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Dear colleagues,

Starting Monday, December 10, and running until Friday, December 14, we are pleased to host a virtual panel discussion on scaling-up the use of the GeneXpert MTB/RIF.

In August, the cost of cartridges used in GeneXpert MTB/RIF was reduced by 40% (going from $16.86 to $9.98), and a few days ago PEPFAR announced an additional $11 million to provide up to 150 GeneXpert MTB/RIF instruments and 450,000 test cartridges in 14 high-burden countries (Cote d’Ivoire, Lesotho, Swaziland, Zimbabwe, DRC, Malawi, Tanzania, Ethiopia, Mozambique, Uganda, Kenya, Nigeria, Zambia, and Burma).

Now is the time to scale-up if we are serious as a community to zero TB. Be part of the solution and join our panelists in drawing practical guidelines for scale-up:
- Fuad Mirzayev and Wayne van Gemert, WHO Stop TB Department
- Elisa Ardizzoni, Médecins Sans Frontières
- Daniela Cirillo, San Raffaele Scientific Institute
- Patrick Gomani, Abwenzi Pa Za Umoyo - Partners In Health Malawi
- Thomas Shinnick, U.S. Centers for Disease Control and Prevention
- Indira Soundiram, Cepheid SAS

To start the discussion, we invite you to reply to this thread and introduce yourself, your work, and share:
- Experiences in planning at the national and regional levels
- Impact of GeneXpert MTB/RIF on patient management, from new diagnostic algorithms to treatment
- Lessons learned with EXPAND-TB
- Training activities and materials for GeneXpert MTB/RIF

Comments and questions related to the use of GeneXpert for increasing TB case finding (including TB/HIV) are also welcome.

We look forward to this discussion. Thank you. Sophie

Attached resources:

Link leads to: http://www.ghdonline.org/drtb/discussion/ghdonline-expert-panel-challenges-in-rolling-out-t/

Link leads to: http://www.ghdonline.org/drtb/discussion/ghdonline-expert-panel-challenges-in-rolling-out-t/brief/

Link leads to: http://uwclh.conference2web.com/content/1678/details?from_view=all&view_address=search%3DElisa

Link leads to: http://uwclh.conference2web.com/content/2008/details?from_view=all&view_address=search%3DGilpin

Link leads to: http://www.youtube.com/embed/ma2-tpsMdxc

 
Philip Lederer
Replied at 1:50 PM, 8 Dec 2012

Glad to hear this will be discussed. One important issue is how patients with Xpert positive, Rif-resistance will obtain DST and get those results back to the provider. Thoughts?

NATALIA TAMAYO
Replied at 3:24 PM, 8 Dec 2012

Hi! My name is Natalia, working now with MSF in Osh, Kyrgyzstan , and previously in Swaziland. I´d like to know your opinon in use of Xpert in extrapulmonary samples, especially CSF and lymphnode aspirates. Thanks for this discussion panel!

Dr. Daniela Cirillo, MD, PhD
Replied at 3:35 PM, 8 Dec 2012

Hi Natalia, Xpert works well with aspirates and pus in general. CSF is
very often extremely paucibacillary and can be negative. False negative
are often observed with pleural fluid due again to the low number of
bacteria
Daniela Maria Cirillo, MD PhD
Head of Emerging Pathogens Unit
TB Supranational Reference laboratory
San Raffaele Scientific Institute
San Gabriele Building
Via Olgettina 58
20132 Milano , Italy

Alexander Pasechnikov
Replied at 10:29 PM, 9 Dec 2012

Dear all. I am wondering if it is some cost effectiveness investigation to compare two strategies: 1) Xpert in the field, then DST with HAIN/Bactec in central lab; 2) samples collection in the field, then transport to central lab and perform identification/full DST with microscopy and HAIN/Bactec? Any other strategies and technologies, like thin layer agar (TLA) for example?

Dr. Daniela Cirillo, MD, PhD
Replied at 12:53 AM, 10 Dec 2012

Dear Natalia and all more papers and information can be found visiting the
global health diagnostic site
This link points to a recent interest related to Xtra pulmonary on the
GlobalHealth diagnostics website.
(
http://globalhealthdiagnostics.tghn.org/community/groups/group/extra-pulmon
ary_tb/topics/236/ )
And at the cepheidcares resources site : (
http://www.cepheidcares.com/tb/resources.html )


Daniela Maria Cirillo, MD PhD
Head of Emerging Pathogens Unit
TB Supranational Reference laboratory
San Raffaele Scientific Institute
San Gabriele Building
Via Olgettina 58
20132 Milano , Italy

Elisa Ardizzoni
Replied at 3:37 AM, 10 Dec 2012

Dear Natalia, in line with Dr Cirillo has underlined, in attachment is a list of the recommended samples to be tested with Xpert in MSF, based on literature review. Still this list may need to be updated based on most recent publications. As mentioned, some paucibacillary samples may lead to false negative results, so we usually recommend to centrifuge them prior testing

Elisa ARDIZZONI
Mycobacteriology Unit
Institute of Tropical Medicine
Nationalestraat, 155
2000 Antwerp
BELGIUM

Fuad Mirzayev
Replied at 4:58 AM, 10 Dec 2012

Very important that patients with Xpert MTB/RIF showing Rif-resistance would be referred for the full DST but how it is going to happen is very much dependent on the context, setting, country, etc.

Cornelia Hennig
Replied at 5:18 AM, 10 Dec 2012

Hi all, I am Cornelia Hennig (WHO, VietNam). Thx for the opportunity to discuss.
Taking the exemple of a Rif positive Xpert in HIV+: should programs advise to initiate a) MDR-TB treatment or b) first determine if the patient is at risk for MDR-TB - considering the PPV and also not withholding the stronger first line treatment regimen.
Thank you very much
Cornelia

Philippe Creach
Replied at 5:23 AM, 10 Dec 2012

What do we mean by the full DST as testing reliability is not the same for all drugs ?

Cedric Cheung
Replied at 7:34 AM, 10 Dec 2012

Hello all,
Thank you participants for all your shared expertise and knowledge. I work in a rural setting in Asia where there is a lot of suspected MDR TB based on nonresponse to 1st line medication in previously treated patients. However we do not have any testing for culture or Genexpert to verify this. The NGO I work for is considering purchasing a Genexpert machine to work together with the local CDC to diagnose TB and rifampin resistance. The question I have for the panel is this: we do not have the ability to treat with 2nd line TB medication, so is having Genexpert in a sense futile? I can understand using the information to survey the level of resistant TB is in the community and perhaps later on in the future using this information to spur action to make 2nd line medication available. Should Genexpert only be deployed if MDR TB treatment is available? Also the infrastructure (insurance/cost/etc) is not there to provide drug susceptibility testing if there is rifampin resistance detected. What then?

Llang Bridget Maama
Replied at 7:57 AM, 10 Dec 2012

Dear Colleagues,
I work for MOH Lesotho as NTP Manager. I am very much interested in the panel considering the challenges regarding the roll out of GX. Lesotho has high co-infection rates and thus high smear negative cases and a good proportion who do not get investigated through microscopy.
My experience is roughly as follows:

Roll
out plan developed and assessment of facilities was carried with partners.
Development of algorithm and training of staff in the pioneering hospitals was done.



More
TB cases picked up among the smear negatives in one learning hospital



Whereby during the period when both smear and GX were done
on suspicion of TB and 19.6 % of GeneXpert positives not recognized by smear
microscopy were confirmed and No smear
positive was negative in GeneXpert

Expand
TB supported Lesotho since 2008 through FIND Supporting molecular laboratory
for LPA, Culture with MGIT. The MOU expires in 2013



Training was conducted by supplier to
laboratory technicians and then clinicians followed in those facilities where
the GX equipment is available.



Thanks
Llang

Dr. Llang Bridget M. Maama-Maime
NTP Manager-Lesotho
Ministry of Health
Box 514 Maseru, 100
Lesotho

Andargachew Kumsa
Replied at 9:07 AM, 10 Dec 2012

Hi all, this is Dr Andargachew Kumsa, TB/HIV Technical Adviser to FMOH, Ethiopia. I am very glad to hear that this issue is discussed. My country has planned the roll-out of GeneXpert as the country is among high TB, high TB/HIV and high MDR TB burden countries. My brief experiences on this issue is just limitted to development of national diagnostic algorithms for TB using GeneXpert/MTB/RIF and national roll-out plan. I want to know more about the operational challenges that may arise as we move on implementing it.

