cHRYSós 2 0 2 3

TB DOTS
Dr. ANA NOELLE DOMINGUEZ
B5m2
Lecture

3. intracellular bacilli
- in acidic compartments of macrophages
Day Pathogenic Events in Tuberculosis - killed by sterilizing drugs
4. TB persisters
0 Inhaled M Tb deposits in alveoli or terminal airways - in hypoxic microenvironments
- non-responsive to most anti-TB drugs
<5 Macrophage (MC) phagocytize M Tb but unable to kill it
(requires immunologic activation/ needs sensitization TREATMENT RECOMMENDATIONS
from past infection) 1. Multiple drugs to witch the organisms are susceptible
2. Drugs must be taken regularly
3. Must continue for a sufficient length of time
5-10 Infected MCs bring M. Tb to the regional nodes. Chest x-
ray may show the Ranke’s complex:
DEFINITION OF TERMS
a. peripheral pneumonitis (Ghon’s focus)
TB DISEASE REGISTRATION GROUPS
b. hilar lymphadenopathy
c. lymphangitis
Primary TB gives minimal symptoms
(Ghon’s focus represents inflammation and damage in the
lung parenchyma which result from the pro inflammatory
substances released from killed or infected macrophages. )

11-20 M Tb reaches the circulation from the lymphatics.

This M. Tb bacteremia seeds all organs
- TB meningitis
- Miliary TB (may seed the lungs again)

Week 3-6 Cell-mediated immunity develops

PPD/Tuberculin skin test (TST) reactive
Prevents further growth of the MTb, most are killed
Some remain dormant in granulomas
(strong immunity)

Reactivation Weakened immunity

day TB in the dormant sites undergo
Rapid multiplication
Symptomatic

OBJECTIVES OF TB TREATMENT:
1. Cure of the patient by rapid elimination of most of the metabolically
active and rapidly replicating bacilli
2. Prevent death form active TB or its late effects
3. Prevention of relapse by eliminating slowly and intermittently- - Isoniazid-resistant TB
multiplying bacilli o MTB strains in which resistance to isoniazid and
susceptibility to rifampicin have been confirmed in vitro
4. Prevention of drug resistance by using a combination of
- Rifampicin-resistant TB (RR-TB)
drugs
o MTB strains that are NOT susceptible to rifampicin on the
5. Decrease TB transmission basis of drug-susceptibility testing
o Eligible for treatment with MDR-TB (multidrug-resistant
WHY SO MANY DRUGS? WHY THE PROLONGED TREATMENT? TB) regimens
TB treatment requires multiple drugs for a minimum of 6 months-1 o Can be detected through Gene Xpert
year - Polyresistance
CHARACTERISTICS OF MTB o Resistance to more than one first-line anti-TB drug, other
1. Live in several sites within the host than isoniazid and rifampicin together
- Each site contains organisms with different - Multidrug-resistant TB (MDR-TB)
o population sizes o Resistance to both isoniazid and rifampicin has been
o replication rates, metabolic activities confirmed in vitro
2. Replicate slowly - First-line TB drugs (FLD)
- Can remain dormant for prolonged periods o Agents used to treat drug-susceptible TB
- Can be eradicated only during replication § Ethambutol
3. Naturally-occurring drug-resistant mutants are present within large bacterial § Isoniazid
populations even before chemotherapy is started § Pyrazinamide
§ Rifampicin
Subgroup of M. tuberculosis populations - Streptomycin is now considered as a second-line TB medicine!
1. Actively - growing bacilli - Second-line TB drugs (SLD)
- in open cavities o Agent/s reserved for the treatment of drug-resistant TB
- killed by bactericidal drugs
2. Slowly multiplying/intermittently replicating bacilli
- in caseous lesions
- killed by STERILIZING drugs
cHRYSós 2 0 2 3
TB DOTS
Dr. ANA NOELLE DOMINGUEZ
B5m2
Lecture

TREATMENT PRINCIPLES
- All diagnosed TB cases shall be provided with adequate and
appropriate anti-TB treatment regimen promptly.
- Anti-TB treatment shall be done through a patient-centered, directly
observed treatment (DOT) to foster adherence
o In a setting that is the most accessible and acceptable to
the patient
- Treatment shall based on:
o anatomical site
o bacteriologic status
o history of previous treatment
o drug resistance
- All retreatment should be screened for MDR-TB before treatment
initiation Gastric aspirate – when children cough they swallow their sputum
- Anti-TB regimen shall comprise of at least 4 first-line drugs

WHAT IS DOTS?
- Directly-Observed Treatment Short course
- Endorsed by the WHO and the International Union Against
Tuberculosis and Lung Diseases (IUATLD) to detect and cure TB
patients
- It involves direct observation of medication intake
- Ensures correct combination and dosage
- Maximizes the likelihood of completion of therapy INTENSIVE PHASE (3-4 DRUGS)
- Prevents the development of drug resistance - Efficient killing of ACTIVELY DIVING organisms
- Rapid reduction of large bacillary population
INITIATION OF TREATMENT - Relief of symptoms
1. Inform/educate the patient that they have TB disease - Terminates transmission
- Basic information: cause, transmission, signs and symptoms, - Prevents the emergence of drug resistance
diagnosis, prevention
- Duration of treatment (at least 6 months)
- Regular follow-up for monitoring treatment response
- Potential adverse events

2. Determine the weight (esp for children) and record baseline clinical findings.
3. Assign the appropriate DS-TB (drug susceptible TB) regimen based on results
of DST (Xpert), or, if not available, based on the history of treatment.
CONTINUATION PHASE (2-3 DRUGS)
- Kills SLOWLY or INTERMITTENTLY-diving bacilli
- Sterilizes lesion
- Prevent relapse

