[Downloadedfreefromhttp://www.sjkdt.orgonMonday,January09,2012,IP:140.234.255.

9]||ClickheretodownloadfreeAndroidapplicationforthisjournal

Saudi J Kidney Dis Transpl 2012;23(1):8-14

2012 Saudi Center for Organ Transplantation

Saudi Journal
of Kidney Diseases
and Transplantation

Review Article
Screening for Latent Tuberculosis in Refugees with Renal Failure
Ghanshyam Palamaner Subash Shantha1, Anita Ashok Kumar1, Viraj Bhise1, Kamesh
Sivagnanam1, Kuyilan Karai Subramanian1, Pushkar Kanade2, Rohit Khanna3
1

Department of General Medicine, Sri Ramachandra University, Chennai, India

Department of Internal MedicineSt. Vincents Charity Medical Center, Cleveland, Ohio, USA,
3
Department of Ophthalmology, L V Prasad Eye Institute, Hyderabad, India

ABSTRACT. Refugee camps are prone for easy spread of infections of various kinds and tuberculosis (TB) is no exception. Refugees with renal failure are often a vulnerable group because
they are immunocompromised due to reasons such as poor nutrition, overcrowding and immune
suppression due to renal failure. Latent pulmonary TB is a particular problem in this patient
population as it is not easily diagnosed and has immense potential for spread. Tuberculin Skin
Test (TST), although easy to perform and is cost-effective, suffers from the limitations of giving
false positive results due to cross-reaction with the vaccination. Chest radiography though cheap,
has not yet been validated in refugee populations for this purpose. Sputum analysis shows
promise due to ease of performing but again has not been validated in refugees. Newer assays
such as IF- show great promise but needs large scale studies for validation and cheaper assays
need to be developed for use in resource poor refugee setting. In short, an ideal tool for effective
screening of latent TB in refugees with renal failure is lacking. Future studies are required to
identify this ideal tool.
Introduction
Infections of various kinds are very common
in refugee camps. Diarrheal diseases, malaria,
tuberculosis (TB), influenza, Lymes disease,
brucellosis, leptospirosis, etc., are common infections that affect refugee populations. This is
especially true among refugees with renal faiCorrespondence to;
Dr. Ghanshyam Palamaner Subash Shantha,
Assistant Professor,
Department of General Medicine,
Sri Ramachandra University,
Ramachandra Nagar, Chennai, India
E-mail: gpalaman@jhsph.edu

lure. The reasons that predispose refugees to

infections are overcrowding, poor sanitation
and waste disposal, unprotected food and water,
and unhygienic living conditions which are inevitable features of refugee camps. Also, renal
failure causes immunosuppression in these patients. Interestingly, many of these infections
are hidden or latent and are not clinically apparent. Such latent infections not only cause
morbidity to the affected individuals but also
to the people who live near them.
TB is a common infection that affects refugees. Owing to overcrowding in refugee
camps, TB spreads easily via droplet infections. It is interesting to note that TB is latent
in many of the refugees. The World Health

[Downloadedfreefromhttp://www.sjkdt.orgonMonday,January09,2012,IP:140.234.255.9]||ClickheretodownloadfreeAndroidapplicationforthisjournal

Latent tuberculosis in refugees with renal failure

Organization has estimated the global prevalence of latent TB infection in 1997 to be 35%
for Africa, 44% for Southeast Asia and 15%
for Europe.1 In countries like the United States
(US), Norway, and United Kingdom where a
sizeable refugee immigration happens, the
rates of TB in the native population is usually
low but the immigrant population has a high
prevalence, which poses a significant public
health problem of potential spread in the
native population. It is reported that in the US,
the rate of active tubercular infection is nearly
9.7 times higher in foreign-born persons than
among US-born persons.2 The incidence of TB
in Norway is generally low (6.3/100,000 population in 2006), but high among immigrants
from countries where TB is endemic.3 The
enormous pool of persons with latent TB
challenges the control of this disease in low
endemic countries. National guidelines for prevention and control of TB in most low endemic countries therefore, recommend targeted
tuberculin testing and treatment of latent infection.4 Interestingly, majority of these infections are believed to be reactivations of tubercular infection that were acquired before
immigration which highlights the inadequacy
in the current preventive strategies.2 There are
continuing efforts to devise effective screening
tools to diagnose latent TB among refugees as
this can be a significant public health problem.
Traditionally, Tuberculin Skin Test (TST) and
chest radiography have been used to screen
refugees. TST is slowly being replaced by
newer interferon-gamma (IFN-) release assays
(IGRAs) which have the potential to address
many of the shortcomings of TST in refugee
populations such as eliminating false positive
results caused by Bacillus Calmette-Guerin
(BCG) vaccination, distinguishing between tuberculous and non-tuberculous mycobacterial
infection (NTB), and providing test results
after a single patient visit.5-7 The objective of
this review is to enumerate the various techniques that are currently available to screen for
latent TB in refugees, compare and contrast
each of these techniques with the other in
terms of cost, validity, and reliability and finally reach an optimal conclusion as to what

