Interventions for Tuberculosis Control and Elimination 2002

Not all drugs are equally suitable for intermittent use. Thioacetazone,
for example, is not suitable for intermittent use. 526 Furthermore, intermittent
treatment is indicated only to facilitate directly observed therapy, not
for self-administered treatment. Thus, unless a rifampicin-containing continuation
phase is selected, the principal issue is the efficacy of the use of
intermittent therapy during the intensive phase of treatment.
Remarkably little is known about the efficacy of intermittent use during
an intensive phase containing four medications, followed by a selfadministered
continuation phase that does not contain rifampicin. Concerns
have been raised that an eight-month regimen with an intermittent intensive
phase from the outset may be inferior in HIV-infected patients. 527 To
facilitate directly observed therapy in national programs, these are critical
issues that need urgent attention.
Treatment regimens of less than six months’ duration
Regimens of four months’ duration (containing rifampicin throughout) for
bacteriologically confirmed pulmonary tuberculosis have been studied in
Singapore, but yielded unacceptably high relapse rates. 510-512
A regimen of four and a half months duration for bacteriologically
(sputum smear and culture) confirmed pulmonary tuberculosis has been
studied in Agra, India. 516,517 In this trial, four drugs (isoniazid, rifampicin,
pyrazinamide, and streptomycin) were given for a total of three months,
followed by one and a half month of isoniazid plus rifampicin, all given
daily. All but one of the 65 patients enrolled were eligible for and followed
up for relapse, and only one patient relapsed during the two-year
follow-up period. 517 Despite the seeming efficacy of this four and a halfmonth
regimen, confirmatory studies have not become available, the regimen
has never been accepted by the medical community, and the credibility
of the result of the study was actually challenged. 528
Among patients with repeatedly negative sputum smears, shorter regimens
have been investigated. 122 If the initial culture was negative (but
radiologically the disease was considered to be active) or positive, relapse
rates were three per cent or less with a three-month or a four-month regimen,
respectively. 529 However, in routine practice even countries involved
in these trials have abandoned the practice of treating patients with newly
diagnosed (but bacteriologically unconfirmed) pulmonary tuberculosis for
less than six months.
Currently, regimens shorter than six months duration are not recommended
by WHO for bacteriologically unconfirmed tuberculosis. A prin-
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