TUBERCULOSIS

in Infancy and Childhood

JOVI NOREEN SOTES MD
SOURCE:
OBJECTIVES:
To discuss TB in infancy and childhood in the
Philippines as to :
• Epidemiology
• Microbiology
• Pathogenesis
• Clinical forms
• Diagnosis
• Management
 Global Target
• Millennium Development Goal 6 (Set for
2015):
• Target 6c: to have halted and begun to
reverse the incidence of TB (target 6C)

• Stop TB Partnership:
• 2015: 50% reduction in TB prevalence
and deaths from 1990 levels
• 2050: elimination (<1 case per million
population)
TB Situation
• half a million children become ill with TB each year
• 70-80% (Pulmonary TB)
• 2014  9.6 million people were estimated to be ill with TB
• 5.4M (men) | 3.2M (women) | 1 Million (Children)
• Among Pulmonary TB 58% (bacteriologically confirmed)
• 359,000 new relapse cases among children
• Death : (890,000) MEN + (480,000)Women + (140,000) Children
• Globally, TB mortality rate (excluding death amongs HIV+ people) fell by
47% between 1990 and 2015 narrowly missing the target of a 50%
reduction
Mycobacterium Tuberculosis

• Aerobic, Nonmotile, Slightly curve or Straight, Acid

Fast bacilli
• Classified into 2:
• M. Tuberculosis Complex ( M. tuberculosis, M.
bovis, M. caprea, M. microti, M. canetti)
• Non-tuberculous Mycobacteria (M avium
intracellulare, M. kansasii and others)

• Grows in 35C-40C
• Trehalose dimycolate (cord factor) and sulfatides
• Lipoarabinomannam( LAM)
 Definition of Terms
TB exposure condition in which a child is in close contact with contagious adult or adolescent TB
case, but without any sign and symptoms of TB , with negative TST reaction, no
radiologic and laboratory finding suggestive of TB

TB infection or Condition in which a child has no s/s presumptive of TB nor radiologic or laboratory
Latent TB evidence but has a positive TST reaction
infection(LTBI)
TB Disease Presumptive TB with clinical and diagnostic evaluation (positive TST and radiology) is
confirmed to have TB
Classification:
• Bacteriologically Confirmed--positive smear microscopy, culture or rapid
diagnostic test(Xpert MTB/RIF)
• Clinically Diagnosed– does not fulfill the criteria for bacteriologically confirmed
but has been diagnosed with active TB by a clinical assessment as to radiologic
findings or suggestive histology
Pulmonary TB –involving the lungs and tracheobronchial tree
Extrapulmonary TB – refers to TB involving other organs ( larynx, pleura, Lymph
nodes, abdomen, GUT, Skin, Bones)
TB PATHOGENESIS

RISK FACTORS FOR ACQUIRING INFECTION

Household contact with a newly diagnosed smear (+) case
Age Less than 5years
Immunocompromised state (severe malnutrition, HIV)
Other high risk for exposure and infection
• Residents and employees of closed setting(nursing
homes, correctional institutions, hospital serving high
risk population
• Medically underserved, low income population
• High-risk racial or ethnic minority populations
• Injection drug users
• Children exposed to adults with certain medical
conditions (DM, Silicosis, cancer, ESRD, gastrectomy)
TB PATHOGENESIS

TRANSMISSION AND PORTAL OF ENTRY

• Inhalation of droplet nuclei from a contagious
source
• Infective nuclei measuring 5 micra, small enough
to avoid being swept away by the mucociliary
system, then deposited into the alveoli
• 5-200 inhaled bacilli are necessary for a successful
infection
• Perinatal transmission : Transplacentally on
mother’s with primary hematogenous TB

