Structured Abstract
Please note: In 2003, the CTF updated its Grades of
Recommendations to include an "I Recommendation" for situations where
insufficient evidence exists to allow a recommendation to be made.
(Formerly, these situations were captured under a "C
Recommendation".) This change is not retroactive, and all
"C Recommendations" made prior to 2003 have not been
reevaluated in light of the new "I" recommendation grade. For a
discussion of these recommendation grades, please link to the 2003 article in
the Canadian Medical Association Journal here.
Screening and Isoniazid Prophylactic Therapy for Tuberculosis
Prepared by Sharon L. Walmsley, MD, FRCPC, Assistant Professor, Department
of Medicine and Microbiology, University of Toronto
These recommendations were finalized by the Task Force in January 1994
Contents
Objective
To make recommendations about screening and isoniazid (INH) chemoprophylactic
therapy for tuberculosis in general and high risk populations in Canada.
This updates a 1979 report.
Burden
of Suffering
The number of cases of active tuberculosis in Canada has been decreasing
gradually over the past few decades, and in the past few years has plateaued,
with 1,995 cases (7.5 per 100,000) reported in 1990. Most reported
cases occur among Canadian-born very young and those in advanced age, Canadian-born
Natives, and immigrants from areas where tuberculosis is endemic, including
Africa, Asia, Central America and certain countries in South America and
the Caribbean. Death rates from tuberculosis have also declined.
In Canada in 1990, 129 persons with tuberculosis died (0.6 per 100,000
population) and in 60 cases, tuberculosis was the cause of, or a significant
contributor to death.
Most new cases of tuberculosis are pulmonary. Persons infected
with large inocula (i.e. following household exposure to a cavitary case)
and those with increased susceptibility to infection (e.g. children less
than 5 years) are at higher risk of acquiring infection. In 90% of
exposed persons, host defenses contain the primary infection, but the individual
develops a positive tuberculin skin test. In the absence of preventive
measures 5-15% will develop reactivation tuberculosis during their lifetime,
the risk being greatest during the first two years following exposure.
Groups at increased risk of reactivation include patients with silicosis,
head and neck cancer, jejunoilial bypass or in those who require hemodialysis
[relative risk (RR) increased 10-30 times]; patients with low body weight
or nutritional deficiency, diabetes mellitus, or gastrectomy (RR increased
2-5 times); and patients infected with HIV (reactivation rates of 8-9%
per year). Other groups identified to be at increased risk are those with
other immunosuppressive disorders (hematologic malignancies), those requiring
immunosuppressive therapy for malignant or non-malignant conditions, patients
requiring high dosages of corticosteroids over prolonged periods, the urban
poor, persons living in shelters, intravenous drug users and alcoholics.
Options
The Mantoux tuberculin skin test is both the screening measure and the
current gold standard. INH was examined as a chemoprophylactic treatment
for preventing reactivation of latent tuberculosis infection.
Outcomes
Effectiveness of INH prophylaxis was assessed in terms of the development
of active tuberculosis.
Evidence
MEDLINE was searched for 1966 to 1992 using the MeSH heading "tuberculosis"
and the subheadings "tuberculin skin test", "prevention and control" and
"isoniazid". Indices of the American Review of Respiratory Diseases (1960
to 1992) were also searched. Study results were synthesized in table or
graphic format only.
Recommendations were graded as:
|
A
|
Good evidence to support the recommendation that the condition
be specifically considered in a PHE. |
|
B
|
Fair evidence to support the recommendation that the condition
be specifically considered in a PHE. |
|
C
|
Poor evidence regarding inclusion or exclusion of the condition
in a PHE, but recommendations may be made on other grounds. |
|
D
|
Fair evidence to support the recommendation that the condition
be specifically excluded from consideration in a PHE. |
|
E
|
Good evidence to support the recommendation that the condition
be specifically excluded from consideration in a PHE. |
Quality of evidence was rated according to 5 levels:
|
I
|
Evidence from at least 1 properly randomized controlled
trial (RCT). |
|
II-1
|
Evidence from well-designed controlled trials without randomization. |
|
II-2
|
Evidence from well-designed cohort or case-control analytic
studies, preferably from more than 1 centre or research group. |
|
II-3
|
Evidence from comparisons between times or places with
or without the intervention. Dramatic results in uncontrolled experiments
could also be included here. |
|
III
|
Opinions of respected authorities, based on clinical experience,
descriptive studies or reports of expert committees. |
Values
The 13-member Task Force of experts in family medicine, geriatric medicine,
pediatrics, psychiatry and epidemiology used an evidence-based method for
evaluating the effectiveness of preventive health care interventions. Recommendations
were not based on cost-effectiveness of options. Patient preferences were
not discussed.
