Following the success of Directly Observed Treatment-Short Course DOTS programme over recent years, a study was carried out to determine prevalence of EPTB, to draw comparison between an
Trang 1Background & Objectives: Extra-pulmonary tuberculosis (EPTB) cases have been treated with a daily short course
chemotherapy (SCC) regimens in past Following the success of Directly Observed Treatment-Short Course (DOTS) programme over recent years, a study was carried out to determine prevalence of EPTB, to draw comparison between annual case detection of pulmonary TB (PTB) and extra-pulmonary TB and to assess outcome of DOTS in EPTB in a patient population of Delhi.
Methods: All consecutive EPTB cases of Delhi, diagnosed within LRS Institute of TB and Respiratory Diseases between
January 1996 to March 2003 and subsequently given DOTS at the area DOTS Centres, constituted the study group.
Results: Of overall 14185 cases, 2849 (20%) had EPTB A significantly higher prevalence was observed in females (57%)
and in young age (mean + standard deviation of 23.4 + 12.8 years) Commonest involved site was lymph node (54%) Whereas number of PTB and EPTB cases have increased over successive years, percentage of former declined significantly through 84 in 1996 to 78 in 2002 and that of latter rose significantly through 16 to 22 correspondingly EPTB to PTB ratio changed significantly from 1:5 at start to about 1:3.5 at study-conclusion Treatment completion was observed in 94% (1775/1885) of EPTB cases.
Conclusions: Under Revised National TB Control Programme (RNTCP) employing a DOTS strategy, annual case
detection has improved for both pulmonary and extra-pulmonary TB Cure of infectious disease is likely to have resulted
in a relative rise of the annual EPTB case detection DOTS effected an acceptable treatment outcome in EPTB case management. [Indian J Tuberc 2006;53:77-83]
Key words: Tuberculosis (TB), Extra-pulmonary tuberculosis (EPTB), Directly Observed Treatment- Short Course
(DOTS).
Original Article
TRENDS OF EXTRA-PULMONARY TUBERCULOSIS UNDER REVISED NATIONAL TUBERCULOSIS CONTROL PROGRAMME: A STUDY FROM SOUTH DELHI*
V K Arora 1 and Rajnish Gupta 2
(Original received on 6.5.2005; Revised version received on 4.8.2005; Accepted on 16.8.2005)
INTRODUCTION
Extra-pulmonary tuberculosis (EPTB) is a
milder form of disease in terms of infectivity as
compared to pulmonary TB (PTB) Whereas sputum
can be easily obtained for the detection of disease in
lungs, diagnosis of EPTB is often difficult requiring
invasive and expensive serological/radiological
investigations A category-wise drug treatment is
similar for the two forms of disease1 However, an
assessment of end point of cure is a problem with
EPTB With the global rise of human
immuno-deficiency viral (HIV) infection over last decade,
studies have reported increasing association of EPTB
in HIV infected individuals2,3. Prevalence of EPTB
has also been found to be high in paediatric TB cases4
In the past, treatment of EPTB has been
carried out with a Short Course Chemotherapy
(SCC), which has given successful results in tubercular affection of lymph nodes5
, pleura2,6
,male7
and female8,9 genitalia, ear10, skin11
, joints12 etc Even the more serious forms like tubercular meningitis (TBM) and miliary TB have been cured with it However, the treatment in past needed to be given
on a daily basis and delayed resolution, default or failure occurred frequently owing to incorrect prescriptions, inappropriate communication/drug intake, erratic medical supplies and inaffordability
A Directly Observed Treatment-Short Course
(DOTS) strategy was recommended for National Tuberculosis Control Programmes globally by the WHO about a decade back1, which was found to be successful in all types of TB cases13-23 Reports have largely focused on smear positive pulmonary TB that posed greater infectivity threat and accounted for a higher morbidity and mortality than EPTB In view
*Paper presented at the 58th National Conference on Tuberculosis & Chest Diseaes held in Mumbai in January 2004.
1 Former Director 2 Chest Physician
Department of TB & Respiratory Diseases, LRS Institute of TB & Respiratory Diseases, New Delhi.
