Annals of Thoracic Medicine Official publication of the Saudi Thoracic Society, affiliated to King Saud University
 
Search Ahead of print Current Issue Archives Instructions Subscribe e-Alerts Login 
Home Email this article link Print this article Bookmark this page Decrease font size Default font size Increase font size


 
REVIEW ARTICLE
Year : 2009  |  Volume : 4  |  Issue : 1  |  Page : 5-9
Diagnosis of latent tuberculosis: Can we do better?


Department of Medicine, College of Medicine, King Saud University, P. O. Box 2925, Riyadh 11426, Saudi Arabia

Date of Submission24-Sep-2008
Date of Acceptance18-Oct-2008

Correspondence Address:
Ibrahim O Al-Orainey
Department of Medicine, College of Medicine, King Saud University, P. O. Box 2925, Riyadh 11426
Saudi Arabia
Login to access the Email id


DOI: 10.4103/1817-1737.44778

PMID: 19561914

Rights and Permissions

   Abstract 

Latent tuberculosis infection (LTBI) is often diagnosed by the tuberculin skin test (TST). The latter has several limitations with regard to its sensitivity and specificity. It may be positive in people with prior bacille Calmette-Guιrin (BCG) vaccination or exposure to nontuberculous mycobacteria. False negative TST results frequently occur in patients with impaired T-cell function. Therefore TST results have to be interpreted taking into consideration the pretest risk of TB infection or reactivation. Recently, interferon gamma release assays (IGRA) were introduced for the diagnosis of LTBI. These include the T-SPOT-TB and the QuantiFERON® -TB Gold tests .These tests measure interferon gamma released in response to T-cell stimulation by specific Mycobacterium tuberculosis antigens. These tests have been shown to be more specific than the TST as they are not affected by BCG vaccination. Their sensitivity was similar to that of the TST and in some studies they correlated better with the degree of exposure. In immune-compromised patients their sensitivity was better than that of the TST. IGRA tests were shown to have better predictive value for the development of active disease among individuals with LTBI. These tests are expensive. Their most cost-effective utilization is as confirmatory tests in patients with positive TST results, particularly in areas with high rates of BCG vaccination.


Keywords: Tuberculosis, latent, tuberculin test


How to cite this article:
Al-Orainey IO. Diagnosis of latent tuberculosis: Can we do better?. Ann Thorac Med 2009;4:5-9

How to cite this URL:
Al-Orainey IO. Diagnosis of latent tuberculosis: Can we do better?. Ann Thorac Med [serial online] 2009 [cited 2020 Jun 6];4:5-9. Available from: http://www.thoracicmedicine.org/text.asp?2009/4/1/5/44778


There are two billion people infected with Mycobacterium tuberculosis all over the world.[1] The majority of these infections are asymptomatic (latent) and are detected by a positive tuberculin skin test (TST). These latent infections may reactivate later in life. This large pool of latent tuberculosis (TB) constitutes an important source of infection.

Longitudinal studies have shown that among people with positive tuberculin test and no other risk factors, the likelihood of developing active TB is about 0.1% every year. [2] The risk is higher in certain situations. Close contacts of infectious TB patients who become tuberculin positive (i.e., converters) have a 5-10% risk of developing active TB in the following 2-5 years and another 5-10% during their lifetime. [3] Other factors that increase the risk of reactivation of latent TB include HIV infection; old TB, with lung scarring; immunosuppression; organ transplantation; malignant disease; end-stage renal failure; and diabetes mellitus. [4]

Diagnosing latent tuberculosis infection (LTBI) is important for the overall control of the disease. Offering antituberculous treatment to individuals with LTBI significantly decreases their risk of developing active tuberculosis. [5] For years, the diagnosis of LTBI infection relied on the TST. The latter is known to have several limitations compromising its sensitivity and specificity. Recently immune-based blood tests were developed with the hope of improving the diagnosis of LTBI. This paper will review the performance of these new tests: their sensitivity and specificity and their role in the diagnosis of latent TB.


