Tuberculosis in childhood differs from the adult clinical form and even has been suggested that it is a different disease due to its differential signs. However, prevention, diagnostics, and therapeutic efforts have been biased toward adult clinical care. Sensibility and specificity of new diagnostic approaches as GeneXpert, electronic nose (E-nose), infrared spectroscopy, accelerated mycobacterial growth induced by magnetism, and flow lateral devices in children populations are needed. Adequate and timely assessment of tuberculosis infection in childhood could diminish epidemiological burden because underdiagnosed pediatric patients can evolve to an active state and have the potential to disseminate the etiological agent Mycobacterium tuberculosis, notably increasing this worldwide public health problem. 1. Introduction Tuberculosis is the leading cause of death worldwide, with over 1.5 million deaths per year. This disease is caused by Mycobacterium tuberculosis, which is an acid-fast bacilli, and it is transmitted mainly by the airway [1]. While adult TB cases are often easily recognizable, due to typical symptoms (radiological features and a positive sputum smear), TB in childhood is frequently more difficult to diagnose due to the atypical radiological features and the difficulty to expectorate [2]. Furthermore, there is a significant morbidity and mortality in children worldwide [3], with a majority of cases of latent TB infection (LTBI) and active disease occurring in developing countries [4]. Childhood tuberculosis is commonly extrapulmonary, disseminated, and severe, especially in children under 3 years of age, and it is associated with high morbidity and mortality [5]. Approximately, 15–20% of all TB cases in sub-Saharan Africa are in children [6]. The natural history of TB in children and pediatric patients follows a series of steps. Phase 1 occurred 3–8 weeks after primary infection. This is the end of incubation period and the initiation of well-defined signs: fever, erythema nodosum, a positive tuberculin skin test response, and formation of the primary complex visible on chest radiography. Phase 2 occurred 1–3 months after the phase 1. In this period, the bacillus can migrate to other parts of the body via the blood and represented the period of the highest risk for the development of tuberculous meningitis and miliary tuberculosis in young children. This is the phase where dissemination of the bacillus most frequently occurs. Phase 3 occurred 3–7 months after primary infection. This is the period of pleural effusions in >5 years old
References
[1]
J. L. Flynn and J. Chan, “Tuberculosis: latency and reactivation,” Infection and Immunity, vol. 69, no. 7, pp. 4195–4201, 2001.
[2]
M. P. Nicol and H. J. Zar, “New specimens and laboratory diagnostics for childhood pulmonary TB: progress and prospects,” Paediatric Respiratory Reviews, vol. 12, no. 1, pp. 16–21, 2011.
[3]
M. P. Nicol, D. Pienaar, K. Wood et al., “Enzyme-linked immunospot assay responses to early secretory antigenic target 6, culture filtrate protein 10, and purified protein derivative among children with tuberculosis: implications for diagnosis and monitoring of therapy,” Clinical Infectious Diseases, vol. 40, no. 9, pp. 1301–1308, 2005.
[4]
S. Dogra, P. Narang, D. K. Mendiratta et al., “Comparison of a whole blood interferon-γ assay with tuberculin skin testing for the detection of tuberculosis infection in hospitalized children in rural India,” Journal of Infection, vol. 54, no. 3, pp. 267–276, 2007.
[5]
A. Lalvani and K. A. Millington, “Screening for tuberculosis infection prior to initiation of anti-TNF therapy,” Autoimmunity Reviews, vol. 8, no. 2, pp. 147–152, 2008.
[6]
D. J. Edwards, F. Kitetele, and A. Van Rie, “Agreement between clinical scoring systems used for the diagnosis of pediatric tuberculosis in the HIV era,” International Journal of Tuberculosis and Lung Disease, vol. 11, no. 3, pp. 263–269, 2007.
[7]
E. A. Khan and J. R. Starke, “Diagnosis of tuberculosis in children: increased need for better methods,” Emerging Infectious Diseases, vol. 1, no. 4, pp. 115–123, 1995.