INCUBATION PERIOD
• 3-12weeks or shorter if inoculum is large
TB PATHOGENESIS
PRIMARY TUBERCULOSIS
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Pulmonary TB
• initial stage in children who inhale the M.
Tuberculosis bacilli
• 3 elements: Ghon focus, lymphadenitis,
and lymphangitis
• 95% of cases, it heals by fibrosis and/or
calcification
• Primary TB in children is asymptomatic in
up to 65% of patients
• Signs and symptoms can vary substantially
in the population
• several days of low-grade fever
• Fever, low-grade in character, can last for
an average of 14 to 21 days
• mild cough
• pleuritic or retrosternal pain of gradual
onset
Progressive Primary TB
condition which develops when
initial infection fails to heal and
continues to progress over a
period of months or years,
causing further pulmonary and
even distant organ involvement
Secondary (reactivation) TB
• represents reactivation of an old, possibly
subclinical infection
• occurs in less than 10% of the cases
• tends to produce more damage to the lungs
than does primary tuberculosis
• more common in adolescents than in younger
children
• Clinical manifestations:
• chronic or persistent cough
• prolonged fever
• chest pain
• Hemoptysis
• Supraclavicular adenitis
• Most of these features may however improve
within several weeks after starting effective
treatment, but the cough may persist for several
months
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Miliary TB
• refers to clinical disease resulting from the
hematogenous dissemination of result of progressive
primary infection
• occurs when clinically significant form of massive
numbers of tubercle bacilli are released into the
bloodstream causing disease in two or more organs
• denote all forms of progressive, widely disseminated
hematogenous TB
• most common extrapulmonary sites of disease
include the lymphatic system, bones and joints and
the liver
• In children clinical presentation :
• Chills, night sweats, hemoptysis, and productive cough have
been reported less frequently in the pediatric population while
peripheral lymphadenopathy and hepatomegaly are more
common in children compared with adults

• Signs or symptoms or peritonitis are found in 20 to

40% of patients with advanced disease
 EXTRAPULMONARY TB
Endobronchial TB • Enlargement of the peribronchial LN with subsequent compression or
intrabronchial, the nodal extension into the bronchus

Cervical LN, • May occur during primary TB infection

Adenitis (Scrofula) • Most common form of extrapulmonary TB, most common cause of Lymphadenitis
in children
• More frequently on ages 10-18 yo
• Mostly involve the Anterior Cervical Space(49%), Axillary and Supraclavicular
areas
• Firm, painless, rubbery discreet or matted, fixed to surroundings and overlying
skin may be indurated Unilateral single or multiple slowly growing nontender
Lymphadenopathy
• Fistula formation(10%) , LN abscess may burst leading to chronic nonhealing sinus
and ulcer formation
CNS : • most severe form of Extra PTB
• Usually 2-6 months after initial infection and accompanies Miliary TB (50%)
• TB Meningitis • Thick gelatinous exudate causes obstruction Hydrocephalus and papilledema,
vasculitis leads to thrombosis and infarction
• 3 stages: 1st(personality changes, irritability) 2nd (increase ICP) 3rd (coma, irregular
pulse or respiration or rising fever)
• CSF: clear, usually opalescent WBC 50-500 cells/mm3, predominant PMN
leukocytes , glucose low to very low late in disease, CHON may be Normal to High
• CT scan: Hydrocephalus(80%), basal meningeal enhancement (75%), cerebral
edema, nodular enhacing lesions
 EXTRAPULMONARY TB
TB Spine ( Potts • The spine is the most common skeletal site affected by TB , followed by hip and knee
disease) • Often history of trauma is present that contributes to the activation of lesions
• Destruction of the vertebral disk space and adjacent vertebral bodies , collapse of the
spinal elements and anterior wedging leading to characteristic angulation and gibbus
(palpable deformity due to involvement of multiples vertebrae) formation , distortion
of of spinal column leads to severe kyphosis (Potts Disease)
• 4-11months ( average onset duration from infection)
• Upper lumbar, lower thoracic and lumbosacral spine are mostly involved
• Back pain (most frequent symptom) , night Cries , neurologic symptoms, restless sleep
and peculiar position(tortciolis), fever
• Paresis or paraplegia (25-39%), bowel and bladder dysfunction in some , paravertebral
abscess

GI/Abdominal TB • Includes infection of the peritoneum, hollow, or solid abdominal organs

(intestines, liver, spleen, pancreas, mesentery) abd abdominal lymph nodes
• Common symptoms: abd enlargement, abd pain, weight loss
• Malnutrition (common feature)
• Distended abdomen, ascites, abdominal mass typically located at RLQ and
hepatomegaly (most common signs)
EXTRAPULMONARY TB
Renal TB • Uncommon, very late complication (15-20 years) after primary
infection
• Hematogenous spread into the glomeruli, with resultant caseating
sloughing lesions which discharge TB bacilli into tubules
• Patients would present with dysuria, hematuria, sterile pyuria, flank
pain
• Children whose urine reveal presence of tubercle bacilli are
considered to be infectious until urine is sterile

