FYI and apologies for cross posting
---------- Forwarded message ---------
From: Laura Lopez Gonzalez
Date: Tue, Jul 9, 2019 at 4:24 AM
Subject: New opinion piece on the benefits and limitations of the TB Lam
This opinion piece sets out the benefits and limitations of the test in a
pretty easy-to-understand way for those in high HIV burden countries. The
piece is available for free republication with prior approval as well via
All the best,
Laura Lopez Gonzalez
+27 (0)76.467.5208 (mobile)
*TB: This pee test could save your life*
*What if diagnosing South Africa’s deadliest disease was as simple as
taking a drug store pregnancy test? That day might be closer than you
*Professor Keertan Dheda*
“The white plague”, consumption — and on South Africa’s gold fields,
phthisis — whatever its name, the bacteria was on the prowl long before
modern science dubbed it tuberculosis.
On March 24 1882, scientist Robert Koch discovered the bug that causes TB,
naming it *Mycobacterium tuberculosis.*
Using the most advanced technology of the time, Koch’s trusted microscope,
the tiny germs had a rod-like appearance — it was a scene that, in 1882,
had only been made possible through Koch’s invention of new types of
staining techniques that would make first TB, then cholera, come alive
under the microscope.
And for more than a century, this is what TB tests looked like: rows of
scientists hunched over their microscopes in labs across the world,
desperately searching for those tiny rods among the gunk and gob that
people could bring themselves to cough up as part of sputum samples.
Then in 2010, the World Health Organisation (WHO) endorsed the GeneXpert
a coffeemaker-sized machine that could deliver a TB diagnosis within two
hours. By 2011, there was a growing field of rapid tests for the disease
that, according to the WHO, would affect more than eight million people in
that year alone.
But there was a problem: whether it was the samples under Koch’s
microscope, or what was loaded into the fancy GeneXpert machines, these
tests all relied on sick people’s ability to produce sputum from deep
within the respiratory tract. It was a task too difficult for most of the 38
000 children the WHO says develop active TB each year in South Africa
Many people with HIV — who account for about 70% of all TB deaths in the
country, according to the latest WHO report
<https://www.who.int/tb/publications/global_report/en/> — also found
producing sputum challenging.
And this gap can prove deadly. A 2015 review of three dozen studies and
more than 3 000 autopsies of adults and children living with HIV in the
Global South found that TB was responsible for four out of 10 deaths. Among
those who died of TB, more than 40% had TB in places other than their lungs
— meaning it would have been missed by conventional testing.
Almost half of the patients had never been diagnosed, the study published
in the journal *Aids* revealed.
But that has now changed.
The world’s first truly point-of-care TB test
Recently, a new low-cost test was developed to diagnose TB in hard-to-catch
patients, particularly those with advanced HIV. It works in much the same
way a pharmacy pregnancy test does, and all in about 25 minutes.
The test looks to detect a type of sugar-bound molecule found in the cell
wall of the TB bug in a few drops of urine placed on an absorbent paper
strip. This molecule is known as lipoarabinomannan, or Lam for short. If
the TB Lam test produces a single red line, it signals to healthcare
workers that patients should be started on TB treatment.
Today, the Lam dipstick is the only point-of-care test for TB we have.
But what does it mean for patients? Well, a team and I conducted the first
real-world controlled study to find out, putting it to the test among
almost 3 000 HIV-positive patients with TB symptoms in 10 hospitals in four
countries: South Africa, Zambia, Tanzania and Zimbabwe. Half of the
patients were randomly tested for TB by means of standard sputum-based
methods, including the GeneXpert and, yes, even Koch’s old,
microscope-based test as well as the TB Lam test. The other 50% of people
only received standard testing.
People who were tested through the Lam diagnostic were not only more likely
to start treatment, the 2016 study published in the medical journal* The
Lancet* found, they were also less likely to die. The research showed that
when used in hospitalised, HIV-positive patients, the Lam test led to a
roughly 20% decrease in death rates.
The early results of the trial led the WHO to recommend
<https://www.who.int/tb/publications/use-of-lf-lam-tb-hiv/en/> the test’s
use in people living with advanced HIV and TB symptoms in 2015, although
the body stopped short of greenlighting the test for broader use based on
Then, in 2018, another study, also published in *The Lancet*, and conducted
among about 3 000 people in Malawi and South Africa, indicated that the
urine dipstick — when combined with GeneXpert testing — could pick up TB in
people with HIV before they’d even begun to experience symptoms of the
But the TB urine test has its limits.
Negative tests don’t necessarily rule out TB so more tests are needed to
confirm a negative diagnosis, and some types of genital fungal infections
will also cause false positive results. It also shouldn’t be used in the
estimated 40% of South Africa’s TB patients who aren’t HIV-positive and
early indications are that it doesn’t work well in children.
And, finally, the TB Lam stick can’t detect whether the kind of TB a person
has is resistant to common drugs used to treat TB. For reasons such as
this, the dipstick will still miss about half of all TB cases in people
living with advanced HIV.
For centuries, the world relied on the naked eye and a microscope to
uncover the bug that is now the leading cause of death in South Africa.
Today, we finally have a test designed for those who need it most, but
diagnosing one out of every two patients correctly is far from perfect. The
good news is that more sensitive versions of the Lam test may soon become
The proverbial holy grail remains a low-cost test that can diagnose TB in
people with or without HIV — and that doesn’t rely on patients to produce
that hard-to-cough-up gunk called sputum. We also need simple tests that
could be given to large numbers of people at a time to rule out TB quickly,
especially in high- risk areas such as informal settlements, where poor
living conditions can drive the spread of the disease.
Day in and day out, our hospitals and clinics are inundated with people who
are at risk of TB or already showing symptoms. We need better, simpler and
faster tests to help to stretch the resources we have further — and to make
sure people do not continue to lose their lives to a treatable disease.
*Professor Keertan Dheda is the head of the University of Cape Town’s (UCT)
division of pulmonology as well as UCT’s Centre for Lung Infection and
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