|Year : 2019 | Volume
| Issue : 1 | Page : 53-59
Comparison of tuberculin skin test and interferon-gamma release assay in the diagnosis of latent tuberculosis infection among indonesian health-care workers
Ratnawati1, Erlina Burhan1, Cempaka Nova Intani1, Heni Handayani2, Fariz Nurwidya1
1 Departement of Pulmonology and Respiratory Medicine, Faculty of Medicine Universitas Indonesia, Persahabatan Hospital, Jakarta, Indonesia
2 Community Lung Health Center, Balai Besar Kesehatan Paru Masyarakat, Bandung, Indonesia
|Date of Web Publication||4-Feb-2019|
Department of Pulmonology and Respiratory Medicine, Universitas Indonesia Faculty of Medicine, Persahabatan Hospital, Jalan Persahabatan Raya No. 1, Rawamangun Jakarta 13230
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Health-care workers are groups that are close contact with tuberculosis (TB) patients. As an alternative to the tuberculin skin test (TST), there is interferon-gamma release assay (IGRA) for the diagnosis of latent TB infection (LTBI). The objective of this study is to compare TST and IGRA in the diagnosis of LTBI among Indonesian health-care workers. Methods: This study design was a cross-sectional study. TST results are consistent for LTBI if there is induration ≥10 mm in individuals without previous TST, or ≥15 mm in participants with a history of previous TST. Medical history interview, physical examination, chest X-ray, and sputum smear examination were performed to exclude active TB infection. Results: Among 84 healthcare workers, the prevalence of LTBI was 51.2% by IGRA and 29.8% by TST with sufficient agreement (κ = 0.34). Age and low education were significantly correlated with the positive results of IGRA (P < 0.05); meanwhile smoking status was correlated with TST (P < 0.05). Conclusion: The prevalence of LTBI is higher with IGRA as compared to TST, with sufficient agreement and there is significant correlation between age and low education with the results of IGRA and in smoking status with TST.
Keywords: Interferon-gamma release assay, latent tuberculosis infection, tuberculin skin test
|How to cite this article:|
Ratnawati, Burhan E, Intani CN, Handayani H, Nurwidya F. Comparison of tuberculin skin test and interferon-gamma release assay in the diagnosis of latent tuberculosis infection among indonesian health-care workers. J Nat Sc Biol Med 2019;10:53-9
|How to cite this URL:|
Ratnawati, Burhan E, Intani CN, Handayani H, Nurwidya F. Comparison of tuberculin skin test and interferon-gamma release assay in the diagnosis of latent tuberculosis infection among indonesian health-care workers. J Nat Sc Biol Med [serial online] 2019 [cited 2019 Dec 9];10:53-9. Available from: http://www.jnsbm.org/text.asp?2019/10/1/53/251508
| Introduction|| |
Tuberculosis (TB) remains a leading cause of mortality worldwide and the WHO reported in 2017 that Indonesia is the second ranked for active cases of TB. About 10% of people infected with Mycobacterium tuberculosis (MTB) will develop active TB and become ill during their lives while others become latent.
A screening tests available for latent TB infection (LTBI) diagnosis are tuberculin skin test (TST) and interferon-gamma release assay (IGRA). Although routine testing is not recommended, in specific groups, the two tests become very useful, such as healthcare workers in close contact with active TB patients. The TST is often used to screen individuals of LTBI but cannot be used to distinguish whether MTB infection is active or latent.
The comparison of TST and IGRA in the diagnosis of LTBI among Indonesia health-care workers is still unknown. The purpose of this study is to reveal the prevalence of LTBI in healthcare workers using IGRA and TST. The study also aimed to compare the TST and IGRA in the diagnosis of LTBI among Indonesian health-care workers as well as the associated factors from the participants' characteristics. Finally, we will define the cutoff point of TST as screening tests in health workers in countries with high TB incidence rates using IGRA and also determine the agreement between TST and IGRA results.
