DOI: 10.5958/2319-5886.2015.00110.

International Journal of Medical Research

&
Health Sciences
www.ijmrhs.com
Volume 4 Issue 3
Coden: IJMRHS
st
Received: 1 Apr 2015
Revised: 15th May 2015
Research article

Copyright @2015
ISSN: 2319-5886
Accepted: 5th Jun 2015

PATTERN OF EXTRA-PULMONARY TUBERCULOSIS IN PATIENTS WITH HUMAN

IMMUNODEFICIENCY VIRUS INFECTION, AT A TERTIARY CARE CENTRE IN EASTERN INDIA
*Mathew Ninan1, Doye George1, P Sukumaran1, Gunanidhi Sahu2, RN Mania2, Philip Mathew3
1

Department of Pulmonary Medicine,3Department of Community Medicine, Pushpagiri Medical College,

Tiruvalla, Kerala, India
2
Department of Pulmonary Medicine, SCB Medical College, Cuttack, Orissa, India.
*Corresponding author email: [email protected]
ABSTRACT
Introduction: Tuberculosis and Human Immunodeficiency Virus (HIV) co infection is becoming one of the most
important public health issues in India. In some developing countries, 40% of all tuberculosis cases are attributed
to HIV infection and in more than 50% of cases, tuberculosis is the first manifestation of HIV infection.
Materials and methods: A cross sectional study was done among the in-patients of a tuberculosis ward in a
tertiary care hospital in Eastern India. Fifty patients with HIV and tuberculosis infection of an extra pulmonary
site, were included in the study. Results: A vast majority of the participants were young males. More than 80%
were using intoxicants like alcohol or tobacco, 76% admitted exposure to commercial sex workers and 12% were
intravenous drug users. Twenty five (50%) of the participants had disseminated tuberculosis, that is tubercular
infection of more than one anatomical site. Maximum (62%) participants had tubercular infection of lymph
nodes, followed by pleura, abdomen and central nervous system. Discussion and conclusions: The sociodemographic correlates of participants were similar to that seen in similar studies in other parts of the world. But
in our study, tubercular lymphadenitis was the most common extra-pulmonary manifestation and proportion of
disseminated tuberculosis cases was as high as 50%. Both these findings are different from studies from other
parts of the world. These findings warrant a larger research study and programmatic changes to address issues of
HIV/TB co infection.
Keywords: Tuberculosis epidemiology, Tuberculosis diagnosis, Risk factors, HIV Infections/epidemiology
INTRODUCTION
Tuberculosis in India is characterised by high
incidence and prevalence of both tuberculosis
infection and disease. Different disease surveys have
yielded varied results, the prevalence of smear
positive pulmonary tuberculosis ranged from 0.6-7.6
per 1000 population while that of culture positive
tuberculosis was in the range 1.7-9.8 per 1000
population.(1)There is also a problem of high
transmission rates and is indicated by a very high
Annual Risk of Tuberculosis Infection (ARTI) of
around 1.5%.[1] Fittingly, India is classified along

with sub-Saharan countries in terms of the

effectiveness of tuberculosis control. [2] Even though
some studies have demonstrated a small downward
trend over a long period of time, especially after the
launch of the Revised National Tuberculosis Control
Programme (RNTCP), most of the tuberculosis
researchers and epidemiologists refuse to believe that
the peak of infection has already been crossed.[2]
According to a global consensus effort by World
Health Organisation (WHO) in 1997, the estimated
number of new cases for the year was around 8
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million and more than 50% of it was contributed by 5

