Scientists have finally developed a
noninvasive tuberculosis test for a pool of people for whom such assessments
have previously been difficult: people who don’t have HIV. The researchers’
test detects active tuberculosis infections from urine samples.
They say the technology has urgently needed and
broad implications for screening, transmission control, and treatment
management. Tuberculosis is one of the most common bacterial infections, with
9.6 million cases and 1.5 million deaths reported worldwide in 2014.
Previous attempts to develop urine tests for TB
(ideal in low-resource settings because samples can be collected noninvasively
and without specialized training) have only detected infections in HIV-positive
patients, possibly because immune suppression leads to substantially elevated
bacteria levels in the body. Seeking to capture small amounts of a
sugar called LAM (which partially comprises the tuberculosis bacterium’s outer
coat) in urine, Luisa Paris and colleagues screened 37 compounds to narrow in
on a copper complex dye called RB221 that they embedded in tiny hydrogel meshes
to form structures called nanocages.
The RB221 nanocages trapped LAM from urine,
increasing detection sensitivity by 100- to 1,000 fold, all while excluding
interfering compounds from the samples that could confound results. In 48
Peruvian HIV-negative tuberculosis patients who hadn’t yet been treated, the
new test detected infections with greater than 95% sensitivity. What’s more, elevated
LAM concentrations in urine correlated with increased amounts of bacteria and
more severe disease (as measured by weight loss or a cough). The
researchers also created nanocages to trap and detect other hallmarks of
infection including very low abundance molecules named ESAT6 and CFP10. According
to the authors, their next steps are to compare urinary LAM in patients before
and after therapy to evaluate potential treatment-induced changes.
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