Post Natal TB Possible route of infection: Hematogenous spread from the umbilical
vein, ingestion in utero or intrapartum infected amniotic fluid or
postpartum inhalation for source case
Congenital TB-–(1 or more of the ff criteria)
1. Present within the 1st week of life
2. A primary hepatic complex, or caseating hepatic granuloma
3. TB infection of the placenta or endometrial TB in the mother or
exclusion of the possibility of postnatal transmission by excluding
TB in other contacts
 Spectrum of TB
TB Exposure TB Infection TB Disease
Exposure positive positive positive
Sign and Symptom negative negative positive
Tuberculin Skin Test negative positivea positivea
Chest Xray negative negative (may be positive)b
Direct Sputum Smear Microscopy negative negative (may be positive)c
Other Diagnostics negative (may be Positive)d (may be Positive)d

a
-may be false negative in many children
b
-may be positive showing hilar adenopathy and the GHON complex
c
-may be negative due to the paucibacillary nature in children and difficulty
of the specimen collection
d
-may be positive in immunology-based test like IGRA
 Classification of TB Disease
• Bacteriologically-confirmed status
-biologic specimen is positive by smear microscopy , culture or WHO
approved raid diagnostic test (such as Xpert MTB/RIF)
Bacteriological
Status • Clinically diagnosed TB case
-does not fulfill the criteria for bacteriologically confirmed but has
been diagnosed with active TB by a clinical assessment as to radiologic
findings or suggestive histology
Anatomical site Pulmonary TB (PTB)
- bacteriologically or clinically diagnosed case of TB involving lung
parenchyma or the tracheobronchial tree ; a patient who has Pulmonary
and Extrapulmonary should be classified under Pulmonary TB
-lesions mainly in lungs
Extrapulmonary TB (EPTB)
-refers to TB involving other organs ( larynx, pleura, Lymph nodes,
abdomen, GUT, Skin, Bones), in the absence of lung infiltrates on CXR
Classification of TB Disease
• New case
- a patient who had never had treatment TB or who has taken anti TB
Previous drugs less than one(<1)month. Isoniazid preventive therapy or other
Treatment preventive regimens are not considered as previous TB treatment
• Retreatment case
-a patient who has been previously treated with anti TB drugs for at
least 1 month in the past
• HIV negative patient
- refers to any bacteriologically confirmed or clinically diagnosed
case of TB who has a negative result of HIV testing at the time of TB
HIV status diagnosis
• HIV positive patient
-refers to any bacteriologically confirmed or clinically diagnosed case
of TB who has a positive result of HIV testing at the time of TB diagnosis
Classification of TB Disease
• Mono-resistant TB
Drug -resistance to one first line anti TB drug only
susceptibility
• Polydrug resistant TB
-resistance to more than 1 first line anti TB drug (other than both isoniazid
and rifampicin )

• Multidrug-Resistant TB (MDR-TB)
-resistance to at least both Isoniazid and Rifampicin

• Extensively Resistant TB (XDR- TB)

-resistance to any fluoroquinolones and to at least one of three second line
injectable drugs( Capreomycin, Kanamycin, and Amikacin) In addition to
the multidrug resistance

• Rifampicin Resistant TB (RR-TB)

-Resistance to Rifampicin , detected using phenotypic or genotypic methods,
with or w/o resistance to other anti TB drugs
 CRITERIA FOR DIAGNOSIS OF TB
• Positive culture with or w/o a positive smear M. tuberculosis (GOLD STANDARD )
• In the Absence of bacteriologic evidence, however, a child is presumed to have
active TB if 3 or more of the ff criteria are present
 Exposure to an adult/adolescent with active TB disease ( EPIDEMIOLOGIC)
 Signs and symptoms suggestive of TB (CLINICAL)
 Positive tuberculin test (IMMUNOLOGIC)
 Abnormal chest radiograph suggestive of TB (RADIOLOGIC)
 Laboratory Findings suggestive of TB (histological, cytological, biochemical,
immunological, and/or molecular) (LABORATORY)
• PRESUMPTIVE TB
-any person adult/child with signs and symptoms suggestive of TB whether
pulmonary or extrapulmonary, or with those CXR findings suggestive of active TB
 Identification of presumptive TB
A. For 15yo and above, a presumptive TB has ANY of the following:
I. Cough of at least 2weeks duration with or without the following symptoms :
• Significant and unintentional weight loss
• Fever
• Bloody sputum (hemoptysis)
• Chest/Back Pains not referrable to any musculoskeletal disorder
• Easy fatigability or malaise
• Night sweats
• Shortness of breath

