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Interferon-Gamma Release Assay for the Diagnosis of
Latent TB Infection – Analysis of Discordant Results,
when Compared to the Tuberculin Skin Test
Albert Nienhaus
1
*, Anja Schablon
1
, Roland Diel
2
1Institution for Statutory Accident Insurance and Prevention in the Health and Welfare Services, Department of Occupational Health Research, Hamburg, Germany,
2School of Public Health, Institute for Medical Sociology, Heinrich Heine University, Du
¨sseldorf, Germany
Abstract
Background:
With the Interferon-crelease assays (IGRA) a new method for the diagnosis of latent tuberculosis infections
(LTBI) is available. Due to the lack of a gold standard for the diagnosis of LTBI, the IGRA is compared to the Mantoux
Tuberculin Skin Test (TST), which yields discordant results in varying numbers. Therefore we assessed to which extent
discordant results can be explained by potential risk factors such as age, BCG vaccination and migration.
Methods and Findings:
In this pooled analysis, two German studies evaluating the Quantiferon-Gold In-Tube test (QFT) by
comparison with the TST (RT23 of SSI) were combined and logistic regressions for potential risk factors for TST+/QFT2as
well as THT2/QFT+discordance were calculated. The analysis comprises 1,033 participants. Discordant results were
observed in 15.4%, most of them being TST+/QFT2combinations. BCG vaccination or migration explained 85.1% of all
TST+/QFT2discordance. Age explained 49.1% of all TST2/QFT+discordance. Agreement between the two tests was 95.6%
in German-born persons younger than 40 years and not BCG-vaccinated.
Conclusions:
After adjustment for potential risk factors for positive or negative TST results, agreement of QFT and TST is
excellent with little potential that the TST is more likely to detect old infections than the QFT. In surveillance programs for
LTBI in high-income, low TB incidence countries like Germany the QFT is especially suited for persons with BCG vaccination
or migrants due to better specificity and in older persons due to its superior sensitivity.
Citation: Nienhaus A, Schablon A, Diel R (2008) Interferon-Gamma Release Assay for the Diagnosis of Latent TB Infection – Analysis of Discordant Results, when
Compared to the Tuberculin Skin Test. PLoS ONE 3(7): e2665. doi:10.1371/journal.pone.0002665
Editor: Adam J. Ratner, Columbia University, United States of America
Received October 30, 2007; Accepted June 11, 2008; Published July 16, 2008
Copyright: ß2008 Nienhaus et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: albert.nienhaus@bgw-online.de
Introduction
The burden of tuberculosis (TB) in healthcare workers (HCW)
remains high in low- and middle-income countries [1] as well as in
high-income countries [1–5]. Therefore an efficient strategy for
surveying exposed HCW or anyone else exposed to active TB
patients is needed. With declining incidence of active TB, the
purpose of these screening programs widened from early active TB
detection to latent TB infection (LTBI) detection and preventive
chemotherapy [6] below. For these screenings a specific test that
allows for the diagnosis of recent TB infections [7] likely to
progress into active TB is warranted.
For the diagnosis of latent tuberculosis infections (LTBI) the
recently developed Interferon-crelease assays (IGRA) are good
alternatives to the unspecific tuberculin skin test (TST) [8–11],
which has been in use for nearly 100 years [12]. Due to the lack of
a gold standard for the diagnosis of LTBI, IGRA is compared to
TST in evaluation studies. In a meta-analysis of studies in healthy
populations with varying risk for LTBI, discordant results between
IGRA and TST were found in 21% (ELISpot, T-SPOT.TB) or
29% (ELISA, QuantiFERON-Gold) of the participants [13].
