Dear Yasmeen,

This is a very interesting topic indeed.

WHO has a policy statement about this but in my opinion a litle bit old.

There is no correct answer to your question, it depends very much on your setting, posibilities and budget.

From my point of view, nowadays there are two techniques that should be considered for diagnosis of MDR-TB in RLS: GeneXpert and MODS. They have both benefits and drawbacks:

- Benefits for GeneXpert are its simplicity and velocity, drawbacks is costs 9.98USD/test and diagnositc accuracy is not as good as desirable especially in HIV infected cases and especially for MDR-TB. Therefore every diagnosis of rifampicine resistant-TB with GeneXpert has to be confirmed with a culture technicique.

- Benefits for MODS is it's extemelly low-cost 0.5-2 USD/test, and diagnostic test accuracy is as good as any other culture technique, and even in some studies sensibility is superior than the other culture techniques(http://www.ncbi.nlm.nih.gov/pubmed/17035648). Also it allows for the diagnosis of INH, RIF, resistance as well as evaluating second-line drug resistances. Drawbacks are it's complexity that, although it is low, it requires a 3 week training, that compared to the 1 day training of GeneXpert is a lot. Also it requires an equipment that is a litle bit more expensive than the GeneXpert, but thanks to the low running costs after 1 year the difference is more than favourable to MODS. Also time to positivity is a median of 6-7 days, that compared to the 2 hours of GeneXpert is a lot.

When comparing this for me it is dificult to choose the best technique. Our group is trying to do a field evaluation head to head of both techniques and we will see the results in due time.

Thanks Philip. Please share your results to be sure.

Well we have excellent experience with MGIT.. the broth based culture systems. Gene expert as narrated above has its own merits and demerits. Then you have NRA .. nitrate reductase assay which if performed meticulously is very good option in resource poor countries.

Well, without doubt MGIT is, to the moment, the technique to beat. It is the one that all the others are comparing to. Nevertheless it is not perfect. It is expensive and slow, but it is the most precise for sure.

NRA yes, but still slow.

Line probe Assay is probably the best method.

Thank you all for the input

Hi Yasmeen,

Straight out, i will say that i hope i do justice to your question. Its a tough one with so many factors that have to be thought about, time to result, cost and accuracy being the most important.

Liquid culture (MGIT/BacTAlert) is the best, but as mentioned earlier, slow. Sensitivity testing further delays the whole process. Therefore you need to cut down on time taken to arrive at a diagnosis, specially for MDR-TB. The best would be for testing to be carried out directly on a sputum sample preferably with a molecular technique.

To that end, the Gene Expert is a good machine as mentioned earlier, but it is very expensive. The other choice is Line Probe Assay, Genotype MTBDRplus (again, as mentioned earlier) which is good (I have worked with it for over two years) and relatively cheaper and pretty accurate particularly for Rifampicin, fast (1-3 days) and relatively cheap, but it is not foolproof. Field trials are currently being conducted by WHO for use of the second line Line Probe Assay, Genotype MTBDRsl.

Both the above methods are approved by WHO. To cut down on costs, you can approach the company directly by mail (HAIN LifeScience, Germany) and if you are doing any kind of work that helps the public at large in your city/country, they will definitely bring down the price and possibly that of the reagents too via their local representatives. I did the same thing and they helped us a lot too.

In addition you may have non-governmental organisations working in your country that help in reducing prices of the test by negotiating directly with the company itself. My laboratory works with one of these, which is in part supported by The Clinton Foundation, which brings down the cost of a liquid culture to about 9 US dollars and the LPA itself to about 25 US dollars. I know it is still expensive, but its better than privately run laboratories charging upto 95 dollars in some instances in my country. The upside is you get a fast, accurate result and can start therapy without losing the patient.

Lastly there is a new method called LAMP technology (Loop Mediated AmPlification), which again sounds very promising. I do not have much idea about the technology itself or the test, but i am sure you can find out more details. I think it is being marketed by a company called bioMerieux.

Regards,

Michael.

There r homeopathic preparations like tuberculinum and bacilinium working fine beside other different remedes. Regrds

i've opined for for remedies in case of MDR TB, not diagnosis.

The most rapid method (1 day) is to detect any one of the 5 mutations that result in resistance to rifampicin. Because mono resistance to rifampicin is rare and when present it is associated with resistance to INH, direct detection of resistance to rifampicin identifies mdr TB. However, this should be confirmed via MGIT/Bactec 960/Expert TB etc. a few days later. For entire method see: Viveiros M, Leandro C, Rodrigues L, Almeida J, Bettencourt R, Couto I, Carrilho L, Diogo J, Fonseca A, Lito L, Lopes J, Pacheco T, Pessanha M, Quirim J, Sancho L, Salfinger M, Amaral L. Direct application of the INNO-LiPA Rif.TB line-probe assay for rapid identification of Mycobacterium tuberculosis complex strains and detection of rifampin resistance in 360 smear-positive respiratory specimens from an area of high incidence of multidrug-resistant tuberculosis. J Clin Microbiol. 2005 Sep;43(9):4880-4. PubMed PMID: 16145166; PubMed Central PMCID: PMC1234138.