Module 5: Principles of Treatment Session Overview –Aims of TB Treatment –General Principles –Treatment Guidelines

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

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

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

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

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

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

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

DOT in Ghantsi…Can you identify the main elements?

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

Treatment of TB Disease

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

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)

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

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)

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 1 st line ARVs may start Category I ATT. Patients on ARV regimen with efavirenz should be reviewed by a specialist. If patient is on 2 nd or 3 rd line ARVs discuss with specialist before starting ATT.

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 Treatment of TB for HIV-Positive Persons

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

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 Infants and Children

Dosing of CPT in Children Age and weight of child Recommended daily dose Suspension 5ML syrup =200mg/40 mg Child Tablet 100mg/20mg Single strength adult tablet 400mg/80mg Double Strength adult tablet 800mg/160m g 6 weeks to 6 months (<5kg) 100mg sulfamethox asole/20mg trimethoprim2.5ml1 tabletn/a 6 months to 5 years (5- 15Kg) 200mg sulfamethox asole/40mg trimethoprim5ml2 tablets1/2 tabletn/a 6 to post pubertal 400 mg sulfamethox asole/80mg trimethoprim10ml4 tablets1 tablet1/2 tablet Post pubertal and Adults 800 mg sulfamethox asole/160mg trimethoprimn/a 2 tablets1 tablet

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

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

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

Caused byAdverse ReactionSigns and Symptoms Any drugAllergySkin rash EthambutolEye damageBlurred or changed vision Changed color vision Isoniazid, Pyrazinamide or Rifampin HepatitisAbdominal pain Abnormal liver function test results Fatigue Lack of appetite Nausea Vomiting Yellowish skin or eyes Dark urine Adverse Drug Reactions

Caused byAdverse ReactionSigns and Symptoms IsoniazidPeripheral neuropathy Tingling sensation in hands and feet PyrazinamideGastrointestinal intolerance Arthralgia Arthritis Upset stomach, vomiting, lack of appetite Joint aches Gout (rare) StreptomycinEar damage Kidney damage Balance problems Hearing loss Ringing in the ears Abnormal kidney function test results

Caused byAdverse ReactionSigns and Symptoms Rifamycins Rifabutin Rifapentine Rifampin Thrombocytopenia Gastrointestinal intolerance Drug interactions Easy bruising Slow blood clotting Upset stomach Interferes with certain medications, such as birth control pills, birth control implants, and methadone treatment Common Adverse Drug Reactions

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