Transcript Document

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LATENT TB IN ADULTS
by
Assoc. Prof. Pang Yong Kek
LEARNING OBJECTIVES
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• To learn about the definition & diagnosis of
LTBI
• To learn about the investigations & algorithm
of investigations of LTBI
• To learn about the treatment target groups &
treatment regimens of LTBI
ESTIMATED INCIDENCE OF ACTIVE TB
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WHO, Global TB Report, 2011
INTRODUCTION
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• In high TB prevalence areas, many have been
exposed to infectious TB through:
o
a direct contact with a known index case
or
o
inadvertent exposure to an unsuspected active TB
patient.
INTRODUCTION
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



Some will acquire the infection.
But, many of those infected will develop adequate
immunity to keep the infection at bay.
Hence, only a small number will eventually develop
active disease.
Those infected but remain asymptomatic are said to
have Latent TB Infection (LTBI).
PATHOGENESIS OF TB
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Charles Bryan MD.
Infectious Disease.
Chapter Five.
Mycobacterial Diseases.
http://pathmicro.med.sc.e
du
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WHAT IS LTBI?
LTBI
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LTBI is diagnosed when an individual:

shows positive reaction to the TST/IGRA
but

does not have any clinical, bacteriological
(if
done), or radiographic evidence of active TB
DIAGNOSTIC CRITERIA
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
No symptoms to suggest active disease

Normal CXR (usually)

Negative sputum smear for AFB (if collected)

“Positive” TST (Mantoux Test)/IGRA
DIAGNOSTIC CRITERIA
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If the CXR is abnormal,
• ensure no changes are seen on repeat CXR (≥ 6
months apart)
• repeat sputum induction or BAL for AFB smear &
culture should be considered, even if no changes are
seen on repeat CXR
DIAGNOSTIC CRITERIA
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Remark:
• Calcified nodular lesions (calcified granulomas) &
apical or basal pleural thickening pose a lower risk
for future progression to active TB
→ Hence, does not require treatment
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WHY TREATMENT OF LTBI IS
NECESSARY?
TB CONTROL PROGRAMME
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
•
We know that:
early detection & prompt treatment of active
TB (esp. infectious TB), constitute one of the
most important strategies to control TB
UNIQUE FEATURES OF TB
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
However, the signs & symptoms of active TB, are
usually quite subtle in early stage.

Consequently, it will not alert the victims to seek
early medical attention.

The lack of florid symptoms & signs often elude
early detection by the health care providers.
UNIQUE FEATURES OF TB
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

Besides, MTB does not immediately debilitate the
host.
This allows the hosts to remain active &
mobile
spreading the infection.
Animation taken from:
http://www.fw-acdeptofhealth.com/images/tbanim2.gif
UNIQUE FEATURES OF TB
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
Once infected,
many could mount sufficient immune response &
control the disease.

Only about 5 - 10% developed reactivation in
later part of their lives.
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SO, WHY BOTHER?
TREATMENT OF LTBI
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
When LTBI reactivated, it will spread the disease in
the community.

LTBI Rx prevents this sporadic reactivation &
dissemination of TB.
 Thus,
it is certainly an essential component of TB
control in the community.
Symptoms
Biopsy
PCR
Signs
Diagnosis
of Active
TB
Culture
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Sputum
AFB
CXR
TST
• Dependent on the
demonstration of
host immune
response toward
tuberculous
proteins.
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Diagnosis
of LTBI
IGRA
TUBERCULIN SKIN TEST (TST)
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Robert Koch 1843 -1910
Pioneered the
Tuberculin Skin Test
PRINCIPLE OF TST
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
TST is based on the principle of delayed-type
hypersensitivity response to intradermal inoculation
of PPD, or tuberculin.
TUBERCULIN SKIN TEST (TST)
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•
However, interpretation of TST posts a big
challenge to the healthcare professionals.
THE SHORTCOMINGS OF TST
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Tuberculin contains
>200 proteins, widely
shared among the
mycobacteria.
TB
BCG
NTM
THE SHORTCOMINGS OF TST
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•
Due to this cross-reactivity, it has a poor specificity in
population which have been extensively vaccinated
with BCG.
•
Furthermore, NTM infection is relatively common in
tropical countries - further compound the diagnosis.
NEW TESTS - IGRA
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
Recently, with the invention of 2 new tests, collectively
known as IGRA
•
QuantiFERON-Gold-In-Tube (QFT-GIT) test
•
Elispot test (T-SPOT)

the prospect of differentiating LTBI from BCG
vaccination/NTM infection has becoming promising.
PRINCIPLE OF IGRA
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2 to 3 specific antigens are utilised,
1.
2.
3.
•
•
ESAT-6 (early secretory antigenic target-6)
CFP-10 (culture-filtrate protein-10)
TB 7.7 (only in QFT test)
expressed in M. tuberculosis complex,
absent from all strains of BCG & majority of NTM
PRINCIPLE OF IGRA
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
Because ESAT-6 & CFP-10 is not shared by
BCG & most NTM, T-cells of individuals with
BCG vaccination or NTM infection alone, will
not be stimulated to produce interferon-γ.
TB
BCG
NTM
PRINCIPLE OF IGRA
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


