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Published in: Indian Journal of Pediatrics 5/2019

01-05-2019 | Tuberculosis | Review Article

Newer Diagnostic Tests and their Application in Pediatric TB

Authors: Chand Wattal, Reena Raveendran

Published in: Indian Journal of Pediatrics | Issue 5/2019

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Abstract

The diagnosis of childhood tuberculosis is a challenge due to the pauci-bacillary nature of infection and the difficulty in obtaining appropriate sample. In the past 2–3 decades, many new tests were introduced for the diagnosis of tuberculosis (TB) and some of them have been evaluated for their application in pediatric tuberculosis as well. There is an attempt to improve smear microscopy by introducing light-emitting diode (LED) fluorescence microscopy and there are also some automated digital microscopy platforms under evaluation. Introduction of automated liquid culture platform along with rapid molecular based identification methods have considerably reduced the time delay in mycobacterial culture. Recent addition of many nucleic acid amplification platforms like Amplicor PCR, Genprobe, Xpert MTB/Rif, line probe assays, loop mediated isothermal amplification etc are also been found to be useful. Latest techniques like microarray and gene sequencing are also being used in clinical laboratories with variable results. Indirect methods of TB diagnosis like T cell based assays including tuberculin skin test and interferon-gamma release assays have their role primarily in the diagnosis of latent TB. Biomarkers are the latest addition in the battery of TB diagnostic tests facilitating diagnosis using easily accessible samples like urine, blood and breath of patients. Many biomarkers are still under evaluation and some of them are found to have a potential role as promising diagnostic tests of future.
Literature
1.
go back to reference Fluorescent Light-Emitting Diode (LED) Microscopy for Diagnosis of Tuberculosis: Policy Statement. Geneva: World Health Organisation; 2011 (WHO/HTM/TB/2011.8). Fluorescent Light-Emitting Diode (LED) Microscopy for Diagnosis of Tuberculosis: Policy Statement. Geneva: World Health Organisation; 2011 (WHO/HTM/TB/2011.8).
3.
go back to reference Gómez-Pastrana Durán D, Torronteras Santiago R, Caro Mateo P, et al. Effectiveness of smears and cultures in gastric aspirate simples in the diagnosis of tuberculosis. An Esp Pediatr (Barc). 2000;53:405–11. Gómez-Pastrana Durán D, Torronteras Santiago R, Caro Mateo P, et al. Effectiveness of smears and cultures in gastric aspirate simples in the diagnosis of tuberculosis. An Esp Pediatr (Barc). 2000;53:405–11.
4.
go back to reference Tuberculosis Diagnostic Technology Landscape, 5th ed, May 2017. Geneva:UNITAID Secretariat, World Health Organization. Available at: unitaid@who.int Tuberculosis Diagnostic Technology Landscape, 5th ed, May 2017. Geneva:UNITAID Secretariat, World Health Organization. Available at: unitaid@who.int
5.
go back to reference Singh M, Moosa NV, Kumar L, Sharma M. Role of gastric lavage and broncho-alveolar lavage in the bacteriological diagnosis of childhood pulmonary tuberculosis. Indian Pediatr. 2000;37:947–51.PubMed Singh M, Moosa NV, Kumar L, Sharma M. Role of gastric lavage and broncho-alveolar lavage in the bacteriological diagnosis of childhood pulmonary tuberculosis. Indian Pediatr. 2000;37:947–51.PubMed
6.
go back to reference Cruz AT, Starke JR. Clinical manifestations of TB in children. Pediatr Respir Rev. 2007;8:107–17.CrossRef Cruz AT, Starke JR. Clinical manifestations of TB in children. Pediatr Respir Rev. 2007;8:107–17.CrossRef
7.
go back to reference Eamranond P, Jaramaillo E. Tuberculosis in children: reassessing the need for improved diagnosis in global control strategies. Int J Tuberc Lung Dis. 2001;5:594–603.PubMed Eamranond P, Jaramaillo E. Tuberculosis in children: reassessing the need for improved diagnosis in global control strategies. Int J Tuberc Lung Dis. 2001;5:594–603.PubMed
8.
go back to reference Marais BJ, Hesseling AC, Gie RP, Schaaf HS, Enarson DA, Beyers N. The bacteriologic yield in children with intrathoracic tuberculosis. Clin Infect Dis. 2006;42:e69–71.CrossRefPubMed Marais BJ, Hesseling AC, Gie RP, Schaaf HS, Enarson DA, Beyers N. The bacteriologic yield in children with intrathoracic tuberculosis. Clin Infect Dis. 2006;42:e69–71.CrossRefPubMed
9.
