Interventions for Tuberculosis Control and Elimination 2002

Tuberculosis was much more frequent among mentally ill patients in
institutions than in the general population in the United States, and it was
natural to consider this group for preventive chemotherapy to reduce the
risk of endogenous reactivation disease. 872 People of all ages were included,
but older patients made up the bulk of participants, with an average age of
around 50 years. After exclusion of those participants known to have had
a negative tuberculin skin test at intake, the protection afforded by isoniazid
during the treatment year was 81%.
Persons in contact with notified tuberculosis patients for various lengths
of time were included in another US Public Health Service clinical trial. 874
Some of the index cases had long since been cured of active disease, while
others were still on treatment. Contacts who had already developed tuberculosis
at the time of enrolment were excluded from the trial. Over half
of the enrolled were initially tuberculin negative and stratification by initial
tuberculin skin test result was not provided. The risk of tuberculosis
during the treatment year was very low and the confidence interval around
the observed point estimate of protection of 69% was thus very wide.
However, eight of the nine observed cases in the placebo group had occurred
among those with an initially positive tuberculin skin test.
In Alaska, a community preventive chemotherapy trial was started when
the annual infection rate was almost 100 times greater than in the continental
United States. 641,873 In the Bethel Hospital service area where the
trial was conducted, the annual risk of infection was 25%, a rate far exceeding
any reported risk elsewhere in the world. 876 By the time of starting
the trial the risk of infection had already substantially decreased. Because
of the adverse climatic and transport conditions it was not feasible to test
all persons with tuberculin. Approximately one third of those tested had
a tuberculin skin test diameter of less than five millimeters. During the
treatment year the protection from isoniazid was 66%. Protection was
demonstrated at all levels of adherence (amount of isoniazid taken), with
an indication that six months of isoniazid might have sufficed. 876
In Greenland it had been realized, by the mid-1950s, that the majority
of tuberculosis cases developed in the years immediately after primary
infection. A trial was thus undertaken to study the efficacy of isoniazid
preventive chemotherapy at the community level. 875,877 Children below the
age of 15 years were excluded from the trial. Placebo or isoniazid were
given weekly for a total duration of nine months. Half of the participants
received all dosages and over 80% received at least three quarters of the
intended dosages. The crude protection afforded by isoniazid during the
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