STATUS OF SHORT COURSE CHEMOTHERAPY UNDER NATIONAL TUBERCULOSIS PROGRAMME
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- Title
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STATUS OF SHORT COURSE CHEMOTHERAPY UNDER NATIONAL TUBERCULOSIS PROGRAMME
- extracted text
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Ind. J. Tub., 1994,41,211
Original Article
I*
STATUS OF SHORT COURSE CHEMOTHERAPY UNDER NATIONAL
TUBERCULOSIS PROGRAMME*
L. Suryanarayana1, K. Vembu2. C. Satyanarayana3 and R. Rajalakshmi3
Summary. Short Course Chemotherapy
(SCC) was introduced under the National
Tuberculosis Programme (NTP) in 1983-85, on
a pilot basis, in 18 districts of the country.
Government of India started its extension in
rest of the districts from 1986-87 onwards in a
phased manner. SCC is provided only to
smear positive patients, aged 15 years and
above, irrespective of their previous history of
treatment. Two types of regimen-an
intermittent supervised regimen of 6 months'
duration (Regimen A) and a self-administered
oral regimen of 8 months duration (Regimen
B)-are offered to the patients under SCC. By
the end of 1992, 252 out of 390 (65%) District
Tuberculosis Programmes (DTPs) in the
country have been covered under SCC. While
248 DTPs un*r SCC are monitored by
National Tubercqjosis Institute (NTI),
Bangalore, four are being monitored by
Tuberculosis Research Centre (TRC), Madras.
In the 248 SCC-DTPs monitored by NTI, only
47% of the implemented Peripheral Health
Institutions (PHIs) on the average, and 75% of
the total PHIs available in the districts are
covered by SCC.
Based on the received quarterly reports, the
average overall efficiency in terms of sputum
examination is more than 100% at District
Tuberculosis Centres (DTC) and 67% at PHIs.
The corresponding figures in respect of case
detection efficiency are 83% and 51% at DTC
and PHI levels respectively. Smear positivity
rates in the SCC-DTPs are 14% At DTCs and
fi°/o at PHIs. In all, 74,459 smear positive cases
49.4% of the total smear positive cases,
diagnosed in the SCC-DTPs have been put on
SCC regimens. A cohort analysis of the
treatment results (for the cohort period
January-December 1991) revealed that 45% of
the patients put on Regimen A and 53% of
those put on Regimen B achieved satisfactory
'
$
level of treatment (i.e. as 75% of expected drug
collections). Among them and where the
result of final follow up sputum examination
was available, 90% of patients put on
Regimen A and 96% put on Regimen B had
become smear negative.
k_____________________
Introduction
The advent of SCC in the early 7Q's can be
considered as a turning point in the evolution
of chemotherapy of tuberculosis. It raised
optimism among those in-charge of
tuberculosis control programme, besides
brightening the prognosis of patients
suffering from tuberculosis. Enthused by the
impressive results of controlled clinical trials
with SCC in different parts of the world, the
Government of India and Tuberculosis
Research Centre (TRC), Madras, introduced
SCC, on a pilot basis in 18 districts in 10
States, in two phases, between 1983 and 1985
to
study
its
operational
aspects.
Subsequently, SCC was extended further
under the National Tuberculosis Programme
(NTP) in a phased manner. Initially, 44
districts were covered between 1983 and 1987
but by the end of December 1992, 252 districts
had been covered.
The SCC regimens introduced were : (a) a
fully supervised biweekly regimen of 6
months' duration - 25211^21,/4H2R2 (regimen
A) and (b) a self administered oral regimen of
8 months' duration - 2EHRZ/6TH (Regimen
B) , with drugs to be collected on a fortnightly
basis in the intensive phase of 2 months, and
monthly in the continuation phase. Efficiency
of the programme before the introduction of
* Paper presented at the 48th National Conference on Tuberculosis and Chest Diseases : Bhopal, 9th 12th December, 1993.
1- Chief Medical Officer; 2. Statistician; 3. Statistical Assistant, National Tuberculosis Institute, No. 8,
Bellary Road, Bangalore 560 003.
2‘
STATUS OF SCC UNDER NTP
SURYANARAYANA etai.
212
t:
DTP*
PIIICIHTMI
SCC was assessed to be 39%' in case-finding
and around 31% for satisfactory treatment
completion. The introduction of SCC was
expected to improve the performance m
terms of treatment outcome. The performance
of the districts covered under SCC, along
with the others, is being monitored by the
NT1 through periodic (quarterly/annual)
reports.
Objective
This paper aims at providing the current
status of the performance of SCC-districts in
terms
of implementation,
reporting,
performance of case-finding and treatment
for the year 1992 and the treatment outcome
of the patients' cohort for the year 1991.
Material and Methods
(iii) Action taking pattern by the TB patient ■
I(iv) Proportion of PHls offering tuberculos, ®
Iservices and (v) Case-finding as well as case S
holding achievements of a reasonably welly
performing DTP in the country.
(b) Sputum smear positivity rate : On thy
basis of experience, the expectation is fixed a W
18% for DTC and 8% for PHls
It is expected, therefore, that in an averagty
district with a population of 1.8 million. DI .ia
detects 500 smear positive cases per year
18% of the total number of sputurj^
examinations conducted and PHls detec«
2,000 smear positive cases @ 8.c smeay
positivity based on the achievements ot y
reasonably well performing DTP. The*a
expectations are slightly lower than thy
potentials which were estimated in tht»
operational studies conducted at NTF3.
g
(D) Initiation on SCC : The expectation is tha g
100% of the smear positives will be put ot ■
Four quarterly reports on case-finding and
treatment activities received from 248 SCC
districts each for the year 1992 and the annual
report on treatment results achieved for the
cohort period 1991 from 234 districts under
SCC constitute the material for this paper.
Only correct and complete reports were
included for analysis : 603 quarterly reports
out of 992 reports expected (about 61 %) and
only 89 (38%) out of the 234 expected annual
reports on cohort analysis of treatment results
have been considered The application of tests
of statistical significance has not been
considered necessary.
Efficiency of a DTP is assessed by
comparing its achievements with the
expectations. The expectations of the various
activities are as follows :
(A) SCC Implementation : The ultimate aim is
to cover all the DTPs, in a phased manner,
and complete coverage of all the implemented
PHls with SCC in each SCC-DTP.
(B) Reporting : Complete 100% reports
received from both DTC and PHls.
(C) Case Finding : (a) In respect of sputum
examination and detection of smear
positive cases, the expectation is calculated
according to (i) Population aged 5 years
and above (as per 1991 census, (ii) Prevalence
rate of bacteriologically positive cases (0.4%),
ij
) 'e^a
2
!k tib
.Tt«C II »>•>*»»’
STATES
. E2*CC-CT»
□ b-oti I
rBTt*
1. A.P.; 2. Assam; 3. Bihar; 4. Gujarat 5. Havana.
11. Maharashtra; '.2. 2-1- . ’’’
’
PHI*
DTC*
too ■<“
SCC.
(E) Treatment Outcome : (a) Treatmen®
Completion rate is the percentage of pallet"B
completing 75% and above of the expecteB
drug collections. Here, the expectation *
100% because a cure rate of 85%4 and abmB
can be achieved only when all the patientg
achieve the coUection/consumption of £ /s g|
of the expected drug collections.
(b) Cure rate is the percentage of smerg
positive patients converted to negative
at the end of treatment period, out of tho^B
initiated on treatment. The expected cure
is a 85% among the newly diagno^
patients, based on the WHO guidelines .
The performance of DTPs under vanot^g
activities is classified as good, satisfactory
poor depending upon the percentage ranp»
of efficiency achieved (Annexure).
rat*
Fig. 2. Reporting in SCC-1992 DTPs and PHls (Percentage)
Serial numbers indicate the same States as in Figure 1
I
PHIS
DTCs
C Z
I? -
-
L "i
j-
Findings
A. SCC Implementation
(a) DTPS: Out of 390 DTPs in the
252 (65%) have been covered under see
4 DTPs monitored by TRC, Madras
excluded leaving 284 DTP for ana^
Gujarat, Tamil Nadu, Maharashtra, Anon-
Fig. 3. Case finding efficiency, 1992
Sputum Examinations & Case Detection
Serial numbers indicate the same states as in Figure 1
214
Pradesh and Madhya Pradesh have covered
80% or more of their DTPs under SCC;
Assam, Himachal Pradesh, Jammu i
Kashmir, Karnataka, Kerala, Orissa, U.P.
West Bengal, and Small States & Union
Territories have covered 50% to 79% while
the other states have covered less than 50%
(Figure 1).
(b) PHIs : In the 248 SCC-DTPs monitored
by NTI, only 47% of the implemented PHIs on
an average have been covered under SCC.
Gujarat and Maharashtra have covered more
than 80% of their PHIs under SCC, Andhra
Pradesh, Bihar and Punjab have covered
between 50% and 79% while other States have
covered less than 50% (Figure 1).
