Interventions for Tuberculosis Control and Elimination 2002

arracks. 878 On entering service in January, 59 of the men sharing the barracks
had a negative tuberculin skin test, while by the beginning of April,
56 of them had become converters. In the entire camp 305 conversions
were registered among 1,105 initially negative men. A double-blind controlled
trial was carried out among the 261 converters who were not excluded
due to departure or because they had already contracted tuberculosis at the
time of starting the trial. After one year, nine cases had developed tuberculosis
in the placebo group compared to only one in the isoniazid group.
During follow-up for a total observation period of four years, three additional
cases developed, all in the placebo group, indicating an overall protection
of 93%.
In Nairobi, Kenya, contacts of newly diagnosed tuberculosis cases were
randomly assigned to receive isoniazid or placebo for one year. 880 During
the treatment year and the two-year follow-up period, preventive chemotherapy
provided 85% protection against culture-confirmed pulmonary tuberculosis.
A large trial was conducted by the US Public Health Service among
contacts of newly identified cases of tuberculosis. 879 Contacts found to
have tuberculosis during the initial examination were excluded from the
trial. Over 25,000 contacts were eligible for enrolment. Of these, 48%
had tuberculin skin test reaction sizes of five or more millimeters of induration.
Approximately two thirds of contacts were less than 20 years old.
About two thirds of study participants were estimated to have taken all of
their medications, and about 80% three quarters or more. Among those
who could be reexamined at the end of the 12-month period of medication,
isoniazid gave 77% protection against tuberculosis.
In Japan, contacts of new cases of tuberculosis were randomly assigned
to receive placebo or isoniazid. 881 The protection afforded was only 30%,
with confidence intervals including zero.
Infection with the human immunodeficiency virus
Infection with HIV is the strongest yet identified risk factor for progression
from tuberculous infection to tuberculosis. Because HIV alters the
biological response to M. tuberculosis so fundamentally, it could not be
taken for granted that isoniazid preventive chemotherapy would work as
well as in immunocompetent patients.
Tuberculosis is accompanied by an increase in tumor necrosis factor
alpha (TNF-α). TNF-α also increases in vitro replication of HIV. 882 It
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