Diagnosing and Treating Latent TB Infection (LTBI) Module 14 – March 2010.

Diagnosing and Treating Latent TB

Infection (LTBI)

Module 14 – March 2010

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 ®

THEN NOW

Tuberculin Skin Test (TST)

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 HIV-infection Other

immunosuppressed Recent contact Fibrotic CXR changes Organ transplant

recipients

≥ 15 mm Consider significant

“positive” for all

≥ 10 mm 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 agoRecent live-virus vaccination/infection (e.g., measles) Overwhelming TB diseaseVery 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:

• All others 6 months

9 months preferred6 months acceptable

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 high-risk 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!