rifampin and Silicosis

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone.

Topics: Antirheumatic Agents; Antitubercular Agents; Coinfection; Comorbidity; Disease Management; Drug Users; Emigrants and Immigrants; Evidence-Based Medicine; Health Personnel; HIV Infections; Humans; Ill-Housed Persons; Interferon-gamma Release Tests; Isoniazid; Kidney Failure, Chronic; Latent Tuberculosis; Mass Screening; Practice Guidelines as Topic; Prisoners; Public Health; Radiography, Thoracic; Renal Dialysis; Rifampin; Risk Assessment; Silicosis; Substance-Related Disorders; Transplant Recipients; Tuberculin Test; Tumor Necrosis Factor-alpha; World Health Organization

Silicosis, the most prevalent of the pneumoconioses, is caused by inhalation of crystalline silica particles. Silica-exposed workers, with or without silicosis, are at increased risk for tuberculosis and nontuberculous mycobacteria-related diseases. The risk of a patient with silicosis developing tuberculosis is higher (2.8 to 39 times higher, depending on the severity of the silicosis) than that found for healthy controls. Various regimens for tuberculosis chemoprophylaxis in patients with silicosis have been studied, all of which present similar efficacy and overall risk reduction to about one half of that obtained with placebo. Long-term regimens have potential side effects (particularly hepatotoxicity). In addition, the use of such regimens can jeopardize adherence to treatment. The current guidelines recommend that tuberculin skin tests be performed, and, if positive, that chemoprophylaxis be instituted. There are several possible regimens, varying in terms of the drugs prescribed, as well as in terms of treatment duration. We recommend the use of isoniazid at 300 mg/day (or 10 mg/kg/day) for six months for patients with silicosis, as well as for healthy patients with periods of exposure to silica longer than 10 years and strongly positive tuberculin skin test results (induration > or = 10 mm). Nevertheless, further studies are necessary so that indications, drugs, doses and duration of chemoprophylaxis regimens can be more properly defined.

Topics: Antibiotics, Antitubercular; Brazil; Humans; Isoniazid; Occupational Exposure; Pyrazinamide; Rifampin; Silicon Dioxide; Silicosis; Silicotuberculosis; Tuberculosis, Pulmonary

The aim was to evaluate the efficacy, safety and completion rate of 3-month, once-weekly rifapentine and isoniazid for tuberculosis (TB) prevention among Chinese silicosis patients.. Male silicosis patients without human immunodeficiency virus infection, aged 18 years to 65 years, with or without latent TB infection, were randomized 1:1 to receive rifapentine/isoniazid under direct observation (3RPT/INH group) or were untreated (observation group). Active TB incidence was compared between the two groups with 37 months of follow-up. Safety profile and complete rates were evaluated.. A total of 1227 adults with silicosis were screened; 513 eligible participants were enrolled and assigned to 3RPT/INH (n = 254) vs. observation (n = 259). Twenty-eight participants were diagnosed with active TB, and 9 and 19 in the 3RPT/INH group and observation groups, respectively. In the intention-to-treat analysis, the cumulative active TB rate was 3.5% (9/254) in the 3RPT/INH group and 7.3% (19/259) in the observation group (log rank p 0.055). On per protocol analysis, the cumulative active TB rates were 0.7% (1/139) and 7.3% (19/259), respectively (log rank p 0.01). Owing to an unexpected high frequency of adverse events (70.4%) and Grade 3 or 4 AEs (7.9%), the completion rate of the 3RPT/INH regimen was 54.7% (139/254). Twenty-six (10.8%) participants had flu-like systemic drug reactions; five (2.1%) experienced hepatotoxicity.. Weekly rifapentine/isoniazid prophylaxis prevented active TB among Chinese people with silicosis when taken, irrespective of LTBI screening; efficacy was reduced by lack of compliance. The regimen must be used with caution because of the high rates of adverse effects.. ClinicalTrials.gov number: NCT02430259.

Topics: Antitubercular Agents; Area Under Curve; China; Drug Administration Schedule; Half-Life; Humans; Isoniazid; Male; Medication Adherence; Middle Aged; Rifampin; Silicosis; Tuberculosis, Pulmonary