will be the best among the available techniques.

TST: Advantages and Disadvantages
Traditionally, TST has been used as a screening tool for latent TB. The advantages of this
test are that it is cheap, easy to perform, safe,
causes minimal discomfort to the patient and is
easily available. These characteristics make it
the first choice in a setting where there are
hundreds of refugees and many have to be
screened. In many countries, the national guidelines recommend targeted TST in refugees and
to treat those who have a positive TST test.4
However, TST has significant limitations as
has been already enumerated. False positive
results due to prior BCG vaccination, other
tubercular infections and false negativity in
immunocompromised people and those with
miliary TB are the common short comings of
TST.
Chest radiography in Screening
An interesting study was conducted where
health-care workers who had a positive TST as
part of their pre-employment evaluation were
retested with chest radiography to look for the
agreement between the two tests. A total of
2586 asymptomatic individuals with positive
TST results were evaluated to determine the
frequency of detection of evidence of active
TB or latent TB infection (LTBI) and the spectrum of imaging findings. The study concluded
that universal chest radiography in a large preemployment TB screening program was of low
yield in the detection of active TB or increased
LTBI reactivation risk, and it provided no
assistance in deciding which individuals to
prioritize for LTBI treatment.8 However, a
similar study that has evaluated the validity of
chest radiography as a screening tool in refugee populations is not available. The results
may or may not be comparable with the study
that has been described above for reasons that
refugees may not be as healthy as health-care
workers due to what is commonly called as
healthy worker effect. So, the effectiveness
of chest radiography as an effective screening

[Downloadedfreefromhttp://www.sjkdt.orgonMonday,January09,2012,IP:140.234.255.9]||ClickheretodownloadfreeAndroidapplicationforthisjournal

10

Shantha GP, Kumar AA, Bhise V, et al

tool in refugee population is still not clear.

Sputum Analysis as a Screening Tool for
Latent TB
A prospective multicenter cohort study comprising 1,171 individuals who were seropositive for human immunodeficiency virus (HIV)
but did not have AIDS at the time of enrollment and 182 HIV-seronegative controls,
were studied by means of routine inducedsputum analysis in an attempt to detect occult
TB.9 The study concluded that routine induced-sputum analysis is not an effective
strategy for screening HIV-infected asymptomatic subjects for TB before the onset of clinically recognizable disease activity. A similar
study assessing the validity of sputum analysis
as a screening tool for latent TB in refugees is
not available. Also, it is not possible to extrapolate the results we got from the HIV infected
patients to healthy seronegative refugee populations. Thus, sputum analysis also lacks supporting data to validate its usefulness as a
screening tool for latent TB in refugees.

clinic in Italy, 44% and 15% were positive

with TST (10 mm) and QFT, respectively.13
How is QFT done?
For the QuantiFERONTB Gold in-tubetest, 1 mL of venous blood is drawn into one
tube pre-coated with synthetic peptide antigens
and one tube without antigens (negative
control sample) and transported the same day
to the analysis center. Samples were incubated,
processed and stored in accordance with the
manufacturers instructions following which
the harvested plasma is subjected to EnzymeLinked Immunosorbent Assay (ELISA) analysis, including IFN- standard for quantification. The quality of all laboratory analyses
and calculation of the results will have to be
controlled by using QFT analysis software. A
sample is considered positive if it exceeds the
standard cut-off value at 0.35 IU IFN-/ mL.
All positive results are then confirmed by reanalysis of the same plasma sample before
reported as positive. If it is not possible to
reproduce a positive result, the QFT result will
be reported as non-conclusive.14