Regards,

Andargachew Kumsa, MD,MPH
TB/HIV Technical Advisor, FMOH Ethiopia

OFORI-AMOAH JUSTICE
Replied at 11:14 AM, 10 Dec 2012

HI ALL
WE ARE FORTUNATE THAT TEPA (GHANA) WE DO NOT HAVE ANY CASE OF MDR ESPECIALLY MY TREATMENT CENTRE
TEPA GOVERNMENT HOSPITAL.
OFORI-AMOAH.

Wayne van Gemert
Replied at 11:26 AM, 10 Dec 2012

Regarding extrapulmonary TB, WHO will convene an Expert Group Meeting in the first half of 2013 to review the available evidence for potential subsequent issuance of guidance. This planned meeting will also review overall the original 2010 WHO guidance on Xpert MTB/RIF for possible refinement. WHO maintains a list of current publications on Xpert MTB/RIF categorized by topic, including extrapulmonary TB as well as cost-effectiveness, paediatric TB, etc. The list is available at http://www.stoptb.org/wg/gli/assets/documents/map/XpertPublications.pdf, or via the link in the right-hand column of our Xpert page at http://www.who.int/tb/laboratory/mtbrifrollout

Wayne VAN GEMERT
Technical Officer | Laboratories, Diagnostics and Drug Resistance Unit, Stop TB Department | World Health Organization

Dr. Daniela Cirillo, MD, PhD
Replied at 11:34 AM, 10 Dec 2012

Treatment for MDR should be started as soon as possible. With or without
INH is under discussion but clear evidence are missing. Rif resistance
should be reconfirmed when and where it is feasible. LPA is the fastest
way to do it. Regarding DST sensitivity tests when the strains are grown
At least R, H , floroquinolones and injectable could be set up to save time

Daniela Maria Cirillo, MD PhD
Head of Emerging Pathogens Unit
TB Supranational Reference laboratory
San Raffaele Scientific Institute
San Gabriele Building
Via Olgettina 58
20132 Milano , Italy

Elisa Ardizzoni
Replied at 11:35 AM, 10 Dec 2012

Dear Andargachew, in our experience installation of the machine required training and close follow up of the results for the first few months. We had quite high rate of inconclusive results initially, mainly using the G.4 cartridge.
I would recommend you to closely follow their frequency, and also the module on which they occur, and communicate it to Cepheid if they are above 3%. Cepheid quickly replaced several of our modules. Correct storage of cartridges is very important, exposure to heat during transport has been indicated as one possible cause for inconclusive results;
There is no QC for the machine, not required, but there is a panel of artificial samples that you can request to GLI , to be tested on modules newly implemented.

Elisa ARDIZZONI
Mycobacteriology Unit
Institute of Tropical Medicine
Nationalestraat, 155
2000 Antwerp
BELGIUM

Sophie Beauvais
Replied at 11:55 AM, 10 Dec 2012

Comment from member Thomas Hanscheid http://www.ghdonline.org/users/thomas-hanscheid/

Hello, my name is Thomas Hanscheid and I work in Portugal, with research
links to central Africa and Portuguese speaking countries.
Recently I came across an interesting paper raising some questions about
the accuracy, or let's say reliability, of molecular detection of RIF
resistance. Not sure what people think in the community?
An evaluation of the Xpert MTB/RIF assay and detection of false-positive
rifampicin
resistance in Mycobacterium tuberculosis Deborah A. Williamson ⁎, Indira
Basu, James Bower, Joshua T. Freeman, Gillian Henderson, Sally A.
Roberts Department of Clinical Microbiology, Auckland District Health
Board, Auckland, New Zealand
Diagnostic Microbiology and Infectious Disease 74 (2012) 207–209.

Fuad Mirzayev
Replied at 12:18 PM, 10 Dec 2012

Dear Cornelia,

In this particular example - Rif positive Xpert in HIV positive individual, several consideration have to be taken into account:
- are we ready to risk with undesirable outcome of this patient knowing how fast seriously ill HIV+ patients can die without appropriate treatment;
- treatment with second line drugs is very active against susceptible TB (it has quinolones, aminoglycosides and more)
- how long it will take to confirm Rif-resistance and do a further DST for first-line drugs
- epidemiology of the setting, for example is it high-MDR-TB place or whether this patient has a history of unsuccessful treatment in the past, etc

If confirmation will take a long time (and using a DST to all FLDs) it might be better to start treatment for your HIV+ patient and modify it when DST results are available.
If it is a high MDR setting PPV will be quite good (see Rapid implementation document on WHO website http://www.who.int/tb/laboratory/mtbrifrollout/en/index.html ), a good reason not to delay life-saving treatment

Kathleen England
Replied at 3:30 PM, 10 Dec 2012

Hello everyone, after the ASLM conference in Cape Town last week, I learned that the roll-out of GeneXpert in SAfrica had many challenges. Mostly regarding the aftermath of diagnosis of "many" MDR patients and limitations in treatment infrastructure and HR to handle the increased numbers. It was suggested that before roll-out of GeneXpert, the MoH must assess the needs for the patients after being diagnosed and prepare ahead for the higher numbers. Additionally, it was demonstrated that turn-around-time to the field was not really improved with Xpert vs LPA methods. Yes, the testing was much faster, but the delivery of the results still took 18-20 days from Regional or National labs back to the peripheral and county levels.


--
Kathleen D. England, Ph.D.
Senior Research Scientist
International TB Laboratory Specialist
B237 Beckman Center
Stanford University School of Medicine
Stanford,CA 94304

soundiram indira
Replied at 4:48 PM, 10 Dec 2012

All,
I am Indira, in charge of the xpert training at cepheid.
If i cqn give an advice: we have the opportunity to discuss here and this is a great opportunity thzt we all have.
Always remember that if something is unclear and inconclusive on the xpert side, please ask us immediatly so we can give advises and help you to take benefit from our experience. Monitoring is the keyword in any initiation of project success.
Anything I can do to help you, please feel free to ask questions so everybody can learn from the answers I will share. Thank you.

Natalie Lorent
Replied at 10:11 PM, 10 Dec 2012

Dear all,
Thanks for giving us the opportunity to share experiences.
I am Natalie Lorent, Pulmonologist, working in Cambodia as technical advisor for an ngo-hospital and supporting the NTP thorugh technical working groups. Last year, we developed national algorithms for the use of Xpert (HIV, MDRTB suspects, ACF). We implemented Xpert in our active-case finding programme in urban poor in feb 2012 (TBREACH) and use it to test MDRTB suspects. Cambodia is a setting with high TB burden but low MDRTB and low HIV prevalence.
In our project Xpert has definitely helped to identify more MDRTB cases (6 in 14 months prior to the project vs 18 over the last 10 months). Patients are identified earlier since we used LJ culture and proprotion method DST before (still now as confirmatory) but not as quick as we had hoped for. Because the low MDRTB prevalence and risk of false-pos results with Xpert in these settings (WHO rapid implementation guide), we decided to perform LPA on all MTB+/RIF+ cases (pending culture). However, this easily adds another week to referral for treatment since LPA is not done at our hospital. The referral site now prefers to have the LPA result, whereas sometimes i think we shouldn't (based on pat's risk profile). What does the panel think? Should we at all bother doing LPA? We have had a few discordant results but always given the clinical condition, referred the patient for treatment with SLD.
How Xpert performs in ACF? We are still analysing the data. To be cost-effective, targeting is the message i think.
I wanted to ask the panel/colleagues about the number of Xperts done/recommended for ex in HIV pos patients. Would you recommend a second Xpert or rather refer the patient for CXR (taking into account transfer to hospital for CXR (community based project), cost of second Xpert, yield etc)?
Many thanks,
Natalie

Natalie Lorent
Replied at 10:17 PM, 10 Dec 2012

Hi Indira,
We have a technical question re: Xpert. Our lab techs keep asking me why they encounter 5007 errors for no obvious reason. They assured enough sample volume and the sputum wasn't too viscous (following your advice, they now wait for 20 min after adding reagent). They tell me the way they pipet sometimes creates bubbles. Could this be a reason? Any other suggestions?
Mind you, we have acceptable numbers of errors (around 2%) but still...
Natalie

Natalie Lorent
Replied at 2:15 AM, 11 Dec 2012

Another practical question, probably for Indira. We have been using our Xpert machine for almost a year now. Following Cepheid's instructions it needs calibrating. Do we still have to send the machine to France (from Cambodia) or are there other, easier options? A colleague told me she heard something about "calibration cartridges". Is this correct?
If we do have to send it, how long does calibration takes? Does Cepheid provide "replacement" machines?
It would be great if calibration could be done locally/regionnally, definitely for programs such as ours who only have one machine. Natalie

Fuad Mirzayev
Replied at 3:16 AM, 11 Dec 2012

Dear Natalie,

While looking for Rifampicin resistance even in the low MDR-TB setting doing proper risk assessment will help to target the testing. This is also a message in the rapid implementation document. Even in low MDR-TB setting there are always groups of patients with high probability of Rif-resistance, where the Xpert MTB/RIF based result of Rif-resistance will obviously be more reliable. Using LPA to confirm Xpert result might not be a best option as the specificity of LPA for Rif-testing is slightly lower than the one of Xpert.

