ESPID REPORTS AND REVIEWS CONTENTS The Diagnosis of Tuberculosis EDITORIAL BOARD Co-Editors: Delane Shingadia and Irja Lutsar Board Members David Burgner (Melbourne, Australia) Nicol Ritz (Basel, Switzerland) Tobias Tenenbaum (Mannhein, Germany) Luisa Galli (Rome, Italy) Ira Shah (Mumbai, India) Marc Terbruegge (Southampton, UK) Christiana Nascimento-Carvalho Matthew Snape (Oxford, UK) Marceline van Furth (Amsterdam, (Bahia, Brazil) George Syrogiannopoulos The Netherlands) Ville Peltola (Turku, Finland) (Larissa, Greece) Anne Vergison (Brussels, Belgium) The Diagnosis of Tuberculosis Delane Shingadia, MPH, MRCP, FRCPCH Abstract: Childhood tuberculosis accounts for a ESTABLISHED DIAGNOSTIC in place. Nasopharyngeal aspiration (NPA) significant proportion of the global tuberculosis METHODS has also been used to obtain respiratory sam- disease burden. However, tuberculosis in children ples, as the passage of a nasal cannula may is difficult to diagnose, because disease tends to be Microscopy and Culture elicit a cough reflex. The culture yield from paucibacillary and sputum samples are often not Microscopic examination of respira- NPA (19/64; 30%) was similar to that of easy to obtain. The diagnosis of tuberculosis in tory samples for acid-fast bacilli using the gastric aspirates (24/64; 38%) among Peru- 8 children is traditionally based on chest radiogra- Ziehl-Neelsen and fluorochrome stains, such vian children. However, subsequent studies phy, tuberculin skin testing, and mycobacterial as the auramine and rhodamine, have been have shown relatively poor yields from staining/culture from appropriate samples. Newer the standard and rapid diagnostic tools for NPA samples compared with gastric aspi- 1,2 9,10 diagnostic strategies have included improved bacte- tuberculosis (TB) diagnosis. Recent ad- rate. Since young children tend to swal- vances in light-emitting diode (LED) tech- riologic and molecular methods, as well as new low their sputum rather than expectorate it, nology have widened the applicability of methods for sample collection from children. Re- mycobacterial culture of stool has been fluorescent microscopy.3 In adults and older considered as an indirect way of analysis cently, immune-based diagnostics, such as the inter- children, sputum samples are often obtained of respiratory secretions. However, studies feron-gamma release assays, have been introduced with sensitivity from 34% to 80%.4 In in children have shown relatively poor re- for clinical use. These tests do not offer substantial younger children, who are unable to produce covery from stool, making this an insensi- improvements in sensitivity over tuberculin skin test- sputum samples, alternative methods of ob- tive method for mycobacterial culture. Fur- ing for the diagnosis of active disease but may be taining respiratory samples, such as gastric thermore, the major drawback of stool useful in excluding false-positive tuberculin skin aspirates, are often used. However, micro- culture is the need for stringent decontam- tests. Further research is needed to develop better scopic yields may be Ͻ20% in children with ination procedures to prevent overgrowth diagnostic tests for tuberculosis in children. probable TB.5 The detection rates on micros- of normal bowel flora, which may also kill Key Words: tuberculosis, diagnosis, child copy from other extrapulmonary samples, or inhibit growth of mycobacteria further such as cerebrospinal fluid, are even lower reducing the sensitivity.11 (Pediatr Infect Dis J 2012;31: 302–305) because of the paucibacillary nature of dis- Another novel method of sampling ease at these sites. swallowed respiratory secretions is the string Mycobacterial culture of respiratory test. The string test was developed for the samples has provided a more useful method diagnosis of intestinal parasites such as giar- of diagnosis in children with suspected pul- diasis. This test involves swallowing a gela- monary TB. Three consecutive daily morn- tin capsule containing a coiled nylon string, ing gastric aspirates yield M. tuberculosis in which unravels as the capsule descends into 30% to 50% of cases and may be as high as the stomach. After 4 hours, the string is From the Department of Infectious Diseases, Great 6 Ormond Street Hospital, Great Ormond Street, 70% in infants. Recently, sputum induction withdrawn and cultured for mycobacteria. London, United Kingdom. using nebulized hypertonic (3%–5%) saline Although this test appears to have a better The author has no funding or conflicts of interest to has been used safely and effectively in young culture yield than sputum induction in adults disclose. children. The culture yield from a single with HIV infection (9% vs. 5%), it has not Address for correspondence: Delane Shingadia, MPH, MRCP, FRCPCH, Department