| Methods|| |
The study design was a cross-sectional study. The study was conducted in the Community Lung Health Center (Balai Besar Kesehatan Paru Masyarakat [BBKPM]), Bandung, West Java Province, Indonesia, from January to April 2015. The population targets are all health-care workers in BBKPM Bandung. The inclusion criteria were participants aged ≥18 years old, health-care workers in contact with active pulmonary TB patients (lung clinic, lung infection wards, microbiology, laboratory, pharmacy, and radiology), has been working in the TB unit BBKPM for more than 2 months, willing to participate by signing informed consent. The exclusion criteria were a history of TB treatment, being treated for TB, active TB, pregnant women, and HIV positive. Sampling was done by total sampling. The variables studied were age, gender, nutritional status, education, socioeconomic status, type of employment, length of employment, location, level of occupational risk, Bacillus Calmette-Guérin (BCG) vaccination, and smoking status. The study protocols include signing the informed consent of research, obtaining basic data by medical interview, physical examination, chest X-ray examination, acid–fast bacilli (AFB) sputum smear (three times), and MTB culture, blood sampling, and the TST procedure. The entire series of studies conducted in BBKPM Bandung and IGRA-QuantiFERRON TB Gold (IGRA-QFT) examination conducted at the Laboratory of Immunology and Biomolecular Universitas Pajajaran, Bandung, Indonesia. This study has been approved by the Institutional Review Board of Faculty of Medicine Universitas Indonesia (Ethical Clearance No. 59/UN2.F1/ETIK/2014).
The conformity level in this study is represented by the Kappa value κ. If the Kappa value κ is 0, it means that the conformity as observed was purely due by chance, meanwhile conformity level as high as 1, it reflects a perfect true conformity. The data collected was processed and analyzed using Statistic Package for Social Science (SPSS) version 20 (IBM Corp, Armonk, New York, USA). The regression logistic test was used to determined P value in comparing data between groups. P < 0.05 was considered to be statistically significant.
| Results|| |
From initially 96 health workers, there were 12 participants that were excluded (3 pregnant women, 8 participants had a history of TB treatment and one subject with active pulmonary TB). The characteristics of 84 participants were described in [Table 1]. The number of females was slightly more than males 51.2% versus 48.8%, respectively. The participants were a predominantly young aged group with mean age 38.06 years, undergraduate education, a high socioeconomic status, normal nutrition status, have been vaccinated with BCG, paramedics type of work, working period ≤10 years, working location of clinics, and the risk level of work was dominantly high-risk groups.
First, we determined the prevalence of LTBI using IGRA and TST and analyzed the risk of LTBI by each subject's demographic variables. The prevalence of LTBI in this study, as reflected by IGRA-positive results, was 51.2% and from the results of a positive TST was 29.8%. The 41–50 years aged group, low education group, and group without history of BCG vaccination, have the significant highest risk of getting IGRA-positive (P < 0.05), meanwhile females, lower socioeconomic class, smokers, abnormal nutritional status, paramedic workers, working period of more than 21 years, work location in clinics, work risk level, were not significantly contributed to higher risk of having positive IGRA results [Table 2]. As for TST test, the smokers have a significant increased risk of having positive TST test (P < 0.05), meanwhile age, gender, level of education, socioeconomic status, nutritional status, history of BCG vaccination, type of work, working duration, working location, and working risk level, were not associated with positive TST result [Table 3].
|Table 2: Sociodemography relationship with interferon-gamma release assay-QuantiFERRON tuberculosis Gold in healthcare workers|
Click here to view
|Table 3: Sociodemography relationship with tuberculin skin test in healthcare workers|
Click here to view
Next, we examined the cutoff point to have sensitivity and specificity of the IGRA test by using the TST test as the gold standard [Table 4]. We obtained the 80.0% sensitivity and 61% specificity at the cutoff point of TST >10 mm, while the 75.6% sensitivity and 72.1% specificity at cutoff point >5 mm. Data specificity was used as a reference of test screening in health-care workers at risk of being infected with TB. In this study, the highest specificity was found at the point of induration ≥5 mm.
We then analyzed the agreement between IGRA and TST that were calculated at various point of cut induration, ≥5 mm, ≥6 mm, ≥7 mm, ≥8 mm, ≥9 mm, and ≥10 mm and obtained a value of conformity amounting to 66.5% with κ = 0.34 [Table 5]. The highest agreement value (72.4%) was found in the cutoff point of TST induration ≥6 mm (κ = 0.48) and ≥5 mm ≥5 mm (κ =0.48) with a degree of agreement was moderate degree.
|Table 5: Agreement between tuberculin skin test and interferon gamma release assay-QuantiFERRON tuberculosis Gold|
Click here to view
Finally, we reveal the discordant between the tuberculin test and IGRA-QFT by sociodemographic variables. We obtained the highest discordant in participants with a higher socioeconomic characteristics found in 25 participants (κ = 0.26) as shown in [Table 6]. The highest discordant were found in the group of age ≥51 age years old, female, high education level, and higher socioeconomic status in the TST (−)/IGRA (+).
|Table 6: Discordant between interferon-gamma release assay-QuantiFERRON tuberculosis gold and tuberculin skin test based on sociodemography|
Click here to view
The highest discordant between tuberculin test and IGRA-QFT based on nutritional status and a history of BCG vaccination was seen in participants (23 participants) with a history of BCG vaccination (κ = 0.23). The largest discordant was found in overweight participants and those with a history of BCG vaccination in the TST (−)/IGRA (+).