countries of the WHOs South East Asian Region
(SEARO). They concluded that the burden of
tuberculosis is remaining so enormous, as the control
efforts have failed in South-Asia, sub-Saharan Africa
and Eastern Europe. [3] Since the global consensus
effort by WHO, Indian health authorities have
stepped up efforts to expand the RNTCP programme.
By 2005, RNTCP was successful in initiating
treatment for over 3.5 million patients and avoided
premature mortality in 600,000 patients. [4] Though
this renewed interest in tuberculosis control and
heavy investment in Directly Observed Treatment,
Short course (DOTS) strategy has yielded results in
urban and rural areas of the country, the tuberculosis
situation in Tribal areas have worsened over the last
few years. [2] In a state like Orissa, where Scheduled
Tribes (STs) form over 22% of the total population,
the ARTI was estimated to be 1.7% to 1.8%, much
above the national average rates. [5] The reasons for
this high infection load can be many; the poor
penetration of healthcare delivery infrastructure
coupled with low awareness levels among people can
be the main ones. In a study done in Orissa, only 16%
of the respondents knew about the cause of
Tuberculosis while 31% knew the correct mode of
spread of the disease. This is much lower than the
statistics from other parts of the country, derived
from similar surveys. [6]
Human Immunodeficiency Virus (HIV) infection is
an independent risk factor for tuberculosis and is
considered as a cause for the resurgence of
tuberculosis in many industrialised countries. The
high incidence of tuberculosis (almost 290/100,000
population) in Africa is also attributed to the high
prevalence of HIV infection in that part of the world.
[7]
In some countries like Tanzania, over 40% of the
tuberculosis cases are attributed to the presence of
HIV infection in those patients. [8] In most of the
developing countries, Tuberculosis is considered as
the most serious opportunistic infection among those
people with HIV infection and is the first
manifestation of Acquired Immunodeficiency
Syndrome (AIDS) in over 50% of the cases. [9] India
has the third most number of HIV patients with 2.1
million people living with HIV/AIDS. Though the
HIV epidemic in India is slowing down with a 57%
reduction in new HIV infections over a period of
2000 to 2011, it has the potential to explode into

gargantuan proportions. These points towards the

need for sustained investment in research activities on
HIV and allied subjects. [10] Diagnosis of tuberculosis
among HIV affected individuals pose a dilemma for
clinicians as most of the cases tend to be extrapulmonary and the routine sputum testing may prove
to be ineffectual. [11] The sites for extra-pulmonary
tuberculosis among HIV infected individuals seem
varied; according to a study from New Delhi,
abdomen (70%) is the most common site for extrapulmonary tuberculosis, followed by lymph nodes
(22%), pleura (15%) and Central Nervous System
(3%). [11] Another study from Shimla, Himachal
Pradesh showed that CNS tuberculosis constituted
over 33% of the extra-pulmonary tuberculosis cases
in HIV patients and was followed by abdominal
tuberculosis (26%). The study also found out that
disseminated tuberculosis was seen only in patients
with CD4 count of less than 200/cmm. [12] In a study
from Gujarat, it was found that among HIV patients,
60% of the tuberculosis disease was extra-pulmonary
in site and mediastinal tuberculosis constituted about
34% of them, followed by extra-thoracic
lymphadenopathy in 18% of the patients. [13]
Conversely, the prevalence of HIV infection among
those with tuberculosis is also much higher when
compared to general population. In a study done in
Agra, Uttar Pradesh, it was observed that the 4.3% of
the adults and 8.5% of the children attending a
tuberculosis clinic were HIV infected. [14, 15]
Tuberculosis and HIV are converging dual epidemics
and constitute the greatest public health challenge of
our time. The diagnosis and treatment of HIVTuberculosis co-infection is a difficult task and
understanding the pattern of disease in such cases
may help to identify patients who may need treatment
for both infections. [16]
MATERIALS AND METHODS
Study design: Cross-sectional, observational study
Inclusion criteria: Patients admitted with a diagnosis
of tuberculosis of any site were screened for HIV
infection using Enzyme Linked Immunosorbent
Assay (ELISA). Those patients, who had positive
results on ELISA, were tested and confirmed using
Western Blot technique. [17] All the patients who had
a positive test in ELISA and Western Blot, and
having suspicion of extra-pulmonary tuberculosis
were included in the study.
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Exclusion criteria: Those patients admitted in

