Genexpert Test TB
become available?
diagnosis and resistance
Testing
The Genexpert test is a new molecular test for TB
which diagnoses TB by detecting the presence of
TB bacteria, as well as testing for resistance to the
drug Rifampicin.
Some organisations have claimed that the
Genexpert test is going to revolutionize the
diagnosis and care of people with TB.1So what are
the advantages and disadvantages of the
Genexpert, how is the Genexpert test used, and is
it really going to result in the breakthroughs that
are claimed?
Genexpert Test
How does the Genexpert test
work?
The test is a molecular test which detects the DNA
in TB bacteria. It uses a sputum sample and can
give a result in less than 2 hours. it can also detect
the genetic mutations associated with resistance to
the drug Rifampicin.2
Who developed the Genexpert
test?
The Genexpert has been developed by the
Foundation for Innovative New Diagnostics (FIND),
who have partnered with the Cepheid corporation
and the University of Medicine and Dentistry of
New Jersey. Some of the funding for the
development of the Genexpert was provided by
the NIH.3
When did the Genexpert test first
The Genexpert system was launched in 2004, and
the development of the Genexpert test, based on
the Genexpert platform, was completed in 2008.4 5
The first clinical validation studies were carried out
in 2009.6 A large scale demonstration project was
then carried out in a number of different countries
including South Africa and India to assess the
implementation of the Genexpert.7
Data from these studies were then submitted to the
World Health Organisation (WHO) for evaluation in
September 2010. In December 2010 WHO
endorsed the Genexpert technology and released
a recommendation and guidance for countries to
incorporate the new test into their programs.
What is the cost of the Genexpert
TB test?
FIND originally negotiated discounts for the
Genexpert test in 120 high burden and in all low
and middle income countries and the initial cost
was approximately US$17 per cartridge.
In June 2012 the organisation UNITAID approved
funding of $30 million with the aim of scaling up
access to the Genexpert test. It was hoped that the
roll out of the test would bring the price down from
US$17 to US$10. However the roll out proceeded
slower than expected and it is believed that many
customers delayed ordering as they expected the
price to be reduced following the UNITAID
announcement.
GeneXpert 4 module machine GHE
It was subsequently announced in August 2012
that Cepheid had entered into an agreement with
the Bill and Melinda Gates Foundation, PEPFAR,
and USAID to further bring down the cost of the
test. It was agreed that the test would immediately
be available for US$9.98 with the difference
between this and the earlier US$16.86 being paid
by the collaborators with an initial US$3.5 million
being provided by the Bill and Melinda Gates
Foundation.8
In addition to the cost of each test there is the cost
of the Genexpert device. The device comes in
different sizes providing for a different number of
samples to be tested simultaneously. The
commonly used GX4 which has 4 modules, has a
cost of approximately US$17,000. There are in
addition costs for delivery and installation, and
there is an annual servicing cost.9
The use of the Genexpert test
WHO recommended that the test should be used
as the initial diagnosis test in individuals suspected
of having MDR TB, or HIV associated TB. They
also suggested that it could be used as a follow on
test to microscopy in settings where MDR TB
and/or HIV is of lesser concern, especially in
smear negative specimens, because of the lack of
accuracy of smear microscopy. They did however
say that they recognised the major resource
implications of using it in this second way.10
WHO did also emphasize that the test does not
eliminate the need for conventional microscopy
culture and drug sensitivity testing, as these are
still required to monitor treatment progress and to
detect other types of drug resistance. The
Genexpert MTB/RIF cannot be used for treatment
monitoring, as it detects both live and dead
bacteria.
Further guidance was subsequently provided by
WHO on the rapid implementation of the new
test.11 12
Advantages and disadvantages of
the test
WHO have been particularly keen on the use of the
test and in 2010 said that:
This new test represents a major milestone for
global TB diagnosis and care. It also represents
new hope for the millions of people who are at the
highest risk of TB and drug resistant disease.
Dr Mario Ravihlione, Director of WHO Stop TB
Department13
The test does however have disadvantages as well
as advantages.
Disadvantages
There are a number of disadvantages which
include:
The shelf life of the cartridges is only 18
months;
A very stable electricity supply is required;
The instrument needs to be recalibrated
annually;
The cost of the test;
The temperature ceiling is critical.14
Advantages
The main advantages of the test are, for diagnosis,
reliability when compared to sputum microscopy
and the speed of getting the result when compared
with culture. For diagnosis of TB, although sputum
microscopy is both quick and cheap, it is often
unreliable. It is particularly unreliable when people
are HIV positive. Although culture gives a definitive
diagnosis, to get the result usually takes weeks
rather than the hours of the Genexpert test.
The main advantage in respect of identifying
rifampicin resistance, is again the matter of speed.
Normally to get any drug resistance result takes
weeks rather than hours.