go back to reference Baghaei P, Tabarsi P, Farnia P, et al. Utility of gastric lavage for diagnosis of tuberculosis in patients who are unable to expectorate sputum. J Global Infect Dis. 2011;3:339–43.CrossRef Baghaei P, Tabarsi P, Farnia P, et al. Utility of gastric lavage for diagnosis of tuberculosis in patients who are unable to expectorate sputum. J Global Infect Dis. 2011;3:339–43.CrossRef
10.
go back to reference Cruz AT, Revell PA, Starke JR. Gastric aspirate yield for children with suspected pulmonary tuberculosis. J Pediatric Infect Dis Soc. 2013;2:171–4.CrossRefPubMed Cruz AT, Revell PA, Starke JR. Gastric aspirate yield for children with suspected pulmonary tuberculosis. J Pediatric Infect Dis Soc. 2013;2:171–4.CrossRefPubMed
11.
go back to reference Owens S, Abdel-Rahman IE, Balyejusa S, et al. Nasopharyngeal aspiration for diagnosis of pulmonary tuberculosis. Arch Dis Child. 2007;92:693–6.CrossRefPubMed Owens S, Abdel-Rahman IE, Balyejusa S, et al. Nasopharyngeal aspiration for diagnosis of pulmonary tuberculosis. Arch Dis Child. 2007;92:693–6.CrossRefPubMed
12.
go back to reference Franchi LM, Cama RI, Gilman RH, Montenegro-James S, Sheen P. Detection of Mycobacterium tuberculosis in nasopharyngeal aspirate samples in children. Lancet. 1998;352:1681–2.CrossRefPubMed Franchi LM, Cama RI, Gilman RH, Montenegro-James S, Sheen P. Detection of Mycobacterium tuberculosis in nasopharyngeal aspirate samples in children. Lancet. 1998;352:1681–2.CrossRefPubMed
13.
go back to reference Swaminathan S, Rekha B. Pediatric tuberculosis: global overview and challenges. Clin Infect Dis. 2010;50:S184–94.CrossRefPubMed Swaminathan S, Rekha B. Pediatric tuberculosis: global overview and challenges. Clin Infect Dis. 2010;50:S184–94.CrossRefPubMed
14.
go back to reference Zar HJ, Hanslo D, Apolles P, Swingler G, Hussey G. Induced sputum versus gastric lavage for microbiological confirmation of pulmonary tuberculosis in infants and young children: a prospective study. Lancet. 2005;365:130–4.CrossRefPubMed Zar HJ, Hanslo D, Apolles P, Swingler G, Hussey G. Induced sputum versus gastric lavage for microbiological confirmation of pulmonary tuberculosis in infants and young children: a prospective study. Lancet. 2005;365:130–4.CrossRefPubMed
15.
go back to reference Abadco DL, Steiner P. Gastric lavage is better than bronchoalveolar lavage for isolation of Mycobacterium tuberculosis in childhood pulmonary tuberculosis. Pediatr Infect Dis J. 1992;11:735–8.CrossRefPubMed Abadco DL, Steiner P. Gastric lavage is better than bronchoalveolar lavage for isolation of Mycobacterium tuberculosis in childhood pulmonary tuberculosis. Pediatr Infect Dis J. 1992;11:735–8.CrossRefPubMed
16.
go back to reference Menon PR, Lodha R, Singh U, Kabra SK. A prospective assessment of the role of bronchoscopy and bronchoalveolar lavage in evaluation of children with pulmonary tuberculosis. J Trop Pediatr. 2011;57:363–7. Menon PR, Lodha R, Singh U, Kabra SK. A prospective assessment of the role of bronchoscopy and bronchoalveolar lavage in evaluation of children with pulmonary tuberculosis. J Trop Pediatr. 2011;57:363–7.
17.
go back to reference Goussard P, Gie RP, Kling S, et al. The diagnostic value and safety of transbronchial needle aspiration biopsy in children with mediastinal lymphadenopathy. Pediatr Pulmonol. 2010;45:1173–9.CrossRefPubMed Goussard P, Gie RP, Kling S, et al. The diagnostic value and safety of transbronchial needle aspiration biopsy in children with mediastinal lymphadenopathy. Pediatr Pulmonol. 2010;45:1173–9.CrossRefPubMed
18.
go back to reference Wright CA, Hesseling AC, Bamford C, Burgess SM, Warren R, Marais BJ. Fine needle aspiration biopsy: a first-line diagnostic procedure in paediatric tuberculosis suspects with peripheral lymphadenopathy? Int J Tuberc Lung Dis. 2009;13:1373–9.PubMed Wright CA, Hesseling AC, Bamford C, Burgess SM, Warren R, Marais BJ. Fine needle aspiration biopsy: a first-line diagnostic procedure in paediatric tuberculosis suspects with peripheral lymphadenopathy? Int J Tuberc Lung Dis. 2009;13:1373–9.PubMed
19.
