Challenges in Rolling-out the GeneXpert MTB/RIF Diagnostic Test in Resource-Limited Settings - May 9-20

By Sophie Beauvais | 09 May, 2011 Last edited by Sophie Beauvais on 29 Dec 2011

Dear colleagues,

Starting today, May 9, and running until May 20, GHDonline is pleased to host an expert panel discussion on the challenges of rolling-out the Xpert MTB/RIF diagnostic test, especially in resource-limited setttings.

Initial questions:

- What factors and strategies are important to consider when integrating the Xpert MTB/RIF Diagnostic Test and GeneXpert system into current TB diagnosis and treatment plans, especially in areas with limited resources?

- What is the appropriate placement of Xpert MTB/RIF Diagnostic Test in the health care system taking into account operational considerations, burden of disease, human resources, supply chain management, and existing TB diagnostics?

- How can countries evaluate the impact of implementing the Xpert MTB/RIF Diagnostic Test and generate evidence for scaling-up?

Joining us for this panel are:

- Dr. Chris Gilpin, scientist at the Stop TB Department of the WHO and part of the team leading the roll-out of the Xpert MTB/RIF assay

- Dr. Daniela Cirillo from the San Raffaele Scientific Institute in Italy

- Dr. Eduardo Gottuzzo from the Instituto de Medicina Tropical Alexander von Humboldt at the Universidad Peruana Cayetano Heredia in Peru who participated in the demonstration study

- Dr. Mark Perkins from FIND, the non-profit organization that co-developed the assay and led the evaluation and demonstration studies.

Does your organization plan on rolling-out the diagnostic test? Did you participate in the early implementers meeting organized by the WHO and and have you already faced challenges that you could share?

All GHDonline members can participate in this virtual discussion. Sign up to the community if you haven’t already joined and keep your email settings to “per post” to track the discussion live in your inbox.

Thank you.

Attached resource:

Replies

 

Sophie Beauvais Replied at 7:46 AM, 9 May 2011

Right away I would like to introduce our expert panelists for this discussion. Thank you all for joining in the discussion, we look forward to it.

Dr. Daniela Cirillo, MD,PhD, is a board certified clinical microbiologist, Head of the Emerging Bacterial Pathogens Unit at the San Raffaele Scientific Institute (HSR) in Milan, Italy. The main activities carried out by the Unit are research on new diagnostic for MDR/XDR-TB, M.tuberculosis pathogenesis, virulence markers, and, as a WHO Tuberculosis SupraNational Reference Laboratory, to provide laboratory-based assistance to high TB burden countries. Dr Cirillo’s particular areas of expertise include clinical bacteriology and infection control, molecular typing of Multidrug resistant organisms, TB Laboratory strengthening, DRS and operational research protocols development, training packages development, research on new diagnostics for active and latent TB infections, nosocomial infection. Currently, she is involved in the implementation on molecular technology (LPAs an Xpert TB-MDR) for Tb diagnosis in several high burden, low resources settings. She is a member of the WHO European Laboratory Strengthening Task Force, of the stirring committee of the TBnet, executive secretary of Stop TB Italia – Onlus and of the Infection Control Committee of the HSR. She is the coordinator of two FP7 projects approved by the EU aimed at development of new diagnostic tools and at the development of a European network for study and clinical management of TB drug resistance. She serves as a peer reviewer for the International Journal of Tuberculosis and Lung Disease, European Respiratory Journal, Journal of Clinical Microbiology, Emerging Infectious Disease, Clinical Infectious Diseases.

Dr. Chris Gilpin is scientist for the TB Laboratory Strengthening and Diagnostics Unit, Stop TB Department, World Health Organization. He is part of the team at WHO leading the roll-out of recently endorsed Xpert MTB/RIF assay. Dr Gilpin has over twenty years experience as a Microbiology Laboratory Scientist managing diagnostic laboratories in Australia and the Middle-East. Chris completed studies in England for his doctorate in the molecular diagnosis and epidemiology of tuberculosis and was formerly Head of the TB Supranational Reference Laboratory in Brisbane, Australia. He has extensive experience in TB laboratory capacity strengthening and training in Africa, Asia and in the Pacific Islands.

Dr. Eduardo Gotuzzo, Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. Dr Gotuzzo participated in the demonstration study.

Dr. Mark Perkins is Chief Scientific Officer at the Foundation for Innovative New Diagnostics (FIND), the non-profit organization that co-developed the Xpert MTB/RIF assay and led the evaluation and demonstration studies. He trained in Internal Medicine and Pediatrics at Vanderbilt in Nashville, Tennessee, then had a research fellowship in the laboratory of Infectious Diseases at the National Institutes of Health where his research focused broadly on the development of respiratory virus vaccines. After returning to Vanderbilt to complete a clinical fellowship in Infectious Diseases, he went to Duke University, first as a Senior Fellow in Clinical Microbiology, and then as a faculty member in the Division of Infectious Diseases and International Health. He worked in Brazil for 5 years to develop and co-direct a collaborative Duke facility for research in tropical diseases and to establish a reference diagnostic laboratory. In 1998 he joined the Global Tuberculosis Programme of the WHO and the following year established a Diagnostics unit in the Special Programme for Research and Training in Infectious Diseases (TDR). His group focused on the development and evaluation of new diagnostics for tuberculosis, malaria, schistosomiasis, leishmania, trypanosomiasis and sexually transmitted diseases. Funding from the Gates Foundation in 2001 allowed the creation of a full program on TB diagnostics within TDR, and another Gates grant in 2003 established FIND to accelerate this work.

Dr. Daniela Cirillo, MD, PhD Replied at 7:57 AM, 9 May 2011

What factors and strategies are important to consider when integrating the Xpert MTB/RIF Diagnostic Test and GeneXpert system into current TB diagnosis and treatment plans, especially in areas with limited resources?

Xpert MTB/ RIF offers the unique opportunity to decentralize the diagnosis of rifampicin resistant tuberculosis.
This opportunity will offer numerous advantages and several challenges.
Main challenges will be related to how to efficiently integrate the Xpert MTB/ RIF platform in existing diagnostic algorithms.
Current diagnostic algorithms for tuberculosis diagnosis, in low resources settings, are mainly based on quality assured smear microscopy. Contribution of solid and liquid culture varies depending on the availability, capacity and proficiency of culture services.
Implementation of Xpert MTB/ RIF platform should be performed gradually, after adequate analysis of local epidemiological data without disturbing the existing laboratory network.
A fully shared local diagnostic algorithm should be developed by NTP, NRL and MoH representatives. The algorithm should consider the local epidemiology of tuberculosis, HIV, drug resistant TB, the local diagnostic capacity both at National and peripheral level, capacity of treatment and financial resources.
The target TB suspects population that will benefit the most from use of Xpert MTB/ RIF should be indentified based on Country priority.
One or few implementation sites should be selected based on their epidemiological characteristics, capacity to implement the technology in all the aspects ( logistic, data collection, etc. - needed to generate the evidence for scaling up the test)
Cost analysis should be performed to verify the resources needed to properly target the selected population and to verify the sustainability over time.
In some particular settings the use and the impact of the “Gene Xpert” platform for diagnosis of other diseases should also be considered as an important factor for the implementation.

