Kinetic Determination of Cerebrospinal Fluid Adenosine Deaminase Activity for the Diagnosis of Tuberculous Meningitis

Verajit Chotmongkol Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;

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Phaosin Thongsaen Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;

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Kittisak Sawanyawisuth Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;

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Sittichai Khamsai Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;

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Narongrit Kasemsap Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;

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Nisa Vorasoot Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;

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Kannikar Kongbunkiat Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;

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Somsak Tiamkao Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand;

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Chanpen Sriphan Clinical Laboratory Section, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

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Lumyai Wonglakorn Clinical Laboratory Section, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand

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ABSTRACT.

Tuberculous meningitis (TBM) is a common infectious disease of the central nervous system. Detection of cerebrospinal fluid (CSF) adenosine deaminase (ADA) activity for the diagnosis of TBM has a relatively high accuracy. Most previous reports determined ADA levels by following the colorimetric method of Giusti (endpoint assay). Recently, a Diazyme ADA assay kit was developed to determine CSF ADA levels. This study aimed to define the cutoff value of CSF ADA that is diagnostic for TBM with the Diazyme ADA assay kit. Adults with meningitis were included in the study. The diagnostic properties of CSF ADA for TBM as determined by the Diazyme ADA assay kit were assessed by the receiver operating characteristic curve, area under the curve, sensitivity, specificity, and likelihood ratios. There were 97 patients enrolled in the study, comprising 15 cases of TBM and 82 cases of non-TBM meningitis. The median CSF ADA activity level in the TBM group was significantly higher than in the non-TBM group (P = 0.002), with a mean difference of 14.5 U/L (95% CI: 5.3–23.8 U/L). A CSF ADA level of 6.1 U/L was the best cutoff value to differentiate between the TBM and non-TBM groups, with a sensitivity of 53.33%, a specificity of 89.02%, a positive likelihood ratio of 4.86, a negative likelihood ratio of 0.52, and an area under the curve of 0.75. A CSF ADA level of 6.1 U/L determined by the Diazyme ADA assay kit could be used as a diagnostic tool in the early diagnosis of TBM.

Author Notes

Disclosure: Ethical approval was provided by the Khon Kaen University Faculty of Medicine Ethics Committee as instituted by the Declaration of Helsinki (Approval #HE611173).

Current contact information: Verajit Chotmongkol, Phaosin Thongsaen, Kittisak Sawanyawisuth, Sittichai Khamsai, Narongrit Kasemsap, Nisa Vorasoot, Kannikar Kongbunkiat, and Somsak Tiamkao, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, E-mails: vercho@kku.ac.th, phaosin@gmail.com, kittisak@kku.ac.th, sittikh@kku.ac.th, naroka@kku.ac.th, nsvrs@hotmail.com, kannikarkon@kku.ac.th, and somtia@kku.ac.th. Chanpen Sriphan and Lumyai Wonglakorn, Clinical Laboratory Section, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, E-mails: chanpen@kku.ac.th and wlumya@kku.ac.th.

Address correspondence to Sittichai Khamsai, Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, 40000. E-mail: sittikh@kku.ac.th
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