   Diagnosis of Latent Tuberculosis Top


LTBI is a subclinical infection with M. tuberculosis without clinical, bacteriological, or radiological evidence of the disease. The standard test for diagnosis of LTBI is the TST. This involves the intradermal injection of purified protein derivative (PPD), which leads to a delayed-type hypersensitivity response causing a cutaneous induration at the site of injection which peaks at 48-72 h. PPD is a mixture of more than 200 antigens that are also shared by other mycobacteria. A positive TST indicates previous exposure to M. tuberculosis or other nontuberculous mycobacteria or prior BCG vaccination. [6],[7],[8],[9] The latter is routinely included in the immunization regimen and is given at birth or in infancy in many countries, including in Saudi Arabia. Twelve weeks after bacille Calmette-Guιrin (BCG) vaccination, 90% of individuals develop tuberculin induration of ≥10 mm. [10] The reaction usually wanes within 1 year if the vaccination was given in infancy. [11] However, if BCG was given after the first year of life, tuberculin reactions may persist for 1-5 years in the majority of recipients. [12] In some instances, tuberculin reactivity may last for up to 15 years after vaccination. [7] Several studies have shown that BCG-vaccinated individuals of any age are more likely to have positive TST results. [9],[13] The booster phenomenon is more common after BCG vaccination, with the tuberculin test becoming positive in 20% of individuals if the test is repeated within 1-4 weeks. [14] Repeated testing (e.g., in health care workers) leads to stronger tuberculin reactions. [15] The low specificity of TST, especially in BCG-vaccinated people, puts into question its use as a "standard" test to diagnose latent TB. The absence of a gold standard to diagnose LTBI makes it difficult to estimate the exact sensitivity and specificity of TST. TST may also be falsely negative in patients with impaired T-cell function (e.g., in those with HIV infection or immunosuppression). Such patients are at high risk of developing TB, but the poor sensitivity of TST limits its utilization in these situations. [16]

Tuberculin skin test interpretation may be affected by the PPD dose and by operator variability in both inoculation and reading. [17] A low PPD dose (e.g., 2 U) may lead to a false negative reaction and a high dose (e.g., 10 U) may cause a false positive result. [18] There is no international consensus on what constitutes TST positivity. Different cutoffs are used in different countries. In the USA, an induration of ≥ 5 mm is considered positive in contacts of infectious TB patients, whereas in the UK an induration of ≥ 15 mm is considered positive for BCG-vaccinated contacts. [4],[19]

To overcome the limitations of the TST, the American guidelines for interpretation of TST were revised to include the pretest risk of TB infection or reactivation. [4] An induration of ≥ 5 mm is considered positive in patients with a high risk of infection or reactivation (e.g., recent contacts of infectious cases or HIV infection). An induration of ≥ 10 mm is considered positive for those with intermediate risk (e.g., residents of long-term facilities or patients with chronic diseases). For those with no risks, an induration of ≥ 15 mm is considered positive. These guidelines ignored the effect of BCG vaccination when interpreting the TST. [4]

Despite its shortcomings, TST remains in widespread use simply because of the lack of better alternatives. This highlights the need to continue the search to find more accurate diagnostic tests for latent TB.


   New Alternative Tests Top


In the absence of a gold standard to diagnose LTBI, it may be difficult to demonstrate that any test is better than the TST. However, the sensitivity of a potential test may be predicted by correlating its results with the degree of exposure (duration and proximity) to a source patient and the likelihood of acquiring infection from that source. A test would be more sensitive than the TST if it is positive in patients with a high risk of exposure. A more specific test would be independent of BCG vaccination.

Recently new immune-based blood tests were developed for the diagnosis of TB. These measure interferon gamma released in response to stimulation of sensitized T-cells by mycobacterial antigens. [20] The first commercially available test was QuantiFERON® TB assay; which measures interferon gamma production by ELISA after in vitro stimulation of white blood cells with PPD. [21] It was found to have sensitivity comparable to that of TST. It may give false positive results in BCG-vaccinated people and in those exposed to nontuberculous mycobacteria. [22]

Comparative genomic studies of mycobacteria identified a genomic region in M. tuberculosis that is not present in BCG strains and in most nontuberculous mycobacteria. [23] This so-called region of difference 1 (RD1) encodes antigens that are highly specific for M. tuberculosis . The best studied of these are ESAT-6 and CFP10. [24] These antigens were used to develop more specific T-cell-based tests for the diagnosis of TB infection. There are two commercially available diagnostic tests incorporating specific antigens. QuantiFERON® -TB gold test (Cellestis Ltd., Australia) and T-SPOT-TB assay (Oxford Immunotec, UK). [25],[26]