Fuad Mirzayev
Replied at 4:58 AM, 11 Dec 2012

Dear Cedric,

If capacity to test for drug-resistance is currently unavailable it doesn't mean it should not be created. The capacity needs to be there especially because you do have those not responding to the 1st line treatment. Many possibilities can be there including the referral to the place where capacity is ready and results can be fed back.
As you have mentioned in your post, knowing and quantifying the magnitude of drug-resistance can help to justify and make appropriate treatment available eventually. We should also try to remember that diagnosing drug-resistance patients doesn't create them in the community, they are there even before we have applied the test, we just do not know that.

Gini Williams
Replied at 5:41 AM, 11 Dec 2012

Thank you for the opportunity to join this discussion. It is obvious there are many concerns of a technical nature to ensure the effective roll-out of Genexpert and I would like to pick up on a couple of these from a patient care perspective. Personally I feel there is a serious ethical question to be addressed with regard to testing patients for DR-TB when no treatment is available. While I agree that we have a duty to find cases of DR-TB we cannot do this ethically without having a plan for what happens when we do. For instance what counselling is offered the patient before the test is carried out and how is the result delivered? Surely we should be implementing the type of pre-test counselling offered to people for HIV tests before treatment was readily available. How should health care providers deliver a result to a patient when they have no treatment to offer? What advice should be given about reducing the risk of transmission and remaining as well as possible? There are historical accounts available of how home visiting nurses used to counsel people living with TB at the beginning of the 20th Century in Europe and the US when TB was rife and no treatment was available.
Even when treatment is more widely available, for instance in South Africa, as noted by Kathleen England it is essential that there are sufficient well-equipped and knowledgeable health care workers to firstly counsel patients before the test and secondly manage treatment and offer support and care to the patient and their family if a test is found to be positive. Without this treatment will not be successful and resistance will grow. Again in line with lessons from the HIV field, if the result shows TB with no rifampicin resistance the patient needs to be counselled about how to avoid developing drug resistance. We have seen the diagnostic phase in TB care as a purely technical intervention for too long. If we start counselling at this point (nurses and other front-line workers are well-placed to do this) we will have better outcomes for all. My hope is that the care and support for the patient will be included in any future advisory documents. We have many experienced nurses from South Africa, Ethiopia and Russia who could participate in developing this guidance.

soundiram indira
Replied at 6:00 AM, 11 Dec 2012

Dear Nathalie,

thanks for your messages. I will reply to both questions at the same time as they are linked.
The message 5007 is related to a probe check control failure. The probe check control is a way to verify the extraction process, sample preparation, mixing steps before running the PCR.
We also use this control to verify that the sample is processed properly: Like you mentionned correctly, sample has to be perfectly fluid and the 2 ml final volume of decontaminated sputum has to be strictly respected.
One important point: the process to decontaminate and liquify the sample
As a reminder: Once sample in presence of decontamination reagent, we have to shake 10-20 time, wait 10 minutes, shake again, then wait 5 further minutes.

--> It can happen that avec these 10+5 minutes, the sample is still a bit/totally viscous.
You can in that case, wait up to 15 further minutes.
(To be very clear, you might sometimes, extend from 20 to 30 min for the full process).


The other reason why you could have also this message is because the calibration is due.
Every year you have to calibrate your system. The process so far was a swap of modules. We do have an easier option now.
The xpert calibration kit is one of the solution available:
In summary,the process takes approx.20 minutes to control and check some very important parameters. Once done, it generates a report that will be returned to cepheid for analysis. Based on this, Cepheid will provide you a calibration certificate to scan and update the modules.
You can ask for a quotation for a calibration kit to our customer service.

Hope this can help you and other users.. (See attached presentation regarding troubleshooting)
I hope this helps.
Indira.

Attached resource:

soundiram indira
Replied at 6:47 AM, 11 Dec 2012

Xpert MTB/RIF and GeneXpert Training material:
Training is still the keyword to make sure sites are following the rules properly.
I am sharing with you the FTP site where I always put the last updated training materials, Operator manual, Xpert MTB/RIF Package insert, etc. . Whereever you are, the FTP is accessible. For this, please copy and paste the hereafter link on EXPLORER (not internet explorer) ftp://hbdc:
If you need to follow any training with us, you can always go to the following link and register online. http://www.cepheidcares.com/tb/resources.html , second link regarding training.

Lucica Ditiu
Replied at 7:04 AM, 11 Dec 2012

Good afternoon and thank you all colleagues for such a great discussion.
This is a question on the CEPHEID Training programme.
On the training part do I understand right that with the exception of the web based training, all other options imply the existence of a budget from the implementers - either to do the training to the CEPHEID venues or in their own location.
Please -clarify.
Secondly - for the web based training - which I understand is free - and is on line - can you share with us how many of these trainings were organized in 2011 and 2012 with a rough number of people trained. I assume - I might be wrong - would be good to know what a web based training imply - is this just a simple connectivity to the internet or anything specific.

Thank you for having this _ from Lucica Ditiu

PAUL NKALODZWA
Replied at 8:35 AM, 11 Dec 2012

keenly following right here in Malawi

Natalie Lorent
Replied at 9:59 AM, 11 Dec 2012

Dear Gini,

Couldn't agree more!
We should indeed go more in line with the HIV example and focus on informing and counselling persons who may have (DR)TB and TB patients. This may well imply a change in set-up of TB services. From my experience of working in developing countries health care workers (outside the HIV care) are not very keen on spending a lot of time explaining patients about the benefits/risks of testing and treating. So, support from WHO in formal documents may well be worth it. Thescale-up of Xpert could be a good opportunity to do so...

Natalie

Sophie Beauvais
Replied at 10:05 AM, 11 Dec 2012

Hi All

Thanks for a very productive exchange so far.

To go back to Kathleen England's comment. Kathleen, curious to hear more
about the issue of delivery of results in ZA you mention. Could you
elaborate a bit or invite the person who shared this issue to discuss with
us?

Also, to all, could we hear from people who attended this year's ASLM
conference if they have heard this/know more? And could everyone expand on
managing how the results are delivered from the testing/alb site to health
posts/where they are needed?

Thank you, Sophie

soundiram indira
Replied at 10:32 AM, 11 Dec 2012

Dear Madam,
Thank you for your questions.
To reply your first question, we have 3 options:
* Cepheid Approved Service Provider is present in the country where systems will be implemented. This service provider will take care of the installation and training of the team.--> No training budget required for this.

Alternatively, people can decide to come at Cepheid to be trained for free (training budget to consider the travel /hotel expenses) ,

- the 3rd solution is the web based training which is free and available if the internet connection works well at the site. The program is what you have seen on the link you visited.
We have videos, and very easy to use documents

Depending on the project size, it could be worthwhile to develop some trainers within the program with the responsibility to maintain competence in the field. Cepheid has undertaken ‘Train the Trainer’ sessions both at Cepheid and in-country. This has been arranged for KNCV, NTRL in the Philippines, NHLS in South Africa, MOH in Moldova and RNTCP in India for e.g.

In 2011 Cepheid has trained 117 in 49 web-based sessions.
In 2012 Cepheid has trained 250 in 60 web-based sessions.

Indira

Patrick Gomani
Replied at 11:28 AM, 11 Dec 2012

Name: Patrick Gomani, MDC
District TB Care II coordinator

- Experiences in planning at the national and regional levels
• TB CARE II has been supporting NTP to roll out the Xpert nationwide.
• The NTP now has an updated roll-out plan of Gene Xpert which will be implemented soon.
• TB CARE II and TB Reach are using the Gene Xpert for patient diagnosis, treatment and care!
• Gene Xpert is currently used in 6 TB Care II supported districts (Neno, Ntcheu, Mulanje, Phalombe, Machinga and Mangochi)
• In 2013 TB Care II will procure 2 additional Gene X-part machines.
- Impact of GeneXpert MTB/RIF on patient management, from new diagnostic algorithms to treatment.
• The NTP recommends the following patients or clients to benefit from gene x-pert:
• All MDR suspected cases
• All smear positive retreatment cases
• All hospitalized HIV positive patients with sputum smear negative
• All treatment failures
• Household contacts of MDR-TB index cases
• Data:
TOTAL 9062 smear negative microscopy done and 3608 sent for Gene Xpert out of which 294 MTB+/RIF- and 3 had RIF resistance.
- without Gene Xpert we could have missed all above patients, thanks for the Gene Xpert.