II. Unexplained cough of any duration in:

• A closed contact of a known active TB case
• High risk clinical groups (HIV/AIDS, DM, ESRD, Cancer, autoimmune disease,
underwent solid organ transplant and patients on prolonged steroids) and High
risk populations(e.g elderly, urban poor, inmates and other congregate settings
 Identification of presumptive TB
B. For Below 15years old, a presumptive TB has ANY of the following:

I. At least three (3) of the following clinical criteria:

• Coughing/wheezing of 2 weeks or more , especially if unexplained ;
• unexplained fever for 2 weeks or more after common cause such as
malaria or pneumonia have been excluded
• Low of weight/failure to gain weight/ weight faltering/loss of appetite;
• Failure to respond to 2weeks of appropriate antibiotic therapy for the
lower respiratory tract infection
• Failure to regain previous state of health 2 weeks after the viral infection or
exanthem ( e.g. Measles) and
• Fatigue, reduced playfulness, or lethargy

II. Any one (1) of the above signs and symptoms(e.g. clinical criteria) in a child who is a
closed contact of a known active TB case
 Identification of presumptive TB
C. Chest X ray findings suggestive of PTB, with or without symptoms,
regardless of age.

D. Presumptive extrapulmonary TB may have any of the following:

• Gibbus, especially of recent one (resulting of vertebral TB)
• Non-painful enlarged cervical lymphadenopathy with or without fistula formation
• Neck stiffness( nuchal rigidity)and/or drowsiness suggestive of meningitis that are
not responding to antibiotics treatment, with a subacute onset or raised ICP
• Pleural effusion
• Pericardial Effusion
• Distended Abdomen (big liver, spleen) with ascites
• non-painful enlarged joint and
• Signs for tuberculin hypersensitivity (e.g Erythema nodosum , Phlyctenular
conjunctivitis )
 Identification of presumptive TB

Ask and verify the following:

a. History of previous anti-TB treatment and its
details
b. Exposure to active TB cases or presumptive
TB ( including MDR-TB if applicable within
the workplace, family, or household)
c. Presence of clinical or high risk factors
DIAGNOSIS
Tuberculin Skin Test
• Based on delayed cellular hypersensitivity to certain antigens
of the TB organism contained in extracts of culture filtrates
known as “tuberculin”

• type IV Immune response mediated by T-lymphocytes and

characterized by indurated response to intradermal injection
of the protein from the cell wall of the tubercle bacillus

• prior infection with the MTB or tuberculo proteins from BCG

vaccine results in T cell sensitization that releases
lymphokines at the site of injection

• Lymphokines induce local vasodilation, edema, firbin

deposition and recruitment of other inflammatory cells to
the area resulting in induration
Tuberculin Skin Test
ADMINISTRATION
• Site: 2 inches below the elbow
joint in the volar aspect of the
forearm
• Tuberculin syringe, gauge 25-
27 short bevel needle (1/4-
1/2inch)
• Aspirate 0.1ml (2 TU PPD-RT23
OR 5TU PPD-S )
• Route: INTRADERMAL
• Form wheal of 6 to 10mm
diameter should be evident
after , otherwise repeat the
test 2 inches away from initial
site
Tuberculin Skin Test
READING AND RECORDING
• Should be read 48-72hrs after (positive TST reaction can be measured up to 7days, while
negative reaction until 72Hours only)

• Assess induration( palpable, raised hardened area) not the erythema

• Measure across the forearm (perpendicular to the axis), get the widest diameter of
induration and mark both edges with a ballpen

• Size should be recordred in millimeters; if no induration is found, “0mm” NOT

“Positive “or “Negative “

64.7%-99.7% Specificity 54
—97.7% Sensitivity
Tuberculin Skin Test
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Interferon Gamma Release Assay Test (IGRA)

• Diagnostics tool for latent TB

infection
• Surrogate markers for M.
tuberculosis infection and
indicate a cellular immune
response

