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Standardization of Mantoux test
... The standard screening procedure for LTBI [14] with modifications described in the subsequent publication [15], were followed. Mantoux test was performed and read exactly as recommended by the experts [4,16,17] with the difference that 10TU/0.1ml PPD (I.P. with Tween 80 as stabilizer corresponding to 0.005% and phenol <=0.5%; ...
... For the interpretation of Mantoux test, recommendations of National Tuberculosis Institute, Bangalore (now Bengaluru), were followed [4,16,17]. ...
... 1. An induration of < 5 mm was considered to be indicative of lack of tuberculin sensitization or having severe immunosuppression [4,16,17]. We used this result as a surrogate for 'never having contracted TB'. ...
... These include the background incidence of LTBI, the TB infection, the background infection with non-TB environmental mycobacteria (NTM), prior vaccination with bacillus Calmette-Gu erin (BCG), strength and the type of tuberculin used, and the cut-off points used to identify a positive TST. Chadha 21,22 and other Indian workers 23 have discussed these issues in-depth. ...
... For this purpose, the national guidelines for performing and reading TST were used. 21,22 After a preliminary round of testing, the method was augmented (aTST) to take into account the anergy seen in patients with RA. Additional testing for LTBI with one of the IGRA-based tests, namely Quantiferon TBgold â (QFTG) test, 29 was also carried out to see if this was of any added value. ...
... The Mantoux test was administered and read as recommended by National Tuberculosis Institute, Bangalore (now Bengaluru), Karnataka, India (an institution under the Department of Public Health, Government of India) and further supported by other Indian workers. [21][22][23][30][31][32] Accordingly, PPD equivalent to 1 tuberculin unit (TU) of RT23 strain (originally supplied by Statens Serum Institut, Denmark, with Tween-80 (as stabilizer) in a volume of 0.1 mL was injected intradermally on the left forearm exactly according to the technique described by Pai and colleagues. 32 The appearance of peau d'orange at the injected site indicated satisfactory administration of the test. ...
Aim:
To test the validity of an augmented tuberculosis skin test (a-TST) combined with Quantiferon TB-gold® (QFTG) test for the screening of latent tuberculosis infection (LTBI) in patients with rheumatoid arthritis (RA) being considered for treatment with biologic disease-modifying anti-rheumatic drugs or targeted synthetic disease-modifying anti-rheumatic drugs.
Method:
Standard TST using 1 tuberculin unit (TU) of purified protein derivative (PPD, RT23 strain) was carried out. If the positivity was less as compared to the general population, then a-TST using 10 TU PPD was employed. Simultaneously, QFTG test was also performed.
Results:
Using standard TST, 6/44 (13.6%), patients were positive compared to the reported figures of ~ 40% of the general population; 38 of the remaining TST-negative patients were then given an a-TST with 10 TU PPD; eight of them dropped out. Of the remaining 30 patients, eight (26.6%) were positive. Another 70 patients tested directly with a-TST; 22 (31.4%) were found positive. Thus, of a total of 100 patients tested with a-TST, 30 (30%) were positive. In 54 a-TST negative patients, QFTG was done; seven (13%) were positive. Thus, in combined a-TST with QFTG, 43% of the RA patients were found positive, suggestive of the presence of LTBI.
Conclusion:
Combined a-TST with QFTG testing gave 43% positivity among RA patients, which is close to the reported ~ 40% Mantoux positivity in the general population. Therefore, this method for the screening of LTBI in Indian patients with RA being considered for tumor necrosis factor alpha treatment could be satisfactory for offsetting TB flare. It may apply to other high-burden TB countries around the world.
... Toward this aim, in 2009, a group from Delhi reported a strategy for the screening of LTBI and its follow-up. [6,7] It recommended (i) systematic clinical screening for TBI; (ii) an "augmented Mantoux test" using ten tuberculin units (TUs), of purified protein derivative (PPD) RT23, with Tween-80; as against the National standard 1 TU PPD recommended by National Tuberculosis Institute (NIT), Ministry of Health, Government of India for the Mantoux test; [8][9][10] (iii) simultaneously carried out the QuantiFERON ® -TB Gold (QFTG) test; [11] (iv) standard chest radiograph; and (v) contrast-enhanced computed tomography (CECT) of the chest. This study demonstrated high efficacy in curtailing the LTBI flare in a small number of patients. ...