-Lessons learned with EXPAND-TB
• there is underutilization of Gene Xpert in Neno district
• Staff inadequacy at the district due to high staff turnover
• Weak referral system for transportation of samples from the peripheral health centers to the G-Xpert facility. The MoH has already committed herself to the dissemination of sample transportation and Riders for Health are to pilot sample transportation in two districts, Neno and Machinga
- Training activities and materials for GeneXpert MTB/RIF
• TB Care II supported the training of 8 health care workers on the use of Gene X-pert
• 1 Refresher trainings will be conducted this year as well in Neno.

Dr. Daniela Cirillo, MD, PhD
Replied at 12:41 PM, 11 Dec 2012

In addition to the comment of Fuad I would like to add that it is
important to diagnose MDR-TB even in the absence of treatment because
infection control measures can be enforced and patients could be
instructed to follow a behavioral etiquette in order to prevent new
infections in hospital/ family / community. All effort should be done
anyway to link diagnosis to effective treatment
Daniela Maria Cirillo, MD PhD
Head of Emerging Pathogens Unit
TB Supranational Reference laboratory
San Raffaele Scientific Institute
San Gabriele Building
Via Olgettina 58
20132 Milano , Italy

Masoud Dara, MD
Replied at 1:14 PM, 11 Dec 2012

In full agreement with Daneila,

Every patient should have the right to free, accurate and timely diagnosis. The programmes shall provide adequate treatment in patient-centered approaches. Advocacy efforts are needed to convince authorities that investing in TB and M/XDR-TB control and efficient use of resources, in addition to alleviating human suffering and serving the public health, saves much further costs in the future.

All the best,
Masoud

Dr Masoud Dara
Programme Manager
TB and M/XDR-TB
WHO Regional Office for Europe

CLEMENT ADESIGBIN
Replied at 2:28 PM, 11 Dec 2012

Dear all,
i am Dr Clement program officer with NTP Nigeria.
Without gainsaying gene xpert has a brought an unprecedented revolution to TB diagnosis in this our world. Having said that i wish to bring a new twist to our discussion and to support an issue raised by one of the discussants about the false positivity of genexpert. In a situation, for example, if a patient was placed on MDR treatment on account of genexpert result and such a patient has been on this treatment for more than 2 months but DST now comes out and shows no resistance to rifampicin and isoniazid. What are your advices? What does this mean to the patient? Are there ethical issues? Pls lets discuss

Hugh McDonough
Replied at 3:38 PM, 11 Dec 2012

My name is Hugh McDonough from Abt Associates where I’ve been working with an interdisciplinary team (technological, clinical and programmatic) to address the “turnaround time” issue raised by Kathleen England (19).
We recently tested a possible solution to prevent these delays and get information across the various levels of the health system—including where patients are being treated. We tested a fairly simple way to connect GeneXpert devices to a cloud-based Internet site. With this tool, the Nigerian Federal Ministry of Health (FMOH) was able to aggregate MDR TB results in real-time, directly into eTB Manager, their M&E database. In addition, the system can send SMS or email messages to labs, patients, and clinical workers.
As Ms. England points out, rapid results can present new caseload and management challenges to MOHs; however, rapid information sharing provides great advantages in the long run. Advantages include 1) better coordination between patients, labs, and clinics, 2) more targeted communication with patients, 3) improved management of drug supplies, cartridge use, and machines. We are eager to see how different MOH capitalize on these improved response systems. Please share any insights you may have.

Attached resource:

Dr. Daniela Cirillo, MD, PhD
Replied at 4:20 PM, 11 Dec 2012

Der Dr Clement, unfortunately some false positive and false negative are
expected in the best scenario and the best tests. The patient has received
an effective treatment anyway so I don't see a big ethical issue. Patients
with NTMs have been treated for MDR-TB when the only test available to
detect failure was smear positivity. Said so, this is the main reason for
the need of retesting with LPA patients not in high risk groups. In
Nigeria LPA is available at least in Lagos and Zaria.
I have to add also that in some case mutations detected with LPA and not
reconfirmed by the sensitivity in MGIT were associated to a poor prognosis.
Daniela Maria Cirillo, MD PhD
Head of Emerging Pathogens Unit
TB Supranational Reference laboratory
San Raffaele Scientific Institute
San Gabriele Building
Via Olgettina 58
20132 Milano , Italy

Salem Barghout
Replied at 8:55 PM, 11 Dec 2012

Dear Dr. Clement:

The same situation was encountered in other programs where patients were placed on DR-TB treatment, based on Gene Xpert results, only to find out 2-3 months later that some cases were found to be sensitive to Rif. based on full DST reports. In this situation my suggestion is that each case should be evaluated individually based on previous clinical and treatment history, previous use of FLD and/or SLD, reliability of laboratory testing, contact with high risk groups and response to treatment etc. before deciding to switch back to FLD vs keeping on SLD regimens.

Best Regards,

Salem Barghout, MD
MDR-TB Consultant

Natalie Lorent
Replied at 9:25 PM, 11 Dec 2012

Dear Sophie,

In our ACF-project in Cambodia, the Xpert machine is located at the referral hospital. Lab techs inform TB doctors about positive results, who then call (and text the result to) the TBWs in the field. TBWs will track the patient down and refer him to the local health centre for treatment. We did (do) encounter some problems of local HC staff accepting text messages. At some point the paper form was required, which delayed of course treatment initiation unnecessarily. TBWs only visit the hospital 1x/week (max 2x).
With MTB+/RIF+ results, it is a little more complicated since patients need to be referred to a designated MDRTB treatment site. Patients are first referred to our hospital for clinical review by a physician (our TBWs do not necessarily have a medical back ground), 'confirmatory' LPA is done (maybe not ideal from the feedback I received earlier) and referral to MDRTB treatment site is organised (paperwork, phone calls etc). Very often the patient is accepted to present a few days later (availability of docs, public holidays, weekends). So easily one or two weeks pass... Meanwhile patients are instructed on how to prevent transmission (whether/how these instructions are followed is not sure though?).

So far, our situation...
Natalie

Kingsley Ochei
Replied at 9:59 PM, 11 Dec 2012

Dear all,
My name is Kingsley Ochei. i work for FHI 360. In response to Dr. clement question and in addition to Dr. Daniella response, I will add by saying that these experiences are quite interesting and we need to take definite decions based on them rether than explaining them away. No doubt that scenario painted will have adverse effect on the patient. Apart from the effect of the SLD, the patient may have bee admitted into the MDR-TB ward. There is the risk of the patient now living with other MDR-TB patients contacting the MDR-TB in the ward. It also have ethical implications. I will suggest that all gene xpert positive results be subjected to LPA and/ or  MGIT DST among other findings (clinical history, etc) before treatment is initiated. all TB Culture labs in Nigeria (Lagos, Zaria and Calabar)has LPA. 
 
Thanks.
Kingsley Ochei
Senior Technical Officer Laboratory Services
FHI 360  - Nigeria

Daniel Winetsky, MD, MS
Replied at 10:38 PM, 11 Dec 2012

Hi All,

I am an internal medicine resident at the University of Pennsylvania but I have previously worked on economic evaluation of Xpert MTB/RIF and other screening/diagnostic algorithms for prisons with high prevalence of MDR-TB, like those in the former Soviet Union. I'd like to reply to Dr. Dara's and Dr. Cirillio's earlier point about the use of Xpert in a setting without second-line treatment. While there are likely some public health benefits to diagnosis of MDR-TB where treatment is unavailable--and from a rights perspective one could argue for implementation in these settings--in terms of efficient use of resources, health dollars may be better spent implementing an MDR treatment program first. In our cost-effectiveness analysis, Xpert MTB/RIF was very cost-effective for high burden prisons, but the cost-effectiveness was driven by the benefits of treating MDR-TB cases early, and thereby driving down the force of infection. In fact, sensitivity analyses we performed suggest that Xpert MTB/RIF may actually be cost-saving as an annual primary screening tool for all inmates if the price does indeed come down below $10. (Our findings, if anyone is interested were published a few weeks ago in PLoS Medicine.) However, in the absence of appropriate second line treatment, it is hard to know if early diagnosis of MDR-TB would have a significant enough effect on the force of infection to justify the cost.

I would also like to ask our discussants if any of you are aware of movement toward implementation in the former Soviet Union. Though the burden of disease is not as high in the general population as other high burden areas, this is a setting which would also likely benefit from Xpert MTB/RIF, but I noticed it is missing from PEPFAR's list.

