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Published in: BMC Pediatrics 1/2021

01-12-2021 | Tuberculosis | Research article

Diagnosis of latent tuberculosis infection among pediatric household contacts of Iranian tuberculosis cases using tuberculin skin test, IFN- γ release assay and IFN-γ-induced protein-10

Authors: Roxana Mansour Ghanaie, Abdollah Karimi, Leila Azimi, Seddon James, Mahshid Nasehi, Abolfazl Panahi Mishkar, Mahnaz Sheikhi, Fatemeh Fallah, Sedigheh Rafiei Tabatabaei, Seyedeh Mahsan Hoseini-Alfatemi

Published in: BMC Pediatrics | Issue 1/2021

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Abstract

Background

Although the World Health Organization has recommended the diagnosis and prophylactic treatment of latent tuberculous infection (LTBI) in child household contacts of tuberculosis (TB) cases, the national programs in high-burden TB regions rarely implement adequate screening of this high-risk group, mainly because of resource limitations. We aimed to evaluate the prevalence of LTBI among pediatric household contacts of TB cases in two high-burden provinces in Iran.

Methods

We conducted a cohort study in children who had been in household contact with a TB index. All subjects were assessed for active TB disease. For LTBI diagnosis, tuberculin skin test (TST) and QuantiFERON®-TB Gold Plus (QFT-Plus) were performed at the time of the index TB case diagnosis, as well as, 3, 12, and 18 months, if the first results were negative. In addition, interferon-γ-induced protein-10(IP-10) concentrations were measured for all participants.

Results

A total of 230 children were enrolled, who had contact with an index TB case. Three contacts were diagnosed with active TB. According to the TST/QFT-Plus results, 104 (45.2%) children were identified with LTBI during our study. Significantly increased IP-10 levels were found in LTBI patients compared to healthy contacts. Accordingly, more than 50% of LTBI contacts and about 10% of healthy contacts were considered as IP-10-positive.

