KHOPOTSO: Around the globe, it is estimated that TB kills 2 million people a year and that 8 million people are diagnosed with the disease annually. Treatment for TB takes a period of 6 months and the medication is effective if patients adopt a strict approach to taking their medicines. Now, 40 years after the first drugs for TB were developed, it is even more critical that new drugs enter the market. Why has there been no activity in this field for so many years? Prof. Valerie Mizrahi is the co-director of the Centre of Excellence for Bio-Medical TB research at Wits University and the National Health Laboratory Service, in Johannesburg.

Prof. VALERIE MIZRAHI: Firstly, the drugs that were developed and the combination of drugs that were developed are effective as long as you’€™ve got drug susceptible TB. That’€™s to be distinguished from drug resistant TB’€¦ Those drugs are effective and they resulted in quite a marked decline in the incidence of TB around the world. And I think that we were all lulled into a state of complacency believing that these drugs were going to eliminate the problem of TB.

KHOPOTSO: In addition, some economic and socio-political reasons contributed to the lack of development in producing new medicines for TB.

Prof. VALERIE MIZRAHI: The second factor is that we must remember that TB is a disease of the poor. The incidence of TB is highest in the most impoverished countries. This falls into the category of what one could refer to as neglected diseases. They’€™re neglected doesn’€™t mean that they’€™re not important’€¦ But, it fell into the category of diseases which have been neglected from the view-point of drug development.            

KHOPOTSO: But in recent years, says the slightly-built woman, the spotlight has fallen back onto TB.

Prof. VALERIE MIZRAHI: Bill Gates has been a major driver of this’€¦ People like Bono. These are individuals recognised by Time magazine as people of the year last year. The spotlight has come back to neglected diseases. TB falls in the category, of course, of AIDS and malaria – the three major, major killers.

KHOPOTSO: The spotlight has brought with it financial resources to do research into new drug developments for TB. The Global Alliance for TB Drug Development is funding trials around the world aimed at producing these drugs. The need for   development of new drugs is three-pronged, says Prof. Mizrahi.  

Prof. VALERIE MIZRAHI: Six months of chemotherapy is too long’€¦ We need to shorten the duration as a way of improving the cure rate and as a way of making a dent on TB control’€¦ The second issue is that there is drug resistance. It’€™s still at low levels ‘€“ certainly, in this country. But we’€™ve got to look at the global picture’€¦ The third issue is that’€¦ we know that most people who are infected with the TB bacillus don’€™t ever develop TB and that the organism goes into a persistent state in which the individual shows no signs of disease and yet, there’€™s a likelihood that so-called reactivation disease can occur.    

KHOPOTSO: Re-activation disease is when a person gets a recurrence of TB several months or years after the initial infection. Prof. Mizrahi goes on to explain the magnitude of this type of TB.

Prof. VALERIE MIZRAHI: You need to appreciate that 1 in 3 people on earth is estimated to have been infected with TB. Each of those individuals has a lifetime risk of about 10% of their lifetime developing reactivation disease. That risk is much, much  greater if you’€™re HIV positive. It becomes 10% per annum as opposed to 10% lifetime risk’€¦ So, we need drugs that are going to be able to look at that problem to try and get to the heart of latent TB infection’€¦

KHOPOTSO:  In her lab at the National Health Laboratory Service, Prof. Mizrahi works on what she calls the discovery process of new TB medicine.

Prof. VALERIE MIZRAHI: The discovery process is really referred to as the very early stage’€¦ where you’€™ve got candidate compounds or candidate molecules that are demonstrating in various ways, efficacy. Now, those ways could be the ability to kill TB in a test-tube’€¦ in some kind of what we call an in-vitro assay. This is not an assay in a living animal or in a person.

KHOPOTSO: We’€™re looking at a very long-term project here?

Prof. VALERIE MIZRAHI: Yes. The Global Alliance for TB Drug Development has set as its first target 2010 for a new drug being available’€¦ Drug development is, by default, a long-term process simply because there are many points at which drug candidates that look really promising, fail. So, you need a very busy and well-populated drug development pipeline to have a few that are going to succeed’€¦ But even then, I think we do need to be realistic and say a 10-year horizon was an optimistic one. I think a more realistic one is 15-20 years.                      

KHOPOTSO: But even so, it looks like the prospects for TB drug development are great. And South Africa is one of the countries playing a leading role.  

Prof. VALERIE MIZRAHI: We’€™re in a very privileged position of having several new drugs, new drug combinations being tested in Phase 2 trials around the world. South Africa is a premier destination for Phase 2 trial testing. And there’€™s very major studies going on in the Cape Town and Durban area in this respect.