Improving Technology to Diagnose Tuberculous Meningitis: Are We There Yet?

Ssebambulidde, Kenneth; Gakuru, Jane; Ellis, Jayne; Cresswell, Fiona V; Bahr, Nathan C

doi:10.3389/fneur.2022.892224

Cited by 17 publications

(10 citation statements)

References 74 publications

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“…The conventional method for culturing mycobacteria, considered the gold standard for diagnosing TB, typically requires six to eight weeks and is consequently inadequate for the early diagnosis of TBM [ 13 ]. Moreover, the CSF in individuals with TBM frequently harbors only a limited number of organisms, leading to a generally low diagnostic yield for CSF smear and culture [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Central Nervous System Tuberculosis in Immunocompromised Patients: A Case Report Emphasizing Immune Status and Early Recognition and Treatment

Quaresma,

Paulino,

Oliveira

et al. 2024

Cureus

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Tuberculosis (TB) remains a global health challenge. Although pulmonary TB is the most frequent presentation, extrapulmonary involvement can occur, especially in immunocompromised patients. HIV-positive individuals are particularly vulnerable to opportunistic infections, such as TB, and CNS involvement is more prevalent in these patients, often leading to a poorer prognosis. CNS TB management is challenging due to nonspecific symptoms and delayed diagnosis, contributing to high mortality. It can manifest diffusely as tuberculous meningitis (TBM), localized as tuberculoma or tuberculous abscess, or as extradural and intradural spinal infections. TBM is the primary CNS manifestation, bearing significant morbidity and mortality, and rarely complicates with involvement of the spinal cord, termed tuberculous myelitis, which is associated with an unfavorable prognosis. A 61-year-old male, smoker with a history of substance abuse, undergoing seven months of antiretroviral therapy (ART) for HIV-1, presented with a two-day history of altered consciousness, sphincter incontinence, and fever. He also reported headaches, dizziness, and sleep disturbances over the past months. The examination revealed fever, asthenia, prostration, disorientation, neck rigidity, and bilateral lower limb weakness. Initial tests indicated lymphopenia, hyponatremia, and a slightly elevated C-reactive protein. Cranial CT showed no abnormalities. Lumbar puncture yielded abnormal cerebrospinal fluid (CSF), xanthochromic, hyperproteinorrheic (2316 g/L), hypoglycorrhagic (24mg/dl), with pleocytosis predominantly of mononuclear cells (98%). Compared to the values prior to ART treatment, the patient had a decreased HIV-1 viral (44 copies/ml) load but also a decreased CD4+ cell count (43 cells/mm 3 ). Given the patient's rapid clinical deterioration, immunosuppression history, and a positive interferon-gamma release assay (IGRA) prior to ART, treatment with antituberculous drugs and dexamethasone was started at admission. Subsequently, Mycobacterium tuberculosis was identified through polymerase chain reaction (PCR) of the CSF. Cranial and spinal MRI revealed leptomeningeal enhancement from C2-C3 to the cauda equina, consistent with meningitis, without intracranial extension, and findings suggestive of myelitis, without evidence of tuberculomas or spinal cord osseous involvement. One week after treatment, the recovery of higher neurological functions became evident. Improvement in lower limb motor deficits had a delayed trajectory, with marginal progress observed at discharge. After an eight-week incubation, CSF mycobacterial culture analysis yielded negative results. This case discusses the importance of early suspicion and intervention in CNS infection prognosis. Attention to signs and symptoms beyond the most frequent ones is crucial, particularly in immunocompromised individuals like HIV patients. Identifying CSF features in different CNS infections and group-specific particula...

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Section: Discussionmentioning

confidence: 99%

Central Nervous System Tuberculosis in Immunocompromised Patients: A Case Report Emphasizing Immune Status and Early Recognition and Treatment

Quaresma,

Paulino,

Oliveira

et al. 2024

Cureus

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“…The GeneXpert MTB/RIF test was evaluated for the diagnosis of TBM in a large group of patients in Vietnam. Although the Ziehl–Neelsen smear remained the most sensitive technique, the GeneXpert MTB/RIF test made an important contribution to the early diagnosis of tuberculous meningitis [ 88 , 89 , 90 ].…”

