Management of Tuberculosis - Kementerian Kesihatan Malaysia

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Management of Tuberculosis (Third Edition)• Positive TST (Mantoux Test). Refer to Appendix 5 on the conduct of the test.Note: Positive TST is interpreted on a graded-system based on PPVs which are largely94, level IIIdependent on the risk of acquiring the disease and risk of latent TB reactivation.Refer to Table 2 on Individuals with moderate/high risk of developing TB reactivation.o IGRA may be used as an alternative test for TST in all situations for adultsThe diagnosis of LTBI is often challenged by the lack of a gold standard diagnostic test andthe absence of clinical symptoms. Until recently, TST was the only diagnostic test availableto confirm the diagnosis. However, the interpretation of the result is compounded by the factthat the reagent (tuberculin) used in the test cross-reacts with BCG and NTM. This gives riseto false positive results in some individuals.At the moment, there are two commercial tests, i.e. the T-SPOT.TB (Oxford, Immunotec)and the QFT-GIT Test (Cellestis) available to diagnose LTBI. Both are known collectivelyas the Interferon-γ Release Assays (IGRAs). They employ certain antigens like the ESAT-6and CFP-10 (for T-SPOT and QFT-GIT), as well as TB7.7 (only for QFT-GIT) to stimulate theproduction of Interferon-γ from the T-cell lymphocytes. These antigens are theoretically morespecific as they do not cross-react with the BCG and most NTM.In a recent published meta-analysis comparing IGRAs and TST in low TB prevalencecountries, IGRAs have been shown to have higher specificity and better PPV and NPV than95, level IIITST in adult population.However, the same conclusion may not be applicable to countries with high incidence of TB96, level III(usually from low- and middle-income countries).• An expert group commissioned by WHO to examine the evidence of IGRAs in low- andmiddle-income countries concluded that the quality of evidence on the use of IGRAs inLTBI screening for healthcare workers, contacts and outbreak investigations in thesecountries is very low. Due to heterogeneity in study designs and outcomes, the data couldnot be pooled. The majority of studies showed comparable LTBI prevalence by TST orIGRA in contacts and four studies reported a statistically significant difference betweenpositivity rates estimated by TST, T-SPOT or QFT. Both IGRAs and the TST seemed toshow positive associations but the strength of the association (after adjustment) variedacross studies, irrespective of BCG vaccination. Results indicated that concordancebetween TST and IGRAs ranged widely.• Three studies included the analysis of IRR stratified by IGRAs and TST. The associationwith subsequent incidence of TB in test-positive individuals compared to test-negativesappeared higher for IGRAs than for TST; however, this was not statistically significant[IRR for IGRA=3.2 (95% CI 0.6 to 5.9) and TST=2.3 (95% CI 0.8 to 3.7].• In addition, there was no statistically significant increase in incidence rates of TB inIGRA-positives compared to IGRA-negatives in vast majority of individuals (>95%) duringfollow-up. Both IGRAs and the TST appeared to have only modest predictive value anddid not help identify those who are at highest risk of progression to disease.• The Development Group suggests that the situations where IGRAs may be used are asthe following:i. As an alternative to TST for• Patients who are not expected to/could not come back for a reading of skininduration after 48 - 72 hours• Patients who had recent BCG vaccination or past NTM infection25
Management of Tuberculosis (Third Edition)ii. Where a 2-step test is considered (TST followed by IGRA)• Close-contacts whose TST is in the range of 5 - 9 mm• Patients who are offered LTBI treatment but are not convinced that they haveLTBI• Individuals who require annual screening of LTBI such as healthcare providersworking in high risk areas)5.3 TreatmentThere is no good evidence to support the various cut-off measurements of TST in diagnosingLTBI for individuals living in high prevalence countries with moderate/high risk of developingTB reactivation. Thus, the Development Group suggests that a TST of ≥10 mm should beconsidered as a positive test for LTBI for most individuals investigated in this country exceptfor categories listed in the table below:-Table 2: Positive TST for LTBIPositive TST Reaction(Measurement)≥5 mm≥15 mm≥10 mmType of Individual● HIV-infected persons● Organ transplant recipients● Persons who are immunosuppressed for otherreasons (such as those taking the equivalentof >15 mg/day prednisolone for ≥1 month ortaking TNF-α antagonists)● Individuals from countries with lowincidence of TB● All other high risk individualsIt is further suggested that only individuals who are at high risk of acquiring LTBI or developingTB reactivation should be investigated. These include:-• HIV-infected persons• Organ transplant recipients• Persons who are receiving immunosuppressant drugs• Recent close contacts (
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Management of Tuberculosis - Kementerian Kesihatan Malaysia

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