Toxicity and adherence to treatment for latent tuberculosis infection in patients with hematologic malignancies.

PURPOSE: Oncohematological patients undergoing chemotherapy who have latent tuberculosis infection (LTBI) are at a high risk of developing active tuberculosis (TB). The identification and treatment of these patients can prevent LTBI progressing to active TB. This study analyzed the degree of adherence with and safety of the treatment of latent tuberculosis infection (TLTBI) in oncohematological patients undergoing antineoplastic chemotherapy. METHODS: This is a retrospective study of a cohort of oncohematological patients receiving TLTBI and antineoplastic chemotherapy simultaneously, between January 2007 and June 2010. The proportions of toxicity and adherence to TLTBI in these patients were compared with a non-oncohematological control group, matched for age, sex, and year in which the TLTBI was started. In addition, a minimum 2-year follow-up was carried out for all patients. RESULTS: A total of 105 patients who received TLTBI were included, 21 of whom had received antineoplastic chemotherapy simultaneously. The mean age of the patients was 63 years. There were no significant baseline differences in transaminase values. The percentages of patients completing treatment were 76.2% in the control group and 71.4% in the oncohematological group [risk ratio (RR): 1.07, 95% confidence interval (CI): 0.79-1.43]. The voluntary dropout proportion was similar in both groups (12.3 vs. 11.8%, RR: 1.05, 95% CI: 0.25-4.42). Treatment was discontinued because of toxicity in three oncohematological patients and in 11 patients from the control group (RR: 1.14; 95% CI: 035-3.66). No patient developed TB during the follow-up period. CONCLUSION: The safety of TLTBI is not influenced by simultaneous antineoplastic chemotherapy in oncohematological patients.

Recent epidemiological trends in extrapulmonary TB in Galicia, Spain.

OBJECTIVE: To describe the epidemiological trends and characteristics of extrapulmonary tuberculosis (EPTB) in Galicia, Spain, from 2000 to 2019.METHODS: This was a retrospective cohort study based on data from the Galician TB information system.RESULTS: Of the total number of TB cases (n = 15,871), 5,428 (34.2%) had EPTB. The absolute number of cases and incidence of EPTB decreased dramatically (from 480 cases and 17.8 cases/100,000 in 2000, to 172 and 6.4 cases/100,000 in 2019, respectively), with a mean annual decrease of respectively 64% and 4.7% for absolute cases and incidence rates. The risk for EPTB was higher in men than in women (RR 3.86, 95% CI 3.66-4.07). The most frequent age group was 15-44 years (2,234 patients, 41.2%); overall reductions per age group were 82% (0-14 years), 75% (15-44 years), 44% (45-64 years) and 63% (≥65 years), with statistically significant differences. The most frequently locations were the pleura (1,916 cases; 35.3%) and the lymph nodes (1,504; 27.7%).CONCLUSION: The incidence of EPTB in Galicia has decreased significantly in the last 20 years. The epidemiological characteristics have not changed, except for the number of patients with risk factors. This improvement of EPTB epidemiological trends coincides with the implementation of the programme for the prevention and control of TB, which suggests that it has been very effective in the control of the EPTB.

Multidrug-resistant tuberculosis in a low-incidence region shows a high rate of transmission.

OBJECTIVE: To describe the characteristics of patients with multidrug-resistant tuberculosis (MDR-TB), a descriptive prospective study was carried out applying a combination of exhaustive conventional epidemiology with molecular genotyping. SETTING: All patients diagnosed with MDR-TB in Galicia, Spain, between 1998 and 2004 were included in the study. DESIGN: Of 9895 diagnosed cases of TB, 58 were MDR-TB (0.59%). The site of disease was pulmonary in 56 cases and 46 were smear-positive. Only two cases were co-infected with the human immunodeficiency virus (HIV) and seven were immigrants. Twenty-five (43%) had received previous TB treatment. These cases presented more risk factors for treatment default and a lower frequency of contact with cases of MDR-TB. RESULTS: Genotyping analysis was performed in 57 patients, showing evidence of four clusters (30 patients, 52.6%), each with identical genetic patterns. The patients included in the clusters were younger, and most had primary forms or had had contact with another case of MDR-TB, especially in hospital. Neither the Beijing/W nor the B strain was identified. CONCLUSION: There is a low prevalence of MDR-TB in Galicia. Unlike previous studies, there was a high rate of transmissibility, including nosocomial transmission. Transmission is not associated with HIV or previously reported strains with a high capacity for transmission.

Detection of interleukin-2 is not useful for distinguishing between latent and active tuberculosis in clinical practice: a prospective cohort study.