Section: Molecular Methodsmentioning

confidence: 99%

Evolution of Laboratory Diagnosis of Tuberculosis

Zaporojan,

Negrean,

Hodișan

et al. 2024

Clinics and Practice

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Tuberculosis (TB) is an infectious disease of global public health importance caused by the Mycobacterium tuberculosis complex. Despite advances in diagnosis and treatment, this disease has worsened with the emergence of multidrug-resistant strains of tuberculosis. We aim to present and review the history, progress, and future directions in the diagnosis of tuberculosis by evaluating the current methods of laboratory diagnosis of tuberculosis, with a special emphasis on microscopic examination and cultivation on solid and liquid media, as well as an approach to molecular assays. The microscopic method, although widely used, has its limitations, and the use and evaluation of other techniques are essential for a complete and accurate diagnosis. Bacterial cultures, both in solid and liquid media, are essential methods in the diagnosis of TB. Culture on a solid medium provides specificity and accuracy, while culture on a liquid medium brings rapidity and increased sensitivity. Molecular tests such as LPA and Xpert MTB/RIF have been found to offer significant benefits in the rapid and accurate diagnosis of TB, including drug-resistant forms. These tests allow the identification of resistance mutations and provide essential information for choosing the right treatment. We conclude that combined diagnostic methods, using several techniques and approaches, provide the best result in the laboratory diagnosis of TB. Improving the quality and accessibility of tests, as well as the implementation of advanced technologies, is essential to help improve the sensitivity, efficiency, and accuracy of TB diagnosis.

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“…NAATs have revolutionized TBM diagnosis by amplifying a specific nucleic acid region (pathogen-specific DNA sequence) that uniquely defines M. tuberculosis [ 7 ]. The polymerase chain reaction (PCR) is the most well-known NAAT that consists of extracting the DNA of the pathogen from the sample, amplifying it, and detecting it.…”

Section: Introductionmentioning

confidence: 99%

“…Cureus 15(1): e33783. DOI 10.7759/cureus.33783DNA sequence) that uniquely defines M. tuberculosis[7]. The polymerase chain reaction (PCR) is the most well-known NAAT that consists of extracting the DNA of the pathogen from the sample, amplifying it, and detecting it.…”

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confidence: 99%

Comparison of Protein B Polymerase Chain Reaction (PCR) With IS6110 PCR for Diagnosis of Tuberculous Meningitis Patients

Sehgal¹,

Sharma²,

LNU³

et al. 2023

Cureus

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Tuberculous meningitis (TBM) is a diagnostic challenge. With the conventional staining and culture techniques being too insensitive and time-consuming, and the commercial detection systems being costly, polymerase chain reaction (PCR) seems lucrative for routine laboratories. The purpose of this study was to evaluate the diagnostic potential of protein b antigen polymerase chain reaction (Pab PCR) for TBM, in comparison to IS6110. Another purpose was to compute a cut-off at which adenosine deaminase (ADA) could diagnose TBM. Material and methodsThis is a prospective case-control study to measure the diagnostic accuracy of PCR, BACTEC culture, Lowenstein-Jensen (LJ) culture, ADA, and acid-fast bacilli (AFB) smear tests in TBM. CSF from 50 TBM patients (10 confirmed, 40 clinically suspected) and 40 controls was subjected to Pab PCR and IS6110 PCR, and performance was compared against culture and composite reference standards. ResultsThe overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of Pab PCR in diagnosing TBM were 82%, 100%, 100%, and 81.63%, respectively, and that of IS6110 PCR were 74%, 100%, 100%, and 75.47%, respectively. Both PCRs outperformed culture (p<0.001). Though performance of both PCRs was comparable (p=0.335) with excellent agreement (k=0.86), Pab PCR detected four additional cases, one culture-positive and three culture-negative clinically suspected. ADA of 6.5 IU/L was able to differentiate between TBM and non-TBM with 86% sensitivity and 63% specificity. ConclusionsMolecular tools such as PCR have the potential to increase the clinician's ability to diagnose tuberculous meningitis. Pab PCR is a rapid and reliable method for diagnosing TBM in routine microbiology laboratories.

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Improving Technology to Diagnose Tuberculous Meningitis: Are We There Yet?

Cited by 17 publications

References 74 publications

Central Nervous System Tuberculosis in Immunocompromised Patients: A Case Report Emphasizing Immune Status and Early Recognition and Treatment

Central Nervous System Tuberculosis in Immunocompromised Patients: A Case Report Emphasizing Immune Status and Early Recognition and Treatment

Evolution of Laboratory Diagnosis of Tuberculosis

Comparison of Protein B Polymerase Chain Reaction (PCR) With IS6110 PCR for Diagnosis of Tuberculous Meningitis Patients

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