(0) Reporting
(a) DTPs : Out of 992 DTP quarterly
reports expected, 785 were received at NTI
amounting to 79% reporting efficiency. Only
603 reports (i.e. 77% of the received or 61% of
the expected) have been analysed because the
remaining reports were found to be
inconsistent and/or defective. More than 90%
of the DTP reports have been received from
Assam, Punjab and Tamil Nadu, less than
80% from Bihar, Haryana, Jammu & Kashmir,
Madhya Pradesh, Uttar Pradesh, West Bengal
and Small States & Union Territories while
the other States have reported in the range of
80%-90% (Figure 2).
(b) PHIs : Overall, 89% of the PHIs
implemented under SCC had reported to
their respective DTCs. Performance in this
regard was more than 90% for Andhra
Pradesh, Gujarat, Kerala, Maharashtra,
Orissa, Rajasthan and West Bengal, in the
range of 80% to 90% in Haryana, Punjab and
Tamil Nadu, and less than 80% in other
States/UTs (Figure 2).
(c) Case-Finding
(a) Sputum Examination
and Case
detection : Overall, the efficiency in sputum
examination is more than 100% at DTCs and
about 67% at PHIs. Eleven out of the
seventeen big States and all the small States &
Union Territories achieved efficiency of 80%
or more at DTC, while Assam, Maharashtra
and Punjab achieved between 50% and 79%
efficiency, and others even less than 50%
efficiency. In respect of PHIs, Punjab achieved
more than 80% efficiency, Gujarat, Haryana,
Maharashtra, and Uttar Pradesh in the range
of 50% to 79% and all the small States and
Union Territories less than 50% efficiency
(Figure 3).
Overall, an 83% efficiency has been
achieved by DTCs in case detection and 51%
by PHIs. Nine big States achieved more than
80% efficiency in case detection by DTCs,
Maharashtra, Rajasthan and small States &
UTs registered efficiency in the range of 50%
to 79%, while all other States had efficiency of
less than 50%. In respect of PHIs, only Punjab
could achieve efficiency of more than 80% in
case detection, Gujarat and Maharasntra fell
in the category of 50% to 79% efficiency, wnile
all other States & UTs had less than 50%
efficiency of case detection (Figure 3).
215
STATUS OF SCC UNDER NTP
SURYANARAYANA ETAL
Table 1. Smear poeitivity rates -1992
< si
> No.
DTPs with SCC
DTPs with SR only
States/
UTs
DTCs
pins
DTPs
DTCs
PHIs
DTPs
4
5
6
7
8
1
2
3
1.
Andhra Pradesh
83
12
2.9
17.6
5.4
92
2.
Assam
63
23
4.4
8.4
35
63
3.
Bihar
92
0.8
4.0
6.1
45
5.9
4.
Gujarat
183
85
10.7
5.
Haryana
11.7
3.6
7.6
16.4
4.8
73
6.
Himachal Pradesh
5.4
3.-0
45
5.3
I. 6
4.4
7.
Jammu & Kashmir
4.8
42
43
11.7
4.9
82
8.
Karnataka
82
7.4
7.7
13.6
5.6
6.9
9.
Kerala
12.0
2.9
6.1
115
32
6.7
10.
Madhya Pradesh
16.4
2.7
6.4
18.3
3.6
9.0
E ii-
Maharashtra
21.0
1.9
3.9
165
8.7
93
£
12.
Onssa
123
3.4
5.6
13.6
5.4
7.9
(b) Smear Positivity Rate
g
13.
Punjab
11.4
45
63
102
6.7
7.1
In DTC, smear positivity rate is more than
18% in the States of Gujarat, Madhya Pradesh,
and West Bengal, less than 10% in Assam,
Bihar, Himachal Pradesh, Tamil Nadu and
Small States & Union Territories, and in the
remaining States in the range of 10% to 18%.
In PHIs, the States of Gujarat, Maharashtra,
Rajasthan and West Bengal registered more
than 8.0% smear positivity rate. It was
between 5.0% and 7.9% in Andhra Pradesh,
Karnataka, Orissa, Punjab and Small States &
UTs and in remaining States the figure was
less than 5% (Table 1).
A comparison of the smear positivity rates
between SCC-DTPs and non-SCC DTPs
shows an appreciably higher rate in the
former, both at DTCs and PHIs. At DTC, the
average smear positivity is 14.1% in SCC
DTPs and 11.6% in SR districts. The
corresponding rates for PHIs are 6.1% and
35% respectively. Smear positivity rates in
SCC-DTPs are generally higher than non-SCC.
DTPs of the same State (Table 1).
Initiation On SCC : Overall, 75,459 smear
positive patients (i.e. 49.4% of the newly
diagnosed smear positive cases) were put on
4 14.
K "
15.
Rajasthan
Tamil Nadu
16.8
5.2
10.4
12.2
8.4
10.7
35
6.1
4.6
7.6
3.0
4.1
16.
Uttar Pradesh
10.4
4.0
55
12.6
13
53
17.
West Bengal
8.4
7.7
8.0
23.1
II. 0
14.7
18.
Small States &
UTs
8.6
1.6
52
65
5.7
6.0
Total
11.6
35
53
14.1
6.1
8.0
«
•J
|
•All DTPs are with SCC
. SCC-2.8% under Regimen A and 46.6% under
| Regimen B (Figure 4). 33,604 patients were in
1 DTCs (i.e. 52.6% of the cases diagnosed at
I DTCs) 2.6% under Regimen A and 50.0%
under Regimen B with the percentage of
patients put on SCC being more than 90% in
g Tamil Nadu and Bihar, 81% in Maharashtra
and less than 80% in other States. In the PHIs,
H there were 41,855 patients (47% of the smear
S positive patients diagnosed at PHIs) 2.9%
5 under Regimen A and 44.2% under Regimen
, B-(Figure 4) of whom the percentage of
, patients put on SCC was high in Bihar but less
than 80% in other States but in some the
3-
..
number of patients put on SCC even exceeded
the number of new cases detected (Figure 4).
(£) Treatment ^utcome
(a) Treatment Completion rate : The smear
positive patients diagnosed during the cohort
period January to December, 1991 and having
an equal opportunity for completing
treatment by October, 1992 at the latest have
been analysed. Out of the 234 SCC-DTP
annual reports expected, only 120 (51.3%)
were received and 89 (72.4%) of the expected
reports could be analysed (38.0%). Of about
&
216
SURYANARAYANA FTAL
217
STATUS OF SCC UNDER NTP
Table 2. Report of cohort analysis-SCC regimens (patients diagnosed from Jan. to Dec. 1991)
100
I
1 69 RMMMCNI
I ■ MMIMfX A
00
I
|
Ifillli
.si.
:no.
1I I
•ini
r
R
40 •
!
:
M
I
|r oimen b 27 TO
[*■ Q1MKM A 4 0
'
_■ s s s.S s t a.i g
o
4,8411? 8 l»
I ■ 7111.2 1114:16. M17 M
S0|B4|m|m
21 |m j-1?;
2« ei
|-12771ie.MMB1»e»7»j
0
0
|ioj
8 1 2110 0 0 | J 0 1 i
0
0
tTAiea
Ml ri< T». 1l«.rM l.r BIHA* »•!■«
.r. ... ....rtw
rarM
Fig. 4. Patients on SCC, 1992 (Percentages)
Serial numbers indicate the same States as in Figure 1
45,000 patients put on treatment in the 89
SCC-DTPs, the treatment completion pattern
of only 36,281 patients was available (2,036
patients on Regimen A and the remaining
34,245 patients on Regimen B).
Out of 2,036 patients put on Regimen A,
44.5% collected consumed A 75% doses and
could be considered to have completed a
satisfactory level of treatment. Likewise,
53.2% of 34,245 patients put on Regimen B
made A 75% of the expected collections.
With regard to Regimen A, only Karnataka
and small States &: UTs could achieve
treatment completion of above 50% while all
the other States achieved less than 50%
treatment completion rate. As regards
Regimen B, only Jammu & Kashmir achieved
more than 75% completion rate. In Gujarat,
Maharashtra, Punjab, Rajasthan, West Bengal
and small States & UTs, the treatment
completion rate was between 50% and 74%
and all the other States had treatment
SCC
DTPs
Report on cohort
_______ analysis_______
Received
0
1
States/
UTs
li
2
3
I. Andhra Pradesh
Discussion
The introduction of SCC in NTP from
1986-87 onwards was an important milestone.
(%)
6
7
19
15
13
86.7
391
2
Assam
8
8
6
75.0
0
3.
