Taking on tuberculosis

With tuberculosis (TB) infection rates higher per capita than the United States, Canada and Australia, World TB Day on Saturday, 24 March 2012, was a timely reminder of New Zealand’s vulnerability to this often overlooked disease.

Tuberculosis is one of the world’s deadliest diseases and is responsible for nearly two million deaths annually. In New Zealand it is estimated that one person a day is newly diagnosed with TB, with the disease more prevalent in conditions of household crowding and relative poverty.

TB is caused by the bacterium Mycobacterium tuberculosis, which is spread from person to person through the air. On rare occasions the immune system of an affected individual can eradicate the bacteria, however in most cases the bacteria lie hidden in specialised granulomas in the lungs, where they avoid detection. TB bacteria are slow-growing and insensitive to drugs and thus require long-term multi-drug therapy to prevent resistance.  Taken together, these factors create unique challenges for the development of new therapeutics to treat TB disease.

World TB day commemorates the date in 1882 when Dr Robert Koch announced his discovery of M. tuberculosis.  This year the slogan to mark the date was “Stop TB in my Lifetime,” a goal that can only be achieved if scientists, clinicians and public health officials work together to develop more effective therapies for treating those at highest risk.

“New Zealand scientists have made a number of critical contributions to the global effort to fight TB,” says Infectious Diseases scientist Dr Joanna Kirman.

Dr Kirman heads a research team at the Malaghan Institute focused on reducing the incidence of TB in New Zealand through the development and implementation of more effective TB vaccines.  

“The current TB vaccine, BCG, fails to reliably protect against adult TB lung disease,” she says.  “Efforts to develop a new more effective vaccine for TB have been hampered by a lack of understanding of the immune response required for long-term protection.”  

Identifying which components of the immune system are the most critical for protecting against TB is akin to finding the proverbial needle in a haystack.  To get around this onerous undertaking, Dr Kirman and colleagues developed a novel strategy that involved trapping immune cells at specific sites in the body, and then looked to see how this influenced the ability of the immune system to protect against TB.

“Our research showed that a vaccine needs to drive the protective cells to the lung if we want to achieve good protection against TB,” says Dr Kirman.

Complementing this work is a drug discovery platform involving the Malaghan Institute’s Immunoglycomics team, led by Dr Bridget Stocker and Dr Mattie Timmer.

“The objective of our research is to better understand the mechanisms by which distinct bacterial components, such as those found on the surface of M. tuberculosis, modulate the host immune response,” says Dr Stocker.  

Her team were the first to determine how the length of a particular mycobacterial cell wall glycolipid can influence the activation of the immune response. PhD student Ashna Khan was able to demonstrate this by synthesising a series of glycolipids of defined size and screening these against specific immune cells.  Her work was published recently in the international scientific journal ChemBioChem, where it featured on the front cover.

Dr Stocker and colleagues are also developing a unique drug delivery system that specially targets macrophages, the immune cells within the granulomas where the M. tuberculosis bacteria reside.

“Our goal is to be able to deliver TB drug(s) directly to the site of infection,” says Dr Stocker. “This will lead to a higher therapeutic index of any given TB-drug. In addition, the immunostimulatory properties of the molecules we are using make it easier to kill the bacteria.”

It is anticipated that the knowledge and technologies emerging from these Malaghan Institute research programmes will lead to the development of better therapeutics and vaccination strategies for the treatment of individuals with TB.  In doing so, the Malaghan Institute is proud to be able to make a small, but significant contribution to the ‘call for a world free of TB’.

Link to the Centers for Disease Control and Prevention website to learn more about tuberculosis

Read more about TB control in New Zealand