of Infectious Dis- induced sputum sample has been shown to been studied in children other than a feasi- eases, Great Ormond Street Hospital, Great Or- be equivalent to that of 3 cumulative gastric bility study where it appears to have been mond Street, London WC1N 3JH, United King- lavage samples.7 There are, however, some well tolerated.12,13 Furthermore, it may be dom. E-mail: [email protected]. concerns regarding the risk of nosocomial of limited use in younger children who will Copyright © 2012 by Lippincott Williams & Wilkins ISSN: 0891-3668/12/3103-0302 transmission following sputum induction if be unable to swallow the capsule in the DOI: 10.1097/INF.0b013e318249f26d adequate infection control procedures are not first place. The ESPID Reports and Reviews of Pediatric Infectious Diseases series topics, authors and contents are chosen and approved independently by the Editorial Board of ESPID. 302 | www.pidj.com The Pediatric Infectious Disease Journal • Volume 31, Number 3, March 2012 The Pediatric Infectious Disease Journal • Volume 31, Number 3, March 2012 ESPID Reports and Reviews The culture yield from other body flu- cination and Ͼ15 mm for those with BCG and require a laboratory infrastructure simi- ids or tissues from children with extrapulmo- vaccination history.22 The US guidelines use lar to that required for standard cultures. nary TB is usually Ͻ50%.14,15 In children a risk categorization based on epidemiologic There is currently only 1 commercially avail- with palpable peripheral lymphadenopathy, and clinical factors: Ͼ5 mm (close contacts, able kit, the FASTPlaque-TB (Biotec Labo- fine needle aspiration and culture is a very TB disease, immunosuppression), Ͼ10 mm ratories, Ipswich, Suffolk, United Kingdom) useful adjunct to culture of respiratory (increased risk of disseminated disease or assay, which can be used directly on sputum specimens and may have a higher yield increased exposure to TB disease), and Ͼ15 samples for diagnosis. A variant of this than such culture (sensitivity 60.8% vs. mm (children Ͼ4 years of age with no risk assay, the FASTPlaque-Response kit is de- 39.2%, respectively).16 factors).23 signed to detect rifampicin resistance in Recently, automated liquid culture TST is prone to both false-negative sputum specimens, which has been used as systems with continuous monitoring for my- and false-positive results. Up to 10% to 15% a reliable marker for multidrug-resistant cobacterial growth (such as BD BACTEC of otherwise immunocompetent children TB. However, no information exists on the MGIT system or Biomerrieux BacT/ALERT with culture-documented TB do not initially utility of these tests in the diagnosis of 3D) have been a significant advance over show TST reactivity.14 Host factors, such as childhood TB. traditional solid culture (Lowenstein-Jensen young age, poor nutrition, immunosuppres- The potential of a gas sensor array media). In adult studies, these tests offer sion, other viral infections (such as measles, electronic “nose” (E-nose) to detect different improved sensitivity (88% vs. 76%) and re- varicella, and influenza), recent TB infec- Mycobacterium species in the headspaces of duced detection time (13.2 vs. 25.8 days) tion, and disseminated TB diseases, can fur- cultures and sputum samples is another in- compared with solid media.17 It is likely that ther decrease TST reactivity. False-positive novative approach that is currently under these findings can be extrapolated to children TST results may also occur following BCG development. The array uses 14 sensors to with TB, although there is a paucity of pe- vaccination and exposure to environmental profile a “smell” by assessing the change in diatric data. Despite their higher cost and the nontuberculous mycobacteria.24 Skin reac- each sensor’s electrical properties when ex- laboratory infrastructure required, liquid cul- tivity can be boosted, probably through an- posed to a specific odor mixture. In a recent ture has been recommended for all culture in tigenic stimulation, by serial testing with study using sputum samples from adult TB resource-rich settings.18 TST in many children and adults who re- patients and non-TB patients, the E-nose had Newer culture-based methods, such as ceived BCG.25 sensitivity of 68% and specificity of 69%.29 TK medium, use multiple dye indicators for Further research is still required to improve the early detection of mycobacterial growth Radiology sensitivity and specificity as well as its po- with the naked eye. The simple colorimetric Chest radiography is used widely for tential in the diagnosis of childhood TB. system reduces turnaround times, but their the detection of pulmonary TB, including accuracy and robustness in field conditions detection of hilar lymphadenopathy,