• QuantiFERON-TB Gold in-Tube

Test (QFT-GIT) and TB-SPOT TB

• the currently FDA approved

IGRA assays for MTB
 Interferon Gamma Release Assay Test (IGRA)

KEY FACTS: TSTS AND IGRAS TESTING FOR TB INFECTION And TB DISEASE
• TST and IGRA generally should not be tested on persons with low risk of TB
• infection and TB disease.
• Neither AGRA nor TST can distinguish active TB from latent tuberculosis infection
• AGRA can distinguish LTBI from previous BCG administration
• Routine testing with both TST and an IGRA is not generally recommended:
• Exceptions i suspected active TB in immune compromised patients, or
• indeterminate ncluderesults from either test
• An IGRA is the test of choice in two instances; for people who have received BCG,
• either as a vaccine or as chemotherapy and under circumstances where the tested
• person is unlikely to return to have the TST read.

• TST is preferred over AGRA for children less than 5 years of age.

Live vaccines may affect both TST and IGRA results

IGRA testing can be done on the same day of live vaccine administration; otherwise it should be
postponed at least four to six weeks from a live-vaccine administration
 RADIOGRAPHIC FINDINGS
• Chest Xray (most basic and common)
• No pathognomonic radiographic findings
• Uniform stippling of both lungs ( Military TB)
• the only findings highly suggestive of TB in infants and children

CXR FINDINGS:
• Lymphadenopathy (83-92%)
• Parenchymal involvement (60.8%)
• Local pleural effusion (6-11%)
• Regional lymphadenitis
 RADIOGRAPHIC FINDINGS
• Chest Xray (most basic and common)
• No pathognomonic radiographic findings
• Uniform stippling of both lungs ( Military TB)
• the only findings highly suggestive of TB in infants and children

CXR FINDINGS:
• Lymphadenopathy (83-92%)
• Parenchymal involvement (60.8%)
• Local pleural effusion (6-11%)
• Regional lymphadenitis
Pott’s disease
DIAGNOSTIC MYCOBACTERIOLOGY
Specimen collection
Gastric Lavage or
SPUTUM TRACHEAL ASPIRATE CSF
aspirate
• Recommended for • Older children who • Collect respiratory • 1-2ml collected
infants and children can expectorate washing or aspirate aseptically
who are unable to • 2 series sputum in a sputum trap • Separate CSF
produce sputum specimens 2 and place the brush sample must be
• Via aerosol different days in a sterile, leak collected for
inhalation before start of proof container with chemistry and
• Collected morning therapy 5ml sterile saline hematology
before eating and • Clean mouth, breath • Minimum desired
while still at bed deeply 3x, cough specimen: 3ml
• 25-50ml sterile hard after the 3rd
distilled water breath , expectorate
injected to stomach sputum
tube • Minimum desired
• 5-10ml gastric specimen volume:
content aspirated 3ml
• Repeated once daily
for 3consecutive
days
 DIAGNOSTIC MYCOBACTERIOLOGY
Specimen collection
Abscess,
Tissue Lymph
cellulitis , skin BLOOD BODY FLUIDS URINE STOOL
Node
lesions
• Collected • Fluid abscess • 10ml whole • 10-15ml • 40ml urine • Not
aseptically can be collected blood collected collected (midstream is recommended
during surgery with syringe or • Minimal volume aseptically never advised) in HIV pts due
or biopsy its tissue required: 1ml collected from a to high
• 2-3ml saline removed catheter and concentration in
must be added aseptically must be sterile stool
• Open lesion or • Minimal volume
abscess can be required 10-
aspirated from 15ml
under the • Preferably
margin of lesion collected in
Morning daily
for 3
consecutive
days
DIAGNOSTIC MYCOBACTERIOLOGY

AFB Smear Culture and Drug sensitivity

• First bacteriologic evidence • Regardless of the AFB result
• Easiest, least expensive, ALL specimens must be
most rapid cultured
• Provides quantitative • Gold standard for diagnosis
estimate of number and • Low sensitivity in children
degree infectiousness (10-50% of TB cases asre
• May present M.tuberculosis culture proven)
or Non- tuberculosis
• Sensitivity 20-80%;
Specificity >97%
SEROLOGICAL TEST
• Sensitivity: 0-100% (pulmonary and extrapulmonary
TB
• Specificity: 31-100% (PTB), 59-100% extrapulmonary
TB
• No studies conducted in children

