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In this issue:
Lesley Odendal page 2
HIV & AIDS Treatment in Practice
Issue 204 | 24 June 2013
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Xpert MTB/RIF diagnostic test for TB: a global update; by
•Background: Improving TB diagnosis through use of the Xpert MTB/RIF assay
•World Health Organization recommendations on use of Xpert MTB/RIF
•Global update on the use of Xpert MTB/RIF
•Addressing funding constraints
•Xpert MTB/RIF roll-out
•Diagnostic yield
•Using Xpert MTB/RIF in active case finding
•Xpert MTB/RIF for detection of rifampicin resistance
•The use of Xpert MTB/RIF in combination with other diagnostic methods
•Conclusion
•Further resources
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HATiP | Issue 204 | 24 June 2013 page 2
Xpert MTB/RIF diagnostic
test for TB: a global update
By Lesley Odendal
Key points
This edition of HATIP was kindly supported by the HIV/AIDS
Department of the World Health Organization. Thanks to Dr Linh
Nhat Nguyen and Dr Wayne Van Gemert of the Stop TB department
(WHO) and Dr Eyerusalem Negussie of the HIV/AIDS department
(WHO) for their review of this edition.
Background: Improving TB diagnosis through use
of the Xpert MTB/RIF assay
Only 66% of the estimated number of incident TB cases were
diagnosed and notified to WHO in 2011. The low rate of case
detection is due in part to an overreliance on sputum smear
microscopy, a diagnostic test with low sensitivity, to diagnose TB inmany low- and middle-income countries where a high HIV
prevalence makes the use of smear-microscopy ineffective.
Smear microscopy is a less sensitive means of detecting TB
bacteria in people living with HIV. This is because people with more
advanced HIV disease tend to have lower levels of TB bacteria in
their sputum. As a result, a larger proportion of people with HIV will
test smear negative than in the general population. In order to
diagnose TB in these smear-negative suspects bacterial culture has
been used, but bacterial culture can take weeks or months to
deliver a result, by which time a person with HIV may have died.
Diagnosis of drug resistance also remains a particular challenge,
given the infrastructure, biosafety requirements and human
resources needed to conduct traditional culture and drug
susceptibility testing (DST).The Xpert MTB/RIF test is able to diagnose tuberculosis (TB) in a
single test from a sputum sample. It can also detect resistance to
rifampicin, which in many settings is a reliable proxy for
multidrug-resistant TB (MDR-TB). However, culture and conventional
drug susceptibility testing against second-line anti-TB drugs are still
necessary to confirm or exclude XDR-TB and to monitor response to
MDR-TB treatment.
One of the main benefits of this novel diagnostic is that it gives
results in two hours, allowing for rapid diagnosis and an earlier start
of treatment whereas TB diagnosis from microscopy takes up to two
days, and culture and DST take weeks for detection of TB drug
resistance.
The Xpert MTB/RIF test also has a sensitivity similar to culture on
solid media, far superior to that of conventional microscopy. The
high sensitivity of Xpert MTB/RIF makes this diagnostic useful in the
diagnosis of TB in people with HIV co-infection, where the sensitivity
of smear microscopy alone is low.
The development of the Xpert MTB/RIF assay for the GeneXpert
platform was completed in 2009 and endorsed by the World Health
Organization (WHO) in 2010.
The successes and challenges of implementing the Xpert
MTB/RIF test received considerable attention at the 43rd Union
World Conference on Lung Health held in Kuala Lumpur in
November 2012.
Previous editions of HATIP have reported on the Xpert MTB/RIF
test and its benefits in active case finding (HATIP 191, May 2012),
as well as how it can be used with other TB diagnostic tools ( HATIP193, May 2012).
This edition examines data and lessons learnt from programmes
where Xpert MTB/RIF has already been implemented in high-burden
TB settings in countries such South Africa, Kenya, India, Cambodia
and Botswana. These findings were presented at the Union
conference and also at the Conference on Retroviruses and
Opportunistic Infections (CROI) in March 2013.
World Health Organization recommendations on
use of Xpert MTB/RIF
The World Health Organization recommends that:1
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• The Xpert MTB/RIF assay is a new test which allows
the diagnosis of tuberculosis within two hours from a
single sputum sample.