What is the appropriate placement of Xpert MTB/RIF Diagnostic Test in the health care system taking into account operational considerations, burden of disease, human resources, supply chain management, and existing TB diagnostics?
Appropriate placement of the Xpert MTB/ RIF platform depends on the on the existing laboratory situation in the Country. The recent world-wide investment in the laboratory sector has allowed the implementation, at least at the national lab level, of liquid cultures and LPAs in many low resources countries. Some countries are still lagging behind and, in few, cultures are still not available at all.
Where cultures are routinely performed, at national or regional level, according to a selected national algorithm, the appropriate placement of the Xpert TB/MDR could be the district level. The selection and the number of districts involved may depend on the local prevalence of HIV, and/or of MDR-TB.
HIV clinics, MDR-TB treatment centers and specialized institutions admitting people at higher risk of developing TB/MDR-TB could also be considered for the implementation of Xpert MTB/ RIF.
In settings in which the culture capacity is still lacking or very limited (and MDRTB treatment is available), the simple implementation of Xpert MTB/ RIF will offer the possibility to microbiologically prove the MDR-TB diagnosis before the beginning of a standard second line regimen. Wherever possible, only Rif resistant samples will be transferred for 1st and 2nd line DST.
Additional consideration:
1) capacity to treat all MDR-TB detected cases: if cases are identified the Country should have the capacity to treat them
2) Retesting MDR-TB cases in low MDR-TB prevalence population and dealing with possible discrepancies between phenotypic and genotypic resistance patterns. False positive rif resistant cases have been reported: the high majority of them are correctly identified as rif sensitive by a second independent test.
3) Scaling up: how will it be feasible to scale up and offer the same diagnostic opportunity to all HIV infected patients in Countries with high prevalence? It is unrealistic, even in the best possible scenario, to imagine that the Xpert MTB/ RIF platform may substitute the microscope at the sub district level, therefore good referral system for patients or samples should be developed
4) Supply chain management: Given the number of tests and the space needed for delivery and storage and the cost of custom clearance it is necessary to apply an appropriate plan for stock and supply management
5) Existing TB diagnostics? Although the TB diagnostic field is moving fast (after decades of paralysis), there is still no single test that can stand alone for the laboratory diagnosis of TB. Availability, at least at the national level, of staff able to perform simple but not fully automated molecular tests, liquid cultures and DST, is still a must for TB diagnosis. A successful implementation of Xpert MTB/ RIF may, in the long run, reduce the number of cultures performed for rif sensitive cases. The overall impact on TB diagnostic costs needs to be evaluated in the long term.
6) Monitoring response to treatment in the absence of the initial smear microscopy result: correlation between Xpert MTB/ RIF and bacterial load may be possible, follow up is difficult (if not impossible) due to the stability of DNA.

How can countries evaluate the impact of implementing the Xpert MTB/RIF Diagnostic Test and generate evidence for scaling-up
Evaluation of the impact of Xpert MTB/ RIF can be performed by analyzing the number of detected TB cases and MDR-TB cases in different categories and the influence of early detection on treatment outcome. Additional parameters to evaluated are the time from diagnosis to treatment in the presence or absence of Xpert MTB/ RIF diagnostic tool.

Daniela Maria Cirillo, MD PhD
Head, Emerging Bacterial Pathogens Unit
San Raffaele Scientific Institute
Via Olgettina 58
20132 Milan Italy

Mark Perkins Replied at 8:12 AM, 9 May 2011

One of the earliest strategy questions is whether or not Xpert would be primarily used to improve case detection, or to screen for MDR-TB. For countries choosing to focus on MDR screening, then clearly the populations selected for testing would be different, as might be the locations of device placement. Another important strategic issue is how the existence of Xpert changes considerations for strengthening laboratory capacity for culture and DST. At FIND, our feeling is that all countries should have national capacity for reference level testing using conventional culture-based methods, but that Xpert might obviate the need for the development of culture and biosafety infrastructure at many regional, district and sub-district settings. Though the cost of Xpert testing will do down as volumes increase, implementation of Xpert will have important budgetary implications, especially in the short term. National programs and other implementers may chose to conserve resources that might otherwise have been dedicated to culture and DST and related infrastructure, and to target Xpert testing on high impact populations such as those with MDR risk factors, or smear-negative TB with a high risk of short-term mortality such as in HIV co-infection.

Xpert was designed to be as simple and rapid as possible, and will have its greatest clinical impact when used in clinical settings where patients can be tested while waiting, and where therapeutic decisions can follow directly. That being said, the more peripheral the testing site the weaker the infrastructure in most settings. There are some clear limitations as to where Xpert can be implemented. Sites must have reliable power supply (including solar, as currently being done in Uganda), security against computer theft, and be able to store cartridges below 30 degrees C (we are working to raise that temperature). Temperature also matters for device operation. Though we have successfully used Xpert at laboratories where temperatures were over 40 degrees C, when temperatures get too high, the device is unable to thermocycle (rapidly heat and cool, which drives the amplification reaction) optimally, and will give an error message.


______________________________________
Mark Perkins, MD
CSO, FIND

Christopher Gilpin, PhD, MPH Moderator Replied at 8:14 AM, 9 May 2011

What factors are important to consider when integrating the Xpert MTB/RIF Diagnostic Test and GeneXpert system into current TB diagnosis and treatment plans, especially in areas with limited resources?

The primary consideration for integrating the Xpert MTB/RIF into country diagnostic and treatment plans will be knowledge of the epidemiology of TB and HIV in each setting. Persons at risk of MDR-TB or HIV-associated TB should have access to the Xpert MTB/RIF as their initial diagnostic test for TB. The Xpert MTB/RIF will not replace the need for AFB microscopy or culture. As implementation of the Xpert MTB/RIF is expected to increase the both the number of rifampicin-resistant and rifampicin-susceptible TB cases, plans to ensure the provision of appropriate treatment and care need to carefully considered.

What is the appropriate placement of Xpert MTB/RIF Diagnostic Test in the health care system taking into account operational considerations, burden of disease, and existing TB diagnostics?

The Xpert MTB/RIF should be placed at intermediate level laboratories within the TB laboratory network. Positioning of the technology must consider local TB epidemiology and needs to be done in such a way that it improves access for risk groups to a rapid diagnosis of MDR-TB and HIV associated TB. Placing the technology at the lowest levels of the laboratory network may result in the technology being underutilised. Placing the Xpert MTB/RIF at intermediate level laboratories can allow for referral of samples from person at risk from lower level laboratories and thus be accessible to and benefit a larger population. The Xpert MTB/RIF requires continuous stable electrical supply and considerations must be given for the use of UPS devices, generators or rechargeable 12V batteries in settings with irregular power supply. Each country will still require at least one quality assured culture and DST facility at central level.

How can countries evaluate the impact of implementing the Xpert MTB/RIF Diagnostic Test and generate evidence for scaling-up?

