Interventions for Tuberculosis Control and Elimination 2002

Many countries have moved towards a first-line regimen which contains
rifampicin throughout. Patients truly failing on such a regimen have
a high probability of initial multidrug resistance (or initial isoniazid resistance
and acquired rifampicin resistance). The re-treatment regimen recommended
by the IUATLD and WHO is highly unlikely to cure such a
patient, and additionally carries the risk of acquisition of ethambutol resistance.
It is not clear whether re-treatment incorporating both ethambutol
and pyrazinamide in the continuation phase will overcome this problem.
Given the relative weakness of these two drugs, there is a risk of losing
both. This has been termed the “amplifier effect” (a new term for an old
phenomenon, successive acquisition of additional drug resistance) and has
been observed to occur in an outbreak in urban Peru. 610,611 It has not been
observed in other settings where a non-rifampicin-containing continuation
phase is routine in the first-line regimen. 612
8-month regimens
The eight-month regimen evaluated in East Africa (a directly observed fourdrug,
two-month intensive phase followed by six months of self-administered
isoniazid plus thioacetazone) has become the principal treatment regimen
for previously untreated smear-positive pulmonary tuberculosis in
IUATLD collaborative programs. 8,604 Programs basing their chemotherapy
on this regimen are using a highly cost-effective intervention. 613
Replacement of streptomycin by ethambutol in the intensive phase did
not adversely affect adherence to directly observed therapy in a study conducted
in large urban settings in Tanzania, 614 and gave similar treatment
outcome under routine conditions in Madagascar, although the proportion
of failures was somewhat higher than in the streptomycin group. 615 It also
yielded good results in Benin. 616
It is likely that replacement of thioacetazone by ethambutol is equally
effective, as demonstrated in a clinical trial in India in a patient population
with a low prevalence of HIV infection. 521,522 When thioacetazone cannot
be used because of a high prevalence of HIV infection, its replacement by
ethambutol is therefore often recommended. 8
6-month regimens
The shortest treatment regimen of proven efficacy for bacteriologically confirmed
tuberculosis consists of six months of isoniazid plus rifampicin, supplemented
by pyrazinamide plus either streptomycin or ethambutol during
the first two months. This has been convincingly demonstrated where all
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