Among discordant results, TST-positive and IGRA-negative
(TST+/IGRA2) combinations prevailed. This is easy to explain
because the IGRA uses few Mycobacteria tuberculosis-specific antigens
(ESAT-6 and CFP-10 of the region of difference, RD1) while the
tuberculin of the TST is a mix of about 200 non-specific antigens
that are shared with nontuberculous mycobacteria (NTM) as well
as with the strains developed from Mycobacterium bovis used for
bacilli Calmette-Gue´rin (BCG) vaccination [9,11]. Nevertheless
the higher rate of TST-positive results compared to those in IGRA
might also indicate that the TST is more likely to detect resolved
or old LTBI while the IGRA mainly detects current or recent
infections [7,14].
In a German contact-tracing study only those with a positive
IGRA progressed towards active TB, while none of those with a
positive TST but negative IGRA (TST+/IGRA2) developed TB
in the two years following close contact to an active TB case [15].
As progression to active TB is higher in those with recent
infections [16], this study supports the hypothesis that IGRA
might rather detect new infections.
In the literature little attention is given to TST-negative but
IGRA-positive results. Assuming the IGRA to be highly specific it
is likely that this combination indicates LTBI [17]. A waning of the
TST with age is discussed in literature [18]. Whether the IGRA is
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waning to the same extent with age as the TST is an open
question.
So far the extent to which BCG vaccination and NTB explain
TST+/IGRA2discordance is not analyzed and the reasons for
positive IGRA that are not verified in the TST (TST2/IGRA+)
are unknown [13,19]. The proportion of TST+/IGRA2results
that can not be explained by known risk factors might be explained
by a higher sensitivity of the TST for old infections. In
consequence the IGRA would be indicative of current or recent
infections. If this rationale is true, a relevant proportion of TST+/
IGRA2results that cannot be explained by BCG vaccination or
exposure to NTM should be observed in a population of a country
like Germany, which experienced the transition from high to low
TB incidence in the last decades. In a country with a decreasing
incidence of active TB, prevalence of LTBI in older age groups
should be higher than in the younger, less exposed age groups.
Again if the rationale is true, this effect should be more
pronounced in the TST than in the IGRA. We analyzed risk
factors for discordant results when the IGRA is compared to the
TST in order to verify the hypothesis that IGRA is sensitive to
recent or current infections while the TST is sensitive to both old
and recent infections.
Methods
For this analysis we combined two study populations consisting
of 1,040 healthy persons. Due to indeterminate results in the
IGRA 7 persons had to be excluded from the analysis. Out of the
remaining 1,033 persons (table 1), 601 were part of the general
population examined in the scope of contact tracing [20] and 432
were healthcare workers routinely screened for TB [21]. Both
studies were carried out in the scope of German legislation
concerning TB surveillance. They both used the same study
protocol and were carried out by the same principal investigators
(R.D., A.N.). Therefore they were suitable for a combined analysis.
Information on BCG vaccination, country of birth, age, gender,
and previous tests was collected in standardized interviews. BCG
vaccination was verified by scars or vaccination records. In
Germany, up until 1982 all newborns were BCG vaccinates.
Thereafter vaccination was recommended only for newborns with
high TB risk. No general recommendation on revaccination was
issued [22]. Since 1998 BCG vaccination has no longer been
recommended in Germany [23].
In both study populations the TST was performed using 2-TU
of PPD RT23 (Statens Serum Institute, Copenhagen, Denmark).
The test was administered to the volar side of the forearm of the
participants and read 72 to 96 hours after the application. The
transverse diameter of the induration was measured. The
observers were blinded to the IGRA results.
Before TST application, the standardized interview was
performed and blood for the IGRA was drawn. For the IGRA,
a variation of the QuantiFERON-TB Gold assay (Cellestis
Limited, Carnegie, Australia), the QuantiFERON-TB Gold In-
Tube test (QFT), was used. This whole-blood assay uses
overlapping peptides corresponding to ESAT-6, CFP-10, and a
portion of tuberculosis antigen TB7.7 (Rv2654). Stimulation of the
antigenic mixture occurs within the tube used to collect the blood.
