Evaluation of the MODS culture technique for the diagnosis of tuberculous meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is a devastating condition. The rapid instigation of appropraite chemotherapy is vital to reduce morbidity and mortality. However rapid diagnosis remains elusive; smear microscopy has extremely low sensitivity on cerebrospinal fluid (CSF) in most laboratorie...

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Main Authors: Caws, M, Dang, T, Torok, E, Campbell, J, Do, D, Tran, T, Nguyen, VC, Nguyen, T, Farrar, J
Format: Journal article
Language:English
Published: Public Library of Science 2007
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author Caws, M
Dang, T
Torok, E
Campbell, J
Do, D
Tran, T
Nguyen, VC
Nguyen, T
Farrar, J
author_facet Caws, M
Dang, T
Torok, E
Campbell, J
Do, D
Tran, T
Nguyen, VC
Nguyen, T
Farrar, J
author_sort Caws, M
collection OXFORD
description BACKGROUND: Tuberculous meningitis (TBM) is a devastating condition. The rapid instigation of appropraite chemotherapy is vital to reduce morbidity and mortality. However rapid diagnosis remains elusive; smear microscopy has extremely low sensitivity on cerebrospinal fluid (CSF) in most laboratories and PCR requires expertise with advanced infrastructure and has sensitivity of only around 60% under optimal conditions. Neither technique allows for the microbiological isolation of M. tuberculosis and subsequent drug susceptibility testing. We evaluated the recently developed microscopic observation drug susceptibility (MODS) assay format for speed and accuracy in diagnosing TBM. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred and thirty consecutive CSF samples collected from 156 patients clinically suspected of TBM on presentation at a tertiary referal hospital in Vietnam were enrolled into the study over a five month period and tested by Ziehl-Neelsen (ZN) smear, MODS, Mycobacterial growth Indicator tube (MGIT) and Lowenstein-Jensen (LJ) culture. Sixty-one samples were from patients already on TB therapy for >1day and 19 samples were excluded due to untraceable patient records. One hundred and fifty samples from 137 newly presenting patients remained. Forty-two percent (n = 57/137) of patients were deemed to have TBM by clinical diagnostic and microbiological criteria (excluding MODS). Sensitivity by patient against clinical gold standard for ZN smear, MODS MGIT and LJ were 52.6%, 64.9%, 70.2% and 70.2%, respectively. Specificity of all microbiological techniques was 100%. Positive and negative predictive values for MODS were 100% and 78.7%, respectively for HIV infected patients and 100% and 82.1% for HIV negative patients. The median time to positive was 6 days (interquartile range 5-7), significantly faster than MGIT at 15.5 days (interquartile range 12-24), and LJ at 24 days (interquartile range 18-35 days) (P<0.01). CONCLUSIONS: We have shown MODS to be a sensitive, rapid technique for the diagnosis of TBM with high sensitivity, ease of performance and low cost (0.53 USD/sample).
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spelling oxford-uuid:fd02e4f2-f797-42e3-ae27-92c94f1d82872022-03-27T13:25:38ZEvaluation of the MODS culture technique for the diagnosis of tuberculous meningitis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fd02e4f2-f797-42e3-ae27-92c94f1d8287EnglishSymplectic Elements at OxfordPublic Library of Science2007Caws, MDang, TTorok, ECampbell, JDo, DTran, TNguyen, VCNguyen, TFarrar, J BACKGROUND: Tuberculous meningitis (TBM) is a devastating condition. The rapid instigation of appropraite chemotherapy is vital to reduce morbidity and mortality. However rapid diagnosis remains elusive; smear microscopy has extremely low sensitivity on cerebrospinal fluid (CSF) in most laboratories and PCR requires expertise with advanced infrastructure and has sensitivity of only around 60% under optimal conditions. Neither technique allows for the microbiological isolation of M. tuberculosis and subsequent drug susceptibility testing. We evaluated the recently developed microscopic observation drug susceptibility (MODS) assay format for speed and accuracy in diagnosing TBM. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred and thirty consecutive CSF samples collected from 156 patients clinically suspected of TBM on presentation at a tertiary referal hospital in Vietnam were enrolled into the study over a five month period and tested by Ziehl-Neelsen (ZN) smear, MODS, Mycobacterial growth Indicator tube (MGIT) and Lowenstein-Jensen (LJ) culture. Sixty-one samples were from patients already on TB therapy for >1day and 19 samples were excluded due to untraceable patient records. One hundred and fifty samples from 137 newly presenting patients remained. Forty-two percent (n = 57/137) of patients were deemed to have TBM by clinical diagnostic and microbiological criteria (excluding MODS). Sensitivity by patient against clinical gold standard for ZN smear, MODS MGIT and LJ were 52.6%, 64.9%, 70.2% and 70.2%, respectively. Specificity of all microbiological techniques was 100%. Positive and negative predictive values for MODS were 100% and 78.7%, respectively for HIV infected patients and 100% and 82.1% for HIV negative patients. The median time to positive was 6 days (interquartile range 5-7), significantly faster than MGIT at 15.5 days (interquartile range 12-24), and LJ at 24 days (interquartile range 18-35 days) (P<0.01). CONCLUSIONS: We have shown MODS to be a sensitive, rapid technique for the diagnosis of TBM with high sensitivity, ease of performance and low cost (0.53 USD/sample).
spellingShingle Caws, M
Dang, T
Torok, E
Campbell, J
Do, D
Tran, T
Nguyen, VC
Nguyen, T
Farrar, J
Evaluation of the MODS culture technique for the diagnosis of tuberculous meningitis.
title Evaluation of the MODS culture technique for the diagnosis of tuberculous meningitis.
title_full Evaluation of the MODS culture technique for the diagnosis of tuberculous meningitis.
title_fullStr Evaluation of the MODS culture technique for the diagnosis of tuberculous meningitis.
title_full_unstemmed Evaluation of the MODS culture technique for the diagnosis of tuberculous meningitis.
title_short Evaluation of the MODS culture technique for the diagnosis of tuberculous meningitis.
title_sort evaluation of the mods culture technique for the diagnosis of tuberculous meningitis
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