Newer Assays
Comparison between TST and QFT
In vitro assays based on cellular production
of IFN- in response to the Mycobacterium
tuberculosis-specific antigens ESAT-6 and
CFP10 have recently been developed. These
protein antigens are present in all species of
the M. tuberculosis-complex (including Mycobacterium bovis), but absent in all vaccine
strains of M. bovis-BCG and most non-tuberculosis mycobacteria, except Mycobacterium
marinum, Mycobacterium zulgai, and Mycobacterium kansasii. These tests can therefore
diagnose infection with M. tuberculosis with a
higher specificity.7,10 One of the IFN- release
assays, QuantiFERONTB Gold (QFT), offers
logistic advantages and may be suitable for
routine screening. The assay has been tested in
numerous contact investigations, among patients with TB disease and exposed health-care
workers, but data are limited for immigrant
screening.11,12 Among 100 immigrants from
high prevalence countries attending an outpatient

A study from Norway 14 where 1000 asylum

seekers who were more than 18 years of age
were tested with both TST and QFT. IFN-
cut-off value was 0.35 U/mL and a skin in
duration of > 6 mm was considered a positive
TST. Fifty percent tested positive on TST and
29% tested positive with QFT. Among the
TST-positive participants, 50% were QFT
negative, whereas 7% of the TST-negative
participants were QFT positive. There was a
significant association between increase in size
of TST result and the likelihood of being QFT
positive. Agreement between the tests was 71
79% depending on the chosen TST cut-off and
it was higher for non-vaccinated individuals.
The agreement as assessed by Kappa statistics
was also similar between QFT and chest Xray. The study finally concluded that by using
QFT instead of TST, further follow-up could
be avoided in nearly 43% of asylum seekers.

[Downloadedfreefromhttp://www.sjkdt.orgonMonday,January09,2012,IP:140.234.255.9]||ClickheretodownloadfreeAndroidapplicationforthisjournal

Latent tuberculosis in refugees with renal failure

Further, QFT alone will be a good screening

tool or it can be used as a tool to retest those
individuals who were positive with TST.
QFT in Special Subcategories of Patients
Drug users
In an interesting study, TST was tested against
QFT in 48 HIV-seronegative former drug
users. The agreement between TST and the
QFT assay for latent TB was 73% ( = 0.45).
The study concluded that QFT was a valid
screening tool and can be used in lieu of TST
in this subgroup.6
High HIV prevalent setting
In a study from Trinidad, investigators compared the QFT assay and TST in screening/diagnosis of latent TB infection (LTBI)
among individuals in Trinidad and Tobago at
high-risk for TB.15 A total of 560 individuals
[TB patient contacts, HIV patients, health-care
workers, prison inmates, and TB patients
(controls)] were recruited for the study. The
QFT detected LTBI in 51% of the subjects
(with most positive results occurring among
the control group) whereas the TST detected it
in 39.4% (P = 0.001). Overall, the QFT assay
detected LTBI more frequently than the TST
among all subjects except the control group,
where detection favored the TST. The QFT
assay produced indeterminate and non-reactive
results in some HIV patients but required less
turn around time than the TST (23.3 h versus
70.2 h; P < 0.0001). The cost of TST is lesser
per subject than the QFT assay (US $3.70
versus US $18.60; P = 0.0008). The investigators concluded that QFT assay costs more
but had a higher detection rate among most
target groups and required less turn around
time than the TST. However, its sensitivity
was lower among immunocompromised subjects. Therefore, the QFT assay should be used
with caution for LBTI screening/diagnosis in
resource-poor, high-HIV prevalence settings
such as Trinidad and Tobago.
Children
QFT was compared with TST in diagnosing

11

TB infection in children, and to analyze discordant results. This prospective study included 98 children from contact-tracing studies
and 68 children with TST >/= 5 mm recruited
during public health screenings.16 The study
concluded that the use of QFT was helpful for
the diagnosis of TB infection, avoiding crossreactions with BCG immunization. Again, this
study involved healthy children. Extrapolation
of the findings of this study to refugee children
needs validation in future studies.
ELISPOT: Another IFN- Assay
In addition to QFT, ELISPOT is the other
commercially available IFN- assay that has
been well studied. Like QFT it involves a similar type of blood test and an assay for IFN-
and newly identified tubercular proteins like
Rv1985c.17 Like QFT it is highly specific for
active infection and usually tests negative in
BCG-vaccinated people and in the presence of
other mycobacterial infections.17
Comparison between ELISPOT and TST
In a study conducted on 69 rheumatic patients where TST and ELISPOT (Enzyme
Linked Immuno spot assay) was applied to all
the participants in the study, 17 (25%) had a
positive TST response and 15 (22%) had a positive ELISPOT response. Among the patients
with a positive TST result, eight had a positive
and nine a negative ELISPOT response,
whereas among the 49 patients with a negative
TST result, 42 were ELISPOT negative, but
seven (14%) were ELISPOT positive, with
three indeterminate results. The agreement between the two tests was poor. Thus, the
ELISPOT-IFN- assay performed better than
the TST in recognizing patients with latent TB,
thus reducing the number of patients submitted
to isoniazid prophylaxis on one hand, and on
the other hand, since the assay is less biased by
immunosuppressive regimens than TST, recognizing LTBI patients among those with a
negative TST response.18 Although this study
shows promise that ELISPOT is indeed a
better assay than TST, it is limited by the fact