The highest discordant based on working characteristics was seen in participants with working period ≥21 years (κ = 0.43) and places of work category “other” (κ = 0.44). The biggest discordant was found in paramedics group and length of work 11–20 years group only in TST (−)/IGRA (+), meanwhile in the work risk level variable, the biggest discordant was found lower risk jobs at TST (+)/IGRA (−).
| Discussion|| |
LTBI is important to be taken into account when evaluating TB infection control program. Investigating the prevalence of LTBI and the risk factors in the community might improve the health policy. However, finding a suitable diagnostic tool to determine LTBI is an issue that needs to be confirmed. The current study compares the TST and IGRA to diagnose LTBI in population at risk of having LTBI.
This study involved nearly an equal amount of men and women which was different with study by Adams et al. that had more women than men. The participants working characteristics, such as type of work, length of work, place of work and level of occupational risk, provide an overview of risk factors that are directly related to work-associated LTBI. The working characteristics were comparable with the study by Torres Costa et al. in Portugal who found that all participants with BCG vaccination history were mostly paramedics that consisted of nurse 45% and doctors 17.3%, and the largest group based on service employment year was <5 years.
Our study found the prevalence of LTBI in healthcare workers using IGRA and TST were 51.2% and 29.8%, respectively. The biggest TST induration was found at ≥5 mm with a prevalence of 61.9%. Our LTBI prevalence by TST is lower than study by Martin et al., who found TST positive prevalence was 53%. Furthermore, Drobniewski et al. in Russia reported that the prevalence of LTBI in health-care workers using IGRA-QFT was 40.8%. In this study, positive IGRA results were associated with age, education, and no history of BCG vaccination. Older age had an increased risk of positive IGFRA with may be due to the immune system. However, the WHO reported in 2011 that the impact of immunosuppression on the IGRA validity is still unknown.
The majority of participants with low education have positive IGRA results, in contrast to the high education group. This may be related to low awareness to protect themselves from becoming infected with TB. A study by Grodzińska-Jurczak et al. shows an insignificant correlation between low education and health knowledge. The group that did not receive BCG vaccination are associated with increased risk of positive IGRA. This shows that those with no BCG vaccination will be more susceptible to TB infection which is consistent with the study by Chan et al., who found that the BCG vaccine has a protective effect on adults.
Smoking status is associated with positive TST result in this study, which is consistent with the study by Horne et al., who found that smoking was independently associated with a significant increase in risk for LTBI. Lindsay et al. showed that cigarette smoke exposure increased the risk of TB infection, reduced the function of bronchial epithelial cilia, reduced the ability of alveolar macrophages, and impaired immune response to bacteria.
Nutritional status was not associated with positive IGFRA result; however, underweight was associated with positive TST results. This is quite consistent with the study by Ryadinency et al., who showed that the nutritional status in children is one of the risk factors that influence a children's susceptibility to TB infection.
There were no significant risks in working variables with positives TST and IGRA results. Our findings are different with study by Harada et al., who reported that working experience as health officer more than 5 years, and has worked as a nurse in the TB inpatient ward, were significantly associated with LTBI. The consistent findings was showed by Pai et al., in which working duration is a significant risk. A study by Plitt et al. stated that the type of work affects the positivity of TST result.
This study intended to see the cutoff point of TST based on the sensitivity and specificity of IGRA-QFT on health workers in countries with a high burden TB. The currently recommended TST results ≥10 mm and IGRA QFT ≥0.35 IU/ml as a positive cutoff showed 80% sensitivity and 61% specificity, but when using a different cutoff level will change the sensitivity and specificity. Specificity was used as a reference of screening tests in health-care workers at risk of becoming infected with TB. In one Canadian study, the specificity of IGRA was 97.7% and was more specific than the TST in participants that have had BCG vaccine.
The conformity level in this study is consistent with previous studies, such as the study by Lamberti et al., who obtained κ = 0, 28 in the UK, Al Hajoj et al. who obtained κ = 0.312 in Saudi Arabia, Adams et al., with κ = 0.28 in South Africa, and Ratnatunga et al. in Sri Lanka found κ = 0.30. Taken together, the conformity level in the current study is comparable with other study and sufficiently reflects the real condition in the population.