WHO will be monitoring the roll-out of the Xpert MTB/RIF and will be continuously mapping implementation sites as they are established. Following the recent Early Implementers Meeting convened by WHO in Geneva, implementation sites in co-ordination with National TB Programmes are being requested to regularly report on operational challenges associated with implementation as well as on number of tests performed and cases detected. Evidence collected during this roll-out phase is expected to enable an assessment of the impact of Xpert MTB/RIF implementation in different epidemiological settings and to guide widespread scale-up of Xpert MTB/RIF implementation in 2012.

Keith Brown Replied at 11:48 AM, 9 May 2011

I would also like to suggest that as a humble toiler in the vineyards of the 3rd/4th/5th world, we need a rapid diagnostic capability to distinguish non-tuberculous mycoplasma infections... far too many patients are being placed on courses of therapy when no confirmation or f/u is available after a rapid diagnostic test is positive. Thanks!

Nathalie MEZGER Replied at 5:27 AM, 10 May 2011

Nathalie Mezger, MD, DTMH, MPh, SMIH - University Hospital Geneva

I would also humbly suggest that some categories could be add to the inclusion criteria for the use of this incredible new diagostic tool.

Beside the HIV status and its prevalence, beside the severity of the clinical status, we could think on confined settings such as prisons and vulnerable status such as, for example, women or unstable population (illegal migrants, IDU...) for whom it is often even more difficult to have access to care, for whom you will not have many tries.

By the way what do we kow on the performance of this machine on the non sputum samples (urine, blood)? I know that it is not recommended for the moment but is there an ongoing research on this subject?

Mark Perkins Replied at 5:37 AM, 10 May 2011

Natalie,

There are a number of studies ongoing for non-respiratory samples. For example, a protocol for blood processing to look for bacteremia has been developed and a trial in a febrile HIV-infected cohort is being carried out with blood culture and sputum culture comparators. Similarly, a CSF protocol has been developed. There are currently no plans for a regulatory filing for an extrapulmonary testing indication.

Mark

______________________________________
Mark Perkins, MD
CSO, FIND

Mark Perkins Replied at 5:39 AM, 10 May 2011

Keith,

The Xpert MTB/RIF assay targets sequences of the rpoB gene that are specific for M. tuberculosis. All NTM species are non-reactive, even at very high concentrations.

Mark

______________________________________
Mark Perkins, MD
CSO, FIND

Dr. Daniela Cirillo, MD, PhD Replied at 9:48 AM, 10 May 2011

Dear keith, I share your concern but the Xpert will detect the presence of
MTB independently from the detection of mutations in rpoB using different
probes.

--
Daniela Maria Cirillo, MD PhD
Head, Emerging Bacterial Pathogens Unit
DIBIT2 San Michele building
San Raffaele Scientific Institute
Via Olgettina 58
20132 Milan Italy

Sophie Beauvais Replied at 10:29 AM, 10 May 2011

Member Diane Nyole asked the following questions after the posting of the Lancet article: Feasibility, diagnostic accuracy, and effectiveness of decentralized use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study (http://www.ghdonline.org/drtb/discussion/xpert-mtbrif/):

Does the operational temperature of the Xpert machine affect the results outcome?

Why was it necessary to capture the operational temperature range in South Africa?

Mark Perkins Replied at 10:50 AM, 10 May 2011

Diane,
Since Xpert testing is a real-time PCR assay, the speed of heating and cooling of the reaction is fundamental to the assay. The device cannot operate at temperatures that are too high or too low. We measured the operating temperature in all the sites during Demonstration to see what kind of conditions they tolerated. In some settings, for example in India, the laboratory temperature was over 40 degrees C but the device still operated well. In the long run, however, we will need to develop special methods to allow the devices to operate in the more extreme conditions seen in a number of endemic countries. We are currently working to address this.
Mark Perkins

Gemeda Abebe Replied at 12:24 PM, 10 May 2011

What factors are important to consider when integrating the Xpert MTB/RIF Diagnostic Test and GeneXpert system into current TB diagnosis and treatment plans, especially in areas with limited resources?

Since GeneXpert detects only resistance to rifampicin it is important to consider further testing for isoniazid so that MDR-TB could be objectively diagnosed. It's placement need to be in combination with other facilities that can test for complete MDR-TB. If this is not possible, the sample referral system must be taken into account so that every rifampicin resistant case could be tested for MDR-TB. The system to make the consumables available for this method must also be taken in to account as the custom clearance in some resource limited settings is too long which may let the reagents expire on their way even before being delivered to the end user.

Dr. Daniela Cirillo, MD, PhD Replied at 12:40 PM, 10 May 2011

I agree, further testing for confirming MDR should be available. A second
Xpert on a new sample could be performed if prevalence of Rif resistance is
low or a LPA. Sample should be referred for culture in a laboratory able to
performe a second line DST as well. Stability of Xpert reagents seems pretty
good and they have a long expiration date

--
Daniela Maria Cirillo, MD PhD
Head, Emerging Bacterial Pathogens Unit
DIBIT2 San Michele building
San Raffaele Scientific Institute
Via Olgettina 58
20132 Milan Italy

Amy Mikhail Replied at 2:08 PM, 10 May 2011

I am currently working in Afghanistan, where we will shortly have the potential to buy this system in support of a national laboratory quality improvement and QA program.

Some of the issues that have already come up are:

1) Placement within the health system - I'm aware that this system was designed to be suitable for users without molecular training. However, given the cost does not support purchasing this system for lower levels due to the numbers involved, it will most likely be placed at the regional laboratory level. There will be 8 regional diagnostic labs in Afghanistan, and 8 systems are a feasible number to buy and maintain. A regional lab is second only to the top most level (national reference lab). I am curious to know where in the health system other countries are placing this system.

2) A closed system is clearly preferable to open culture, which places laboratory employees at very real risk. Ideally confirmatory diagnosis for TB would only need to be done at the health system level where systems such as the Xpert are available - however I realise the feasibility of this depends on local prevalence and incidence. I agree with the other posters in that this system needs to be complemented with an initial diagnostic in rapid test format that would be cheap and easily deliverable to lower levels of the health system.

3) To manage the relative expense of the cartridges, a good referring diagnostic algorythm is necessary. This need not go as far as identifying persons suspected of having MDR TB but should at least involve another diagnostic test for TB itself. Have any other users tried different referring algorythms and if so, what was both safer for the staff and cost effective (in terms of correct referral for use of the Xpert)?

4) Disposal of used cartridges also needs to be considered. I have not used the system myself yet, but I hear from colleagues that they are bulky - can they be incinerated or safely compressed in any way? What advice is currently being given about cartridge disposal?

5) Some posters already mentioned environmental conditions - here in Kabul in addition to temperature we also have altitude to consider (altitude here is 1800m and some other locations are even higher e.g. Quito, or Addis Ababa). The boiling point of water here is 93 degrees centegrade. Has the system been tested at high altitude?

6) Last but not least - another poster mentioned possibly culturing a sample as well as running it on the Xpert. I think the whole point of systems like the Xpert is to facilitate a move away from culture. I cannot emphasize enough how dangerous this practice is for laboratory employees - I personally know 3 who have contracted TB from working in laboratories where TB culture was performed. In practice, it is extremely difficult to guarantee that staff will adhere to the necessary personal safety measures or are sufficiently aware of the precautions they should take. The problem becomes more chronic the lower in the health system you go.