PROPERTIES OF ANTI TB DRUGS

1. Bactericidal activity
- Killing in log-phase growth
2. Sterilizing activity
- Kill slowly-growing or intermittently-replicating bacilli
3. Ability to prevent resistance

ISONIAZID (H) AND RIFAMPICIN (R)

- Most effective bactericidal drugs
- Active against ALL populations of TB bacilli

RIFAMPICIN (R)
- Also the most potent sterilizing drug available

PYRAZINAMIDE (Z) AND STREPTOMYCIN (S)

- bactericidal against SOME populations of TB bacilli

PYRAZINAMIDE (Z)
- only active in the ACIDIC intracellular environment of macrophages
- Sterilizing effect in areas of acute inflammation

ETHAMBUTOL
- with other drugs, prevents emergence of resistant bacilli

STREPTOMYCIN
- bactericidal against RAPIDLY MULTIPLYING bacilli
- exerts effect on high O2 tension and neutral pH
cHRYSós 2 0 2 3
TB DOTS
Dr. ANA NOELLE DOMINGUEZ
B5m2
Lecture

Initiation of treatment cont. Initiation of treatment cont.

4. Instruct on proper dosage based on weight 5. Other important points to consider
- Allocating the required supply for the entire duration of the
treatment
- Determining comorbidities; adjust the regimen when necessary (px
with renal dse)
- HIV counseling and testing to all TB patients ≥15 yo
6. Discuss the appropriate treatment adherence mechanism. Consider the MOST
SUITABLE LOCATION of drug intake and treatment supporter based on the
(take tablets at the same time) patient’s condition. Options include:
Location:
- Home
- Community
- Workplace
- Health facility
Treatment supporter
- Oriented family member
- Trained lay volunteer
- Trained Health worker
*the choice should be mutually agreed upon between the patient and the
provider

If daily intake is NOT in the health facility:

- Initially provide a one-week supply to the treatment supporter
- Adjust the supply later to a maximum of MONTHLY dispensing
- Regular communication between the HCW and the patient
(psychosocial support)

MONITORING TREATMENT RESPONSE

- Follow up TWO WEEKS after initiation of treatment and then at least
MONTHLY thereafter
- Perform clinical assessment during follow-up visits
1. Weigh patient monthly. Adjust the dose accordingly
2. Ask about resolution of TB signs and symptoms
3. Manage any adverse drug reactions
4. Continue the management of co-morbid conditions

(tablet can be dissolved in water)

(inform px of the adverse reactions)

(gradual reintroduction)
cHRYSós
2 0 2 3
TB DOTS
Dr. ANA NOELLE DOMINGUEZ
B5m2
Lecture

TREATMENT OUTCOMES

TUBERCULOSIS PREVENTIVE TREATMENT

- Treatment offered to individuals who are at risk of developing active
TB disease to reduce that risk
- Also referred to as LTBI (latent TB infection) treatment or preventive
therapy
Terms:
- Household contact
o A person who shares the same enclosed living space as
the index person with TB
- Close contact
o A person who shares an enclosed space, other than the
household, for extended periods during the day with the
index person with TB during the 3 months before
commencement of the current treatment episode
- Index case
o Initially identified people with TB of any age in a specific
household or other comparable setting in which others
may have been exposed
- Latent TB infection (LTBI)
o A state of persistent immune response to stimulation by
MTb antigens with no evidence of clinical manifestations
of active TB disease

Who are eligible for TPT? (populations at risk for developing TB)
1. People living with HIV (PLHIV) regardless of history of contact
2. ALL household contacts of bacteriologically-confirmed PTB
3. Children less than 5 years old who are housel=hold contacts of
clinically-diagnosed PTB
4. Close contacts of bacteriologically-confirmed PTB (outside the
household)
5. Other risk groups (dialysis, transplant, TNF, scoliosis)
cHRYSós 2 0 2 3
TB DOTS
Dr. ANA NOELLE DOMINGUEZ
B5m2
Lecture

For contacts whose index case is MDR-TB or RR-TB: ISONIAZID PREVENTIVE THERAPY
- TPT should NOT be given - IPT dose: INH 10mg/kg/day
- Should be followed up every 6 months for at least 2 years with - Assess the child every 2 months and check for signs and symptoms
o Symptom screening of TB disease
o Chest x-ray screening, or
- If the child develops tb DISEASE: STOP IPT and treat as TB
o Xpert test
disease
- Exclude active TB prior to considering TPT
o TB signs and symptoms BABY BORN TO MOTHER WITH TB DISEASE
o Do chest xray - Assess the newborn
- Well newborn (absence of signs or symptoms presumptive
Do I need to perform a Mantoux test/ Tuberculin Skin Test (TST) on all these high- of TB)
risk individuals? o do not give BCG yet!
o Give TB preventive therapy
o Give pyridoxine 5-10mg/day
- At the end of the treatment, perform TST
o If TST negative or not available, give BCG
- TPT is not necessary if the mother has received >2 months of
anti-TB treatment and is not considered infectious
- A mother on anti-TB drugs can SAFELY continue to breastfeed
o Feed the baby before taking the medications
o Most anti-TB drugs found in breastmilk are in
concentrations equal to only a small fraction of
therapeutic dose used in infants
o Pyridoxine supplement to the infant
- The mother and baby should stay together
- The baby may be breastfed while on TB preventive treatment