The study limitations are it lacks of baseline profile of TB participants before LTBI before working in study place. This study also did not involve patients with AFB smear-positive active TB population as a positive control group. Finally, as a consequence of a cross-sectional methodology, the participants were only viewed at the time the study was conducted.
| Conclusion|| |
Healthcare workers exposed to active TB patients have a higher prevalence of LTBI by positive IGRA test results than the TST. TST induration ≥5 mm can be used as a cutoff point for screening tests on health workers in countries with high TB burden. Age, lower education, smoking and have not received BCG vaccination were the risk factors of LTBI in health workers.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
World Health Organization: Global Tuberculosis Report 2017. Geneva: World Health Organization; 2015. p. 7-10.
World Health Organization. Global Tuberculosis Report 2013. Geneva: World Health Organization; 2013. p. 3-15.
Center for Disease Control Division of Tuberculosis Elimination. Latent tuberculosis infection: A guide for primary health care providers. Cent Dis Control 2013;49:6.
World Health Organization. The Sixteenth Global Report on Tuberculosis 2011. Geneva: World Health Organization; 2011. p. 1-20.
Adams S, Ehrlich R, Baatjies R, van Zyl-Smit RN, Said-Hartley Q, Dawson R, et al.
Incidence of occupational latent tuberculosis infection in South African healthcare workers. Eur Respir J 2015;45:1364-73.
Torres Costa J, Sá R, Cardoso MJ, Silva R, Ferreira J, Ribeiro C, et al.
Tuberculosis screening in portuguese healthcare workers using the tuberculin skin test and the interferon-gamma release assay. Eur Respir J 2009;34:1423-8.
Martin U, Hasibuan P. Prevalensi TB laten pada petugas kesehatan di RSUP H. Adam Malik Medan. J Respir Indo 2010;30:112-8.
Drobniewski F, Balabanova Y, Zakamova E, Nikolayevskyy V, Fedorin I. Rates of latent tuberculosis in health care staff in Russia. PLoS Med 2007;4:e55.
Grodzińska-Jurczak M. The relation between education, knowledge and action for better waste management in Poland. Waste Manag Res 2003;21:2-18.
Chan PC, Yang CH, Chang LY, Wang KF, Kuo YC, Lin CJ, et al.
Lower prevalence of tuberculosis infection in BCG vaccinees: A cross-sectional study in adult prison inmates. Thorax 2013;68:263-8.
Horne DJ, Campo M, Ortiz JR, Oren E, Arentz M, Crothers K, et al.
Association between smoking and latent tuberculosis in the U.S. Population: An analysis of the national health and nutrition examination survey. PLoS One 2012;7:e49050.
Lindsay RP, Shin SS, Garfein RS, Rusch ML, Novotny TE. The association between active and passive smoking and latent tuberculosis infection in adults and children in the United States: Results from NHANES. PLoS One 2014;9:e93137.
Ryadinency R, Hadju V, Syam A. Macro-nutrient intake, infectious diseases and 6-7 year old children growth status in the final disposal area of Makasar city. Media Gizi Masyarakat Indones 2012;2:49-53.
Harada N, Nakajima Y, Higuchi K, Sekiya Y, Rothel J, Mori T, et al.
Screening for tuberculosis infection using whole-blood interferon-gamma and mantoux testing among Japanese healthcare workers. Infect Control Hosp Epidemiol 2006;27:442-8.
Pai M, Gokhale K, Joshi R, Dogra S, Kalantri S, Mendiratta DK, et al.
Mycobacterium tuberculosis infection in health care workers in rural India, comparison of a whole-blood interferon γ release assay with tuberculin skin testing. JAMA. 2005;293:2746-55
Plitt SS, Soskolne CL, Fanning EA, Newman SC. Prevalence and determinants of tuberculin reactivity among physicians in Edmonton, Canada: 1996-1997. Int J Epidemiol 2001;30:1022-8.
Lamberti M, Uccello R, Monaco MG, Muoio M, Feola D, Sannolo N, et al.
Tuberculin skin test and quantiferon test agreement and influencing factors in tuberculosis screening of healthcare workers: A systematic review and meta-analysis. J Occup Med Toxicol 2015;10:2.
Al Hajoj S, Varghese B, Datijan A, Shoukri M, Alzahrani A, Alkhenizan A, et al.
Interferon gamma release assay versus tuberculin skin testing among healthcare workers of highly diverse origin in a moderate tuberculosis burden country. PLoS One 2016;11:e0154803.
Ratnatunga CN, Thevanesam V, Nandadeva D, Madegedara D, Kumara KG. Cross-sectional screening of healthcare workers at a regional chest clinic with an interferon gamma release assay: Frist report from Sri Lanka. Eur Respir J 2014;44 Suppl 58:2680-5.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]