go back to reference Chow F, Espiritu N, Gilman RH, et al. La cuerdadulce—a tolerability and acceptability study of a novel approach to specimen collection for diagnosis of paediatric pulmonary tuberculosis. BMC Infect Dis. 2006;6:67.CrossRefPubMedPubMedCentral Chow F, Espiritu N, Gilman RH, et al. La cuerdadulce—a tolerability and acceptability study of a novel approach to specimen collection for diagnosis of paediatric pulmonary tuberculosis. BMC Infect Dis. 2006;6:67.CrossRefPubMedPubMedCentral
20.
21.
go back to reference Drancourt M. Please, no more gastric aspirate to diagnose pulmonary tuberculosis in children. Clin Infect Dis. 2017;65:2158 Drancourt M. Please, no more gastric aspirate to diagnose pulmonary tuberculosis in children. Clin Infect Dis. 2017;65:2158
22.
go back to reference Parsons LM, Somoskövi A, Gutierrez C, et al. Laboratory diagnosis of tuberculosis in resource poor countries: challenges and opportunities. Clin Microbiol Rev. 2011;24:314–50. Parsons LM, Somoskövi A, Gutierrez C, et al. Laboratory diagnosis of tuberculosis in resource poor countries: challenges and opportunities. Clin Microbiol Rev. 2011;24:314–50.
23.
go back to reference Singh AK, Maurya AK, Umrao J, et al. Role of GenoType(®) mycobacterium common mycobacteria/additional species assay for rapid differentiation between mycobacterium tuberculosis complex and different species of non-tuberculous mycobacteria. J Lab Physicians. 2013;5:83–9.CrossRefPubMedPubMedCentral Singh AK, Maurya AK, Umrao J, et al. Role of GenoType(®) mycobacterium common mycobacteria/additional species assay for rapid differentiation between mycobacterium tuberculosis complex and different species of non-tuberculous mycobacteria. J Lab Physicians. 2013;5:83–9.CrossRefPubMedPubMedCentral
24.
go back to reference Tuberculosis Diagnostic Technology Landscape, 2012. Geneva: UNITAID Secretariat, World Health Organization, Available at: unitaid@who.int Tuberculosis Diagnostic Technology Landscape, 2012. Geneva: UNITAID Secretariat, World Health Organization, Available at: unitaid@who.int
25.
go back to reference Gomez-Pastrana D. Tuberculosis in children—is PCR the diagnostic solution? Clin Microbiol Infect. 2002;8:541–4.CrossRefPubMed Gomez-Pastrana D. Tuberculosis in children—is PCR the diagnostic solution? Clin Microbiol Infect. 2002;8:541–4.CrossRefPubMed
26.
go back to reference Delacourt C, Poveda JD, Churean C, et al. Use of polymerase chain reaction for improved diagnosis of tuberculosis in children. J Pediatr. 1995;126:703–9.CrossRefPubMed Delacourt C, Poveda JD, Churean C, et al. Use of polymerase chain reaction for improved diagnosis of tuberculosis in children. J Pediatr. 1995;126:703–9.CrossRefPubMed
27.
go back to reference Ling DI, Zwerling AA, Pai M. GenoTypeMTBDRplus assays for the diagnosis of multidrug-resistant tuberculosis: a meta-analysis. Eur Respir J. 2008;32:1165–74.CrossRefPubMed Ling DI, Zwerling AA, Pai M. GenoTypeMTBDRplus assays for the diagnosis of multidrug-resistant tuberculosis: a meta-analysis. Eur Respir J. 2008;32:1165–74.CrossRefPubMed
28.
go back to reference World Health Organization. The Use of Molecular Line-Probe Assays for the Detection of Resistance to Second-Line Anti-Tuberculosis Drugs: Policy Guidance. Geneva: WHO; 2016. World Health Organization. The Use of Molecular Line-Probe Assays for the Detection of Resistance to Second-Line Anti-Tuberculosis Drugs: Policy Guidance. Geneva: WHO; 2016.
29.
go back to reference Theron G, Peter J, Richardson M, et al. The diagnostic accuracy of the GenoType(®) MTBDRsl assay for the detection of resistance to second-line anti-tuberculosis drugs. Cochrane Database Syst Rev. 2014;10:CD010705. Theron G, Peter J, Richardson M, et al. The diagnostic accuracy of the GenoType(®) MTBDRsl assay for the detection of resistance to second-line anti-tuberculosis drugs. Cochrane Database Syst Rev. 2014;10:CD010705.