Correspondence: Prof (Dr.) V.K Arora,Director Principal, Santosh Medical College & Hospital, Ghaziabad, (U.P.)
Tel: 95-120-3200937 E-mail: vk_raksha@yahoo.com
Trang 2of the scarce data in respect of EPTB case-management
with DOTS, especially in Indian context, a study was
designed with the objectives: i) to determine prevalence
of EPTB, ii) to draw comparison between annual case
detection of PTB and EPTB, and iii) to assess outcome
of DOTS in extra-pulmonary form of disease in a
locality in Delhi
MATERIAL AND METHODS
Present study is a retrospective analysis of
the patients’ record among a population of Delhi
living in the area catered by L.R.S Institute of TB
and Respiratory Diseases The record comprised of
parameters such as age, sex, site of disease (lymph
node, pleura, abdomen, bone, joint, genitalia, kidney,
skin, meninges and miliary), TB category (I, II or
III) and treatment outcome (completion, default,
failure, transfer out or death) for all consecutive
cases, diagnosed as having EPTB at the Institute and
administered DOTS at the area DOTS centres
between January 1996 and March 2003
The diagnosis of EPTB cases was
established following the programme guidelines,
which required one culture positive specimen from
an extra-pulmonary site, or histological evidence, or
strong clinical evidence consistent with active EPTB
followed by a Medical Officer’s decision to treat
with a full course of anti-TB therapy1 The type of
investigation necessary to prove the presence of
disease depended upon the site of EPTB Whenever
needed, invasive procedures were carried out under
an ultrasonic or a computed tomographic guidance
and the specimen subjected to a culture or
histopathology for evidence of TB Following
diagnosis and categorisation, EPTB cases were
referred to their respective area DOTS centres, where
regular drug administration and follow up visits took
place as per the programme guidelines for a specified
duration of therapy1 Health education and motivation
to them was imparted within Institute prior to the
referral, as well as during the subsequent follow-up
visits at DOTS centres The trained staff of these
centres, while administering the drugs, inquired about
the tolerance and possible side-effects, if any The
number of PTB cases of area, who were diagnosed
and treated with DOTS at the DOTS centres, was
also recorded over the same study-period for a comparative analysis with EPTB cases Analysis of treatment outcome was done for EPTB cases, whose data was available
RESULTS
Of the overall 14,185 area cases treated under DOTS during study-period, 11,336 (80%) had pulmonary TB and 2849 (20%) suffered from EPTB The latter comprised a higher number of females (1615 (57%)) than males (1234 (43%)) constituting
a significantly different (p< 0.01) male: female ratio
of 1: 1.3 Age-distribution of EPTB cases (Table 1) showed higher disease prevalence in the young age, with a mean + standard deviation (SD) of 23.4 +12.8 years Case-distribution with regard to the age as well as the male: female ratio demonstrated respectively similar annual trends Commonest site
of EPTB involvement was lymph nodes (Table 2) followed by affection of pleura The category-wise distribution placed highest number of study cases in Category III (1943 or 68%) followed by those in Categories I (537 or 19%) and II (369 or 13%)
Excluding an insignificant (p >0.05) dip in number of cases detected in 1998 as compared to the preceding year, detection of total, as well as, of PTB and EPTB cases increased progressively over the successive study years (Figure 1) Percentage
Table 1: Age distribution of extra-pulmonary
tuberculosis cases
V K ARORA AND RAJNISH GUPTA
Age (in years) Case-number (%)
<14 15-24 25-34 35-44 45-54 55-64
>65
Total
611 (21)
1074 (38)
725 (25)
274 (10)
92 (3)
45 (2)
28 (1)
2849 (100) 78
Trang 3of annual EPTB case detection (Figure 2) increased significantly (p < 0.01) through 16 in 1996 to 22 in
2002, whereas that of PTB decreased significantly (p < 0.01) through 84 to 78 during same time, though change for the either was not uniformly similar over intervening years A further comparison of EPTB to PTB case detection ratio between the base and final years of study showed a significant (p < 0.05) fall in the value of PTB cases from 1:5 to 1:3.5 (Figure 3)
The available outcome for the 1885 EPTB cases, ranging from the milder lymphadenopathy to the serious ones like meningeal or miliary TB etc, who were treated with DOTS from January 1996 to December 2001, showed treatment completion in
