|A CONCURRENT COMPARISON OF AN UNSUPERVISED SELF-ADMINISTERED
DAILY REGIMEN AND A FULLY SUPERVISED TWICE WEEKLY REGIMEN OF CHEMOTHERAPY
IN A ROUTINE OUT-PATIENT TREATMENT PROGRAMME
|GVJ Baily, GE Rupert Samuel & DR Nagpaul: Indian
J TB 1974, 21, 152-67.
The relative merits of a fully supervised twice
weekly regimen of Streptomycin and INH (SHtW) and an unsupervised
daily regimen of INH and Thioacetazone (TH) in routine programme
conditions in an urban area are compared in terms of acceptability
and response to treatment at one year. Of the 474 newly diagnosed
sputum positive cases at Lady Willingdon TB Demonstration &
Training Centre, Bangalore during 1968-69, 134 were allocated to
SHtW regimen and 189 to TH regimen. All others who were unwilling
to take the allocated regimen or were excretors of bacilli resistant
to INH and or SM were analysed as a subsidiary group.
About 25% of the patients allocated to SHtW regimen
expressed unwillingness to start treatment on account of unsuitability
of working hours and or distance. Refusal to TH regimen was negligible
(5%). As regards drug acceptability after start of treatment, while
the duration of treatment taken was similar for both the regimens,
the level of drug intake achieved by the SHtW patients was lower
compared with TH patients i.e., 31.3% of the SHtW patients and 56.1%
of TH patients took more than 80% of treatment. If concealed irregularity
among TH patients is taken into consideration, it is likely that
the drug intake among TH patients would be similar to the drug intake
among SHtW patients. The acceptability was therefore almost similar
among SHtW and TH patients. Very low level (28%) of treatment completion
was achieved by SHtW patients. With TH regimen, 46% had made 10
or more monthly collections during 12 months. Among the SHtW patients
there was greater irregularity in the later months which was not
apparent among TH patients. However, the favourable response among
patients on SHtW and on TH regimen was 68% and 60%
respectively. Deaths among SHtW patients were 4%,
13.5% among TH patients, the difference being statistically significant.
The response was directly related to the level of drug collection
or supervised consumption. The large proportion of the patients
who stopped treatment prematurely, continued to remain positive
with drug sensitive organisms, if initially they were so. In the
subsidiary group there were 62 patients who were excretors
of drug resistant organisms. They were treated with drugs to which
their organisms were resistant and nearly 30% of these patients
had negative culture at the end of one year.
It is concluded that (i) SHtW regimen was superior
to TH as it prevented deaths and showed better bacteriological conversion
among patients with level 3 & 4 of treatment and (ii) treatment
organization is the most important factor in obtaining better results
in routine chemotherapy with available drug regimens.
|KEY WORDS: TH REGIMEN, DAILY REGIMEN, SUPERVISED
INTERMITTENT REGIMEN, ACCEPTABILITY, EFFICACY, CONTROL PROGRAMME.
|A CONTROLLED CLINICAL TRIAL OF 3 AND 5 MONTH REGIMENS
IN THE TREATMENT OF SPUTUM POSITIVE PULMONARY TUBERCULOSIS IN SOUTH
|Tuberculosis Research Centre, Madras and National Tuberculosis
Institute, Bangalore: Ame Rev Respir Dis 1986, 134, 27-33.
