Anti TB Drugs

Evelyn B. Yumiaco M.D.Department of PharmacologySchool of MedicineAngeles University Foundation

Country PictureCountry Picture Population 2007 = 88 Million Global rank – 9th among HBCs Regional rank – 3rd among WPR

countries TB Incidence (New SS+)(New SS+) = 131/100,000 Case Detection Rate 2006 = 74% Cure Rate (New SS+)(New SS+) 2005 = 82% Success Rate (New SS+)(New SS+) 2005 = 90%

MORBIDITY 2009

1. ARI2. ALTI/PNEUMONIA3. BRONCHITIS/BRONCHIOLITIS4.HYPERTENSION5. ACUTE WATERY DIARRHEA6.INFLUENZA7. UTI8. TB (RESPIRATORY)9. INJURIES10. ACUTE FEBRILE ILLNESS

DEPARTMENT OF HEALTH

MORTALITY 2009

1. DISEASES OF THE HEART2. DISEASES OF THE VASCULAR SYSTEM3. MALIGNANT NEOPLASM4. PNEUMONIA5. ACCIDENTS6. TB (ALL FORMS)7. CHRONICLOWER RESPIRATORY DISEASES8. DIABETES9. NEPHRITIS/NEPHROTIC SYNDROME10. PERINATAL CONDITIONS

DEPARTMENT OF HEALTH

National TB Program Manual of Procedure (MOP)

HON. FRANCISCO T. DUQUE III, MD, MSc.

Secretary of Health Department of Health

December 2005

VISION, MISSION, AND GOAL OF THE NTP Vision: A country where TB is no

longer a public health problem Mission: Ensure that TB DOTS

services are available, accessible, and affordable to the communities in collaboration with the LGUs and other partners

Goal: To reduce prevalence and mortality from TB by half by the year 2015 (Millennium Development Goals)

D irectly

O bserved

T herapy

S hortcourse

A strategy!

DOTS Strategy: Elements

1. Political commitment to tuberculosis control

2. Facilities for the microscopic diagnosis of sputum smear–positive tuberculosis

3. An uninterrupted supply of good quality anti-tuberculosis drugs

4. Direct observation of therapy

5. Good record-keeping to facilitate assessment of the effectiveness of the control program

Direct Observation of Treatment

1. Who will undergo DOT? All smear (+) TB2. Who can be treatment partner?

Staff of the health center or clinic Member of the community such as the BHW,

local government official or former Tb patient. Member of the patient’s family (last priority)

3. Where to do DOT? in any accessible and convenient place (RHU, home, school)

4. How long is the DOT? whole treatment

CASE FINDING THE INDENTIFICATION AND

DIAGNOSIS OF TB CASES AMONG INDIVIDUALS WITH SUSPECTED SIGNS AND SYMPTOMS OF TB

DIRECT SPUTUM SAMPLE MICROSCOPY (DSSM) PRINCIPAL DIAGNOSTIC METHOD

CASE FINDING DIRECT SPUTUM

SAMPLE MICROSCOPY (DSSM) PROVIDES DEFITIVE

DIAGNOSIS PROCEDURE IS SIMPLE ECONOMICAL CAN BE AVAILABLE IN

REMOTE AREAS

TB SYMPTOMATIC(cough for 2 weeks or more)

Three (3) sputum collection

2 or 3 sputum (+) 1 smear positive all smears negative

Classify as smear-positive TB

Collect another 3 sputum specimens

Symptoms persist, collect another 3 sputum

specimens and refer to Medical Officer (refer to

next flow chart)

If all smear negative

If at least one (1) smear positive

Refer to Medical Officer(observe pt; give symptoma-tic treatment for 2 - 3 wks.)

Classify smear positive TB

Request for Chest Xray

If consistent with active TB If not consistent with active TB

Observe/further exams, if neededClassify as smear-positive TB

All 3 smears NEGATIVE

REFER to MHO(symp. Tx for 2-3 wks)

If symptoms persist, collect another three (3) sputum specimens

2 or 3 smear POSITIVE only one (1) smear positive all 3 smear NEGATIVE

Classify as SMEAR-POSITIVE TB

See previous slide CXR

Abnormal findings No abnormal findings

TB Diagnostic Committee Observation / further exam.

Consistent with active TB Not consistent with active TB

Classify as Smear-Negative TB Observation / further exam.

CLASSIFICATION OF TB CASES

PULMONARY TB SMEAR (+)

SPECIMEN WITH AT LEAST 2 SPUTUM (+) AFB SMEAR WITH OR WITHOUT X RAY ABNORMALITYONE SPUTUM (+) WITH RADIOGRAPHIC ABNORMALITYONE SPUTUM (+) WITH CULTURE (+)

SMEAR (-) THREE SPUTUM (-) WITH X RAY CONSISTENT WITH TB

EXTRA PULMONARY TB

M.Tb (+) smear /culture from extra pulmonary sitesHistological or clinical evidence consistent with active extra pulmonary tb and there is a decision to treat

NTP Classification of TB Cases

Types* Definition of TermsNew A patient who has never had treatment for TB

or who has taken anti-tuberculosis drugs for less than one month.

NTP TB classificationTypes Definition of Terms

Relapse A patient previously treated for tuberculosis who has been declared cured or treatment completed, and is diagnosed with bacteriologically positive (smear or culture) tuberculosis.

Failure A patient who, while on treatment, is sputum smear positive at five months or later during the course of treatment.

Return afterDefault (RAD)

A patient who returns to treatment with positive bacteriology (smear or culture), following interruption of treatment for two months or more.

