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Lack of Sensitivity of QuantiFERON-TB Gold Test in Tube in a Child With Tuberculous Meningitis

2010; Lippincott Williams & Wilkins; Volume: 29; Issue: 7 Linguagem: Inglês

10.1097/inf.0b013e3181e218b7

1532-0987

Ana Méndez‐Echevarría, Fernando Baquero‐Artigao, Miguel González‐Muñoz, Fernando De Castillo, María José Mellado, R. Velázquez-Fragua,

Orthopedic Infections and Treatments

To the Editors: Diagnosis of tuberculous meningitis remains an important clinical challenge. About half of patients will present with normal chest radiography or a negative tuberculin skin test (TST). Negative smears for acid-fast bacilli and lack of isolation of Mycobacteriumtuberculosis in cerebral spinal fluid (CSF) culture are observed in more than 50% of cases. The CSF polymerase chain reaction (PCR) assay represents a diagnostic advance, but is insensitive to confidently exclude the diagnosis. Recently, interferon-gamma release assays (IGRAS) have been reported to improve diagnostic sensitivity of tuberculosis in adults and children, but studies in tuberculous meningitis are lacking. We have recently diagnosed a tuberculous meningitis in a 2-year-old Rumanian girl who presented with a negative TST (0 mm), normal chest radiograph, negative CSF smears for acid-fast bacilli, negative CSF-PCR assay for M. tuberculosis and negative QuantiFERON-TB Gold Test In Tube (QTF) (0.27 UI/mL; positive value ≥0.35 UI/mL) with proper interferon production in mitogen control (6.21 UI/mL). At time of admission, CSF had a mildly elevated pleocytosis (60 leukocytes/mm3; 85% neutrophils), a slight raised protein (90.7 mg/dL) and a low glucose value (14 mg/dL) and computed tomography scan revealed mild basilar meningeal enhancement. There was no evidence of tuberculosis exposure. One month after admission, M.tuberculosis was isolated in CSF and gastric aspirate contents. A new QTF and TST were again performed and were positive (0.72 UI/mL and 13 mm, respectively). The few available data of the use of IGRAS for diagnosing extrapulmonary tuberculosis suggest that these assays have the same sensitivity as in pulmonary disease.1Regarding the use of QFT for tuberculous meningitis diagnosis, few articles have been published.2,3 All of them estimate that QTF sensitivity is higher than acid-fast-bacilli-CSF smears, CSF culture or CSF-PCR assay for M. tuberculosis. The T-SPOT. TB test (Oxford Immunotec) for tuberculous meningitis diagnosis has a higher sensitivity (62%–100%) than conventional diagnosis techniques and better than that described for TST.1,4–7 Some authors suggest that IGRAS could be performed in CSF instead of in plasma with better sensitivity.2,5,6 In young children, deficiencies in dendritic cell and TH-1-type T-cells function, which play a central role in avoiding lymphohematogenous spread of M. tuberculosis after the infection, contribute to the susceptibility to develop disseminated disease.8 Up to 50% of children with TB meningitis have negative TST results9 and this is believed to be consequence of diminished functioning of T lymphocytes with less cytokine production. For this reason, in young children with TB meningitis and negative TST we would expect to find a high percentage of indeterminate IGRA results due to absence of response in mitogen control. Nevertheless, our patient presented an initial negative result with a good IFN-γ production in the mitogen control, and a positive result after 6 weeks of evolution. Considering that tuberculous meningitis are early developed after the infection,9 some negative TST and IGRAS results observed will be probably due to prompt spread of the mycobacteria in new acquired infections without an effective T lymphocytes response development. In a child with suspected tuberculous meningitis and a negative IGRA, we believe it is prudent to initiate antituberculous therapy. ACKNOWLEDGMENTS The authors thank Spanish Pediatric Association (AEP) for the 19th Ausonia-Arbora Grant that has contributed to perform all the studies of the Spanish Collaborative Group for the study of QuantiFERON-TB Gold Test In Tube in children. Ana Méndez Echevarría, MD, PhD Fernando Baquero-Artigao, MD Paediatric Infectious Disease Unit La Paz Hospital Miguel González-Muñoz, MD, PhD Immunology Department Carlos III Hospital Fernando De Castillo, MD, PhD Paediatric Infectious Disease Unit La Paz Hospital Maria José Mellado Peña, MD, PhD Paediatric Department Carlos III Hospital Ramón Velázquez-Fragua, MD Paediatric Neurology Department La Paz Hospital Madrid, Spain