Bihar
6
1
0
4
8
9
10
47.3
4380
46.3
378
43.9
Gujarat
16
16
12
75.0
56
8732
56.1
5. Haryana
2
1
1
100.0
0
25
32.0
6. Himachal Pradesh
6
2
1
50.0
0
35
0.0
7. Jammu & Kashmir
7
1
1
100.0
0
? 155
78.1
8. Karnataka
14
11
11
100.0
911
53.0
1291
40.0
6
4
66.7
6
333
1190
43.4
1
20.0
25
40.0
258
46.9
11869
56.1
1201
40.3
289
65.4
35.7
9. Kerala
7
10. Madhya Pradesh
33
II. Maharashtra
23
15
9
60.0
0
12. Orissa*
1 13. Punjab
7
4
4
100.0
140
4
4
1
25.0
0
« 14. Rajasthan
10
4
2
50.0
40
0.0
308
59.7
Tamil Nadu
14
8
7
875
415
33.0
1885
48.6
Uttar Pradesh
West Bengal
27
7
4
^7.1
23
8.7
351
43.9
11
3
3
100.0
14
28.6
1361
61.4
Small States &
UTs
20
9
9
100.0
15
66.7
537
568
Total
234
120
.89
72.4
2036
445
34245
53.2
1
completion rate of less than 50% (Table 2).
(a) Cure Rate : Out of the 2,036 smear -3 15.
positive patients on Regimen A, the results of 3
| 16.
smear examination at the end of W 17.
chemotherapy were reported only for 498
(24.4%) patients. Likewise, out of 34,245 S 18.
patients on Regimen B, results of smear 1.
examination were available only for 14,541
patients (42.4%). Under the circumstances, it
has not been found possible to calculate the
cure rate. In view of the impracticability of
arriving at the cure rate, an alternative
method is to calculate the cure rates from
studies relating them to observed treatment
completion rates. An overall assessment of
States with regard to various activities is
presented in Table 3.
5
A_______
Pts. Completed Pts. Compleinclu- ted
inclu%
ded
%
ded
Analy- Analysed
sed
4
Regimen
B
Regimen
|The rate of coverage can be considered as
§ fairly rapid in view of the fact that only 44
s districts were covered under SCC between
3 1983-1987 and the number rose to 252 by the
"J end of December, 1992.
The fact that only about 47% of the
| implemented PHIs in these 252 districts
were covered under SCC is a matter of
j concern because the PHIs have to detect and
I treat around 80% of the cases in each
■ district. The SCC coverage gets reduced to
29.3
35% (47% x j^%) taking into consideration
that on an average only 75% of the available
PHIs in a district an' implemented to offer
tuberculosis services. All the States except
Gujarat, Maharashtra and Punjab need to
intensify efforts to cover more PHIs in their
districts with SCC.
Though reporting by PHIs to SCC DTCs
(89%) was somewhat satisfactory, the
reporting by SCC DTCs to higher level (only
79%) was inadequate. This may be due to lack
zV
218
STATUS OF SCC UNDER NTP
SURYANARAYANA ETAL
Table 3. Assessment o/SCC DTP activitfes-perfonnance levels
SL
No.
State
Assam
Bihar
Gujarat
10.
Madhya Pradesh
11.
Maharashtra
s’ of trained Statistical Assistants or diversion of
e trained staff because 23% of the reports were
Performance leveb
t rejected for analysis due to defects/
! inconsistencies. Therefore, the reported
Implemen- ReportSputum
Case
Smear
Patients Treatment
i conclusion can be considered to represent
tation
ing
exam
detection
positivity
put
compleI only 61% of the SCC-DTPs. The annual
_____________ _________
on SCC
bon
I reporting of cohort analysis of treatment
PTC PHI PTC PHI PTC PH] PTC PHI PTC PHI PTC PHI PTP
i results was still more deficient.
!
Considering DTCs, 11 big and all the small
H
12
13
14
15
f States & UTs, achieved an efficiency of more
i than 80% in respect of sputum examinations,
B
A
C
C
C
j This can be considered as good. While the
B
f States of Bihar and West Bengal with less than
B
c B C c c
50% efficiency need to intensity their efforts in
i subjecting the chest symptomatics to sputum
B*
c B* A’ A* NK
' examination, all other States should aim at the
achievable 80% efficiency. The reported more
B
B
A
A
C
c B
than 100% efficiency is perhaps due to
indiscriminate selection of cases for sputum
B
B
B
examination (Figure 3).
As regards PHIs, the sputum examination
performance of only Punjab was good, that of
Gujarat, Haryana Maharashtra and Uttar
B
B
Pradesh, satisfactory while that of all other
States in need of vast improvement (Fig. 3).
B
B
B
B
Overall; the case detection efficiency was
83% at DTC, and only 51% at PHIs. At DTCs,
B
B
C
the performance of Andhra Pradesh, Gujarat,
Haryana, Himachal Pradesh, Jammu Sz
Kashmir, Kerala, Madhya Pradesh, Orissa
c
and Uttar Pradesh could be considered as
B
B
B
B
B
B
A
B
good, that of Maharashtra, small States &: UTs
C
B
satisfactory’ and that of all the other States in
B
B
B
B
need of great improvement. At PHIs, the
C
c c
a efficiency of case-detection was alarmingly
B
C
low in all the States except Gujarat,
B
B
c B
s Maharashtra and Punjab. In Himachal
a Pradesh, Jammu and Kashmir, Kerala, Orissa,
B
c B
1 U.P. and Small States & UTs, the efficiency of
13.
Punjab
14.
Rajasthan
15.
Tamil Nadu
16.
Uttar IVadesh
B
17.
West Bengal
B
18.
Small States &
UTs
B
B
B
B
C
B
Note: (i) A = Good; B = Satisfactory; C = Poor; NR = Not Reported
(U) For different performance levels, see ANNEXURE
(iii) ’Based on very few reports.
''
B
B
B
C
C
B
C
C
c
B
C
B
a
|
.>
3
k
/
3
case detection at DTCs was not
commensurate with the high efficiency of
sputum examination.
DTCs in 6 States could attain the expected
rate of 18% and in all other States sputum
positivity rate was variable, calling for an
inquiry into the likely reasons. The
performance of PHIs could be regarded as
distressing in the sense that only 4 out of the
17 big States could achieve the expectation of
8% positivity. Strengthening of the
laboratory services, both at DTCs and PHIs
219
and adequate supervision are the obvious
needs. A higher percentage of smear
positivity was noticed both at PHIs and
DTCs of SCC-DTPs compare to SR-DTPs
(Table 1) This needs to be viewed
cautiously. The likely possibility of
"motivated positivity" in the eagerness to
put patients on SCC needs to be kept in
mind (Table 1) and further investigated.
Only 49.4%, on the average, of the smear
positive patients diagnosed in DTPs were put
on SCC-2.8% on Regimen A and 46.6% on
Regimen B. The low acceptability of
Regimen A may perhaps be due to the
inability of the patients to attend twice a
week for supervised administration of
drugs. It is also possible that staff opted for
the operationally more convenient self
administered oral Regimen B. The coverage
of all PHIs with SCC needs to be intensified
before extending SCC to other districts. In
DTCs, the percentage of patients put on SCC
was below 80% against the expectation of
100% in all the states except Bihar,
Maharashtra, Tamil Nadu, West Bengal and
Small States & UTs. In some States where the
percentage exceeded 100%, possibly some old
patients were also put on SCC. At PHIs, none
of the States crossed 80% level except Bihar
where the percentage was deceptively high,
based Vn very few reports.
Out of the total of 75,459 patients put
under SCC, 5,080 patients (6.7%) in the
country had to change over to the long term
standard regimen, mostly due to non
availability of SCC drugs. It is imperative to
procure and supply adequate SCC drugs so
that there is no interruption of treatment.
It was expected to achieve a higher
treatment conwletion and consequently a
higher cure rare with the use of SCC. This
requires a prompt follow up smear
examination at the end of chemotherapy and
proper reporting of results for a given cohort
period. Out of about 45,000 smear positive
patients put on SCC regimens, during the
cohort period Jan-Dec 1991 (in 89 SCC-DIP
reports analysed), the final follow up smear
results of only 15,039 patients who had
completed satisfactory level of drug collection
were available for analysis. In view of this
i
220
limitation, it was not possible to arrive at a
reliable cure rate. However, among these
15,039 patients, 90% of patients on regimen A
and 96% patients on Regimen B (not given in
Table) had become smear negative. This
result is almost in conformity with the
findings of another study conducted by NTI4.
It, therefore, calls for intensified efforts on the
part of medical and para-medical personnel
in DTPs to subject all the patients to smear
examination at the end of chemotherapy, by
proper motivation, and then proper recording
and reporting of the results.
The alternative method ok studying the
treatment outcome through ■wjitudy of drug
collection pattern is less reliable. None the
less, out of about 45,000 patients put on
treatment under SCC regimens, during 1.1.91
to 31.12.91 details of drug collections were
available only for 36,281 patients; for about
20% the treatment cards weie not available.
