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28 HOW TO TREAT: LATENT TB INFECTION IN IMMUNO- COMPROMISED PATIENTS

28 HOW TO TREAT: LATENT TB INFECTION IN IMMUNO- COMPROMISED PATIENTS

20 MARCH 2026 ausdoc. com. au
Epidemiological
A history of being born or residing in a TB-endemic area or being a close contact of a patient with active pulmonary TB places the patient at risk of LTBI. A list of countries where TB is endemic can be accessed on the WHO website. 1 It is important to note that TB was endemic in Australia before the 1940s, so anyone alive during that period may have
CC / Sanjay Mukhopadhyay: bit. ly / 3SHd0ep
A comparison of TST and IGRA appears in table 1.
The author’ s approach to making a diagnosis of LTBI using a combination of epidemiological, radiological and immunological factors is shown in figure 7.
EXCLUSION OF ACTIVE TB
EXCLUSION of active TB is impor-
been exposed. 14
tant before embarking upon a man-
These epidemiological risk fac-
agement plan for LTBI as the features
tors can be, and often are, tem-
and treatment are different( see fig-
porally distant. For example, an
ure 2).
elderly person who spent most of
History and examination are
their life in Australia but spent their
important in screening for active TB.
childhood years in India is at risk
Specifically ask the patient if they
of LTBI.
have experienced fever, night sweats,
Within Australia, there are dis-
weight loss, cough, haemoptysis or
proportionately high rates of TB in
the development of new masses.
the NT: a 2021 report showed that
Extrapulmonary TB is more frequent
44 % of TB in the NT occurred in
in immunocompromised patients, so
Indigenous Australians. 15
it is important to have a high index of
Radiological
Chest imaging may show evidence
suspicion that any new symptom or sign might be TB. 25
Findings on chest imaging can
of previous TB infection. In immunocompromised patients, the author orders a chest X-ray in addition to a tuberculin skin test( TST) or an
Figure 1. Non-necrotising granuloma in a lymph node in the neck.
help distinguish LTBI from active TB. If there are symptoms suggestive of TB and abnormalities are present on chest X-ray, order a CT scan
interferon-gamma release assay
to further investigate. If features on
( IGRA) for three reasons: first, the
Gold( Qiagen, Germantown, US)
lymphocytes, reduced lymphocyte
example, in patients with HIV, 1.5-
the CT scan are suspicious for TB,
X-ray may reveal signs of LTBI in
is currently the only commer-
activity from improper specimen
16 % have an indeterminate IGRA
obtain specimens for mycobacterial
patients with a false-negative TST
cially available assay in Australia.
handling, incorrect filling or mix-
result. Furthermore, the risk of an
staining, culture and PCR. If sputum
or IGRA; second, to stratify the risk
In immunocompromised patients,
ing of the mitogen tube or an inabil-
indeterminate result is increased in
cannot be obtained, referral for fur-
of reactivation of LTBI; and third, to
the key limitations of IGRAs are
ity of the patient’ s lymphocytes to
patients with lower CD4 + lympho-
ther tests, such as bronchoscopy, is
exclude active pulmonary TB. 16
About 15 % of patients with LTBI have abnormalities on chest X-ray. 16 These changes may include calcified
false-negative and indeterminate results. 12, 22 In an IGRA assay, a mitogen is used as the positive control. This mitogen is a powerful
generate interferon gamma. If the mitogen does not produce adequate amounts of interferon gamma, this represents failure of the positive
12, 23, 24
cyte counts.
There is no gold-standard immunological test for the diagnosis of LTBI; TST and IGRA each have
recommended.
The author recommends against initiating treatment for LTBI until active TB has been investigated and
nodules, fibrotic lesions and pleu-
non-specific T-cell stimulant and
control. The most frequent reason
their own advantages and disad-
excluded.
ral thickening; however, none of these are pathognomonic of TB. 16 A fibrotic scar 2cm2 or greater and / or a calcified nodule 1.5mm or greater have been shown to be significantly associated with LTBI. 17 Patients with LTBI who have abnormali-
should produce interferon gamma when combined with the patient’ s serum. If the mitogen response is low, the test is considered indeterminate. An indeterminate response can occur because of insufficient
for mitogen failure is deficiency of T-cell function.
The mitogen itself may be a barometer of the net state of immunocompromise and, in itself, may have prognostic significance. 23 For
vantages. Recommendations vary between guidelines, with older guidelines recommending the use of TST, while more recent guidelines endorse the use of IGRA. 7 The author uses IGRA to screen for LTBI.
ASSESSING THE RISK OF LTBI REACTIVATION
IMMUNOCOMPETENT patients
with LTBI have approximately a
ties on chest X-ray are more likely to reactivate than those without abnormalities. 18
The author does not routinely perform CT scans when screening patients for LTBI or in patients with positive TST / IGRA but uses this modality to differentiate between active TB and LTBI.
Figure created in BioRENDER. com
In immunocompromised
patients, it can be clinically difficult
to exclude active TB because
of the multiple comorbidities and
the possible associated lung disease
. Features on a chest CT that
are more likely to represent active
TB compared with LTBI include the
presence of tree-in-bud, non-calcified
nodules, lymph node enlargement
and splenic calcified nodules. 19 Figure 6 demonstrates CT chest
findings of cavitating lesions of pulmonary
TB.
Immunological
Screening for latent TB can be done via IGRAs or TSTs. 11 The TST involves the intradermal injection of tuberculin-purified protein derivative that induces a T-cell-mediated hypersensitivity response in patients with prior TB exposure, leading to an area of induration at the injection site within 48 – 72 hours. The diameter of the induration is then measured by a trained clinician. 20
An IGRA involves testing a patient’ s blood for a T-cell response with interferon-gamma release after stimulation with antigens specific to M. tuberculosis. 21 QuantiFERON
Figure 2. Comparison of latent and active TB.