Thanks,
Daniel Winetsky, MD, MS
Resident Physician in Internal Medicine
University of Pennsylvania Health System

Je Kan Adler-Collins
Replied at 11:12 PM, 11 Dec 2012

Respected colleagues. I am so happy to be able to see the debates that are going on in this list as they are very informative. I do however feel at odds with the silence of other healthcare professionals such as my profession of nursing. Have I joined the wrong list? If so I apologise. I My area or work and research in nurse education, health promotion and public health. I write curriculum and teach varying forms of nursing. I have a deep concerns about nurses at the point of care delivery becoming vectors of the disease and many concerns about education of health and safety practices in the field when related to MDRTB and XMDRTB.I believe that we need to develop more multi cross professional approaches to look at the bio-social aspects and assist more with education across borders that not only covers grand policy designs but evolves good practice in the field. If any one can point me in the right direction. I would be deeply grateful. Dr Je Kan Adler-Collins.PhD REMT PGCE RN..

Dr Shanta Ghatak
Replied at 11:35 PM, 11 Dec 2012

Hi Gini your concern is so very very true and apt. YES YES & YES . The
communication strategy and having a " go" in the lines of HIV should
happen. Most medicos do not get the risk of transmission delivered. So if
we are talking of upscaling the diagnostics , we must fund more - at least
make more provisions for good counselling techniques and services. And come
to drug resistance there is not a thing about "CHIRALITY"?In our
discussions . If possible we would want to get some information regarding
this crucial burning issue which has taken over the drug world by a big
storm?
Thanks !
Hoping to learn some more
Shanta

Frank Cobelens, MD
Replied at 3:03 AM, 12 Dec 2012

Dr Winetsky makes a valid point but I think we have to distinguish use for screening (active case finding) from use for patients presenting with symptoms suggestive of TB (passive case finding). The cost-effectiveness of Xpert, at least for the short term (i.e. not taking into account transmission effects, which will differ between confined populations such as prisons and the general population), will be considerably less for active than for passive case finding (see Vassall et al. PLos Med 2011;8: e1001120).

Frank Cobelens
Academic Medical Center, Amsterdam
Netherlands

Alaine Umubyeyi Nyaruhirira
Replied at 3:28 AM, 12 Dec 2012

Dear All

Thank you for the opportunity to discuss on the Gene Xpert MTB/RIF Roll out, I agree with Gini and Dr Shanta, We have at the country level to do a good coordination and
link between diagnosis and treatment. This will help to provide the overall picture of the TB control program for the benefit of patient using Xpert but also to sustain this techmnology particularly in low income countries where partners are more involve on this activity. ''Let's learn from the HIV movement''


Dr Umubyeyi Nyaruhirira Alaine
Senior Program Associate for Laboratory Services
MSH- Center for Pharmaceutical Managment (CPM)
Pretoria Office

Thomas Mohr
Replied at 3:37 AM, 12 Dec 2012

Dear Colleagues,

In response to Daniel's question about implementation of GeneXpert MTB Rif in the former Soviet Union (FSU). I am working in the Central Asia region for Project HOPE. While I am aware of implementation in Russia (Arch Angelsk), I can't provide in-depth insight into the scope of implementation in Russia or other parts of the FSU beyond Central Asia.

Meanwhile, in the five Republics of Central Asia (Kazakhstan, Kyrgyzstan, Tajikistan, Turkmenistan, and Uzbekistan) implementation of Xpert is still in the early stages and many of the points discussed thus far have been part of the ongoing discussion in this region. All countries except Turkmenistan already have small numbers of Xpert units in place provided by a range of donors, projects, and NGOs. Plans for roll-out are ongoing in all countries.

I should note that all countries in the region also have gaps between the numbers of MDR cases diagnosed and numbers that they are able to treat. Thus the ethical questions have been raised about introducing Xpert widely but I do not think there is much to debate. Clearly MDR rates are too high throughout the region not to diagnose these cases as early as possible in order to take whatever actions are possible (TB-IC, Counselling, advocacy, etc).

I would be curious to see a cost effectiveness study that would take into account the cost for not implementing Xpert sooner in such a context where not utilizing Xpert will result in many patients starting ineffective treatment that will contribute to further amplification of resistance.

At the same time clinicians and medical staff are still learning to trust the technology; in at least one location in Kazakhstan after receiving Rif+ Xpert results medical workers still wait for confirmation (LJ culture or MGIT) before initiating treatment. While much work remains to be done it is still important that in this regions countries will proceed in their efforts.

Thanks,

Tom Mohr
Tom Mohr | Том Мор
Deputy Chief of Party / Regional TB Manager | Заместитель регионального директора проекта / Региональный ТБ Менеджер USAID Quality Health Care Project | Проект USAID "Качественное здравоохранение"

Elisa Ardizzoni
Replied at 3:44 AM, 12 Dec 2012

Dear Mr Kingsley Ochei, in our experience in low MDR prevalence settings retesting RMP resistant results always gave consistent results, this probably due also to the use of the new cartridge, supposed to increase specificity of Xpert for RMP detection; If LPA is available and can provide results in a short turnaround time probably you could wait for confirmation, but I would not wait for results from MGIT to start treatment , MGIT in the best case would take at least 20 days (between culture and DST). Still consider that there are reported cases of discrepant results between Xpert and MGIT where the strains indeed had mutants conferring low level resistance, missed by MGIT and correlated to treatment failure;

Elisa ARDIZZONI
Mycobacteriology Unit
Institute of Tropical Medicine
Nationalestraat, 155
2000 Antwerp
BELGIUM

NATALIA TAMAYO
Replied at 6:18 AM, 12 Dec 2012

Dear all, thanks for the very interesting discussion!
I´d like to share two ideas regarding implementation and use of Xpert:
1) introduction of a new technology should be one more step in a complete prevention/detection/diagnosis/treatment/rehabilitation strategy. No "magic bullets" in TB
2) as a clinician, and regarding discussions about specificity, sensitivity, confirmation, etc, I should remind that a diagnostic method is one more element in the diagnostic process. We are treating patients not lab results
Attach a publication regarding Xpert and "why context matters"
Kindly regards
Natalia

Attached resource:

Alain Disu
Replied at 11:23 AM, 12 Dec 2012

Dear All,Thanks for this opportunity to discuss on this new rapid tool. I would like to reply to Daniel in the second part of your intervention regarding the implementation of GeneXpert in the former soviet union. In Russia where I'm currently working for WHO, it took time to the country before starting the implementation of GeneXpert, this for many reasons, one of them being that in the country many competing technologies such TB-Biochip, Real Time PCR, Sintol and others for the diagnostic of M/XDR-TB are available. In this context, it has not always been easy to advocate for "foreign" technology while plenty of locally made are available. Nevertheless, with a positive feed back from regions where this tool was placed mainly through donor's support, many regions started to be interested and purchased units. Currently, fifty eight machines have been implemented mainly in second level laboratories. We do expect that this figure will continue to increase. Data are being collected for Xpert MTB/RIF impact by partners in some of these settings.Thanks.

Michel Kaswa
Replied at 6:01 PM, 12 Dec 2012

Dear All,
I am Dr. Michel Kaswa : Head of Technical Division in NTP/DR Congo.
Many thanks to all colleagues for taking their time to interact on Xpert important issues. Let me share with you the experience of DRC on the Xpert implementation. Actually more than 25 Xpert machines are performing TB and RIF resistant diagnosis nationwide through the support mainly of TB REACH projects funded by CIDA. Data are being collected….
During this discussion, several interesting issues related to the roll out of Xpert have been already stated ….however I would like to raise on the floor a couple of Xpert questions very relevant especially when you analyze those questions in a programmatic perspective in TB High Burden Countries.
According to preliminary data, on pilot Xpert project implementation in DR Congo, following issues have been considered :
- Xpert is currently offering an unprecedented revolution in TB diagnosis : how to ensure that very vulnerable and poor people, more risk for the disease, get access to in POC to the new tool ?
- New generation of Xpert cartridges does seem to be more sensitive for RIF detection …Clear algorithm should be defined firstly to avoid delay in patient treatment and secondly to keep a window for treatment modification based on DST results is relevant to consider…
- Behond « a solid TB program » which did promote since several years DOTS interventions : how to facilitate the implementation of a new tool and to avoid its underutilization ?
Finally, Xpert will contribute efficiently in global TB control in a vision of an accurate TB program which implementing innovative approaches with a strong commitment and collaboration between MOH and key partners under the support of donors in the perspective of the entire health system improvement.