intensive care units or on assisted ventilation were
excluded from the study
Ethical approval: Clearance was obtained from the
Institutional Review Board of SCB Medical College,
Cuttack, before the start of the study. Also, written
informed consent was obtained from all participants.
Duration of study: January 2004 to December 2005.
Methodology: Extra-pulmonary tuberculosis was
confirmed by mycobacterial and histopathological
examination of the relevant samples. For lymph node
tuberculosis, a lymph node biopsy or a Fine Needle
Aspiration Cytology (FNAC) was done to obtain
samples. Ascitic fluid or pleural fluid was taken to
confirm pleural or abdominal tuberculosis
respectively. Cerebro-Spinal Fluid (CSF) was taken
and examined to diagnose Central Nervous System
tuberculosis. Radiological investigations like contrast
enhanced CT scans were used for diagnosis when
mycobacterial and histopathological examination was
inconclusive or when appropriate samples were not
obtained.
The participants were administered a standardised,
pilot-tested questionnaire to find out their sociodemographic correlates, risk factors, symptoms, past
history and treatment history. A focussed clinical
examination was done to elicit all the associated
clinical signs. A sputum sample was collected for
Ziehl-Neelsen(ZN) staining [18], to rule out pulmonary
tuberculosis and a venous blood sample was collected
for measuring CD4 (Cluster of Differentiation 4)
counts, which is a surrogate marker for disease
activity
in
HIV
infection[19].

Table 1: Baseline characteristics (n=50)

Attribute
Age
(in Years)

Sex
Marital
Status
Occupational
status

HIV status of
spouse(n=41)

Characteristics
15-24
25-34
35-44
45 and above
Male
Female
Married/ Unmarried/
Separated/Divorced
Spouse died
Manual labourer
Driver
Small business
Army/Police
Housewife
Others
Positive
Negative
Unknown

%
6%
44%
44%
6%
92%
8%
82%
18%
0
54%
22%
10%
2%
8%
4%
58.5%
29.2%
12.2%

A vast majority of the participants were using

intoxicants regularly. Forty four (88%) of the
participants admitted using Alcohol, 40(80%) said
they use tobacco in some form and 4(8%) used
cannabis/cannabinoids. Among the other social risk
factors for HIV infection, 35(70%) had history of
migration from the place of birth and 5(10%) had
history of imprisonment or incarceration by a court of
law. A vast majority of the participants (38, 76%)
admitted having contact with commercial sex workers
and 6(12%) have used intravenous drugs in the past.
Interestingly, none of the participants were
homosexuals [Table 2]
Table 2: Social risk factors for HIV infection
(n=50)
Risk factor
Use of intoxicants

RESULTS
A total of 50 patients with HIV/TB co-infection and
with extra-pulmonary manifestation of tuberculosis
infection, were included in the study. The maximum
numbers of participants were from the age group 2534 years (44%) and 35-44 years (44%). Males
constituted 92% of the total study participants and
82% of the participants were married. Most of the
study participants were manual labourers (54%) and
drivers (22%). Twenty four (58.5%) of the currently
married participants had their spouses with a positive
HIV status, while it was negative for 29.2% and
unknown for 12.2%. [Table 1]

Number
3
22
22
3
46
4
41
9
0
27
11
5
1
4
2
24
12
5

History of Migration
History of
Imprisonment
Contact with
Commercial Sex
Worker
Men Having Sex with
Men (MSM) (n=46)
Intravenous drug user

Characteristic
Alcohol
Tobacco
Cannabis
Hallucinogens
Yes
No
Yes
No
Yes
No

Number(%)
44(88%)
40(80%)
4(8%)
6(12%)
35(70%)
15(30%)
5 (10%)
45(90%)
38(76%)
12(24%)

Yes
No
Yes
No

0
46(100%)
6(12%)
44(88%)

