27 February 2015 - INTERVIEW

Tuberculosis treatment: Multidrug-resistance is a major challenge

In the journal The Lancet, DZIF researchers from the Research Center Borstel and their colleagues from England and South Africa make the case for optimising tuberculosis drug development. They recommend more and earlier consideration of potential resistance mechanisms. Co-author Stefan Niemann explains which problems need to be solved.

Niemann 162 neu

Niemann 162 neu© Forschungszentrum Borstel

Every year, around nine million people contract tuberculosis worldwide. How good are the existing treatment options?

Prof Stefan Niemann: The treatment options are actually very good for patients with “normal” tuberculosis, i.e. in cases without multidrug-resistance. Treatment becomes problematic with the rise of resistance, because then we can no longer use the standard drugs for treatment and have to resort to so-called second-line drugs.

How often does this problem of resistance occur in tuberculosis patients?

Prof Stefan Niemann: There are regional differences. Parts of the world already exist where every second patient is infected with multidrug-resistant tuberculosis, and consequently, the two standard drugs for tuberculosis treatment—isoniazid and rifampicin—can no longer be used. Belarus exemplifies a region with very high rates of resistance, and several other regions in the former Soviet Union are also marked by very high rates, with multidrug-resistant tuberculosis patients accounting for 10 to maximum 50 percent all cases.

How can we fight multidrug-resistant tuberculosis bacteria?

Prof Stefan Niemann: Overall, the problem is multi-layered. We have to try and contain the spread of various multidrug-resistant bacteria in the affected regions, and prevent them from developing in other regions. Here, it is important to work on all levels in the fight against tuberculosis—diagnosis, treatment and infection control. Take diagnosis, for example, where it is important to rapidly confirm: Has the patient been infected with multidrug-resistant tuberculosis and does he/she need special treatment?

In the current issue of The Lancet, together with your international colleagues, you suggest optimising drug development to include testing for antibiotic resistance and resistance mechanisms. What exactly would you like to achieve?

Prof Stefan Niemann: When you know a patient is infected with multidrug-resistant bacteria and can no longer be treated with the standard drugs, you then need new drugs. There are several interesting candidates, e.g. bedaquilin and delamanid. Here, avoiding the development of new resistance is particularly important. The basis for doing this is founded in the knowledge of how the pathogens become resistant. So in the end, you not only need the new drugs, but also accompanying, sensible diagnostic tests to detect potential new resistance. For tuberculosis bacteria, diagnostic testing can be conducted in two ways, either: with conventional microbiological methods which include culturing and phenotypic testing, or: through detecting genome changes in the bacteria.

Why has drug-susceptibility testing for resistance previously not been considered for drug development?

Prof Stefan Niemann: Basically, this has failed because companies probably have not had such great a priori interest in investing in this field. Additionally, these companies do not actually develop the microbiological tests on their own, scientific expertise is also partly required. This is best achieved through directly involving the research community in such questions, and providing the necessary materials.

Is this information usually publicly available?

Prof Stefan Niemann: One problem, which is increasingly coming into the foreground, is patenting—especially of genetic markers for resistance. These patents do not permit a broader use of the markers for developing diagnostic testing methods. An agreement should be made to stop patenting resistance mechanisms.

What does the DZIF contribute to tuberculosis research?

Prof Stefan Niemann: At the DZIF, we have a broad research agenda in this field. On the one hand, of course, we analyse the spread of such pathogens, meaning that we conduct so-called fingerprint studies to investigate their global spread: do the strains from Eastern Europe actually spread to Germany and if so, what consequences arise from this regarding the regional epidemiology? There is certainly potential for such spreading to occur, considering that migration to Germany is currently rising sharply again. At the same time, we are able to describe resistance mechanisms more precisely through genome analysis of the pathogens. We also make this information available to companies, who subsequently develop new tests.

Is there consequently also a danger of these resistant pathogens increasingly emerging in Germany?

Prof Stefan Niemann: The numbers from the Robert Koch Institute clearly show that cases of multidrug-resistant tuberculosis have increased significantly over the last year. Overall, the case numbers are still low, at 100 new infections per year, because they are predominantly imported. The spread in Germany depends on many factors, e.g. the general health status of its inhabitants. The living conditions are very high here and people do not necessarily fall ill with tuberculosis. However, even here, every single transmission from patients with multidrug-resistant tuberculosis must be avoided.

Publication

Köser CU, Javid B , Liddell K, Ellington MJ, Feuerriegel S , Niemann S, Brown NM , Burman WJ, Abubakar I, Ismail NA , Moore D , Peacock SJ , Török ME
Drug-resistance mechanisms and tuberculosis drugs.
The Lancet. 2015 Jan 24;385(9965):305-7. doi: 10.1016/S0140-6736(14)62450-8.



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