Immunological diagnosis as an adjunctive tool for an early diagnosis of tuberculous meningitis of an immune competent child in a low tuberculosis endemic country: a case report

BMC Research Notes, Mar 2017

Background Pediatric tuberculous meningitis is a highly morbid, often fatal disease. Its prompt diagnosis and treatment saves lives, in fact delays in the initiation of therapy have been associated with high mortality rates. Case presentation This is a case of an Italian child who was diagnosed with tuberculous meningitis after a history of a month of headache, fatigue and weight loss. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis with predominance and decreased glucose concentration. Microscopy and conventional diagnostic tests to identify Mycobacterium tuberculosis were negative, while a non classical method based on intracellular cytokine flow cytometry response of CD4 cells in cerebral spinal fluid helped us to address the diagnosis, that was subsequently confirmed by a nested polymerase chain reaction amplifying a 123 base pair fragment of the M. tuberculosis DNA. Conclusions We diagnosed tuberculous meningitis at an early stage through an innovative immunological approach, supported by a nested polymerase chain reaction for detection of M. tuberculosis DNA. An early diagnosis is required in order to promptly initiate a therapy and to increase the patient’s survival.

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Immunological diagnosis as an adjunctive tool for an early diagnosis of tuberculous meningitis of an immune competent child in a low tuberculosis endemic country: a case report

Vita et al. BMC Res Notes Immunological diagnosis as an adjunctive tool for an early diagnosis of tuberculous meningitis of an immune competent child in a low tuberculosis endemic country: a case report Serena Vita 0 2 Camilla Ajassa 0 2 Emanuela Caraffa 0 2 Miriam Lichtner 1 2 Claudia Mascia 0 2 Fabio Mengoni 0 2 Maria Grazia Paglia 2 Cristina Mancarella 2 4 Davide Colistra 2 4 Claudio Di Biasi 2 3 Rosa Maria Ciardi 0 2 Claudio Maria Mastroianni 1 2 Vincenzo Vullo 0 2 0 Department of Public Health and Infectious Diseases, Sapienza University , 00185 Rome , Italy 1 Department of Public Health and Infectious Diseases, Sapienza University , Polo Pontino, 04100 Latina , Italy 2 Laboratory, National Institute for Infectious Diseases , Lazzaro Spallanzani, 00149 Rome , Italy 3 Department of Emergency and Acceptance, Unit of Radiology, Policlinico Umberto I , Rome , Italy 4 Department of Neurology and Psychiatry, Division of Neurosurgery , Sapienza, 00185 Rome , Italy Background: Pediatric tuberculous meningitis is a highly morbid, often fatal disease. Its prompt diagnosis and treatment saves lives, in fact delays in the initiation of therapy have been associated with high mortality rates. Case presentation: This is a case of an Italian child who was diagnosed with tuberculous meningitis after a history of a month of headache, fatigue and weight loss. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis with predominance and decreased glucose concentration. Microscopy and conventional diagnostic tests to identify Mycobacterium tuberculosis were negative, while a non classical method based on intracellular cytokine flow cytometry response of CD4 cells in cerebral spinal fluid helped us to address the diagnosis, that was subsequently confirmed by a nested polymerase chain reaction amplifying a 123 base pair fragment of the M. tuberculosis DNA. Conclusions: We diagnosed tuberculous meningitis at an early stage through an innovative immunological approach, supported by a nested polymerase chain reaction for detection of M. tuberculosis DNA. An early diagnosis is required in order to promptly initiate a therapy and to increase the patient's survival. Tuberculous meningitis; Children; Hydrocephalus; Immunological diagnosis; ICCFC - Tuberculous meningitis (TBM) represents roughly 1% of all cases of TB and it is associated with high mortality and residual neurologic sequelae, even with adequate treatment. In endemic countries the highest incidence of TBM is reported in children aged 2–4  years [1]. Early diagnosis is notoriously difficult and often delayed and it has long been recognized as the single most important factor determining outcome [2]. In fact the microbiological diagnosis of TBM is difficult due to the paucibacillary nature of the cerebrospinal fluid (CSF) in which the microscopy for acid-fast bacilli (AFB) and culture for Mycobacterium (M.) tuberculosis have a low sensitivity [1, 3, 4]. Also commercial nucleic acid amplification tests (NAATs) showed a low sensitivity and specificity compared to culture for the diagnosis of TBM [5]. An additional test is the Adenosine deaminase (ADA) measurements in CSF [6], even if the specificity is low and the cut-off level has not been determined [7]. We present a case study of an Italian child with TBM who was hospitalized in the Pediatric Infectious diseases department of Umberto I° Hospital in Rome, and in whom the early diagnosis, based on immunological flow © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. cytometry test and molecular assay, allowed us to start an early treatment, fundamental requirement to increase patient’s survival. Case report A 9-year-old Italian girl developed headache, fatigue and weight loss of about 6 kg 1 month prior the admission to our hospital. One week before admission, because of the occurrence of dizziness and vomiting, she was hospitalized to the Neurology Department of another hospital in Rome, where the computed tomography (CT) scan of head and audiovestibular exams were normal. The patient was discharged with a diagnosis of “Symptomatic paroxysmal vertigo, migraine without aura and acute gastroenteritis”. Few days after the discharge, she reported history of sleepiness, persistence of migraine and fever. Thereafter, she was admitted to the Pediatric Emergency Department of our hospital where she had normal blood tests and a normal brain magnetic resonance imaging (MRI). (...truncated)


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Serena Vita, Camilla Ajassa, Emanuela Caraffa, Miriam Lichtner, Claudia Mascia, Fabio Mengoni, Maria Grazia Paglia, Cristina Mancarella, Davide Colistra, Claudio Di Biasi, Rosa Maria Ciardi, Claudio Maria Mastroianni, Vincenzo Vullo. Immunological diagnosis as an adjunctive tool for an early diagnosis of tuberculous meningitis of an immune competent child in a low tuberculosis endemic country: a case report, BMC Research Notes, 2017, pp. 123, Volume 10, Issue 1, DOI: 10.1186/s13104-017-2444-9