Interventions for Tuberculosis Control and Elimination 2002

Number of cases per 100,000 population
1.2
0.8
0.4
0.0
1.2
0.8
0.4
0.0
1.2
0.8
0.4
0.0
1980 1982 1984 1986 1988 1990 1992
Year of notification
gest that the transmissibility is the same for isoniazid-susceptible and isoniazid-resistant
strains, 634,635 while others indicate that transmissibility of
isoniazid-resistant strains is reduced; 122 thus the question of transmissibility
has not been fully resolved. However, strains which are resistant because
of katG gene deletion have lower virulence in experimental animal models,
636,637 while mutation of the inhA gene has no effect on virulence. 636
Thus, a fraction of isoniazid-resistant strains may have a comparative selection
disadvantage. In an effective tuberculosis program with a directly
observed intensive phase utilizing the four most potent drugs, followed by
a self-administered, non-rifampicin-containing continuation phase, no significant
multidrug resistance (resistance to at least isoniazid and rifampicin)
has emerged over 12 years of usage. 632 This could indicate that a qualitatively
good program may outpace the rate of emergence of drug resistance.
However, a study from The Netherlands indicates that some specific
mutations of the katG gene lead to high-level resistance and as great
a probability of producing secondary cases as isoniazid-susceptible strains. 638
85
Multidrug-resistant relapse
Primary resistance
Acquired resistance
Figure 52. Effect of directly observed therapy on relapse, primary resistance, and
acquired resistance, in Tarrant County, Texas, United States. Arrow indicates point
in time of introduction of universal directly observed therapy. Reproduced from 631
by the permission of the publisher Massachusetts Medical Society.