A Sydney researcher is seeking to improve treatment of TB by tracking resistance to it among thousands of rural Chinese people with the help of a $750,000 NHMRC grant
We still don’t know why only one in ten of the two billion people carrying the Mycobacteria tuberculosis bacterium become sick with tuberculosis (TB). But the disease kills more than one million people worldwide every year – three every minute.
Dr Magda Ellis of the Centenary Institute is already using her grant to search the highways and byways —and genomes— of rural China to find genetic clues that may one day unravel this mystery and lead to new targets for TB treatments or vaccines.
Magda has previously done fieldwork across China as a PhD student looking at soil-borne diseases. As part of her later work with the Wellcome Trust, Magda visited Ningxia, an autonomous region of China, where her latest study is being conducted.
“I was able to see the impact that TB has, particularly in the developing world where treatment is more difficult,” Magda says.
China generates more than 1.5 million new TB cases every year, with 54,000 people dying.
“Now I’m tapping into my collaborative links with China to analyse thousands of genetic samples for the biggest genome-wide study of TB patients ever conducted in Asia,” Magda says.
Magda and her Chinese colleagues are coordinating a grassroots campaign to collect samples. They will then analyse each genome to find genetic differences between those infected with TB and those who aren’t.
“When patients who have TB come in from the farms and villages to receive TB treatment, they are asked to bring a (healthy) friend from home the next time they come in,” she says,
“By comparing thousands of TB patients and healthy people from the same geographic region and similar Chinese heritage, there’s more chance we can find the mutations that play a role increasing the likelihood of getting TB.”
The Chinese National Human Genome Centre in Shanghai is using the latest genome technologies to look at millions of variations in each person’s genome.
The announcement of Magda’s grant is timely given that World TB Day is coming up on March 24.
On that day 130 years ago, Dr Robert Koch announced he had discovered the cause of TB: a bacterium that infects the lungs where it grows slowly and spreads via the air when it’s coughed out.
Centenary’s TB research head, Professor Warwick Britton, says the findings from Magda’s study could be applicable across Centenary’s entire portfolio of TB research.
“We’re working to develop a deep understanding of how the parasite infects us and so successfully hides from our immune defences for decades. We’re working to understand why some people are more susceptible. We’re working on management of infected people to stop the spread. And we’re applying all that we learn to develop new ways to fight TB – potential new drugs to treat TB and new vaccines to protect us all from this scourge.”
“Winning this grant is a significant achievement for a young researcher,” says Professor Mathew Vadas, the Director of the Centenary Institute. “Finding genes that make people more, or less, vulnerable to TB will be a huge step forward in the fight against this ancient curse.”
Magda’s collaborators include her former supervisor, Professor Adrian Hill from the Wellcome Trust Centre for Human Genetics in the UK, and her Chinese colleague, Dr Yurong Yang of Queensland Institute of Medical Research and Ningxia Medical University.
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What is TB?
- Tuberculosis (TB) is a disease that is caused by a bacterium called Mycobacterium tuberculosis.
- TB infection attacks the lungs, but can also have an impact on other areas of the body.
- TB is spread when a person with an active pulmonary infection sneezes, coughs, spits or simply speaks. Like the common cold, infectious droplets are sprayed into the air and can be inhaled by people nearby.
- Two billion people carry TB bacteria, with no symptoms—but one in 10 of them will develop active TB. They will become contagious and be at risk of serious illness and death.
Current treatments and efforts
- TB bacteria can usually be treated with a course of four standard antibiotics, known as ‘first line’ drugs, taken over six months or more.
- Multi-drug resistant TB (MDR-TB) is spreading.
- This takes longer to treat and can only be cured by ‘second-line’ drugs.
- Even tougher forms of TB are starting to appear. There are no effective drugs against these extensively drug-resistant forms of TB (XDR-TB).
- The World Health Organisation (WHO) estimates that there may be as many as 25,000 cases of XDR-TB. Most cases are fatal.
TB globally and in our region
- Per capita, the global TB incidence rate is falling, but the rate of decline is very slow – less than 1%. There were 9.4 million new TB cases worldwide in 2009.
- 22 countries account for 80% of the tuberculosis cases in the world.
- Vietnam: 29,000 died from TB, 290,000 infected in 2010.
- China: 54,000 died from TB, 1.5 million infected in 2010.
- 500,000 people in South-East Asia died from TB in 2010.
- Bangladesh and Cambodia have the highest prevalence rates of TB in the world outside Africa.
- A third of all new cases are in India and China.
TB in Australia
The incidence of TB in Australia has remained at a stable rate since 1986. A total of 1,135 cases of TB were reported in Australia in 2007, representing a crude rate of 5.4 cases per 100,000 population
In 1960, the rate was closer to 40 per 100,000.
But TB is already expanding its reach into Australia via our closest neighbour Papua New Guinea (PNG).
The rate of TB in PNG has increased by 42 per cent in the past decade and is still rising, according to national health data. The WHO estimates about 3600 people in PNG die from TB every year, though uncertainties around surveillance and diagnosis mean the toll may well be higher.
Challenges in TB
Need for new drugs—rise of drug resistance-new drugs needed
The emergence of multidrug-resistant (MDR) TB and, more recently, extensively drug-resistant (XDR) TB has intensified the need for new TB drugs
Determining the role of genetics
TB genetics is complex—One in three people on earth carries the bacterium in their lungs… so why do only one in 10 become ill? There are three different scenarios when exposed: you become sick, your immune system fights back, or the bacteria sits in your lungs (latent).
About the Centenary Institute:
The Centenary Institute is an independent leader in medical research seeking improved treatments and cures for cancer, cardiovascular and infectious diseases. We are working to discover new prevention, early diagnosis and treatment options to enable each generation to live longer, healthier lives than the one before.
Centenary’s affiliation with the RPA Hospital and the University of Sydney means that our discoveries can be quickly applied to the fight against disease in the clinic. More at: http://www.centenary.org.au/