role of quantiferon-tb gold in diagnosis of tuberculosis

Role of QuantiFERON-TB Gold in diagnosis of Tuberculosis

International Archives of Integrated Medicine, Vol.

Copy right © 2014, IAIM, All Rights Reserved.

Original Research Article

Role of QuantiFERON

Aparna Pandey1Department of Laboratory

2Department of Laboratory Services

*Corresponding author email:

How to cite this article: Aparna Pandey

diagnosis of Tuberculosis. IAIM, 2014; 1(3):

Available online at

Received on: 06-11-2014

Abstract

Introduction: The definitive diagnosis

features can be demonstrated or mycobacteria can be isolated from the body fluids or from sputum

or from gastric lavage. Various other methods, such as

polymerase chain reaction are also available. It is wel

and culture is difficult and time consuming and other tests are complex and technically more

demanding. In this study, we correlated the results of QuantiFERON

test and sputum positivity.

Material and methods: Total 150 subjects were included in this study. The clinical features and

detailed history of each case wa

physical examination. Patients were tested for

Results: The results obtained in this study showed

patients may not be able to detect all

methods for the diagnosis of tuberculosis patients is more

tuberculosis patients. The combination of tuberculin skin

test had yield 96.6% cases as positive in our study which is far better than using a single test.

Conclusion: Use of QuantiFERON

conventional methods of diagno

tuberculin skin test yields the maximum number of true positive cases of tuberculosis. The levels of

new markers, serum interferon gamma (

combining it with tuberculin skin t

even in latent cases.

Key words

Interferon gamma, Sputum, Tuberculin skin t

TB Gold in diagnosis of Tuberculosis

International Archives of Integrated Medicine, Vol. 1, Issue. 3, November, 2014.


Role of QuantiFERON-TB Gold in diagnosis of

Tuberculosis

Aparna Pandey1*

, Jayesh P. Warade2

Department of Laboratory Services, Apollo Specialty Hospital, Madurai, Tamil

Services, Meenakshi Mission Hospital and Research Centre, Madurai,

Tamilnadu, India

*Corresponding author email: [email protected]

Aparna Pandey, Jayesh P. Warade. Role of QuantiFERON

IAIM, 2014; 1(3): 9-12.

vailable online at www.iaimjournal.com

2014 Accepted on:

The definitive diagnosis of Tuberculosis is established when typical histological


or from gastric lavage. Various other methods, such as gel electrophoresis, radiometric assay and

polymerase chain reaction are also available. It is well documented that isolation of m


we correlated the results of QuantiFERON-TB Gold test with tuberculi

150 subjects were included in this study. The clinical features and

detailed history of each case was recorded in a standard format including exposure to infection and

physical examination. Patients were tested for QuantiFERON-TB Gold.

lts obtained in this study showed that single method for diagnosis of tuberculosis

patients may not be able to detect all the positive cases of tuberculosis. Whereas combining two

methods for the diagnosis of tuberculosis patients is more advantageous way for the detec

tuberculosis patients. The combination of tuberculin skin test along with the QuantiFERON

yield 96.6% cases as positive in our study which is far better than using a single test.

Use of QuantiFERON-TB Gold test for the diagnosis of tuberculosis is superior to

conventional methods of diagnosis, above which the QuantiFERON-TB Gold test

est yields the maximum number of true positive cases of tuberculosis. The levels of

interferon gamma (IFN-γ) after stimulation by foreign antigen by

skin test yields a good amount of true positive cases of tuberculosis

eron gamma, Sputum, Tuberculin skin test, Mycobacterium, Microscopic.

