MDR-TB Treatment & Prevention

Hello Ms. Torrea,

I have forwarded your question on to some experts Parterns In Health collaborates with in Tomsk, Russia and here in the US.

Hopefully I will be able to provide you with some resources on this topic very soon.

Best,
Tom Nicholson

Dear Tom Nicholson,

Thank you very much for your response, I greatly appreciate your kindness as I am keen on developing this topic as soon as possible.

Quality Assurance, particularly for cultures, remains a critical challenge for TB laboratories in resource limited settings. I do not have on-the-ground experience in this arena but several colleagues suggested a few reference documents, links, and articles – see list below. Our team has also invited members of the Supra-National Reference Laboratories to join the discussion, and I hope that members of the community will share their implementation guidelines and experience. I would guess that answers will vary greatly depending on the settings and NTPs.

* Guidelines for Surveillance of Drug Resistance in Tuberculosis put together by the WHO and the International Union Against Tuberculosis and Lung Disease (The Union) published in 2003: http://whqlibdoc.who.int/publications/2003/9241546336.pdf
Particularly Chapter 29: National Reference Laboratory and Supra-National Reference Laboratories information, also the forms and check lists in Annexes

* The Interim recommendations for the surveillance of drug resistance in tuberculosis, WHO, May 2007: http://whqlibdoc.who.int/hq/2007/WHO_HTM_TB_2007.385_eng.pdf
Chapter 3: Laboratory

* In 2005, the Union also published a handbook with the Institute of Medical and Veterinary Science in Australia for the Pacific Island Countries: Laboratory Diagnosis of Tuberculosis by Sputum Microscopy: http://www.theunion.org/download/labcontrol/Adelaide_document ...

Quality Assurance, particularly for cultures, remains a critical challenge for TB laboratories in resource limited settings. I do not have on-the-ground experience in this arena but several colleagues suggested a few reference documents, links, and articles – see list below. Our team has also invited members of the Supra-National Reference Laboratories to join the discussion, and I hope that members of the community will share their implementation guidelines and experience. I would guess that answers will vary greatly depending on the settings and NTPs.

* Guidelines for Surveillance of Drug Resistance in Tuberculosis put together by the WHO and the International Union Against Tuberculosis and Lung Disease (The Union) published in 2003: http://whqlibdoc.who.int/publications/2003/9241546336.pdf
Particularly Chapter 29: National Reference Laboratory and Supra-National Reference Laboratories information, also the forms and check lists in Annexes

* The Interim recommendations for the surveillance of drug resistance in tuberculosis, WHO, May 2007: http://whqlibdoc.who.int/hq/2007/WHO_HTM_TB_2007.385_eng.pdf
Chapter 3: Laboratory

* In 2005, the Union also published a handbook with the Institute of Medical and Veterinary Science in Australia for the Pacific Island Countries: Laboratory Diagnosis of Tuberculosis by Sputum Microscopy: http://www.theunion.org/download/labcontrol/Adelaide_document.pdf which gives pointers for QC in the appendices (page 37).

* This short communication published in February 2008, is also a valuable resource: External quality control of Mycobacterium tuberculosis drug susceptibility testing: results of two rounds in endemic countries: http://www.ingentaconnect.com/content/iuatld/ijtld/2008/00000012/00000002/art00016?crawler=true

Hope this helps.

Dear colleagues,
The Russian National Centre for EQA in laboratory medicine is conducting proficiency testing in culturing and DST since 2001-2002. As DST PTs' methodology is well known and is already described in previous replies, I will briefly describe the culture PT module. We use a panel of 10 control samples, which includes lyophilized cultures of M. tuberculosis in two CFU concentrations (103 and 104 f.e), fast growing NTBM and E.coli. PTs are performed once a year. It can be used for egg media and for liquid media as well. Absolute majority of participants are using egg media. Low concentrations of M. tuberculosis can be probably used for liquid media culturing. Decontamination is not included into the samples’ processing so we are actually assessing the media, cultivation process and performance 0f identification procedure by time of growth, AFB staining and type of colonies. We are planning to use liquid suspension of bacteria as control samples for limited number of laboratories this year. In this case we will include decontamination procedure into the samples processing.

Dear Rebecca Weintraub,

Thank you for your valuable reply. I know very well these documents that are relevant for this topic. Actually, I meant the EQA for culture as a process by which we can compare results and performance of several labs during the same period of time.
I agree with you that quality assurance remain a challenge for TB laboratories and a previous step for lab accreditations.

Best regards
Gabriela Torrea

Also refer to: Quality Assurance of Sputum Microscopy in DOTS Programmes, Regional Guidelines for Countries in the Western Pacific, published in 2003 by the WHO. These provide recommendations for external quality assessment and implementation.

Related to Gabriela's original question, does anyone know of a PT program that provides a panel of simulated sputa, from which we can not only measure their ability to identify MTB (or the appropriate organism)and perform DST, but also check the decontamination process and smear preparation? Thanks for any advice!

Dear all,
We are (Russian Federal EQA Sytem) performing PT for Bactec MGIT culturing,
subsequent identificat and DSTfor two years and had started PT culturing on
solid media and MTB identification in 2010. The control samples are MTB,
NTMB strains' suspensions in Middlebrook with different CFU concentrations.
Some of the samples are contaminated with E. coli or corynebacterium. The
procesing is started from decontamination.
Best regards

Hi all
Kelly - if you discover such a resource please let us know - we have struggled with how to do panel proficiency testing for MODS which uses sputa not strains to give direst RH DST - I have heard of somewhere in the US that can provide simulated sputa but as I recall it cost hundreds (if not thousands) of dollars, and we have not identified a straightforward way to do it - moreover one also would need sputa with drug resistant TB in order to quality check the DST element.
These same issues also apply to the direct NRA, direct TLA, direct MTBDR-plus and now GeneXpert so perhaps more people will start thinking about how to solve it!
cheers
Dave

GLI is developing a panel testing programme to roll-out with the implementation of the Xpert MTB/RIF. Each panel will contain approximately 5 samples of artificial sputum spiked with heat killed MTB with and without resistance mutations in the rpoB gene. As the Xpert MTB/RIF assay requires intact bacilli and not free DNA for the procedure, a validation procedure is currently underway to ensure that the panel samples can be prepared in a way which contains non-viable intact bacilli.

I would like to ask if this panel testing programme of GLI will include
proficiency testing for line probe assay using HAIN. Some settings that are
geared towards PMDT scale up like Vietnam have put this technique in place
as the main diagnostic tool, so it is crucial to also put in place an
external quality assurance system prior to the expansion. Many thanks.

The proficiency panel being developed by the GLI for roll-out with the Xpert MTB/RIF assay will also be validated for use the Hain Lifesciences MTB-DR plus lineprobe assay. It is anticipated that the same panel of EQA samples will be suitable to help quality assure both of these WHO endorsed technologies.

These are some of the books that we used to conduct our TB culture and drug sensitivity.

These are three books. But we should not that quality control for TB smear microscopy slides are nolonger kept separately. All positive and negative slides are kept togetheer and then you do the blinded recheckng of reading the slides.

I will attach the second book.