Xpert MTB/RIF Assay for Diagnosis of Tuberculous Meningitis (TBM) in Maharaj Nakorn Chiang Mai Hospital

March 12, 2023 updated by: Poramed Winichakoon, Chiang Mai University
Early diagnosis and appropriate treatment of tuberculous meningitis (TBM) are crucial steps to reduce morbidity and mortality. The WHO recommended to use Xpert MTB/RIF assay to diagnose pulmonary TB, pediatrics TB, extra pulmonary TB and rifampicin resistance. However, the data of accuracy in diagnosis of TBM is still lacking. This study aimed to find out the diagnostic performance of Xpert MTB/RIF assay for the diagnosis of tuberculous meningitis, especially in patients who presented with subacute lymphocytic meningitis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Tuberculous meningitis (TBM) was the most serious manifestation of Mycobacterium tuberculosis infection with high rates of morbidity and mortality if treatment is delayed, especially in HIV-infected patients. The fatality rates increased to 60 percent compared to about one third in non-HIV infection. Prevalence and incidence of TBM worldwide is unclear. In 2015, the incidences of TBM were approximately 6-10 percent. In Northern Thailand, from the national survey programs, the prevalence rates of TBM were about 9.7 per 100,000 people, and TBM was the most common cause of death in extra-pulmonary TB patients with mortality rates about 0.54 per 100,000 people. However, these may be underreported due to diagnostic problems.

Prompt and accurate diagnoses with early treatments, were the key elements to reduce deaths and disabilities in TBM. However, there were some major obstacles in the diagnostic procedures concerning the limitations, such as low sensitivity in conventional acid-fast bacilli (AFB) microscopy staining techniques or long turnaround times in gold-standard culture. Therefore, the delays in diagnoses lead to late managements and increased mortalities in TBM, especially in multidrug-resistance (MDR) cases. In the past, a lot of studies tried to solve these problems urgently, but the low frequency of confirmed cases and the absence of a consensus clinical case definition were the huge barriers causing a lack of progression in new clinical trials. In 2010, a uniform clinical case definition for use in clinical research about TBM was established. They used criteria from clinical characteristics, cerebrospinal fluid (CSF) examinations, neuroimaging studies, and evidence of tuberculosis elsewhere. Additionally, microbiological or pathological proof was used to classify the patients who had signs and symptoms of meningitis and were defined as definite, probable, possible, and not tuberculous meningitis. Since then, many clinical studies about TBM diagnosis were developed and made more convenient.

The Xpert MTB/RIF assay was the closed-cartridge-based system heminested PCR for the diagnosis of tuberculosis (TB), and detecting the rifampicin resistant gene in sputum and the CSF. This can be used as a marker for MDR-TB, focused on endemic areas and HIV coinfection. This test has better diagnostic threshold levels (80-100 cfu/ml) than the 5,000 cfu/ml in AFB microscopy staining techniques, shorter duration for the results than conventional TB cultures, and more simplification than nucleic-acid amplification tests. Many studies about the diagnostic accuracy revealed that sensitivity and specificity of this new test varied from 50-86 % and 94-98 % depended on method, population, and laboratory techniques. There were some discussions about the application practicality in the diagnosis of TBM, such as in a large-population study in Vietnam that questioned the lower sensitivity and cost-effectiveness compared with conventional staining and culture. Subsequently, this newer rapid test was approved by WHO for TBM diagnosis.

In Thailand, one of the countries with a high burden of tuberculosis, despite many advantages, use of this test was limited in CSF specimens due to the lack of data, including accuracy in CSF specimens for TBM diagnosis among the Thai population. This study aims to prospectively find out the diagnostic performance and accuracy of Xpert MTB/RIF in CSF samples from patients who presented with subacute lymphocytic meningitis in Northern Thailand, which can be the database for extending the study to cover patients in other parts of Thailand.

Study Type

Interventional

Enrollment (Actual)

62

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Presence of meningitis symptoms and signs including one or more of the following: headache, irritability, vomiting, fever, neck stiff ness, convulsions, focal neurological deficits, altered consciousness, or lethargy at least 5 days prior to admission, plus

  2. CSF with abnormalities of at least two of these three characters;

    • Lymphocytic pleocytosis (≥ 50%)
    • More than 40 mg/ml of protein
    • Lower than 0.5 of CSF: blood sugar ratio

Exclusion Criteria:

  1. Contraindicated in lumbar puncture
  2. Positive for cryptococcal antigen in the CSF.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Xpert
Centrifuged CSF sent for Xpert MTB/RIF
Diagnostic test: Xpert MTB/RIF
CSF samples was centrifuged at 3,000 - 4,000 X g for 15 minutes. Supernatant was removed to leave a 1-ml precipitate, which was then used for Ziehl-Neelsen AFB staining (100 μl), inoculation of MGIT culture (100 μl), and Xpert MTB/RIF testing (800 μl).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Detection of M. tuberculosis from CSF specimen
Time Frame: 2 years
Diagnostic values of Xpert MTB/RIF for detecting M. tuberculosis from CSF
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chiang Mai University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2015

Primary Completion (Actual)

March 30, 2016

Study Completion (Actual)

December 31, 2016

Study Registration Dates

First Submitted

March 29, 2017

First Submitted That Met QC Criteria

March 12, 2023

First Posted (Actual)

March 23, 2023

Study Record Updates

Last Update Posted (Actual)

March 23, 2023

Last Update Submitted That Met QC Criteria

March 12, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CMUXpertTBM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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