30.
go back to reference WHO. Automated Real-time Nucleic Acid Amplification Technology for Rapid and Simultaneous Detection of Tuberculosis and Rifampicin Resistance. Xpert MTB/RIF System. Policy Statement. Geneva: World Health Organisation; 2011. WHO. Automated Real-time Nucleic Acid Amplification Technology for Rapid and Simultaneous Detection of Tuberculosis and Rifampicin Resistance. Xpert MTB/RIF System. Policy Statement. Geneva: World Health Organisation; 2011.
31.
go back to reference Nicol MP, Workman L, Isaacs W, et al. Accuracy of the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in hospitalized children in a high HIV-prevalence area. Lancet Infect Dis. 2011;11:819–24.CrossRefPubMedPubMedCentral Nicol MP, Workman L, Isaacs W, et al. Accuracy of the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in hospitalized children in a high HIV-prevalence area. Lancet Infect Dis. 2011;11:819–24.CrossRefPubMedPubMedCentral
32.
go back to reference Zar HJ, Workman L, Isaacs W, et al. Rapid molecular diagnosis of pulmonary tuberculosis in children using nasopharyngeal specimens. Clin Infect Dis. 2012;55:1088–95.CrossRefPubMedPubMedCentral Zar HJ, Workman L, Isaacs W, et al. Rapid molecular diagnosis of pulmonary tuberculosis in children using nasopharyngeal specimens. Clin Infect Dis. 2012;55:1088–95.CrossRefPubMedPubMedCentral
33.
go back to reference Singh S, Singh A, Prajapati S, et al. Xpert MTB/RIF assay can be used on archived gastric aspirate and induced sputum samples for sensitive diagnosis of paediatric tuberculosis. BMC Microbiol. 2015;15:19. Singh S, Singh A, Prajapati S, et al. Xpert MTB/RIF assay can be used on archived gastric aspirate and induced sputum samples for sensitive diagnosis of paediatric tuberculosis. BMC Microbiol. 2015;15:19.
34.
go back to reference World Health Organization. The Use of Loop-Mediated Isothermal Amplification (TB-LAMP) for the Diagnosis of Pulmonary Tuberculosis. Policy Guidance. WHO/HTM/TB/2016, vol. 11. Geneva, Switzerland: WHO; 2016. World Health Organization. The Use of Loop-Mediated Isothermal Amplification (TB-LAMP) for the Diagnosis of Pulmonary Tuberculosis. Policy Guidance. WHO/HTM/TB/2016, vol. 11. Geneva, Switzerland: WHO; 2016.
35.
go back to reference Yadav R, Sharma N, Khaneja R, et al. Evaluation of the TB-LAMP assay for the rapid diagnosis of pulmonary tuberculosis in Northern India. Int J Tuberc Lung Dis. 2017;21:1150–3. Yadav R, Sharma N, Khaneja R, et al. Evaluation of the TB-LAMP assay for the rapid diagnosis of pulmonary tuberculosis in Northern India. Int J Tuberc Lung Dis. 2017;21:1150–3.
36.
go back to reference Pang Y, Xia H, Zhang Z, et al. Multicenter evaluation of genechip for detection of multidrug-resistant Mycobacterium tuberculosis. J Clin Microbiol. 2013;51:1707–13.CrossRefPubMedPubMedCentral Pang Y, Xia H, Zhang Z, et al. Multicenter evaluation of genechip for detection of multidrug-resistant Mycobacterium tuberculosis. J Clin Microbiol. 2013;51:1707–13.CrossRefPubMedPubMedCentral
37.
go back to reference Quan TP, Bawa Z, Foster D, et al. Evaluation of whole-genome sequencing for mycobacterial species identification and drug susceptibility testing in a clinical setting: a large-scale prospective assessment of performance against line probe assays and phenotyping. J Clin Microbiol. 2018;56:e01480–17. Quan TP, Bawa Z, Foster D, et al. Evaluation of whole-genome sequencing for mycobacterial species identification and drug susceptibility testing in a clinical setting: a large-scale prospective assessment of performance against line probe assays and phenotyping. J Clin Microbiol. 2018;56:e01480–17.
