TB the global picture Dave Moore Consultant in Infectious Diseases - - PowerPoint PPT Presentation

TB – the global picture

Dave Moore

Consultant in Infectious Diseases and Tropical Medicine UCLH member event 22nd June 2015

1 2 3 4 5 6 7 1800 1810 1820 1830 1840 1850 1860

Year Sibling number

Anne Emily Branwell Charlotte Elizabeth Maria

The Brontes

2

Latent TB infection (LTBI) Active TB disease 10%

pulmonary extra-pulmonary

infection with Mycobacterium tuberculosis doesn’t necessarily lead to disease

3

Estimated number

• f cases, 2013

Estimated number

• f deaths, 2013

1.5 million 9.0 million

(8.6–9.4 million)

~ 480,000 All forms of TB Multidrug- resistant TB HIV-associated TB 1.0 million (1.0–1.2 million) 360,000 ~ 210,000

there’s a lot of it about...

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the risk of TB is greatest if you are a citizen of sub-saharan Africa

India, China, Indonesia, Nigeria, Bangladesh, Pakistan, South Africa account for 5.1m cases alone 4100 deaths every single day = 10 Boeing 747s. Every day.

Latent TB infection (LTBI) Active TB disease 10%

pulmonary extra-pulmonary drug-susceptible drug-resistant

HIV increases probability of TB reactivation

10% PER YEAR

HIV-TB is different

• natural history
• symptoms
• diagnosis

HIV increases probability of early progression Diabetes, chronic kidney disease, immunosuppressant drugs, chemotherapy, all increase chance of reactivation

Source: TB Alliance website

Diego

Cough and fever 1/52 Cough and fever 3/52 Night sweats 1/52 Sputum smear microscopy

treatment of active TB disease requires standardized drug regimen for six months H Isoniazid R Rifampicin Z Pyrazinamide E Ethambutol

1 2 3 5 4 6 E Z R H E Z R H R H R H R H R H month

=MDR

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universal BCG vaccination trials of multidrug therapy

Enarson and Rouillon, 1998 Canadian Inuit 1967 Norway 1927 Tanzania 1990

1993

"Tuberculosis today is humanity's greatest killer, and it is out of control in many parts

• f the world," said Arati Kochi, manager of

WHO's tuberculosis program, at a news conference announcing a plan to combat what has been dubbed the "forgotten epidemic." WHO Calls Tuberculosis a Global Emergency April 24th, 1993 Reuters

LONDON — The World Health Organization on Friday declared tuberculosis a global emergency, saying the disease will claim more than 30 million lives in the next decade unless action is taken now.

what new tools can we bring to the battleground?

• new vaccines
• new diagnostic tests
• new drugs

Lancet 2013; 381: 1021-8 2800 six-month old infants

No effect on TB disease No effect on TB infection

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TB vaccines are not looking like a near-future solution

latent TB infection can now be diagnosed by either a skin test or a blood test

tuberculin skin test IGRA blood test

active TB disease can now be diagnosed within 2 hours by detection of TB DNA

culture can take weeks PCR can be done in hours

MTB

Lowenstein-Jensen culture Xpert MTB/RIF molecular assay

• ther experimental approaches to

diagnosis include T-Bees (yes, really)

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MDR treatment in 2015 – not pretty

• treatment success

– Standardized regimen 54% – Individualized regimen 64% – “Bangladesh regimen” 88% cure

• estimated costs in the U.S.

– MDR $134,000 – drug-susceptible TB $17,000

• 1.6% of UK TB is MDR

% of TB that is MDR New patient Previously treated Swaziland 15% 50% Uzbekistan 23% 62%

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new drugs and novel combinations

treatment shortening

• four months?

treatment of MDRTB

• bedaquiline and delamanid
• recycling old drugs
• new (shortish) regimens

UK has been at the forefront from the beginning

Streptomycin and combination chemotherapy trials MDR treatment shortening 2015

• MRC. The prevention of streptomycin

resistance by combined chemotherapy. Brit Med J 1952; 1: 1157-62

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in summary

• TB is not a historical footnote
• global TB control is a formidable challenge

– HIV and increasingly diabetes – multidrug-resistant TB

• new diagnostics and drugs starting to help