Of these 36,281 patients, only about 45% and
53% of the patients put on Regimens A & B
respectively had completed a satisfactory
level of treatment. Besides small States &
UTs, only one State could achieve a treatment
completion rate of above 50% in respect of
Regimen A while for Regimen B, only one
State could achieve more than 75% treatment
completion rate. Five big States and small
States & UTs achieved completion rate in the
range of 50%-74% and all other States were
below 50% rate (Table 2). This gain is not
substantial taking into consideration that
even for standard chemotherapy, 41%‘ of the
patients have satisfactory level of treatment
completion and the aim of SCC is a cure rate
of 2 85%.
The above conclusions drawn from smear
conversions and treatment completion
patterns derived from truncated reports
cannot be generalised or extrapolated to all
the SCC-DTPs. Regular periodic supervision
in the overall improvement of all the activities
under the DTP including their reporting
Atmexan
which alone can lead to more realistic
conclusions.
Assessment of DTP Activities
Performance Levels
Acknowledgements
The authors are grateful to Dr. D.T. Uke,
Director, NTI for his wholehearted support
and encouragement; Dr A.K. Chakraborty,
Addl. Director for his valuable guidance and
members of the Technical Coordination
Committee especially Sri T.R. Sreenivas,
Statistician, Dr V.H. Balasangameshwara,
Chief Medical Officer and Dr (Mrs) Sophia
Vijay, TB Specialist for their valuable
comments. The authors also thank Sri
M.S.Krishnamurthy, Team Leader and Sri
V.V. Krishnamurthy, Statistical Assistant for
thier valuable suggestions, Sri M.V. Jaigopal
& Sri S.G. Radhaknshna, for their assistance
in compiling the data. Miss T.J. Alamelu for
the secretarial assistance, and Sri P.S.
Jagannatha, assistance in graphics.
References
National Tuberculosis Institute : Report on
National Tuberulosis Programme 1987; NTI,
Bangalore, India.
2. Baily, G.V.J., Savic, D„ Gothi, D.G., Naidu,
V.B. and Nair, SS. : Potential yield of
pulmonary tuberculosis cases by direct
smear microscopy of sputum in a district of
south India; Bui. Wld. Hlth. Orgn.; 1967, 37,
875.
3. Nagpaul, D.R., Savic, D„ Rao, K.P. and
Baily, G.V.J.: Case finding by microscopy;
Bull I.UA.T 1968,41,148.
4. Chaudhuri K., Jagota P and Parimala N :
Results of treatment with a SCC regimen
used under field conditios in DTP; Ind. J.
Tuberj 1993, 40,83.
5. World Health Organisation : Tuberculosis
research and development - Report of a
WHO working group meeting, Geneva 9-11
Sep.; 1991, WHO, Geneva.
National Tuberculosis Institute : Annual
Report on cohort analysis. 1991, NTI,
Bangalore.
1.
i®.. '
221
STATUS OF SCC UNDER NTP
SURYANARAYANA ETAL
|
1
1
j
!
|
1
i
I
I
|
\
|
1
Activity
Good
Satisfactory
Poor
1
2
3
4
(b) PHI
s 80%
180%
50-79%
50-79%
<50%
<50%
Reporting
(a) DTC
(b) PHI
>90%
>90%
80-90%
80-90%
<80%
<80%
Case-Finding
(i) Sputum Examination:
(a) DTC
(b) PHI
180%
180%
50-79%
50-79%
<50%
<50%
(ii) Case Detection:
(a) DTC
(b) PHI
180%
180%
50-79%
50-79%
<50%
<50%
(iii) Smear Positivity Rate :
(a) DTC
(b) PHI
'
118%
1 8%
10-17.9%
5-7.9%
<10%
<5%
Patients put on SCC
(a) DTC
(b) PHI
>90%
>90%
80-90%
80-90%
<80%
<80%
50-74%
<50%
Implementation
(a) DTC
Treatment ou tcome
Percentage of patients
completing 175% of
drug collection/consumption.
*75%
4
Original Article
Research and Develop
J- Tub., 1993i 4() gj
RESULTS OF TREATMENT WITH A SMadt
regimen used under FIELD CONDmoSS™™^'’
tuberculosis frogramme
™ict
ersity Press, 1990
,,cUpdate, Fo.
'Ommissi0n on Hca(^
and the Countries of
^'oflleaPhs^;
S
K.Chaudhuri.,P.jagota2andNpar.maiaj
a Public IIeahh
khp"!11 Associati°n
hh Policies and Pr0-
(Received on 3.2.92; Accepted
I
on 14.10.92)
1 Services Develop.
A/nia Ata and lhc
C A K- (ed.),
fe of Social Sci'• ^To/r on Haor the Year 19sq .
health institutions (PHI) f
°f ,tS pe^lphe^i,,
extra efforts except ensuring T a' StUdV area’ No
\r?-*
treatment results of an I
-^TPundertberouSS-^
of drugs at
obtain patients- compliant7ln " |
tuberculosis Unit.
' a"(f Futiue piat,
Culture in b,.
'Delhi, 1982.
ofession, Health
initiated on treatment with theH1^ C°U,d nOt be
stored SCC regimen
Objectives
°f ,hc StUdy are 'o observe •
f°rmation and
o'^mic
and
W- Treatment
Programme,
20, 917,
T ^etvs-fetter,
)n Mul(ipur.
'lily Planning
e). Report ;
nn'ng. New
Present and
•• 1990, J?.
rogramme
X 67.
bcrations,
^is Pro
'S of the
Group ;
ence betw^n PHI and^C
n° dirr^
higher in the PHI patients Thk^^ ^b5 were I
to a significantly hiphLV $ ,l,s cou,d be attributed I
taking treatment at PHHh^n^ DTC P^r Patients 1
drug sensitive bacilli h-.d . h" h
t,entS With
gativity (70%) as compared hnhiisXitM1"""'6
Material and Methods
Introduction
Short Course Chemolhcicrapy (SCC) is being
'• However, its initial
SXTeffiXoo7^care",comp'ian“-and
June^ 1989.
freshly
XlapSMote r°C'Efficacy
_______i'.1
lo
considerations ^ich
I Director; 2 Chief Median Officer; 3 Statistical Assis,;
ConWicc ; Director, Naiional Tubercillos]s p :ant:
nsntute, 8, Bellaty Road, Bangalore-560 003.
* liK; ('cju-k ^^0 Ll i >-0 x x i
’ '-V >
1 Uiu - '■
------------------------
'T
“ uJTms
(X.vl
►-CJ.Qd
85
SHORT COURSE CHEMOTHERAPY IN DTP
84
K. CHAUDHURIETAL
not eligible for inclusion in the study, ^jhejemain-. ing 533 patients, treatment with the SCC regimen
could not be initiated in 151 (28.3%) because cither
the patient did not comeback for result of examinaIron (21.6%) or refused (6^%yio be treated with
the drug regimen offered (Figure in Appendix),
leaving 382 patients for analysis.
Pre-treatrnent In vestigations
Apart from the initial sputum smear examination
done at the DTC/PH1 just before the intake, one
spot specimen of sputum was collected by the PHI/
DTC staff at the time of initiation of treatment to be
independently examined at the National Tuberculosis Institute (NTI) laboratory, by direct smear and
culture. These specimens were stored at t he respec
tive centres in a irefrigerator
''
till collected by NTI
messengers, once a week.
SCC Regimen
The study patients were offered
< "
the following
C/-'/-'
____ I_______ _
self-administered 8-month oral
SCC Iregimen
**••••
(2EHRZ/6TH or 6 EH) which is also the regimci
:n
B recommended for DTP :
(a) Intensive Phase
Ethambutol
Isoniazid
Rifampicin
Pyrazinamide
2EHRZ
(E) 1g
•
All drugs
consumed
(H) 300 mg together, daily, for
(R) 450 mg!
2 months
(Z) 1.5 g
(b) Continuation phase 6TH or 6EH in case of hypersen
sitivity to Thioacetazone
Isoniazid
(H) 300 mg
Both drugs taken
Thioacetazone (T) 150 mg
orally, together,
or
daily, for 6 months
Ethambutol
(E) 800 mg
■
Total
Male
Female
Total
Male
Total
15-24
11
(12.8)
6
(15.4)
17
(13.6)
21
(12-1)
18
(21 4)
39
(15.2)
32
(123)
24
(19.5)
56
(14.7)
25-44
42
(48.8)
25
(64.1)
67
(53.6)
60
(34.7)
42
(50.0)
102
(39.7)
102
(39.4)
67
(54.5)
169
(44.2)
45 +
33
(38.4)
8
(20.5)
41
(32.8)
92
(53.2)
24
(28.6)
116
(45.1)
125
(48.3)
32
(26.0)
157
(411)
125
173
84
257
259
382
86
39
123
Total
Difference tn age structure
of patients between PHI & DTC significant (X - 6.93. df 2, P < 0 05)
Follow-up Examination
Table 2 Covcmge for sputum examination at follow up
on conclusion of tnatment period
Two foUow-up examinations, one at the end^f
the intensive phase and the other at the end of
chemotherapy were to be done. Sputa collected at
the respective centres were examined at the NTI
laboratory by direct smear & culture and drug
sensitivity tests were performed for positive cullures. While the spot/overnight sputum specimen at
.1
1
f.f
•
.