The specificity of interferon gamma release assays (IGRA) was studied in healthy low-risk individuals with BCG vaccination. QuantiFERON® -TB test was evaluated in 216 Japanese nursing students with no risk factors for TB exposure. All of them had had BCG vaccination. TST was positive (≥ 10 mm) in 64.6% (specificity 35.4) while QuantiFERON® -TB test was positive in 1.9% (specificity 98.1%). [27] A Korean study evaluated QuantiFERON® -TB Gold in 99 healthy adults with no risks for TB. [28] The majority (90%) of them were BCG vaccinated. QuantiFERON® -TB was positive in only 4% (specificity 96%) while TST was positive in 51% (specificity 49%). Another study found that QuantiFERON® -TB was negative in all 50 healthy medical students (74% BCG vaccinated). [29] TST was positive in 36% of them. These studies and others demonstrate clearly that IGRA tests are significantly more specific for the diagnosis of LTBI than the TST [Table 1]. [30],[31],[32],[33],[34],[35]

The sensitivity of IGRA tests was studied in patients with active TB and contacts of infectious TB patients. In patients with active TB, IGRA tests were found to have a sensitivity of 74-96%, while TST had a sensitivity of 64-69% in this population. [28],[29],[30]

In contact-tracing studies, IGRA tests were found to be as sensitive as TST for LTBI and, in some studies, they correlated better with the degree of exposure. [36],[37],[38] They also showed high specificity in BCG-vaccinated contacts. In the largest of these studies, the T-SPOT-TB test was evaluated in 535 secondary school students who had been exposed to an infectious TB case. [36] Most of them were BCG vaccinated. T-SPOT-TB test correlated more strongly than TST with the degree of exposure (closeness and duration of contact), indicating the superior sensitivity of the test. It also was not affected by BCG vaccination status. QuantiFERON® -TB Gold was evaluated in contact tracing of 85 BCG-unvaccinated individuals. [39] Its sensitivity was found to be similar to that of TST. These findings were confirmed by other investigators [Table 2]. [40],[41],[42],[43]

In immunocompromised patients, the data is too scarce to make any definite conclusions. In a study of 39 HIV-positive patients with TB, the sensitivity of the T-SPOT-TB test was found to be 92%. [31] TST was not done in this group but it is known that its sensitivity is low in this population. Another study of 590 HIV-infected patients showed that QuantiFERON® -TB Gold test correlated with known risk factors for LTBI or past history of TB. [44] HIV-positive patients with low CD4 counts were more likely to have indeterminate QuantiFERON® results.

A few studies have looked at the predictive value of IGRA tests for future development of TB. [45] The gold standard proof of LTBI is the eventual development of active disease.

This can only be evaluated by longitudinal cohort studies that follow tested individuals for development of TB. Diel et al ., in Germany, evaluated 601 close contacts of infective TB patients of whom 278 (46.3%) had had BCG vaccination. [43] TST was positive in 243 (40%), while QuantiFERON® -TB Gold was positive in 66 (11%) contacts. Isoniazid was offered only to contacts with positive QuantiFERON® -TB test. Forty-one contacts declined to take isoniazid. All contacts were followed for 2 years. Six of contacts developed active TB during follow-up and all six were QuantiFERON® positive. None of the QuantiFERON®-negative individuals developed TB. This important study indicates that QuantiFERON® -TB Gold is a more accurate indicator for LTBI and a better predictor for the development of TB. In another study, 88 TST-positive contacts of an index case were followed for 3.5 years. Only four of them had positive QuantiFERON® -TB test. None of the 84 QuantiFERON® -negative contacts developed TB during follow-up. This clearly confirms the high specificity and predictive value of the QuantiFERON® -TB Gold assay.

IGRA tests have several operational advantages over TST. They require only one visit for blood sampling. Automated reading reduces the reader bias in interpretation. There is no booster effect of the test and, therefore, repeated testing (e.g., in health care workers) does not affect results. The test is read within 24 h. IGRA tests require at least a basic laboratory and some technical skills. Blood need to be processed within 6 h of venipuncture. Storing samples for longer periods makes results less reliable. The development of QuantiFERON® in-tube assay is likely to overcome this problem.


