COMPARISON OF PPD AND QUANTIFERON IN DETERMINING

LATENT TUBERCULOSIS IN PATIENTS WHO ARE DIRECTED TO

TNF ANTAGONISTS

T.ÇAĞATAY¹, M.AYDIN¹ , Z. GÜLBARAN¹, R. YILDIZ¹, L. PUR¹ A.GÜL¹, M. İNANÇ ², S. KAMALI², K.KÖKSALAN³,

Z.KILIÇASLAN²

İstanbul University, Faculty of Medicine Department of Pulmoner Medicine1İstanbul University, Faculty of Medicine Department of Rheumatology Medicine2İstanbul University Molecular TB Epidemiology Laboratory 3

Introduction And AimIntroduction And Aim

TNF antagonist drugs are used in rheumatologic and other inflammatory diseases as the ultimate choice

These drugs increase the risk of infectious diseases especially tuberculosis(TB).

Introduction And AimIntroduction And Aim It is crucial to determine latent

tuberculosis infection (LTI) before the onset of these drugs.

The decision of prophylaxis has to be made.

Nowadays, PPD is the cheapest and the most easy to perform test to diagnose the latent TB infection.

Introduction And AimIntroduction And Aim

However, false negative PPD responses decreases the reliability of the test as those patients who are going to use TNF antagonist drugs are in an immunsuppressive state .

Interferon-gamma (IFN-γ) release assays (IGRA’s) have started to be used in recent years for providing more information in the diagnosis of latent infection especially in those patients with an immunocompromised condition

AimAim

This study is;This study is; A pre-statement for the planned research

for evaluation of PPD and Quantiferon-TB-Gold test which is an IGRA test to diagnose the latent TB infection in the rheumatismal disease group.

Material & MethodMaterial & Method

Patients are examined for (LTI) prior to TNF antagonist treatment. Before the onset of TNF antagonist drugs who were referred to pulmonary outpatient clinic

70 patients with rheumatoid arthritis (RA) and ankylosing spondylitis(AS) were taken into this study.

Material & MethodMaterial & Method

Active TB firstly is exluded by clinic and Active TB firstly is exluded by clinic and radiologic methods.radiologic methods.

PPD has been performed by standart PPD has been performed by standart method after taking blood sample for method after taking blood sample for quantiferon-TB goldquantiferon-TB gold. .

Statistical EvaluationStatistical Evaluation

““Kappa Test’’Kappa Test’’ is used for the adjustement of is used for the adjustement of the two tests and the two tests and

‘’‘’Logistic Regression’’Logistic Regression’’ analysis is used to analysis is used to show the relation of these two tests by show the relation of these two tests by demographic and clinic parameters.demographic and clinic parameters.

ResultsResults

FEMALE

53%

MALE

47%

FEMALE

MALE AS =31RA =39

ResultsResults

37 48

10 11 10 9

MEAN AGE MEAN AGE OFDISEASE

CIGARETTE PACK OFYEAR

AS

RA

Characteristic Of PPD PositiveCharacteristic Of PPD Positive (n=37) (n=37)

90%

47%

64%43%

67%

41%

TB CONTACT(+) TB CONTACT (-)MALE FEMALESMOKER NON SMOKER

Characteristic Of PPD NegativeCharacteristic Of PPD Negative (n=33) (n=33)

10%53%

36%

57%

33%

59%

TB CONTACT (+) TB CONTACT (-) MALE FEMALESMOKER NON- SMOKER

ResultsResults

PPD Results; There was no difference in PPD positive and

negative groups according to their age and gender.

Positive PPD results were significantly higher in AS patients compared to those with RA (p<0.01).

Positive PPD results of 90% was found in patients with a TB contact (p<0.014).

There was no correlation between the positive PPD results with a sequel in chest X-ray and a BCG scar.

Quantiferon Results

16%

53%

32%

QUANTI FERON POZİ Tİ F QUANTI FERON NEGATİ F

QUANTI FERON I NTERMEDI ATE

16

6

17

20

47

QUANTIFERONPOSITIF

QUANTIFERONNEGATIF

QUANTIFERONINTERMEDIATE

PPD- Quantiferon Results

PPD (+)

PPD (-)

11%

46% 43%

QUANTİ FERON POZİ Tİ F

QUANTİ FERON NEGATİ F

QUANTİ FERON I NDETERMI NATE

PPD (-) -Quantiferon Results

Results of PPD (+) - QuantiferonResults of PPD (+) - Quantiferon

21%

18%

61%

QUANTİ FERON POSI TI F

QUANTİ FERON NEGATİ F

QUANTİ FERON I NDETERMI NATE

ResultsResults

Quntiferon Results;Quntiferon Results; There was no difference between a positive

Quantiferon test with age and gender There was no difference between AS and RA There was negative Quantiferon results in 92 % of

patients with no TB contact history,positive Quantiferon results in 6 of 9 patients with TB contact.

Quantiferon pozitifliği ile PA grafide sekel ve BCG skarı yönünden fark bulunmadı

There was no relation between positive Quantiferon results with a sequel lesion in chest X-ray and BCG scar.

Disease duration was found to be higher in patients with negative Quantiferon tests (p=0.059).

BCG-PPD and Quantiferon Relation

32

5

24

9

29

8

16

611

PPD POSITIF PPD NEGATIF QUANTİFERON NEGATİF QUANTİFERON POSITIF QUANTİFERON

INDETERMINATE

BCG POZİTİF BCG NEGATİF

When Quantiferon test is considered the When Quantiferon test is considered the gold standart and 5 mm PPD gold standart and 5 mm PPD

Induration is accepted as a positive test ; Induration is accepted as a positive test ; sensitivity of the PPD was found to be 72% sensitivity of the PPD was found to be 72% and specifity as 56% and a weak and specifity as 56% and a weak correlation was found between the two correlation was found between the two methods methods (kappa=0,27).(kappa=0,27).

If the PPD induration limit would be If the PPD induration limit would be accepted as 10 mm or higher these ratios accepted as 10 mm or higher these ratios would then be would then be 63% and 70%63% and 70% respectively. respectively.

ResultsResults

11 patients had BCG scars with indeterminate Quantiferon test results.

For the remainder of 48 patients with BCG scars , when 5 mm or more of an induration was accepted as a positive PPD test then the reliability of the test was lowered to 50%.

ResultsResults

ConclusionConclusion

It is indicated that Quantiferon TB- Gold Test is more sensitive to identify the latent TB infection in immunesupressive patients

It is not affected by the BCG and atypical mycobacterial infections.

For the diagnosis of latent TB infection in immunesuppressive patients who are going to take TNF antagonist drugs PPD results and Quantiferon results showed a weak correlation.

If the Quantiferon results are accepted as

the correct ones then there seems to be an important rate of trouble with our decisions of prophylaxis on the basis of PPD tests.

ConclusionConclusion

However as there are 15% of indeterminate results in all of our patients with BCG scars, this shows also the limitation of the Quantiferon Test.

ConclusionConclusion

ConclusionConclusion

There is a need for more number of studies with lot of patients to be done but these preliminary results show the need of IGRA Test performances in diagnosing the latent TB infection in the group of patients with Rheumatismal diseases.