.. ..
a . .
the end of “intensive phase” was collected within 15
days of the due date, the “treatment end” sputum
specimen was collected between 15 days prior to
and l‘/2 months after the prescribed date of end of
chemotherapy. In case of death, special efforts were
made to obtain the history of previous treatment
and the probable cause of death, from the relatives.
Initially sensitive
patients
Total patients
Followed up
148(79.6)
297(77.7)
Examined
125(84 5)
252(84 8)
Dead
23(15 5)
45(15.2)
No response
38(20.4)
85(22.2)
Total
186
382
Level of Treatment Compliance
Table 3 shows the distribution of patients by lev
els of treatment compliance. A patient making less
than 75% of drug collections due in the intensive
phase as well as in the continuation phase was
considered to be in the compliance level 1. Those
making less than 75% of the due collections in
intensive phase, but 75% and more in continuation
phase were considered to be in level 2. Of the total
382 patients who were initiated on treatment, 86
(22.5%) had made less than 75%, of drug collections
mlheintensive phase, irrespectiveofthccollections
in the continuation pfiase.Thcy (levels 1 and 2) were
not eligible for analysis under the study. Therefore,
their compliance with treatment in the continuation
phase is not presented and patients in levels 1&2
have been combined in Table 3. Their follow up
results at the end of treatment period have, how
ever. been presented.
In the third level of treatment compliance, (i.e.
> 75% collections in intensive phase but < 75% of
due collections in continuation phase), there were
169 patients (44.2%). Compliance level14 com prised
(Percentages in brackets)
Table 3 Distnbution of cases by level of dmg collection & initial culture status
Results
was eight months, without additional time granted
to defaulting patients for completing the prescribed
A patient was considered a defaulter if he did not
attend the centre on the due date for drug collection,
First defaulter action was a letter posted on the due
'
shock, jaundice, exfoliative dermatitis, etc. were
managed by withdrawal of the offending drug.
Drugs
were issued to the r
patients fortnightly
for
—
....A....J awself-admihistration at home. The treatment period
Management of Drug Default
Female
Female
Male
Adverse Reactions
The prescribed regimen was continued inspite of
minor adverse reactions like itching, nausea, vomit
ing, etc., which subsided with or without symptomatic treatment. Major reactions like anaphylactic
Total
PHls
DTC
Age
group
date itself or the next day. Second action was taken
on the fourth day of default, as a second letter or
home visit or message sent through a multipurpose 7/
health worker (MPW).
Table 1 gives the age/sex distribution of the 382
patients analysed.
Table 2 gives the coverage for sputum follow up
examination after the end of treatment. It is seen
that 297 (77.7%) patients could be followed up, of
whom.—45
were dead (15.2%)
and sputum
——
- . — - — — — —a— v ——
'<J t kaaau JUUL Mill W3S e.Xiini ined for 252 persons (84.8% of eligibles).
treatment, as is done in the DTP.
The supply of antituberculosis drugs in adequate
quantities was ensured by NTI.
Table 1 Distribution ofpatients by age and see
Compliance
level
Proportion of expected
no of collections made
during 8 months
Continuation
phase
Intensive
phase
§
Total
Sensitive
Resistant
Others
44
20
22
43
47
1
<75*76
2
<75% —
3
>75%
< 75'7
79
4
>75%
>75'1
63
30
18<>
93
Total
c. 3^
Number of patients
;
(Percentages in bracket)
•No. of patients not eligible for continuation phase-86 (sec text)
34
86*
(22 5)
169
V142)
127^
(33 2) .
103
382
86
87
SHORT COURSE CHEMOTHERAPY IN DTP
K. CHAUDHURIETAL
Table 5 Bacteriological response at various levels of treat
ment compliance according to initial drug sensitivity
patients who had collected 75% or more drugs due Table 4 Fate ofpatients at the end of treatment period by
in both the intensive as well as continuation phases.
compliance levels & place oftreatment
Of the patients initiated on treatment, 127(332%f
Kolar District
had completed the fourth level of treatment compK ---------------------------------------------------------------------------Treatment
8th month sputum smear status
The?e is no difference in the treatment compli compliance
level
Neg.
Pos. Dead ND
Total
ance patterns between the patients collecting drugs
at the PHIs in comparison with those at the DTC
1&2
31
22
24
9
86
(Table 4).
3
Bacteriological response related to treatment compli
ance levels
Table 4 presents the status of 382 patients al the
end of treatment period, by place of treatment,
compliance level, and bacteriological response as
judged by sputum smear examination. For the Kolar
district, out of the 382 patients, 36 could not be
followed up and 45 were dead. Thus, sputum could
be examined by direct smear only in 301. Of these,
228 were sputum negative after the completion of
treatment period (75.7%); the proportion for DTC
Kolar was 72.8% and for all PHIs taken together,
773%. However, considering that death is an unfa
vorable outcome of treatment, the proportions having
favourable results i.e. those in whom sputum was
negative, excluding only the non-response group
from the denominator, 69,4f
favourable result at the
tpart to 64.3%
Considering sputum conversion on the basis of
smear results, according to levels of treatment
compliance for Kolar District as a wholcJ8^%witl>
I 'W^h^^47^4iQhMprtMbAiere were no differJ ences between these proportions, i.e. treatment
4
Total
(58.5)*
87
(70.2)’
110
(88.7)
228
(75.7)*a
37
20
25
14
1
2
73
45
36
Sth month culture status
Pos-S Pos-R
Dead
Not Total
done
Initially drug sensitive
(22.5)
169
(44.2)
127
(33-2)
3
4
Total
382
(100.0)
11
10
6
11
6
44
31
46
15
2
3
1
11
1
19
13
79
63
88
(70.4)*a
27
10
23
38
186
53.2% over all result.
Of the 186 initially drug sensitive patients, sputa
could be cultured for 125 at the end of treatment
period. Of them, 88(70.4%) were converted. However, i he proportion of favourable results (in 88 out I
of 148 patients) fell to 59.5% when death was con- I
sidered as an unfavourable result.
Among the initially resistantgroup of 93 patients,
follow-up sputa could be examined for 60. Of them,
29 were culture negative al the end of treatment
period (48.3%). Considering death as unfavourable
result, 29 out of 72 patients (40.3%) had favourable
remits,.
»
Major toxic and side cffectyvere infrequent in
the stud^only 7 required stoppage of treatment due
to these (L8%) reactions.
Intially drug resistant
DTC
1&2
3
4
Tota:
11
(50.0)*
26
(66.7)*
38
(90.5)*
11
75
(72.8) ‘b
28
13
4
1
5
10
2
4
5
17
Discussion
31
(24.8)
50
(40.0)
44
(35.2)
6
PHIs
1&2
3
4
20
(64.5)*
61
(71.8)
72
(87.8) *
Total
'Total
153
------------------ (773)*c
11
20
4
2-!
19
15
10
1
45
40
19
Bacteriological response according to treatment
compliance level and drug sensitivity status.
Table 5 presents the bacteriological response to
Table 5 presents the bacteriological response to
treatment at various levels of compliance according
to drug sensitivity status at start oftreatment. Out of
382 patients, the initial culture was positive only in
279, whose results arc presented in Table 5. In the
remaining 103 patients, culture was either not done
2
20
12
7
43
30
3
1
11
11
5
Total
29'
(48.3)*b
5
26
12
21
93
All
117
(63.2)’c
32
36
35
59
279”
b_l0 3
c.53 2
257
(100.0)
was in the treatment compliance level 3 and none in
level 4. Of the 257 undergoing treatment at PHIs, 40
-j jihad died (15.6%) antThalf of them were in levels
113&4. The proportion of deaths was higher at PHIs
7
The present study was conducted to investigate
the efficiency of a short course regimen, accepted
for DTP. in terms of initial acceptance, treatment
compliance and result of treatment in a typical
Indian district. While carrying out the study, no
interference was made by NTI research staff, either
at the DTC or PHIs except that adequate drugs
supply was maintained at the respective centres for
the study period. Care was taken al the outset to
explain to the programme staff the criteria of admis
•Proportion among sputum examined; (P<0.05)
sion of patients to the study and other requirements.
a b.c: ’Proportion of favourable results (death being unTherefore,
the situation
was similar
to any DTP
, .
1 ncreiorc,
me siiuauuu
»<» omiuai
tv
a-S^S L°UIC°mC
using
supply
using short
short course
course regimens
regimens but
btH lack
lack of
of drug
drugAUgpJy
55
(21.4)
119
(46.3)
83
(32.3)
•Proportion among sputum examined after excluding
deaths and not followed up
ND Not done
a’b-c '■ Proportion of favourable results (death being unfavorable outcome)
3-65 9
b-T’9-4
c-64.3
4
1
12
.11
3
4
125
(100.0)
compliance at various levels and sputum conversion
by these levels, between DTC & PHIs.