   Role of IGRA Tests in the Diagnosis of LTBI Top


The main advantage of IGRA tests is their high specificity compared to TST. This significantly eliminates false positive results in BCG-vaccinated individuals and therefore avoids the costs and toxicity associated with unnecessary treatment. The sensitivity of IGRA tests is similar to that of TST. In contact-tracing studies, they showed good correlation with the degree of exposure to an index case. In some studies, sensitivity of the IGRA tests was better, particularly among immune-compromised patients. Detection of LTBI in these patients is highly important because of their increased risk of progression to active disease.

As mentioned previously, IGRA tests have several operational advantages. Their main disadvantage, however, is their high cost. A single assay usually costs around $30-40. The cost to the healthcare system may initially increase but the overall cost will decrease, as less LTBI patients are treated and less visits are required. The costs are likely to decline with increasing usage of these tests. Both T-SPOT-TB and QuantiFERON® -TB Gold tests are approved in Western Europe for the diagnosis of LTBI. QuantiFERON® -TB Gold is also approved by the USA Food and Drug Administration (FDA). [46]

The question is whether IGRA tests should complement or replace TST. The latter test is cheap and sensitive for diagnosis of LTBI. However, in BCG-vaccinated individuals, its specificity is clearly inferior to that of the IGRA tests. These expensive tests may not be affordable to many developing countries. Therefore, it is likely that TST will remain in use in many parts of the world.

In resource-rich countries, IGRA tests are increasingly utilized. In their guidelines, the Center for Disease Control and Prevention (USA) have suggested replacing TST by QuantiFERON® -TB Gold. [46] The objective is to have only one system in place and to improve the sensitivity and specificity of testing for LTBI. On the other hand, British guidelines recommend using IGRA tests as confirmatory tests in those with positive TST results. [19] In their evaluation, they found that this two-step approach is the most cost-effective. They also recommended using IGRA tests in situations where TST may not be reliable (e.g., in immune-compromised patients). A cost-analysis study in Germany found that screening of contacts by TST followed by QuantiFERON® -TB Gold assay in positive TST reactors was the most cost-effective method for screening for latent TB. [47]

In countries where the BCG vaccination rate is high (as in Saudi Arabia), the two-step approach is probably more efficient for screening of high-risk individuals (e.g., contacts of infectious patients, health care workers, etc). It improves the diagnostic accuracy and reduces false positive results. This is likely to have a significant positive impact on the control of latent TB.

Interferon gamma assays are an important step in the search for better diagnostic tests for latent TB. However, more research is required to improve their performance, especially in immunocompromised patients. Longitudinal studies are also needed to assess the value of these tests in predicting the development of active TB and to demonstrate clearly their superiority to the TST.