Twenty five (50%) of the participants had

disseminated tuberculosis, that is tuberculosis
infection of more than one anatomical site. The rest
of the participants had tuberculosis limited to one
extra-pulmonary site. Lymph nodes were the most
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Int J Med Res Health Sci. 2015;4(3):572-577

common site (62%) followed by pleura (32%),

abdomen (22%), Central Nervous System (8%) and
bone marrow (2%). None of the participants had
tuberculosis infection of the spine or the
mediastinum. [Table 3]
Table 3: Pattern of Extra-pulmonary tuberculosis
(n=50)
Extra-pulmonary site
Number Percentage
Lymph node(s)
31
62%
Pleura
16
32%
Abdomen
11
22%
Central Nervous system 4
8%
Bone marrow
1
2%
Spine
0
0
Mediastinum
0
0
Among the 25 participants with disseminated
tuberculosis infection, 7(28%) had infection of lymph
nodes and lung, 5 (20%) had infection of lymph node
and pleura and 4(16%) had infection of lymph nodes
and abdomen. One (4%) participant each had
tuberculosis infection of bone marrow and miliary
tuberculosis. [Table 4]
Table 4: Pattern of Disseminated tuberculosis
(n=25)
Sites of Dissemination
Lymph node and lung
Lymph node and pleura
Lymph node and abdomen
Lymph node, pleura and abdomen
Lymph node and CNS
Lymph node, CNS and lung
Pleura and abdomen
Pleura and lung
Abdomen and lung
Bone marrow
Miliary

Number
7
5
4
1
1
1
2
1
1
1
1

%
28%
20%
16%
4%
4%
4%
8%
4%
4%
4%
4%

Among the 25 participants where the tuberculosis

infection was limited to one extra-pulmonary site,
12(48%) had infection of the lymph nodes, 8(32%)
had infection of the pleura, 3(12%) had abdominal
tuberculosis and 2(4%) had Central Nervous system
tuberculosis. [Table 5]
Table 5: Pattern of isolated extra-pulmonary
tuberculosis (n=25)
Extra-pulmonary site
Number Percentage
Lymph node
12
48%
Pleura
8
32%
Abdomen
3
12%
Central Nervous System
2
4%

DISCUSSION
The study reveals a familiar trend seen in other parts
of the world, where HIV infection and tuberculosis
are generally considered as a disease of social
inequities. The participants in our study are from
occupations which are relatively lowly paid, a large
number of them are migrants, and the use of
intoxicants is very high. A similar finding is seen in
studies done in other parts of the world, especially
South Asian nations and African countries. [20] A vast
majority (76%) of the participants reported exposure
to commercial sex workers and this may be the
reason behind the baseline demographic correlates
being skewed in favour of young males. This finding
is also in concordance with the results of similar
studies from other parts of the country which states
that commercial sex is the primary mode of HIV
infection for males and sexual relations with the
infected husband is the most important mode of
acquiring infection for females. [21]
In our study, the most common site of extrapulmonary tuberculosis infection was lymph nodes,
followed by pleura and abdomen. Tubercular
lymphadenitis was seen commonly in disseminated
tuberculosis infection as well as in isolated extrapulmonary tuberculosis. This finding is quite
different from the findings in other parts of the
country which stated that infection of the abdomen
and Central Nervous System were the most common
extra-pulmonary sites in HIV/TB co infection. The
proportion of disseminated tuberculosis cases among
all the extra-pulmonary tuberculosis patients was as
high as 50%, and this is much higher when compared
to data from other parts of the world. [22] This may be
due to the late diagnosis of tuberculosis and HIV
infection, Orissa being a relatively backward state in
socio-economic progress and healthcare delivery
indicators.
CONCLUSION
This study points towards the need to do more
extensive research in HIV/TB co-infection. All the
stakeholders of the Revised National Tuberculosis
Control Programme (RNTCP) and the National Aids
Control Programme (NACP) needs to be sensitised
on the need to screen for the other infection when one
of it is diagnosed in a patient. Since the diagnosis of
extra-pulmonary tuberculosis is difficult and
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expensive, it poses a clinical dilemma to the treating

doctors. Diagnostic protocols and cost-effective
techniques need to be formulated in diagnosing and
treating these conditions when both the infections
occur together.

10.
11.

ACKNOWLEDGEMENT
The authors would like to thank the patients and staff
of SCB Medical College and Hospital, Cuttack for all
their cooperation and help.

12.

Conflict of interest: Nil

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