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CORRESPONDENCE Reduced sensitivity of immunodiagnostic tests for active tuberculosis in children Michael Eisenhut Received: 17 December 2009 / Accepted: 9 February 2010 / Published online: 27 February 2010 # Springer-Verlag 2010 Dear Editor, A recent review article summarized approaches to diagnosis of childhood tuberculosis [2]. The author emphasized the paucibacillary nature of tuberculosis in children with a low probability of bacteriological confirmation. The author then omitted to mention that cornerstones of diagnosis of tuberculosis in children remain immunodiagnostic methods like tuberculin skin testing and interferon gamma release assays (IGRA). It is therefore important to discuss the limitations of immunodiagnostic testing which arise specif- ically in tuberculosis in children. The author mentions the low sensitivity of tuberculin skin testing in malnutrition and human immunodeficiency virus infection. In manifestations of active tuberculosis in children like tuberculous meningi- tis and miliary tuberculosis, the tuberculin skin test is equally insensitive with sensitivities of 30% (positivity of Mantoux test defined as induration >10 mm) reported for tuberculous meningitis [3]. The sensitivity of IGRA's in active culture confirmed tuberculosis in adults was in a meta-analysis found to be 90 (95% confidence interval, 8693%). In children, recent investigations found a sensitivity in all forms of active tuberculosis of 58% for the ELISPOT version of the IGRA [1]. The cause for this reduced immune response in children may be a lower bacterial load and/or an immaturity of the Th-1-driven immune response in childhood plus in active tuberculosis an immunosup- pressive effects on the Th-1 response by Mycobacterium tuberculosis through induction of interleukin-10. It is therefore important to confirm M. tuberculosis infection in children with suspected active tuberculosis by using both skin test and IGRA. Using both tests increased sensitivity to 100% in culture-confirmed active tuberculosis [1]. References 1. Kampmann B, Whittaker E, Williams A, Walters S, Gordon A, Martinez-Alier N, Williams B, Crook AM, Hutton AM, Anderson ST (2009) Interferon-gamma release assays do not identify more children with active tuberculosis than the tuberculin skin test. Eur Respir J 33:13741382 2. Rigouts L (2009) Clinical practice: diagnosis of childhood tuberculosis. Eur J Pediatr 168:12851290 3. Yaramis A, Gurkan F, Elevli M, Soeker M, Haspolat K, Kirbas G, Tas MA (1998) Central nervous system tuberculosis in children: a review of 214 cases. Pediatrics 102:E49 M. Eisenhut (*) Luton & Dunstable Hospital NHS Foundation Trust, Lewsey Road, Luton LU4 ODZ, UK e-mail: [email protected] Eur J Pediatr (2010) 169:775 DOI 10.1007/s00431-010-1166-y

Reduced sensitivity of immunodiagnostic tests for active tuberculosis in children

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CORRESPONDENCE

Reduced sensitivity of immunodiagnostic tests for activetuberculosis in children

Michael Eisenhut

Received: 17 December 2009 /Accepted: 9 February 2010 /Published online: 27 February 2010# Springer-Verlag 2010

Dear Editor,A recent review article summarized approaches to diagnosisof childhood tuberculosis [2]. The author emphasized thepaucibacillary nature of tuberculosis in children with a lowprobability of bacteriological confirmation. The author thenomitted to mention that cornerstones of diagnosis oftuberculosis in children remain immunodiagnostic methodslike tuberculin skin testing and interferon gamma releaseassays (IGRA). It is therefore important to discuss thelimitations of immunodiagnostic testing which arise specif-ically in tuberculosis in children. The author mentions thelow sensitivity of tuberculin skin testing in malnutrition andhuman immunodeficiency virus infection. In manifestationsof active tuberculosis in children like tuberculous meningi-tis and miliary tuberculosis, the tuberculin skin test isequally insensitive with sensitivities of 30% (positivity ofMantoux test defined as induration >10 mm) reported fortuberculous meningitis [3]. The sensitivity of IGRA's inactive culture confirmed tuberculosis in adults was in ameta-analysis found to be 90 (95% confidence interval, 86–93%). In children, recent investigations found a sensitivityin all forms of active tuberculosis of 58% for the ELISPOT

version of the IGRA [1]. The cause for this reducedimmune response in children may be a lower bacterial loadand/or an immaturity of the Th-1-driven immune responsein childhood plus in active tuberculosis an immunosup-pressive effects on the Th-1 response by Mycobacteriumtuberculosis through induction of interleukin-10. It istherefore important to confirm M. tuberculosis infection inchildren with suspected active tuberculosis by using bothskin test and IGRA. Using both tests increased sensitivity to100% in culture-confirmed active tuberculosis [1].

References

1. Kampmann B, Whittaker E, Williams A, Walters S, Gordon A,Martinez-Alier N, Williams B, Crook AM, Hutton AM, AndersonST (2009) Interferon-gamma release assays do not identify morechildren with active tuberculosis than the tuberculin skin test. EurRespir J 33:1374–1382

2. Rigouts L (2009) Clinical practice: diagnosis of childhoodtuberculosis. Eur J Pediatr 168:1285–1290

3. Yaramis A, Gurkan F, Elevli M, Soeker M, Haspolat K, Kirbas G,Tas MA (1998) Central nervous system tuberculosis in children: areview of 214 cases. Pediatrics 102:E49

M. Eisenhut (*)Luton & Dunstable Hospital NHS Foundation Trust,Lewsey Road,Luton LU4 ODZ, UKe-mail: [email protected]

Eur J Pediatr (2010) 169:775DOI 10.1007/s00431-010-1166-y