Conclusion

This study alarmingly illustrates a high prevalence of LTBI among Iranian children exposed to TB cases. We, therefore, emphasize that the children living in close contact with an infectious TB case should be screened effectively and receive prophylactic therapy.
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Literature
3.
go back to reference Perez-Porcuna TM, Pereira-da-Silva HD, Ascaso C, Malheiro A, Buhrer S, Martinez-Espinosa F, et al. Prevalence and diagnosis of latent tuberculosis infection in young children in the absence of a gold standard. PLoS One. 2016;11(10):e0164181.PubMedPubMedCentralCrossRef Perez-Porcuna TM, Pereira-da-Silva HD, Ascaso C, Malheiro A, Buhrer S, Martinez-Espinosa F, et al. Prevalence and diagnosis of latent tuberculosis infection in young children in the absence of a gold standard. PLoS One. 2016;11(10):e0164181.PubMedPubMedCentralCrossRef
4.
go back to reference Organization WH. Global tuberculosis report 2013. Geneva: WHO. 23 Oct; 2013; 2019. Organization WH. Global tuberculosis report 2013. Geneva: WHO. 23 Oct; 2013; 2019.
5.
go back to reference Lönnroth K, Migliori GB, Abubakar I, D'Ambrosio L, de Vries G, Diel R, et al. Towards tuberculosis elimination: an action framework for low-incidence countries. Eur Respir J. 2015;45(4):928–52.PubMedPubMedCentralCrossRef Lönnroth K, Migliori GB, Abubakar I, D'Ambrosio L, de Vries G, Diel R, et al. Towards tuberculosis elimination: an action framework for low-incidence countries. Eur Respir J. 2015;45(4):928–52.PubMedPubMedCentralCrossRef
6.
go back to reference Marais BJ, Gie RP, Schaaf HS, Hesseling AC, Obihara CC, Starke JJ, et al. The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era. Int J Tuberc Lung Dis. 2004;8(4):392–402.PubMed Marais BJ, Gie RP, Schaaf HS, Hesseling AC, Obihara CC, Starke JJ, et al. The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era. Int J Tuberc Lung Dis. 2004;8(4):392–402.PubMed
7.
go back to reference Singh M, Saini AG, Anil N, Aggarwal A. Latent tuberculosis in children: diagnosis and management. Indian J Pediatrics. 2011;78(4):464–8.CrossRef Singh M, Saini AG, Anil N, Aggarwal A. Latent tuberculosis in children: diagnosis and management. Indian J Pediatrics. 2011;78(4):464–8.CrossRef
8.
go back to reference Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol. 1974;99(2):131–8.PubMedCrossRef Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol. 1974;99(2):131–8.PubMedCrossRef
9.
go back to reference Cruz AT, Starke JR, Lobato MN. Old and new approaches to diagnosing and treating latent tuberculosis in children in low-incidence countries. Curr Opin Pediatr. 2014;26(1):106–13.PubMedPubMedCentralCrossRef Cruz AT, Starke JR, Lobato MN. Old and new approaches to diagnosing and treating latent tuberculosis in children in low-incidence countries. Curr Opin Pediatr. 2014;26(1):106–13.PubMedPubMedCentralCrossRef
10.
go back to reference Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society. MMWR Recommendations and reports: Morbidity and mortality weekly report Recommendations and reports. Am J Respir Crit Care Med. 2000;161:S221–S247. Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society. MMWR Recommendations and reports: Morbidity and mortality weekly report Recommendations and reports. Am J Respir Crit Care Med. 2000;161:S221–S247.
12.
go back to reference Cruz AT, Starke JR. Clinical manifestations of tuberculosis in children. Paediatr Respir Rev. 2007;8(2):107–17.PubMedCrossRef Cruz AT, Starke JR. Clinical manifestations of tuberculosis in children. Paediatr Respir Rev. 2007;8(2):107–17.PubMedCrossRef
13.
go back to reference Goletti D, Sanduzzi A, Delogu G. Performance of the tuberculin skin test and interferon-γ release assays: an update on the accuracy, Cutoff Stratification, and New Potential Immune-based Approaches. J Rheumatol Suppl. 2014;91:24–31.PubMedCrossRef Goletti D, Sanduzzi A, Delogu G. Performance of the tuberculin skin test and interferon-γ release assays: an update on the accuracy, Cutoff Stratification, and New Potential Immune-based Approaches. J Rheumatol Suppl. 2014;91:24–31.PubMedCrossRef
14.
go back to reference Starke JR. Interferon-γ Release Assays for Diagnosis of Tuberculosis Infection and Disease in Children. Pediatrics. 2014;134(6):e1763–e73.PubMedCrossRef Starke JR. Interferon-γ Release Assays for Diagnosis of Tuberculosis Infection and Disease in Children. Pediatrics. 2014;134(6):e1763–e73.PubMedCrossRef
15.