Also in Table 4, the deaths are shown according
to place of treatment and compliance level of treatmcnl. Five of the 125 (4%) patients undergoing
treatment at Kolar DTC had died; only one of them
than at DTC but not high enough to affect the
respective proportions of favourable results. The
distribution of deaths by age and sex as proportion
of patients pul on treatment showed no difference
(Table not put up).
Treatment
compliance
Neg.
level
I
63.2% were found to have converted compared with
(P<0.05)
1
••Initial culture neg/contaminatcd/not done, excluded-
103
S-Drug sensitive; R-Drug resistant
or was contaminated. However, 10 of the 103 patients were dead; 54 were culture negative; 13 were
culture positive (resistant 9), and in 26 patients the
follow-up examination could not be carried out at
uteend
enuof
ottreatment
ucau,.™period (not
v. on Table).
the
Of the 279 patients in whom pre-trcalmenl culture was positive, 220 alone could be followed up
i. . .
(Table 5) Of the latter, 117(53.2%) were culture
negative, 35(15.9%) were dead and 68(30.9%) were
f1
still culture positive at the end_pl the period of
____ unlavor11 treatment (drug resistant 36). Therefore,
"46.8%; by leaving out the dead
able response was ‘... ...
and non-response group from the denominator,
was not allowed to become a constrai
constraint^
nt.
of the study having
-Despite
Despite the
the methodology
met
)>ccn fully explained to the participating medical
officers,28 patients otherwise eligible were excluded
by them without valid reason and 23 were correctly
excluded from 584 patients diagnosed during the
period.
_
Of the remaining533 patients, 151(28.3%) cither
did not come back to receive the results of investigalions or refused the SCC regimen. It is not known
why such a substantial proportion of patients bchaved as they did. The place of tre
treatment
atment (PTC
(PTC or
min
dqL
PHI) did not »vinttnr
matter hnr'oiicp
because thry
the Proportions
proporttons.nol
initiated
treatment- *were
4 on ------------------ 32.4% and 26.1% respbdively (not on Table), 'f
Of the 382 patients in whom the SCC could be
initiated, 22.5%, 44.2% and 33.2% respechvely
complied with the treatment at levels 1 and 2,3 and
88
APPENDIX FIGURE
Classification of smear positive patients diagnosed during April 1988-June 1989
4 respectively. There was no difference in the pat- keeping in mind the operational conditions of the
ternt'
of treatment compliance, whether the patient programme, where culture and sensitivity test are
—a at Ts-iv
not applicable. .
was .treated
DTC or at n.<.
PHIs (Table 4j.
proportion of patients complying at level 4 was
Deaths among patients put on treatment were
about one third of the patients initiated on 8
higher at the PHIs (16%) compared to DTC (4%).
whether at the DTC or PHIs.
However, considering that death is an unfavourable
In spite of the low compliance at 1level 4, lhe result of treatment, along with persistent sputum
sputum smear negativity achieved al the end of positivity among the patients followed up, the properiod of treatment, among those for whom sputa portion of those who had favourable result, on
could be examined ranged between 73% and 77% smear examination, was similar for the DTC and the
(Table 4), irrespective of the level of compliance, PHI, i.e. DTC : 69.4% and PHI: 64.3% (Table 4).
initial drug sensitivity status, and whether the pa- The possible reason for higher death rate at PHIs
tients was
treated at------the DTC
or PHIs.
<’ tcompliance
: \
2patterns
_o
\
despite similar drug
observedr
--------------- - -------I" JablC 5’ ‘ • C0U'd bC obscn'cd
lhe, Palicn‘s at DTC and PHI is not clear. One possibility U thal
with drug sensitive organisms initially achieved a a significantly higher proportion of aged patients
significantly higher rate of sputum culture negativity were on treatment at the PHIs than at the DTC
(70.4%), than those with drug resistant bacilli (483%). (Table 1).
Further, among 49 out of 63 patients with sensitive
organisms initially who completed level 4 of treat Acknowledgement
ment and whose sputa could be examined, 46 were
The authors are grateful to the members of the
culture negative (93.8%).The corresponding figure OR Forum for helpful suggestions. The District
for patients ..-i.
with drug resistant
....bacilli
...j was only Tuberculosis Officer, the staff of the District Tuber47.8% (11 of 23). Thus, SCC can <achicve
'
good culosis Centre and the medical officers of the PHIs
sputum culture negative status in patients with ini- in Kolar district merit special mention for their
tial drug sensitive bacilli even in
i patients
'
"
taking
enthusiastic participation in the study. Dr. (Miss)
unsupervised but adequate treatment, i.e. the pa- Sudha Xirasagar, erstwhile medical officer at the
tients in level 4. Even the overall treatment result of NTI was associated with lhe study in its initial
75.7% (Table 4), expressed as sputum smear nega stages. Mr. T.R. Srccnivas, Statistician, and Mr.
tivity and without considering level of treatment M.V.
.. Jaigopal, Computer,
„.w., rendered assistance „in
compliance,
Besides, ucouis
deaths liie
lhe siaiisticai
statistical analysis,
analysis. ur.
Dr. A.K.
A.K. Cbakraborty,
Chakraborty, AddiAddi---- r------- , is quite considerable.
auiv. Mvsiuca,
were almost equal in both lhe sensitive and resistant tional Director, took part in the analysis and pregroups (12.4% and 12.9% respectively).The results, pared the final draft. Miss K.R. Pramecla prepared
though far short of the expectations raised by con- the
the typescript
typescript and
and Shri
Shri B.R.
B.R. Narayana
Narayana Prasad,
Prasad, lhe
the
trolled clinical trials, are, nevertheless, favourable drawing. The authors arc thankful to them.
Total Smear Positives
584
t
DTC
PHI
Female
Total
Male
Female
Total
Male
Female
Total
16
(12.9)
6
(9.8)
22
(11-9)
22
(9.5)
23
(19.8)
45
(12.9)
38
(14.7)
29
(16.4)
(12.6)
25-44
56
(45.2)
42
(68.9)
98
(53.0)
80
(84.5)
55
(47.4)
135
(38.8)
136
(38.2)
97
(548)
233
(43.7)
15 +
52
(41.9)
13
(21.3)
65
(35.1)
130
(56.0)
38
(32.8)
168
(48.3)
182
(51.1)
51
(28.8)
233
(43.7)
5+
124
61
185
232
116
348
356
177
533’
15-24
’Excluding 51 not eligible for intake
t
I
I
Regimen Not Initiated
Not come for Results
Regimen Refused
Regimen
Initiated
382
151
115
36
--- —t
Culture
Negative
62
Sensitive
Resistant
Contaminated
Culture not done
186
93
41
References
1. Jagota P.. Venkataramana Gupta E.V , Nagaraja
Rao B.S., Parimaia N. and BailyG.V J The accepta
bility and efficacy of two regimens of short course
chemotherapy under conditionsof an urban tubercu-
Total
Male
------
Excluded 51
Outside District 20
Age < 15 years 3
Excl. by M.O. 28
Study Patients
533
Appendix Table : Agc-Scx distribution of smear positive patients
Age
Group
89
SHORT COURSE CHEMOTHERAPY IN DTP
K. CHAUDHURIETAL
67
I
losis programme but J. Tub.-, 1989. 36. 18.
2 Jagota P, Venkataramana Gupta E.V.. Sreemvas
T.R., Parimaia N and Chaudhun K. Operational
feasibility of unsupcrvised intermittent short course
chemotherapy regimen at the District Tuberculosis
Centre but J. Tub. , 1991, 38, 55.
f^l PI i>TP
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Current Topic
NT! Bulletin 1995,31/1&2.1-6
I>
E
Dynamics of Treatment : Under Various Chemotherapy
Situations in the Tubercueosis Control Programme
I
P Jagota**
public health and to measure its efforts. Individualistic
medicine was to graduate into having an
epidemiological consideration in it. Thus the concept
of ‘organization’ and ‘treatment delivery’ came to the
fore. This was a new system altogether. Advent of
SCC did not necessitate a change in the system nor
even a special reorganisation. This aspect has been
stressed by Wallace Fox.2 Why I choose to highlight
it, is because one must realise that the organization lor
delivering effective SCC, like as it is in SR, means
improving the organization for chemotherapy
‘delivery’, and not creating a new system. Thus
delivery is crucial to both. To quote Fox, “it is vital to
apply SCC in an efficient organizational frame work”
and “the organizational aspect of chemotherapy
cannot be over emphasised2”.
A review of the functioning of the District Tuberculosis
•^^■Programme (DTP) in various states in India has
revealed that these are functioning at different levels. At
present neither case-finding nor the treatment activity can
be considered as satisfactory.