... The discussion on the differences in the strategies for the screening of LTBI by the various authorities (World Health Organization, Centers for Disease Control, USA, The American Thoracic Society, The NIT (Bengaluru), Ministry of Health, Govt. of India) is beyond the scope of this work; for that the reader is referred to several key references cited in this paper. [6][7][8][9][10][11][12] A very detailed discussion of the different LTBI-screening strategies has recently been published by Handa et al. [16] In this regard, the extensive work by Madhukar Pai deserves mention. In his 2005 publication, he describes the current evidence on the performance of interferon-gamma (IFN-γ) assays and the TST. ...
Objective: The objective of the study was to study the effectiveness of a recommended screening strategy for latent tuberculosis infection (LTBI) in patients with systemic inflammatory rheumatic diseases (SIRDs) treated with biological disease-modifying antirheumatic drugs (bDMARDs).
Methods: The study included patients being considered for bDMARD treatment. Screening strategy included screening with “4S symptom complex (current cough, fever, weight loss, and night sweats) for TB,” augmented Mantoux test using ten tuberculin unit (TU) strength simultaneously with QuantiFERON®-TB Gold (QFTG) test. Those with a Mantoux test reading of ≥10 mm induration at 48–72 h and/or with a positive QFTG test, were given TB prophylaxis before initiating bDMARDs. They were followed and monitored for any features of tuberculosis flare.
Results: A total of 730 patients (265 rheumatoid arthritis, 400 axial spondyloarthritis [axSpA], 34 psoriatic arthritis, and 31 others) were considered for bDMARDs. Two hundred and sixty-seven (36.6%) were positive for LTBI. They were treated either with isoniazid monotherapy for 6 months or with rifampicin + isoniazid for 4 months. bDMARDs were started 1 month after initiating chemoprophylaxis. Five (0.68%) patients developed active TB disease in the follow-up. In a total of 2930 “control” patients with the same diseases but never having taken bDMARDs, 18 (0.61%) developed active TB disease. The proportion of patients developing active TBI during the same period of follow-up did not differ between those who were and those who were not treated with bDMARDs. None of the study participants had “4S” symptoms.
Conclusion: The strategy of clinical screening for active TBI with “4S complex,” standard chest radiograph, and an augmented Mantoux testing (10 TU purified protein derivative, [PPD]) simultaneously with QFTG test for the screening of LTBI, was successful in identifying active TBI in patients treated with bDMARDs.
India has a huge patient burden of rheumatic diseases (RDs) including rheumatoid arthritis. The use of biologics has transformed the treatment paradigm for RD; however, biologic treatment-related infections (especially tuberculosis [TB]) are an area of potential concern for TB-endemic nations like India. Anti-tumor necrosis factor (TNF) therapy impairs the physiological TNF-mediated signaling and may cause reactivation and dissemination of latent TB infection (LTBI). Careful screening is, thus, crucial in RD patients who are about to commence anti-TNF treatment. To date, there is no consensus available for the screening, evaluation and treatment of LTBI as well as on the drug dosage and duration regimen (monotherapy or combination therapy) in the Indian population. An evidence-based algorithm for LTBI screening and management in RD patients undergoing biologic disease-modifying anti-rheumatic drug therapy is suggested in this review for Indian rheumatologists. The proposed algorithm guides physicians through a step-wise screening approach, including medical history, tuberculin skin test, interferon gamma release assay, chest radiograph and management of LTBI with isoniazid therapy or its combination with rifampicin. Further, the provided algorithm can aid the national bodies (such as National TB Control Program) in formulating recommendations for LTBI in this high-risk population.