ISSN: 2394-0026 (P)

ISSN: 2394-0034 (O)

Page 9

TB Gold in diagnosis of

Apollo Specialty Hospital, Madurai, Tamilnadu, India

Mission Hospital and Research Centre, Madurai,

Role of QuantiFERON-TB Gold in

Accepted on: 10-11-2014

is established when typical histological


gel electrophoresis, radiometric assay and

l documented that isolation of mycobacteria


old test with tuberculin skin

150 subjects were included in this study. The clinical features and

ncluding exposure to infection and

that single method for diagnosis of tuberculosis

the positive cases of tuberculosis. Whereas combining two

advantageous way for the detection of

test along with the QuantiFERON-TB Gold

yield 96.6% cases as positive in our study which is far better than using a single test.

old test for the diagnosis of tuberculosis is superior to

old test in combination with

est yields the maximum number of true positive cases of tuberculosis. The levels of

after stimulation by foreign antigen by QFT test and

est yields a good amount of true positive cases of tuberculosis




Introduction

Tuberculosis (TB) is one of the dreadful diseases

affecting a number of people in developing

countries including India. It is one of the most

common diseases causing a high mortality and

morbidity. The total number of cases is rising

every year because of rapidly growing

population, socio-cultural reasons, increasing

number of HIV cases, increasing number of poor

people and non-compliance to the treatment.

Another emerging issue is widespread

dissemination of multiple drug resistant cases of

TB, which has raised the eyebrows of publ

health experts because it not only makes the

disease condition more lethal, it also required

very high costs to cure the condition. The

definitive diagnosis is established when typical

histological features can be demonstrated or

mycobacteria can be isolated from the body

fluids or from sputum or from gastric lavage.

Various other methods, such as gel

electrophoresis, radiometric assay and

polymerase chain reaction are also available. It

is well documented that isolation of

mycobacteria and culture is di

consuming and other tests are complex and

technically more demanding, most of the times

diagnosis is based on radiological features,

clinical features and positive tuberculin testing

[1]. Recently, attempts are on to find most

simple techniques which are reliable

feasible; less costly and giving quick results and

are largely comparable with standard

techniques. In this study, we

results of QuantiFERON-TB Gold test with

tuberculin skin test and sputum positivity.

Material and methods

The present study was carried out i

Department of Pathology of G.S.V.

College, Kanpur from January 2008 to October

2010. Total 150 subjects were included in this




f the dreadful diseases

affecting a number of people in developing

countries including India. It is one of the most

common diseases causing a high mortality and

morbidity. The total number of cases is rising

every year because of rapidly growing

cultural reasons, increasing

number of HIV cases, increasing number of poor

compliance to the treatment.

Another emerging issue is widespread

dissemination of multiple drug resistant cases of

TB, which has raised the eyebrows of public

health experts because it not only makes the

disease condition more lethal, it also required

very high costs to cure the condition. The

definitive diagnosis is established when typical

histological features can be demonstrated or

lated from the body

fluids or from sputum or from gastric lavage.

Various other methods, such as gel

electrophoresis, radiometric assay and

polymerase chain reaction are also available. It

l documented that isolation of

s difficult and time

and other tests are complex and

technically more demanding, most of the times

diagnosis is based on radiological features,

and positive tuberculin testing

Recently, attempts are on to find most

iques which are reliable, more

feasible; less costly and giving quick results and

are largely comparable with standard

, we correlated the

TB Gold test with

kin test and sputum positivity.

The present study was carried out in

Department of Pathology of G.S.V.M. Medical

uary 2008 to October

150 subjects were included in this

study. The clinical features and detailed history

of each case was recorded in a standard format

including exposure to infection and

examination. Patients were tested for

QuantiFERON-TB Gold and other ro

up including tuberculin skin test

examination. The method used in our study wa

QFTG-IT. The statistical analysis was done

accordingly with simple mathematical

calculation.

Results

The results obtained from the study we

tabulated and interpreted as per

combination of tuberculin skin

the QuantiFERON-TB Gold test had

cases as positive which was far b

a single test like sputum e

tuberculin skin test (68%) and QuantiFERON

Gold (70%). It had also

combining test like sputum positivity +

tuberculin skin test (84.6%)

TB Gold + sputum examination (76.6%)

Table - 1.

