Interview conducted by April Cashin-Garbutt, BA Hons (Cantab)
Please could you give a brief introduction to drug-resistant tuberculosis?
In contrast to drug-susceptible tuberculosis, which can be cured with available drug therapies, drug-resistant, and especially multi-drug resistant, tuberculosis is much more difficult to cure and it takes a much longer time for patients to become non-infectious.
For susceptible tuberculosis we recommend a combination of drugs for up to 6 months, but for multi-drug resistant (MDR) cases two years or more might be needed.
What causes drug-resistant tuberculosis?
Drug resistance in M tuberculosis is caused by spontaneous chromosomal mutations conferring resistance. Bacteria with resistance associated mutations are selected during sub-optimal therapy. Additional mutations will occur and could lead to bacteria becoming resistant also to additional drugs.
The problem of drug resistant TB is man-made, without any exposure to drugs no resistance will be developed. Resistant strains can infect healthy individuals and cause additional cases of MDR-TB.
In poor areas of the world, with limited exposure to TB drugs, the prevalence of resistant strains is much lower than in certain middle income settings where various anti-TB drugs have been available, but their use not strictly controlled.
Please could you explain what the difference is between resistance to first-line and second-line drugs?
The first-line drugs are for fully drug-susceptible cases of tuberculosis. The treatment outcome is normally very good and most patients who start first-line drug therapy will be non-infectious and feel much better within a few weeks.
Second-line drugs are used to treat patients with resistant strains of M. tuberculosis. These drugs are often less effective than the first-line drugs in susceptible cases and they have to be administered over very prolonged periods. They are also significantly more expensive and have a number of side effects.
How prevalent was drug-resistant tuberculosis previously thought to be?
According to data from WHO the global prevalence of multidrug-resistant tuberculosis is around 5 %, but there are huge geographical differences.
What did your research show about the levels of drug-resistant tuberculosis?
Our Institute has taken part in studies of the prevalence of resistant TB in different geographical areas, including parts of the former Soviet Union. In for example Belarus almost 1 out of 2 patients with tuberculosis are infected with MDR-TB strains. This is unexpectedly high and many of the internationally recommended control procedures are not adapted to this level of resistance.
What sparked your interest in drug resistant tuberculosis?
I see drug resistant tuberculosis as a severe public health concern, especially here in North West Europe. Many of our neighboring countries to the East have severe problems with this form of hard-to-treat tuberculosis.
Being a laboratory scientist with a general interest of drug resistance, it was natural for me to focus on tuberculosis. It is definitely a very clinically relevant topic and there is a need for a deeper understanding on the mechanism of resistance and how to counteract further development and spread of resistant TB. There is also a need to identify new targets in the bacteria to make the development of new anti TB-drugs possible.
How do drug-resistant tuberculosis levels vary in different countries?
It varies a lot and this is the reason it is difficult to develop general control principles that are easily applicable all over the world.
Certain areas, such as parts of former Soviet Union, are seeing increasing problems with drug-resistant tuberculosis, in some places reaching worrying levels.
Most patients with resistant TB are to be found in India and China, where the problem is less well documented. There is a pronounced need for further studies to get the full picture of the size of the problem in a global perspective.
Should we be worried about the current levels of drug-resistant tuberculosis?
I think the recent studies indicating higher levels of drug-resistant tuberculosis than expected should be taken with great concern. We should make optimal efforts to counteract further increases in this public health problem.
Can anything be done to reduce levels of drug-resistant tuberculosis?
One key step in reducing levels of drug-resistant tuberculosis is the early detection of patients infected with these kinds of strains. Recently, molecular laboratory tests have been developed and introduced for detection of drug-resistant tuberculosis.
These techniques offer a much more timely detection of patients transmitting drug-resistant strains of tuberculosis. This would allow an earlier change to effective drug therapy and an appropriate level of infection control to be established.
We also need new and improved drugs for drug-resistant tuberculosis. Luckily enough for the first time in many years we now see two new drugs coming into the market in the not so far future.
Are there any plans in place to achieve this?
There are a lot of activities of improving laboratory techniques of detection of this problem. Also, there is a lot of research into new and improved drugs. In the long run we also hope for an improved and more effective vaccine against tuberculosis.
How do you think the future of drug-resistant tuberculosis levels will develop?
Even though we have recently seen a fairly sharp increase of this problem, I am optimistic that this trend could be broken and we will see the levels coming down again. Especially if we manage to adapt the available new tools in the correct way and also develop further and even more useful tools. Also if the early laboratory detection made possible is followed by adequate therapy and infection control measures to counteract the problem to spread into healthy individuals.
Do you have any plans for further research into this field?
We are actively involved in European research networks to increase the broad understanding of the problem with resistant TB and how to best counteracting it.
Would you like to make any further comments?
I hope that resistant TB will not be neglected and that the necessary resources are made available for strengthening research to improve the control of the problem. I also hope for a strong international collaboration to be successful in this struggle in the global perspective.
Where can readers find more information?
Good sources of information on TB generally and its drug-resistance globally are the WHO (www.who.int) and The International Union Against Tuberculosis and Lung Disease (www.theunion.org). Another very informative site is: www.findtbresources.org
About Sven Hoffner
Sven Hoffner an Assoc Prof in clinical microbiology at the Karolinska Institute, Stockholm, Sweden.
He is the Director of the WHO Supranational TB Reference Laboratory at the Swedish Institute for Communicable Disease Control in Solna, Sweden, where he holds a position as chief microbiologist.
He has been working in the field of drug resistant tuberculosis for more than 25 years and has an extensive international network. He is the author of 160 scientific publications and has been the main supervisor for 10 PhD students in his field of research.