TB classificationTypes Definition of Terms

Transfer-In A patient who has been transferred from another facility with proper referral slip to continue treatment.

Other All cases that do not fit into any of the above definitions. This group includes:

• A patient who is starting treatment again after interrupting treatment for more than two months and has remained or became smear-negative.

• A sputum smear negative patient initially before starting treatment and became sputum smear-positive during the tx.

TB classificationTypes Definition of Terms

Other All cases that do not fit into any of the above definitions. This group includes:

• A patient who is starting treatment again after interrupting treatment for more than two months and has remained or became smear-negative.

• A sputum smear negative patient initially before starting treatment and became sputum smear-positive during the tx.

• Chronic case-remained sputum (+) at the end of treatment

NTP: Outcomes of Treatment Treatment Completed

a patient who has completed treatment but has not met the criteria for cure or failure

A sputum smear-positive patient who has completed treatment but without DSSM follow - up during the treatment, or with only one negative DSSM during the treatment, or without DSSM in the last month of treatment.

Sputum smear negative who has completed treatment

NTP: Outcomes of Treatment Cure

a sputum smear-positive patient who has completed treatment and is sputum smear negative in the last month of treatment and on at least one previous occasion in the continuation phase

NTP: Outcomes of Treatment Died

a patient who died for any reason during the course of treatment

Transfer out A patient who transferred to another

DOTS facility with proper referral slip for continuation of treatment and whose treatment outcome is not known

NTP: Outcomes of Treatment Defaulted - a patient who

interrupted treatment for two consecutive months or more

NTP: Outcomes of Treatment Failed

A patient who is sputum smear-positive at five months or later during the treatment

An initially sputum smear-negative patient before starting treatment who becomes smear-positive during the treatment. (Note: This case will be re-registered as Other with a new TB case number.)

Drug symbol Cavity Macrophage Caseation

Rifampicin R ++ + +/0

INH H ++ + +

Ethambutol E +/0 +/0 0

Pyrazinamide Z 0 ++ 0

Streptomycin S +++ 0 0

Mechanism of Action

Treatment Regimens in the NTP

Regimen Type of TB Patient Drug / Duration of Treatment

Regimen I 2HRZE / 4HR

New pulmonary smear (+) cases New seriously ill pulmonary smear (-) cases w/ extensive lung lesions New severely ill extra-pulmo TB

HRZE for 2 mo during the intensive phase.HR for 4 mos during maintenance phase

Regimen II2HRZES/1HREZ / 5HRE

Failure cases Relapse cases Return after default RAD (smear +) Other (smear +)

HRZES for 2 mos. then HRZE for 1 mo. intensive phase.HRE for 5 mos as maintenance phase

Treatment Regimens in the NTP

Regimen Type of TB Patient Drug / Duration of Treatment

Regimen III2HRZ / 4HR

New smear(-) but with minimal pulmonary TB on radiography as confirmed by a medical officer New extra-pulmo TB (not serious)

HRZ for 2 mos. during the intensive phase.HR for 4 months as maintenance phase

Regimen IV Chronic case Still smear (+)after re treatment

Referred to a specialized facility/ provincial or city or NTP coordinator

NTP: DRUG DOSAGE ADJUSTMENT

Drug Dose per kg body weight and maximum dose

Isoniazid 5 (4-6) mg/kg, and not exceed 400mg daily

Rifampicin 10 (8-12) mg/kg, and not to exceed 600mg daily

Pyrazinamide

25 (20-30) mg/kg, and not to exceed 2g daily

Ethambutol 15 (15-20) mg/kg, and not to exceed 1.2g daily

Streptomycin

15 (12-18) mg/kg, and not to exceed 1g daily

Regimen Type of TB Patient MONITORING

Regimen I 2HRZE / 4HR

New pulmonary smear (+) cases New seriously ill pulmonary smear (-) cases w/ extensive lung lesions New severely ill extra-pulmo TB

2 ,4, 6

Regimen II2HRZES/1HREZ / 5HRE

Failure cases Relapse cases Return after default RAD (smear +) Other (smear +)

3,5,8

Regimen III2HRZ / 4HR

New smear(-) but with minimal pulmonary TB on radiography as confirmed by a medical officer New extra-pulmo TB (not serious)

2

Private Public Mix DOTSSTRATEGY ADOPTED BY THE NTP1. INCREASE CASE DETECTION2. SYNCHRONIZE DIAGNOSIS AND

TREATMENT IN THE PRIVATE AND PUBLIC SECTOR

• Type I (Privately initiated DOTS)

Private physician refer patients to private DOTS center

Drugs are provided by DOH

PUBLIC

P

PRIVATE

P

Examples:UST Makati MedDLSU MDHUnilab Friendly CareAUFMC UERM

COMPONENTS OF DOTS

PUBLIC PRIVATE

1.POLITICAL COMMITMENT + +

2. DIAGNOSIS BY SPUTUM MICROSCOPY

+

3. SUPERVISED TREATMENT(DOT)

+

4. UNINTERRUPTED SUPPLY OF DRUG

+

5. STANDARD REPORTING AND RECORDING

+

COMPONENTS PUBLIC PRIVATE

1.POLITICAL COMMITMENT + +

2. DIAGNOSIS BY SPUTUM MICROSCOPY

+

3. SUPERVISED TREATMENT(DOT)

+

4. UNINTERRUPTED SUPPLY OF DRUG

+

5. STANDARD REPORTING AND RECORDING

+

• Type II (Publicly initiated DOTS)

• Private physicians refer to govt DOTS center

P

P

PP

PUBLIC

Available in all health centers