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HOW TO TREAT 29
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HOW TO TREAT 29

Table 1. Comparison of interferon-gamma release assay and tuberculin skin test
Diagnostic test
Gammainterferon release assay
False positives
False negatives
Practical
considerations
Exposure to a limited number of non-TB mycobacteria
Active TB infection Impaired cell-mediated immunity Incorrect handling of blood tubes Incorrect performance of the assay
Requires one visit with a venepuncture More expensive, so there may be an out-of-pocket cost for the patient
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Tuberculin skin test
Exposure to a broad range of non-TB mycobacteria Prior BCG vaccination Boosting: the phenomenon from prior TST tests whereby an increased TST reaction is caused by stimulation of the immune response to the TST, rather than new infection
Active TB infection Recent live-virus vaccination( measles, mumps, polio) Anergy Improper administration of test
Figure 3. Steps for the screening and management of latent TB infection( LTBI).
5 % lifetime risk of reactivation of
— contribute to this risk assessment.
is not available in Australia. 8, 41 The
Unfortunately, a number of patients
should the LTBI preventive treatment
TB, while immunocompromised
The TST calculator can also be used
author does not routinely use the
are receiving, or are planned to
be started in relation to the immuno-
patients are at higher risk of reactivating LTBI. 26 However, not all immunocompromised patients reac-
as a bedside test to qualify the risk of adverse drug reactions of LTBI
27, 39 therapy.
combination of rifampicin and isoniazid in immunocompromised patients because of the potential increased
receive, medications that interact with rifampicin, precluding its use. In general, the author is cautious about
suppression?” This is a difficult question and requires clinical judgement as there is minimal evidence to guide
tivate; the risk is dependent on the
risk of hepatotoxicity, leaving the
initiating LTBI preventive treatment
decision making.
degree of immunosuppression, as
CHOICE OF REGIMEN
options of either single-agent isonia-
in elderly patients because increas-
In immunocompromised patients,
well how recently M. tuberculosis was acquired. 27, 28 Abnormalities seen on chest X-ray can also inform the risk of
For decades, single-agent isoniazid was recommended for the treatment of LTBI. However, in the past
zid or single-agent rifampicin. A comparison of these regimens appears in table 2.
ing age is a very strong risk factor for hepatotoxicity. 43 In these cases, balance the risk of hepatotoxicity against
reactivation of TB is rarely immediate
5, 29, 44 and ranges from months to years. Patients receiving TNF-alpha antag-
16, 17 reactivation.
There are limited data to directly compare the reactivation risk based on the immunosuppressive con-
few years, several other regimens have been studied and have found their way onto guidelines. 40-42 These include therapies such as rifampicin,
The author prefers to use four months of single-agent rifampicin in immunocompromised patients because of its shorter course dura-
the risk of TB reactivation.
TIMING OF PREVENTIVE TREATMENT RELATIVE TO IMMUNOSUPPRESSION
onists( infliximab or etanercept) for immune-mediated inflammatory diseases demonstrated that, in those who reactivated, the median time
dition or the drugs being taken. 29 Patients with solid organ malignan-
isoniazid plus rifampicin, and isoniazid plus rifapentine. 42 Rifapentine
tion. It has been shown to be non-inferior to nine months of isoniazid. 42
A common question posed to infectious diseases specialists is,“ When
from first prescription to reactivation was 17 and 79 weeks, respectively. 45
cies or bone marrow transplants have
a 36-74-fold and 10-40-fold higher risk compared with immunocompetent patients, respectively. 30-32 Patients receiving biologic agents are also at excess risk of reactivation. A systematic review and meta-analysis of 29 randomised controlled trials of patients treated with TNF-al-
Figure created in BioRENDER. com
pha antagonists demonstrated an
odds ratio of 1.94( 95 % CI 1.10-3.44,
p = 0.02) compared with the control groups. 37 The risk of LTBI reactivation in patients with HIV infection can be
more than 20 times higher than that
of the general population. 38
It is challenging for clinicians to
estimate the risk of LTBI reactivation
at the bedside. The author finds the
Online TST / IGRA Interpreter( TST calculator
) very useful to approximate the risk of reactivation. 27, 28 However, there are several medications and
immunosuppressive conditions that
cannot be entered into this online
calculator.
MANAGEMENT
Preventive treatment
ONCE the diagnosis of LTBI has been made, the next step is to decide whether to initiate preventive treatment. This decision is made by balancing the risk of reactivation against the risk of serious adverse events from the preventive treatment.
Just as the risk of reactivation is not easy to quantify accurately, it is also difficult to quantify the risk of adverse events from preventive treatment. Parameters— such as choice of agent; patient age; and comorbidities, for example, liver disease
Figure 4. Screening of immunocompromised patients for latent TB infection.
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Based on Lewinsohn DM et al 2017 7, Stock D 2017 11