Immunocytochemical Method for Early Laboratory Diagnosis of Tuberculous Meningitis

Sumi, Masaki; Mathai, A; Reuben, S; Sarada, C; Radhakrishnan, V. V.

doi:10.1128/cdli.9.2.344-347.2002

Cited by 13 publications

(16 citation statements)

References 11 publications

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“…In addition to measuring M. tuberculosisspecific antibodies or antibody-secreting cells, assays to measure M. tuberculosis-specific antigens directly in the CSF have also been evaluated (32,82,86,92,103,125,202,203,205,236) (Table 3). A theoretical advantage of antigen detection over antibody detection would be that they would be released only as a result of the host's immune response or the result of treatment.…”

Section: Molecular and Biochemical Analysismentioning

confidence: 99%

Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects

et al. 2008

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SUMMARY Tuberculosis of the central nervous system (CNS) is a highly devastating form of tuberculosis, which, even in the setting of appropriate antitubercular therapy, leads to unacceptable levels of morbidity and mortality. Despite the development of promising molecular diagnostic techniques, diagnosis of CNS tuberculosis relies largely on microbiological methods that are insensitive, and as such, CNS tuberculosis remains a formidable diagnostic challenge. Insights into the basic neuropathogenesis of Mycobacterium tuberculosis and the development of an appropriate animal model are desperately needed. The optimal regimen and length of treatment are largely unknown, and with the rising incidence of multidrug-resistant strains of M. tuberculosis, the development of well-tolerated and effective antibiotics remains a continued need. While the most widely used vaccine in the world largely targets this manifestation of tuberculosis, the BCG vaccine has not fulfilled the promise of eliminating CNS tuberculosis. We put forth this review to highlight the current understanding of the neuropathogenesis of M. tuberculosis, to discuss certain epidemiological, clinical, diagnostic, and therapeutic aspects of CNS tuberculosis, and also to underscore the many unmet needs in this important field.

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Section: Molecular and Biochemical Analysismentioning

confidence: 99%

Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects

et al. 2008

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“…In another study by Brienz et al, two PCR protocols showed low sensitivities (36% and 53% for the TB AMPLICOR assay and the MPB64 nested PCR, respectively) compared with those of classic microbiological methods (73% and 54% for Ziehl-Neelsen staining and culture, respectively) for the diagnosis of TBM in 91 patients in southeastern Brazil (3). An immunocytological method with CSF-cytospin smears was used by Sumi et al to detect Mycobacterium antigens in the cytoplasm of CSF monocytes and showed a sensitivity of 72% (20). The overall sensitivities of dot ELISA (for the detection of Mycobacterium antigen in CSF) and PCR were 75% and 40%, respectively (21).…”

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confidence: 99%

Comparative Evaluation of Early Diagnosis of Tuberculous Meningitis by Different Assays

et al. 2006

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Cerebrospinal fluid (CSF) and peripheral blood (PBL) were sampled multiple times from 25 patients with a clinical diagnosis of tuberculous meningitis (TBM) and 49 controls, including 27 patients with other infectious diseases of the central nervous system and 22 patients with other noninfectious neurological diseases. We used an enzyme-linked immunospot assay (ELISPOT) to detect anti-Mycobacterium bovis BCG antibody-secreting cells in CSF and PBL, PCR to detect a repeated insertion sequence (IS6110) specific for Mycobacterium tuberculosis in CSF, and an enzyme-linked immunosorbent assay (ELISA) to detect anti-BCG antibodies in CSF and PBL. In the meantime, culture of CSF from every TBM and control patient was done on Lowenstein-Jensen medium. ELISPOT proved to be the most valuable test, with a sensitivity of 84.0% and a specificity of 91.8%, and showed a sensitivity of 100.0% with the CSF specimens obtained within 4 weeks after the onset of TBM. The numbers of CSF anti-BCG immunoglobulin-secreting cells tested by ELISPOT were even higher in the early phase of TBM and declined while the disease was going on (P ‫؍‬ 0.008), which allowed an early diagnosis to be made. The sensitivities of PCR and ELISA were only 75.0% and 52.3%, respectively; and the specificities were 93.7% and 91.6%, respectively. Culture of CSF on Lowenstein-Jensen medium was the least sensitive (16%) compared to the sensitivities of the other three assays. Our results demonstrate that the ELISPOT technique is worthy for routine use in the laboratory to support the clinical diagnosis of TBM.In the past several years there has been a global increase in the incidence of tuberculosis along with the prevalence of AIDS and the emergence of multidrug-resistant strains. Tuberculous meningitis (TBM) is a major global health problem and is the most severe form of extrapulmonary tuberculosis, with a high rate mortality. TBM is diagnosed on the basis of clinical features, cerebrospinal fluid (CSF) studies, and radiological findings. Due to the variable clinical presentations and CSF findings, which can be confused with those of other chronic infections of the central nervous system (CNS), TBM is sometimes difficult to diagnosis with certainty, especially in its early phase (about 1 to 2 weeks after onset, according to our clinical observations). During this time period, the typical clinical manifestations of TBM have not fully developed. The polymorphonuclear pleocytosis in CSF can occur early and may give an erroneous impression of bacterial meningitis. Also during this time period, the antibiotic or antituberculous treatment has lasted for just a short time, and the effect of therapy is not obvious enough to be able to make a judgment. The contrast enhancement of the basal cisterns, hydrocephalus, or lesions in the brain parenchyma on a computed tomography (CT) image or a magnetic resonance imaging image specific for TBM may not occur so early. Previous clinical studies have clearly demonstrated that the timing of the onset of chemotherapy is the most cr...

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“…During the second stage, bacilli grow logarithmically within newly recruited macrophages (7). Thus, the cytoplasm of the macrophages in active TBM patients contains TBAg (23). Theoretically the positive immunostaining of cytoplasm of CSF macrophages means that viable tubercle bacilli are present.…”

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confidence: 99%

“…Theoretically the positive immunostaining of cytoplasm of CSF macrophages means that viable tubercle bacilli are present. Correspondingly, Sumi et al (23) reported that the method had promising sensitivity and specificity (72.5% and 100%, respectively). Nevertheless, the sample size in their study was relatively small (22 cases).…”

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confidence: 99%