Sarder Hossain
Replied at 3:04 AM, 13 Dec 2012

Dear All:
This is Sarder Tanzir Hossain ,and worked 2.5 years in NTP Afghanistan.Recently,I have joined as microbiologist( TB lab and IC Consultant) in BHP of BRAC,Bangladesh.
GenXpert has been introduced recently in Bangladesh ,and to me, it seems working good to diagnose Rif resistant TB in short time in this context.Anyway ,Like other members I have a concern over the rapid diagnosis system in terms properly implementing community-PMDT.Increasing number of Rif resistant patients are being detected through Xpert which will be gradually surpassing the country's capacity for providing them treatment as the hospital beds, medicine and resources are limited.Many patients are on waiting to get enrolled for MDR-TB treatment .What would we do for a newly diagnosed MDR -TB patient anxiously waiting for treatment?How can we support him?Will it not create a big chaos to manage the MDR-TB treatment properly if we are failed provide treatment on time?.Any comments or thoughts ?
Regards,
Sarder Tanzir Hossain

Llang Bridget Maama
Replied at 4:03 AM, 13 Dec 2012

Dear Colleagues,
I have been going participating on this discussion even though my input so far as just to show how far we have gone as Lesotho. This time arround, let me put through the following key challenges that we face and seek your advice.



Decision on the algorithm,
whereby we torn apart in using GX as point of entry for diagnosis for all
suspects, then doing the microscopy for classification. This contradicts
the WHO recommendations to still do microscopy for all and those who will
be smear positive would not require GX. As a country and resource
constrained and with high burden of HIV at 23% prevalence, we often get
smear negatives and saw this as a tool for improved case
finding, but it not feasible for us to totally abandon microscopy which is
what many of partners supporting felt that there is no need to hang on
microscopy. Meeting each other half way caused a lot of back and forth in
deciding on algorithm. Can you share with Lesotho the algorithms used in
your areas and experience them in terms or reduction in workload and
increased case detection?Another challenge is in
rationalizing the number of xpert needed in the country. We have so far
allocated the 5 that we have in hospital laboratories, as the lowest
level, since microscopy centres at Health centre level are still not
functional. We have at 6 more in the pipeline, and have just heard that
PEPFAR is pleadings as per that list you shared on this panel. While it is
good to cover all our 18 hospital with at least one GX, we are concerned
about the future in terms of maintenance of the equipment and cartridges,
so much that some schools of thought advise us to look at down time (since
some hospitals have lower work load than others) of the machines and
whether we should just have them there even if they will not be fully
utilized. If we put one per region and allow other to refer samples
through riders for health, it defeats the purpose of reduced TAT for
results and initiation of treatment.
Will we be able to continue with procurement of ca What’s your take
on this one? We are population of 1,8mlnUse of safety cabinet is
like totally ruled out in the case on GX, how honest and fair is this?
There is an element of manipulation of specimen before inserting the
cartridge into the machine, so if one does that daily and for a lifetime,
does it not cumulatively put this person at risk?

Thank you. Llang

Dr. Llang Bridget M. Maama-Maime
NTP Manager-Lesotho
Ministry of Health
Box 514 Maseru, 100
Lesotho
contacts:Office (+266) 22325314/22226300
Fax (+266) 22322445
Mobile (+266) 58949666



> Subject: Re: [MDR-TB Treatment & Prevention] Expert Panel Dec. 10-14: Scaling-up GeneXpert MTB/RIF
> From:
> To:
> Date: Thu, 13 Dec 2012 03:05:14 -0500
>
>
> Sarder Hossain replied to the discussion "Expert Panel Dec. 10-14: Scaling-up GeneXpert MTB/RIF" in the MDR-TB Treatment & Prevention community.
>
> Reply contents:
> "Dear All:
> This is Sarder Tanzir Hossain ,and worked 2.5 years in NTP Afghanistan.Recently,I have joined as microbiologist( TB lab and IC Consultant) in BHP of BRAC,Bangladesh.
> GenXpert has been introduced recently in Bangladesh ,and to me, it seems working good to diagnose Rif resistant TB in short time in this context.Anyway ,Like other members I have a concern over the rapid diagnosis system in terms properly implementing community-PMDT.Increasing number of Rif resistant patients are being detected through Xpert which will be gradually surpassing the country's capacity for providing them treatment as the hospital beds, medicine and resources are limited.Many patients are on waiting to get enrolled for MDR-TB treatment .What would we do for a newly diagnosed MDR -TB patient anxiously waiting for treatment?How can we support him?Will it not create a big chaos to manage the MDR-TB treatment properly if we are failed provide treatment on time?.Any comments or thoughts ?
> Regards,
> Sarder Tanzir Hossain"
>
> --
> View this post online:
> <http://www.ghdonline.org/drtb/discussion/expert-panel-dec-10-14-scaling-up-ge...>
>
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Neil Gupta
Replied at 4:11 AM, 13 Dec 2012

Thank you for the discussion. Partners In Health in Rwanda is currently supporting Xpert roll-out by the Rwandan MOH. One issue that I don't believe has been discussed in this virtual panel is new strategies for pediatric Tb diagnosis using gene xpert. Does any know of any efforts to systemetize pediatric diagnosis, particularly with non-sputum samples (NG aspirate, stool, urine, etc)? I have only found very small experiences in the literature.

thanks,
Neil Gupta MD MPH
Director of ID Program
Partners In Health, Rwanda

Marcel Yotebieng
Replied at 5:38 AM, 13 Dec 2012

Thank you for the discussion.
With funding from TB Reach the University of North Carolina has scaled-up Xpert as a follow-up diagnostic for smear negative TB suspect in 22 health Zones in Kinshasa. We have been testing patient for the last 5 months and so far the main operational issues we have encountered are as followed:
1- the lack of French version of the Xpert software. it's very difficult enough to train people who have never used a computer before on how to used a new machine that is operated entirely on a computer. It's harder if this has to be in a completely new language. Is Ceiphed translating the software in other languages?
2- Electricity: All our machines runs on generators and this is costly, particularly for services that are provided free of charge and health facilities that are barely getting by can't be expected to support this cost despite their enthusiasm. Are there plan underway to get new machine that can work on batteries?
3- Algorithms: At least here in DRC, the adherence to the current diagnostic algorithm that require smear negative patients to come back for a second set of smear test after a broad spectrum antibitics is not high. in our experience, only 5% return. this should take in account for those who are devising algorithms for future scale-up.
4- the need for supply chain: most of those primary health facilities with no power supply do not have a refrigerator, meaning that test have to be delivered in small amount which is logistically challenging

Thanks
Marcel Yotebieng, MD, MPH, PhD
Research Assistant Professor
Department of Epidemiology
Gillings School of Public Health
University of North Carolina at Chapel Hill

Thomas Mohr
Replied at 6:06 AM, 13 Dec 2012

This reply is to help Marcel on a couple of the issues he has asked about.

In regards to your second question on electricity, it would be good to know a little more about whether or not the health facilites where you are working have any electricity or not. Regardless, it is possible to put the Xpert on a Inverter/charger system so that the Xpert will run off a source of battery power that will provide a stable power supply. Those batteries would be charged during the times that the facility does have electricity. The inverter/charger will also convert the DC from the batteries back to AC power to run the Xpert.

If there is no electricity at all the same system can be powered through a solar system that also would charge the batteries. There are a lot of advantages to using an inverter/charger system (e.g. Will protect against power spikes, high and low voltage, and can be designed to operate the Xpert for extended periods of time). We set up two such systems in Central Asia to address conditions where we have and are placing GeneXperts.

I am not familiar with which NGO's or other agencies are in Kinshasa but certainly ICRC and MSF must be present and I am sure their logisticians would be happy to advise. The good new is there are options currently available to address this issue.

In regards to the refrigerator situation, have you considered or do you have the funding to purchase a refrigerator that is powered by Kerosene? These are used around the world and I guess UNICEF might be able to help you since such refrigerators are common to support cold chains around the world. Also MSF certainly has contacts with suppliers of such refrigerators.

Of course there are more details but I hope that provides you with enough information to follow-up on some of the already available options to address two of your issues.

Best Regards,

Tom
Tom Mohr | Том Мор
Deputy Chief of Party / Regional TB Manager | Заместитель регионального директора проекта / Региональный ТБ Менеджер USAID Quality Health Care Project | Проект USAID "Качественное здравоохранение"

Thomas Mohr
Replied at 6:14 AM, 13 Dec 2012

Another possible resource for Marcel Yotibieng:

I had this in my files. It is from FIND. You obviously would need more information but it is similar to the system(s) I was referring to in my message. Depending on types, size, and number of batteries this type of system can easily run an Xpert (4 module unit) for a full 8 hours or more.

Good luck!!!

Tom

Tom Mohr | Том Мор
Deputy Chief of Party / Regional TB Manager | Заместитель регионального директора проекта / Региональный ТБ Менеджер USAID Quality Health Care Project | Проект USAID "Качественное здравоохранение"

Attached resource:

soundiram indira
Replied at 7:38 AM, 13 Dec 2012

Dear Marcel, Tom,
thank you for your questions/answers: all very interesting. I can reply to points 1 and 2.