go back to reference Qiu X, Tang Y, Zou R, Zeng Y, Yue Y, Li W, et al. Diagnostic accuracy of interferon-gamma-induced protein 10 for differentiating active tuberculosis from latent tuberculosis: a meta-analysis. Sci Rep. 2019;9(1):11408.PubMedPubMedCentralCrossRef Qiu X, Tang Y, Zou R, Zeng Y, Yue Y, Li W, et al. Diagnostic accuracy of interferon-gamma-induced protein 10 for differentiating active tuberculosis from latent tuberculosis: a meta-analysis. Sci Rep. 2019;9(1):11408.PubMedPubMedCentralCrossRef
16.
go back to reference Sollai S, Galli L, de Martino M, Chiappini E. Systematic review and meta-analysis on the utility of interferon-gamma release assays for the diagnosis of mycobacterium tuberculosis finfection in children: a 2013 update. BMC Infect Dis. 2014;14(1):S6.PubMedPubMedCentralCrossRef Sollai S, Galli L, de Martino M, Chiappini E. Systematic review and meta-analysis on the utility of interferon-gamma release assays for the diagnosis of mycobacterium tuberculosis finfection in children: a 2013 update. BMC Infect Dis. 2014;14(1):S6.PubMedPubMedCentralCrossRef
17.
go back to reference Goletti D, Lee M-R, Wang J-Y, Walter N, Ottenhoff THM. Update on tuberculosis biomarkers: From correlates of risk, to correlates of active disease and of cure from disease. Respirology. 2018;23(5):455–66.PubMedCrossRef Goletti D, Lee M-R, Wang J-Y, Walter N, Ottenhoff THM. Update on tuberculosis biomarkers: From correlates of risk, to correlates of active disease and of cure from disease. Respirology. 2018;23(5):455–66.PubMedCrossRef
18.
go back to reference Petrone L, Vanini V, Chiacchio T, Petruccioli E, Cuzzi G, Schinina V, et al. Evaluation of IP-10 in Quantiferon-Plus as biomarker for the diagnosis of latent tuberculosis infection. Tuberculosis (Edinburgh, Scotland). 2018;111:147–53.CrossRef Petrone L, Vanini V, Chiacchio T, Petruccioli E, Cuzzi G, Schinina V, et al. Evaluation of IP-10 in Quantiferon-Plus as biomarker for the diagnosis of latent tuberculosis infection. Tuberculosis (Edinburgh, Scotland). 2018;111:147–53.CrossRef
19.
go back to reference Rozot V, Vigano S, Mazza-Stalder J, Idrizi E, Day CL, Perreau M, et al. Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease. Eur J Immunol. 2013;43(6):1568–77.PubMedPubMedCentralCrossRef Rozot V, Vigano S, Mazza-Stalder J, Idrizi E, Day CL, Perreau M, et al. Mycobacterium tuberculosis-specific CD8+ T cells are functionally and phenotypically different between latent infection and active disease. Eur J Immunol. 2013;43(6):1568–77.PubMedPubMedCentralCrossRef
20.
go back to reference Petruccioli E, Chiacchio T, Pepponi I, Vanini V, Urso R, Cuzzi G, et al. First characterization of the CD4 and CD8 T-cell responses to QuantiFERON-TB plus. J Inf Secur. 2016;73(6):588–97. Petruccioli E, Chiacchio T, Pepponi I, Vanini V, Urso R, Cuzzi G, et al. First characterization of the CD4 and CD8 T-cell responses to QuantiFERON-TB plus. J Inf Secur. 2016;73(6):588–97.
21.
go back to reference Petrone L, Cannas A, Vanini V, Cuzzi G, Aloi F, Nsubuga M, et al. Blood and urine inducible protein 10 as potential markers of disease activity. Int J Tuberc Lung Dis. 2016;20(11):1554–61.PubMedCrossRef Petrone L, Cannas A, Vanini V, Cuzzi G, Aloi F, Nsubuga M, et al. Blood and urine inducible protein 10 as potential markers of disease activity. Int J Tuberc Lung Dis. 2016;20(11):1554–61.PubMedCrossRef
22.
go back to reference Yassin MA, Petrucci R, Garie KT, Harper G, Teshome A, Arbide I, et al. Use of tuberculin skin test, IFN-gamma release assays and IFN-gamma-induced protein-10 to identify children with TB infection. Eur Respir J. 2013;41(3):644–8.PubMedCrossRef Yassin MA, Petrucci R, Garie KT, Harper G, Teshome A, Arbide I, et al. Use of tuberculin skin test, IFN-gamma release assays and IFN-gamma-induced protein-10 to identify children with TB infection. Eur Respir J. 2013;41(3):644–8.PubMedCrossRef
23.
go back to reference Petruccioli E, Vanini V, Chiacchio T, Cuzzi G, Cirillo DM, Palmieri F, et al. Analytical evaluation of QuantiFERON- plus and QuantiFERON- gold in-tube assays in subjects with or without tuberculosis. Tuberculosis. 2017;106:38–43.PubMedCrossRef Petruccioli E, Vanini V, Chiacchio T, Cuzzi G, Cirillo DM, Palmieri F, et al. Analytical evaluation of QuantiFERON- plus and QuantiFERON- gold in-tube assays in subjects with or without tuberculosis. Tuberculosis. 2017;106:38–43.PubMedCrossRef
24.