Tubes were incubated at 37uC overnight before centrifugation,
and INF-crelease was measured by ELISA following the protocol
of the manufacturer. All the assays performed met the manufac-
turer’s quality-control standards. The test was considered positive
when INF-cwas $0.35 IU after correction for the negative
control. Observers were blinded to the results of the TST.
Due to the lack of a gold standard, sensitivity and specificity
were not calculated. The Pearson Chi-square test was used to
compare frequencies of test results among different groups of
participants. For ordered risks, the proportions of positive test
results were compared using the chi-square test of trend. P,0.05
was considered to be statistically significant. Agreement and
Kappa values were calculated for the two tests with varying cut-
offs for a positive TST (.5 mm, .= 10 mm, .= 15 mm). Odds
ratios (OR) for discordant test results depending on different
putative predictive variables were calculated using logistic
regression. Model building was performed backwards using the
chance criteria for variable selection [24]. The expected number
of discordant results was calculated by the product of the
proportion of discordant results in the unexposed strata and the
number of observations in the exposed strata. The difference
between observed and expected discordance was considered as the
proportion of the discordant results explained by the analyzed risk
factor. The expected discordance was used to calculate a corrected
agreement between TST and QFT.
Data analysis was performed using SPSS, Version 14 (SPSS
Inc., Chicago, Illinois). The study protocols of both studies
combined for this paper were approved by the ethics committee of
the Hamburg Medical Council. All persons gave their written
informed consent prior to their inclusion in the studies.
Results
Table 1 describes the study population. 30.1% had an
induration diameter in the TST of .5 mm and 18.5% had a
diameter of 10 mm or more. The QFT was positive in 9.7%. For 5
participants born in Germany and not BCG-vaccinated, the
induration diameter in the TST was $15 mm. All of these had a
positive QFT (table 2). Kappa was influenced by BCG vaccination
and birthplace. Kappa was lowest when a cut-off point .5 mm for
TST was used and the participants were foreign-born and BCG-
vaccinated (0.04). Kappa was highest in German-born, not BCG-
Table 1. Description of the study population.
Mean Standard deviation
Age* N %
1–29 years 490 47.4
30–39 years 226 21.9
40–49 years 246 23.8
50–68 years 71 6.9
Female 638 61.8
Foreign-born** 262 25.4
Previous BCG vaccination 448 43.4
Previous TST 312 30.2
HCW 432 41.8
TST .5 mm 311 30.1
TST $10 mm 191 18.5
TST $15 mm 69 6.7
QFT-positive 100 9.7
Total 1,033 100.0
*
Age: mean 31.6, standard deviation 12.7.
**
All but 6 emigrants were born in countries with a TB incidence (.20/100.000)
well above that of Germany (,6/100.000), mainly Turkey, other Eastern
European countries, or Africa.
doi:10.1371/journal.pone.0002665.t001
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vaccinated participants when $10 mm was used as cut-off point
for the TST. Agreement between QFT and TST was best with a
TST diameter of at least 15 mm as cut-off point (89.8%). But
Kappa was best with at least 10 mm as cut-off point for the TST
in the whole sample (0.37) and in the different subgroups (table 2).
Therefore further analysis was carried out with 10 mm as cut-off
point for the TST. Foreign birth was a risk factor for LTBI in both
TST and QFT (table 3). The OR for BCG vaccination was 5.1
(95%CI 3.51–7.33) in the TST while the QFT was not affected by
vaccination (OR 1.1; 95%CI 0.71–1.68). Prevalence of LTBI
increased with age with the QFT (test for trend p,0.005), but not
with the TST (p = 0.67).