Discussion

The results obtained in this study showed

single method for diagnosis of tuberculosis

patients may not be able to detect all the

positive cases of tuberculosis. Whereas

combining two methods for the diagnosis of

tuberculosis patients is more

for the detection of tuberculosis patients. The

combination of tuberculin skin

the QuantiFERON-TB Gold test had

cases as positive in our study which is far b

than using a single test sputum e

(63.3%), tuberculin skin t

QuantiFERON-TB Gold (70%). It has also

advantage over combining test like sputum

positivity + tuberculin skin t

QuantiFERON-TB Gold + sputum e

(76.6%).

ISSN: 2394-0026 (P)

ISSN: 2394-0034 (O)

Page 10

study. The clinical features and detailed history

s recorded in a standard format

exposure to infection and physical

examination. Patients were tested for

old and other routine work

up including tuberculin skin test and sputum

examination. The method used in our study was

The statistical analysis was done

accordingly with simple mathematical

esults obtained from the study were

as per Table – 1. The

tion of tuberculin skin test along with

TB Gold test had yield 96.6%

s far better than using

a single test like sputum examination (63.3%),

and QuantiFERON-TB

also advantage over

combining test like sputum positivity +

est (84.6%) while QuantiFERON-

xamination (76.6%) as per

lts obtained in this study showed that

single method for diagnosis of tuberculosis

patients may not be able to detect all the

positive cases of tuberculosis. Whereas

combining two methods for the diagnosis of

tuberculosis patients is more advantageous way

tion of tuberculosis patients. The

combination of tuberculin skin test along with

TB Gold test had yield 96.6%

cases as positive in our study which is far better

than using a single test sputum examination

, tuberculin skin test (68%) and

old (70%). It has also

advantage over combining test like sputum

positivity + tuberculin skin test (84.6%) while

TB Gold + sputum examination




IFN-γ release assays (IGRAs) are exciting new

developments in TB infection testing. IGRAs are

based on the ability of the

tuberculosis antigens for early secretory antigen

target 6 (ESAT-6) and culture filtrate protein 10

(CFP-10) to stimulate host production of IFN

[2]. Because these antigens are not present in

non-tuberculous mycobacteria or in any B

vaccine variant, these tests can distinguish

latent TB infection (LTBI). The blood tests QFT

Gold in Tube and TSPOT. TB use these antigens

to detect people with TB. Lymphocytes from the

patient's blood are incubated with the antigens.

These tests are called IFN-γ tests and are not

equivalent. If the patient has been exposed to

TB before, T lymphocytes produce IFN

response. The QFT Gold in Tube uses an ELISA

format to detect the whole blood production of

IFN-γ with great sensitivity (89%). The distin

between the tests is that QFT Gold quantifies

the total amount of IFN-γ when whole blood is

exposed to the antigens (ESAT-6, CFP

7.7(p4)).

Due to this working principle of the

QuantiFERON-TB Gold test, it is possible to

detect even the latent infection in the so called

healthy subjects. Miguel, et al. (2007) studied

clinical utility of IFN-γ Assay in the diagnosis of

TB [3]. This study discussed

benefits and drawbacks in patients, including

those who are immune compromised. Thi

that measure the production of IFN

after sensitization with mycobacterium

antigens are available and, at least theoretically,

may overcome some of the limitations of

tuberculin skin test. Connell,

studied performance of a whole blood IFN

assay for detecting latent infection with

mycobacterium TB in children. The study was

undertaken to compare the performance of the

whole blood IFN-γ assay with the tuberculin skin

test in diagnosing LTTB infection or TB disease in

children in routine clinical practice 106 children




release assays (IGRAs) are exciting new

developments in TB infection testing. IGRAs are

of the mycobacterium

antigens for early secretory antigen

iltrate protein 10

stimulate host production of IFN-γ

Because these antigens are not present in

tuberculous mycobacteria or in any BCG

vaccine variant, these tests can distinguish

. The blood tests QFT

Gold in Tube and TSPOT. TB use these antigens

to detect people with TB. Lymphocytes from the

patient's blood are incubated with the antigens.