 
   References Top

1.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. J Am Med Assoc 1999;282:677-86.  Back to cited text no. 1    
2.Ferebee SH, Mount FW, Murray FJ, Livesay VT. A controlled trial of isoniazid prophylaxis in mental institutions. Am Rev Respir Dis 1963;88:161-75.  Back to cited text no. 2  [PUBMED]  
3.Styblo K. Recent advances in epidemiological research in tuberculosis. Adv Tuberc Res 1980;20:1-63.  Back to cited text no. 3  [PUBMED]  
4.American Thoracic Society. Targeted tuberculin testing and treatment of latent tuberculosis infection. Am J Respir Crit Care Med 2000;161:S221-47.  Back to cited text no. 4    
5.Comstock GW, Edwards LB, Livesay VT. Tuberculosis morbidity in the US Navy: Its distribution and decline. Am Rev Respir Dis 1974;110:571-80.  Back to cited text no. 5    
6.Huebner RE, Schein MF, Bass JB Jr. The tuberculin skin test. Clin Infect Dis 1993;17:968-75.  Back to cited text no. 6  [PUBMED]  
7.Wang L, Turner MO, Elwood RK, Schulzer M, FitzGerald JM. A meta-analysis of the effect of Bacille Calmette Guerin vaccination on tuberculin skin test measurements. Thorax 2002;57:804-9.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Kwamanga DO, Swai OB, Agwanda R, Githui W. Effect of non-tuberculous Mycobacteria infection on tuberculin results among primary school children in Kenya. East Afr Med J 1995;72:222-7.  Back to cited text no. 8  [PUBMED]  
9.Comstock GW. False tuberculin test results. Chest 1975;68:465-9.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Menzies RI, Vissandjee B. Effect of bacilli Calmette-Guerin vaccination on tuberculin reactivity. Am Rev Respir Dis 1992;145:621-5.  Back to cited text no. 10    
11.Lifschitz M. The value of the tuberculin skin test as a screening test for tuberculosis among BCG-vaccinated children. Pediatrics 1965;36:624-7.  Back to cited text no. 11  [PUBMED]  
12.Horwitz O, Bunch-Christensen K. Correlation between tuberculin sensitivity after 2 months and 5 years among BCG vaccinated subjects. Bull World Health Organ 1972;47:49-58.  Back to cited text no. 12  [PUBMED]  
13.Tissot F, Zanetti G, Francioli P, Zellweger JP, Zysset F. Influence of Bacille Calmette-Guerin vaccination on size of tuberculin skin test reaction to what size? Clin Infect Dis 2005;40:211-7.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Sepulveda R, Ferrer X, Latrach C, Sorensen R. The influence of Calmette-Guerin bacillus immunization on the booster effect of tuberculin testing in healthy young adults. Am Rev Respir Dis 1990;142:24-8.  Back to cited text no. 14    
15.Magnus K, Edwards L. The effect of repeated tuberculin testing on post-vaccination allergy. Lancet 1955;24:643-4.  Back to cited text no. 15    
16.Markowitz N, Hansen NI, Wilcosky TC, Hopewell PC, Glassroth J, Kvale PA, et al . Tuberculin and energy testing in HIV-seropositive and HIV-seronegative persons: Pulmonary complications of HIV infection study group. Ann Intern Med 1993;119:185-93.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]
17.Chaparas SD, Vandiviere HM, Melvin I, Koch G, Becker C. Tuberculin test: Variability with the Mantoux procedure. Am Rev Respir Dis 1985;132:175-7.  Back to cited text no. 17  [PUBMED]  
18.Stuart RL, Bennett N, Forbes A, Grayson ML. A paired comparison of tuberculin skin test results in health care workers using 5 TU and 10 TU tuberculin. Thorax 2000;55:693-5.  Back to cited text no. 18  [PUBMED]  [FULLTEXT]
19.National Collaborating Centre for Chronic Conditions. Tuberculosis: Clinical diagnosis and management of tuberculosis, and measures for its prevention and control. London: Royal College of Physicians; 2006.   Back to cited text no. 19    