1775 (94%), default in 69 (3.7%), failure in 18 (1%), transfer-out in 12 (0.7%) and death in 11 (0.6%) cases Drug tolerance was good No significant drug modifications were required due to side-effects such
as drug induced hepatitis etc
DISCUSSION
The present study has shown a rising trend
of annual TB case detection in the area over recent years for both PTB and EPTB cases This rise is believed to have occurred due to the extensive case management efforts undertaken within the area under
Table 2: Site distribution of extra-pulmonary
tuberculosis cases
0
500
1000
1500
2000
2500
3000
3500
1996 1997 1998 1999 2000 2001 2002
Years
EPTB PTB Total
Fig 1: Annual case detection trend in numbers Fig 2: Annual case detection trend in %
EXTRA-PULMONARY TB AND DOTS
0 10 20 30 40 50 60 70 80 90
1996 1997 1998 1999 2000 2001 2002
Years
Involved site Case-number (%)
Lymph node
Cervical
Axillary
Para-tracheal
Mediastinal
Pleural
Effusion
Empyema
Abdominal
Bone and joint
Genital
Renal
Ocular
Dermal
Meningeal
Miliary
Total
1530 (53.7)
1444
66
6
14
817 (28.7)
809
8
192 (6.7)
201 (7.0)
36 (1.3)
2 (0.1)
4 (0.2)
5 (0.2)
29 (1.0)
33 (1.1) 2849(100.0)
79
Trang 4DOTS programme over last decade, which have
enhanced the case enrollment of both forms of
TB4,16,17,24,25.During same period, with a population
growth, the overall number of cases is also expected
to rise HIV could be another contributory factor
However, a recent study from LRS Institute has
found a low HIV sero-prevalence (0.9%) in area TB
cases (unpublished data) in comparison to other
regions of country outside Delhi26,27,implying thereby,
that the factor is less likely to have played a significant
role in the observed trend of disease Exact cause
for the rise in annual TB cases in area needs to be
better defined
The study has shown that the percentage
of annual case detection has been gradually declining
for PTB (from 84 in 1996 to 78 in 2002) and rising
for EPTB (from 16 in 1996 to 22 in 2002) Both
observations appear to be linked because high cure
rate for new smear positive cases with DOTS over
last decade is likely to have reduced the TB
transmission level in area, thereby, accounting for the decline in percentage of observed annual PTB cases, as well as, the change in EPTB: PTB ratio (from about 1: 5 at start to about 1: 3.5 at conclusion
of study) The decline of annual PTB case detection percentage is assumed to have contributed in a relative rise of the annual EPTB case percentage from the expected prevalence of 7.4% (10/135)28 under DOTS programme to the significantly higher (p < 0.01) observed level of 22% More studies need to be carried out, in order to determine the trend change
of EPTB and the factors responsible for this especially desirable in developing countries, where more TB cases exist and HIV is also on the rise
Demographic characteristics of EPTB cases have shown higher detection in females and in patients of young age Similar observations have been made in past29,30 Recent Indian studies have also noted
a higher prevalence of EPTB in children than adults
(47% vs 16% respectively), with greater affection
0
1
2
3
4
5
6
Years
Fig 3: Annual trend of case detection ratio
V K ARORA AND RAJNISH GUPTA 80
Trang 5of females (63% vs 33% respectively)4 In contrast,
a higher prevalence of PTB has been observed in
elderly than younger patients (16:1 respectively),
with male preponderance of disease (3:1
respectively)24.Thus, demography of disease has not
changed over the years
Most commonly involved EPTB site was
lymph node in more than one-half of
patient-population followed by the pleural effusion in more
than one-fourth of study cases This finding is in
accordance with the epidemiological trend seen in
developed countries over past couple of decades,
where a rise in tubercular lymphadenitiscaseshas
been noticed after the onset of HIV era29 Although
a pre-dominance of lymphadenopathy among EPTB
cases in HIV and TB co-infected cases has been
recently reported from the capital31, more studies
need to be carried out, in order to ascertain the
association of tubercular lymphadenitis and HIV
infection within the region as well as within the
country
It is notable that the observed outcome of
area, with a treatment completion of 94%, default
of <4% and failure of 1%, was better than that
reported for the country under the past and the
present NTP17-19.Although, treatment outcome is