Using a diameter of 10 mm as cut-off point for the TST yielded
159 (15.4%) discordant test results (table 2); most of them had the
combination TST+/QFT2(125 out of 159 or 78.6%). A previous
BCG vaccination and being foreign born increased the probability
of TST+/QFT2discordance (table 4) with statistically significant
OR of 8.6 and 4.1, respectively. The highest proportion of TST+/
QFT2was seen in foreign-born participants with a BCG
vaccination (42.5% of all participants in these strata). The
combination of a BCG vaccination and being foreign-born yielded
an OR for TST+/QFT2discordance of 40.9 (95%CI 18.6–89.4)
which was higher than the sum of the OR for birthplace (OR 5.4,
95%CI 2.2–13.5) and for BCG vaccination (OR 10.4, 95%CI 4.9–
22.3). In the subgroup which was BCG vaccinated and foreign-
born, 2.3 TST+/QFT2results were expected. Therefore 95.7%
(51.7 out of 54) of TST+/QFT2results in this subgroup are
explained by BCG vaccination and being foreign-born. If BCG
vaccination and being foreign-born did not influence the probability
of TST+/QFT2discordance, in the whole study group 18.6 of
TST+/QFT2results would have been expected compared to 125
that were observed. This makes it likely that 85.1% (106.4 out of
125) of the TST+/QFT2observations do not indicate LTBI. If
BCG vaccination is considered separately, 85.5 (89.8 out of 105) of
all TST+/QFT2results are explained by BCG vaccination.
TST2/QFT+discordance was observed in 34 (3.3%) partic-
ipants (table 2). Out of 100 cases positive in the QFT, 34 (34.0%)
were negative in the TST. The probability of these discordant
results increased with age (test for trend p,0.0005; table 5). It was
not influenced by gender, working in the healthcare system, BCG
vaccination, being foreign-born, and previous TST. For partici-
pants aged between 50 and 68 years, the odds ratio for a TST2/
QFT+discordance was 5.0 (95%CI 1.9–13.2) compared to those
younger than 40 years. In young people a positive QFT which is
not confirmed by TST is rare (1.7%, table 5). If the probability of
TST2/QFT+discordance was not influenced by age, 17.3 of
these results would have been expected compared to the 34
observed. This makes it likely that 49.1% (16.7 out of 34) of the
TST2/QFT+observations can be explained by waning sensitivity
of the TST with increasing age.
Table 2. Positive results of the TST with different cut-off points confirmed by QFT for various subgroups and kappa-value.
TST .5 mm/QFT+TST $10 mm/QFT+TST $15 mm/QFT+
BCG n (TST)* [QFT]** kappa n (TST)* [QFT]** kappa n (TST)* [QFT]** kappa
No (n = 585) 38 (46.3) [69.1] 0.50 31 (60.8) [56.4] 0.54 11 (84.6) [20.0] 0.30
Yes (n = 448) 37 (16.2) [82.2] 0.12 35 (25.0) [77.8] 0.28 21 (37.5) [53.3] 0.34
Born
Germany 40 (23.7) [70.2] 0.27 34 (36.6) [59.6] 0.40 14 (53.8) [24.6] 0.30
foreign born 35 (24.6) [81.4] 0.17 32 (32.7) [74.4] 0.29 18 (41.9) [41.9] 0.30
BCG vaccination and born
no BCG, born in Germany 23 (50.0) [67.6] 0.54 18 (69.2) [52.9] 0.57 5 (100.0)[14.7] 0.24
no BCG, foreign born 15 (41.7) [71.4] 0.41 13 (52.0) [61.9] 0.48 6 (75.0) [28.6] 0.36
BCG, born in Germany 17 (13.8) [73.9] 0.13 16 (23.9) [69.6] 0.28 9 (42.9) [39.1] 0.37
BCG, foreign born 20 (18.9) [90.9] 0.04 19 (26.0) [86.4] 0.18 12 (34.3) [54.5] 0.27
All 75 (24.1) [75.0] 0.26 66 (34.6) [66.0] 0.37 32 (46.4) [32.0] 0.33
Agreement: TST .5 mm: 74.8% TST $10 mm: 84.2% TST $15 mm: 89.8%.