• Its use as the initial diagnostic test is recommended
by the World Health Organization for all people with
suspected multidrug-resistant TB (MDR-TB) and for all
people with HIV who have suspected TB.
• Its use is also recommended as a follow-on test after
smear microscopy where MDR-TB or HIV is of lesser
concern, especially in suspected smear-negative TB.
• The roll-out of the Xpert MTB/RIF test is being
supported by funding from several donors across a
wide range of countries with a high prevalence of
MDR-TB and/or HIV.
• The test improves the rate of diagnosis of both
drug-sensitive and drug-resistant TB.
• The test also supports active case finding, by both
improving the diagnostic yield and by limiting the
waiting time for results. This reduces loss to
follow-up.
• Very rapid initiation of TB treatment has been
achieved by use of Xpert MTB/RIF supported byCommunity Health Facilitators, who provide the link
between the labs, the clinics and the community
health workers.
• Use of Xpert MTB/RIF has also been shown to reduce
the delay in treatment initiation in smear-negative TB
patients.
• While Xpert MTB/RIF and culture testing may have
similar positivity rates, Xpert MTB/RIF significantly
decreases the turnaround time for diagnosis of
rifampicin resistance and can be placed in
decentralised settings.
• Testing for susceptibility to isoniazid and second-linedrugs should be done for all patients identified as
rifampicin-resistant by the GXP.
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“These are the two groups of people who will benefit most from
this diagnostic. HIV-infected individuals co-infected with TB are more
difficult to diagnose with smear microscopy, resulting in delays in
diagnosis, which can lead to death in HIV-infected individuals. We
also want to diagnose people suspected of having MDR-TB asquickly as possible to ensure that they are started on effective
treatment without delay, which in turn reduces the risk of
transmission of MDR-TB in the community,” Dr Christopher Gilpin of
the WHO Stop TB Department told the conference.2
These recommendations apply to the use of Xpert MTB/RIF in
sputum specimens only, as data on the utility of Xpert MTB/RIF in
extra-pulmonary specimens are still limited. Based on the
generalisation of data from adults, these recommendations alsoapply to children. Although studies have shown that multiple sputum
specimens increase the sensitivity of the Xpert MTB/RIF, WHO
recommends the use of one sputum specimen for diagnostic
testing, given the resource implications of using multiple
specimens.
WHO acknowledges the need for a review of the accuracy of GXP
in detecting extra-pulmonary TB and paediatric TB, and organised
an Expert Group meeting to evaluate the evidence base in May
2013.
Global update on the use of Xpert MTB/RIF
Globally, 966 GXP instruments, comprising of 5017 modules and
1,891,970 Xpert MTB/RIF cartridges had been procured in the
public sector, as of 31 December 2012. The majority of the modules
(2,049) and cartridges (1,108,140) have been procured by South
Africa, where Xpert MTB/RIF testing as the initial diagnostic is
national policy. Other countries which are investing heavily in the
procurement of the GXP platform include Brazil, Cambodia, the
Democratic Republic of Congo, India, Kenya, Tanzania and
Zimbabwe.3
A consultative meeting was held in April 2012 for implementers
and technical partners in the Xpert MTB/RIF roll out, with the aim of
sharing current information and experiences on the use of the
diagnostic, developing a greater understanding of implementers'
needs and to plan improved co-ordination between country
programmes, donors and partners.
The major recurrent points raised by the implementers included:4
Addressing funding constraints
The high price of the GeneXpert platform and test is the main
barrier to the sustainable scale-up of the technology. SinceDecember 2010, a single Xpert MTB/RIF cartridge cost USD 16.86
at the concessionary price for the public sector, including
non-governmental organisations, in 145 eligible countries.
In August 2012 the price of cartridges was reduced to USD 9.98
for the public sector in the 145 countries due to a ‘buy down’ by
PEPFAR, USAID, UNITAID and the Bill and Melinda Gates
Foundation, from Cepheid, the only manufacturers of the GeneXpert
technology. This concessionary price is not available to the for-profit
private sector.5 (See a full list of eligible countries on the FIND
website.)
