1. TUBERCULOSIS Fai Hassan & Rashida Brown

2. What is TB? A lung infection Mostly caused by M. tuberculosis Generation time 15-20 hrs Genetically diverse Aerobic, Gram-positive No outer cell membrane High lipid content in cell wall Infects alveolar macrophages Immune response is very complicated

3. Stages of Infection

4. Picture of M. tuberculosis

5. TB: Not so humble beginnings Index case: The mystery of the 500 000 year old mummy 3000 BCE – 100 CE: Independent international epidemics Treatments varied from urine to blood, and from living in the mountains to living underground Middle ages – 1850s Death toll rises to 25%

6. Franz Kafka George Orwell Most of the Brontë family Louis Braille Famous Victims of TB

7. 19th & 20 th Centuries 1993 TB is worldwide epidemic 1980s Vaccination campaign 1967 Rifampicin becomes part of treatment 1952 Isoniazid is discovered 1944 Streptomycin is discovered 1906 BCG vaccine is discovered 1882 Robert Koch discovers M. tuberculosis 1854 First sanatorium is opened

8. The Vaccination Campaigns of TB Started in the 1940s WHO was under a lot of criticism for the campaign Vaccination campaign of the 1980s Why? Because of MDR-TB & HIV Vaccination rejuvenated in 2006 Why? Because of XDR-TB Also because of the South African outbreak (discussed later)

9. Vaccination Campaign: New Hope Standard Vaccine: BCG Safety concern with HIV+ patients Potential solution for HIV+ patients: M. viccae Vaccines currently in development: MVA85A rBCG30 72F fusion protein ESAT6-Ag85b fusion protein

10. What about TB in Canada?

12. New Smear Positive Cases in Canada 1990-2007

13. Global TB Incidence Comparison

14. Diagnosis Skin Test Test exposure to TB PPD is injected just under skin of the inner forearm AFB Smear and culture Acid-fast bacillus Positive cultures identify the mycobacterium and drug resistance

15. Diagnosis Chest X-Ray Gold Test Whole-blood test to diagnose LTBI and tuberculosis TB disease

16. Chest X-ray of Patient with TB

17. Treatment Protocol DOTS Directly Observed Treatment, Short-course Most efficient and cost-effective method of treating TB Integrated Strategy Appropriate diagnosis of TB Registration of each patient detected Standardized multi-drug Individual patient outcome evaluation

18. DOTS costs only US $3 - $7 for every healthy year of life gained Fact

19. TB Medication The most common anti-TB medicines are: Isoniazid Rifampicin Pyrazinamide Ethambutol Minimum of 3 drugs over a 6-month period Isoniazid, Rifampicin and Pyrazinamide for 2 months Followed by Isoniazid and Rifampicin for a further 4 months

20. Drug Resistance The improper use of antibiotics in chemotherapy of drug- susceptible TB patients Administration of improper treatment regimens by health- care workers Failure to ensure that patients complete the whole course of treatment Treatment requires extensive chemotherapy for up to two years

21. Drug Resistant TB Multidrug-resistant TB (MDR-TB) Does not respond to first-line drugs Bacillus resistant to at least Isoniazid and Rifampicin Present in all countries Extensively drug-resistant TB (XDR-TB) Does not respond to second-line drugs Extremely difficult to treat Cases have been confirmed in more than 50 countries

22. MDR-TB

24. Geographic Distribution of XDR-TB

25. Current Issues Rapid spread due to increased air travel and immigration Immense socioeconomic burden Growing at-risk populations Instances of limited access to diagnosis and treatment

26. Poverty Majority of TB-related deaths are in the developing world There were 9.27 million new TB cases in 2007 80% were in 22 countries 13 of the 15 countries with the highest estimated TB incidence rates are in Africa Half of all new cases are in six Asian countries Bangladesh, China, India, Indonesia, Pakistan and the Philippines

27. Gapminder Number of Infectious TB Cases Reported vs. Poverty (% living below nationally defined poverty line) Gapminder graph

28. TB Distribution in 2006

29. Poverty distribution in 2006

30. TB/HIV Co-infection Major cause of death among people living with HIV/AIDS Compromised immune systems A total of 1.77 million people died from TB in 2008, 456 000 of those people were living with HIV 9.4 million new cases in 2008, 1.4 million are HIV-related Most of these cases in Sub-Saharan Africa Collaborative TB/HIV programming is needed

31. HIV prevalence in incident TB cases (%), By Country, Total, 2007

32. TB Vaccination of HIV+ Individuals New TB vaccine specifically designed for HIV-positive people Pre-clinical trials with guinea pigs Safer and more potent than the current TB vaccine Current BCG vaccine can cause serious long-term complications if HIV weakens the immune system New method to limit replication of the vaccine in the body Enough to stimulate the immune system to produce T cells, but not enough to overwhelm the immune system

33. Gender Higher TB mortality in men than among women TB is a leading infectious cause of death among women Affects women mainly in their economically and reproductively active years Tremendous social impact Annually, 750 000 women die of TB Over 3 million contract the disease Accounts for about 17 million DALYs

34. Prisons The level of TB, and MDR-TB in prisons significantly higher than that of the civilian population Due to: Late diagnosis, inadequate treatment, overcrowding, poor ventilation and repeated transfers HIV infection and other pathology more common in prisons (e.g. malnutrition, substance abuse)

35. Smokers Smoking increases the risk of TB disease by more than two-and-a-half times More than 20% of global TB incidence may be attributable to smoking

36. Correlation between Smoking and TB

37. Current Research LXR proteins in the mouse immune response to airway infection New target for therapeutics Molecules that activate LXRs provided protection from both a new infection and established infections Using gene chips to look at how TB bacteria behave in different environments Slowly growing bacteria are non-responsive to treatment with isoniazid Reason why it takes six months to treat pulmonary TB successfully

38. Halve the prevalence of infectious TB as well as TB-attributable mortality, and begin to reduce incidence. 2015 Millennium Development Goal

39. Millennium Development Goal Stop TB Strategy: Pursue high-quality DOTS expansion Address TB/HIV, MDR-TB, and at-risk groups Contribute to health system strengthening Engage all care providers Empower people with TB through partnership Promote research