Module 5: Principles of Treatment

1. Module 5: Principles of Treatment Session Overview • Aims of TB Treatment • General Principles • Treatment Guidelines

2. Learning Objectives • Describe 3 basic principles of TB treatment • Explain the difference between the 4 treatment categories (Cat I-IV) • Understand and describe when and why a regimen may be extended

3. Aims of TB Treatment • Cure the patient of TB • Prevent death from active TB or its latent effects • Prevent relapse of TB • Decrease transmission of TB to others • Prevent the development of acquired resistance

4. Fundamental Responsibility and Approach in TB Treatment • Assure that appropriate regimen is prescribed by MOs • Ensure successful completion of therapy (adherence) • Utilize directly observed therapy (DOT) as standard-of-care

5. Adherence • Nonadherence is a major problem in TB control • Patient education is the most effective tool to prevent default—USE IT!! • Use case management and directly observed therapy (DOT) to ensure patients complete treatment

6. Why Do Patients Default? • As their condition improves they may feel better and decide they don’t need meds • They may experience side effects • Forgetfulness/lack of a reminder! • Travel to cattle posts without refills • Difficulty getting to clinic b/c of work/distance

7. What is Case Management? • Assignment of responsibility within clinic to • oversee patient monitoring • -bacteriology • -DOT • -side effects • Systematic regular review of patient data • Plans in place to address barriers to adherence BEFORE default occurs

8. Directly Observed Therapy (DOT) • Health care worker watches patient swallow • each • -Dose of medication • -Every pill, every day • -Self-administered is NOT DOT • REMEMBER • DOT for all patients on all regimens • NO exceptions

9. DOT in Ghantsi…Can you identify the main elements?

10. Directly Observed Therapy (DOT) • DOT can lead to reductions in relapse and acquired drug resistance • Use DOT with other measures to promote adherence • DOT is the key to CURE

11. Treatment of TB Disease

12. Epidemiologic information e.g., circulating strains, resistance patterns Clinical, pathological, chest x-ray findings Microscopic examination of acid-fast bacilli (AFB) in sputum smears Factors Guiding Treatment Initiation

13. Basic Principles of Treatment • Determine the patient’s HIV status- this could save their life! • Provide safest, most effective therapy in shortest time • Multiple drugs to which the organisms are susceptible • Never add single drug to failing regimen • Ensure adherence to therapy (DOT)

14. Standard Treatment Regimen • Initial phase: standard four drug regimens (INH, RIF, PZA, EMB), for 2 months • Continuation phase: additional 4 months

15. Treatment of TB for HIV-Negative Persons • 2 months HRZE followed by 4HR • Four drugs in initial regimen always • Isoniazid (INH) • Rifampin (RIF) • Pyrazinamide (PZA) • Ethambutol (EMB) or streptomycin (SM) • (Streptomycin replaces Ethambutol in TB meningitis)

16. Treatment of TB for HIV-Positive Persons • Management of HIV-related TB is complex • and patient care needs to be coordinated with • IDCC • HIV-infected patients already on ARVs who develop TB should begin anti-TB meds immediately • Patients on 1st line ARVs may start Category I ATT. • Patients on ARV regimen with efavirenz • should be reviewed by a specialist. • If patient is on 2nd or 3rd line ARVs discuss with specialist before starting ATT.

17. Treatment of TB for HIV-Positive Persons • HIV-infected TB patients should be evaluated for ARVs immediately • Pts with CD4<=200 should start ARVs within two weeks after start of ATT • Pts with CD4s>200 may defer until end of ATT

18. Extrapulmonary TB • In most cases, treat with same regimens • used for pulmonary TB Bone and Joint TB, Miliary TB, or TB Meningitis in Children • Treatment extended > 6 months depending on site of disease • In TB meningitis Streptomycin replaces Ethambutol

19. Infants and Children • Children • Children are at an increased risk for TB disease • If the disease is severe (meningitis, military TB, etc.) use Category I treatment, SM replaces EMB in small children • For less severe disease: treat with category III regimen • In most cases, treat with same regimens used for adults Infants • Treat as soon as diagnosis is suspected

20. Dosing of CPT in Children

21. Multidrug-Resistant TB (MDR TB) • Presents difficult treatment problems • Lengthy, multi-drug regimen • Side effects common • Management complex • Treatment must be individualized • Clinicians unfamiliar with treatment of MDR TB should seek expert consultation • Always use DOT to ensure adherence

22. Multidrug-Resistant TB (MDR TB) Con’t • 6 months intensive treatment (always including an injectable drug) followed by at least an 18 month continuation phase • Only specialist physicians at the referral hospitals can initiate MDR treatment

23. Treatment Monitoring • Sputum smear microscopy for AFB at 2 months and 6 months • If positive at two months, repeat at 3 • If still smear positive at 3 months, continuation phase (4HR) is still started while awaiting DST results • Continue drug-susceptibility tests if smear-positive after 3 months of treatment

24. Adverse Drug Reactions

25. Adverse Drug Reactions

26. Common Adverse Drug Reactions

27. Drug Interactions • Relatively few drug interactions substantially change concentrations of antituberculosis drugs • Antituberculosis drugs sometimes change concentrations of other drugs -Rifamycins can decrease serum concentrations of many drugs, (e.g., most of the HIV-1 protease inhibitors), to subtherapeutic levels -Isoniazid increases concentrations of some drugs (e.g., phenytoin) to toxic levels