Mark Perkins Replied at 5:34 PM, 10 May 2011

Amy,

A quick numbered response:

1 - The Xpert assay has only been WHO-endorsed for a few months, so experience in disease-endemic countries is limited. In Brazil, some Xpert machines are going into health centers without laboratory capacity and being run by nurses. In other countries like South Africa, a substantial amount of regional or centralized testing is ongoing or planned. Placement depends on where patients seek care, where the security and power is available for maintenance, and what obstacles exist to information flow.

2 - Xpert is felt to pose no significant biohazard, as the first step is to add a reagent that is mycobacteriocidal. You are right that pretesting in the community, should such a test exist, to select for those suspects with the greatest risk would decrease cost per patient detected.

3 - Would leave to users to comment

4 - Current disposal advice from WHO is to dispose of the cartridges in the same manner as sputum cups. We are exploring environmentally sound methods of burning/recycling/disposing.

5 - The system was not tested for high altitude use that I know of in development, but this is an interesting question. I believe systems are working well from Kampala to Addis, but will check to see if any background work has been done on high-altitude testing.

6 - Agree. The point of developing a molecular assay with similar sensitivity to culture is to get away from having to do culture.

Mark Perkins



______________________________________
Mark Perkins, MD
CSO, FIND

Gemeda Abebe Replied at 1:56 AM, 11 May 2011

Amy,
As to the placement specific situations need to be considered. For instance here in Ethiopia all regional labs are not in the same compound with a hospital which necessitates the transport of samples. Transporting the samples by itself will increase the time gap between sample delivery and resulting dispatching.

Christopher Gilpin, PhD, MPH Moderator Replied at 6:36 AM, 13 May 2011

Dear Amy,
Good referral mechanisms of specimens from lower level (peripheral laboratories) to intermediate level laboratories (e.g. District level ) will be needed for all persons at risk of MDR and HIV -associated TB. Xpert MTB/RIF is recommended as the initial diagnostic test for these two risk groups but can be performed as an add-on test to AFB microscopy where resources allow. Positioning of the techniology will however depend on the epidemiology of TB and HIV in each setting.
The Xpert MTB/RIF assay needs to be positioned in a setting where it is being fully utilised to maximise its effectiveness in TB case detection.

Edward Nardell, MD Replied at 1:35 PM, 13 May 2011

Dear colleagues: This is an interloper comment from the TB IC community. I would like to make the following points:
1) Effective treatment - meaning knowing and promptly treating drug resistance - is likely the most rapid and effective means of transmission control - for MDR as well as drug susceptible TB(maybe not XDR).
2) Active case finding through screening of coughing patients at the entrance point of hospital and clinic by Gene-Xpert could assure that there are no undiagnosed TB cases, and no unsuspected drug resistant cases transmitting. This assumes that a FQ test becomes available to dx XDR.
3) this fits in with a forthcoming TB CARE camgaign currently in draft form: FAST = Find cases Actively,Separate and Treat.
4) to be really useful, Gene Xpert needs to be at the point of care.

Ed Nardell

Shelly Batra, MD Replied at 2:08 PM, 13 May 2011

Thank you , all for the enlightening discussion.
I have a question for Ed Nardell and others :- What is your understanding
of the 'Separate ' component of FAST ? How would you ensure it in resource
limited settings?
warm regards
shelly

--
*Shelly Batra, MD
*
President*

egh Eduardo Gotuzzo Replied at 12:27 PM, 15 May 2011

Re:

3) To manage the relative expense of the cartridges, a good referring diagnostic algorythm is necessary. This need not go as far as identifying persons suspected of having MDR TB but should at least involve another diagnostic test for TB itself. Have any other users tried different referring algorythms and if so, what was both safer for the staff and cost effective (in terms of correct referral for use of the Xpert)?

Looking for MDR-TB depends on the frequency of this condition in your region

Culture in liquid medium make a fast diagnoses and the strain could be sent to be studied of rapid sensitivity of rifampicin

In addition, we recommend MODS system, which also reduced the time of resistance diagnoses

Use epidemiologic clinic criteria are important, For example the most important MDR-TB risk factors in Peru are

1. HIV AIDS
2. Diabetes
3. MDR-TB household contacts
4. Household contacts of cases who died recently (in the last 3 years) for TB with response at standard treatment even without test of resistance
5. Drug abuser IV or oral or smoker
6. Be in jail recently
7. Living in high resistance epidemiologic areas
8. Health care worker (MD nurse, technician, etc)

With these criteria, you could reduce your culture to the most indispensable, considering economical restriction and you only make a culture to those with high option of having MDR-TB

If you are in high endemic areas, it is better to have tests more fast, such as GenXpert, but I agree that they are expensive, but we hope to have different prices for the 3rd world countries

Best regards,

Eduardo Gotuzzo

Philip Lederer Replied at 3:19 PM, 15 May 2011

Hello, thanks so much for a terrific discussion! I work in Mozambique and San Diego. Two questions:

1) Is there an Xpert website/ internet presence that can keep up the momentum?

2)Where can people go if their organization wants to purchase an Xpert?

Thanks!
Philip Lederer

NATALIA TAMAYO Replied at 9:23 AM, 16 May 2011

Hello, and thanks for such interesting discussion.
What about the performance of Xpert on the gastric lavage? It`s a respiratory sample, but i`m not sure about the experience on this sample. Thanks ! Natalia

Frederic LEME Replied at 10:55 AM, 16 May 2011

This is to address the two Questions of Philip Lederer (N°21). The two links below will surely help

http://www.finddiagnostics.org/programs/tb/find-negotiated-prices/xpert_mtb_r...

And feel free to visit Cepheid specific web site @
www.cepheidcares.com ,
from where you can fill in a request form, using the CONTACT US button.

Or email me direct.
Sincerely,
Frederic LEME
Cepheid SAS

Nathalie MEZGER Replied at 12:15 PM, 16 May 2011

Dear Mark,

Many thanks for your previous answer and to have given the opportunity to have such an exchange.
As the machine was designed to be used in relatively simple settings, is there any plan to developp a russian version of the machine soft ware? In my knowledge this is not available for the moment (do I have the correct information?) and usually there are not a lot of the lab technician of for ex. the ex-URSS countries who can speak english? Language is a very practical issue for the implementation. Thanks ! Nathalie, SMIH, University of Geneva

Mark Perkins Replied at 11:07 PM, 16 May 2011

Nathalie and Natalia,
There is a limited amount of information on the use of samples other than sputum for testing. In theory, there is no reason gastric aspirates will not work well. We should be able to say with greater confidence as the results of ongoing studies come in.
There is not currently a Russian language version of the software as you point out. We have been in discussion with Cepheid on approaches to broaden the utility of the system with either additional languages or the use of symbols.

