1. Sarah Al-Obaydi M.B.Ch.B, MPH(c) Fulbright scholar

2. Tuberculosis Tuberculosis (TB) is an infection caused mostly by Mycobacterium tuberculosis. TB is a multisystem disease (affects most organs) TB can also be caused by other Mycobacteria like: M. bovis M. africanum M. microti M. canetti Not all Mycobacteria cause TB e.g., M. avium intercellulare complex M. tuberculosis

3. Tuberculosis (TB): History TB is an ancient disease Historically known by a variety of names, including: Consumption Wasting disease White plague

4. 4 Before TB drugs were available most went to sanatoriums: TB hospitals regimen of bed rest, open air, and sunshine TB patients who could not afford sanatoriums often died at home Sanatorium patients resting outside Tuberculosis (TB): History

6. Non-infected person Primary TB (usually in Lungs) Often Asymptomatic Latent TBActive TB Transmission by Respiratory droplets Healthy individual with good immunity Poor Immunity TB germs are put into the air when a person with TB disease of the lungs or throat coughs, sneezes, speaks, or sings

7. Latent TB vs TB Disease Latent TB Infection (LTBI) TB Disease (in the lungs) Inactive, contained tubercle bacilli in the body Active, multiplying tubercle bacilli in the body TST or blood test results usually positive Chest x-ray usually normalChest x-ray usually abnormal Sputum smears and cultures negative Sputum smears and cultures may be positive No symptomsSymptoms such as cough, fever, weight loss Not infectiousOften infectious before treatment Not a case of TBA case of TB

8. 8 Progression to TB Disease Risk of developing TB disease is highest in the first 2 years after infection Progression from Latent TB infection to TB disease can be prevented with TB drug (usually one TB drug): TB prophylaxis However, not practiced in many developing countries where TB is endemic Therefore detecting TB infection, early starting TB drugs helps to prevent new cases of TB disease

10. Non- infected person Primary TBLatent TBActive TB Prevent Transmission

11. How to Prevent TB Transmission? Isolate infectious persons Those with Lung TB disease only Treat TB dis. as soon as possible They stop shedding TB bacteria with in a few weeks after starting treatment

12. Non- infected person Primary TBLatent TBActive TB Prevent progression Testing Treating latent Control risk factors

13. Prevention of Latent TB to Active TB progression : Testing high risk groups for Latent TB Treating Latent TB Control risk factors

14. 14 TB in USA: High-Risk: Foreign- Born/Immigrants In 2011, foreign-born people 12 times likely to have TB Among US-born non- Hispanic blacks are six times more likely to have TB

15. HIV infection Diabetes Mellitus Prolonged steroids treatment Substance abuse Recent TB infection: If exposed to TB in the last 2 yrs High-Risk – decreased immunity:

16. Non- infected person Primary TBLatent TBActive TB Treat TB disease Treatment Challenges

18. Treatment of TB disease Several drugs for 6 to 9 months. Why? Regimens for treating TB disease have initial phase of 2 months continuation phase of either 4 or 7 months Treatment must contain multiple drugs to which organisms are susceptible Treatment with a single drug can lead to the development of drug-resistant TB

19. Initial Phase 8 weeks with 4 drugs (INH, RIF, EMB, Pyrazinamide) Most bacilli killed during this phase They don’t spread TB Continuation Phase 4- 7 months with 2 TB drugs only remaining Bacilli (in reservoirs) are cleared in this phase Treatment: Different Phases

20. Challenges to TB treatment and prevention: 1. Relapse: when treatment is not continued for long enough Surviving bacilli may cause TB recurrence 2. Multidrug resistant TB (MDR TB) is TB resistant to at least two of the best anti-TB drugs-INH and Rifampin. Mostly because of poor adherence to treatment regimen How to ensure adherence to treatment? Directly Observed Therapy (DOT)

21. Challenges 3. Drug interactions interfere with treatment In TB and HIV co-infection: many ART drug interact with Rifampin 4. Lack of awareness of TB or HIV status can prevent adequate treatment How to prevent this? Anyone who is newly diagnosed with HIV or TB should be tested for co-infection.

23. Resurgence of TB

24. Risk of TB disease The risk of developing TB disease 10% each year in people with HIV infection 10% over a lifetime if otherwise healthy

25. Globally: Dual Epidemic Globally TB is a leading cause of death in HIV patients What is the leading cause of death among HIV patients in USA? Hepatitis C

26. Effect of CD4 count on risk of TB among HIV-infected people 0 5 10 15 20 ItalyUSSouth Africa >350200-350<200 Incidence of TB (per 100 pyrs) Antonucci JAMA 1995;274:143; Markowitz Ann Int Med 1997;126:123; Badri Lancet 2002;359:2059

27. Generally same as for those without HIV- infection But there are challenges - Drug interaction between TB and HIV drugs - Adherence to TB and HIV drugs Treatment of TB in HIV co-infection

28. In patients with TB & HIV infection If TB is not diagnosed ART started for HIV treatment Patient worsens This is a PARADOXICAL reaction Immunity is improving but patient appears worse temporary and usually not dangerous But important to inform patient, watch and manage Immune Reconstitution Inflammatory Syndrome (IRIS)

29. Quiz The risk of developing TB disease in healthy v/s HIV population? 10% each year in people with HIV infection 10% over a lifetime if otherwise healthy What is the leading cause of death among HIV patients in USA? Hepatitis C