To compare the adverse effects and treatment adherence between 2 months of rifampin plus pyrazinamide (2RZ) and 6 months of isoniazid (6H).. Patients with silicosis in Hong Kong are at high risk of acquiring tuberculosis. A previous study showed that treatment with 6H reduced the risk of silico-tuberculosis by one half.. Patients with silicosis and a Mantoux skin test reaction > or =10 mm were randomized to receive either 2RZ or 6H daily. Liver function testing was done monthly during the initial 2 months. The adverse effects and treatment adherence were compared between the two regimens.. Forty patients (mean age, 61.6 +/- 9.1 years) and 36 patients (mean age, 57.6 +/- 9.7 years) were randomized to the 2RZ and 6H arms, respectively (p > 0.05) [+/- SD]. Baseline characteristics were comparable. Nineteen patients in the 2RZ arm had peak alanine transaminase (ALT) levels > 1.5 times the upper limit of normal (ULN) in comparison with only five study subjects of the 6H arm (47.5% vs 13.9%, p < 0.01). Fourteen patients (35%) in the 2RZ arm and 1 patient (2.8%) in the 6H arm had peak ALT levels more than five times the ULN (p < 0.001). Only seven patients had symptoms suggestive of hepatitis; none of the patients had jaundice. All recovered after withholding treatment. In the 2RZ study arm, none of the baseline characteristics predicted hepatotoxicity. Other adverse effects were generally mild and comparable between both study arms. Treatment was stopped prematurely in 45% and 36.1% of patients in the 2RZ and 6H arms, respectively (p = 0.43). The main reasons were hepatotoxicity for the 2RZ arm and voluntary withdrawal after experiencing other minor adverse effects for the 6H arm.. A higher incidence of hepatotoxicity was associated with rifampin plus pyrazinamide than isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong.

Topics: Aged; Antitubercular Agents; Drug Administration Schedule; Female; Hong Kong; Humans; Isoniazid; Male; Middle Aged; Patient Compliance; Pyrazinamide; Rifampin; Risk Factors; Silicosis; Tuberculosis

A double-blind placebo-controlled trial of antituberculosis chemoprophylaxis was undertaken in sillicotic subjects in Hong Kong where there is a high prevalence of both silicosis and tuberculosis. During 1981 to 1987, 679 Chinese men with silicosis, with no history of previous antituberculosis chemotherapy and no evidence of active tuberculosis, were admitted to the trial and have been studied for between 2 and 5 yr. They were allocated at random to four series-rifampin for 12 wk (R3), isoniazid and rifampin for 12 wk (HR3), isoniazid alone for 24 wk (H6), or placebo (Pl)--in a double-blind design with matching placebos for isoniazid and rifampin as appropriate. Active pulmonary tuberculosis developed more frequently during the 5 yr in the placebo series than in the three chemoprophylaxis series (p less than 0.01, log-rank test), but there were no significant differences between the chemoprophylaxis series. The estimated proportions of patients with active pulmonary disease in the placebo series were 9% at 2 yr, 15% at 3 yr, 20% at 4 yr, and 27% at 5 yr. In contrast, in the three chemoprophylaxis series combined they were 5, 8, 10, and 13%, respectively. Thus, although chemoprophylaxis halved the proportion of patients in whom tuberculosis developed, this proportion was still substantial. There was no evidence that chemoprophylaxis led to the selection of drug-resistant strains of bacilli. Adverse effects were reported with a similar frequency in all four series, suggesting that few were drug related. During the first 12 wk, hepatic toxicity was reported in 8 (1%) patients (3 HR3, 3 H6, and 2 Pl), but only 1 (H6) had symptomatic hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Alanine Transaminase; Disease Susceptibility; Double-Blind Method; Follow-Up Studies; Humans; Isoniazid; Male; Middle Aged; Rifampin; Silicosis; Tuberculosis, Pulmonary

To assess the relationship between mixed dust fibrosis (MDF) and tuberculosis.. We performed a comparative analysis with MDF, silicosis, and macular pneumoconiosis (Mac), using autopsy records from 1975 to 1994.. Prevalences of having tuberculosis among MDF, silicosis, and Mac were not significantly different, albeit a tendency of higher prevalence in silicosis. Cure rates of tuberculosis were, in order, silicosis < MDF < Mac (P=0. 085). Death rates associated with tuberculosis were, in order, silicosis > MDF=Mac (P=0.911). With respect to the two types of association with tuberculosis, i.e., combined type (tuberculopneumoconiosis) and complicated one (pneumoconiosis with tuberculosis); the former was significantly dominant in silicosis, the latter was significantly dominant in Mac, and intermediate in MDF. As a whole, the complicated type had a tendency of a higher cure rate than the combined type (P=0.071). Although the differences of profiles between the combined and complicated types were not statistically significant, the combined type had a tendency to have longer duration of exposure to dusts, earlier registration for treatment, higher profusion score, and earlier death compared with the complicated type.. From our findings, MDF takes an intermediate position between silicosis and Mac regarding the relationship with tuberculosis. The type of association with tuberculosis rather than the kind of background pneumoconiosis seemed to be more important in light of responsiveness to the treatment.

Topics: Autopsy; Dust; Female; Humans; Japan; Male; Mining; Occupational Exposure; Pneumoconiosis; Pulmonary Fibrosis; Rifampin; Silicon Dioxide; Silicosis; Tuberculosis, Pulmonary

Topics: Antitubercular Agents; Gold; Humans; Isoniazid; Mining; Patient Compliance; Pyrazinamide; Rifampin; Silicosis; Treatment Outcome; Tuberculosis