[Downloadedfreefromhttp://www.sjkdt.orgonMonday,January09,2012,IP:140.234.255.9]||ClickheretodownloadfreeAndroidapplicationforthisjournal

12

that this was conducted on rheumatic patients.

Thus, extrapolation of these findings to a
refugee population will be difficult. A similar
data from refugee population is lacking and it
is for future studies to analyze this possibility.
Comparison between ELISPOT, QFT and
TST
A prospective study was conducted involving
393 consecutively enrolled patients who were
tested simultaneously with ELISPOT and QFT
because of suspected latent or active TB. Of
these patients, 318 had results of TST also
available. The study observed that the overall
agreement with the skin test was similar
(ELISPOT =0.508, QFT =0.460), but fewer
BCG-vaccinated individuals were identified as
positive by the two blood assays than by the
TST (P=0.003 for ELISPOT and P<0.0001 for
QFT). Indeterminate results were significantly
more frequent with QFT (11%, 43 of 383) than
with ELISPOT (3%, 12 of 383; P<0.0001) and
were associated with immunosuppressive treatment for both tests. Age younger than five
years was significantly associated with indeterminate results with QFT (P= 0.003), but not
with ELISPOT. Overall, ELISPOT produced
significantly more positive results (38%, n =
144, vs 26%, n = 100, with QFT; P< 0.0001),
and close contacts of patients with active TB
were more likely to be positive with ELISPOT
than with QFT (P= 0.0010). The study concluded that ELISPOT and QFT have higher
specificity than the TST. Rates of indeterminate and positive results, however, differ
between the blood tests, suggesting that they
might provide different results in routine clinical practice.5 Again, this study was conducted on normal healthy people and not on refugees. The validity of these assays on refugees needs to be tested in future studies.
Effect of Repeated Testing (Reproducibility)
It is a well-reported fact that serial TST can
result in a boosting of the skin test result, with
the greatest effect seen when the interval between tests is 15 weeks; this has been tested in

Shantha GP, Kumar AA, Bhise V, et al

the general and the refugee populations.19,20 A

recently published study assessed the performance of the QFT in a refugee population
relocating to the US. The goals of this study
were to evaluate the utility of QFT as a
screening tool for LTBI in a refugee population from TB-endemic countries and to
assess the reproducibility of the test in the
setting of an antecedent TST. In the 198 refugees who were studied, diagnostic agreement between the first QFT and simultaneous
TST was 78% (= 0.56) and between serial
QFT was 89% (= 0.76). In serial QFT testing,
70% of subjects had an increased QFT value,
perhaps the result of an antecedent TST in the
setting of previous TB exposure. This boosting
seemed to become less prevalent with time
following TST and occurred less frequently in
those with negative first QFT readings. Despite small changes in the quantitative results
caused by nonspecific variation and boosting,
the diagnostic result of the QFT was reliable.
The QFT had the potential to replace the TST
for LTBI screening in refugees from TBendemic areas.
Meta Analysis on the Usefulness of IFN-
Assays in the Screening of Latent TB
This systematic review proposed to estimate
sensitivity, specificity and reproducibility of
IGRAs (QFT and ELISPOT) for diagnosing
latent TB infection in healthy and immunesuppressed persons. The study observed that
the pooled specificity was 97.7% (95% CI,
96% to 99%) and 92.5% (CI, 86% to 99%) for
QFT and for ELISPOT, respectively. Both
assays were more specific than the TST in
samples vaccinated with BCG. Both assays
had good reproducibility. The review, however, identified the following limitations. Most
studies used cross-sectional designs with the
inherent limitation of no gold standard for
latent TB infection; also, most of them involved small samples with a widely varying
likelihood of true-positive and false-positive
test results. There is insufficient evidence on
IGRA performance in children, immune-compromised persons, and the elderly. The meta-