38.
go back to reference Colman RE, Anderson J, Lemmer D, et al. Rapid drug susceptibility testing of drug resistant Mycobacterium tuberculosis isolates directly from clinical samples by use of amplicon sequencing: a proof-of concept study. J Clin Microbiol. 2016;54:2058–67.CrossRefPubMedPubMedCentral Colman RE, Anderson J, Lemmer D, et al. Rapid drug susceptibility testing of drug resistant Mycobacterium tuberculosis isolates directly from clinical samples by use of amplicon sequencing: a proof-of concept study. J Clin Microbiol. 2016;54:2058–67.CrossRefPubMedPubMedCentral
39.
go back to reference Pankhurst LJ, Del Ojo EC, Votintseva AA, et al. Rapid, comprehensive, and affordable mycobacterial diagnosis with whole-genome sequencing: a prospective study. Lancet Respir Med. 2016;4:49–58.CrossRefPubMedPubMedCentral Pankhurst LJ, Del Ojo EC, Votintseva AA, et al. Rapid, comprehensive, and affordable mycobacterial diagnosis with whole-genome sequencing: a prospective study. Lancet Respir Med. 2016;4:49–58.CrossRefPubMedPubMedCentral
41.
go back to reference World Health Organisation. Use of Tuberculosis Interferon-Gamma Release Assays (IGRAS) in Low- and Middle-Income Countries: Policy Statement. WHO/HTM/TB/2011.18. Geneva: WHO; 2016. World Health Organisation. Use of Tuberculosis Interferon-Gamma Release Assays (IGRAS) in Low- and Middle-Income Countries: Policy Statement. WHO/HTM/TB/2011.18. Geneva: WHO; 2016.
42.
go back to reference Shah M, Martinson NA, Chaisson RE, Martin DJ, Variava E, Dorman SE. Quantitative analysis of a urine-based assay for detection of lipoarabinomannan in patients with tuberculosis. J Clin Microbiol. 2010;48:2972–4.CrossRefPubMedPubMedCentral Shah M, Martinson NA, Chaisson RE, Martin DJ, Variava E, Dorman SE. Quantitative analysis of a urine-based assay for detection of lipoarabinomannan in patients with tuberculosis. J Clin Microbiol. 2010;48:2972–4.CrossRefPubMedPubMedCentral
43.
go back to reference Boehme C, Molokova E, Minja F, et al. Detection of mycobacterial lipoarabinomannan with an antigen-capture ELISA in unprocessed urine of Tanzanian patients with suspected tuberculosis. Trans R Soc Trop Med Hyg. 2005;99:893–900.CrossRefPubMed Boehme C, Molokova E, Minja F, et al. Detection of mycobacterial lipoarabinomannan with an antigen-capture ELISA in unprocessed urine of Tanzanian patients with suspected tuberculosis. Trans R Soc Trop Med Hyg. 2005;99:893–900.CrossRefPubMed
44.
go back to reference Nakamura RM, Einck L, Velmonte MA, et al. Detection of active tuberculosis by an MPB-64 transdermal patch: a field study. Scand J Infect Dis. 2001;33:405–7.CrossRefPubMed Nakamura RM, Einck L, Velmonte MA, et al. Detection of active tuberculosis by an MPB-64 transdermal patch: a field study. Scand J Infect Dis. 2001;33:405–7.CrossRefPubMed
46.
go back to reference Traunmüller F, Zeitlinger MA, Stoiser B, et al. Circulating tuberculostearic acid in tuberculosis patients. Scand J Infect Dis. 2003;35:790–3. Traunmüller F, Zeitlinger MA, Stoiser B, et al. Circulating tuberculostearic acid in tuberculosis patients. Scand J Infect Dis. 2003;35:790–3.
47.
go back to reference Philips M, Basa-Dalay V, Bothamley G, et al. Breath biomarkers of active pulmonary tuberculosis. Tubercusis (Edinb). 2010;90:145–51.CrossRef Philips M, Basa-Dalay V, Bothamley G, et al. Breath biomarkers of active pulmonary tuberculosis. Tubercusis (Edinb). 2010;90:145–51.CrossRef
48.
go back to reference Boonyagars L, Kiertiburanakul S. Use of adenosine deaminase for the diagnosis of tuberculosis: a review. J Infect Dis Antimicrob Agents. 2010;27:111–8. Boonyagars L, Kiertiburanakul S. Use of adenosine deaminase for the diagnosis of tuberculosis: a review. J Infect Dis Antimicrob Agents. 2010;27:111–8.
Metadata
Title
Newer Diagnostic Tests and their Application in Pediatric TB
Authors
Chand Wattal
Reena Raveendran
Publication date
01-05-2019
Publisher
Springer India
Published in
Indian Journal of Pediatrics / Issue 5/2019
Print ISSN: 0019-5456
Electronic ISSN: 0973-7693
DOI
https://doi.org/10.1007/s12098-018-2811-0

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