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.
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.
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.