For point 1: Cepheid is working on an updated version of the software that will easier some of your life!
For point 2: I would have given same information as Tom, a little bit more completed from FIND in Uganda where they have done very good work thanks to Uganda's sun! You will find the implementation, the cost of this solar solution and the daily use... vey interesting.
BR,
Indira

Attached resource:

Fuad Mirzayev
Replied at 8:02 AM, 13 Dec 2012

This is in reply and addition to Daniel's and Alain's posts.
For all who do not yet know, a lot of information is available on the Xpert implementation AND plans in some countries on the website that is maintained by our team based on all information that is being made available to us by partners and countries: http://www.stoptb.org/wg/gli/assets/documents/map/1/atlas.html
Please also note that on the second map you can also access the detailed information in the PDF file that is there for countries that have some information reported.

We appreciate the support of partners and if someone has further info available or can advise a correction please do get back to us, contacts can be found on the website as well.

Regards,

Fuad

Fuad Mirzayev
Replied at 8:22 AM, 13 Dec 2012

Dear All,

I see that in this post from Daniel and in some other posts several issue related to ethics were coming up. This is why I suggest to have a look at this document posted on the WHO website:
http://www.who.int/tb/features_archive/ethics/en/index.html WHO Guidance on Ethics of tuberculosis prevention, care and control,
where some answers on sensitive issues around ethics of TB diagnosis and care can be found.

To give an idea, these are the questions that are answered in this guidance from the ethical standpoint:

- is it ethically acceptable to offer drug susceptibility testing when treatments for drug-resistant strains are not available?
- how can clinicians make ethically appropriate treatment decisions for patients
when drug susceptibility testing is not available?
- What is the ethical justification for giving individuals information and
counselling about tests and treatments they are being asked to undergo?
- how does the ethical concept of “informed consent” apply to tb testing and treatment?


Regards,

Fuad

Dédamani Thomas SANWOGOU
Replied at 9:44 AM, 13 Dec 2012

It is true that the use of Gene Xpert in countries where treatment against MDR is not available leads to ethical problems. In Togo, this technology is not yet implemented. In countries where it has recently put in place, serious questions arise.

Without the gene Xpert, bacteriological culture whose results last about 10 weeks, resulted a death of patients before the exam results. At the same time the poor country that put emphasis on the detection of
MDR quickly confronted with the problem of the supply of second-line
drugs. Patient screening and placed on waiting list die without access to treatment. Caregivers who diagnosed these MDR watch them die helplessly. The ordering process and supply of these drugs are long and patients are
imcapable to buy themselves drugs because of their high prices. In addition there are no services where patients can be  kept and monitored to avoid contaminating their environment.
This can also have a significant impact on the quality of MDR patients care . That the Xpert will expand the list of expectations without treatment,
nurses who care for MDR, and are also poorly equipped in personal
protective equipment, will increasingly afraid of being closer patients. They will be afraid to die if they contracted MDR-TB. It will therefore reduce their contact with patients. This will decrease the qaulité care which is already bad.
 
However, detecting an MDR patient, will help prevent contamination of the
environment, if the patient is well educated and is aware of the dangers they may pose to his family.

Ultimately the Xpert is a significant step in the fight against TB and MDR-TB, but other arrangements need to be taken to maximize the benefits of Xpert. Urgent action is the availability of second-line drugs.
 
SANWOGOU Dédamani Thomas
IDE, MD sciences de l'éducation
Secrétaire Exécutif du REEISAOF
Etudiant en master santé internationale
Université Senghor d'Alexandrie.

Llang Bridget Maama
Replied at 10:04 AM, 13 Dec 2012

Reply contents:
> "It is true that the use of Gene Xpert in countries where treatment against MDR is not available leads to ethical problems

I find the ongoing discussions very interesting, useful and enriching. I just realise the confusion that we all in since the advent of GX and am overwhelmed by how similar are all our concerns. We are making good attempts but it is clear that many areas will require refining to clear all the uncertainties we raise here.
We have been advised to download a very good on ethical considerations around TB and having done I realise how useful and comprehensive this book is since it responds to all the concerns and questions raised by many of us on this panel. I therefore recommend that we download the book. I also agree Thomas below, that detecting MDR-TB is better than when we do not even know who is infectious. This good books advises that such countries should have a time frame as to when they will be able to initiate treatment to their scale up plans. Knowing the cases also can fast track the process of resource mobilizations for these expensive medicines. It is not all doom and gloom as some of the statements may sound.

I am still waiting for reactions to concerns I raised today

Thank you to the expert panel and all of members
Llang

Dr. Llang Bridget M. Maama-Maime
NTP Manager-Lesotho
Ministry of Health
Box 514 Maseru, 100
Lesotho

Kathleen England
Replied at 11:10 AM, 13 Dec 2012

This is a very important concern. As Dedamani presents here, there are still many limitations in many areas of the world that make great challenges for the effective use of this new (yet excellent) tool. The real concern for many of us is "access to drugs" and how to care for our patients. We must start working toward these challenges. In order to STOP TB, we need treatment for all.

Sophie Beauvais
Replied at 12:39 PM, 13 Dec 2012

Hi All,

Adding a comment in this panel from Mostafizur Rahman, Laboratory Coordinator (Microbiologist), TB Care II Project, University Research Co,LLC.

Thanks for your comments, fantastic discussion!
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Dear All,
This is Mostafizur Rahman.Working as a Laboratory Coordinator(Microbiologist) at NTRL,Bangladesh under TB CARE-II project,URC,USAID.In Bangladesh we have started GeneXpert form March, 2012. Upto till date we have tested more than thousand MDR suspects by GeneXpert.The result is very good.We have detected around 300 RIF resistant cases.From my practical experience i am shearing with you that we found eight (8) cases that is smear positive but Xpert negative. We know that Xpert can not detect NTM.Beside Gene Xpert we performed solid culture(L-J) of that sample and the growth was appeared for all 8 cases that was negative by GeneXpert.We performed capilla of the selected samples and capilla was negative too.So, in that case what should we do for reporting? We will deliver the report after confirmation by capilla or inoculating in PNB and it will report as NTM/MOTT?
Thanks

Mostafizur Rahman, Laboratory Coordinator (Microbiologist), TB Care II Project, University Research Co,LLC.

Mark Micek
Replied at 12:10 AM, 14 Dec 2012

Dear all,
Thanks for this interesting and informative discussion.
I am Mark Micek, and I work with Health Alliance International on a project to introduce Xpert with the Mozambique Ministry of Health in 2 of Mozambique's central provinces, with funding from TB REACH. Several thoughts on the issues presented above:
1. I agree with the premise that Xpert testing should be done in areas with access to DST and MDR treatment. We indeed have these conditions in our project. We also note, however, that culture and DST in Mozambique- as elsewhere- is a centralized process, and therefore relies on transportation of specimens from peripheral health facilities to centralized locations. We have found that the logistics is often difficult, as it requires repeating sputum collections and creating/maintaining consistent transport networks that may not normally exist (both for the sample and results).
2. When considering attempts to maximize the coverage of Xpert roll-out, one option is to have a limited amount of machines serving a wide geograhic area. However, we have also found the logistics of such a system to be difficult, and that it can be associated with delays and drop-offs between Xpert testing, results reporting, and starting TB treatment, that are not seen in sites with point-of-care testing. I am curious what other projects have found with attempts at centralized Xpert testing.
3. Lastly, I am very interested in some of the cost-effectiveness analyses mentioned above. We are planning an analysis looking at the relative costs and effectiveness of various algorithms to improve TB case-finding with Xpert (sequential with smears vs. in place of smears) and compared with other technologies (in particular LED, which we have found also increases diagnostic yield, although by less than half as much as Xpert).
Cheers,
Mark

Llang Bridget Maama
Replied at 1:15 AM, 14 Dec 2012

Dear colleagues,
The discussions are very useful to me. I really appreciated what Mark is saying and this just proofs the commonality of our concerns. I will be more than happy to hear your opinion on this as his questions are similar to one I raised yesterday.
Thank you for this wonderful week

Llang

Dr. Llang Bridget M. Maama-Maime
NTP Manager-Lesotho
Ministry of Health
Box 514 Maseru, 100
Lesotho

Elisa Ardizzoni
Replied at 2:05 AM, 14 Dec 2012

Manipulation of samples for Xpert does not require a biosafety cabinet, requirements are equal to microscopy, for which you can use a workstation, much more simple and far less expensive. Manipulation of samples for Xpert generates even less infectious aerosol then for microscopy. Anyway please see the article from Banada et al. 2010 "Containment of bioaerosol infection risk of Xpert and its applicability to point of care settings"