20.Lein AD, Von Reyn CF. In vitro cellular and cytokine responses to mycobacterial antigens: Application to diagnosis of tuberculosis infection and assessment of response to mycobacterial vaccines. Am J Med Sci 1997;313:364-71.  Back to cited text no. 20  [PUBMED]  [FULLTEXT]
21.Pottumarthy S, Morris AJ, Harrison AC, Wells VC. Evaluation of the tuberculin gamma interferon assay: Potential to replace the Mantoux skin test. J Clin Microbiol 1999;37:3229-32.  Back to cited text no. 21  [PUBMED]  [FULLTEXT]
22.Streeton JA, Desem N, Jones SL. Sensitivity and specificity of a gamma interferon blood test for tuberculosis infection. Int J Tuberc Lung Dis 1998;2:443-50.  Back to cited text no. 22  [PUBMED]  [FULLTEXT]
23.Lalvani A, Nagvenkar P, Udwadia Z, Pathan AA, Wilkinson KA, Shastri JS, et al . Enumeration of T-cells specific for RD1-encoded antigens suggests a high prevalence of latent Mycobacterium tuberculosis infection in healthy urban Indians. J Infect Dis 2001;183:469-77.  Back to cited text no. 23  [PUBMED]  [FULLTEXT]
24.Liu XQ, Dosanjh D, Varia H, Ewer K, Cockle P, Pasvol G, et al . Evaluation of T-cell responses to novel RD1- and RD2-encoded Mycobacterium tuberculosis gene products for specific detection of human tuberculosis infection. Infect Immun 2004;72:2574-81.  Back to cited text no. 24  [PUBMED]  [FULLTEXT]
25.T Spot TB-Oxford Immunotec Limited. Available from: http://www.oxfordimmunotec.com/products.htm. [cited in 2004].  Back to cited text no. 25    
26.Clinicians Guide to Quantiferon-TB Gold. Available from: http://www.cellestis.com/IRM/contentAU/gold/cliniciansguide.pdf. [cited in 2004].  Back to cited text no. 26    
27.Mori T, Sakatani M, Yamagishi F, Takashima T, Kawabe Y, Nagao K, et al . Specific detection of tuberculosis infection: An interferon-gamma-based assay using new antigens. Am J Respir Crit Care Med 2004;170:59-64.  Back to cited text no. 27  [PUBMED]  [FULLTEXT]
28.Kang YA, Lee HW, Yoon HI, Cho B, Han SK, Shim YS, et al . Discrepancy between the tuberculin skin test and the whole-blood Interferon gamma assay for the diagnosis of latent tuberculosis infection in an intermediate tuberculosis-burden country. JAMA 2005;293:2756-61.  Back to cited text no. 28  [PUBMED]  [FULLTEXT]
29.Kobashi Y, Obase Y, Fukuda M, Yoshida K, Miyashita N, Oka M. Clinical Reevaluation of the QuantiFERON TB-2G Test as a diagnostic method for differentiating active Tuberculosis from non-tuberculous Mycobacteriosis. Clin Infect Dis 2006;43:1540-6.  Back to cited text no. 29    
30.Lalvani A, Pathan AA, McShane H, Wilkinson RJ, Latif M, Conlon CP, et al . Rapid detection of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Am J Respir Crit Care Med 2001;163:824-8.   Back to cited text no. 30  [PUBMED]  [FULLTEXT]
31.Chapman AL, Munkanta M, Wilkinson KA, Pathan AA, Ewer K, Ayles H, et al . Rapid detection of active and latent tuberculosis infection in HIV-positive individuals by enumeration of Mycobacterium tuberculosis-specific Tcells. AIDS 2002;16:2285-93.  Back to cited text no. 31  [PUBMED]  [FULLTEXT]
32.Pathan AA, Wilkinson KA, Klenerman P, McShane H, Davidson RN, Pasvol G, et al . Direct ex vivo analysis of antigen -specific IFN-gamma-secreting CD4 T cells in Mycobacterium tuberculosis infected individuals: Associations with clinical disease state and effect of treatment. J Immunol 2001;167:5217-25.  Back to cited text no. 32  [PUBMED]  [FULLTEXT]