A controlled clinical trial of the three Short
Course Chemotherapy (SCC) regimens was carried out at the Lady Willingdon
State Tuberculosis Centre, Bangalore and Tuberculosis Research Centre,
Madras with the collaboration of National Tuberculosis Institute,
Bangalore. The regimens were (1) R3: (rifampicin, streptomycin,
isoniazid and pyrazinamide daily for 3 months (3RSHZ); (2) R5: same
as regimen R3, followed by streptomycin, isoniazid, pyrazinamide
twice weekly for 2 months (3RSHZ/2S2H2Z2); (3) Z5: same as regimen
R5 but without rifampicin (3SHZ/2S2H2Z2). Newly diagnosed tuberculosis
patients who were aged 12 years or more had no history of previous
treatment and two sputum cultures positive for M.tuberculosis were
taken to the study and allocated at random to one of the above stated
three regimens. The patients were given supervised chemotherapy
as out patients. Sputum specimens were examined by fluorescent microscopy,
culture by modified Petroff's method, tested for sensitivity to
INH, rifampicin, streptomycin and ethambutol. The follow up was
done by sputum smear and culture examination at the end of every
month for 2 years. The distribution of various pre treatment characteristics
like age, sex, and initial sensitivity status were similar in the
three series. At the end of 3 months, of the 455 patients on R3,
and R5 series, 96% with drug sensitive organism became culture negative
and of 235 on Z5 series 93% became culture negative. For R5 and
Z5 series favourable response at the end of chemotherapy were 96%,
99% and 97% respectively. In all, 6 patients (3 R3 & 3 Z5) were
classified as having unfavourable response. At the end of 24th month
from the date of start of treatment, 20% of the 200 patients
on R3, 4% of 187 patients on R5 and 13% of 199 patients on
Z5 had bacteriological relapse. The difference between R3 and Z5
series was highly significant. (p = 0.00001). The relapse rates
in R3 & Z5 series were significantly higher than that in R5.
Of the 57 patients with initial drug resistance organisms in R3
and R5 series combined 4 had an unfavourable response to treatment
compared with 13 of 26 in the Z5 series (p = 0.0001). Of the 4 patients
with an unfavourable response in R3 and R5 series combined, resistance
to rifampicin emerged in 2 patients. Complaints of arthralgia were
made by 45% of the R3 and R5 patients combined and 70% of Z5 patients
(p = 0.00001). However, chemotherapy was modified in only 5 and
12% respectively. Jaundice occurred in 7% of the R3 and R5 patients
and 1% of the Z5 patients (p = 0.0001).
|KEY WORDS: SCC REGIMEN, DAILY REGIMEN, CLINICAL
TRIAL, EFFICACY, ADVERSE REACTIONS.
|A STUDY ON ADVERSE DRUG REACTIONS IN TWO REGIMENS
OF SHORT COURSE CHEMOTHERAPY
|Sudha Xirasagar, P Jagota, N Parimala & K Chaudhuri:
NTI Newsletter 1989, 25, 51-60.
In a study of feasibility of treatment of smear
positive patients with Short Course Chemotherapy (SCC) regimens
under District TB Programme (DTP) conditions in a city, adverse
drug reactions in terms of frequency of episodes, incidence in the
cohort of patients, time of occurrence, major adverse reactions
requiring modification of chemotherapy and or symptomatic treatment,
Patients were allocated to one of the two 8 month
SCC regimens i.e., Regimen 'A' 1 SHRZ/6TH, Regimen 'B' 2SHR/6TH.
Overall incidence of adverse drug reaction in cohort of 265 patients
was 37%, 9% of which were considered as major in nature. 34 episodes
of such reactions resulted in modification of chemotherapy in 15
patients during intensive phase. Though gastro intestinal symptoms
were predominant, cutaneous toxicity was the pre eminent cause of
modification of regimen. No case of exfoliative dermatitis occurred.
A total of 333 episodes of adverse drug reactions of minor nature
occurred; 50% being gastro intestinal symptoms followed by cutaneous
symptoms. More than 70% of all adverse drug reactions of intensive
phase occurred in the first half of the period. There was no significant
difference between the two regimens in the incidence of adverse
drug reactions of either major or minor in nature.
SCC is being implemented in a phased manner in
the DTP. Before introducing SCC in large number of districts, it
would be prudent to find out whether SCC would be acceptable to
both doctor and patient in terms of adverse drug reactions.