likely to have been influenced by the presence of a
large number of EPTB cases with the Category III
disease (as compared to the Categories I or II), the
observation of quality assurance in case management
is also believed to have been contributory Whereas,
information, education and communication (IEC)
campaigns were conducted for the community
awareness, funds and administrative will adequately
supported the DOTS programme
It was encouraging to note that DOTS could
satisfactorily treat all forms of EPTB without
requiring significant treatment modifications due to
drug-induced hepatitis Its absence has been reported
earlier during the treatment of EPTB from the hilly
region of Himachal Pradesh, where presence of
hypoxia was believed to exist as an additional
contributory factor in causation of hepatic
impairment32 Exact reason for the observation in
EPTB needs to be explored However, the absence
of side-effects is likely to have contributed in a good treatment compliance
Future Issues
The EPTB cases employed in service tend
to ignore their disease by giving priority to occupational compulsions Recent study from Delhi has reported a high treatment success with service utilisation of DOTS providers for those TB cases engaged in job, study or household work 25 Utility
of providers in delivering DOTS to TB cases has been reported in other studies as well.33,34 Similarly,
an involvement of private practitioners (PPs) in DOTS programme has been suggested as another way of increasing the case enrollment and treatment success in TB control because usual PP practices have been found to be ill advised and poorly performed Recent efforts to bring about a PP participation in Delhi resulted in EPTB case detection
of 23% (143 out of 612 cases) and a treatment completion of 68% (13 out of 19 cases in just 1 quarter)35 Feasibility of improved case detection through involvement of PPs has been similarly reported from Vietnam.36 In a probable changing scenario of disease, with an increasing EPTB prevalence, role of DOTS providers and private practitioners could become even greater, for, they could assist in the further enhancement of case enrolment, as well as, treatment success
As of now, EPTB cases continue to be referred for the management from a DOTS centre
to the tertiary institute However, future health policies may necessitate the placement of EPTB at a greater level of priority than that in existence DOTS centres could be also strengthened to play a greater role in EPTB case management
In conclusion, annual case detection has improved for both pulmonary and extra-pulmonary TB under Revised National TB Control Programme employing a DOTS strategy Cure of infectious disease is likely
to have contributed in a relative rise of the annual EPTB case detection DOTS effected
an acceptable treatment outcome in EPTB case management.
Trang 6Present study did not undertake a carriage
of the HIV serology that has been presumed to be
responsible for the rise in the number of tubercular
lymphadenitis cases in developed countries Another
limitation of this study related to the difficulty in
declaring an EPTB case cured in the absence of
objective evidence at end of treatment A prolonged
follow-up of the treated cases could provide data
with regard to the number of relapses
ACKNOWLEDGEMENTS
Authors are grateful to the RNTCP
department of Institute, which has been active in
conducting DOTS programme within Institute
Thanks are also due to Mr Anup Kumar Singh, for
carrying out a statistical analysis, and team of Anil
Awasthi, Rajni Kant and Pradeep for providing a
secretarial assistance
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Essay Competition For Medical Students-2006
The Tuberculosis Association of India awards every year a cash prize of
Rs 500/- to a final year medical student in India for an original essay on tuberculosis
The subject selected for the year 2006 competition is ‘HIV and Tuberculosis’
The essay should be written in English, typed double spaced, on foolscap size
paper and should not exceed 15 pages (approximately 3,000 words, including tables,
diagrams, etc.) Four copies of the typescript should be forwarded through the
Dean or Principal of a College/University to reach the Secretary-General,
Tuberculosis Association of India, 3 Red Cross Road, New Delhi-110 001, before
30th June, 2006 along with a certificate that the author is a final year medical
student.