Llang Bridget Maama
Replied at 2:37 AM, 14 Dec 2012

Response on Manipulation of sample for xpert.
Thank you responding the issue of bio safety cabinet and gene-xpert. Just to share with you that Lesotho TB laboratory are all BSL2 as a standard and all microscopy is done under those conditions?
I will share the information with laboratory colleagues, but BSL is their conviction hence inclusion in the guidelines
Llang

Dr. Llang Bridget M. Maama-Maime
NTP Manager-Lesotho
Ministry of Health
Box 514 Maseru, 100
Lesotho

Fuad Mirzayev
Replied at 6:50 AM, 14 Dec 2012

Dear All,

I have noticed one of the comments with concerns on biosafety vis-avis performing the Xpert MTB/RIF assay. The panel may further detail and expand this response but in a nutshell, the processing of a sample in the cartridge was shown not to create dangerous aerosols. However, there is a part where the sputum sample is manipulated to prepare, decontaminate and digest it before adding the adequate volume into the cartridge. These steps, if done using proper techniques are low risk and do not impose a higher risk than the preparation of sputum smears for microscopy. This is why, biosafety procedures required for processing sputum for Xpert MTB/RIF are referred to as similar to the sputum smear microscopy.

Fuad Mirzayev
Replied at 6:58 AM, 14 Dec 2012

Dear Neil,

The data is scarce on paediatric diagnosis but there are a couple of papers in the list on the WHO website link to which Wayne has provided earlier on. Here it is for convenience, all papers are classified by topic so look for paediatric TB there: http://www.stoptb.org/wg/gli/assets/documents/map/XpertPublications.pdf

Hanan Ahmed
Replied at 7:31 AM, 14 Dec 2012

Dear members, I'm glad the topic is raised. I work in Gondar MDR-TB ward, in Northwest Ethiopia. As Dr Andargachew commented, there is a plan to expand the use of GeneXpert in Ethiopia. In our hospital where I'm working we are using it since last month. And it has been very very helpful. I believe it is life saving especially for MDR-TB contacts in high burden countries. In a setting where the prevalence of TB is very high even in the general population, contacts of confirmed/suspected MDR-TB patients who are also likely to have contact from someone else can be managed properly and timely with rapid diagnostics. I have recently done a study on suspects, those with previous treatment, and surprisingly, contact history was present in 29.3% of suspects and they were 3 times more likely to develop MDR-TB. So now I am treating contacts with Rif resistance with 2nd line drugs with/without full DST.

Thanks
Hanan Ahmed MD, MPH, Assistant professor
University of Gondar
Ethiopia

soundiram indira
Replied at 7:42 AM, 14 Dec 2012

Dear all,

Thank you all for your very productive discussion ( on my below email- some discussion have held in parallel in another panel).
To clarify some points for all of you. All information are written on the FIND website, negociated price:

- The price of the full system is 17000 usd if provided with a desktop / 17500 usd if provided with laptop: condition for this price is ex-works , from europe, and prepaid.

- The price of the cartridge is 9.98 usd ex-work, from europe and prepaid as well.

- Warranty for all new systems sold is 2 years IF and only if the system is re calibrated ( annual calibration) after year 1.
- UPS and surge protector are required and have to be budgeted.
- maintenance is a very limited process
- annual calibration is now a new process that will drastically reduce the need of swap of module: it will be a 20 minutes process after buying a calibration kit, Ex-works, prepaid.
This will easier your life. We will communicate a full explained document about this.

Most of you now know the system and the easiness of its use. Training materials are available, training partners in various country now, and training at cepheid as well.

For the training you can refer to the earlier section of this discussion where i explained the process with link http://apps.key4events.com/key4register/?e=168

Indira Soundiram
Customer Care & Training Manager
Cepheid HBDC

Dr. Daniela Cirillo, MD, PhD
Replied at 10:46 AM, 14 Dec 2012

I would like to underline a different problem: availability of xpert and reagents but very limited use of the test and request s by the clinicians. I believe that efforts should be made to educate and increase the knowledge and the confidence on the test

Dr. Daniela Cirillo, MD, PhD
Replied at 10:47 AM, 14 Dec 2012

The most probable diagnosis is NTM. It is very unlikely that your strains are false negative for two different tests

Sophie Beauvais
Replied at 10:40 AM, 17 Dec 2012

Dear All,

Thank you for a very productive discussion; we highly appreciate everyone taking time to contribute to this virtual panel on scaling-up GeneXpert MTB/RIF and would like to acknowledge our esteemed panelists for their extensive participation last week.

We are preparing a discussion brief that will summarize key areas of discussion and lessons learned. It will be reviewed and published as soon as possible in the MDR-TB Treatment & Prevention community (http://www.ghdonline.org/drtb/) for all members.

Wishing you all the best during the holidays, and looking forward to a new year of collaboration and learning in the community.

Best, Sophie

Sophie Beauvais
Replied at 10:45 AM, 17 Dec 2012

And please stay tuned in the community: We will be hosting another virtual panel in 2013 on GeneXpert MTB/RIF. Best, Sophie

Lucica Ditiu
Replied at 2:33 AM, 19 Dec 2012

Good morning.
Once the discussion brief is done and posted, we can also make sure we widely share - as I found the comments and discussion points extremelly rich.
The 2013 planned discussion might consider discussing the access to genXpert, who gets tested with genXpert, how the results are used, communicated and what actions are taken for the people diagnosed positive.
Thank you for this great discussion
Lucica

pascal verhoeven
Replied at 8:30 PM, 10 Mar 2013

Hi all

in Laos there is a new TB proposal which will provide a few first Xpert machines to the country. I am now looking at the procurement etc plans and was wondering reading about the need to store cartridges cool on the sites, what the size (dimensions) are of lets say 800 cartridges. Would we - for example- need to prepare like significant cold room space at central and ensure a dedicated refrigerator on each of the sites?
you experience/feedback will be helpful to us

thanks
pascal

Urvashi Singh
Replied at 7:00 AM, 11 Mar 2013

Each card -board box of 60 cartridges measures 36cm length,18cm ht. ,18 cm width.
The storage is recommended below 25 degrees C, need not worry about cold room.

Fulgence Nzabintwali
Replied at 9:10 AM, 11 Mar 2013

Good after noon,

The answer from Urvashi is ok.

But knowing station of Laos, you have some consideration to take in context , For Vientinane Capital you can use National Reference Laboratory BSL 2 room , You have also National Central Unit using for all procurement in MOH including all procurement for TB .

For transport , some time in Laos is very hot but still ok , problem can be storage in regional Lab like Savanakhet , Luang namutha ext.. where space of room still small for TB lab Unit , but in a very hospital they have a place for drug spay and general are good for storage (<25°C) , you can discuss with all hospital where you will need to send small stock for short using.

pascal verhoeven
Replied at 10:48 AM, 11 Mar 2013

Thanks, appreciate the details on Laos situation.
As you say the ambient conditions in Laos normally well exceed 25c,
drugs are still transported on the public bus etc
we are all excited to get Xpert diagnostics here soon
under GF grant but
will have to see how this goes with roll out from first NRL
in VTC to the more challenging locations

Fulgence Nzabintwali
Replied at 11:09 AM, 11 Mar 2013

Ok , your team in NRL (Vientiane) can manage that machine with out problems because is very easy to use. But with my experience in country please think about of number, electric system ( KVA 3000 is need if problem for electric system to be used 2 hour with out national electric system), other to consider is a umber of "cartouche ", if they still have lower number of samples thinks to expired period

Georgia Sambunaris
Replied at 6:22 PM, 11 Mar 2013

http://blogs.wsj.com/health/2012/08/10/groups-slash-cost-of-advanced-tb-test-...
(New $9.98 cost at 40% reduction for each cartridge.--as I'm sure you
already know).

I'd recommend a PUBMED search on economic cost effectiveness and cost
utility analysis, adjusted for estimates on cold storage. I will ask at
USAID for more information as well, specifically on the refrigeration
issues. We also use the Management Sciences for Health drug guides on
costing.

All the best,
Georgia

MIKASHMI KOHLI
Replied at 2:17 PM, 26 Apr 2013

Can somebody please tell me about the GeneXpert cartridges expiration? if there are extra cartridges in stock can they be used after their expiry dates? PS: the cartridges are stored at optimal temperature.

Urvashi Singh
Replied at 11:11 PM, 26 Apr 2013

We have used cartridges beyond the expiry date and those worked just fine.I
guess you could use them,you'd just have to change the date in the system
so it would accept these cartridges.

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