Transcript Global Significance of TB and its Impact on HIV

TB Testing Update
Lee B. Reichman, MD, MPH
Northeastern National TB Center
Audio Conference
History of Treatment of
Latent Tuberculosis Infection
For more than 3 decades, treatment of
persons with latent Mycobacterium
tuberculosis infection to prevent active
disease has been an essential component
of TB control in the US
History of Treatment of
Latent Tuberculosis Infection
1965: First recommended for use in the US for
previously untreated TB, PPD converters,
and all children <3 years with a positive
tuberculin test result
1967: Recommendations broadened to include
all TST + (>10 mm) and close contacts
History of Treatment of
Latent Tuberculosis Infection
1970: 2 deaths and 19 developed liver disease
out of 2000 contacts exposed to an
infectious case on Capitol Hill
1974: Development of guidelines regarding
pretreatment screening and monitoring to
minimize risk for hepatitis and exclusion
of low-risk persons older than 35 as
candidates for treatment
History of Treatment of
Latent Tuberculosis Infection
1983:
Guidelines further revised to recommend routine
clinical and laboratory monitoring for persons older
than 35 or with increased risk for hepatotoxicity
1998:
2 months of RIF + PZA (2RZ) recommended
for HIV+, subsequently HIV-
2000:
9 months Isoniazid decreed better than 6
2RZ decreed equal to 9 Isoniazid
2001:
2RZ deemphasized due to liver toxicity in favor of 9
month Isoniazid
2004:
4R suggested as effective advantageous regimen
Targeted Tuberculin Testing and
Treatment of Latent TB Infection
As the rate of active TB in the United States
has decreased, identification and treatment of
persons with latent infection who are at high
risk for active TB have become essential
components of the TB elimination strategy
Terminology
• “Treatment of latent TB infection” replaces the
terms “preventive therapy” and
“chemoprophylaxis” to promote greater
understanding of the concept for both patients
and providers.
• Targeted tuberculin testing is used to focus
program activities and provider practices on
groups at the highest risk for TB.
Targeted Tuberculin Testing
• Detects persons with LTBI who would
benefit from treatment
• De-emphasizes testing of groups that are
not at high risk for TB
• Can help reduce the waste of resources and
prevent inappropriate treatment
What’s New (1)
Tuberculin skin testing
• Emphasis on targeting persons at high risk
• 5-mm induration cutoff level for organ
transplant recipients and other
immunosuppressed patients being treated with
prednisone or TNF-α antagonists4
• Skin-test conversion defined as increase of
 10 mm of induration within a 2-year period,
regardless of age
____________________________________________________
MMWR August 61, 2004; 53(33): 683-686
What’s New (2)
Treatment of LTBI
• HIV-negative persons – INH for 9 months
preferred regimen
• HIV-positive persons and those with fibrotic
lesions on chest x-ray (consistent with
previous TB) – INH should be given for 9
months
• For all persons – RIF for 4 months is an
option
What’s New (3)
Clinical and laboratory monitoring
• Routine baseline and follow-up monitoring not
required except for
– HIV-infected persons
– Pregnant women or those in early postpartum period
– Persons with chronic liver disease or who use alcohol
regularly
• Monthly monitoring for signs or symptoms of
possible adverse effects
Identifying Risk Factors
That Lead to Development of
TB Disease
Persons at Risk for Developing
TB Disease
Persons at high risk for developing TB disease
fall into 2 categories
• Those who have been recently infected
• Those with clinical conditions that increase
their risk of progressing from LTBI to TB
disease
Recent Infection as a
Risk Factor (1)
Persons more likely to have been recently
infected include
• Close contacts to person with infectious TB
• Skin test converters (within past 2 years)
• Recent immigrants from TB-endemic regions
of the world (within 5 years of arrival to the
U.S.)
