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Canada Communicable Disease Report
Vol. 23 (ACS-5)
1 November 1997
An Advisory Committee Statement (ACS)
Committee to Advise on Tropical Medicine and Travel (CATMAT)*
THE RISK AND PREVENTION OF TUBERCULOSIS IN TRAVELLERS
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Introduction
The annual risk of Mycobacterium tuberculosis infection may be
as much as 300-fold higher in some tropical and developing countries than
in western Europe and North America(1,2). Infection with M.
tuberculosis and active tuberculous (TB) disease can be a consequence
of travel, but there are very few data from which to accurately estimate
this risk. Available information suggests that individuals travelling
or living overseas may have an exposure risk similar to that of the local
population, depending on their activities and contact with local people(3,4).
1. DETERMINANTS OF A TRAVELLER'S RISK OF TUBERCULOSIS EXPOSURE
Risk of exposure is likely to be influenced by local TB rates. World
Health Organization (WHO) estimates of TB case rates per 100,000 population
in 1995 are as follows: Southeast Asia 241, western Pacific 140,
Africa 242, eastern Mediterranean 168, Americas (except United States
and Canada) 123, Eastern Europe 47, and Western industrialized countries
and Japan 23(5). By contrast, the incidence of TB in non-Aboriginal
people born in Canada was 1.9 per 100,000 in 1992(6).
Risk of exposure is likely to be related to duration of stay or travel
in high-prevalence areas. The nature and circumstances of contact
with local people are likely to be important determinants of risk of exposure.
Work in a health-care setting in a high-prevalence country may be
associated with a particularly high risk of exposure to TB.
2. THE RISK OF DEVELOPING ACTIVE TUBERCULOSIS FOLLOWING M. TUBERCULOSIS
INFECTION
After infection with M. tuberculosis, indicated by tuberculin skin test
(TST) conversion, an immunocompetent individual is estimated to have a
5% to 15% lifetime risk of progression to active TB. The annual
risk is highest in the first 1 to 2 years after infection(7).
A number of factors, including diabetes mellitus, prolonged corticosteroid
therapy, chronic renal failure, and malignant lymphoma may increase this
risk. Co-infection with HIV is associated with the greatest risk
of developing active TB, approximately 7% to 10% per year(8,9).
3. MEASURES FOR REDUCING THE RISK OF TUBERCULOSIS
3.1 Skin Testing and Chemoprophylaxis
One strategy for prevention of TB is regular tuberculin skin testing
with consideration of chemoprophylaxis if infection occurs. Chemoprophylaxis
with isoniazid can reduce the risk of active TB by up to 90% in positive
individuals when the infecting organism is sensitive to isoniazid and
when compliance is high(10,11). There is a small risk
of hepatotoxicity with isoniazid use which increases with age, alcohol
use, or underlying liver disease(12).
Several factors may limit the effectiveness of this strategy. Compliance
with skin testing or chemoprophylaxis, or both, is often very poor in
the general population and among health workers(13-17). The
optimal frequency of skin testing is uncertain; some cases of infection
may progress to active TB in the intervals between TSTs. Isoniazid
prophylaxis is likely to be ineffective if the infecting strain of M.
tuberculosis is resistant or if the individual cannot tolerate the
drug; experience with alternative chemoprophylactic regimens is limited.
3.2 Bacille Calmette-Guérin Vaccination
Bacille Calmette-Guérin (BCG) is a live vaccine developed in 1921 by
repeated passage of M. bovis in culture. Several billion human
doses of this vaccine have been administered. Two BCG products are approved
in Canada for intradermal/intracutaneous use(18). One-half
the adult dose is recommended for children < 1 or < 2 years
of age, depending on which product is used. Manufacturers' instructions
list extensive skin disease and conditions associated with depressed cell-mediated
immunity as contraindications. They recommend against concurrent administration
with other vaccines, and advise caution with use in pregnancy although
adverse effects on the fetus have not been demonstrated.
3.2.1 Efficacy of Bacille Calmette-Guérin Vaccine
The results of a large number of studies of BCG efficacy have varied
widely, from no demonstrable protection to more than 80% efficacy. The
interpretation of these results remains controversial. A reappraisal
of BCG studies has suggested that those with better methodology and with
narrower confidence intervals around the estimate of efficacy tend to
show greater protection(19). A meta-analysis of 16 clinical
trials and 11 case-control studies found an overall efficacy of 50% to
51%(20), and demonstrated a positive association between distance
from the equator and vaccine efficacy(21). Many BCG studies
have been limited to children. Evidence for BCG efficacy is better
established in children(22), and BCG may afford greater protection
against severe forms of TB such as miliary TB and meningitis(23).
Limited information suggests that BCG confers some protection against
TB in health-care workers(24).
Several studies have shown protection against leprosy(25,26).
Several hypotheses have been proposed to explain the considerable
variation in efficacy among BCG studies. The most widely accepted explanation
is an effect of exposure to environmental mycobacteria, which appears
to either reduce or mask the protection conferred by BCG. Such exposure
is more likely to occur in warmer climates, consistent with the meta-analysis
finding of lower efficacy in populations closer to the equator(20,21).