Circulating T-cells of infected individuals are sensitised to TB
antigens (which include ESAT-6 & CFP-10).
When the T-cells are incubated with these 2 antigens in the
lab, they are stimulated to secrete interferon-γ.
The interferon-γ could be measured by:
ELISA technique (Quantiferon Test)

ELISPOT technique (T-SPOT)
QUANTIFERON TEST
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T-SPOT
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SENSITIVITY & SPECIFICITY
OF IGRA
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 Although
this test is more specific, it still
cannot overcome the limitation that

the test result is dependent on the immune
status of the tested individuals
WHO SHOULD BE TESTED?
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

Only individuals who are at high risk of acquiring
LTBI or developing TB reactivation should be
investigated.
Treatment might be considered for those who are
positive for LTBI.
POSITIVE TST FOR LTBI
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Positive TST
(Measurement)
≥5 mm
Type of Individuals
• HIV-infected persons
• Organ transplant recipients
• Persons who are immunosuppressed for
other reasons (such as those taking the
equivalent of >15 mg/day of prednisolone
for ≥1 month or taking TNF-α antagonists)
POSITIVE TST FOR LTBI
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Positive TST
(Measurement)
≥10 mm
Type of Individuals
• Close contacts
• Recent immigrants (< 2 years)
• Injecting drug users
• Residents & employees of high risk
congregate settings(such as correctional
facilities, nursing homes, homeless
shelters, hospitals & other healthcare
facilities)
• Persons with fibrotic changes on CXR
POSITIVE TST FOR LTBI
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Positive TST
(Measurement)
≥15 mm
Type of Individuals
• Individuals from countries with low
incidence of TB
WHO SHOULD BE TESTED?
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•
The goal of testing – to identify persons who are
going to benefit most from treatment.
•
A pre-test evaluation should be made to identify
these individuals.
•
There are two broad categories of individuals
1.
Persons who have recent close contact
2.
Immunocompromised individuals
WHO ELSE SHOULD BE SCREENED?
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1. Individuals who are at increased risk of acquiring
TB infection (e.g. prison-warden, nursing home
residents/workers, intravenous drug users &
healthcare workers)
2. Immunocompromised individuals who are at
increased risk of reactivation (e.g. HIV infection,
patients on immunosuppresants, patients with
advanced organ failure)
ALGORITHM FOR SCREENING &
TREATMENT
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Target individuals - screen for symptoms of
active TB
• If active TB suspected - CXR & sputum
direct smear & Mantoux test
• If otherwise – TST (Mantoux test)
• TST <5 mm – no further test
• TST ≥5 mm, may proceed with IGRA test
PROPOSED ALGORITHM
OF SCREENING &
TREATMENT OF LTBI
Close contacts
Immune
compromised
individuals
Immune competent
individuals
TST
< 5 mm
TST
5 – 9 mm
TST ≥ 10 mm
IGRA Test
positive
IGRA test
negative
S&S / CXR /
sputum positive
Active TB
Active TB Rx
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Work-up for active
TB
Active TB
confirmed
S&S / CXR /
sputum negative
Latent TB
LTBI Rx
Active TB ruled out
Consider
prophylactic Rx
irrespective of LTBI
status
SHORTCOMING OF THIS ALGORITHM
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
Lack of longitudinal study that treatment of LTBI
using TST/IGRA is effective in preventing disease
reactivation in high burden countries.

A study of this nature is desperately required.
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WHAT IS THE ADVANTAGE OF
TARGETED SCREENING?
Active
TB
Latent
TB
THE OCCULT TARGETS ARE FLAGGED!
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ADVANTAGES OF TARGETED CONTACT
SCREENING
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1. A positive TST is more likely to indicate LTBI - less
false positive result.
2. They are likely to benefit most from the treatment -
reactivation risk is higher in recent contact.
3. Besides, they may be more likely to accept therapy
& adhere to it.
ANTITB REGIMENS FOR LTBI
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Drugs
Isoniazid
Duration
Interval
6-9
months
Daily
Completion criteria
 180 doses in 9 months
month regimen)
 270 doses in 12 months
month regimen)
Isoniazid
+
rifampicin
Rifampicin
4 months
Daily
 120 doses within 6 months
4 months
Daily
 120 doses within 6 months
Isoniazid &
rifapentine*
3 months
Once weekly
 12 doses
• *Rifapentine is not currently registered in Malaysia.
• *Its use should be restricted to those on DOT
(6(9-
TAKE HOME MESSAGES
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1. Sporadic reactivation is a cause of continuous
dissemination of TB in Malaysia.
2. Treatment of LTBI may be incorporated into TB
elimination programme.
3. Nonetheless, longitudinal study is needed to prove
the long-term effectiveness of this strategy.
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THANK YOU
[email protected]
