Interventions for Tuberculosis Control and Elimination 2002

thus suggested equivalence (the hypothesis of the study) between the two
regimens. Completion of therapy was superior in the experimental compared
to the control arm.
In the United States, preventive chemotherapy regimens using rifampicin
(plus pyrazinamide) of two to four months’ duration have been recommended.
897 However, recent reports on fatal and severe hepatitis associated
with preventive therapy using rifampicin plus pyrazinamide 904 have
led to a change of the recommendation and advising great caution in the
use of this combination. 904
Effectiveness of preventive chemotherapy
There can be little doubt about the efficacy of preventive chemotherapy, at
least with isoniazid if given for twelve months to persons with tuberculous
infection without additional risk factors. There are indications that a regimen
of nine months’ duration might still be similarly efficacious in reducing
the risk of tuberculosis. The efficacy of isoniazid in patients with risk
factors is much less well established, and many studies dealing with HIVinfected
patients suffer from inadequate sample sizes. It also seems that
rifampicin-containing regimens of shorter duration can afford similar protection,
but the optimal duration and the role of companion drugs have not
been sufficiently well established. A short-coming of most preventive
chemotherapy trials has been the self-administration of medications, thus
portraying more the effectiveness than the potential efficacy of the regimen
in question.
All studies that have evaluated that component have clearly demonstrated
the adverse effect of non-adherence on the regimen’s efficacy, as
would be expected. This has been the case even in the setting of clinical
trials where adherence might be better than under daily operations within
the context of a national program.
Several studies have also demonstrated that the type of patients who
are selected for preventive chemotherapy is important, and that large numbers
may have to be treated to prevent a single case if the persons selected
have a low risk of tuberculosis.
In a simplified form, operational effectiveness can thus be summarized
as the product of tuberculosis risk given the presence of tuberculous infection,
the efficacy of the regimen, and adherence to the prescribed medications.
In a few examples, table 11 summarizes different situations and the
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