Dr. Daniela Cirillo, MD, PhD Replied at 4:35 AM, 17 May 2011

Dear Philip, I see that you have received the appropriate link. Would like
to inform you that there is a plan to purchase at least 3 Xpert to be
installed in Mozambique. Different partners are making plan an I hope the
action will be somehow coordinated.
Best regards
Daniela

Dr. Daniela Cirillo, MD, PhD Replied at 1:41 PM, 17 May 2011

Dear natalia, the gastric aspirate is not included in the respiratory samples, the Italian pediatric center that is using the Xpert on gastric aspirate is reporting a satisfactory performance

Imtiaz Ali Replied at 2:21 PM, 17 May 2011

Dear Amy,
Where you work in Afghanistan, I am a laboratory supervisor, based in Faizabad provincial hospital Badakhshan Afghanistan.Xpert/MTB RIF technology looks appropriate for provincial level lab. I would like to know more about your TB Lab activities in Afghanistan.

Jane Tang Replied at 3:17 PM, 17 May 2011

Thank you for such interesting discussions. I appreciate if Xpert MTB/RIF users can share some lessons-learned.

NATALIA TAMAYO Replied at 10:44 AM, 18 May 2011

Daniela, thanks for your answer. I`m working in Swaziland, where DR TB is a huge problem; and children are difficult population for diagnosis (as everywhere). Do you know about any written report of this Italian Ped Center?

Dr. Daniela Cirillo, MD, PhD Replied at 10:51 AM, 18 May 2011

Not yet, but I can give you the contact of Dr Cristina Russo if you are
interested

Dr. Saswata Dutt Replied at 11:14 AM, 18 May 2011

Dear Dr. Natalia & Dr. Daniela,

I am working at Nigeria. Please send me a copy, if you find one.

Thanks.
Saswata.

Dr. Daniela Cirillo, MD, PhD Replied at 1:41 PM, 18 May 2011

I also suggest to look at this recent paper by Doris hilleman

J Clin Microbiol. <javascript:AL_get(this, 'jour', 'J Clin Microbiol.');>
2011 Apr;49(4):1202-5. Epub 2011 Jan 26.
Rapid Molecular Detection of Extrapulmonary Tuberculosis by the Automated
GeneXpert MTB/RIF System.
Hillemann D Rüsch-Gerdes S , Boehme C Richter E
Nationales Referenzzentrum für Mykobakterien, Forschungszentrum Borstel,
Parkallee 18, 23845 Borstel, Germany. .

Abstract
In total, 521 nonrespiratory specimens (91 urine, 30 gastric aspirate, 245
tissue, 113 pleural fluid, 19 cerebrospinal fluid [CSF], and 23 stool
specimens) submitted to the German National Reference Laboratory for
Mycobacteria (NRL) from May 2009 to August 2010 were comparatively
investigated with the new molecular-based GeneXpert MTB/RIF (Xpert) assay
system and conventional liquid and solid culture methods. Twenty (3.8%) of
the 521 specimens gave no interpretable result. Whereas the sensitivity of
the Xpert assay with tissue specimens was 69.0% (20 out of 29
culture-positive cases detected), 100% sensitivity was found with the urine
and stool specimens. The combined sensitivity and specificity of the Xpert
assay were calculated to be 77.3% and 98.2%, respectively

NATALIA TAMAYO Replied at 4:20 PM, 18 May 2011

Daniela, i`m very interested in contact somebody working with Xpert in gastric lavage. I`d appreciate Dr.Russo`s mail. Thanks

Dr. Daniela Cirillo, MD, PhD Replied at 5:05 AM, 19 May 2011

Dr Cristina Russo will be invited in the chat but if you like to contact her
directly she is available to share her experience




Best regards
daniela

--
Daniela Maria Cirillo, MD PhD
Head, Emerging Bacterial Pathogens Unit
DIBIT2 San Michele building
San Raffaele Scientific Institute
Via Olgettina 58
20132 Milan Italy
Ph +390226437947
Fax +390226435183


LEGAL DISCLAIMER: This communication (including any attachments) contains
proprietary information some or all of which may be legally privileged.
Unless you are the intended recipient (or authorized to receive for the
intended recipient), you must not print, retain, use, copy, distribute or
disclose to anyone this message or any information contained in it. If you
receive this e-mail in error, please notify the author immediately by
replying to this e-mail and then delete it from your system. E-mail
transmission cannot be guaranteed to be secure or error-free as information
could be intercepted, corrupted, lost, destroyed, arrive late or incomplete,
or contain viruses. The sender therefore does not accept liability for any
errors or omissions in the contents of this message, which arise as a result
of e-mail transmission.
Please think of the environment before you print this message and any
attachments.




-----------------------------------------------------------------

Dai il tuo 5XMILLE al San Raffaele. Basta una firma.
Se firmi per la ricerca sanitaria del San Raffaele di Milano, firmi per tutti.
C.F. 03 06 42 80 153.
INFO: - www.5xmille.org

Dr. Saswata Dutt Replied at 6:40 AM, 19 May 2011

Thanks Dr. Daniela. If Dr.Russo can share her experiences, mainly about the
diagnosis of DR-TB in children, both pulmonary and extra-pulmonary.
Thanks & regards.
Saswata Dutt.

Regina Bhebhe Replied at 9:20 AM, 19 May 2011

Dear Colleagues
Can Chris Gilpin assist in these questions:
Question 1.I have a question as we do the xpert there is a need to identify which type of mycobactrium it is? Because as we used to do culture and then identify the type of mycobactrium. Do we now assume that as the results would be resistant to rifampicin it is all the same mycobactrium. There is nolonger any different species such as: mycobactrium bovis or mycobactrium avium. Or it not a challenge as they need the same treatment.
Question 2: My second question is in doing TB cultures I have observed in our laboratory that when the TB organisms have grown in the culture medium, we make a smear from the growth and when we find cording in reading of the smear slides it is identified as mott and is issued out as a result. This is a new procedure that I am not used and not sure because I used to know that you would make your smear from the culture growth if there is cording you continueing do your catalase i.e. identification of the species and then report and send out your results together with how many colonies have grown.
Regina (SMLSc)
National Tuberculosis Reference Laboratory
Bulawayo
Zimbabwe

Christopher Gilpin, PhD, MPH Moderator Replied at 10:23 AM, 19 May 2011

Dear Regina,
Question 1: The Xpert MTB/RIF is highly specific for the detection of DNA for the Mycobacterium tuberculosis complex. If a sputum sample contains nontuberculous mycobacteria (e.g M.avium) only, the test will be negative for both the detection of MTB DNA and for the detection of rifampicin resistance.
Question 2. All positive mycobacterial cultures containing AFBs need to have a confirmatory test performed. Cording of AFBs in positive cultures is suggestive of MTB but is not confirmation. WHO recommends that liquid culture with rapid speciation using a lateral immunflow test for identification (e.g. Capilia test) is the gold standard method for mycobacterial culture. Biochemical testing can be used to confirm MTB when at least two different tests including inhibition by PNB, nitrate reduction, niacin accumulation and/or catase production are performed.

Mark Perkins Replied at 10:26 AM, 19 May 2011

Regina,

The Xpert MTB/RIF assay is specific for M. tuberculosis, so you will not experience the device detecting rifampin resistance from non-tuberculous mycobacteria. In terms of identifying species, my own experience is that mycobacteriology labs often waste too much time defining the precise species of NTMs with biochemical methods, especially in the frequent cases when it is not clinically relevant. Samples that are smear-positive but Xpert negative would be reasonable samples to culture and do species identification on.

