Download Latent TB infection (LTBI)

Module 14 – March 2010
Diagnosing and
Treating Latent TB
Infection (LTBI)
Project Partners
Funded by the Health Resources and Services Administration (HRSA)
Module Overview
 Current methods for diagnosing TB infection
 Treatment options
 Monitoring
Learning Objectives
Upon completion of this session, participants
will be able to:
 State the two methods for diagnosing TB
infection
 Determine the groups that would most benefit
from treatment for latent TB infection (LTBI)
 Determine LTBI treatment options and related
monitoring
Current Terms and Definitions
 Latent TB infection (LTBI) = presence
of M. tb organisms without symptoms or
radiographic evidence of TB disease
 Treatment of LTBI replaces “preventive
therapy” and “chemoprophylaxis”
 Tuberculin Skin Test (TST) replaces
PPD when referring to the Mantoux
tuberculin skin test procedure or result
Diagnosing LTBI
Mantoux TB Skin Test
(TST)
Blood Assays for
M. tb:
 QuantiFERON® Gold and In-Tube
 T-SPOT.TB ®
Tuberculin Skin Test (TST)
THEN
NOW
Standard Tuberculin Preparations
 Current preparations of tuberculin contain
a purified protein derivative (PPD) of
Koch’s Old Tuberculin
 The two standard preparations are:
• USA: PPD-S – dose of 0.1 ml contains 5
tuberculin units (TU) of PPD
• UK: PPD-RT-23 – dose of 0.1 ml contains
2 TU (equivalent to 5TU of PPD-S)
Administering the TST
 Locate and clean
site, stretch skin with
thumb
 Inject 0.1 ml of 5 TU
PPD-S intradermally
at a 10°-15° angle, on
volar surface of lower
arm using a 27-gauge needle, bevel up
 Produce a wheal 6 - 10mm in diameter
 Do not massage injection site
Reading the TST
 Record site, date and time
of injection as well as PPD
lot number
 Measure reaction in 48 to 72
hours
 Measure induration (palpable
swelling), not erythema
 Forearm: Transversely to the
long axis of the forearm. Record in mm!
 Ensure trained health care professional
measures and interprets the TST
TST Interpretation
≥ 5 mm
≥ 10 mm
 HIV-infection
 Other
immunosuppressed
 Recent contact
 Fibrotic CXR changes
 Organ transplant
recipients




≥ 15 mm
 Consider significant
“positive” for all
Recent immigrants
Injection drug users
Lab personnel
Residents/employees of
congregate settings
 Persons with clinical risk
factors
 Children < 5-years-old
or child/adolescent
exposed to high-risk
adult
What factors might produce a
false-positive TST result?
False-Positive TST (2)
Factors that may cause false-positive TST
are:
 Non-tuberculous mycobacteria (NTM)
 BCG vaccination
• Consider a positive TST result to indicate TB
infection if risk factors are present
BCG and TST Interpretation
 BCG is the most widely used vaccine in
the world
 Wang, et al – meta-analysis
• Effect of BCG vaccination on TST results was
less after 15 years
• Positive TST with indurations of >15 mm
more likely to be result of TB infection than of
BCG vaccination
L Wang, et al. Thorax 2002;57:804-809
What factors might produce a
false-negative TST result?
False-Negative TST (2)
Factors that may affect the ability to respond to the
TST include:
 Anergy (the inability to react to a TST because of a
weakened immune system)
 Recent TB infection (up to 8-10 weeks following
exposure) or infection many years ago
 Recent live-virus vaccination/infection (e.g.,
measles)
 Overwhelming TB disease
 Very young age (newborns < 6 months old)
 Poor administration technique (e.g., TST placed too
shallow or too deep)
Blood Assays for M. tuberculosis
 QuantiFERON®-TB Gold In-Tube
(Cellestis Ltd, Victoria, Australia)
• Measures Interferon-gamma (IFN-y)
 T-SPOT.TB
(Oxford Immunotec Ltd, Oxford, UK)
• Measures peripheral blood mononuclear cells
that produce IFN-γ
Blood Assays for M. tuberculosis (2)
 There is limited data on how these tests
perform in certain populations:
• Children (≤ 5yrs)
• Recent contacts
 Cost and access to these tests may be
two of the greatest barriers to use in the
Caribbean
Clinical Pearl-Testing
 Negative TST or Blood Assay for
M. tuberculosis does not exclude TB
disease!
Rule Out Active TB
 Before initiating single-drug treatment
(monotherapy) for LTBI, active TB
disease must be ruled out with:
• Chest X-ray
• Clinical evaluation
Treating Latent
TB Infection
LTBI Treatment: Isoniazid (1)
 INH remains the mainstay of LTBI
treatment
 Duration of treatment?