Approximately 1.4 million Xpert MTB/RIF test cartridges and over
200 GeneXpert instruments will be made available from 2013
-2015 through the TBXpert Project to 21 countries including
Bangladesh, Belarus, Cambodia, the Democratic Republic of Congo,Ethiopia, India, Indonesia, Kenya, Kyrgyzstan, Malawi, Mozambique,
Myanmar, Nepal, Pakistan, Philippines, Moldova, Swaziland,
Uganda, Tanzania, Uzbekistan and Vietnam.
The USD 25.9 million project is funded by UNITAID and
implemented by the WHO Stop TB Department and the Stop TB
Partnership, including partners such as the Global Laboratory
Initiative (GLI), TB REACH, the EXPAND-TB Project, Interactive
Research and Development (IRD) and the African Society for
Laboratory Medicine (ASLM). By linking this broad network of
partners and existing initiatives for TB laboratory strengthening and
innovative approaches to expand access to vulnerable populations,
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•Xpert MTB/RIF should be used as the initial diagnostic test in
individuals suspected of having MDR-TB or HIV-associated TB.
(Strong recommendation).
•Xpert MTB/RIF may be considered as a follow-on test to
microscopy in settings where MDR-TB or HIV is of lesser concern,
especially in further testing of smear-negative specimens.
(Conditional recommendation acknowledging major resource
implications.)
•User satisfaction: Implementers indicated an overall high level of
satisfaction, describing Xpert MTB/RIF as “fast, easy-to-use,
modern and much less cumbersome than conventional TB
diagnostic techniques.”
•Need for price reduction: The price of the test cartridge was
repeatedly stated as the main obstacle to an accelerated and
sustainable roll-out of the test (but it should be noted that this
consultation took place before the price reduction to USD 9.89).
•Diagnostic and clinical algorithms: Investment in time and
resources to develop and implement effective diagnostic and
clinical management algorithms incorporating the new
technology is needed.
•Errors and invalid results: In a small but significant number of
sites, errors and invalid results in the initial phase of
implementation raised anxiety regarding use of Xpert MTB/RIF.
•Scaling up treatment capacity to match diagnostic capacity:
Treatment of rifampicin-resistant TB cases that are diagnosed by
Xpert MTB/RIF was a major concern in many sites which did nothave the effective second-line drugs to treat newly diagnosed
patients. Correct diagnosis in the absence of appropriate
treatment nevertheless allows for patients to protect the health
of their families.
•Need for innovation: Technical innovation is needed to allow for
Xpert MTB/RIF to be used in more settings at levels closer to the
point of care, where lack of reliable electricity and high
temperatures may otherwise prevent the reliable use of the test.
Implementation of electronic information management systems
and mHealth initiatives through the use of mobile telephones will
facilitate stronger links between diagnosis and follow-up care.
•Private sector access: Adoption of Xpert MTB/RIF by the large
private sector in many high-burden countries would be highlybeneficial for increasing patient access to rapid and reliable
diagnosis, and at the same time replacing technologies that are
not endorsed by WHO. The establishment of collaborations
between private providers and national TB control programmes
would be mutually beneficial, allowing for private providers to
access concessional prices and for national TB control
programmes to ensure that patients whose TB is diagnosed in
the private sector are duly reported and subsequently registered
for appropriate treatment.
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HATiP | Issue 204 | 24 June 2013 page 4
the TBXpert Project hopes to build the capacity of countries to
receive and effectively use the GXP technology.
Information on the availability of the GXP technology, country by
country, is available through a WHO-managed mapping website.
Xpert MTB/RIF roll-out
WHO Stop TB Department’s Laboratories, Diagnostics and Drug
Resistance Unit has been collecting data from early implementers of Xpert MTB/RIF since 2011. The data collection is intended to
monitor laboratory workload, numbers of tests being performed and
results, and main logistical and operational problems being
encountered, on a facility basis.
Evidence regarding the impact of the new diagnostic continues to
be gathered. A register of Xpert MTB/RIF research projects is also
being compiled. Twenty-six studies were either underway or already
completed in February 2013, including a large randomised trial to
evaluate the use of Xpert MTB/RIF in primary health clinics for TB
diagnosis in people living with HIV. The TB Neat study is recruiting
participants in South Africa, Tanzania, Zambia and Zimbabwe.