OBJECTIVE: Previous reports have identified interleukin-2 (IL-2), quantified in the supernatants of QuantiFERON®-TB Gold In-tube (QFT) after 72 h of incubation, as a potential biomarker for distinguishing between latent and active tuberculosis (TB). However, its validity has not been tested in an appropriate clinical cohort. METHODS: A multicentre study of 161 consecutive adult patients undergoing evaluation for active TB at eight TB Units in Spain. Interferon-γ (IFN-γ) and IL-2 were assessed in the supernatant of QFT after 16-24 h and 72 h of incubation. The accuracy of IL-2 for indicating latent TB infection (LTBI) was assessed by receiving operating characteristic curves. . RESULTS: Twenty-eight participants were not infected, 43 had LTBI, 69 had TB, and 21 were not classifiable. Median (interquartile range) IL-2 concentrations after 72 h of incubation were 0.0 pg/mL (0.0-0.0) in uninfected individuals, 261.0 pg/mL (81.0-853.0) in LTBI individuals, 166.5 pg/mL (33.5-551.5) in patients with extrapulmonary TB, 95.0 pg/mL (26.0-283.0) in patients with smear-negative pulmonary TB, and 38.5 pg/mL (7.5-178.0) in patients with smear-positive pulmonary TB (p <0.0001). The area under the curve of the receiving operating characteristic curve (95% CI) of IL-2 after 72 h of incubation for the diagnosis of LTBI was 0.63 (0.53-0.74) when all TB cases were considered as a single group, ranging from 0.59 (0.47-0.71) to 0.72 (0.58-0.85) when only extrapulmonary and smear-positive pulmonary TB cases respectively were considered. CONCLUSIONS: Quantification of IL-2 in the supernatant of QFT after a prolonged incubation is not useful to distinguish between LTBI and active disease in clinical practice.

Study of Mycobacterium tuberculosis drug resistance in the region of Galicia, Spain.

FRAMEWORK: Galicia, a region in north-east Spain with its own government and health system and a population of 2 695 880. OBJECTIVE: To study the epidemiology of resistant tuberculosis (TB). DESIGN: A prospective, descriptive, and observational study of all Mycobacterium tuberculosis isolates processed by each of the laboratories in Galicia that perform mycobacterial cultures. The study followed the methodology recommended by the World Health Organization and the International Union Against Tuberculosis and Lung Disease, and included isolates processed between 1 November 2001 and 1 June 2002. FINDINGS: Of 400 strains analysed, 360 corresponded to previously untreated cases and 40 to previously treated cases. Of the previously untreated cases, 88.3% contained strains susceptible to isoniazid, rifampicin, streptomycin and ethambutol, while 4.4% were resistant to isoniazid. The rate of susceptibility to the four drugs was 77.5% in the previously treated cases. Multidrug-resistant TB was detected in 1.4% of the previously untreated cases and in 7.5% of the previously treated cases. CONCLUSION: Although Galicia has a high incidence of TB (49.4 cases per 100 000 population in 2001), the resistance levels detected by the study do not currently pose a serious problem for the region.

Epidemiology of tuberculosis in Galicia, Spain, 16 years after the launch of the Galician tuberculosis programme.

SETTING: Galicia, Spain. OBJECTIVE: To describe changes in tuberculosis (TB) epidemiology and characteristics in Galicia, Spain, during the period 1996-2011. DESIGN: Retrospective observational descriptive study of data obtained from the Tuberculosis Information System. The Galician Tuberculosis Prevention and Control Programme, created in 1994, is based in seven tuberculosis units that actively collect data on case finding and follow-up of all cases of TB in the region. RESULTS: TB incidence fell from 72.9 cases per 100,000 population in 1996 to 24.6 in 2011 (respectively 40.5 and 14.2 in patients aged <15 years). In 2011, 49.8% (n = 343) of patients were aged between 25-54 years; 62.3% (n = 429) were male; 52.1% (n = 359) had pulmonary TB (PTB) alone, of whom 33.5% (n = 144) had cavitary lesions; 50.7% (n = 218 PTB cases) were sputum smear-positive and 80.5% (346 PTB cases) were culture-positive. The median diagnostic delay was 56 days; 4.6% (n = 32) were human immunodeficiency virus positive and 5.2% (n = 36) were immigrants. The treatment success rate was close to 90%. Contacts of 86.7% of the smear-positive index cases were evaluated. CONCLUSION: TB incidence in Galicia is progressively decreasing; however, it is still higher than that of neighbouring regions. A long diagnostic delay was observed, which may have contributed to the high incidence rate in children.

Treatment completion in latent tuberculosis infection at specialist tuberculosis units in Spain.

