Utility of MODS for Diagnosis of MDR-TB and Second-Line Antituberculous Drug Susceptibility Testing in Mali
Utility of MODS for Diagnosis of MDR-TB and Second-Line Antituberculous Drug Susceptibility Testing in Mali
Background:

 -Tuberculosis (TB) is an infection of the lungs caused by bacteria. In Mali, TB is diagnosed
 with a test that is fast and inexpensive but not always accurate. The purpose of this study
 is to test a new method for diagnosing TB, called the microscopic-observation
 drug-susceptibility (MODS) test. The MODS test takes 7 days to show results. The test also
 gives information on which drugs will work best in each case.

 Objective:

 -To test a new method for diagnosing tuberculosis called the microscopic observation drug
 susceptibility test.

 Eligibility:

 -  Participants must be 12 years of age or older.

 -  They must have a diagnosis of TB from a sputum smear, or have symptoms of TB and an
 x-ray indicating that TB is present.

 Design:

 -  Participants will take part in the study from 6 months to 21 months and be assigned to
 one of three groups, depending on what type of TB they have.

 -  At the first visit, researchers ask questions about general health and symptoms of TB.
 They check vital signs, draw blood, and ask for a sputum sample. The blood is used to
 check for HIV infection and for the number of CD4 cells, which measures the severity of
 the HIV infection.

 -  The 2-, 5-, and 6-month visits are similar to the first. Those who do not have
 multidrug-resistant (MDR) TB will end their participation after the 6-month visit. MDR
 TB is tuberculosis that has not responded to isoniazid and rifampicin. Participants with
 MDR TB will remain in the study for 21 months.

 -  No treatment is provided as part of this study.
Approximately one-third of the world s population is infected with tuberculosis (TB), and
 over 1 million deaths occur annually worldwide because of it (1,2). Accurate diagnosis and TB
 drug susceptibility testing is necessary to treat the infection appropriately and bring this
 epidemic under control. Inappropriate treatment of TB, on the other hand, has led to the
 recent spread in multidrug-resistant TB (MDR-TB), estimated to affect over half of million
 people worldwide (2,4,5). Sputum smear microscopy, the diagnostic method commonly used in
 developing countries, is not as sensitive at detecting TB as culture-based techniques
 utilized in developed countries. Furthermore, drug-susceptibility testing is not routinely
 performed in resource-limited settings. Consequently, many individuals with TB in developing
 countries are treated with inadequate regimens, and MDR-TB continues to spread.

 The microscopic-observation drug-sensitivity (MODS) assay has been recently developed for
 rapid diagnosis of TB and simultaneous detection of resistance to first-line TB medications
 in resource-limited settings (11). MODS has been shown to be as sensitive as traditional
 culturebased methods for the detection of TB, providing results for drug susceptibility
 testing that are highly concordant with standard techniques (10).

 We propose to study the utility of the MODS assay for the diagnosis of TB in subjects who are
 sputum-smear positive or sputum-smear negative, and those with chronic TB. Susceptibility
 testing will be performed for first-line antituberculous drugs and, subsequently, second-line
 drugs, if subjects are found to have MDR-TB. The first primary objective is to calculate the
 sensitivity of detection of the MODS assay, compared with the Middlebrook culture method, in
 subjects suspected of having TB who are sputum-smear positive by microscopy. The second
 primary objective is to calculate the concordance of drug-susceptibility testing between the
 MODS assay and the agar proportion method for subjects who are sputum-smear positive,
 sputum-smear negative, or diagnosed with chronic TB.

 Secondary objectives include evaluating the utility of the MODS assay in the diagnosis of TB
 in subjects who are sputum-smear negative and those with chronic TB, the performance of
 second-line drug-susceptibility testing using the MODS assay in subjects diagnosed with
 MDRTB, the utility of the MODS assay in the diagnosis of TB in subjects coinfected with human
 immunodeficiency virus (HIV)-1 or -2, and the ability of the MODS assay to identify
 nontuberculous mycobacteria in subjects harboring these organisms.
-  INCLUSION CRITERIA:

 Individuals (12 years of age) who meet the following criteria are eligible for enrollment
 in the study:

 Have a sputum smear that is positive for acid-fast bacilli by microscopy or have clinical
 symptoms and abnormal findings compatible with active TB on a previously performed chest
 radiograph.

 Have either completed at least 5 months of treatment with antituberculous therapy within
 the past year or have not received any antituberculous treatment in the preceding 5 years.

 Willingness to provide a sputum sample for the study.

 Ability to follow verbal instructions for producing sputum.

 Willingness to undergo testing for HIV.

 Willingness to allow storage of samples for future research.

 EXCLUSION CRITERIA:

 Subjects who meet any of the following criteria are not eligible for enrollment in the
 study:

 Any condition that in the investigator s opinion places the subject at undue risk by
 participating in the study.

 Subjects younger than 12 years of age will be excluded from the study due to the difficulty
 of obtaining adequate sputum samples for the diagnosis of TB in this population and because
 there are no means for obtaining gastric aspirates at the reference centers.