Urine Test To Detect Active Tuberculosis in HIV-negative Patients

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Highlights:

• A noninvasive urine test can now detect active pulmonary tuberculosis (TB) infection in patients who do not have HIV.
• The test detects a sugar moiety called lipoarabinomannan (LAM) that is a marker for TB infection that the bacterium sheds into the urine.
• Hydrogel nanocages embedded with a chemical dye bait were used to trap LAM in order to increase its detection sensitivity by 100- to 1,000 fold.

Scientists have come out with a noninvasive urine test that can detect the presence of active pulmonary tuberculosis in patients who are not infected with the HIV virus. This test has been used in HIV-positive patients and is now available in HIV-negative patients.

The urine test detects a sugar entity called lipoarabinomannan (LAM) that is a marker of TB. LAM is a cell wall component that is shed into the urine by the bacterium that causes the disease, Mycobacterium tuberculosis. Thus far, LAM could only be detected in patients co-infected with HIV with detection methods failing to detect the sugar in HIV-negative patients. This was probably because immune suppression that occurred in HIV-infected patients led to a sufficient amount of bacteria that could be detected.

‘The detection of a sugar molecule present on the cell wall of the bacterium that causes tuberculosis is now possible even in patients who do not have HIV infection.’

A urine test for TB is ideal in low-resource settings because samples can be collected noninvasively and without specialized training. Also, in general an accurate test for TB is more critical in HIV-negative patients who account for 85% of the TB patients. For this reason, the following study was conducted using analytical nanocage technology in order to increase the sensitivity of the test to detect LAM even in non-HIV tuberculosis patients.

Study

The scientists chose a high-affinity chemical dye bait which was a copper complex reactive dye called RB221 that they embedded in tiny hydrogel meshes to form structures called nanocages. Nanocages have the ability to detect cytokines and other antigens present in low concentrations in urine. The RB221 nanocages were used to trap LAM from urine, increasing detection sensitivity by 100- to 1,000 fold, while at the same time excluding interfering compounds from the samples that could give mixed results.

Forty eight Peruvian patients were chosen, all with active pulmonary TB tested microbiologically, and none infected with HIV and none who had received treatment for TB. The pretreatment urine samples were collected from these patients and LAM was quantitatively measured in the urine as compared to non-TB, healthy and diseased (with other conditions), age-matched controls.

• TB infections were detected with greater than 95% sensitivity, with TB-positive, HIV-negative patients having detectably higher concentrations of LAM in their urine compared to the controls.
• The elevated LAM concentrations in the urine matched with increased body disease burden, meaning more LAM concentrations were found in patients who had higher degree of disease (as measured by the degree of patient weight loss, TB organism count in the cough, cough frequency and appetite).

The current technology has broad implications for screening, transmission control, and treatment management for HIV-negative pulmonary TB patients. The future plan for the study researchers is to compare urinary LAM in patients before and after therapy so as to know the difference the treatment has made.

Nanocages can also be used as a method to detect and monitor other infections making it a very versatile technology.

Tuberculosis

Tuberculosis (TB) is caused by the bacterium, Mycobacterium tuberculosis. The disease most often affects the lungs but can affect other body parts. It is a curable and preventable condition. The mode of transmission of the TB germs is through the air, spreading as people with lung TB cough, sneeze or spit.

TB is listed as one of the top 10 causes of death worldwide. In 2016 there were 10.4 million people (including 1 million children) who had fallen ill with the disease and 1.7 million (including 250000 children) who succumbed to death because of the disease. TB was also the cause of 40% of HIV deaths in 2016. The highest mortality due to TB occurs in low- and middle-income countries, with India leading ahead. Hence, ideally, using a noninvasive body fluid such as urine for the test would be tremendously useful in a low-resource setting.

References:

1. Luisa Paris, Ruben Magni, Fatima Zaidi, Robyn Araujo, Neal Saini, Michael Harpole, Jorge Coronel, Daniela E. Kirwan, Hannah Steinberg, Robert H. Gilman, Emanuel F. Petricoin III, Roberto Nisini, Alessandra Luchini, and Lance Liotta. Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity. Science Translational Medicine 13 Dec 2017: Vol. 9, Issue 420, 2807 DOI: 10.1126/scitranslmed.aal2807
2. Tuberculosis - (http://www.who.int/mediacentre/factsheets/fs104/en/)

Source: Medindia

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