Recent Infection as a
Risk Factor (2)
• Children  5 years with a positive TST result
• Residents and employees of high-risk
congregate settings (e.g., correctional
facilities, homeless shelters, health care
facilities)
Increased Risk for Progression to
TB Disease (1)
Persons more likely to progress from LTBI to TB
disease include
• HIV-infected persons
• Those with a history of prior, untreated TB
or fibrotic lesions on chest radiograph
Increased Risk for Progression to
TB Disease (2)
• Underweight or malnourished persons
• Injection drug users
• Those receiving TNF-α antagonists for
treatment of rheumatoid arthritis or
Crohn’s disease
Increased Risk for Progression to
TB Disease (3)
• Persons with certain medical conditions
such as
– Silicosis
– Diabetes mellitus
– Chronic renal failure or on hemodialysis
– Solid organ transplantation (e.g., heart, kidney)
– Carcinoma of head or neck
– Gastrectomy or jejunoilial bypass
Risk Assessment Tools
With renewed emphasis on targeted
tuberculin testing, the use of a risk
assessment tool, such as a questionnaire,
is one way to help TB Programs direct
their resources and focus their efforts
Tuberculin Testing
Testing for M. tuberculosis Infection
Mantoux tuberculin skin test (TST)
Skin test that produces delayed-type
hypersensitivity reaction in persons with M.
tuberculosis infection
QuantiFERON® -TB test and QuantiFERON® Gold
Blood test that measures and compares amount
of interferon-gamma (IFN-) released by blood
cells in response to antigens
Mantoux Tuberculin Skin Test
• Preferred method of skin testing for M.
tuberculosis infection
• TST is useful for
– Determining how many people in a group are
infected (e.g., contact investigation)
– Examining persons who have symptoms of TB
• Multiple puncture tests (e.g., Tine Test) are
inaccurate and not recommended
Administering the TST
• Inject 0.1 ml of 5 TU PPD
tuberculin solution
intradermally on volar
surface of lower arm
using a 27-gauge needle
• Produce a wheal 6 to 10
mm in diameter
•
Reading the TST (1)
• Measure reaction in 48 to 72
hours
• Measure induration, not
erythema
• Record reaction in millimeters,
not “negative” or “positive”
• Ensure trained health care
professional measures and
interprets the TST result
Reading the TST (2)
• Educate patient and family regarding
significance of a positive TST result
• Positive TST reactions can be measured
accurately for up to 7 days
• Negative reactions can be read accurately
for only 72 hours
TST Interpretation (1)
5-mm induration is interpreted as positive in
• HIV-infected persons
• Close contacts to an infectious TB case
• Persons with chest radiographs consistent
with prior untreated TB
TST Interpretation (2)
5-mm induration is interpreted as positive in
(cont.)
• Organ transplant recipients
• Other immunosuppressed patients (e.g.,
those taking the equivalent of >15 mg/d of
prednisone for 1 month or those taking TNFα antagonists)
TST Interpretation (3)
10-mm induration is interpreted as positive in
• Recent immigrants
• Injection drug users
• Residents or employees of congregate
settings
• Mycobacteriology laboratory personnel
TST Interpretation (4)
10-mm induration is interpreted as positive in
(cont.)
• Persons with clinical conditions that place
them at high risk
• Children < 4 years; infants, children, and
adolescents exposed to adults at high-risk
TST Interpretation (5)
15-mm induration is interpreted as
positive in
• Persons with no known risk
factors for TB.*
____________________________________________________
*Although skin testing programs should be conducted only among highrisk groups, certain individuals may require TST for employment or
school attendance. Diagnosis and treatment of LTBI should always be
tied to risk assessment
Factors that May Cause
False-Positive and False-Negative
Reactions to the Tuberculin Skin Test
Type of Reaction
Possible Cause
False-positive
Nontuberculous mycobacteria
BCG vaccination
False-negative
Anergy
Recent TB infection
Very young age: < 8 mos. old
Live-virus vaccination
Overwhelming TB disease
BCG – Fantasy and Fact
FANTASY
FACT
• BCG protects against getting TB
infection
•BCG will not protect against becoming infected
with TB
• BCG provides lifetime protection against
developing active TB
•BCG protects against severe complications of
TB disease in young children,
but provides little or no protection in adolescents
and adults
• BCG causes the tuberculin skin test (TST)
to be positive for life
•BCG causes the TST to be positive for
a few years and then the TST reaction becomes