• WHO strongly recommends that commercial

serodiagnostic or serological tests should NOT be
used for the diagnosis of pulmonary and
Extrapulmonary TB
NUCLEIC ACID AMPLIFICATION TEST (NAATs)

• utilize techniques to amplify nucleic acid regions specific to the MTB complex
• In theory, NAATs can detect a single bacillus in a
specimen such as sputum, gastric aspirate, pleural fluid, cerebrospinal fluid,
or blood
• Available as “ in house assays or commercial kits
• In house assays - vary in protocol
• Commercial NAATs – standardized methods of amplification
72-94 % sensitivity
96-100% specificity
• Amplicor PCR test
• Amplified MTB test
• BD ProbeTec ET Direct TB Assay
• Cobas Amplicor
NUCLEIC ACID AMPLIFICATION TEST (NAATs)

• Rapid and early detection of causative mycobacteria in clinical samples.

• Important in the following:
• Diagnosis is urgently needed due to the severity of the disease
• Diagnosis is difficult (smear negative cases)
• Paucibacillary disease
• Extrapulmonary TB
• TB in immunocompromised patients
• Disseminated TB
NUCLEIC ACID AMPLIFICATION TEST (NAATs)

• NAATs in Pediatric Tuberculosis

• Low and variable sensitivity (4-90%)
• Specificity: 75-97%
• Can have False positive from previous reaction
or cross-contamination
 GENE XPERT MTB/RIF ASSAY
• First fully automated, cartridge-
based NAAT for TB
• Can simultaneously detect TB
bacteria and rifampicin resistance
in less than 2 hours
• Sensitivity:
• 55- 90%: Expectorated sputum
• 40-100%: induced sputum
• 40-100%: gastric lavage or
aspirate
• Specificity:
• 93-100%: all specimen
 GENE XPERT MTB/RIF ASSAY
• RIF resistance
• Sensitivity: 83.3% Specificity: 99.1%
WHO recommendation:
• XPERT MTB/RIF ASSAY should be used as a replacement for
conventional microscopy, culture and drug susceptibility testing as the
initial diagnostic test in both adults and children with PTB and suspected
at risk for drug resistant TB or have HIV associated TB

• May be used rather than conventional microscopy and culture as the

initial diagnostic test in all other individuals suspected of having TB, if
resources are available
 GENE XPERT MTB/RIF ASSAY on ExtraPTB

• TB meningitis – limited studies

• Gene Xpert is Preferred due to rapid diagnosis
• Sensitivity of GENE XPERT MTB/RIF ASSAY still lower than culture
confirmation or clinical diagnosis for Extrapulmonary TB.
• Further studies needed for EPTB at most common sites: Pleural TB, TB
meningitis
• Should NOT be used as sole test for evaluation
 T-CELL-BASED ASSAYS
(INTERFERON GAMMA RELEASE ASSAYS) IGRA

• Measures a person’s immune reactivity to MTB

• Fresh blood samples are mixed with antigens specific for
MTB complex strains and absent from the BCG vaccine
strain
• WBC from infected persons (T-lymphocytes) release IFN-g
• RESULTS:
• Positive: suggest that MTB infection is likely
• Negative: infection is unlikely
IGRA
• WHO recommendation:
• Either IGRA or TST can be used to test for latent TB
infection (LTBI) in high-income and upper middle income
countries which have a low burden of TB disease (<100
per 100,000 population)
Use of IGRA for Diagnosis of Latent TB infection

• IGRAs and the TST are surrogate markers of MTB infection.

• Both tests indicate a cellular immune response to response to
recent or remote sensitization with MTB.
• Neither can distinguish TB infection from active disease
• Developed to replace TST in the diagnosis of latent TB infection
• Not intended for detecting cases of active TB
• Should not be used for the diagnosis of pulmonary or
extrapulmonary TB in low and middle-income countries
• Should not be used for the diagnostic work-up of adults and
children suspected of active TB, irrespective of HIV status
Management
Management
OBJECTIVES:
• Cure of the patient by rapid elimination of most of
the metabolically active and rapidly replicating bacilli
• Prevention of death from active TB or its late effects
• Prevention of relapse by elimination slowly and
intermittently multiplying bacilli
• Prevention of drug resistance by using a combination
of drugs
• Decrease of TB Transmission to others
4 Groups of TB Populations
• defined by drug efficacy:
1. Actively growing bacilli found in open cavities bactericidal drugs Isoniazid, Rifampicin,
Strepto,Pyrazinamide
2. slowly multiplying or intermittently replicating TB sterilizing drugs Rifampicin (most
bacilli located in caseous lesions that undergo spurts potent sterilizer)
of metabolism

