The Diagnostic Value of Urinary Secretory Antigen Target of 6 kDa in Childhood Pulmonary Tuberculosis

Agustin Iskandar; Ella Melissa  Lawanto; Maimun Zulhaidah; Ery  Olivianto; Kusworini  Handono; Muhammad  Anshory; Andrea  Aprilia; Aryati Aryati

doi:10.3889/oamjms.2021.6558

Authors

Agustin Iskandar Department of Clinical Pathology and Parasitology
Ella Melissa Lawanto Department of Clinical Pathology and Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
Maimun Zulhaidah Department of Clinical Pathology and Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
Ery Olivianto Department of Child Health, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
Kusworini Handono Department of Clinical Pathology and Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
Muhammad Anshory Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
Andrea Aprilia Department of Clinical Pathology and Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
Aryati Aryati Department of Clinical Pathology, Faculty of Medicine, Airlangga University, Surabaya, Indonesia https://orcid.org/0000-0002-9383-6354

DOI:

https://doi.org/10.3889/oamjms.2021.6558

Keywords:

Antigen, Tuberculosis, Childhood, Urinary early secretory target of 6 kDa antigen

Abstract

Introduction. Childhood tuberculosis (TB) is difficult to diagnosed and is based together on clinical and microbiology examinations. Since in children signs and symptoms of TB are not typical and sputum is difficult to be obtained, Mycobacterium tuberculosis (Mtb) antigen detection could be considered as a non invasive method for early detection of childhood TB. ESAT-6 is a low molecular weight specific protein that plays an important role in Mtb virulence.

Aim. To determine the diagnostic value of urinary ESAT-6 for the diagnosis of childhood tuberculosis.

Methodology.This was a cross-sectional study, with consecutive sampling collection . in children aging between 0-14 years suspected for pulmonary TB based on the clinical presence of :cough lasting more than 2 weeks, fever without clear ethiology, loss of body weight or poor weight gain, fatigue, malaise with positive history of contact with sputum smear from adult TB patients. Diagnosis of pulmonary TB was based on clinical presentation plus tuberculin positive skin test, chest x-ray, AFB staining and/or sputum culture. Subjects who met the inclusion criteria but unconfirmed by clinical and microbiological were considered as control (non-TB group). Urinary ESAT-6 level was analyzed by using ELISA. Cut off value and AUC was determined using ROC Statistical Analysis (SPSS 20.0). Sensitivity and specificity was measured from 2x2 crosstable.

Result. Between the 61 studied children with suspected TB, 46/61 (75%) were finally diagnosed with TB, with 34/46 (74%) microbiologically confirmed cases either by sputum microscopy 31/34 (91%) or culture 3/34 (9%), whereas 15/61 (25%) subjects were not-confirmed cases (non-TB group). The mean value of urinary ESAT-6 level was higher in TB than non-TB group, Mean (SD) [4.855(6.714)] ng/mLvs [1.503(0.946)] ng/mL; p=<0.001(Mann-Whitney test). At ROC curve analysis ,the cut off value of urinary ESAT-6 in subjects TB confirmed both with clinical plus microbiology evaluation as reference standard was 1,91 ng/mL, with sensitivity 72% and specificity 67%. While the cut off value of ESAT-6 in TB subjects confirmed group only by clinical signs was 2.45 ng/mL, with sensitivity 65% and specificity 67%.

Conclusion. For TB Diagnosis in Children, Urinary ESAT-6 urine could be considered of value when utilized in addition to microbiological tests and clinical examination.

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References

Chakaya J, Khan M, Ntoumi F, Aklillu E, Fatima R, Mwaba P, et al. Global tuberculosis report 2020-reflections on the global TB burden, treatment and prevention efforts. Int J Infect Dis. 2021;S1201-9712(21)00193-4. https://doi.org/10.1016/j.ijid.2021.02.107 DOI: https://doi.org/10.1016/j.ijid.2021.02.107

Indonesian Ministry of Health. Technical Guidelines for Management of TB Children. Jakarta: Indonesian Ministry of Health; 2013.

Indonesia IDA. Diagnosis dan Tatalaksana Tuberkulosis Anak. Jakarta: Indonesian Ministry of Health; 2008.