[8]
B. J. Marais, R. P. Gie, H. S. Schaaf et al., “The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era,” International Journal of Tuberculosis and Lung Disease, vol. 8, no. 4, pp. 392–402, 2004.
[9]
M. P. Nicol, M. A. Davies, K. Wood et al., “Comparison of T-SPOT. TB assay and tuberculin skin test for the evaluation of young children at high risk for tuberculosis in a community setting,” Pediatrics, vol. 123, no. 1, pp. 38–43, 2009.
[10]
B. J. Marais, R. P. Gie, H. S. Schaaf, A. C. Hesseling, D. A. Enarson, and N. Beyers, “The spectrum of disease in children treated for tuberculosis in a highly endemic area,” International Journal of Tuberculosis and Lung Disease, vol. 10, no. 7, pp. 732–738, 2006.
[11]
S. H. Montenegro, R. H. Gilman, P. Sheen et al., “Improved detection of Mycobacterium tuberculosis in Peruvian children by use of a heminested IS6110 polymerase chain reaction assay,” Clinical Infectious Diseases, vol. 36, no. 1, pp. 16–23, 2003.
[12]
B. J. Marais, R. P. Gie, A. C. Hesseling et al., “A refined symptom-based approach to diagnose pulmonary tuberculosis in children,” Pediatrics, vol. 118, no. 5, pp. e1350–e1359, 2006.
[13]
L. J. Nelson and C. D. Wells, “Tuberculosis in children: considerations for children from developing countries,” Seminars in Pediatric Infectious Diseases, vol. 15, no. 3, pp. 150–154, 2004.
[14]
L. J. Nelson and C. D. Wells, “Global epidemiology of childhood tuberculosis,” International Journal of Tuberculosis and Lung Disease, vol. 8, no. 5, pp. 636–647, 2004.
[15]
S. M. Graham, R. P. Gie, H. S. Schaaf, J. B. S. Coulter, M. A. Espinal, and N. Beyers, “Childhood tuberculosis: clinical research needs,” International Journal of Tuberculosis and Lung Disease, vol. 8, no. 5, pp. 648–657, 2004.
[16]
D. A. Lewinsohn, M. L. Gennaro, L. Scholvinck, and D. M. Lewinsohn, “Tuberculosis immunology in children: diagnostic and therapeutic challenges and opportunities,” International Journal of Tuberculosis and Lung Disease, vol. 8, no. 5, pp. 658–674, 2004.
[17]
B. J. Marais, R. P. Gie, H. S. Schaaf, N. Beyers, P. R. Donald, and J. R. Starke, “Childhood pulmonary tuberculosis: old wisdom and new challenges,” American Journal of Respiratory and Critical Care Medicine, vol. 173, no. 10, pp. 1078–1090, 2006.
[18]
S. M. Newton, A. J. Brent, S. Anderson, E. Whittaker, and B. Kampmann, “Paediatric tuberculosis,” The Lancet Infectious Diseases, vol. 8, no. 8, pp. 498–510, 2008.
[19]
B. J. Marais and M. Pai, “Recent advances in the diagnosis of childhood tuberculosis,” Archives of Disease in Childhood, vol. 92, no. 5, pp. 446–452, 2007.
[20]
A. C. Hesseling, H. S. Schaaf, R. P. Gie, J. R. Starke, and N. Beyers, “A critical review of diagnostic approaches used in the diagnosis of childhood tuberculosis,” International Journal of Tuberculosis and Lung Disease, vol. 6, no. 12, pp. 1038–1045, 2002.
[21]
S. Swaminathan and B. Rekha, “Pediatric tuberculosis: global overview and challenges,” Clinical Infectious Diseases, vol. 50, no. 3, pp. S184–S194, 2010.
[22]
L. J. Nelson, E. Schneider, C. D. Wells, and M. Moore, “Epidemiology of childhood tuberculosis in the United States, 1993–2001: the need for continued vigilance,” Pediatrics, vol. 114, no. 2 I, pp. 333–341, 2004.