SETTING: Treatment of latent tuberculosis infection (LTBI) is essential for tuberculosis (TB) control in low-prevalence countries. However, the long treatment duration and adverse events frequently result in suboptimal treatment completion. OBJECTIVE: To determine completion rates of LTBI treatment and to identify risk factors for non-completion of treatment. DESIGN: Retrospective, observational cohort study. METHODS: All non-human immunodeficiency virus infected adults who started treatment for LTBI at two specialist TB units in Spain between January 2004 and March 2007 were included. Those who discontinued treatment due to toxicity were excluded. RESULTS: Of 599 people who started on treatment, 484 (80.8%, 95%CI 77.5-83.8) completed it. Age <36 years (OR 0.33, 95%CI 0.30-0.76, P = 0.001), male sex (OR 0.58, 95%CI 0.37-0.92, P = 0.02), immigrant status <5 years of residence (OR 0.21, 95%CI 0.12-0.37, P < 0.001) and the presence of social risk factors (OR 0.21, 95%CI 0.11-0.39, P < 0.001) were associated with lower rates of treatment completion. Short treatment regimens were not associated with better treatment completion compared with isoniazid for 6-9 months (OR 0.89, 95%CI 0.45-1.80, P = 0.76). CONCLUSIONS: Overall, completion rates of LTBI treatment in specialist TB units are good. Nevertheless, counselling should be strengthened and new strategies to enhance adherence should be sought for recent immigrants and for people in unfavourable social situations.

Diagnosis of functional kidney failure of cirrhosis with Doppler sonography: prognostic value of resistive index.

Time-velocity wave-form analysis of Doppler signals from small intrarenal arteries allows estimation of intrarenal arteriolar vascular resistance. Among the various indexes proposed, the resistive index is the most widely used for this estimation. To investigate whether the resistive index is useful in the diagnosis of functional kidney failure and prediction of survival in cirrhotic patients with ascites, we measured resistive index, kidney and liver function and plasma levels of renin, aldosterone and antidiuretic hormone in 10 healthy subjects, 12 patients with compensated cirrhosis and 32 patients with cirrhosis and ascites (17 with kidney failure). A total of 28 clinical and laboratory variables were analyzed for prognostic value. Resistive index was significantly increased in patients with kidney failure (0.74 +/- 0.01) compared with those in the other three groups (0.64 +/- 0.01, 0.64 +/- 0.02 and 0.67 +/- 0.01) and correlated significantly with glomerular filtration rate, arterial pressure, plasma renin activity and free water clearance in the cirrhotic patients. The sensitivity and specificity of the resistive index in detecting kidney failure in patients with ascites were 71% and 80%, respectively. Nine variables were correlated with survival in the univariate analysis, including resistive index, age, hepatomegaly, blood urea nitrogen, serum creatinine, plasma sodium concentration, glomerular filtration rate, plasma renin activity and plasma concentration of antidiuretic hormone. Multivariate analysis disclosed only three independent predictors of survival: plasma renin activity, plasma concentration of antidiuretic hormone and serum sodium concentration. In conclusion, resistive index is a sensitive method to assess intrarenal hemodynamics in patients with cirrhosis and ascites. It also has predictive value for survival in these patients.

Effect of upright posture and physical exercise on endogenous neurohormonal systems in cirrhotic patients with sodium retention and normal supine plasma renin, aldosterone, and norepinephrine levels.

It is well known that sodium retention occurs in a significant proportion of patients with cirrhosis despite normal supine plasma levels of renin, aldosterone (ALDO), and norepinephrine (NE). The current study was performed to assess whether this subset of patients also present normal activity of the renin-aldosterone and sympathetic nervous systems during upright posture in sitting position and moderate physical exercise. Nine healthy controls, 14 patients with compensated cirrhosis and 10 patients with cirrhosis, ascites, sodium retention, and normal supine plasma renin activity (PRA) and ALDO and NE concentration were sequentially studied after 60 minutes in supine rest, 30 minutes in sitting position, and 30 minutes of cycloergometric exercise (3-METs). Sitting position and exercise were associated with similar stimulation of the renin-aldosterone and sympathetic nervous systems in the three groups of subjects. Consequently, cirrhotic patients with ascites showed values of PRA and plasma concentration of ALDO and NE similar to healthy subjects and patients with compensated cirrhosis during supine rest (renin: 1.4 +/- 0.3, 0.8 +/- 0.2, and 0.8 +/- 0.3 ng/mL; aldosterone: 24.3 +/- 4.7, 20.2 +/- 3.9 and 21.4 +/- 3.4 ng/dL; norepinephrine: 252 +/- 23, 250 +/- 16, and 255 +/- 23 pg/mL), sitting position (renin: 2.1 +/- 0.5, 1.1 +/- 0.3, and 1.6 +/- 0.4; aldosterone: 32.2 +/- 7.3, 23.7 +/- 5.3, and 26.2 +/- 4.5; norepinephrine: 356 +/- 38, 401 +/- 63, and 420 +/- 35), and exercise (renin: 2.9 +/- 0.8, 1.6 +/- 0.4, and 2.2 +/- 0.5; aldosterone: 43 +/- 6.4, 34.9 +/- 8.5, and 38.2 +/- 5.3; norepinephrine: 481 +/- 35, 499 +/- 54, and 534 +/- 48).(ABSTRACT TRUNCATED AT 250 WORDS)