33.Brock I, Weldingh K, Leyten EM, Arend SM, Ravn P, Andersen P. Specific T-cell epitopes for immunoassay-based diagnosis of Mycobacterium tuberculosis infection. J Clin Microbiol 2004;42:2379-87.  Back to cited text no. 33  [PUBMED]  [FULLTEXT]
34.Ravn P, Munk ME, Andersen AB. The diagnostic potential of the Quantiferon-RD1 test in patients with active tuberculosis. Clin Microbiol Infect 2004;10:80.  Back to cited text no. 34    
35.Menzies D, PaiComstock G. Meta-analysis: New tests for the diagnosis of latent tuberculousis infection: Areas of uncertainty and recommendations for research. Ann Intern Med 2007;146:340-54.   Back to cited text no. 35    
36.Ewer K, Deeks J, Alvarez L, Bryant G, Waller S, Andersen P, et al . Comparison of T-cell based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak. Lancet 2003;361:1168-73.  Back to cited text no. 36  [PUBMED]  [FULLTEXT]
37.Lalvani A, Pathan AA, Durkan H, Wilkinson KA, Whelan A, Deeks JJ, et al . Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Lancet 2001;357:2017-21.  Back to cited text no. 37  [PUBMED]  [FULLTEXT]
38.Nakaoka H, Lawson L, Squire SB, Coulter B, Ravn P, Brock I, et al . Risk for tuberculosis among children. Emerg Infect Dis 2006;12:1383-8.  Back to cited text no. 38  [PUBMED]  [FULLTEXT]
39.Brock I, Weldingh K, Lilleback T, Follmann F, Andersen P. Comparison of tuberculin skin test and new specific blood test in tuberculosis contacts. Am J Respir Crit Care Med 2004;170:65-9.  Back to cited text no. 39    
40.Shams H, Weis SE, Klucar P, Lalvani A, Moonan PK, Pogoda JM, et al . Enzyme-linked immunospot and tuberculin skin testing to detect latent tuberculosis infection. Am J Respir Crit Care Med 2005;172:1161-8.  Back to cited text no. 40  [PUBMED]  [FULLTEXT]
41.Zellweger JP, Zellweger A, Ansermet S, de Senarclens B, Wrighton-Smith P. Contact tracing using a new T-cell based test: Better correlation with tuberculosis exposure than the tuberculin skin test. Int J Tuberc Lung Dis 2005;9:1242-7.  Back to cited text no. 41  [PUBMED]  [FULLTEXT]
42.Hill PC, Brookes RH, Adetifa IM, Fox A, Jackson-Sillah D, Lugos MD, et al . Comparison of enzyme-linked immunospot assay and tuberculin skin test in healthy children exposed to Mycobacterium tuberculosis. Pediatrics 2006;117:1542-8.  Back to cited text no. 42  [PUBMED]  [FULLTEXT]
43.Diel R, Loddenkemper R, Meywald-Walter K, Niemann S, Nienhaus A. Predictive value of a whole-blood IFN-y assay for the development of active tuberculosis disease after recent infection with Mycobacterium tuberculosis. Am J Respir Crit Care Med 2008;177:1164-70.  Back to cited text no. 43  [PUBMED]  [FULLTEXT]
44.Brock I, Ruhwald M, Lundgren B, Westh H, Mathiesen LR, Rawn P. Latent tuberculosis in HIV positive, diagnosed by the M. Tuberculosis. Specific Interferon Gamma test. Respir Res 2006;7:56.   Back to cited text no. 44    
45.Higuchi K, Harada N, Mori T, Sekiya Y. Use of Quantiferon-TB Gold to investigate tuberculosis contacts in a high school. Respirology 2007;12:88-92.   Back to cited text no. 45  [PUBMED]  [FULLTEXT]
46.Mazurek GH, Jereb J, Lobue P, Iademarco MF, Metchock B, Vernon A. Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection. United States. MMWR Recomm Rep 2005;54:49-55.  Back to cited text no. 46    
47.Diel R, Loddenkemper R, Meywald-Walter K, Niemann S, Nienhaus A. Predictive value of a whole-blood IFN-y assay for the development of active tuberculosis disease after recent infection with Mycobacterium tuberculosis. Am J Respir Crit Care Med 2008;177:1164-70.  Back to cited text no. 47  [PUBMED]  [FULLTEXT]



