987 hasta 1999 / Tuberculosis notification from 1987 to 1999 for the public health area of the community of Valencia (Spain)

OBJETIVOS: La infradeclaración de la tuberculosis (TBC) es un hecho frecuente a escala mundial que ha sido escasamente estudiado en nuestro país. El objetivo de nuestro estudio fue conocer el estado de la declaración de los casos de TBC en nuestra área sanitaria. MATERIAL Y MÉTODO: Desde 1987 a 1999 se estudió de forma directa la incidencia y el estado de declaración de los casos de TBC en nuestra área (censo: 106.632 habitantes). Los casos se obtuvieron desde el registro de EDO, anatomía patológica y bacteriología, con posterior revisión de la historia clínica. RESULTADOS: Se diagnosticaron 410 casos de TBC, de los cuales 378 eran recientes del área (incidencia media anual: 27 por 100.000 habitantes) declarándose 223 (54 por ciento). Eran menores de 15 años 48 pacientes, de los que se declaró el 67 por ciento, frente al 53 por ciento en el grupo de más edad (p = NS). De los 78 casos coinfectados por el VIH se declararon sólo el 32 por ciento, frente al 60 por ciento en VIH negativos (p < 0,001). De los 300 casos con afección pulmonar, se declaró el 56 por ciento frente al 50 por ciento de localización extrapulmonar exclusiva (p = NS). De los 149 pacientes con tinción de Ziehl-Neelsen de esputo positiva se declaró el 61 frente al 51 por ciento con la prueba negativa (p = NS). Tenían diagnóstico clínico 65 pacientes (16 por ciento) de los que se declaró el 51 por ciento frente al 55 por ciento con alguna muestra bacteriológica o histológica compatible (p = NS). La evolución global de la infradeclaración durante el período puso de manifiesto una tendencia descendente (r = -0,73, p < 0,005), así como para el grupo de afección pulmonar (r = -0,83; p < 0,0001) y para los pacientes con Ziehl-Neelsen positivo en esputo (r = -0,79; p < 0,0001). Cuando consideramos la condición del VIH, la tendencia fue asimismo descendente para los pacientes VIH negativos (r = -0,74; p < 0,02) pero no fue significativa para los pacientes VIH positivos (p = 0,44; p = NS). CONCLUSIONES: La cuantificación directa evidencia una infradeclaración importante, con tendencia a disminuir. Es mayor en el grupo de pacientes VIH positivos sin cambios en su tendencia. No existen diferencias entre pacientes bacilíferos y no bacilíferos, localización pulmonar y extrapulmonar, diagnóstico clínico frente a no clínico y entre menores o mayores de 15 años. Sería necesario mejorar la declaración para tomar las medidas adecuadas para disminuir su incidencia (AU)

Linfangioleiomiomatosis pulmonar asociada a epilepsia. ¿Un paso más hacia la esclerosis tuberosa? / Pulmonary lymphangiomeyomiomatosis associated with epilepsy. Another step toward tuberous sclerosis?

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Comparative study of inhaled amiloride and inhaled furosemide in exercise-induced asthma.

BACKGROUND: Certain diuretics such as furosemide, when inhaled, have been found to be useful in preventing Exercise-Induced Asthma (EIA). STUDY OBJECTIVE: To assess the possible preventive effect of inhaled amiloride in EIA. DESIGN: A double blind, randomized, cross-over study comparing the effect of inhaled amiloride, inhaled furosemide and placebo in EIA. PATIENTS: Sixteen asthmatic patients (8 males and 8 females) with an average age of 21 years (range 9-31) who presented a FEV1 decrease of over 15% in a previous free-running exercise test. INTERVENTIONS: Solutions were inhaled with a Hudson nebulizer connected to an oxygen source in different days before exercise testing. A Vitalograph Compact (Ohmeda, England) spirometer was used and FEV1 was obtained at baseline, three minutes after solution inhalation, immediately after exercise and then every 5 min. until 20 minutes post-exercise. The changes in FEV1 percentages (FEV1%) and the mean FEV1 decreases expressed as percentages for each solution were compared. RESULTS: Inhaled furosemide diminished the fall in the FEV1 at every time after exercise. The maximum decrease in mean FEV1 was at 5 minutes post-exercise and was 11 +/- 7% with furosemide, 24 +/- 14% (p < 0.01) with amiloride and 19 +/- 12% (p < 0.05) with placebo. Amiloride administration resulted in a slight but significative increase in the FEV1 fall (p < 0.01 when compared with placebo). CONCLUSIONS: Amiloride is not useful to protect EIA whereas Furosemide does it. These differences results may be related to the differents mechanisms of action of the two diuretics.

