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

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.