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 22 nd June 2015

The Brontes 7 Anne 6 Sibling number Emily 5 Branwell 4 3 Charlotte 2 Elizabeth 1 Maria 0 1800 1810 1820 1830 1840 1850 1860 Year 2

infection with Mycobacterium tuberculosis doesn’t necessarily lead to disease Latent TB infection (LTBI) 10% Active TB disease pulmonary extra-pulmonary 3

there’s a lot of it about... Estimated number Estimated number of cases, 2013 of deaths, 2013 9.0 million 1.5 million All forms of TB (8.6 – 9.4 million) HIV-associated TB 1.0 million 360,000 (1.0 – 1.2 million) Multidrug- ~ 480,000 ~ 210,000 resistant TB 4

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) 10% 10% Diabetes, chronic kidney disease, HIV increases immunosuppressant drugs, chemotherapy, PER probability of all increase chance of reactivation YEAR early progression HIV-TB is different Active TB • natural history HIV increases disease • symptoms probability of TB reactivation • diagnosis drug-susceptible drug-resistant pulmonary extra-pulmonary

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 =MDR R Rifampicin Z Pyrazinamide H H H H H H E Ethambutol R R R R R R Z Z E E 1 2 3 4 5 6 month 10

R e s p i r a t o r y T B m o r t a l i t y i n m a l e s i n E n g l a n d a n d W a l e s 4 0 0 3 0 0 2 0 0 trials of multidrug 0 therapy 0 ,0 0 0 r 1 1 0 0 e p te a R universal BCG vaccination 0 1 8 4 01 8 6 01 8 8 01 9 0 01 9 2 01 9 4 01 9 6 01 9 8 02 0 0 0 Y e a r N o t e : d a t a a g e - s t a n d a r d i z e d t o t h e 1 9 0 1 p o p u l a t i o n

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

WHO Calls Tuberculosis a Global Emergency 1993 April 24 th , 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. "Tuberculosis today is humanity's greatest killer, and it is out of control in many parts of 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."

what new tools can we bring to the battleground? • new vaccines • new diagnostic tests • new drugs

TB vaccines are not looking like a near-future solution Lancet 2013; 381: 1021-8 2800 six-month old infants No effect on TB disease No effect on TB infection 17

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

other experimental approaches to diagnosis include T-Bees (yes, really) 20

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% 21

new drugs and novel combinations treatment shortening • four months? treatment of MDRTB • bedaquiline and delamanid • recycling old drugs • new (short ish ) regimens

UK has been at the forefront from the beginning MDR treatment shortening Streptomycin and combination chemotherapy trials 2015 MRC. The prevention of streptomycin resistance by combined chemotherapy. Brit Med J 1952; 1: 1157-62 23

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