go back to reference Yassin MA, Petrucci R, Garie KT, Harper G, Arbide I, Aschalew M, et al. Can interferon-gamma or interferon-gamma-induced-protein-10 differentiate tuberculosis infection and disease in children of high endemic areas? PLoS One. 2011;6(9):e23733.PubMedPubMedCentralCrossRef Yassin MA, Petrucci R, Garie KT, Harper G, Arbide I, Aschalew M, et al. Can interferon-gamma or interferon-gamma-induced-protein-10 differentiate tuberculosis infection and disease in children of high endemic areas? PLoS One. 2011;6(9):e23733.PubMedPubMedCentralCrossRef
25.
go back to reference Organization WH. WHO. Guidance for National Tuberculosis Programmes on the Management of Tuberculosis in Children. Geneva: World Health Organization; 2014. Accessed 26 July 2017 Organization WH. WHO. Guidance for National Tuberculosis Programmes on the Management of Tuberculosis in Children. Geneva: World Health Organization; 2014. Accessed 26 July 2017
26.
go back to reference van Wyk SS, Reid AJ, Mandalakas AM, Enarson DA, Beyers N, Morrison J, et al. Operational challenges in managing isoniazid preventive therapy in child contacts: a high-burden setting perspective. BMC Public Health. 2011;11(1):544.PubMedPubMedCentralCrossRef van Wyk SS, Reid AJ, Mandalakas AM, Enarson DA, Beyers N, Morrison J, et al. Operational challenges in managing isoniazid preventive therapy in child contacts: a high-burden setting perspective. BMC Public Health. 2011;11(1):544.PubMedPubMedCentralCrossRef
27.
go back to reference Morrison J, Pai M, Hopewell PC. Tuberculosis and latent tuberculosis infection in close contacts of people with pulmonary tuberculosis in low-income and middle-income countries: a systematic review and meta-analysis. Lancet Infect Dis. 2008;8(6):359–68.PubMedCrossRef Morrison J, Pai M, Hopewell PC. Tuberculosis and latent tuberculosis infection in close contacts of people with pulmonary tuberculosis in low-income and middle-income countries: a systematic review and meta-analysis. Lancet Infect Dis. 2008;8(6):359–68.PubMedCrossRef
28.
go back to reference Fox GJ, Barry SE, Britton WJ, Marks GB. Contact investigation for tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2013;41(1):140–56.PubMedCrossRef Fox GJ, Barry SE, Britton WJ, Marks GB. Contact investigation for tuberculosis: a systematic review and meta-analysis. Eur Respir J. 2013;41(1):140–56.PubMedCrossRef
29.
go back to reference Nguyen TH, Odermatt P, Slesak G, Barennes H. Risk of latent tuberculosis infection in children living in households with tuberculosis patients: a cross sectional survey in remote northern Lao People's Democratic Republic. BMC Infect Dis. 2009;9:96.PubMedPubMedCentralCrossRef Nguyen TH, Odermatt P, Slesak G, Barennes H. Risk of latent tuberculosis infection in children living in households with tuberculosis patients: a cross sectional survey in remote northern Lao People's Democratic Republic. BMC Infect Dis. 2009;9:96.PubMedPubMedCentralCrossRef
30.
go back to reference Shamaei M, Esmaeili S, Marjani M, Tabarsi P. Implementing Tuberculosis Close-contact Investigation in a Tertiary Hospital in Iran. Int J Prev Med. 2018;9:48.PubMedPubMedCentralCrossRef Shamaei M, Esmaeili S, Marjani M, Tabarsi P. Implementing Tuberculosis Close-contact Investigation in a Tertiary Hospital in Iran. Int J Prev Med. 2018;9:48.PubMedPubMedCentralCrossRef
31.
go back to reference Lee E, Holzman RS. Evolution and current use of the tuberculin test. Clin Infect Dis. 2002;34(3):365–70.PubMedCrossRef Lee E, Holzman RS. Evolution and current use of the tuberculin test. Clin Infect Dis. 2002;34(3):365–70.PubMedCrossRef
32.
go back to reference Seyhan EC, Gunluoglu G, Gunluoglu MZ, Tural S, Sökücü S. Predictive value of the tuberculin skin test and QuantiFERON-tuberculosis gold in-tube test for development of active tuberculosis in hemodialysis patients. Ann Thorac Med. 2016;11(2):114–20.PubMedPubMedCentralCrossRef Seyhan EC, Gunluoglu G, Gunluoglu MZ, Tural S, Sökücü S. Predictive value of the tuberculin skin test and QuantiFERON-tuberculosis gold in-tube test for development of active tuberculosis in hemodialysis patients. Ann Thorac Med. 2016;11(2):114–20.PubMedPubMedCentralCrossRef
33.
go back to reference Denkinger CM, Dheda K, Pai M. Guidelines on interferon-gamma release assays for tuberculosis infection: concordance, discordance or confusion? Clin Microbiol Infect Dis. 2011;17(6):806–14.CrossRef Denkinger CM, Dheda K, Pai M. Guidelines on interferon-gamma release assays for tuberculosis infection: concordance, discordance or confusion? Clin Microbiol Infect Dis. 2011;17(6):806–14.CrossRef