3.2.2 Safety and Adverse Effects of Bacille Calmette-Guérin Vaccination
Serious adverse events such as mycobacterial dissemination or death are
very rare(27). Local ulceration with a resultant scar
is very common and regional lymphadenopathy may also occur. The
risk of dissemination appears to be higher in immunocompromised vaccine
recipients.
3.2.3 Effect of Bacille Calmette-Guérin Vaccination on the Tuberculin
Skin Test Reaction
A potential problem in the use of BCG is the effect on subsequent use
of tuberculin skin testing. Estimates of the frequency with which
BCG vaccination results in a positive TST vary widely(28),
and may be affected by vaccine strain, age at vaccination, or other factors.
BCG in infancy rarely explains the presence of a strong TST reaction
years later(29,30). Current recommendations suggest that
the diameter of induration, the time elapsed since BCG administration,
and the likelihood of exposure to TB be considered when interpreting a
TST in an individual with a history of BCG vaccination(31,32).
The tuberculin response following BCG vaccination does not correlate
with protection(33,34).
3.3 Choice of Strategy for an Individual Traveller
The advantages and disadvantages of both TB prevention strategies must
be considered on an individual basis. A decision analysis, comparing BCG
with TST or chemoprophylaxis for house staff in a "high-prevalence" American
hospital, favoured BCG under most assumptions(35).
Recommendations Table 1 presents evidence-based
medicine categories(36) for the strength and quality of evidence
for each of the recommendations that follow.
-
All travellers to high-prevalence countries, particularly those
travelling or living overseas with children, should be informed of
the risk of TB (B III).
-
Travellers with significant immune compromise, such as HIV, should
be informed of the serious risk associated with TB exposure and of
the important limitations of either a BCG vaccination or periodic
skin testing with chemoprophylaxis in the event of conversion (A
III).
-
Travellers should be advised to avoid consumption of unpasteurized
milk since it may contain M. bovis or other pathogenic
organisms (A III).
-
Medical assessment of domestic workers or other host-country nationals
who are in close contact with the traveller or the traveller's family
particularly if a chronic cough is present, may reduce the risk of
TB exposure as well as potentially benefiting the local person involved
(C III).
-
Canadians working in health-care settings in developing countries
should follow current infection control recommendations to the greatest
degree possible to minimize the risk of exposure to TB(37-39)
(B III).
Table 1 Strength and quality of evidence - summary
sheet
Categories for strength of each recommendation
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CATEGORY
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DEFINITION
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A
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Good evidence to support a recommendation for use.
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B
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Moderate evidence to support a recommendation for use.
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C
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Poor evidence to support a recommendation for or against use.
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D
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Moderate evidence to support a recommendation against use.
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E
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Good evidence to support a recommendation against use.
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Categories for quality of evidence on which recommendations
are made
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GRADE
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DEFINITION
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I
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Evidence from at least one properly randomized, controlled trial.
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II
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Evidence from at lest one-well-designed clinical trial without
randomization, from cohort or case-controlled analytic studies,
preferably from more than one centre, from multiple time series,
or from dramatic results in uncontrolled experiments.
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III
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Evidence from opinions of respected authorities on the basis of
clinical experience, descriptive studies, or reports of expert committees.
|
-
Travellers going to high-prevalence countries for extended periods
(e.g. 3 months; less, if risk is expected to be high) or working in
a health-care setting in a developing country for any period of time
should be offered a TST with five tuberculin units of purified protein
derivative (including two-step testing where indicated) unless there
is a past history of tuberculosis or a well-documented previous positive
TST(40) (B III).
-
If the initial TST is found to be positive (³ 10 mm induration
in healthy immunocompetent travellers), current management guidelines
should be followed(32) (B III).
-
If the TST is negative, the individual should be informed about
practical means of avoiding TB exposure. Persons should be advised
to choose either BCG vaccination or a TST at least every 2 years,
but preferably annually, as well as 3 to 6 months after leaving the
high-prevalence area (B III). If a TST becomes positive,
the traveller should be assessed by someone with expertise in TB to
consider the use of chemoprophylaxis and to determine the chemoprophylactic
regimen (A I).
- In making the choice between BCG vaccination or periodic skin testing
with prophylaxis in the event of conversion, the following factors should
be considered:
- anticipated feasibility of, and compliance with, repeated skin testing
and chemoprophylaxis
- likelihood of isoniazid intolerance (age, liver disease, excess alcohol
use) likelihood that an infecting strain of M. tuberculosis may
be isoniazid-resistant (depends on local rates of primary resistance)
- individual preference
- age - the role of BCG vaccination may be particularly important in
children especially those < 1 year of age (B III).
-
Where possible, BCG should be administered at least 4 weeks before
the anticipated exposure to tuberculosis (B III).
-
A "baseline" measurement of the tuberculin reaction 3 months after
BCG vaccination may be considered to aid in the interpretation of
any subsequent TSTs(31) (C III).
-
Regardless of the duration of travel or the preventive measures
employed, TB must be considered in the differential diagnosis of illness
in Canadians returning from high-prevalence countries as well as in
immigrants from those countries (A III).
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[Canada Communicable
Disease Report]
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