tests and are not

equivalent. If the patient has been exposed to

TB before, T lymphocytes produce IFN-γ in

response. The QFT Gold in Tube uses an ELISA

format to detect the whole blood production of

with great sensitivity (89%). The distinction

between the tests is that QFT Gold quantifies

when whole blood is

6, CFP-10 and TB

inciple of the

old test, it is possible to

nt infection in the so called

, et al. (2007) studied

Assay in the diagnosis of

TB [3]. This study discussed the potential

benefits and drawbacks in patients, including

compromised. This tests

that measure the production of IFN-γ by T-cells

after sensitization with mycobacterium TB

antigens are available and, at least theoretically,

may overcome some of the limitations of the

, et al. (2006)

ce of a whole blood IFN-γ

assay for detecting latent infection with

ycobacterium TB in children. The study was

undertaken to compare the performance of the

assay with the tuberculin skin

est in diagnosing LTTB infection or TB disease in

children in routine clinical practice 106 children

with a high risk of LTBI or TB dis

enrolled in the study [4]. Nahid P

proposed review on alternatives to the

tuberculin skin test: IFN-γ assays in the diagnosis

of mycobacterium TB infection. The

alternatives to the tuberculin skin t

diagnosing latent TB infection. Because of

advances in immunology and genomics, for the

first time, an alternative has emerged in the

form of T cell based IFN

generation of in vitro tests of cellular immunity.

These assays measure cell mediated immune

response by quantifying IFN-

in response to stimulation by

antigens. A review of current evidence on the

performance of IFN-γ assays an

Test suggests that both the Tuberculin Skin Test

and IFN-γ assays have advantages and

limitations, and both tests ap

this time [5]. Inoue, et al. (2009) in their study

found that all eight active TB patients had

positive QFT results, and none of the 95 patients

with negative results had active any TB.

sensitivity of the QFT reported is 100% (8 of 8)

and the specificity is 89.7% (87 of 97 cases) [6].

Archip, et al. (2008) compared the QFT test with

microscopic examination smear. They found that

the test is more useful than microscopic studies

of the smear. More ever it is also a faster and

easier method for the diagnosis of TB [7].

above evidences shows that use of

QuantiFERON-TB Gold test for the diagnosis of

tuberculosis is superior to conventional methods

of diagnosis, above which the QuantiFERON

gold test in combination with tuberculin skin

test yields the maximum number of true positive

cases of tuberculosis.

Conclusion

The levels of new markers, serum IFN

stimulation by foreign antigen by

combining it with tuberculin skin t

ISSN: 2394-0026 (P)

ISSN: 2394-0034 (O)

Page 11

with a high risk of LTBI or TB disease were

Nahid P, et al. (2006)

proposed review on alternatives to the

assays in the diagnosis

infection. There were no

alternatives to the tuberculin skin test for

diagnosing latent TB infection. Because of

advances in immunology and genomics, for the

first time, an alternative has emerged in the

form of T cell based IFN-γ assays, a new

of in vitro tests of cellular immunity.

These assays measure cell mediated immune

-γ released by T cells

in response to stimulation by mycobacterium TB

antigens. A review of current evidence on the

assays and Tuberculin Skin

Test suggests that both the Tuberculin Skin Test

assays have advantages and

limitations, and both tests appear to be useful at

et al. (2009) in their study

found that all eight active TB patients had

ve QFT results, and none of the 95 patients

with negative results had active any TB. The

sensitivity of the QFT reported is 100% (8 of 8)

city is 89.7% (87 of 97 cases) [6].

et al. (2008) compared the QFT test with

microscopic examination smear. They found that

the test is more useful than microscopic studies

of the smear. More ever it is also a faster and

method for the diagnosis of TB [7]. All the

ws that use of

old test for the diagnosis of

tuberculosis is superior to conventional methods

sis, above which the QuantiFERON-TB

in combination with tuberculin skin

est yields the maximum number of true positive

The levels of new markers, serum IFN-γ after

stimulation by foreign antigen by QFT test and

combining it with tuberculin skin test yields a




good amount of true positive cases of

tuberculosis even in latent cases.