34.
go back to reference Mandalakas AM, Detjen AK, Hesseling AC. Can we accurately diagnose tuberculosis infection in children? Pediatr Infect Dis J. 2011;30(9):817–8.PubMedCrossRef Mandalakas AM, Detjen AK, Hesseling AC. Can we accurately diagnose tuberculosis infection in children? Pediatr Infect Dis J. 2011;30(9):817–8.PubMedCrossRef
35.
go back to reference Hill PC, Brookes RH, Fox A, Jackson-Sillah D, Jeffries DJ, Lugos MD, et al. Longitudinal assessment of an ELISPOT test for mycobacterium tuberculosis infection. PLoS Med. 2007;4(6):e192.PubMedPubMedCentralCrossRef Hill PC, Brookes RH, Fox A, Jackson-Sillah D, Jeffries DJ, Lugos MD, et al. Longitudinal assessment of an ELISPOT test for mycobacterium tuberculosis infection. PLoS Med. 2007;4(6):e192.PubMedPubMedCentralCrossRef
36.
go back to reference Zwerling A, Pai M, Michael JS, Christopher DJ. Serial testing using interferon-γ release assays in nursing students in India. Eur Respir J. 2014;44(1):257–60.PubMedCrossRef Zwerling A, Pai M, Michael JS, Christopher DJ. Serial testing using interferon-γ release assays in nursing students in India. Eur Respir J. 2014;44(1):257–60.PubMedCrossRef
37.
go back to reference Lee SS, Liu YC, Huang TS, Chen YS, Tsai HC, Wann SR, et al. Comparison of the interferon- gamma release assay and the tuberculin skin test for contact investigation of tuberculosis in BCG-vaccinated health care workers. Scand J Infect Dis. 2008;40(5):373–80.PubMedCrossRef Lee SS, Liu YC, Huang TS, Chen YS, Tsai HC, Wann SR, et al. Comparison of the interferon- gamma release assay and the tuberculin skin test for contact investigation of tuberculosis in BCG-vaccinated health care workers. Scand J Infect Dis. 2008;40(5):373–80.PubMedCrossRef
38.
go back to reference 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 (London, England). 2003;361(9364):1168–73.CrossRef 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 (London, England). 2003;361(9364):1168–73.CrossRef
39.
go back to reference Brock I, Weldingh K, Lillebaek 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(1):65–9.PubMedCrossRef Brock I, Weldingh K, Lillebaek 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(1):65–9.PubMedCrossRef
40.
go back to reference Biraro IA, Kimuda S, Egesa M, Cose S, Webb EL, Joloba M, et al. The Use of Interferon Gamma Inducible Protein 10 as a Potential Biomarker in the Diagnosis of Latent Tuberculosis Infection in Uganda. PLoS One. 2016;11(1):e0146098-e.CrossRef Biraro IA, Kimuda S, Egesa M, Cose S, Webb EL, Joloba M, et al. The Use of Interferon Gamma Inducible Protein 10 as a Potential Biomarker in the Diagnosis of Latent Tuberculosis Infection in Uganda. PLoS One. 2016;11(1):e0146098-e.CrossRef
41.
go back to reference Petrone L, Chiacchio T, Vanini V, Petruccioli E, Cuzzi G, Di Giacomo C, et al. High urine IP-10 levels associate with chronic HCV infection. J Infect. 2014;68(6):591–600.PubMedCrossRef Petrone L, Chiacchio T, Vanini V, Petruccioli E, Cuzzi G, Di Giacomo C, et al. High urine IP-10 levels associate with chronic HCV infection. J Infect. 2014;68(6):591–600.PubMedCrossRef
42.
go back to reference Aabye MG, Eugen-Olsen J, Werlinrud AM, Holm LL, Tuuminen T, Ravn P, et al. A simple method to quantitate IP-10 in dried blood and plasma spots. PLoS One. 2012;7(6):e39228-e.CrossRef Aabye MG, Eugen-Olsen J, Werlinrud AM, Holm LL, Tuuminen T, Ravn P, et al. A simple method to quantitate IP-10 in dried blood and plasma spots. PLoS One. 2012;7(6):e39228-e.CrossRef
43.
go back to reference Whittaker E, Gordon A, Kampmann B. Is IP-10 a better biomarker for active and latent tuberculosis in children than IFNgamma? PLoS One. 2008;3(12):e3901-e.CrossRef Whittaker E, Gordon A, Kampmann B. Is IP-10 a better biomarker for active and latent tuberculosis in children than IFNgamma? PLoS One. 2008;3(12):e3901-e.CrossRef
Metadata
Title
Diagnosis of latent tuberculosis infection among pediatric household contacts of Iranian tuberculosis cases using tuberculin skin test, IFN- γ release assay and IFN-γ-induced protein-10
Authors
Roxana Mansour Ghanaie
Abdollah Karimi
Leila Azimi
Seddon James
Mahshid Nasehi
Abolfazl Panahi Mishkar
Mahnaz Sheikhi
Fatemeh Fallah
Sedigheh Rafiei Tabatabaei
Seyedeh Mahsan Hoseini-Alfatemi
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2021
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-021-02524-3

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