*
(TST) = percentage of all TST+confirmed by QFT.
**
[QFT] = percentage off all QFT+confirmed by TST.
doi:10.1371/journal.pone.0002665.t002
Table 3. Adjusted Odds Ratios for TST and QFT depending on
age, gender, migration, or BCG vaccination.
Age TST .= 10 mm QFT positive
N (row%) OR 95%CI N (row%) OR 95%CI
1–29 years 91 (18.6) 1 – 31 (6.3) 1 –
30–39 years 39 (17.3) 1.3 0,82–2.03 18 (8.0) 1.4 0.77–2.62
40–49 years 47 (19.1) 1.4 0.93–2.22 37 (15.0) 2.9 1.78–5.01
50–68 years 14 (19.7) 1.6 0.82–3.28 14 (19.7) 4.2 2.06–8.59
p for trend 0.67 ,0.0005
Gender
Female 104 (16.3) 1 – 57 (8.9) 1 –
Male 87 (22.0) 1.4 0.99–1.99 43 (10.9) 1.3 0.85–2.02
p-value 0.021 0.303
Birthplace
Germany 93 (12.1) 1 – 57 (7.4) 1 –
Other 98 (37.4) 4.6 3.21–6.53 43 (16.3) 2.6 1.71–4.09
p-value ,0.0005 ,0.0005
BCG
No 51 (8.7) 1 – 55 (9.4) 1 –
Yes 140 (31.3) 5.1 3.51–7.33 45 (10.0) 1.1 0.71–1.68
p-value ,0.0005 0.729
doi:10.1371/journal.pone.0002665.t003
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35.9 (3.5%) discordant results (18.6 TST+/QFT2and 17.3
TST2/QFT+) remain unexplained by risk factors which yields a
corrected agreement for the two test of 96.5%. This agreement
corresponds with the agreement of the two tests in young people
(under 40 years), born in Germany and not BCG vaccinated
(table 6).
Discussion
With our data we were able to analyze migration, BCG
vaccination and age as risk factors for 159 discordant results in
contacts of TB cases tested with TST and QFT simultaneously.
The proportion of discordant results we observed in our pooled
analysis was somewhat lower (15% instead of 24%) than that
described in a recent meta-analysis [13]. This might be explained
by a higher proportion of risk factors for discordance in the studies
that gave rise to this meta-analysis, i.e. the proportion of
participants with BCG vaccination was 59% in the meta-analysis
and 43% in our pooled population. As in this meta-analysis, the
combination of TST+/QFT2results dominated the discordant
results. Most of these discordant results can be explained by BCG
vaccination or birth in a foreign country, which might be an
indicator for NTM infection [25]. Being foreign-born and BCG-
vaccinated explained 95.7% TST+/QFT2results that occurred
in this subgroup. This might be explained by repeated BCG-
vaccination in juveniles or by older age at which vaccination is
performed. Both increase the probability of a positive TST [27].
In Germany BCG vaccination was performed in newborns only
while in other countries (e.g. Poland, Czech Republic, Slovakia,
Turkey) BCG vaccination is repeated [23,26]. In a meta-analysis
[27] it was estimated that depending on the time spent between
vaccination and testing (#10 years or .10 years) 21% to 41% of
those with a BCG vaccination after the first birthday had a positive
TST (diameter 10+mm) explained by BCG. These estimates were
based on comparisons of the TST in unvaccinated and vaccinated
populations. Based on our comparison of the TST with the QFT
and using the same approach, 85.5% of all TST+/QFT2results
in vaccinated participants are most likely attributable to the BCG
vaccination.
Table 4. BCG vaccination or foreign born as putative cause for TST+/QFT2Discordance.