References

1. Shah N, Aslan N. Adenosine deaminase

activity levels and its diagnostic value.

Pakistan medical journal, 1992; 251:

217-221.

2. Cellestis Limited. QuantiFERON

(in tube method) [package insert].

Available at http://

www.cellestis.com/IRM/Company/Show

Page.aspx-?CPID_1023.

2009-01-03.

3. Miguel G., et al. Clinical Utility of

Interferon Gamma Assay in the

Diagnosis of Tuberculosis. JABFM, 2007;

20(6): 540-547.

4. Connell TG, et al. Performance of a

Whole Blood Interferon Assay in

Detecting Latent Infection with M. TB in

Children. Thorax, 2006; 61: 616.

Table – 1: Results of various tests for diagnosing T

Various tests for diagnosing TB

Sputum examination

Tuberculin skin test

QuantiFERON-TB Gold

Tuberculin skin test + QuantiFERON

Sputum examination + Tuberculin

QuantiFERON-TB Gold + Sputum




good amount of true positive cases of

tuberculosis even in latent cases.

ah N, Aslan N. Adenosine deaminase

activity levels and its diagnostic value.

Pakistan medical journal, 1992; 251:

Cellestis Limited. QuantiFERON-TB Gold

(in tube method) [package insert].

Available at http://

www.cellestis.com/IRM/Company/Show

1023. Retrieved on

Miguel G., et al. Clinical Utility of

Interferon Gamma Assay in the

Diagnosis of Tuberculosis. JABFM, 2007;

Connell TG, et al. Performance of a

Whole Blood Interferon Assay in

Infection with M. TB in

Children. Thorax, 2006; 61: 616.

5. Nahid P, Pai M, Hopewell P. Advances in

the diagnosis and treatment of

tuberculosis. Proc Am Thorac Soc, 2006;

3(1): 103–10.

6. Inoue T, Nakamura T, Katsuma A. The

value of QuantiFERON®TB Gold in the

diagnosis of tuberculosis among dialysis

patients. Nephrology Dialysis

Transplantation, 2009; 24(7): 2252

2257.

7. Archip C, Diculencu D, Constantinescu,

Ignat A. The quantiferon testing and the

diagnosis of tuberculosis. Thematic

Poster Session: Interferon gam

release assay tests for diagnosing

tuberculosis infection and disease. Hall

6.2-36, Session 253, 12:50

Source of support: Nil

Conflict of interest: None declared.

Results of various tests for diagnosing TB.

Various tests for diagnosing TB Positive

95 (63.3%)

102 (68%)

105 (70%)

erculin skin test + QuantiFERON-TB Gold 145 (96.6%)

+ Tuberculin skin test 127 (84.6%)

old + Sputum examination 115 (76.6%)

ISSN: 2394-0026 (P)

ISSN: 2394-0034 (O)

Page 12

Nahid P, Pai M, Hopewell P. Advances in

the diagnosis and treatment of

tuberculosis. Proc Am Thorac Soc, 2006;

Inoue T, Nakamura T, Katsuma A. The

value of QuantiFERON®TB Gold in the

agnosis of tuberculosis among dialysis

patients. Nephrology Dialysis

Transplantation, 2009; 24(7): 2252-

Archip C, Diculencu D, Constantinescu,

Ignat A. The quantiferon testing and the

diagnosis of tuberculosis. Thematic

Poster Session: Interferon gamma

release assay tests for diagnosing

tuberculosis infection and disease. Hall

36, Session 253, 12:50-14:40 P2516.

None declared.

Negative

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48

45

05

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role of quantiferon-tb gold in diagnosis of tuberculosis

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