In terms of species identification based on cording, M. tuberculosis tends to show cording in liquid culture, but non-tuberculous species tend not to. It is a reasonable, but imperfect method, and many groups now use the simple rapid tests detecting the TB-specific protein MPT64 to determine whether a positive culture is M. tuberculosis or another species.

Mark Perkins

______________________________________
Mark Perkins, MD
CSO, FIND

Andrew Bresnahan Replied at 11:22 AM, 19 May 2011

Thanks for a great discussion. I work with Labrador-Grenfell Health in TB prevention and control, and our TB team is currently discussing the application of this diagnostic tool here in Canada’s north.

Does anyone know if Xpert MTB/RIF roll out or operational research is taking place in any rural or remote northern settings, such as the Canadian arctic/sub-arctic, Greenland, Scandinavia, Russia, or Alaska? TB remains endemic in Canada’s north, especially among indigenous Inuit and First Nations populations. In 2008, active TB incidence in Nunavut, NWT, and Yukon was 73/100,000 – much lower than so many places in the global south, but scandalously high for such a wealthy country.

Information on good referring diagnostic algorithms and cost in these settings would also be very helpful.

many thanks,
Andrew Bresnahan, MSc, MPH(c)

Eduardo Hernandez Replied at 7:05 PM, 19 May 2011

Wonder whether the GeneXpert has also been performed in blood? I'd appreciate the reference if that is the case

Thank you

Eduardo Hernández-Garduño MD MHSc
TB Epidemiology
British Columbia Centre for Disease Control
1066-655 West 12th Ave
Vancouver BC
V5Z 4R4

David Moore Replied at 8:53 AM, 20 May 2011

Congratulations to all for a fascinating discussion.
A point of clarification regarding the use of cording as confirmation of MTB in liquid cultures (comment 38).
Using MGIT cultures in South Africa Chihota et al (IJTLD 2010; 14 (8): 1024-1031) demonstrated that the sensitivity and specificity of demonstration of cording for identification of MTB was identical to the use of MPB64 testing (99.0% and 97.9% respectively) confirming the findings of all groups who have published their work on MODS, including our own, who have argued that this is a reliable and safe method for differentiating M tuberculosis from MOTT/NTMs.
I was surprised to hear that WHO had endorsed MPB64/MPT64 lateral flow assays as the method of choice as I was unaware of this - I would be grateful if Dr Gilpin could direct us to the relevant policy document.
Dave Moore
LSHTM

Attached resource:
  • Speciation (download, 299.1 KB)

    Summary: Congratulations to all for a fascinating discussion.
    A point of clarification regarding the use of cording as confirmation of MTB in liquid cultures (comment 38).
    Using MGIT cultures in South Africa Chihota et al (IJTLD 2010; 14 (8): 1024-1031) demonstrated that the sensitivity and specificity of demonstration of cording for identification of MTB was identical to the use of MPB64 testing (99.0% and 97.9% respectively) confirming the findings of all groups who have published their work on MODS, including our own, who have argued that this is a reliable and safe method for differentiating M tuberculosis from MOTT/NTMs.
     I was surprised to hear that WHO had endorsed MPB64/MPT64 lateral flow assays as the method of choice as I was unaware of this - I would be grateful if Dr Gilpin could direct us to the relevant policy document.
    Dave Moore
    LSHTM

    Source: London School of Hygiene & Tropical Medicine

    Keywords: Clinical Assistance, Laboratory, Program Management, TB CARE II, technical assistance

Sophie Beauvais Replied at 11:34 AM, 21 May 2011

Dear All,

We would like to thank everyone, panelists and members, for a great panel discussion on the challenges of rolling-out GeneXpert MTB/RIF in resource-limited settings. We will soon publish a peer-reviewed discussion brief to share some of the lessons learned here so check out for updates soon.

Last but not least, although the panel has officially ended, there are still a few questions open so please feel free to continue the discussion:
Has the GeneXpert been performed in blood? If yes, please share references.
Is there any Xpert MTB/RIF roll-out or operational research taking place in rural or remote northern settings, such as the Canadian arctic/sub-arctic, Greenland, Scandinavia, Russia, or Alaska?
Please share information on referring diagnostic algorithms and cost in rural/remote settings.
To those involved in studies and early implementers discussions on the Xpert MTB/RIF roll-out: please share lessons-learned.

Sincerely, Sophie

Cornelia Hennig Replied at 9:33 PM, 21 May 2011

Dear all,

can you please advise on validation procedures for the Xpert MTB/RIF.
I have learnt about in-built quality checks in the cartridges.
However, when receiving the machines and before starting to test samples, does each module need to undergo validation with known positive and negative samples, i.e. positive and negative for M. TB, susceptible and resistant to Rif?
If yes, how often would that process have to be repeated?
This might have implications when ordering cartridges.

Many thanks

Cornelia HENNIG
WHO
Medical Officer STOP TB
Viet Nam

Christopher Gilpin, PhD, MPH Moderator Replied at 3:14 AM, 23 May 2011

When using liquid culture, with the expectation that time-to-detection will be significantly reduced, it is also imperative that a rapid method of species identification be used. Recommendations for speciation of mycobacterial isolates can be found at http://www.who.int/tb/laboratory/use_of_liquid_tb_culture_summary_report.pdf

Christopher Gilpin, PhD, MPH Moderator Replied at 3:26 AM, 23 May 2011

Each Xpert MTB/RIF contains the following internal controls:
The sample processing control (SPC) contains non-infectious spores in the form of a dry spore cake that is included in each cartridge to verify adequate processing of MTB.
• Verifies that lysis of MTB has occurred if the organisms are present
• Verifies the specimen processing is adequate.
• Detects specimen associated inhibition of the real-time PCR assay.
• SPC should be positive in a negative sample and
• SPC can be negative or positive in a positive sample.
• SPC passes if it meets assigned acceptance criteria.

The Probe Check Control (PCC) is a check undertaken before the start of the PCR reaction. The system measures the fluorescence signal from the probes to monitor bead rehydration, reaction-tube filling, probe integrity and dye stability.
PCC passes if it meets assigned acceptance criteria.

As an addition measure of quality assurance, the Global Laboratory Initiate Core-Group recommended the use of a validation panel of artificial sputum samples containing heat-killed MTB organisms to be shipped with each new GeneXpert instrument and following calibration of individual modules so that modules can be validated before routine test results are reported. WHO is co-ordinating the initial development of these validation panels including a review of results from testing sites. This QA programme is expected to be fully operational from June 2011.

Emmanuel Fajardo Replied at 7:18 AM, 23 May 2011

Dear Cornelia,

We have implemented Xpert/MTB in a number of projects in Southern Africa and we have been told there is no need to validate each module before starting routine work. Although the instrumen self- checks all parameters of the module, and the cartridges QC (SPC and PCC) ensures cartridge and specimen integrity, we have opted to run positive samples (smear +++) and a negative control on a montly basis as part of IQC while we wait for the WHO validation panels.