To understand the basic principles of laboratory tests
In the Malaysian setting of multi-ethnicity and high BCG coverage, interpretation of Tuberculin Skin Testing (TST) may be difficult. Between January 2001 and December 2003, a retrospective study on all adult patients with documented TST results treated for tuberculosis (TB) in chest clinics of two government hospitals was conducted to determine the reliability of TST and factors affecting its interpretation. One hundred and three patients [mean age (SD): 43 (17); male: 67%] were eligible for data collection: 72% and 57% of patients had positive TST results based on cut-off points of 10mm and 15mm respectively. The only significant univariate association with TST results was the severity of co-morbidity. A patient with co-morbidity score of 3 defined as those with any cancer, end-stage renal or liver disease, or HIV disease, was more likely to have a negative TST results [10mm cut-off point: Odd Ratio (95% CI) 6.6 (1.82 to 24.35), p = 0.003; 15mm cut-off point: 4.8 (1.21 to 18.95), p = 0.012]. A TST reading of 10mm had a higher sensitivity than 15mm as the cut-off point in diagnosing TB infection. Considering all possible confounding factors like ethnicity, prior BCG vaccination and TB burden in the population, severity of co-morbidity remains strongly predictive of a negative TST. Caution should be exercised in interpreting TST in these patients.
Previous studies have suggested that the bacille Calmette-Guérin (BCG) vaccine may have a non-specific beneficial effect on childhood survival in areas with high mortality. We examined whether BCG-vaccinated children with a BCG scar or a positive tuberculin reaction had better survival than children without such reactions. As part of an ongoing two-dose measles vaccine trial for which children were recruited at 6 months of age, we examined 1813 children for BCG scar at 6 months of age and 813 BCG-vaccinated children were skin-tested for delayed hypersensitivity to tuberculin, tetanus and diphtheria. We found that BCG-vaccinated children with a BCG scar had significantly lower mortality compared with BCG scar-negative children, the mortality ratio in the first 12 months of follow-up being 0.41 (0.25-0.67). BCG-vaccinated children with a positive tuberculin test had a mortality ratio of 0.45 (0.24-0.85) compared with tuberculin negative children. These results were unchanged by control for potential confounders or using different cut-off points for a tuberculin-positive response. Exclusion of dead children who had HIV antibodies did not modify the estimate (mortality rate (MR)=0.46 (0.23-0.94)). After censoring for tuberculosis (TB) exposure at home, the mortality ratios for having a scar and being tuberculin-positive were 0.46 (0.27-0.79) or 0.42 (0.21-0.84), respectively. Children positive to tetanus or diphtheria in the skin test had the same mortality as children not responding to these vaccine-related antigens. Thus, BCG scar and a positive tuberculin reaction were associated with better survival in early childhood in an area with high mortality. Since nothing similar was found for responders to diphtheria-tetanus-pertussis (DTP) vaccine, and the effect could not be explained by protection against tuberculosis, the effect of BCG vaccination could be due to non-specific immune-stimulation protecting against other infections.
Cutaneous tuberculosis in children is a major health problem in India. It accounts for about 1.5% of all the cases of extrapulmonary tuberculosis. Scrofuloderma and lupus vulgaris are the two most common forms of tuberculosis. However, the trend in the pattern of cutaneous tuberculosis is changing, as the tuberculid, lichen scrofulosorum, has become more common in recent years. Overall, the clinical patterns are comparable with adults. However, children can have widespread and severe involvement because many unusual and uncommon patterns are known to occur in children. Underlying systemic involvement is more common in children, compared with adults.
To study the tuberculin sensitivity patterns among BCG vaccinated and unvaccinated children and possibility of estimating annual risk of tuberculosis infection (ARI) from among BCG vaccinated children, a total of 11,132 children (5,107 aged 0-4 years and 6,025 aged 5-9 years)
were tested using ITU of PPD RT23 with Tween 80. Children with BCG scar comprised 68.2% of the
test-read population aged 0-4 years and 47.5% of those aged 5-9 years.