Multi-Drug Resistant Tuberculosis in Korea
Multi-Drug Resistant Tuberculosis in Korea
This study, conducted in Korea, will examine why some people are more susceptible to
 tuberculosis (TB) than others and why some strains of M tuberculosis (the bacteria that
 causes TB) are more difficult to treat or become resistant to drug treatments. The study will
 compare blood samples and other medical information from patients with different kinds of
 tuberculosis and with healthy volunteers to identify patient and bacterial characteristics
 that contribute to disease susceptibility, treatment failure, disease recurrence and
 multi-drug resistance.

 Healthy volunteers and patients with tuberculosis who are 20 years of age or older may be
 eligible for this study. Subjects are recruited from among patients receiving treatment for
 tuberculosis at the National Masan Tuberculosis Hospital in the Republic of Korea and from
 healthy people visiting government health care centers for annual medical checkups. The
 latter include people who have had TB but are cured; people who have been exposed to TB, but
 currently have no signs of disease; and those who have not been exposed to TB.

 Participants with tuberculosis undergo the following tests and procedures:

 -  Medical history, including past treatments for TB, and review of medical records

 -  Interview about home and work

 -  Sputum collection to test for the kind of TB bacteria present and for genetic studies of
 the bacteria

 -  Drug treatment for TB

 -  Blood draws as part of regular patient care, for HIV testing, and for genetic studies

 -  Chest x-rays as part of routine patient care

 -  In patients with recurrent disease, examination of the strains from both bouts of
 disease to determine if it is a recurrence of the same organism or infection with a new
 strain.

 Healthy volunteers undergo the following tests and procedures:

 -  Brief medical history

 -  Blood draw to look for exposure to TB and for genetic studies

 -  Review of previous x-ray to look for active TB
This natural history study seeks to determine some of the mycobacterial and host factors
 involved in the failure of antituberculous chemotherapy, disease recurrence, and the
 development of multidrug resistance by M. tuberculosis. Despite optimal treatment with
 directly-observed short-course therapy (DOTS), about 5-10% of compliant patients with "cured"
 tuberculosis relapse, usually within a year after completion of therapy. In Korea, where DOTS
 is not practiced, the relapse rate has been reported to be 15 to 20 %. In individual
 patients, failure to eradicate disease contributes directly to the development of
 drug-resistance and to low overall cure rates. While factors such as patient drug compliance
 and HIV status have been extensively studied in relation to rates of relapse; host genetic
 factors and the specific relevance of the infecting mycobacterial strain have not yet been
 investigated in detail. Identification of patient characteristics and specific strains of M.
 tuberculosis that are associated with relapse and the evolution of drug resistance would
 greatly facilitate the development of treatment protocols that might avoid these
 complications.

 Our study population will consist of subjects with pulmonary tuberculosis receiving treatment
 at our study sites. Healthy volunteers will be selected as the genotypic control population.
 All subjects with tuberculosis enrolled in the study will be followed by periodic chart
 review and data extraction during their treatment and follow-up at participating study sites.
 For 2.5 years after completing drug treatment, tuberculosis recurrence among study subjects
 will be identified using periodic chart abstraction and follow-up phone calls every 6 months
 to determine the 2 year recurrence rate for tuberculosis (TB). M. tuberculosis isolates may
 be collected from subjects with recurrent TB and analyzed to distinguish between relapse and
 re-infection.

 Study subjects will be asked to provide 10 mL of blood and 5 to 30 mL of sputum for acid-fast
 bacilli (AFB) smear and culture at entry. Sputum will be cultured for M. tuberculosis and
 isolates will be tested for drug resistance (DR). The research staff may use molecular DR
 tests to confirm the agar-growth DR results. In addition, subjects will be asked a series of
 medical history questions including history of prior tuberculosis, antituberculous treatment,
 disease contacts, and risk factors associated with tuberculosis; and will be asked to give
 consent to allow clinical research staff to abstract treatment regimens and results from
 their inpatient and outpatient medical charts for the duration of their participation in the
 study (treatment and follow-up).
-  INCLUSION CRITERIA:

 For the new cases disease group (Cohort A):

 1. Age greater than or equal to 20 years old;

 2. Primary treatment (new TB subject by WHO definition) for tuberculosis without
 treatment interruption (greater than or equal to 60 days) and with at least 4 months
 of treatment remaining;

 3. Clinical signs or symptoms suggestive of tuberculosis;

 4. Sputum AFB smear-positivity or confirmed MTB using any molecular test

 For previously treated disease group (Cohort B):

 1. Age greater than or equal to 20 years old;

 2. Treated for tuberculosis previously with more than 30 days of drug treatment and
 either:

 1. a treatment interruption of greater than or equal to 60 days (includes relapse
 and treatment after interruption), or

 2. who have experienced treatment failure or have chronic TB.

 3. Clinical signs or symptoms suggestive of tuberculosis;

 4. Sputum AFB smear-positivity or confirmed MTB using any molecular test

 For healthy controls (Cohort C):

 1. Age greater than or equal to 20 years old;

 2. No previous diagnosis of TB as reported by the subject;

 EXCLUSION CRITERIA:

 For TB Subjects

 1. Women who report themselves to be pregnant or possibly pregnant during the protocol
 introduction and consent process (pregnant women are not normally treated at NMTH).

 For Healthy Volunteers:

 1. Women who report themselves to be pregnant or those found to be pregnant by a urine
 Beta-HCG test during the protocol introduction and consent process.

 2. Those having a chest X-ray suggestive of active tuberculosis.