Oral Urea Breath Testing for Diagnosis and Treatment Response in Pulmonary Tuberculosis
Oral Urea Breath Testing for Diagnosis and Treatment Response in Pulmonary Tuberculosis
Background:

 -  Tuberculosis is a disease of the lungs caused by the bacteria Mycobacterium tuberculosis
 (M. tuberculosis). The most popular and least expensive tool used to detect the presence
 of the tuberculosis bacteria is called sputum smears, which is a lab test used to look
 for bacteria in the sputum via a microscope. However, the test s results are not always
 accurate, and the test cannot determine if the bacteria will be resistant to standard
 tuberculosis treatments. The most sensitive test currently available is called sputum
 culture, in which a sputum sample is used to check for the growth of tuberculosis
 bacteria. However, this test takes at least a month to produce accurate results, and
 requires expensive equipment that is not available in many countries where M.
 tuberculosis is found.

 -  The urea breath test (UBT) has been used to detect infection with Helicobacter pylori, a
 bacteria associated with stomach ulcers, by testing individual breath samples.
 Researchers are interested in determining whether breath samples can also be used to
 detect the presence of M. tuberculosis in the lungs of subjects with tuberculosis, and
 to see if tuberculosis treatments are successful.

 Objectives:

 - To assess the sensitivity and specificity of urea breath testing in the diagnosis and
 treatment response of pulmonary tuberculosis.

 Eligibility:

 -  Individuals at least 18 years of age who either have been diagnosed with tuberculosis or
 are healthy volunteers with no past history of tuberculosis.

 -  The study will be conducted in Bamako, Mali.

 Design:

 -  This study will involve three groups: two pilot groups of individuals who have already
 been diagnosed with tuberculosis, and a primary study group of both healthy volunteers
 and individuals who have been diagnosed with tuberculosis.

 -  Participants will be screened with a physical examination and medical history, as well
 as blood, sputum, stool, and urine samples.

 -  First pilot group (one visit):

 -  Participants should not eat, drink, or smoke for at least 1 hour prior to the UBT test.

 -  Participants will provide a baseline exhaled air sample, and then will receive the UBT
 test, which involves a dose of Pranactin -Citric dissolved in water. Additional exhaled
 air samples will be collected at eight time points (10, 20, 45, 60, 90, 120, 180, and
 240 minutes after the dose).

 -  Second pilot group (one or two visits):

 -  Participants should not eat, drink, or smoke for at least 1 hour prior to the UBT test.

 -  Participants will provide a baseline exhaled air sample, and then will receive the UBT
 test. Half of the participants will receive a dose of bismuth (Pepto-Bismol) prior to
 collection of air samples to see how this affects the results of the UBT test.
 Additional exhaled air samples will be collected at three time points specified by the
 study researchers.

 -  On the following day, participants will return for a second visit to provide three more
 exhaled air samples.

 -  Primary study group (five visits for participants with tuberculosis, two visits for
 healthy volunteers):

 -  All participants will have two visits, following the procedures given for the second
 pilot group. Half will receive a dose of bismuth prior to collection of air samples.

 -  Participants with tuberculosis will have three additional visits (days 6, 10, and 16
 following the first study visit) to provide additional sputum and exhaled air samples to
 monitor the progress of tuberculosis treatment.
Tuberculosis (TB) is a disease that affects the population worldwide, with 9 million people
 being infected every year. It is associated with high rates of mortality and morbidity.
 Reports show that a person dies from tuberculosis every 20 seconds worldwide. Current
 diagnostic techniques are either inadequate at detecting TB cases with precision, or they are
 time consuming, expensive, and require laboratory equipment not available in developing
 countries, where the disease is endemic. Furthermore, rates of multi-drug-resistant (MDR) TB
 are estimated to be over 5 percent of the incident cases globally and extremely
 drug-resistant (XDR) TB rates are on the rise. These statistics highlight the need for new
 and improved diagnostic tools for TB, as well as biomarkers that can quickly detect drug
 resistant organisms or treatment failures to first-line antimicrobials.

 Urea breath test (UBT) has been approved by the Food and Drug Administration (FDA) for the
 detection of Helicobacter pylori. It is known that H. pylori possesses a urease enzyme that
 degrades urea in the stomach, producing carbon dioxide (CO (2)), which is then exhaled and
 can be detected in the lungs. Mycobacterium tuberculosis like H. pylori possesses a urease
 enzyme, which converts urea to carbon dioxide and ammonia. In a preclinical study, Jassal and
 colleagues demonstrated that TB-infected rabbits convert [(13)C]-labeled urea into
 [(13)C]-carbon dioxide ((13)CO(2)) in a matter of minutes. The (13)CO(2) in exhaled breath
 could be rapidly detected with an isotopic ratio mass spectrometer or a small ultraviolet
 (UV) absorbance spectrometer.

 The primary objective of the current study is to evaluate the sensitivity and specificity of
 UBT in the diagnosis and treatment response of pulmonary TB. Secondary objectives are to
 assess the specificity of UBT for M. tuberculosis (UBT-TB) diagnosis in volunteers with and
 without H. pylori infection, examine the benefit of bismuth to make UBT-TB more specific for
 M. tuberculosis, and evaluate the correlation of the labeled (13)CO(2) signal with sputum
 colony forming unit (CFU) counts and the lower limit of signal detection versus CFU counts.
-  INCLUSION CRITERIA:

 Individuals (greater than or equal to18 years of age) are eligible to enter the study, if
 they meet the following criteria:

 -  Healthy volunteers (primary study group) or have a diagnosis of TB (as diagnosed by
 sputum smear tests; all three study groups).

 -  Willingness and ability to give informed consent.

 -  Willingness to undergo HIV testing.

 -  Willingness to have samples stored for future studies.

 EXCLUSION CRITERIA:

 Subjects are not eligible to enter the study, if they meet any of the following criteria:

 -  HIV infection.

 -  Past history of TB (Healthy volunteers only)

 -  Pregnancy and lactation

 -  Known history of diabetes

 -  Use of Tuberculosis treatment proton pump inhibitor treatments or use of bismuth
 containing preparations in the last 15 days prior to study entry.

 -  History of failed TB treatment

 -  Known allergy to aspirin or hypersensitivity to mannitol, citric acid or aspartame
 such as a clinical history suggestive of aminoacidurias.

 -  Any known medical disorder or other circumstance, which in the opinion of the PI,
 might make the participation of the individual unsafe or difficult. The reason for
 exclusion will be documented in the screening log.