Improvement in the functioning of the DTP can
considerably improve case-finding but cannot possibly
influence treatment results. Improvement in case-holding
demands that its technical and organizational
methodology will have to be improved to obtain better
completion and thus better treatment efficacy. This is a
decisive factor in the treatment delivery system if one
were to avert a situation of already diagnosed cases
continuing to form part of later prevalence cases, so aptly
described by Grzybowski1 as “epidemiological mess”.
I will take up this aspect in a little more detail later.
There have been two crucial breakthroughs in the field
of anti- tuberculosis treatment in the recent past. The first
one by Tuberculosis Chemotherapy Centre, Madras, in the
fifties, was the demonstration of the efficacy of
domiciliary chemotherapy which made it amenable to be
self-administered. The second has been the development
of Short Course Chemotherapy (SCC) in the seventies.
1)
♦
Domiciliary treatment: When domiciliary treatment
with Standard Regimen (SR) was introduced, it
needed a change from hospital to ambulatory system.
From the sanatorium mode of treatment in vogue, one
had to develop an ‘organization’ for treatment
delivery. A machinery had to be built to place patients
on treatment, to make it available to them as
conveniently as possible, to work out a method of
identification of defaulters and their retrieval, as well
as to document treatment results and their effect on
reducing pool of transmitters in the community. In
other words, the system had to be developed to deliver
Dr I’.V. Benjamin Memorial Oration delivered at 21st Andhra
Pradesh Tuberculosis & Chest Diseases Conference held at S.V.
Medical College, Timpathi, on 9th July 1994.
** Additional Director, National Tuberculosis Institute, 8, Bellary
Road, Bangalore 560003.
2)
Short course chemotherapy: Introduction of SCC is
considered as a technical advancement of the
seventies. Its epidemiological and sociological gains
arc supposed to be so far reaching that we lor the fust
time, find ourselves talking of the possibility of
ridding human bodies of the tubercle bacilli i.e.,
‘cure’, instead of ‘quiescence’. However, the efficient
delivery of SCC is one of the pre-requisites to
chemotherapy programme, much more crucial than it
had been anytime in the past. The benefit of SCC is
summarised below:2
Advantages of SCC
1.
Reduction in the total duration of treatment:
a) Less chronic toxicity
b) Cost effective
2.
Reduction in the work load on the health services.
3.
Better attention for case-finding and case-holding.
4.
Low relapse rate even after incomplete treatment.
£
To this we could also add and operational advantage of
SCC that the outcome of chemotherapy at the end of
treatment is not dependent on mid term follow-up. It is
1
<-
I.
seen from a study at the NT13 that irrespective of sputum
being negative or positive in two or three monthly
follow-ups, in an overwhelming majority, cases would
turn negative at the end of treatment.
Efficiency of Treatment Delivery
The all important requirement of SR or SCC thus is the
efficiency of treatment delivery, not merely that ‘efficacy’
of the regimen. It must again be realised here that the
difference is not for etymological distinction only.
Nagpaul, as early as in 1972, has found it useful to
distinguish between ‘efficacy’ and ‘efficiency’ of the
chemotherapy of tuberculosis4. The former was defined by
him as related to results obtained with drug regimens in
controlled clinical trials, denoting the maximum that was
attainable under favourable conditions. ‘Efficiency’, on
the other hand, could be recognised as what could actually
be achieved with varying technical, operational as well as
organisational conditions, which could not essentially be
controlled. He had recognised that ‘efficiency’ could vary
widely, whilst ‘efficacy’ of a particular regimen would not.
A gap between efficacy and eiliciency of chemotherapy
may be expected. It was ‘fond hope’ of the clinicians that
whatever treatment results could be demonstrated in
clinical trials, would be achieved among the patients
treated by them. It was of course not so, since therapeutic
efficacy was but only one aspect of the complexity of
tuberculosis treatment.
Similarly, those who had conceptualised the DTP were
shocked to realise that the term ‘efficiency’ under
programme conditions was not a standardised
unindimensional factor.
Table 1
Potential & Performance
It was envisaged that National Tuberculosis Institute
(NTI) should do operational studies to find out the
maximum efficacy by following the recommendations laid
down in the manuals for the District Tuberculosis
Programme (DTP). The results of these studies were
defined as potential efficacy, a parameter which could be
used to compare the results of DTP units with wide range
of conditions i.e., actual efficiency of individual DTP or
performance.
It is important for us to understand the dynamics of
treatment situations in the country, as it would enable us to
adopt appropriate chemotherapy policy. Starting from a
naturally occurring one, where no organised intervention
was carried out to a fairly well organised situation with
SCC in the programme.
The fate of the smear positive patients in various
situations as given in table 1 was as follows:
In the sputum positive patients, initially diagnosed on a
house to house survey under a situation where neither a
communication was made to the patients on their
diagnosis, nor any effort was made to treat them, 27.8%
became culture negative, 30.2% died and 42% remained
culture positive at the end of eighteen months. At the end
of five years 18% were still culture positive and while
about half of them were dead5. This study provided
excellent data on the ‘no intervention situation’ referred to
here as ‘Natural Dynamics’. In a study conducted by NTI,
treatment was given in accordance with the guidelines for
DTP at an urban District Tuberculosis Centre (DTC). At
the end of 12 months, irrespective of level of drug
collection, 63% became culture negative, 10% died, 27%
Fate of cases as reported in several operational studies on chemotherapy
At the end of five years
At the end of chemotherapy
Chemotherapy situations
<
<
I
<1
Unfavourable outcome
Favourable
outcome
Unfavourable outcome
Culture
negative
Dead
Culture
positive
Culture
negative
Dead
Culture
positive
Natural dynamics
27.8
30.2
42.0
32.5
49.2
18.3
Potential of regimen
SR at DTC4,6
SCC at DTC7
63
90
10
0
27
9
59
76.2
30
2.7
11
21.1
66
13
21
45.7
80.8
40.5
12.1
13.8
7.1
Performance Under DTP
SCC8
Under DTC
SR9
SCC
2
Favourable
outcome
continued to be culture positive. The five year follow-up
results of these patients showed 59% culture negative,
30% died and 11% remained culture positive6.
Thus it could be seen that natural dynamics could be
improved after introduction of SR on domiciliary basis.
Potential of SCC was further studied under the same urban
DT.7. It was seen from the table 1 again that at the end of
treatment 90% became culture negative, none died and
10% were culture positive. The two year follow-up results
of these patients showed that 76.2% remained culture
negative, 2.7';l> died and 21.1% were culture positive.
The point to observe in such a comparative study is that
as compared to SR, SCC was found to have a considerably
lower fatality and nearly 20% improved negativity status
on sputum examination at the end of the treatment as well
as at the end of follow-up.
In another study on SCC, the performance was
evaluated under DTP. The treatment was given in a real
field situation where none of the organisational factors
were controlled except drug supply. It was observed that at
the end of 8 months of treatment period, 66% were culture
negative, 13% had died and 21% continued to be culture
positive8. The results were thus inferior to potential.
Further in a retrospective study on performance of SR
and SCC in the same urban DTC at the end of five years
45.7% of the patients on SR were found to be culture
negative, 13.8% were culture positive and 40.5% dead.
While in patients treated with SCC concurrently 80.8%
became culture negative, 7.1% remained culture positive
and 12.1% died. The gap between potential and
performance with SR was wide while with SCC it was
10% only.
It can be seen from table 2 that in spite of very good
results with SCC, the overall results under a situation of
this mix of SR and SCC were 54.8% culture negative,
12.2% culture positive and 33% dead.
I
Table 2
Reasons lor Fall in Efficacy
Attempts were made to find out the reasons for loss of
efficacy of the chemotherapy. Two key variables i.e.,
non-compliance and initial drug resistance were found to
be associated with it. The patients were classified .into two
groups according to treatment status.
i)
Adequately treated group: Those who were on SR
and took 80% or more of the prescribed treatment
(level 4 treatment). In case of SCC it was 75% or
more.
i>)
Inadequate treated group: Patients who took less
than 80% on SR and less than 75% on SCC (level 1-3).
In the potential study on SR4 the outcome according to
the treatment status as seen in table 3 was as follows: those
who took adequate treatment (level 4) irrespective of
initial sensitivity status, 77.6% became culture negative,
20.5% remained positive and 1.9% dead, while in the
other group with inadequate treatment 46.4% were culture
negative, 34.7% remained culture positive and 18.9%
were dead .
Similar observations were made on SCC from the DTP
study8 of the patients who took 75% of treatment (level 4);
as seen from table 4, 88% became smear negative, 1%
died and 11% remained positive, while in patients having
less than 75% of treatment (level 1-3) only 53.4% became
negative, 26.7% remained positive and 20% died8. Thus
the loss of efficacy of regimens was mainly due to
inadequate treatment.
Similar observations were made from another study on
performance9. As per table 5, the patients on SR who had
inadequate treatment, about half of them were dead alter 5
years indicating that death was a major outcome.