• HIV-infected or radiographic evidence of
prior TB:
9 months preferred
6 months acceptable
• All others
6 months
Completion of Treatment
 Completion of therapy is based on total
number of doses administered, not on
duration alone!
 Count doses, not months
• 9 mo INH daily — 270 doses within 12 mo
• 6 mo INH daily — 180 doses within 9 mo
• 4 mo RIF daily — 120 doses within 6 mo
 Interruption of more than 2 mo — medical
evaluation to rule out active TB before
restart
Isoniazid: Hepatitis
 Incidence of hepatitis in persons taking
INH is lower than previously thought (0.1
to 0.15%)
 Hepatitis risk increases with age
• Uncommon in persons <20 years old
• Nearly 2% in persons 50 to 64-years-old
 Risk increased with underlying liver
disease or heavy alcohol consumption
Monitoring During Treatment
 Baseline laboratory testing should be
obtained for patients starting INH when:
• HIV infected
• Pregnant or immediate postpartum (within 3
months)
• History of chronic liver disease or heavy
alcohol use
• Initial evaluation suggests a liver disorder
 Evaluate monthly for:
• Adherence
• Symptoms (particularly for hepatitis)
Supplemental Pyridoxine (B6)
 Peripheral neuropathy occurs in < 0.2 %
using conventional Isoniazid (INH) doses
 Add vitamin B6 (pyridoxine) supplement
(25-50mg daily) for patients with:
• Diabetes, HIV, renal failure, alcoholism,
malnutrition, advanced age
• Pregnant or breastfeeding mothers (and
infant)
• Patients with a seizure disorder
Patient Education
 Patients should be instructed to stop medication
and seek immediate medical consultation if they
experience loss of appetite, abdominal pain,
nausea, vomiting, jaundice or other symptoms
of hepatitis.
Monthly face-to-face interview
 Rationale for treatment
 Adherence
 Symptoms of adverse drug
effects
 Plans to continue treatment
Withholding Isoniazid
INH should be withheld when:
 Transaminase levels exceed
• 3 times the upper limit of normal if associated
with symptoms; or
• 5 times the upper limit of normal if the patient
is asymptomatic
Treating Latent TB Infection
Special Situations
LTBI Treatment: INH Resistant
 Contacts of INH-resistant TB:
• 4-6 months of rifampicin (longer for children
and immunocompromised) daily
• Consider use of rifabutin in HIV-infected
patients on rifampicin-incompatible protease
inhibitors
 For persons intolerant of INH, use 4
months of rifampicin daily
• 6 months RIF for children and persons with
HIV infection
LTBI Treatment: Pregnancy
 Treatment for LTBI during pregnancy is
controversial
• Wait until after delivery?
• Possible increase hepatotoxicity during
pregnancy and early post-partum
 Treatment for LTBI with close clinical and
laboratory monitoring should be
encouraged if the woman is also:
• HIV-infected or
• a close contact to an infectious TB patient
LTBI Treatment: Breastfeeding
 Breastfeeding is not a contraindication
• Infant will get a small amount of INH
(sub-therapeutic)
• No toxic effects reported
 Give both mother and infant vitamin B6
(pyridoxine)
LTBI Treatment: MDR-TB
 No drug regimens with proven efficacy for
LTBI resulting from exposure to MDR-TB
 Treatment may be indicated in some highrisk situations (seek consultation with an
MDR-TB expert)
 Clinical follow-up recommended for 2
years post-contact
Window Period Prophylaxis
 Window period – refers to the interval between
infection and detectable reactivity to the TST
 Treatment during the window period:
• should be considered for children < 5 and
persons with significant immunosuppression
• can be discontinued if, after 8 weeks, a repeat
TST is negative and child remains asymptomatic
 Contacts with HIV or severe
immunosuppression should complete the full
course of treatment regardless of repeat TST
Re-treatment of LTBI
 Real issue is the probability of acquiring
new infection
 Recommended for those who have HIV
infection and children who have been in
contact with a sputum smear-positive
case
Counseling A Patient With LTBI
NEVER say: You’ve been “exposed” so you
need to be treated.
INSTEAD say: You have been exposed and
infected with the TB germ. But don’t worry…
 Good news: You do not have the disease
and you are not contagious to anyone
 Bad news: It is sleeping in your body, can
wake up later, make you very ill and
contagious to others
Counseling A Patient With LTBI (2)
Why get treated? Treatment will prevent
future disease and protect you and those
close to you.
Warning:
 Taking medication for 6-9 months is a
long time but it takes that long to kill all or
most of the TB germs
 “TOUGH bugs”… so take your medicine
correctly and completely!
Treatment of LTBI: Summary
 Assess for TB risk factors
 If risk is present, perform test for TB
infection (TST or blood assay for M.tb)
 If test for TB infection is positive, rule out
TB disease
 If TB disease is ruled out, initiate
treatment for LTBI
 If treatment is initiated, monitor patient
regularly and ensure completion!