TST+/QFT2p-value Odds Ratio* 95%CI
Yes No
BCG O (%) [E] N (%)
No 20 (3.4) [20] 565 (96.6) ,0.0005 1 –
Yes 105 (23.4)[15.2] 343 (76.6) 8.6 5.3–14.2
Born
Germany 59 (7.7) [59] 712 (92.3) ,0,0005 1 –
foreign born 66 (25.2) [20.2] 196 (74.8) 4.1 2.8–5.8
BCG vaccination and born
no BCG, born in Germany 8 (1.8) [8] 442 (98.2) ,0.0005 1 –
no BCG, foreign born 12 (8.9) [2.4] 123 (91.1) 5.4 2.2–13.5
BCG, born in Germany 51 (15.9) [5.8] 270 (84.1) 10.4 4.9–22.3
BCG, foreign born 54 (42.5) [2.3] 73 (57.5) 40.9 18.7–89.4
Total 125 (12.1)[18.6] 908 (87.9)
*
Gender, age, previous TST, and source population (HCW or contact tracing in general population) were not associated with TST+/QFT2discordance; TST+is defined as
TST .= 10 mm.
O = observed, E = expected.
doi:10.1371/journal.pone.0002665.t004
Table 5. Age as putative cause for TST2/QFT+Discordance.
TST2/QFT+p-value
Odds
Ratio* 95%CI
yes no
Age O (%) [E] N (%)
1–39 years 12 (1.7) [12] 704 (98.3) ,0.0005 1 -
40–49 years 14 (5.7) [4.2] 232 (94.3) 3.1 1.3–6.8
50–68 years 8 (11.3) [1.2] 63 (88.7) 5.0 1.9–13.2
Total 34 (3.3) [17.3] 999 (96.7)
Gender, being foreign born, previous TST, BCG vaccination and source
population were not associated with TST2/QFT+discordance; TST+is defined
as TST $10 mm.
O = observed, E = expected.
doi:10.1371/journal.pone.0002665.t005
Table 6. Results of the QFT and the TST with a diameter of
10 mm or more in German born persons younger than 40
years who were not BCG vaccinated.
TST .=10 mm All
positive negative
QFT N (%) N (%) N (%)
Positive 7 (3.9) 5 (2.8) 12 (6.6)
Negative 3 (1.7) 166 (91.7) 169 (93.4)
Total 10 (5.5) 171 (94.5) 181 (100.0)
TST .5 mm: Agreement 90.0%, Kappa 0.42, p,0.0005.
TST .= 10 mm: Agreement 95.6%, Kappa 0.61, p,0.0005.
TST .= 15 mm: Agreement 94.5%, Kappa 0.27, p,0.0005.
doi:10.1371/journal.pone.0002665.t006
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As a limitation of our study, we had no information on the age
at vaccination, revaccination or exposure to NTM. Therefore we
were not able to analyze the influence of these factors on TST. But
we believe it to be likely that the observed interaction between
being foreign-born and BCG vaccination might be explained by
these factors.
Birthplace was a risk factor for a positive TST and QFT as well as
for TST+/QFT2discordance in our data. Similar results were
observed in US Navy recruits [14]. For the TST no positive
correlation with age is seen in our data. Therefore it is unlikely that
these TST+/QFT2results are explained by old infections due to
the higher exposure in the countries where the immigrants were
born (Turkey, East-Europe, Africa). In the Navy study it was shown
that NTM infections (M. avium) were 5 times more likely in recruits
born outside the US [14]. The effect of BCG vaccination could not
be analyzed in the Navy study because none of the US-born recruits
were vaccinated and therefore vaccination and being born in a
country with high TB incidence was strongly correlated. Our data
allow for combining birthplace and BCG vaccination. This allows
us to analyze the effects of migration and BCG vaccination
independently and to analyze the combined effect of migration and
BCG vaccination. BCG vaccination might be associated with TB
incidence in the sense that countries with high incidence continue
vaccination or revaccination [23]. Therefore TST+/QFT2results
might be explained by resolved or old TB infections that are
detected by TST and not by QFT [28]. This hypothesis is not
supported by our data. BCG vaccination is a strong predictor for
TST+/QFT2results not only in foreign-born but also in German-
born participants and the assumed association between age and
resolved or old LTBI is found with the QFT but not with the TST.