much weaker. Generally, no reaction is present
after 5 years
• In a BCG-vaccinated person, a positive TST
result is most likely due to BCG
•There is no way to tell whether a positive TST
result is due to BCG or to TB infection
• A positive TST result in a person of any age
from any country is most likely due to BCG,
not TB infection
•A positive TST result in an adolescent or adult
from a TB high-burden country is almost always
due to TB infection, not BCG
• There is no need for a BCG-vaccinated
person with a positive TST result to be
treated
•Persons from countries with high TB burden are
at risk of developing active TB and should be
treated
BCG Vaccine and TB Testing (1)
• Many have a history of bacille Calmette-Guèrin (BCG)
vaccination in infancy, and a blind faith in their vaccination
seems to prevent them from availing themselves of
treatment for latent TB infection to prevent active TB
• Since the 1920's, BCG has been given to children in
developing countries, including most on the current World
Health Organization (WHO) list of TB "hot spots"
• Approximately 100 million children receive BCG annually,
and most experts agree that it is highly variable in
protecting adults against TB
NEJM 2002; 347:1453-1454
BCG Vaccine and TB Testing (2)
• Tuberculin reactions from BCG given in infancy
invariably wane within five years
• No method can reliably distinguish tuberculin
reactions caused by BCG from those caused by
natural mycobacterial infections
• "A positive reaction to tuberculin in BCG vaccinated
persons indicates infection with M.tuberculosis
when the person tested is at increased risk for recent
infection"
NEJM 2002; 347:1453-1454
Boosting
• Some people with LTBI may have negative skin
test reaction when tested years after infection
• Initial skin test may stimulate (boost) ability to
react to tuberculin
• Positive reactions to subsequent tests may be
misinterpreted as a new infection
Two Step Testing
Use two step testing for initial skin testing of
adults who will be retested periodically
• If first test positive, consider the person infected
• If first test negative, give second test 1-3 weeks later
• If second test positive, consider person infected
• If second test negative, consider person uninfected
The Elderly: A Special Population
TB in the Elderly (1)
Most commonly due to reactivation of
previously dormant pulmonary foci
related to TB exposure earlier in life
TB in the Elderly (2)
• Boosting is more common in those 55 years of
age, but is unusual after the age of 75 years
• Two-step method should be used whenever a TB
skin test will be repeated periodically for example
residents or employees of LTCF that care for the
elderly
TB in the Elderly (3)
• Efforts to carefully select and monitor patients who
may be candidates for treatment of LTBI
• Current evidence favors treatment of LTBI in
elderly individuals who are at increased risk for
developing TB disease
TB in the Elderly (4)
Monitoring should include
• Baseline liver function tests
• Repeat LFTs to monitor hepatotoxicity
• Assess monthly for signs and symptoms of liver
toxicity
®
QuantiFERON
Tests
QuantiFERON®-TB Test and
QuantiFERON®-Gold Test (1)
• Whole-blood test used to detect M.
tuberculosis infection
• Approved by the U.S. Food and Drug
Administration (FDA)
• Entails mixing blood samples with antigens
from M. tuberculosis, M. avium complex, and
controls and incubating for 16 to 24 hours
QuantiFERON®-TB Test and
QuantiFERON®-Gold Test (2)
• Cells that recognize the antigen release
interferon-
• Amount of interferon released in response
to tuberculin is compared to amount
released in response to other antigens5
____________________________________________________
MMWR January 31, 2003; 52 (RR-02): 15-18 and CDC Fact Sheet Document #
250103, March 2003
Comparison of QFT and TST
QFT
TST
• In vitro test
• In vivo test
• Specific antigens
• Single antigen
• No boosting
• Boosting
• 1 patient visit
• 2 patient visits
• Minimal inter-reader variability
• Inter-reader variability
• Results possible in 1 day
• Results in 2-3 days
• Requires phlebotomy
All testing activities
should be accompanied by a plan
for follow-up care
LTBI Treatment for TST (+) Contacts
n = 1725
n = 58
n = 11
Marks, Taylor, Qualls, et al: Outcomes of TB Contact Investigations, AJRCCM, Dec. 2000
n = 132
n = 721
Summary
• Targeted testing = testing only those with risk factors
• Treatment of LTBI is an essential TB control strategy
• A decision to test is a decision to treat
INFORMATION LINE
1 • 800 • 4 TB DOCS
1 • 800 • 482 • 3627
www.umdnj.edu/ntbcweb