PPD in a Nutshell

 

By C. Chong

Background

 

Tuberculosis caused by
Mycobacterium tuberculosis, and rarely by others, had been a public health
scourge for centuries.  The disease has
been linked with overcrowding, poor nutrition, low socioeconomic status, and
more recently with immunosuppression.
Historically, tuberculosis was very common, presented in many forms, and
killed.  With the advent of
chemotherapy, streptomycin and isoniazid, the in the 1950s, treatment of TB
entered a new era and there were hopes that TB, like smallpox, would be
eradicated.  However, the late 1980s and
early 1990s saw a resurgence of TB with more multidrug resistant cases.  This makes a case for screening and
prophylaxis. 

 

Primary infection, usually
asymptomatic, by Mycobacterium tuberculosis (Mtb) occurs largely through
inhalation of the bacterium (droplet spread) usually over a sustained period of
time.  Pulmonary TB is the most common
form in adults, but other sites, through hematogenous and lymphatic spread,
include bone, marrow, CNS, GI tract, kidneys, and lymph nodes.  Disease usually presents after reactivation
of an asymptomatic or subclinical primary infection that had been contained by
the host.  Host factors increasing the
susceptibility to reactivation include poor general health, immunosuppression
(disease or medication), and comorbid illnesses.  Strategies for combating tuberculosis included improved living
conditions, vaccination with BCG attenuated M. bovis, and screening for primary
infection and prophylaxis. 

 

Primary vaccination with BCG is
offered outside the United States, Canada and Western Europe where the disease
is more prevalent, financial resources more limited and therefore vaccination
is felt to be more cost effective.
However, BCG is not standardized, felt to confer variable protection and
causes a delayed hypersensitivity reaction to PPD.  Studies of BCG vaccinated populations showed great variability in
the PPD reaction (5 to 25 mm) and whether or not it diminishes over time. In
addition, BCG boosters are given in some areas.  These factors make it difficult to interpret PPD reactions in BCG
vaccinated populations.  Therefore the
decision to offer this population TB prophylaxis is based on standard
interpretations of PPD results, disregarding the BCG history.

 

The rise in TB in the United
States 1980s and ’90s was felt to be related to 1) increased immigration from
areas where TB is endemic, 2) HIV, 3) immunosuppressive medications and
conditions, and 4) diminished screening and prophylaxis.  The rise in multidrug resistant infections
was felt to be related to the availability of common TB medications in areas
where TB was prevalent and improper and incomplete treatment contributing to
creating resistant strains.

 

Screening

 

Standard screening utilizes 5 TU
of purified protein derivative (PPD) injected intradermally.  It is read between 48 and 72 hours for
induration size.  The Tine and other
multiple puncture tests are not recommended due to lack of standardization and
lack of compliance in patient self-reports.
In persons with a prior positive PPD, chest x-rays can be used to screen
for active disease.  PPD screening is
only universally recommended for children < 5.  Periodic screening is recommended for
high-risk individuals.

 

High-risk individuals have a high
risk of exposure, high morbidity of disease, or high risk of developing
disease.  High risk of exposure is seen
in people who are health care workers, in group homes, dormitory like
conditions, shelters, prison, close contacts of people with active disease, or
from areas where TB is endemic.  High
morbidity of disease would be present in those with immunosuppression, comorbid
illnesses, and are either very young or elderly.  Those with a higher risk of developing disease include HIV +
persons, active IV drug abusers, the homeless, persons taking prednisone or
other immunosuppressants, and persons with comorbid conditions.

 

Interpretation

 

A reactive PPD is a measured area
of induration.  The reading must be
between 48 and 72 hours after planting.
Staff need to be trained to be consistent in the reading.  Positive readings can be ³ 5,
10 or 15 mm depending on the following circumstances:

 

³
5 mm is positive for the following individuals regardless of BCG status:

 

¨
HIV seropositive persons

¨
persons with HIV risk factors who had declined testing,
including history of IVDA and unknown HIV status

¨
close contacts of the person who has pulmonary or
laryngeal TB

¨
persons with radiographic evidence of old, healed TB

 

³
10 mm is positive for the following individuals if they do not meet the
criteria for the 5-mm cut off, regardless of BCG status:

 

¨
persons with medical risk factors for developing active
TB other than HIV, such as DM, silicosis, prolonged corticosteroid therapy,
other immunosuppressive therapy, cancer of the head and neck, hematologic and
reticuloendothelial disease, ESRD, intestinal bypass or gastrectomy, chronic
malabsorption syndromes, or low body weight (10% or more below ideal)

¨
persons with a history of drug injection or substance
abuse who are known to be HIV seronegative

¨
persons from an area of the world where the incidence
of TB is high

¨
persons from a medically underserved, low income
community

¨
employees or residents of congregate settings, such as
hospitals, jails, shelters, nursing homes, and drug treatment centers

¨
health care providers

¨
children younger than five years old

 

³
15 mm is positive for individuals who meet none of the criteria for the
5-mm or 10 mm cutoffs, regardless of BCG status.

 

Candidates for Prophylaxis

 

Provide treatment for all
high-risk individuals with a positive PPD, regardless of age.  High-risk individuals include:

 

¨
persons with medical risk factors for developing active
TB including but not limited to HIV infection, diabetes, immunosuppression,

¨
persons with high risk of exposure to TB including but
not limited to close contacts, recent converters, persons with occupational or
environmental exposures.

 

 

Prophylaxis Regardless of the PPD
Status

 

Recent exposure to TB will not
result in a reactive PPD immediately.
They should be retested 12 weeks after their last exposure.  During the window period between the two
PPD’s, the following individuals should start prophylaxis even if PPD negative:

 

¨
contacts younger than five years old

¨
contacts between 5 and 15 years old, at the physician’s
discretion

¨
contacts with HIV infection or other medical risk
factor for TB, and contacts with behavioral risk for HIV who decline HIV
testing

 

Pregnancy

 

Prophylaxis should be offered to:

 

¨
HIV seropositive women or women with HIV risk factors
who are PPD positive – first trimester

¨
PPD+ close contacts with a smear + pulmonary TB patient
– first trimester

¨
recent converters – after the first trimester

¨
all others, including positive PPD’s of indeterminate
age, radiographic evidence of old TB – 2 to 3 months after delivery

 

Evaluation for active disease can
include a chest x-ray with appropriate use of a lead shield.

 

Treatment and Monitoring

 

Treatment generally consists of
INH 300 mg with or without vitamin B6 25 mg daily for 9 months, depending on
indication.  Monitoring for signs of
hepatic toxicity should include physical examination and serial LFTs in
patients with a higher risk of hepatotoxicity.
A sustained, fivefold increase in LFT’s indicate hepatotoxicity and
should lead to discontinuation of the INH.
Other hepatic toxins including alcohol should be avoided during this
period.  Follow-up visits to ensure
compliance and completion of therapy are important.  If the INH is taken for less than the prescribed period,
prophylactic therapy will be incomplete.
Rifampin can be considered as an alternative.