It can, therefore, be concluded that adverse reactions may not be
a major constraint for inclusion of SCC under DTP for treating sputum
positive tuberculosis patients provided that additional resources
and man power are allocated to the DTCs to manage patients in the
centre and extend effective guidance to staff working in peripheral
|KEY WORDS: SCC REGIMEN, DAILY REGIMEN, ADVERSE
REACTIONS, CONTROL PROGRAMME, FEASIBILITY.
|A STUDY OF OPERATIONAL FACTORS INFLUENCING THE APPLICABILITY
OF TWO REGIMENS OF SHORT COURSE CHEMOTHERAPY UNDER CONDITIONS OF AN
URBAN TUBERCULOSIS PROGRAMME
|P Jagota, Sudha Xirasagar, N Parimala & K Chaudhuri:
Indian J TB 1989, 36, 213-23.
An operational study of two regimens of Short Course
Chemotherapy (SCC) to assess their efficacy under programme conditions,
applicability and feasibility in District TB Programme (DTP) was
undertaken in an urban TB centre. The two regimens studied were
1SHRZ/7TH and 2SHR/6TH. Their operational efficacy (efficiency)
was found to be 87% and 92% respectively which had already been
reported in an earlier paper. The various factors i.e., initial
willingness, drug default, treatment completion pattern, adverse
drug reactions and initial drug resistance with their potential
harmful effects on the treatment outcome as well as work load and
extra cost these regimens entail for DTP organisation are discussed
in this paper.
Out of a total of 1822 smear positive patients
diagnosed at the Lady Willingdon State TB Centre during intake period
(Feb '84 to March '85), 1126 were residents of Bangalore City. Of
these 695 (61.7%) were unwilling to attend the clinic daily for
2 months, 27 were unfit and one was excluded by mistake. Thus, 403
(38.3%) initially willing patients were classified either as 'core
group' or 'Non core group, according to the history of previous
anti TB treatment (321 and 82 respectively). Of the 695 (77.6%)
unwilling persons, majority were those who pleaded inability to
attend daily for 2 months without specifying any particular reason.
Refusal of SCC due to injections accounted for 12.8% and 9.5% wanted
to take treatment elsewhere. Old age influenced willingness adversely.
Of the 321 patients in the core group, 56 were
excluded due to missing more than 50% of intensive phase doses.
Among the remaining patients, 61 (48%) out of 127 patients on Regimen
A and 48 (34%) out of 138 on Regimen B, did not make a single default
in the intensive phase. Of the total 910 defaults for which actions
were taken, 640 (70%) were retrieved by letter writing,
among the remaining 293 (72%) were retrieved by home visiting.
Main reasons for default elicited during home visits were: going
out of station (52.9%) followed by patients being busy with work
(19.1%). Compensatory phase was availed by 156 of the 265 patients
who missed one or more doses due to default in the treatment. The
pattern of treatment completion of 321 core group patients in the
two regimens were similar i.e., in both the phases 65% for Regimen
A and 63% for Regimen B. Incidence of minor adverse reactions was
28% and major toxic reactions were experienced by 8.4% of patients.
Workload for treating 321 patients was due to supervised administration
of drug 45 patients per day. Letter writing to 3.1 per patients,
home visiting 1.1 per patient and doctor's attention for adverse
reaction 2 occasions per patient. This could be managed with the
existing staff. The cost of Regimen A was Rs.220/ per patient and
for Regimen B, 268/ per patient. Cost to patient for transportation
was Rs.70/ and Rs.113/ for Regimen A and B respectively.The major
disturbing finding of the study was initial low acceptability of
about 40% for SCC. The home visiting which was crucial in increasing
the completion rate in this study is usually not available in most
of the DTCs. Workload, adverse reactions etc. were not of any problem
for implementation of SCC in the programme.
|KEY WORDS: SCC, DAILY REGIMEN, OPERATIONAL FACTORS,
APPLICABILITY, CONTROL PROGRAMME.