Feasibility of a Lateral Flow Urine Lipoarabinomannan (LAM) Test for Diagnosis of Tuberculosis
Feasibility of a Lateral Flow Urine Lipoarabinomannan (LAM) Test for Diagnosis of Tuberculosis
The purpose of this study is to evaluate the accuracy, diagnostic yield, operational
 performance, and time to diagnosis of a novel lateral-flow urine lipoarabinomannan (LAM) test
 in detecting tuberculosis in HIV-infected adults.

 A secondary study objective is to determine the accuracy, efficiency, costs, and
 cost-effectiveness of various combinations of Tuberculosis (TB) diagnostic tests, including
 the novel Xpert MTB/Rif test.
Background: Tuberculosis (TB) incidence and mortality have increased dramatically as a result
 of the HIV epidemic. In parts of sub-Saharan Africa, TB is the leading cause of death among
 HIV-infected patients and approximately 50% of TB patients are HIV co-infected. Early
 treatment of TB is hindered by the lack of rapid, accurate diagnostic modalities that can be
 applied in resource-constrained settings. Mycobacterial culture is the laboratory standard
 for diagnosis of active TB, but it is costly, requires access to specialized laboratories,
 and takes weeks to provide results. Sputum smear microscopy detects less than half of
 HIV-infected TB cases in many settings. The Global Plan to Stop TB has prioritized the
 development of simple, accurate, inexpensive tests for TB case detection in HIV-positive
 individuals.

 LAM: As a strategy for rapid TB diagnosis, the detection of Mycobacterium tuberculosis
 antigens has been explored over several decades. Lipoarabinomannan (LAM), a glycolipid
 component of the outer cell wall of mycobacteria, is an attractive diagnostic target for
 several reasons: it is heat-stable; cleared by the kidney; detectable in urine; and as a
 bacterial product, has the theoretical potential to discriminate active TB from latent TB
 infection independent of human immune responses. A urine test could facilitate TB diagnosis
 in patients in whom sputum is uninformative or not obtainable, and lacks the
 infection-control risks associated with sputum production or blood collection. Urine LAM
 detection may be amenable to simple, rapid, inexpensive point-of-care platforms.

 This is a prospective study to evaluate the accuracy, diagnostic yield, operational
 performance, and time to diagnosis of a novel lateral-flow urine LAM test in detecting
 tuberculosis in HIV-infected adults. HIV-positive adults suspected to have TB will be
 enrolled after providing informed consent. Urine will be obtained for testing using the novel
 lateral flow urine LAM assay and an existing ELISA-based urine LAM assay. Conventional
 microbiological tests for TB and chest x-rays will also be performed. These tests will be
 performed on all participants enrolled (target sample size = 500).

 A secondary study objective is to determine the accuracy, efficiency, costs, and
 cost-effectiveness of various combinations of TB diagnostic tests, including the novel Xpert
 MTB/Rif test. The Xpert MTB/Rif test will be performed on a subset of participants
 (approximately 200 participants out of the total of 500 participants we expect to enroll for
 the LAM component of the study.)
Inclusion Criteria (Individuals must meet all of the following inclusion criteria in order
 to be eligible to participate):

 -  Informed consent

 -  Suspected active tuberculosis

 -  Willingness and ability to comply with study procedures

 -  Any one or more of the following:

 -  Current cough

 -  Fever at any time within the preceding 4 weeks

 -  Night sweats at any time within the preceding 4 weeks

 -  Weight loss within the preceding 4 weeks

 -  HIV-positive based on any one or more of the following:

 -  written results of a positive HIV antibody test, and/or

 -  written results of a positive HIV viral load, and/or

 -  documentation in the medical record of positive HIV status by a treating
 clinician.

 Exclusion Criteria (Any subjects meeting any of the following exclusion criteria at
 baseline will be excluded from study participation):

 -  Multidrug tuberculosis treatment for greater than two days within the previous 60 days

 -  Unwillingness or inability to provide a urine sample

 -  Known chronic pulmonary condition, e.g. asthma, chronic obstructive pulmonary disease,
 emphysema

 -  Respiratory distress, defined as respiratory rate of >30 or oxygen saturation <90%

 -  Any specific condition that in the judgment of the investigator precludes
 participation because it could affect a subject's safety.