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

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0.75

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Wild-type Homozygote

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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

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