[Microepidemics of tuberculosis; apropos of 2 school outbreaks in the area 15 of the Valencia community]. / Microepidemias de tuberculosis: a propósito de dos brotes escolares en el área 15 de la Comunidad Valenciana.

Schools are settings with high concentrations of young people with little exposure to Mycobacterium tuberculosis and greater risk of developing disease when infection occurs as the result of sporadic localized outbreaks. We studied two outbreaks in two elementary schools (A and B) after two cases of bacilliferous pulmonary tuberculosis were detected in teachers in 1990 and 1994. Contacts were trace din school A by the primary care physician and in school B by the pneumologist and public health authorities. Contacts were classified as belonging to the risk group (RG) or the low risk group (LRG). The RG was composed of 187 contacts in school A and 59 in school B. Individuals in the LRG numbered 429 and 116 respectively. Mantoux positives numbered 108 in the RG and 45 in the LRG in school A (p < 0.001). In school B 50 RG individuals and 29 LRG individuals were positive (p < 0.001). The proportion of Mantoux positives was greater in the RG of school B than in the RG of school A (p < 0.01), probably owing to longer time of evolution of disease and possible laryngeal involvement in the index case. Likewise, tuberculin positives were fewer in the LRG of school A than in the LRG of school B (p < 0.001), owing to the small size of the LRG in school A. Thirteen cases of tuberculosis were seen in school A, six of which called for drug prophylaxis after contacts were traced. The nature of the index case and the conditions of exposure are both important in such outbreaks, demonstrating the need to act appropriately to trace contacts, preferably under the supervision of a pneumologists.

Endobronchial tuberculosis in HIV-infected patients.

OBJECTIVE: To evaluate the presence of endobronchial tuberculosis in HIV-infected patients. METHODS: Review of the clinical records of HIV-infected patients in whom diagnostic bronchoscopy was performed because of pulmonary signs or symptoms during a 3-year period. RESULTS: Seventy bronchoscopies were performed in 59 HIV-infected patients. tuberculosis was diagnosed in 25 patients, of whom six showed endobronchial tuberculosis. The most noteworthy radiological finding was mediastinal and/or hilar lymphadenopathy in five patients, occasionally associated with chest miliary infiltrates (in one), or a small pleural effusion (in two). Chest radiograph was normal in one case. The endoscopic findings were hyperaemia in five, caseating bronchial masses in four, or protrusion of extratracheal lymph nodes (broad, thickened carina and patchy bronchial lesions) in three out of the six patients. Mycobacterium tuberculosis infection was confirmed by smear and culture from bronchial aspirate, bronchoalveolar lavage or bronchial biopsies. In three cases the diagnosis was confirmed by transcarinal needle mediastinal puncture aspiration. Tuberculosis was the first opportunistic pulmonary infection in every case. The clinical course with standard treatment was satisfactory in all cases with no bronchial sequelae. CONCLUSION: Endobronchial tuberculosis may be more frequent than suspected in HIV-infected patients. Routine fibrobronchoscopy in HIV-positive patients with tuberculosis could show the true frequency of endobronchial tuberculosis.

[Respiratory distress and multiple organ failure after intravesical instillation of BCG]. / Distress respiratorio y fracaso multiorgánico tras instilación intravesical de BCG.

A case of probable hypersensitivity reaction with multi-organic failure, following bladder installation of BCG, in a male with a diagnosis of bladder carcinoma is presented. The patient developed respiratory, renal and liver failure as well as leukocytosis, thrombopenia and an increase in muscular enzymes. It was resolved with hemodynamic support. The rare complication, occasionally described in medical literature and its probable pathogenic mechanisms are discussed.