[Downloadedfreefromhttp://www.sjkdt.orgonMonday,January09,2012,IP:140.234.255.9]||ClickheretodownloadfreeAndroidapplicationforthisjournal

Latent tuberculosis in refugees with renal failure

analysis finally concluded that the new IGRAs

show considerable promise and have excellent
specificity. Additional studies are needed to
better define their performance in high-risk
populations and in serial testing. Longitudinal
studies are needed to define the predictive
value of IGRAs.21
Latent TB in HIV-Infected Individuals
This study was conducted to evaluate whether interferon-inducible protein (IP)-10, monocyte chemotactic protein (MCP)-2 and interleukin (IL)-2 can be useful biomarkers for
evaluating a specific response to RD1 antigens
associated to latent TB disease in HIV-infected
individuals. Sixty-six HIV-infected individuals
were prospectively enrolled, 28 with latent TB
and 38 without. The results of the study indicate that IP-10 and QFT have a sensitivity of
75% and 85.7%, respectively, in identifying
latent TB.
Conclusions
Latent TB is indeed a significant public health
problem in refugee camps. When refugees
move from a high TB-endemic area to a low
endemic area, there is a significant threat for
TB spread in this new area. TST, sputum analysis and chest radiography have been routinely used in refugee camps to diagnose TB.
Properties like low cost, easy availability, minimal patient discomfort, etc., make TST, sputum analysis and chest radiography the ideal
choice in a refugee setting. Also, these techniques have been in use for many years and
there are many trained health-care workers
who are experts in the interpretation of these
results. Elaborate lab facilities are not required
for TST, sputum analysis and chest radiography. Studies have clearly shown that chest
radiography and sputum analysis have poor
validity as screening tools for latent TB. TST
is often complicated by false positive results to
BCG vaccination, and other mycobacterial infections. Also, all the available data are from
the general population and similar data from
refugee population is lacking. In spite of these

13

limitations, TST, chest radiography and sputum analysis continue to be used in refugee
populations due to financial reasons that are
often prevalent in refugee camps.
Two IFN- assays namely QFT and ELISPOT
show significant promise as effective screening tools for latent TB in refugees. They have
good validity and reproducibility. They have
been tested to be much better with a higher
specificity than TST in refugee populations.
They give fewer false positive results than
TST. However, they are costly, require lab
setting and expertise in interpretation, and
their utility in immunosuppressed individuals,
children, pregnant women are questionable
and are yet to be validated. In HIV-infected individuals, IP-10 antigen assay stands promise
for the future. But its effectiveness as a screening tool has not yet been studied.
In conclusion, in a refugee setting where
resources are scanty, TST, sputum analysis
and chest radiography will continue to be used
to test for latent TB not because they are the
best but because they are cheap. The poor validity that comes with these tests is inevitable.
QFT and ELISPOT are tools that may be used
in the future when the cost for these techniques
comes down. The other approach that can be
adopted is that only patients who test positive
with TST may be retested using QFT or
ELISPOT. This way, by sequential testing, one
can be cost-effective and also the specificity
will increase.
References
1.

2.
3.

Dye C, Scheele S, Dolin P, Pathania V,

Raviglione MC. Consensus statement. Global
burden of tuberculosis: estimated incidence,
prevalence, and mortality by country. WHO
Global Surveillance and Monitoring Project.
JAMA 1999;282:67786.
Centers for Disease Control, 2008. Trends in
tuberculosisUnited States, 2007. Morbid
Mortal Wkly Rev MMWR 57:2815.
Dahle UR, Eldholm V, Winje BA, Mannsaker
T, Heldal E. Impact of immigration on the
molecular epidemiology of Mycobacterium
tuberculosis in a low incidence country. Am J
Respir Crit Care Med. 2007;176(9):9305.

[Downloadedfreefromhttp://www.sjkdt.orgonMonday,January09,2012,IP:140.234.255.9]||ClickheretodownloadfreeAndroidapplicationforthisjournal

14

Shantha GP, Kumar AA, Bhise V, et al

4.

