Pulmonary tuberculosis (TB) is a
contagious bacterial infection that
mainly involves the lungs, but may
spread to other organs.

The effective treatment of tuberculosis
is a lifesaving intervention. The global
scale-up of tuberculosis therapy has
averted 6 million deaths over the past
15 years, making it one of the greatest
public health interventions of our
lifetime. Unfortunately, by the time
most patients are treated, they have
already infected many others. This
failure to interrupt transmission fuels
the global epidemic so that every year
there are more new cases of
tuberculosis than in the previous year.

In the new test, known as Xpert
MTB/RIF, a technician deposits a
sputum sample in a cartridge, which is
inserted into a machine. According to a
study published  by The New England
Journal of Medicine, the test is 98
percent accurate when compared with
positive results from the old method —
examination of sputum by a trained
microscopist. It was only about 73
percent accurate on the hardest-to-
analyze samples, but that is better
than microscopy, which is wrong about
half the time. And it was 98 percent
accurate in detecting antibiotic
resistance, the step that adds weeks to
the old process.

The test was developed by Cepheid, a
private company, and the Foundation
for Innovative New Diagnostics in
Switzerland, with support from the
National Institutes of Health and the Bill
& Melinda Gates Foundation.

It has some limitations. The machines
cost $30,000 and each test is about
$60, which means poor countries,
where the TB problem is the worst, will
have to rely on donors to supply it.
And it detects resistance to only one
antibiotic, rifampicin. Rifampicin
resistance is a useful signal that a
patient has a dangerous drug-resistant
strain, but does not tell the whole story.

For decades there has been little effort
to improve techniques for diagnosing
tuberculosis. Consequently,
tuberculosis tests are antiquated and
inadequate. The most widely used test
(smear microscopy) is 125 years old
and routinely misses half of all cases.

Fortunately, in the past few years,
several improved tuberculosis tests
have received WHO endorsement for
widespread use
In a large, well-conducted, multicountry
study, Boehme et al. evaluated an
automated tuberculosis assay (Xpert
MTB/RIF) for the presence of
Mycobacterium tuberculosis (MTB) and
resistance to rifampin (RIF). With a
single test, this assay identified 98% of
patients with smear-positive and
culture-positive tuberculosis (including
more than 70% of patients with smear-
negative and culture-positive disease)
and correctly identified 98% of bacteria
that were resistant to rifampin.

Since the heyday of TB drug
development in the 1950s and '60s, no
new class of TB drugs has been
approved to treat the disease.
However, over the past few years TB
drug development has experienced a
minor renaissance. Seven drug
candidates with novel mechanisms of
action against TB are in human
studies, most to treat MDR-TB
(multidrug-resistant TB), and two
broad-spectrum antibiotics are under
wide-scale evaluation for drug-
susceptible TB.
Two of the drugs farthest along in the
TB pipeline are Tibotec
Pharmaceuticals' TMC207 and Otsuka
Pharmaceuticals' OPC-67683. Both
drug candidates are in phase II clinical
studies for treatment of drug-resistant
The Global Alliance for TB Drug
Development (aka the TB Alliance) is
planning to initiate phase II studies of
its nitroimidazole, PA824, within the
The other three new compounds in
phase I human trials are Sequella's SQ-
109, which is a diamine, Pfizer's PNU-
100480, and AstraZeneca's AZ5847,
which are both oxazolidinones, along
with the already approved (for sepsis)
linezolid (Pfizer's Zyvox), which is being
looked at in low doses for MDR-TB.

For the first time in history, Tibotec has
begun an open-label safety study for a
TB drug. The study currently has three
sites up and running in South Africa,
with other potential sites in Russia,
Eastern Europe, and Asia. The trial will
enroll up to 225 people with confirmed

TO 1
Archivel Farma, S.L. has announced
that its breakthrough treatment for
tuberculosis (TB) will shortly start
phase II clinical trials. The treatment
uses the company's unique
combination of its novel therapeutic
vaccine called RUTI in conjunction with
an antibiotic. This cuts treatment time
from nine months to one month, which
reduces side effects and healthcare
costs, by preventing re-infection during
the eradication process. The company
expects commercial availability in 2015.

It has now been discovered that TB
does not lie "dormant" but is actually
waging a constant war with the host,
constantly re-infecting the lungs.
Provided that the host is healthy, it has
the upper hand and usually keeps the
TB in check.
TB is particularly tricky to eliminate as
it can be either replicating, when it can
be killed by the antibiotics, or non-
replicating when antibiotics are
useless. The long, nine month course
of antibiotics is needed to ensure that
all traces of the non-replicating form
are eliminated from the lungs.

Archivel's novel, two pronged
approach combines a one month
course of antibiotic to eliminate the
bacteria in the replicating stage and
two injections of the company's RUTI
vaccine that stimulates the body's own
immune system to fight the bacteria.
This combination approach reduces
the treatment time from nine months to
one, is easier to manage, less
expensive, more effective and more
likely to be done completely. The
company estimates that cost
comparison between the current and
new treatment, when allowing for all
the logistical costs means that the new
treatment costs around half that of the
old treatment.