In a recent editorial introducing a Cochrane Collaboration
Diagnostic Test Accuracy Review, Professor Elizabeth Corbett of the
London School of Hygiene and Tropical Medicine, and Dr DanielleCohen of the Malawi-Liverpool-Wellcome Clinical Research
Programme, raised a number of questions regarding the use of
Xpert MTB/RIF that still need to be addressed by research.
Research presented at the 2012 World Lung Health meeting
began to address some of these questions, relating to diagnostic
yield, to use of Xpert MTB/RIF to support TB and drug-resistant TB
diagnosis in peripheral health centres, and in relation to diagnosis
of drug-resistant TB.
Diagnostic yield
Xpert MTB/RIF implementation is intended to improve case
detection of both drug-sensitive and rifampicin-resistant TB cases.
Studies presented from South Africa, India and Cambodia
showed that in settings with a high burden of TB and DR-TB, Xpert
MTB-RIF resulted in encouraging improvements in diagnostic yield.
The studies also showed that increases in diagnostic yield could be
achieved when testing was decentralised to lower levels of the
health system.
South Africa
In Cape Town, South Africa, the phased introduction of Xpert
MTB/RIF across five of the city’s eight sub-districts resulted in an
increase of approximately 20% in diagnostic yield in the first quarter
after introduction, although this increase was not sustained in
subsequent quarters.7
All TB suspects were screened according to the following
algorithm:
The 2011 fourth-quarter mean diagnostic yield across the
sub-districts for DS-TB was found to be 20.3% for the Xpert MTB/RIF
algorithm compared to 16.9% for the standard-of-care smear
microscopy/culture algorithm. However, this difference was not
sustained for the second time period. For the second quarter of
2012, the Xpert algorithm’s mean diagnostic yield decreased to
16.8% compared to 16.3% for the smear/culture algorithm.
The mean MDR-TB yield for the Xpert MTB/RIF algorithm was
7.3% and 5.3% in the first and second time periods respectivelycompared to 4.7% and 5.3% for the smear/culture algorithm. “The
increase in the MDR-TB diagnostic yield suggests some benefit for
DR-TB, but extra time points would be needed,” said Dr Naidoo.
In this study, it is important to note that the yield refers to the
algorithm and that the number of sub-districts implementing the
Xpert MTB/RIF testing algorithm increased from two in the fourth
quarter of 2011 to three in the first quarter of 2012. This may have
had an effect on the result. In addition, not all suspected TB cases
in the districts implementing the Xpert MTB/RIF algorithm
underwent Xpert MTB/RIF testing, making the decline in yield in the
second quarter of 2012 hard to interpret.
India
A 7.2% increase in the diagnostic yield when using XpertMTB/RIF for TB case finding compared to smear microscopy was
found in a feasibility and impact study of using the test at
decentralised laboratories in India, as reported by Dr Naraj Raizada,
Project Manager of Xpert MTB/RIF projects for FIND in India.8
All patients with suspected pulmonary TB (PTB) and
drug-resistant TB (DR-TB) were offered a single Xpert MTB/RIF test
situated at 18 sites in varying settings across India serving a
population of 8.7 million people. 22,345 pulmonary TB and 1,738
DR-TB suspected cases were tested between March and October
2012.
The study compared the diagnostic yield of TB before and after
the establishment of the Xpert MTB/RIF testing facilities. Of the
9124 suspected TB cases tested using smear microscopy at
baseline, 1312 confirmed cases of TB were detected (a 14.3%smear positivity rate). This resulted in an average of 29 TB cases
per site per month. This increased to 47 TB cases per site per
month when using Xpert MTB/RIF. 4422 of the 22,345 TB
suspected cases were confirmed as having TB when the Xpert
MTB/RIF tests were used (a 20% positivity rate).
However, they also conducted an internal comparison of
diagnostic yield by performing smear microscopy on the same
sputum specimens used in the Xpert MTB/RIF testing. Smear
microscopy yielded a positivity rate of only 12.8%, compared to the
20% positivity rate using Xpert MTB/RIF on the same sputum
specimens. 1559 cases of TB were missed using smear microscopy.
Xpert MTB/RIF also diagnosed 569 cases of rifampicin-resistant TB
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•How can Xpert MTB/RIF be integrated into systematic screening
activities, particularly in populations at very high risk of TB, such
as people living with HIV?