13. Carvalho AC, Pezzoli MC, El Hamad I, et al.

QuantiFERON((R))-TB Gold test in the
identification of latent tuberculosis infection in
immigrants. J Infect 2007;55:1648.
14. Winje BA, Oftung F, Korsvold GE, et al.
Screening for tuberculosis infection among
newly arrived asylum seekers: comparison of
QuantiFERONTB Gold with tuberculin skin
test. BMC Infect Dis 2008(14);8:65.
15. Baboolal S, Ramoutar D, Akpaka PE.
Comparison of the QuantiFERON-TB Gold
assay and tuberculin skin test to detect latent
tuberculosis infection among target groups in
Trinidad & Tobago. Rev Panam Salud Publica
2010;28(1):36-42.
16. Altet-Gmez N, De Souza-Galvao M, Latorre
I, et al. Diagnosing TB infection in children:
analysis of discordances using in vitro tests
and tuberculin skin test. Eur Respir J 2010;
37(5):1166-74.
17. Chen J, Wang S, Zhang Y, et al. Rv1985c, a
promising novel antigen for diagnosis of
tuberculosis infection from BCG-vaccinated
controls. BMC Infect Dis 2010; 10:273.
18. Girlanda S, Mantegani P, Baldissera E, et al.
ELISPOT-IFN-gamma assay instead of
tuberculin skin test for detecting latent
Mycobacterium tuberculosis infection in
rheumatic patients candidate to anti-TNF-alpha
treatment. Clin Rheumatol 2010;29(10):113541.
19. Menzies D. Interpretation of repeated tuberculin tests. Boosting, conversion, and reversion. Am J Respir Crit Care Med 1999; 159:
1521.
20. Cauthen GM, Snider DE Jr, Onorato IM.
Boosting of tuberculin sensitivity among
Southeast Asian refugees. Am J Respir Crit
Care Med 1994;149:1597600.
21. Menzies D, Pai M, Comstock G. Metaanalysis: new tests for the diagnosis of latent
tuberculosis infection: areas of uncertainty and
recommendations for research. Ann Intern
Med 2007;146:34054.

Guidelines on the management of tuberculosis

and HIV infection in the United Kingdom.
Subcommittee of the joint tuberculosis
committee of the British Thoracic Society.
BMJ 1992;304(6836):1231-3.
5. Ferrara G, Losi M, DAmico R, et al. Use in
routine clinical practice of two commercial
blood tests for diagnosis of infection with
Mycobacterium tuberculosis: a prospective
study. Lancet 2006;367:132834.
6. Shah SS, McGowan JP, Klein RS, Converse
PJ, Blum S, Gourevitch MN. Agreement between Mantoux skin testing and QuantiFERONTB assay using dual mycobacterial antigens in
current and former injection drug users. Med
Sci Monit 2006;12: MT11MT16.
7. Taggart EW, Hill HR, Ruegner RG, Litwin
CM. Evaluation of an in vitro assay for
interferon gamma production in response to the
Mycobacterium tuberculosis-synthesized peptide
antigens ESAT-6 and CFP-10 and the PPD
skin test. Am J Clin Pathol 2006;125: 46773.
8. Eisenberg RL, Pollock NR. Low yield of chest
radiography in a large tuberculosis screening
program. Radiology 2010;256(3):998-1004.
9. Kvale PA, Hansen NI, Markowitz N, et al.
Routine analysis of induced sputum is not an
effective strategy for screening persons infected with human immunodeficiency virus for
Mycobacterium tuberculosis or Pneumocystis
carinii. Pulmonary Complications of HIV
Infection Study Group. Clin Infect Dis 1994;
19(3):410-6.
10. Andersen P, Munk ME, Pollock JM, Doherty
TM. Specific immune-based diagnosis of
tuberculosis. Lancet 2000;356:1099104.
11. Pai M, Riley LW, Colford JM, Jr. Interferongamma assays in the immunodiagnosis of tuberculosis: a systematic review. Lancet Infect
Dis 2004;4:76176.
12. Arend SM, Thijsen SF, Leyten EM, et al.
Comparison of two interferon-gamma assays
and tuberculin skin test for tracing tuberculosis
contacts. Am J Respir Crit Care Med 2007;
175:61827.

Copyright of Saudi Journal of Kidney Diseases & Transplantation is the property of Saudi Center for Organ
Transplantation, Publication Office and its content may not be copied or emailed to multiple sites or posted to a
listserv without the copyright holder's express written permission. However, users may print, download, or
email articles for individual use.