The unfavourable outcome was mainly due to poor
compliance by the patients on SR. It can be seen from the
table that majority of the SR patients (79.5%) w ~e lost
from treatment, while those on SCC, only about 30% were
Result according to SR and SCC mix
Results after five years
Ratio
SR SCC mix
No. of
patients
Culture
negative
%
Positive
%
Dead
%
SR
SCC
80
20
45.7
80.8
13.8
7.1
40.5
12.1
Total
SR+SCC
368
130
498^
100
54.8
12.2
33.0
Regimen
_________ (100)
Jogota Pct al: Ind J Tub 1994,41,223
3
■ir
Table 3
Treatment results at the end of 12 months
according to level of treatment taken
Total
Culture
negative
%
Culture
positive
%
Dead
%
Aquate > 80%
(level 4)
210
77.6
20.5
1.9
Inadequate < 80%
(level 1-3)
196
46.4
34.7
18.9
406
62.6
27.3
10.1
Treatment group
Total
(100)
Nagpaul DR: WHO/TB/73.99, 1972
Table 4
Fate of patients on a SCC regimen at the end of treatment by level of compliance
Outcome at the end of 8 months
Smear status
Treatment completed
Total
Adequate treatment > 75 %
Level 4
Inadequate treatment < 75%
Level 1-3
127
255
382
Total
Dead
Not
done
Positive
Negative
No.
%
No.
%
No.
%
110
88.0
14
11.0
1
1.0
2
118
53.4
59
26.7
44
19.9
34
228
65.9
73
21.1
45
13.0
36
Chaudhuri K ct al, Ind J Tub 1993 40/2, 83-89
Table 5
Results at the end of 5 years according to treatment status and regimen
No.
Culture negative
%
Dead
%
Culture positive
%
Completed
76
75.0
6.6
18.4
Lost
292
38.0
49.7
12.3
Total
368
45.7
40.5
13.8
Completed
90
86.7
9.8
3.5
Lost
40
67.5
17.5
15.0
Total
130
80.8
12.1
7.1
Regimen and treatment
status
SR
SCC
r
JagotaPetal; Ind J Tub 1994,41, 223
lost from treatment. This helped in reducing the overall
loss of patients from treatment marginally, as the number
of patients treated with SCC were probably less.
It will not be out of place here to report Grzybowski’s
observation on Chingleput BCG Trial as seen from table 7,
where all the cases detected during each survey were
treated with SR by the general health services. Treatment
The patients with initial drug resistant organisms had
less favourable outcome in comparison with patients
having sensitive organisms4.
was so ineffective that out of total cases found in the fifth
survey, only 29% were new and the remaining 71% were
old cases detected during previous rounds, over a period of
12 1/2 years.
4
i
Table 6
Table 8
Regimenwise treatment completion pattern
of smear positive patients treated at urban
district tuberculosis centre
Number
Completed
(%)
Lost
(%)
SR
370
76 (20.5)
294 (79.5)
SCC
132
92 (69.7)
40 (30.3)
SR + SCC
502
168 (33.5)
334 (66.5)
Primary
treatment
Fate of smear positive patients
in two different situations
Fate at the end of five years
Chemotherapy
situation
Culture
negative
%
Culture
positive
%
Dead
% .
Natural dynamics
Performance
SR lost group
32.5
18.3
49.2
38.0
12.3
49.7
Jagota P et al; Ind J Tub (accepted for publication)
SR lost group 38.0 12.3 49.7
Table 7
Proportion of culture positive old cases
among patients found at fifth round of
Chingleput BCG trial (after 12 1/2 years)
Status at previous round
Culture positive
Active on X-ray
Normal X-ray
Total
No.
%
473
77
228
778
61
10
29
100
Grzybowski S: Bull IUATLD 1991, 66, 193
We thus now have a replica of the situations commonly
seen at an average DTP in India. Therefore, when
computing the results it could be seen from table 8 that the
patients who were treated with SR and were lost from
treatment had fate exactly similar to the natural dynamics
and as seen from table 5 patients belonging to SR
completed group had results very near to the trial efficacy.
Compared to SR, SCC was found to have a considerably
lower fatality and nearly 20% improved negativity by
culture on
sputum
examinations.
Much
more
organisational effort is necessary to ensure compliance in
patients on SR than on SCC. Moreover, results of patients
lost on SCC were not as unfavourable as seen in the SR
lost
patients.
These
factors
tilt
the balance
overwhelmingly in favour of SCC as the regimen of
choice, not only for the clinicians but for public health use.
There arc some other decisive factors related to efficient
treatment delivery system. One of them is availability of
anti tuberculosis drugs, at all levels, at all times. This can
be achieved by providing required funds and having
indigenous production of the drugs. The other factor
which is equally important to remember is that there is no
likelihood of getting a new anti tuberculosis drug in the
near future. Hence strengthening of the delivery system is
the only way to get better results from the existing
regimens.
Chakraborty et al (1992) in their model on variable
efficiency of the DTP as a system showed that not only
treatment
results
would
differ
depending
on
the
operational efficiency of the treatment delivery system,
but would also directly correlate with the case-finding
efficiency10. Efforts to change the treatment efficiency
only through selected augmented inputs, without
improvement in case-finding efficiency, is hardly the way
to control tuberculosis. However, whether a new system is
to be developed for organised treatment administration
under supervision, as distinct from the current system and
practice of an organised treatment delivery, requires
further research. Alternatively, it will be ideal to
administer every dose under supervision to ensure the
achievement of maximum efficiency. Revised strategy
being organised currently in several parts of India will
show whether or not the expectation for maximum
efficiency is something more appropriate to remain
enshrined on fungoid parchments.
To conclude, the SR incomplete treatment group had a
serious outcome, the overall results in this group was
almost similar to natural dynamics itself. Organised
treatment delivery is thus of paramount importance,
whether the treatment regimen is SR or SCC. When only a
small proportion of patients in the community are put on
SCC, its epidemiological impact could be minimal, even
with the high cure rate.
References
1.
Grzybowski S: Natural history of tuberculosis
epidemiology; Bull IUATLD 1991,66:193-194.
2.
Fox Wallace: The chemotherapy of pulmonary
tuberculosis - A review; Chest 1979, 76 (Supl):
785-796.
3.
Sujatha
Chand rase karan:
Value
of
sputum
examination in predicting prognosis during short
course chemotherapy; NTI Bulletin, 1993, 29, 41-44.
4.
Nagpaul
DR:
Results
of chemotherapy
under
programme conditions: 1972, WHO/TB/73.99.
5
.r
5.
National
Tuberculosis
Institute,
Bangalore:
Tuberculosis in a rural population of south India: A
live years epidemiological study; Hull Wld Hllh Org
1974, 51: 473-488.
8. Chaudhuri K, Jagota P and Parimala N: Results of
treatment with a short course chemotherapy regimen
used under field conditions in a district tuberculosis
programme; Ind J Tub 1993; 40:83-89.
6.
Baily GVJ and Gothi CD: The problem of drug
resistance under conditions of routine chemotherapy:
proceedings of IX IUAT & XXIX National
Conference on Tuberculosis & Chest Diseases 1974,
367-371.
9. Jagota P, Venkatarama Gupta EV, Channabasavaiah R:
Fate of smear positive patients of pulmonary
tuberculosis at an urban district tuberculosis centre five years after treatment. Ind J Tub 1994, 41,
223-232.
Jagota P, Venkatarama Gupta EV, Nagaraja Rao BS,
Pari mala N and Baily GVJ: The acceptability and
efficacy of two regimen of SCC under conditions of
an urban tuberculosis programme; Ind J Tub 1989,
36:18-26.
10. Chakraborty AK, Balasangameshwara VH, Jagota P,
Sreenivas TR and Chaudhuri K: Short course
chemotherapy and efficiency variables in NTP — A
model; Ind J Tub 1992; 39:9-20.
7.
J!
I
E
I
6
-
Points to Remember ‘White 'Entering Treatment Outcome
Resubts in Treatment Cards
B
A patient is said to have:
COMPLETED TREATMENT
4-
if a smear positive patient has completed the required number of drug collections but final follow-up
4-
smear result is not available.
a smear negative extrapulmonary patient has completed the required number of collections.
CURED
smear positive patient has completed treatment and is smear negative at the end of treatment.
4-
ii a
4-
if the patient has not collected drugs for more than one month from the due date.
LOST
TRANSFERRED
•4
if transferred to another district.
FAILED TO TREATMENT
4-
if the smear is positive at the end of treatment also.
TREATMENT STOPPED
4-
if treatment stopped by Medical Officer due to adverse reaction or change in diagnosis.
DEAD
4-
if dies during treatment period.
Source: National Tuberculosis Institute, Bangalore: Manual for Peripheral
Health Institutions, ED-4, Bangalore, NTI, 1994.
6
8;
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