•At what level of the health system should access to Xpert
MTB/RIF be prioritised? How does it perform in peripheral health
centres?
•How can TB programmes best use this valuable new tool for
detection and management of rifampicin resistance?
•How can we effectively evaluate this test in routine practice,
where access to culture is generally non-existent and where
patient-important outcomes are more important?6
•Smear and culture sub-districts: two smears in low-MDR risk
patients, and two smear plus culture and drug susceptibility
testing in high-MDR risk patients.
•Xpert MTB/RIF sub-districts: two sputum samples collected from
all suspected TB cases. If sample 1 was negative and the patient
was HIV negative the second sample was discarded. If sample 1
was negative and the patient was HIV positive the second
sample was submitted for culture. If sample 1 was positive butrifampicin-sensitive, a confirmatory smear was carried out on
sample 2. If sample 1 was positive and rifampicin-resistant,
sample 2 was submitted for smear, culture, LPA and second-line
drug susceptibility testing.
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needing to return to the facility to provide a second sample.
Although TB care and diagnostic tests are free in Kenya, patients
are charged a minimum of KSh100 (equal to one day’s wage) to
register at the health facility.
Of the 1171 culture tests performed on non-contaminated
specimens between December 2011 and July 2012, 9.4 % (n=99)
were found to be culture positive. The culture arm had to be
stopped prematurely due to poor supply chain management which
did not allow for reliable supply of the culture reagent, leading all
smear-negative samples to receive Xpert MTB/RIF testing.
The Xpert MTB/RIF test found a similar positivity rate for
drug-resistant (DR)TB. Of the 824 smear-negative patients screened
using Xpert MTB/RIF between December 2011 and September
2012, 8.6 % (n=71) were found to have TB, while two cases of
rifampicin resistant TB were found.
One of the main advantages of using Xpert MTB/RIF over the
culture testing was that the time it took for the clinician to receive
results after sending the sputum sample decreased from five weeks
to five days.
Xpert MTB/RIF for detection of rifampicin
resistanceRifampicin resistance as a proxy for MDR-TB
According to WHO guidelines on the use of Xpert MTB/RIF,
resistance to rifampicin, as identified by Xpert MTB/RIF, should be
used as a proxy for MDR-TB. However, a retrospective patient-based
analysis which assessed the proportion of isoniazid-susceptible TB
cases among rifampicin-resistant TB cases in Botswana, has found
that a high proportion of rifampicin-resistant TB isolates are still
susceptible to isoniazid.12
The study by Dr Valentina Anisimova of KNCV in Botswana
gathered data on isoniazid susceptibility among rifampicin-resistant
TB isolates by examining the results from DR-TB surveys conducted
in the country in 1996, 1999, 2002 and 2007 to 2008. It also used
drug-sensitivity testing results from the Botswana NationalReference Laboratory from 2006 until 2010.
32.2% and 23.8% of new rifampicin-resistant TB cases were
found to be susceptible to isoniazid in the DR-TB surveys and
routine data respectively. Among rifampicin-resistant retreatment
cases 43.1% and 25.2% were found to be susceptible to isoniazid in
the DR-TB surveys and routine data respectively. Combined, 37.9%
of rifampicin-resistant cases in the DR-TB and routine surveys were
found to be isoniazid-susceptible . The study also found
considerable fluctuation in the proportion of patients with
isoniazid-susceptible TB between surveys at different time points.
“Testing for susceptibility to isoniazid should be done for all
patients identified as rifampicin-resistant by the Gene Xpert,” said
Dr Anisimova. “The proportion of isoniazid-susceptible
rifampicin-resistant isolates is changing over time and should beclosely monitored to inform management of patients with DR-TB.”
Dr Anisimova also recommended that isoniazid should be
included in the treatment regimen until isoniazid resistance is
confirmed. This study has important implications for the current
WHO guidance of using rifampicin resistance as a proxy for MDR-TB
which should be reviewed. Although it is recommended to send
rifampicin-resistant TB samples for further DST, including isoniazid
in the treatment regimen until resistance is confirmed may result in
better treatment outcomes for patients.
