The Xpert® MTB/RIF test (Gene Xpert, Cepheid, Sunnyvale, CA, USA) is a recently developed diagnostic test for identifying mycobacterium tuberculosis (MTB) and potential rifampicin resistance. After being touted as the potential game changer for TB control, it has understandable generated a great deal of interest.
From the manufactures website it looks ideal. It is: highly specific (97-100%), quick (takes a few hours) and easy to use. The WHO technical advisory group (STAG-TB) has recommended Gene Xpert for swift and large-scale implementation at the peripheral level. The hope is to use Xpert to tackle the ever-growing worldwide MDR-TB problem. Gene Xpert can ensure quality diagnosis and at the same time detect a common form of MTB drug resistance.
The planned large-scale implementation of gene Xpert in India is due to commence within the next couple of years. It is proposed that an Xpert machine be installed in each Tuberculosis unit (a TU covers 500,00 population or 250,000 in tribal/difficult areas). It has been said that the existing microscopy network is going to be maintained. However gene Xpert is going to be used for patients who are: re-treatment cases, HIV positive or any group at risk of developing MDR-TB. Now the calculation of what proportion of samples this represents is beyond me. If anyone can calculate it I would be very interested. Although I would predict that it is reasonable high, the number of TB patients with HIV is around 5% (RNTCP – 3rd quarter 2011) and treatment failure is close to 13% (RNTCP– 3rd quarter 2011).
Multiple different authors have raised concerns over applying gene Xpert in developing countries. Here are the major issues:
- It requires a constant electricity supply. This is major problem in India because the power regularly fails. Back up generators are available however these are costly to run and are not always reliable.
- The operating temperature needs to be constantly below 30 °C . India’s climate regularly tops 30 °C, so constant air conditioning would be required. This alongside temperamental electricity supply could cause some major technical and economic problems.
- The cartridges required are bulky therefore pose storage issues. These also need to be stored >28 °C . Consequently a separate storage room with air-conditioning could be required. These cartridges can also only be stored for 18 months.
These issues although weighty can be solved. The biggest issue, which I can see, is financial and wherever it is actually required in the first place. So the company Cepheid who make Xpert, alongside FIND, have agreed a highly discounted unit price of around $17,000. This is very reasonable compared to the prices advertised in the USA and Europe. However this could be a clever business tactic from Cepheid. Sell lots of units at a cheap price and by doing so create a huge captured market for selling Cepheid’s test cartridges. Sort of like what the Amazon Kindle are doing with eBooks, Cepheid is instead replacing books for the TB symptomatic.
If the Indian government buys one Xpert unit per TU it will cost a little under $40,000,000 or 2,000,000,000 INR. So this is maybe a ‘bargain’ but it is still a lot of money. Could this money be used better elsewhere? This is not all; the apparatus requires Cepheid supplied cartridges to carry out each test. For a single test (this includes recalibration of machine etc.) it costs $20 per sample. This is quite a bit more expensive than an Amazon Kindle book, about $8 (sorry bad example). A better comparison is in India this could probably feed a family for perhaps a month. So it’s not cheap. Now I don’t have the numbers for how many tests they expect to do. So I am going to show how much it would cost to do all TB tests using gene Xpert. I know this isn’t totally representative, however it gives you a good idea of the costs involved. So in 3rd quarter 2011 the RNTCP performed 2,017,536 sputum examinations. If Gene Xpert did these it would cost $40,350,720 per quarter. That’s around $438,595 per day. When you compare this to the price of sputum smear microscopy its quite staggering. Sputum smear microscopy costs $~0.5 per test. That equals $1,008,768 per quarter and around 11,000 per day. A quick bit of maths shows that Gene Xpert is 40 times more expensive than sputum smear microscopy.
So to me and many others it seems strange for the WHO to be pushing this. It seems costly and largely impractical. I understand that MDR-TB is a major issue. Its presence is an indicator of a global crisis waiting to happen, a crisis that needs to be dealt with fast and effectively. However it has been cited that currently there are big issues with the procurement of second line drugs to treat MDR-TB. So why bother diagnosing MDR-TB if you can’t treat it? This poses not just a logistical issue but also a major ethical one.
As I have said it doesn’t really make much sense. So I had a little look into Cepheid. Upon searching Cepheid I found that in 2009 there was a spike in their lobbying expenditure from $100 thousand to well over $300 thousand for that year. The money was spent lobbying misc. manufacturing and distribution programmes. Is there the potential here for a tied aid agreement? Governments often tie aid to certain conditions such as purchase agreements and market restrictions. Has Cepheid lobbied the USA government in-order to push gene Xpert to developing nations? This would mean commercial interests are at the heart of this decision, rather than positive health outcomes. I do feel slightly uncomfortable writing that, because I understand I could be out of my depth, putting 2+2 together and getting 10. However I believe it is a possibility and one that needs to be thought about. Maybe we are being told “we must implement gene Xpert now, to stop MDR-TB’ however it’s really a financial coup for Cepheid and not a cost effective way to tackle MDR-TB.
So in conclusion it does not seem appropriate to start the large-scale implementation. Pilot studies need to be carried out to determine feasibility. Also other options need to be evaluated to see if this is really the most cost effective way to tackle the ever-growing MDR-TB problem. I believe there are other companies developing similar tests. We require solutions, but these solutions need to be appropriate. Especially when they are concerning such large amounts of money. The major questions I raise are: is the supply of second line drugs sufficient? Are these drugs going to make it to the patients? Are current cure rates good enough in the country to justify the need for increased diagnosis? Is this really the best intervention for tackling TB? Is India ready for Gene Xpert?
Thanks for reading, please comment.
Scott, L. E., McCarthy, K., Gous, N., Nduna, M., Van Rie, A., Sanne, I., Venter, W. F., et al. (2011). Comparison of Xpert MTB/RIF with Other Nucleic Acid Technologies for Diagnosing Pulmonary Tuberculosis in a High HIV Prevalence Setting: A Prospective Study. (M. Pai, Ed.)PLoS Medicine, 8(7), e1001061. doi:10.1371/journal.pmed.1001061
Trébucq, a, Enarson, D. a, Chiang, C. Y., Van Deun, a, Harries, a D., Boillot, F., Detjen, a, et al. (2011). Xpert® MTB/RIF for national tuberculosis programmes in low-income countries: when, where and how? The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 15(12), 1567-72. doi:10.5588/ijtld.11.0392
WHO. (2011). Rapid Implementation of the Xpert MTB / RIF diagnostic test. World Health.