 
 
    Tables

  [Table 1], [Table 2]

This article has been cited by
1 Methods Used in Economic Evaluations of Tuberculin Skin Tests and Interferon Gamma Release Assays for the Screening of Latent Tuberculosis Infection: A Systematic Review
Maria Koufopoulou,Andrew John Sutton,Katie Breheny,Lavanya Diwakar
Value in Health. 2016;
[Pubmed] | [DOI]
2 Practical aspects of backward bifurcation in a mathematical model for tuberculosis
David J. Gerberry
Journal of Theoretical Biology. 2016; 388: 15
[Pubmed] | [DOI]
3 Biomarker detection of global infectious diseases based on magnetic particles
Soledad Carinelli,Mercè Martí,Salvador Alegret,María Isabel Pividori
New Biotechnology. 2015; 32(5): 521
[Pubmed] | [DOI]
4 Profile of interferon-gamma response to latency-associated and novel in vivo expressed antigens in a cohort of subjects recently exposed to Mycobacterium tuberculosis
Leonardo Silva de Araujo,Nidai de Bárbara Moreira da Silva,Renan Jeremias da Silva,Janaina Aparecida Medeiros Leung,Fernanda Carvalho Queiroz Mello,Maria Helena Féres Saad
Tuberculosis. 2015; 95(6): 751
[Pubmed] | [DOI]
5 Latent Tuberculosis Infection Among Immigrant and Refugee Children Arriving in the United States: 2010
Eboni M. Taylor,John Painter,Drew L. Posey,Weigong Zhou,Sharmila Shetty
Journal of Immigrant and Minority Health. 2015;
[Pubmed] | [DOI]
6 Identification of a novel immunodominant antigen Rv2645 from RD13 with potential as a cell-mediated immunity-based TB diagnostic agent
Wei Luo,Zi-Lu Qu,Yan Xie,Jie Xiang,Xiao-Lian Zhang
Journal of Infection. 2015; 71(5): 534
[Pubmed] | [DOI]
7 Mycobacterial Dormancy Regulon Protein Rv2623 as a Novel Biomarker for the Diagnosis of Latent and Active Tuberculous Meningitis
Ruchika K. Jain,Amit R. Nayak,Aliabbas A. Husain,Milind S. Panchbhai,Nitin Chandak,Hemant J. Purohit,Girdhar M. Taori,Hatim F. Daginawala,Rajpal S. Kashyap
Disease Markers. 2013; 35: 311
[Pubmed] | [DOI]
8 Mycobacterium avium ss paratuberculosis-associated diseases: Piecing the Crohnæs puzzle together
Gitlin, L. and Borody, T.J. and Chamberlin, W. and Campbell, J.
Journal of Clinical Gastroenterology. 2012; 46(8): 649-655
[Pubmed]
9 Could changes in national tuberculosis vaccination policies be ill-informed ?
Gerberry, D.J. and Milner, F.A.
Mathematical Modelling of Natural Phenomena. 2012; 7(3): 78-98
[Pubmed]
10 Immunosurveillance for Mycobacterium tuberculosis of health care personnel in a third level care hospital
Larcher, C., Frizzera, E., Pretto, P., Lang, M., Sonnleitner, N., Huemer, H.P.
Medicina del Lavoro. 2012; 103(1): 26-36
[Pubmed]
11 How to minimise risk of acquiring tuberculosis when working in a high prevalence setting: A guide for healthcare workers
Harrop, T., Aird, J., Thwaites, G.
BMJ. 2011; 342(7801)
[Pubmed]
12 Assessment and management of latent tuberculosis infection in a refugee population in the Northern Territory
Trauer, J.M., Krause, V.L.
Medical Journal of Australia. 2011; 194(11): 579-582
[Pubmed]
13 Non-compliance with health surveillance is a matter of Biosafety: A survey of latent tuberculosis infection in a highly endemic setting
Rocha, S.S.D., Marinho, J.M., Oliveira, E.S., Rodrigues, J.S., Conceiçao, E.L., Meira Jr., A.E., Almeida, A., (...), Barbosa, T.
BMJ Open ,. 2011; art A17
[Pubmed]
14 Nanotechnology: A focus on treatment of Tuberculosis
Kumar, N. and Kumar, P. and Kumar, P. and Kumar, M. and Kumar, R.
International Journal of Drug Delivery. 2011; 3(1): 25-42
[Pubmed]
15 Tuberculosis: Prevention in travellers
Neilson, A.A. and Mayer, C.A.
Australian Family Physician. 2010; 39(10): 743-750
[Pubmed]
16 Splenic abscess as a paradoxical response to chemotherapy in tuberculous pleural effusion
Dixit, R., Nuwal, P., Arya, M.
Annals of Thoracic Medicine. 2010; 5(1): 50-51
[Pubmed]
17 Nanotechnology diagnostics for infectious diseases prevalent in developing countries
Tanya S. Hauck,Supratim Giri,Yali Gao,Warren C.W. Chan
Advanced Drug Delivery Reviews. 2010; 62(4-5): 438
[Pubmed] | [DOI]
18 Tuberculin skin test in child immigrant population | [La prueba de tuberculina en la población pediátrica inmigrada]
Aliberch, R.M.M., Ugarte, A.A., Gil, B.M., Buxó, A.E., de Frutos Gallego, E., Rodríguez, C.C., Vidal, D.R.
Pediatria de Atencion Primaria. 2010; 12(47): 399-411
[Pubmed]
19 Nanotechnology diagnostics for infectious diseases prevalent in developing countries
Hauck, T.S., Giri, S., Gao, Y., Chan, W.C.W.
Advanced Drug Delivery Reviews. 2010; 62((4-5)): 438-448
[Pubmed]
20 Can we change the way we look at BCG vaccine
Al-Hajoj, S.A.
Annals of Thoracic Medicine. 2009; 4(2): 92-93
[Pubmed]
21 Interferon-gamma release assays and TB diagnosis
Drug and Therapeutics Bulletin. 2009; 47(6): 67-70
[Pubmed]



 

Top
Print this article  Email this article
 
  Search
 
   Next article
   Previous article 
   Table of Contents
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Article in PDF (715 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
    Diagnosis of Lat...
    New Alternative ...
    Role of IGRA Tes...
    References
    Article Tables

 Article Access Statistics
    Viewed9398    
    Printed347    
    Emailed6    
    PDF Downloaded1698    
    Comments [Add]    
    Cited by others 21    

Recommend this journal