Background papers providing critical appraisal of the evidence and tentative
recommendations prepared by the chapter author were pre-circulated to the
members. Evidence for this topic was presented and deliberated upon in
1- to 2-day meetings, 2 to 3 times per year from January 1993 to June 1993.
Consensus was reached on final recommendations.
Benefits,
Harms, and Costs
The Mantoux test is an intradermal injection into the dorsal surface of
the forearm to produce a discrete wheal of 6 to 10 mm in diameter. Test
reading is done at 48 to 72 hours, and cut-off values vary depending on
risk for infection and cross reaction with atypical mycobacteria. Localized
allergic reactions (wheal and flare, rash) occur in 2% to 3% of persons.
INH is the only drug which has been extensively studied as a chemoprophylactic
agent. While early studies had a variety of methodological flaws 19 of,
more than 20 clinical trials, all with methodological flaws, have reported
significant benefits for of INH prophylaxis.
No controlled studies exist regarding underlying medical conditions
and risk of latent infection reactivation.
Adverse effects of INH include hypersensitivity reactions, INH-induced
lupus-like syndrome, peripheral neuropathy, gastrointestinal distress,
CNS abnormalities (memory loss to psychosis or seizures) and hepatitis.
Risk of INH-related hepatitis is estimated to be 0.5%, with a mortality
rate of 14 per 100,000.
Recommendations
Recommendation grade [A, B, C, D, E] and level of evidence
[I, II-1, II-2, II-3, III] are indicated after each recommendation. Citations
in support of individual recommendations are identified in the guideline
text.
-
Good evidence exists to support screening individuals at high risk [immigrants
from Africa, Asia, Central America, and some countries in South America
and the Caribbean; Canadian-born aboriginals; close contacts of active
cases; persons with abnormal chest radiographs consistent with healed tuberculosis;
and those with underlying medical conditions that increase the risk of
tuberculosis infection (silicosis, jejunoileal by-pass, hemodialysis, gastrectomy,
malnutrition, intravenous drug use, alcohol abuse, known or suspected HIV
infection)] [A, II-2]
-
Good evidence exists for not screening individuals from the
general population [E, II-2].
-
Good evidence exists to recommend INH prophylaxis for household contacts,
skin test converters [A, I
], and persons with conditions such as HIV that increase risk of tuberculosis
reactivation [A, III].
-
Fair evidence exists to recommend INH prophylaxis for persons <35 years
with positive skin tests or those with fibrotic scars on chest x-ray [B,
I].
-
Poor evidence exists to recommend for or against INH prophylaxis for persons
> 35 years with positive skin tests [C].
Validation
This report was externally peer-reviewed. The American Thoracic Society
(ATS), Centers for Disease Control, and the1989 United States Preventive
Services Task Force (USPSTF) recommend screening persons at high risk.
The ATS and 1989 USPSTF recommend INH prophylaxis for all patients with
known or suspected HIV, and a positive skin test. Persons with a positive
test plus fibrotic lesions on x-ray should be treated for active disease.
The American Academy of Pediatrics Redbook recommends annual screening
of children at high risk, 3 age-specific screenings for children at low
risk, and INH prophylaxis for all persons <35 years with positive skin
test.
Sponsors
The Canadian Task Force on Preventive Health Care
developed this guideline with funding from Health Canada.
Documents
Source
Other
-
Canadian Task Force on the Periodic Health Examination. The periodic health
examination. Can Med Assoc J. 1979;121:1193-1254.
Link to Full Text of this
review
Link to Summary Table of Recommendations of this review
Link to Selected References list of this review
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