[23]
P. Eamranond and E. Jaramillo, “Tuberculosis in children: reassessing the need for improved diagnosis in global control strategies,” International Journal of Tuberculosis and Lung Disease, vol. 5, no. 7, pp. 594–603, 2001.
[24]
B. J. Marais and M. Pai, “New approaches and emerging technologies in the diagnosis of childhood tuberculosis,” Paediatric Respiratory Reviews, vol. 8, no. 2, pp. 124–133, 2007.
[25]
M. S. Imaz, M. A. Comini, E. Zerbini et al., “Evaluation of the diagnostic value of measuring IgG, IgM and IgA antibodies to the recombinant 16-kilodalton antigen of Mycobacterium tuberculosis in childhood tuberculosis,” International Journal of Tuberculosis and Lung Disease, vol. 5, no. 11, pp. 1036–1043, 2001.
[26]
A. K. Detjen, T. Keil, S. Roll et al., “Interferon-γ release assays improve the diagnosis of tuberculosis and nontuberculous mycobacterial disease in children in a country with a low incidence of tuberculosis,” Clinical Infectious Diseases, vol. 45, no. 3, pp. 322–328, 2007.
[27]
R. Lodha and S. K. Kabra, “Newer diagnostic modalities for tuberculosis,” Indian Journal of Pediatrics, vol. 71, no. 3, pp. 221–227, 2004.
[28]
B. J. Marais, C. C. Obihara, R. P. Gie et al., “The prevalence of symptoms associated with pulmonary tuberculosis in randomly selected children from a high burden community,” Archives of Disease in Childhood, vol. 90, no. 11, pp. 1166–1170, 2005.
[29]
D. Gomez-Pastrana, R. Torronteras, P. Caro et al., “Comparison of amplicor, in-house polymerase chain reaction, and conventional culture for the diagnosis of tuberculosis in children,” Clinical Infectious Diseases, vol. 32, no. 1, pp. 17–22, 2001.
[30]
K. A. F. Houwert, P. A. Borggreven, H. S. Schaaf, E. Nel, P. R. Donald, and J. Stolk, “Prospective evaluation of World Health Organization criteria to assist diagnosis of tuberculosis in children,” European Respiratory Journal, vol. 11, no. 5, pp. 1116–1120, 1998.
[31]
D. I. Ling, A. A. Zwerling, K. R. Steingart, and M. Pai, “Immune-based diagnostics for TB in children: what is the evidence?” Paediatric Respiratory Reviews, vol. 12, no. 1, pp. 9–15, 2011.
[32]
F. Chow, N. Espiritu, R. H. Gilman et al., “La cuerda dulce—a tolerability and acceptability study of a novel approach to specimen collection for diagnosis of paediatric pulmonary tuberculosis,” BMC Infectious Diseases, vol. 6, article 67, 2006.
[33]
C. M. Osborne, “The challenge of diagnosing childhood tuberculosis in a developing country,” Archives of Disease in Childhood, vol. 72, no. 4, pp. 369–374, 1995.
[34]
B. J. Marais, R. P. Gie, C. C. Obihara, A. C. Hesseling, H. S. Schaaf, and N. Beyers, “Well defined symptoms are of value in the diagnosis of childhood pulmonary tuberculosis,” Archives of Disease in Childhood, vol. 90, no. 11, pp. 1162–1165, 2005.
[35]
H. J. Zar, E. Tannenbaum, P. Apolles, P. Roux, D. Hanslo, and G. Hussey, “Sputum induction for the diagnosis of pulmonary tuberculosis in infants and young children in an urban setting in South Africa,” Archives of Disease in Childhood, vol. 82, no. 4, pp. 305–308, 2000.
[36]
G. A. Lassman, “Evaluation of different techniques in obtaining gastric specimens for examination for the presence of tubercle bacilli,” Chest, vol. 5, pp. 15–17, 1939.
[37]
M. Salfinger and G. E. Pfyffer, “The new diagnostic mycobacteriology laboratory,” European Journal of Clinical Microbiology and Infectious Diseases, vol. 13, no. 11, pp. 961–979, 1994.