Xpert MTB/RIF and detection of DR-TB
TB/HIV Care Association’s intervention in Sisonke district in
KwaZulu-Natal, South Africa13 (described previously) detected 140
cases of rifampicin-resistant TB (a diagnostic yield of 9.9%)
compared to 8.7% in the rest of the province. DR-TB patients have
been initiated on treatment at a decentralised hospital at
sub-district level, compared to the standard approach of being
hospitalised at a centralised facility, 150 km from Sisonke district.
This has alleviated the burden on the patient’s family members to
visit their relatives.
DR-TB patients are also discharged after two consecutive
negative smears, as opposed to the policy in the province of only
discharging patients at the end of the six-month injectables period.
TB/HIV Care Association is also using outreach teams made up of
an enrolled nurse and a counsellor to provide patients with
injections at home.
The use of Xpert MTB/RIF has also allowed for the time from
sputum collection to treatment initiation to be dramatically reduced,
rendering patients uninfectious sooner. Between January and June
2012, 36% of MDR-TB patients were initiated on treatment less
than 48 hours after providing a sputum specimen, while 18% were
initiated on treatment between two and five days after providing
sputum.FIND has also established 12 new Xpert MTB/RIF testing sites in
difficult-to-reach areas in India for rifampicin drug-sensitivity testing
to supplement the capacity of the existing reference laboratory
network of the National TB Programme.14 It aims to conduct 24,000
rifampicin-resistance tests and expects to detect 7,000 cases of
MDR-TB annually. Six of the 12 Xpert MTB/RIF testing sites had
been established and used between August and October 2012. Of
the 2900 suspected DR-TB cases tested using the Xpert MTB/RIF,
462 (16%) were diagnosed with MDR-TB.
The use of Xpert MTB/RIF in combination with
other diagnostic methods
The benefits of using a range of TB diagnostics such as smearmicroscopy, urinary lipoarabinomannan (LAM) assays and Xpert
MTB/RIF have been discussed in previous editions of HATIP. The
advantage of these diagnostic tools is that they are more sensitive
and specific. The sensitivity of a test is the percentage of results
that will be correctly positive when a disease is actually present.
Lower rates of sensitivity will produce more false negative results.
The specificity of a test is the percentage of results that will be
correctly negative when a disease is not present. Lower rates of
specificity will produce more false positive results.
These more sensitive and specific diagnostic tools for TB are
especially important for diagnosing TB in people with HIV, whose
smear microscopy TB test results are often false negatives. Despite
being more sensitive and specific than smear microscopy alone,
Xpert MTB/RIF and urinary lipoarabinomannan (LAM) assays arerapid diagnostics that have suboptimal sensitivity when used alone
in people with HIV who may have TB. Until recently the diagnostic
yield of these tests used in combination for the diagnosis of active
TB was unknown.
However, a study conducted in Uganda in people with HIV found
the sensitivity of the combination of Xpert plus LF-LAM was 87%
(n=88 of 101, 95% CI 0.79-0.93), which was superior to either test
alone (p<0.05) and was similar to the sensitivity of liquid culture
(94%, 95% CI 0.88-0.98, p = 0.17).15
The study, which was presented at the 20th Conference on
Retroviruses and Opportunistic Infections in Atlanta in March 2012,
compared the diagnostic accuracy of sputum smear microscopy,
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sputum culture (solid and liquid), mycobacterial blood culture, Xpert
MTB/RIF testing of archived sputum pellets, and urinary testing for
LAM using a point-of-care lateral flow test (LF-LAM) in people with
HIV with signs or symptoms of TB.
Participants included 101 individuals with culture-confirmed TB
and 107 people with suspected TB in whom TB was excluded
clinically and microbiologically. The study found that among the 101
individuals with confirmed TB, the sensitivity of Xpert MTB/RIF was
77% (95% CI, 0.68-0.85), and was superior to that of LF-LAM which
was found to have a sensitivity of 50% (95% CI, 0.39-0.60, p
<0.001), and smear-microscopy with a sensitivity of 31% (95% CI,
0.22-0.41, p <0.001). Specificity of the Xpert MTB/RIFand LF-LAM
among the 107 individuals without TB was more than 97%.