Age is a strong predictor for a positive QFT that is not
confirmed by the TST. In young people TST2/QFT+results are
rare. In 856 Navy recruits (mean age 20 years) no TST2/QFT+
combination was found [14]. We observed 34 of these combina-
tions that mainly occurred in older participants. Because age is
also a predictor for a LTBI it is likely that these discordant results
are due to a higher waning of the T-cell mediated immune
response to TST than to QFT. Our observation is indirectly
confirmed by a Japanese study in which the association between
age and LTBI was shown for IGRA but not for TST [29]. So far
the immunologic interpretation of this observation is not clear.
Either the QFT is positive because it is more sensitive to an old TB
infection or the skin loses its capability to react and therefore both
former and recent infections do not result in a positive TST with
the same likelihood than in younger persons. Comparison of TST
sensitivity in patients with active tuberculosis showed that TST
sensitivity gets weaker with increasing age of the patient [30]. Thus
it is likely that with increasing age the TST not only does not react
to former infections but also is less sensitive to recent infections.
This might either be due to difficulties to apply the tuberculin
correctly into the aging skin or by decreasing mobility of the T
lymphocytes that have to migrate to the forearm were the test is
applied. The waning of the specific interferon-gamma response
after years of tuberculosis infection was described in a Japanese
population based on estimates of the expected prevalence of LTBI
[18]. Our data suggest that waning is higher with the TST than
with the QFT. The hypothesis that TST might be more sensitive
to old infections while the IGRA mainly indicates recent infections
is not supported by our data.
So far two prospective studies investigating the progression to
active TB have been published [15,31]. In the German study [15],
progression to active TB was observed in those with a positive
QFT only while in the Gambian study active TB was observed
during the follow-up in 2 contacts, negative in the ELISPOT but
positive in the TST at baseline [31]. Therefore so far the risk of
progression to active TB can not be ruled out in TST+/QFT2
contacts. However, based on our data, it is ikely that the
proportion of those with a TST+/QFT2result that are at
potential risk to progress towards active TB is rather small.
The proportion of discordant results that can not be explained
by BCG vaccination, being foreign-born or by age is rather small
(4.4%), indicating little potential for false-negative or false-positive
QFT results. These findings support the hypothesis that the QFT
is the test of choice in populations with a high BCG vaccination
rate or with an increased chance of exposure to non-tuberculous
mycobacteria (NTM), or in people older than 40 years. In young
persons not vaccinated and unlikely to be exposed to NTM, the
TST and the QFT are of comparable quality and the agreement
between the two tests is above 95%. In older populations the TST
is less sensitive than the QFT and in the German population with
a migration background and/or a BCG vaccination the TST is far
less specific than the QFT. In Germany, HCW with regular
contact to TB patients are surveyed and in the general population
contacts to TB patients are traced [32]. Using IGRA instead of
TST would save HCW or other TB contacts from unnecessary
follow-up [33]. Following our data, about 40% of migrants with
BCG vaccination would profit from replacing TST by IGRA.
In conclusion, according to our data, it is not likely that the TST
is more sensitive to old LTBI than the IGRA. Therefore we would
like to suggest the use of an IGRA as the first test after exposure to
a patient with active TB and in periodic screening for LTBI
among exposed HCW, especially for those of foreign birth.
Acknowledgments
The authors would like to thank the staff of the office of TB control at the
Public Health Department Hamburg-Central and the occupational
physicians Ms G. Beckmann, Ms S. Nausester, and Ms. R. Sternfeldt for
the medical examinations and data collection.
Author Contributions
Analyzed the data: AN SA RD. Wrote the paper: AN RD.
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