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Centenary Institute TB researcher Dr Bernadette Saunders talks about tuberculosis and her team's research into genetic susceptibility
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Unraveling the Mysteries of Tuberculosis
Bernadette SaundersHost Response to Tuberculosis
Mycobacterial Research
TB- Consumption
Many famous artists died of TB
DH Lawrence, Robert Louis Stevenson, George Orwell, Emily & Charlotte Bronte, Chopin, Gauguin, Chekov, Keats, Florence Nightingale, Numerous Kings of France/England
TB an ancient disease
• Studies have identified TB in mummies from Peru and Egypt 3000-5000yrs old.
Dr Granvilles mummy on display at the British Museum in LondonDied 2600 yrs ago from TB
TB The Global Disease
• World Health Organisation estimates that 1/3 of the world (over 2 billion people) are infected with TB
• 9-10 million new cases of clinical TB every year
• 1.8 million deaths annually
• TB is the number one killer of HIV/AIDS patients
TB – The Global Challenges
• We NEED A BETTER VACCINE- – The current vaccine, known as BCG fails to provide life-
long immunity in developing countries
• We NEED NEW ANTIBIOTICS to treat and cure TB, – treatment requires 6-12 months of continuous, multiple
(usually 4) antibiotic treatment
– Multi-drug resistant strains of TB are increasing
– Much harder to treat and may require long periods of quarantine
– 450,000 MDR cases of TB in 2009.
TB Disease
• 90% of people infected with TB bacteria, never develop TB disease (never get sick)
• But 10% of 2 billion is a lot of people at risk
• WE NEED A WAY TO DETERMINE WHO IS MOST AT RISK of getting sick-
TB – The BIG Questions
• Why do 10% people develop TB disease?
• How do we predict those people who are most at risk of developing TB disease?
TB- The Risk Factors
Host
Genetic
Mycobacterium
Virulence
Dose
Other mycobacterial exposure
Environment
Poverty, crowding,
social disorder
Nutrition
Infections – HIV
P2X7 Receptor and Control of TB
P2X7 Receptor
Highly expressed on White blood Cells that eat TB (macophages)
Activation of this receptor is one mechanism of killing TB.
Identified a single amino acid change in this receptor A1513C
Reduced killing of TB
0
0.25
0.5
0.75
1
1.25
Wild-type Homozygote
Lo
g1
0 r
ed
uct
ion
in b
act
eri
al v
iab
ility
(A
TP
pu
lse
d -
un
tre
ate
d c
ells
)
Study to determine if the SNP in P2X7 increases susceptibility to TB
Refugees from Southwest Sydney screened for LTBI upon arrival
24652
Latent TB
8609
Subjects with TB in NSW
11913.6 year median follow up
Enrolled in Liverpool genotyping study
>200 active disease free
subjects
1513 C allele is associated with increased risk of developing TB
AA(Normal)
AC/CC (mutant)
% with C OddsRatio
p
Control 105 62 37 - -
Extrapulmonary TB 9 21 70 4.0 .001
Vietnam-Australia TB Partnership
Collect DNA from1500 TB patients and 1500 controls to screen for SNPs that may be associated with increased risk of developing TB.
National Lung HospitalHanoi
Tuberculosis Research ProgramNational Lung HospitalHanoi Vietnam•A/Professor Dinh Ngoc Sy•Dr Nguyen Viet Nhung •Nguyen Van Hung •Phan Minh Tuan, •Nguyen Kim Cuong •Dr Phuong •Dr Ngoc
Purinergic Research Group, Nepean Hospital• Jim Wiley• Ronald Sluyter• Kristen Skarratt
Woolcock Institute• Guy Marks• Kitty Ng
Group Photo
You Can Help!