[38]
A. Lalvani and K. A. Millington, “T cell-based diagnosis of childhood tuberculosis infection,” Current Opinion in Infectious Diseases, vol. 20, no. 3, pp. 264–271, 2007.
[39]
M. Bakir, K. A. Millington, A. Soysal et al., “Prognostic value of a T-cell-based, interferon-γ biomarker in children with tuberculosis contact,” Annals of Internal Medicine, vol. 149, no. 11, pp. 777–786, 2008.
[40]
M. P. Nicol, L. Workman, W. Isaacs et al., “Accuracy of the Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in children admitted to hospital in Cape Town, South Africa: a descriptive study,” The Lancet Infectious Diseases, vol. 11, no. 11, pp. 819–824, 2011.
[41]
J. Dinnes, J. Deeks, H. Kunst et al., “A systematic review of rapid diagnostic tests for the detection of tuberculosis infection,” Health Technology Assessment, vol. 11, no. 3, pp. 1–196, 2007.
[42]
A. Rachow, A. Zumla, N. Heinrich et al., “Rapid and accurate detection of Mycobacterium tuberculosis in sputum samples by Cepheid Xpert MTB/RIF assay—a clinical validation study,” PLoS ONE, vol. 6, no. 6, article e20458, 2011.
[43]
S. Cole, R. Brosch, S. Gordon, et al., “Sequences specifcally deleted from Mycobacterium tuberculosis genome and their use in diagnosistics and as vaccines,” Patent no. 1338657, INSTITUT Pasteur France, 2011.
[44]
D. Bandyopadhyay, S. Gupta, S. Banerjee et al., “Adenosine deaminase estimation and multiplex polymerase chain reaction in diagnosis of extra-pulmonary tuberculosis,” International Journal of Tuberculosis and Lung Disease, vol. 12, no. 10, pp. 1203–1208, 2008.
[45]
Q. L. Liang, H. Z. Shi, K. Wang, S. M. Qin, and X. J. Qin, “Diagnostic accuracy of adenosine deaminase in tuberculous pleurisy: a meta-analysis,” Respiratory Medicine, vol. 102, no. 5, pp. 744–754, 2008.
[46]
G. Hussey, M. Kibel, and W. Dempster, “The serodiagnosis of tuberculosis in children: an evaluation of an ELISA test using IgG antibodies to M. tuberculosis, strain H37 RV,” Annals of Tropical Paediatrics, vol. 11, no. 2, pp. 113–118, 1991.
[47]
S. D. Lawn and M. P. Nicol, “Xpert MTB/RIF assay: development, evaluation and implementation of a new rapid molecular diagnostic for tuberculosis and rifampicin resistance,” Future Microbiology, vol. 6, no. 9, pp. 1067–1082, 2011.
[48]
A. K. Trilling, H. de Ronde, L. Noteboom et al., “A broad set of different llama antibodies specific for a 16 kda heat shock protein of mycobacterium tuberculosis,” PLoS ONE, vol. 6, no. 10, article e26754, 2011.
[49]
A. S. Gordetsov, L. A. Mamaeva, V. N. Krylov, and A. V. Lebedev, “Method of respiratory active tuberculosis diagnostics,” RU2327990 (C1), Russia, 2008.
[50]
M. L. Gel'fond, A. S. Gordetsov, V. Z. Zhadnov, and P. I. Postrgan, “Feasibilities of infrared spectroscopy of bronchoalveolar lavages in patients with pulmonary tuberculosis,” Problemy tuberkuleza, no. 5, pp. 34–36, 1997.
[51]
B. V. Noreiko and S. M. Liepshyna, “Method for express diagnostics of tuberculosis,” UA28120 (U), Ukraine, 2007.
[52]
L. P. Wang, C. L. Young, C. L. Huang, and T. K. A. Chou, “Breath analysis systems and methods for asthma, tuberculosis and lung cancer diagnostics and disease management,” EP2369989 (A1), USA, 2011.