Jahromi MK, Sharifi-Mood B. Pulmonary tuberculosis in children. Int J Infect. 2014;1(3):e21116. DOI: https://doi.org/10.17795/iji-21116

Triasih R, Graham SM. Limitations of the Indonesian pediatric tuberculosis scoring system in the context of child contact investigation. Paediatr Indones. 2011;51(6):332-7. https://doi.org/10.14238/pi51.6.2011.332-7 DOI: https://doi.org/10.14238/pi51.6.2011.332-7

Tucci P, González-Sapienza G, Marin M. Pathogen-derived biomarkers for active tuberculosis diagnosis. Front Microbiol. 2014;5:549. https://doi.org/10.3389/fmicb.2014.00549 PMid:25368609 DOI: https://doi.org/10.3389/fmicb.2014.00549

Maes RF. Was the WHO ban on TB serodiagnosis justified? Sci J Med Clin Trials. 2013;2013:292.

Ganguly N, Sharma P. Mycobacterium tuberculosis RD-1 Secreted Antigens as Protective and Risk Factors for Tuberculosis. Germany: BoD-Books on Demand; 2012. https://doi.org/10.5772/30532 DOI: https://doi.org/10.5772/30532

Holechek MJ. Glomerular filtration: An overview. Nephrol Nurs J. 2003;30(3):285. PMid:12861896

Van Pinxteren LA, Ravn P, Agger EM, Pollock J, Andersen P. Diagnosis of tuberculosis based on the two specific antigens ESAT-6 and CFP10. Clin Diagn Lab Immunol. 2000;7(2):155-60. https://doi.org/10.1128/cdli.7.2.155-160.2000 PMid:10702486 DOI: https://doi.org/10.1128/CDLI.7.2.155-160.2000

Mukundan H, Kumar S, Price DN, Ray SM, Lee YJ, Min S, et al. Rapid detection of Mycobacterium tuberculosis biomarkers in a sandwich immunoassay format using a waveguide-based optical biosensor. Tuberculosis. 2012;92(5):407-16. https://doi.org/10.1016/j.tube.2012.05.009 PMid:22710249 DOI: https://doi.org/10.1016/j.tube.2012.05.009

Song F, Sun X, Wang X, Nai Y, Liu Z. Early diagnosis of tuberculous meningitis by an indirect ELISA protocol based on the detection of the antigen ESAT-6 in cerebrospinal fluid. Ir J Med Sci. 2014;183(1):85-8. https://doi.org/10.1007/s11845-013-0980-4 PMid:23864405 DOI: https://doi.org/10.1007/s11845-013-0980-4

Nayak S, Acharjya B. Mantoux test and its interpretation. Indian Dermatol Online J. 2012;3(1):2-6. https://doi.org/10.4103/2229-5178.93479 PMid:23130251 DOI: https://doi.org/10.4103/2229-5178.93479

Product BL, Human M. Tuberculosis 6kDa/ESAT-6 ELISA Kit. Catalog No E3493Hu. Shanghai: Shanghai Crystal Day Biotech Co., Ltd.; 2016.

Chow SC. Sample Size and Determining Sample in Medical Research. 2nd ed. Jakarta: Salemba Medika; 2009. p. 84-5.

López Ávalos GG, Prado Montes de Oca E. Classic and new diagnostic approaches to childhood tuberculosis. J Trop Med. 2012;2012:18219. https://doi.org/10.1155/2012/818219 PMid:22529869 DOI: https://doi.org/10.1155/2012/818219

World Health Organization. Global Tuberculosis Report 2013. Geneva: World Health Organization; 2013.

Wootton SH, Gonzalez BE, Pawlak R, Teeter LD, Smith KC, Musser JM, et al. Epidemiology of pediatric tuberculosis using traditional and molecular techniques: Houston, Texas. Pediatrics. 2005;116(5):1141-7. https://doi.org/10.1542/peds.2004-2701 PMid:16264001 DOI: https://doi.org/10.1542/peds.2004-2701

Ahmad S. Pathogenesis, immunology, and diagnosis of latent Mycobacterium tuberculosis infection. Clin Dev Immunol. 2011;2011:814943. PMid:21234341

Kashino S, Pollock N, Napolitano D, Rodrigues V Jr., Campos-Neto A. Identification and characterization of Mycobacterium tuberculosis antigens in urine of patients with active pulmonary tuberculosis: An innovative and alternative approach of antigen discovery of useful microbial molecules. Clin Exp Immunol. 2008;153(1):56-62. https://doi.org/10.1111/j.1365-2249.2008.03672.x PMid:18460016 DOI: https://doi.org/10.1111/j.1365-2249.2008.03672.x