Regards,

Emmanuel Fajardo
Laboratory Specialist
Doctors Without Borders
MSF-OCB Medical Department
Cape Town - South Africa

Regina Bhebhe Replied at 7:31 AM, 23 May 2011

Thank you Gilpin for answer and wht is is required to be done to confirm the MTB. As I had seen people confirming with the coding I thought this was something new. Thank you for the clarity for both questions.
Regina (MLSc)
Bulawayo
Zimbabwe

Dr. Daniela Cirillo, MD, PhD Replied at 7:44 AM, 23 May 2011

Dear Cornelia the quality checks performed by the machine validate the rune.
In addition you can test a TB positive and a negative sample as Qas. I don't
think it is necessary to test rif resistant and sensitive samples The
schedule for testing may depend on the availability of reagents. In
addition you may consider testing new batches of cartridges.

Regina Bhebhe Replied at 7:45 AM, 23 May 2011

Dear Mark Perkin
Thank you for the clarity, but as we work in the laboratories we need to know whether we still have different species. It can be a waste of time but of interest it is good to know whether all what we have as tuberculosis is a different specie. Maybe the solution we need is a simple and an easy method to identify these species like what we have now the Xpert that makes it easy to diagnose TB and start treatment as early as possible.
Regina Medical Laboratory Scientist
National Tuberculosis Reference Laboratory
Bulawayo
Zimbabwe

egh Eduardo Gotuzzo Replied at 4:06 PM, 23 May 2011

Two additional comments:

1. This equipment is easy of use and without option to disseminate the infection during the test.

2. In Peru, one of the countries of America having the most quantity of MDR-TB cases (and XDR-TB) the problem of delay is the identification of MDR-TB and the minimum of appropriate treatment; it is one of the most important causes of this MDR-TB high frequency having had with the National Program with the major DOTs of nation.

If there is not the appropriate treatment, this delay can infect 15-20 persons in 6 months, but a standard culture is expected in 6 weeks, sensitivity tests (6-8 weeks) and then sensitivity to drugs of second line. As we have seen, this delay is an important resource and this situation in important endemic areas (>7-10%) it is really useful to make these tests in endemic areas and in persons having high risk of suffering MDR-TB (AIDS, D. mellitus, drug abusers, household of case with MDR-TB, health care workers, etc.) reducing the costs and focus the cost. That way will be the most initial use of this high quality technology for persons of 3rd world.

Best regards,

Eduardo Gotuzzo

Dr. Daniela Cirillo, MD, PhD Replied at 10:50 AM, 27 May 2011

To answer Eduardo Hernández-Garduño (comment #41) asking whether the GeneXpert has also been performed in blood: It is feasible but no published results are available. The protocol suggested is:
1 ml of blood + 2.5ml Sample Reagent and 15 minutes incubation. 2 mL of material are then transferred into the cartridge for the analysis.

Mark Perkins Replied at 7:08 PM, 27 May 2011

An alternative protocol with larger volumes is being assessed, and data supporting a final protocol should be ready next year.
Mark Perkins

Mark Micek Replied at 7:18 PM, 31 May 2011

Dear all,
Thanks for a great discussion, and sorry to join late.
I am involved with introducing Xpert MTB/RIF in Mozambique. As suggested, one possibility to increase coverage with a few machines is the placement of machines in central areas, and then transporting sputum from a wide area to these central locations. We are envisioning such a system, but are worried about the time we have for specimen transportation. How long is the sputum good for? Does it need to be refrigerated the entire way? Does it make sense (from both an expiration and sample-volume standpoint) to hope that a single sputum specimen can be used for AFB smear, and if negative get transported to another site for Xpert testing, and if positive for RIF resistance, get transported again to another site for culture/DST?
Thanks-
Mark Micek, University of Washington

Gabriela Torrea Replied at 3:42 AM, 1 Jun 2011

Dear Mark Micek,
I attended to a training in Toulouse (CEPHEID) and I think I can answer your question. Sputum specimens should be held at 2-8°C prior to processing "whenever possible". However, the specimen can be stored at a maximum of 35°C for less or equal than 3 days and at 4°C for 4 to 10 days. A minimum of 1 ml of sputum is used only for preforming this test so for other tests you mentioned you need more than 3 ml, 5 ml is better. This recommendation comes from CEPHEID , however you can gain your own experience performing some experiments to validate your results even if some additional cartridges have to be used. In case you have to transport specimens for more than 3 days to another site to submitt the sample to culture and DST it is recommended using a preservative as CPC at Room temperature only when solid medium is used (LJ), while broth culture requires specimens to be refrigerated.
Hope I answered your questions.

Best regards,

Dr Gabriela Torrea, PhD
Mycobacteriology Unit
Prince Leopold Institute of Tropical Medicine
Nationalestraat 155
2000, Anwerp, Belgium
Phone: +32 3 247 63 36
Fax: +32 3 247 63 33
email: /

Levan Gagnidze Replied at 4:06 AM, 1 Jun 2011

Dear Mark,
If a specimen is used for Xpert you cannot use it for culture examination anymore. Though it is possible to inoculate culture media first and than use left over sample for Xpert testing.
You will need a new sample for culture examination.
Regards,
Levan Gagnidze
Regional Coordinator for Lab Services, Asia & the Pacific
IOM Regional Office, Bangkok

Sophie Beauvais Replied at 2:44 PM, 10 Jun 2011

Dear All,

Thank you for a fantastic discussion. We've tried to capture the lessons learned from this exchange in a new peer-reviewed discussion brief that is now available online in the community. Thank you in advance for any feedback you may have. Best, Sophie

Romain Prieur Replied at 3:01 PM, 10 Jun 2011

Thanks Sophie.

Can you provide a quick link to this brief?

Thanks

Romain

Sophie Beauvais Replied at 3:14 PM, 10 Jun 2011

http://www.ghdonline.org/drtb/discussion/ghdonline-expert-panel-challenges-in...

but you have to sign in to GHDonline to view or download a PDF version

Best, Sophie

Sophie Beauvais Replied at 11:34 AM, 30 Sep 2011

Hi Everyone, you might have seen this already but thought I'd share: In July, a new paper on the accuracy of the Xpert MTB/RIF test was published in The Lancet. The summary is below and you can access the full text on the Lancet's website when you sign in (free registration): http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(11)70167-0/ful...

Summary:

Background
WHO recommends that Xpert MTB/RIF replaces smear microscopy for initial diagnosis of suspected HIV-associated tuberculosis or multidrug-resistant pulmonary tuberculosis, but no data exist for its use in children. We aimed to assess the accuracy of the test for the diagnosis of pulmonary tuberculosis in children in an area with high tuberculosis and HIV prevalences.

Methods
In this prospective, descriptive study, we enrolled children aged 15 years or younger who had been admitted to one of two hospitals in Cape Town, South Africa, with suspected pulmonary tuberculosis between Feb 19, 2009, and Nov 30, 2010. We compared the diagnostic accuracy of MTB/RIF and concentrated, fluorescent acid-fast smear with a reference standard of liquid culture from two sequential induced sputum specimens (primary analysis).