Urinary LAM testing with Xpert MTB/RIF was also highly
cost-effective compared to using either smear microscopy or Xpert
MTB/RIF alone. The study found that the incremental
cost-effectiveness ratio (ICER) when comparing the combination of
Xpert MTB/RIF and LAM to smear alone was USD50 per
disability-adjusted life year (DALY) and USD29 when compared to
Xpert MTB/RIF alone.
ConclusionWhile the introduction of Xpert MTB/RIF has been hailed as one of
the greatest achievements for the diagnosis of TB and MDR-TB, the
price of the machine and the cartridges is the main obstacle which
implementers face, despite the decrease in the price. Innovations to
reduce the price are necessary to ensure that this useful technology
can be scaled up and used effectively globally. As the India study
showed, the use of this technology is feasible when certain
measures are put in place.
Xpert MTB/RIF has demonstrated significant gains in intensified
case finding of TB and MDR-TB, as shown by numerous studies
presented at last year’s Union World Lung Health Conference. In
every study conducted in operational settings, there was a
significant increase in diagnostic yield, demonstrating the potential
for Xpert MTB/RIF to assisting in detecting all TB cases. The Xpert
MTB/RIF’s superior sensitivity in detecting TB, especially in
smear-negative cases is also greatly beneficial to people with
TB/HIV co-infection.
Most importantly, the two-hour turnaround time from sputum
specimen to result means that the time to treatment initiation can
be decreased significantly, as shown in the Sisonke District study by
TB/HIV Care Association.
However, challenges remain such as ensuring reliable electricity
supply and giving staff adequate training and supervision to avoid
uninterpretable results. These are aspects which will need to be
addressed going forward.
Further resources
http://www.who.int/tb/laboratory/mtbrifrollout/en/index.html
http://xrmt.treattb.org/
https://extranet.who.int/xpertmtbrif/content/home
References[1] World Health Organization.Rapid implementation of the Xpert MTB/RIF
diagnostic test: technical and operational ‘How-to’ practical considerations.
Geneva, March 2011
[2] Gilpin, C. Introduction and status of the global roll-out of Xpert MTB/RIF
for the diagnosis of tuberculosis.43rd Union World Conference on Lung
Health, Kuala Lumpur, 2012.
[3] http://www.who.int/tb/laboratory/mtbrifrollout/en/
[4] World Health Organization Stop TB Department.Update: Implementation
and roll-out of Xpert MTB/RIF . May 2012
[5] Gilpin, C. op cit
[6] Cohen D, Corbett S. Evidence supports TB test, so what now?[editorial].
Cochrane Database of Systematic Reviews 2013 Jan 31;1:ED000051. doi:
10.1002/14651858.ED000051.
[7] Naidoo, P. Does the introduction of the Xpert® MTB/RIF test result in an
increased TB diagnostic yield in a routine operational setting in Cape Town?
43rd Union World Conference on Lung Health, Kuala Lumpur, 2012.
[8] Raizada, N. Experience with implementation of Xpert MTB/RIF in India.43rd Union World Conference on Lung Health, Kuala Lumpur, 2012.
[9] Boy, S. The impact of the Xpert MTB/RIF assay for detecting
Mycobacterium tuberulosis among TB suspects in Cambodia. 43rd Union
World Conference on Lung Health, Kuala Lumpur, 2012.
[10] Hausler, H. Using community resources and new tools for active TB
case detection in South Africa.43rd Union World Conference on Lung Health,
Kuala Lumpur, 2012.
[11] Carter, J. Providing access to new diagnostics for vulnerable rural
populations in Kenya.43rd Union World Conference on Lung Health, Kuala
Lumpur, 2012.
[12] Anisimova,V et al. Rifampicin resistance as a proxy for multi-drug
resistant tuberculosis in Botswana. 43rd Union World Conference on Lung
Health, Kuala Lumpur, abstract OP-101-15, 2012.
[13] Hausler, H. op cit
[14] Raizada, N. op cit
[15] Shah, M. Comparative performance of rapid urinary lipoarabinomannan
assays and Xpert MTB/RIF in HIV+ TB suspects: Uganda. 20th Conference
on Retroviruses and Opportunistic Infections, Atlanta, abstract 127, 2013.
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•WHO Stop TB Department Xpert MTB/RIF roll out monitoring
website
•Mapping of Xpert roll out research projects
•Data collection on the use of Xpert MTB/RIF by early
implementers since 2011
