Questions and Challenges in Tuberculosis Research

An Interview with Dr. Megan Murray of the Harvard School of Public Health

A NextGen Free Standing Perspective Article
By Graciela Carrasco

When asked which areas of TB research currently require the most attention, Dr. Megan Murray has a great deal to say. "There is a whole series of things that need attention" she begins, and proceeds to list four areas of particular importance: understanding multi-drug resistant TB and developing new drugs to deal with resistant strains, developing new diagnostics for multi-drug resistant TB, understanding TB persistence, vaccine development.

A Great Need

A medical doctor and scientist, Dr. Murray is the Principal Investigator of a laboratory at the Harvard School of Public Health, which focuses on the transmission dynamics of TB. Her work, like that of other scientists, doctors, and public health specialists who focus on TB, is of great relevance given the current global scenario: according to recent WHO statistics, approximately 1.6 million people died of tuberculosis in 2005 [1]. It has been reported, moreover, that currently available chemotherapeutic drugs are insufficient for a truly effective response against the ongoing epidemic [2]; better diagnostic tools have also been called for [3].

Tuberculosis, caused by the bacteria Mycobacterium tuberculosis, is rare in many Western countries and because of this it is often thought of as a disease of the distant past, but it is actually a major global health challenge [4], as the figures above attest. As WHO summarizes in its factsheet for the disease, it is highly contagious, and it is estimated that about 33% of the world's population is infected with mycobacterium tuberculosis, although only about 5 to 10% of individuals infected actually experience the active form of the disease, with HIV co-infected individuals being at a particularly high risk [5].

Areas of Investigation

A special focus on multi-drug resistant TB is necessary, Dr. Murray explains, because of the recent high prevalence in several countries, and because of how little scientists actually know about it. "There is a lot about how organisms acquire drug resistance we don't understand," she points out. New drugs are needed to respond to the resistant strains, and speedier tools for diagnosing multi-drug resistant TB are also necessary-- current methods rely on culturing, which can take months.

Persistence, she adds, is another aspect of tuberculosis that is not understood- scientists do not know exactly what happens to the bacteria that remain behind in the patient's body after the active form of the disease has been successfully treated, or how these bacteria stay latent.

Last but certainly not least, Dr. Murray stresses that there is currently no effective vaccine against TB, although a number of candidates are currently being worked on. The problem lies in part, she explains, in that not enough is understood about the immune response to TB, and why it is successful in some individuals and not others.

Current Support

When asked whether there is sufficient interest on TB among the research community in the United States, Dr. Murray explains that while TB had been all but forgotten by the research community at one point, over the last roughly fifteen years there has been a significant surge in interest, and many young researchers have been recruited in this area. She is quick to add, however, that the magnitude of the problem always calls for more and better research. She also points out that acquiring necessary funding can still be challenging for scientists, although in recent years some private foundations have donated generously to TB research. In particular, she stresses, field research focused on studying what's happening "on the ground" in countries where TB is a problem is often difficult to fund.

When asked how scientists can try to ensure that the new knowledge they create will be used for the benefit of the patients who need it most, particularly given the fact that so many tuberculosis patients live in very poor countries, Dr. Murray responds that this is a difficult but very important question. Traditionally, she explains, there has been no obvious mechanism in place for translating basic research into interventions; the last few years, however, have seen the rise of a more multidisciplinary community that is better equipped to handle these kinds of questions. In particular, she points to the efforts of private organizations like the Bill and Melinda Gates Foundation, which focuses on funding projects that might be translated into practical interventions in the "foreseeable future", as she cautiously terms it. An important point to note, she adds, is that scientists doing research in this area have to be prepared to talk to individuals in industry and pharmaceuticals, which means assuming a different kind of role, and can be a challenge in itself.
 

References

  1. World Health Organization. Global Tuberculosis Control Report 2007 Key Findings. http://www.who.int/tb/publications/global_report/2007/pdf/key_findings.pdf
  2. Spigelman, M. "New Tuberculosis Therapeutics: A Growing Pipeline". JID. 2007; 196: S28-S34.
  3. Perkins, M., and J. Cunningham. "Facing the Crisis: Improving the Diagnosis of Tuberculosis in the HIV Era". JID. 2007; 196: S15-27.
  4. Sacchettini, J., E. Rubin and J. Freundlich. "Drugs versus bugs: In pursuit of the persistent predator Mycobacterium tuberculosis". Nat Rev Microbiol. 2008; 6:1 41-52.
  5. World Health Organization. Tuberculosis. http://www.who.int/mediacentre/factsheets/fs104/en/index.html


Graciela Carrasco is an Editor for the Next Generation and a member of the Harvard class of 2009.

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