Results
452 children (median age 19·4 months, IQR 11·1—46·2) had at least one induced sputum specimen; 108 children (24%) had HIV infection. 27 children (6%) had a positive smear result, 70 (16%) had a positive culture result, and 58 (13%) had a positive MTB/RIF test result. With mycobacterial culture as the reference standard, MTB/RIF tests when done on two induced sputum samples detected twice as many cases (75·9%, 95% CI 64·5—87·2) as did smear microscopy (37·9%, 25·1—50·8), detecting all of 22 smear-positive cases and 22 of 36 (61·1%, 44·4—77·8) smear-negative cases. For smear-negative cases, the incremental increase in sensitivity from testing a second specimen was 27·8% for MTB/RIF, compared with 13·8% for culture. The specificity of MTB/RIF was 98·8% (97·6—99·9). MTB/RIF results were available in median 1 day (IQR 0—4) compared with median 12 days (9—17) for culture (p<0·0001).

Interpretation
MTB/RIF testing of two induced sputum specimens is warranted as the first-line diagnostic test for children with suspected pulmonary tuberculosis.

Funding
National Institutes of Health, the National Health Laboratory Service Research Trust, the Medical Research Council of South Africa, and Wellcome Trust.

Authors: Prof Mark P Nicol PhD, Lesley Workman MSc, Washiefa Isaacs BSc, Jacinta Munro, Faye Black MBBCh, Brian Eley FCPaed, Catharina C Boehme MD, Widaad Zemanay PhD, Prof Heather J Zar PhD

MIKASHMI KOHLI Replied at 2:01 PM, 26 Apr 2013

Can anybody please tell me about the Genexpert cartridge expiry? if there are extra cartridges left in stock, can they be used after the expiry dates?
PS: the cartridges are stored at optimal temperature.

Elisa Ardizzoni Replied at 2:10 PM, 26 Apr 2013

Good evening, if I'm not mistaken the machine does not accept expired catridges, the expiry date is detected though the barcode

soundiram indira Replied at 2:20 PM, 26 Apr 2013

Thank you for your question.

Cartridges cannot been used after expiry. This is a diagnostic kit and even if the cartridges are stored at optimal temperature, the cartridges should be used before expiry.

The idea is that each site manages the stock appropriatly, i.e monitoring the stock 2-3 months before expiry date.
- Eventually, checking with some other sites that could need cartridges to avoid waste might be the solution.
- Estimate and adjust the volume ordered to cepheid to avoid such type of situation.

Please feel free to come back to us before the expiry!

Regards,
Indira Soundiram
Customer Care & Training Manager
Cepheid HBDC
+33 642068877

Le 26 avr. 2013 à 20:02, "MIKASHMI KOHLI via GHDonline" <<mailto:>> a écrit :

MIKASHMI KOHLI<http://email.ghdonline.org/c/ZD0zNzczJmg9N2UxZjUxYmE3ZDQ5YjUxMDM1MDg2Yz... replied to a discussion@@http://email.ghdonline.org/c/ZD0zNzczJmg9NmMwMmE0ODQ1MzRkNDZhOWVkMWFjYjRkMjU0ZTM0ZGImdXNlcnByb2ZpbGVfaWQ9MTc4MDE3NjEmY29tbXVuaXR5X2lkPTIwMDAzJmw9aHR0cCUzQSUyRiUyRnd3dy5naGRvbmxpbmUub3JnJTJGZHJ0YiUyRmRpc2N1c3Npb24lMkZnaGRvbmxpbmUtZXhwZXJ0LXBhbmVsLWNoYWxsZW5nZXMtaW4tcm9sbGluZy1vdXQtdCUyRiUzRmlkJTNEMTc4MDE3NjElMjZmb3JtYXQlM0RodG1sJTI2dHlwZSUzRGluc3RhbnQlMjNyZXBseS04MDUwJnI9aW5kaXJhLnNvdW5kaXJhbSU0MGNlcGhlaWRoYmRjLmNvbQ@@ in MDR-TB Treatment & Prevention@@http://email.ghdonline.org/c/ZD0zNzczJmg9MDY2MTE3Yzg3MmRkMzc5NTVmMGRiOTY0MWNiN2QxN2EmdXNlcnByb2ZpbGVfaWQ9MTc4MDE3NjEmY29tbXVuaXR5X2lkPTIwMDAzJmw9aHR0cCUzQSUyRiUyRnd3dy5naGRvbmxpbmUub3JnJTJGZHJ0YiUyRiUzRmlkJTNEMTc4MDE3NjElMjZmb3JtYXQlM0RodG1sJTI2dHlwZSUzRGluc3RhbnQmcj1pbmRpcmEuc291bmRpcmFtJTQwY2VwaGVpZGhiZGMuY29t@@:

Can anybody please tell me about the Genexpert cartridge expiry? if there are extra cartridges left in stock, can they be used after the expiry dates?
PS: the cartridges are stored at optimal temperature.

egh Eduardo Gotuzzo Replied at 3:52 PM, 26 Apr 2013

we used in the past even 5 months and the results are good however the
experience was small
regards
eduardo gotuzzo

El viernes, 26 de abril de 2013, MIKASHMI KOHLI via GHDonline escribió:

--
************************
Dr. Eduardo Gotuzzo
Director
Instituto de Medicina Tropical
Alexander von Humboldt
UPCH
e-mail:

www.upch.edu.pe/tropicales
www.gorgas.org

--

------------------------------

Trabajamos con seguridad y velamos por la protección del Medio Ambiente.
Antes de Imprimir este mail confirme que sea necesario. Gracias

El presente e-mail y cualquier documento adjunto al mismo, pertenecen al
emisor y puede contener información confidencial legalmente protegida. La
información contenida en este e-mail es remitida únicamente para uso del
destinatario indicado en el mismo. La divulgación, copia, distribución o
cualquier otro uso de la información contenida en el presente e-mail por
parte de personas distintas al destinatario se encuentra prohibido. Si Ud.
ha recibido este e-mail por error, rogamos borrar el mismo e informar dicha
circunstancia por mail a la dirección <>
. Muchas gracias.

This electronic mail transmission and any attached documents contain
information belonging to the sender which may be confidential and legally
privileged. The information is intended for the use of the named
recipient(s) only. If you are not the intended recipient(s), any
disclosure, copying, distribution or action taken regarding the information
on this email is strictly prohibited. If you have received this email in
error please notify and delete the email from your
computer. Thank you.

LLeni Pach Miller Replied at 4:49 PM, 26 Apr 2013

Eduardo,

Quisiera saber de tu experiencia, conversemos cuando vengas a la
Convencion de la PAMS en Huanuco del 7 al 10 de Agosto, 2013,
Un abrazo,

Paramasivan CHINNAMBEDU.N Replied at 11:21 PM, 26 Apr 2013

Thank you Indira for your explicit recommendation on this issue. One cannot afford to compromise on GLP. Thank you also for your suggestions on forecasting the requirements well in advance.
We need to always remind ourselves behind each specimen there is a patient.

Regards,
Param

C.N. Paramasivan

MIKASHMI KOHLI Replied at 12:33 PM, 27 Apr 2013

Thank you for your replies here. They were really helpful. Just wanted to ask if the system would take the cartridge and not reject it because we were just planning to use them for some training purpose, definitely not for patient care.
Thanks a lot.

Regards,
Mikashmi Kohli