3. Intracellular bacilli present in the acidic sterilizing drugs

compartments of macrophages or in acidic lung
lesions
4. TB persistent found in hypoxic microenvironments non-responsive
to most anti-TB drugs
 REGISTRATION GROUP DEFINITION OF TERMS

NEW A patient who has never had treatment for TB or who has
taken anti-TB drugs for < 1 month

Relapse A patient previously treated for TB who has been declared cured, or completed treatment in
their most recent treatment episode, and is presently diagnosed with bacteriologically-
confirmed or clinically-diagnosed TB

Treatment after A patient who has been previously treated for TB and whose treatment failed at the end of
failure their most recent course. This includes:
• A patient whose sputum smear or culture is positive at 5 months or later during
treatment.
• A clinically diagnosed patient (e.g child or extrapulmonary TB) for whom sputum
RETREATMENT

examination cannot be done and who does not show clinical improvement anytime during
treatment.

Treatment after lost A patient who was previously treated for TB but was lost to follow-up for 2 months in their
to follow up (TALF) most recent course of treatment, and is current]y diagnosed with either bacteriologically-
confirmed or clinically-diagnosed TB

Previous treatment Patients who have been previously treated for TB but whose outcomes after their most recent
outcome unknown course of treatment are unknown or undocumented
(PTOU)

Other Patients who do not fit into any of the categories listed above
CATEGORY OF CLASSIFICATION AND TREATMENT REGMIEN
TREATMENT REGISTRATION GROUP
CATEGORY I Pulmonary TB, New 2 HRZE/4 HR

Extrapulmonary TB, New(Except

CNS/Bones or joints)

CATEGORY IA Extrapulmonary TB, New 2 HRZE/10 HR

(CNS/bones, joints)
CATEGORY II Pulmonary or Extrapulmonary, 2 HRZES/1 HRZE/5 HRE
Previously treated drug-
susceptible TB
• Relapse
• Treatment failure
• Treatment after lost to follow-
up (TALF)
• Previous treatment outcome
unknown

CATEGORY IIA Extrapulmonary, Previously treated 2 HRZES/1 HRZE/9 HRE

drug-susceptible TB
 First-line anti-tuberculosis drugs
DRUG RECOMMENDED DOSE
Children Adult
ISONIAZID 10(10-15mg/kg) 5(4-6mg/kg)

RIFAMPICIN 15(10-20mg/kg) 10(8-12mg/kg)

PYRAZINAMIDE 30(20-40mg/kg) 25(20-30mg/kg)

ETHAMBUTOL 20(15-25mg/kg) 15(15-20mg/kg)

Adult Dose: 25Kgs

 Child Friendly Fixed-Dose Combination
•Advantages
• Prescription error less likely
• Less tablets/suspension to ingest
• Decrease chances of monotherapy

Intensive Phase: Continuation Phase:

• Rifampicin 75mg + Isoniazid • Rifampicin 75 + Isoniazid 50
50mg + Pyrazinamide 150mg

Ethambutol (15-25mg/K) should be added in the intensive

Phase for children with extensive disease or living setting
where prevalence of HIV or Isoniazid resistance as in the
Phils.
 Dosing table for FDCs
Number of tablets
WEIGHT BAND INTENSIVE PHASE: CONTINUATION PHASE
RHZ 75/50/150 RH 75/50
4-7 KG 1 1
8-11 KG 2 2
12-15 KG 3 3
16-24 KG 4 4
25+ KG Adult dosages recommended
Ethambutol (15-25mg/K) should be added in the intensive Phase for
children with extensive disease or living setting where prevalence of
HIV or Isoniazid resistance as in the Phils.
 Second-line anti-tuberculosis drugs
DRUG RECOMMENDED DOSE
Children (mg/kg/day) Adult
AMINOGLYCOSIDES 15 OD (max 1g)
Amikacin 15-30 IM/IV OD (max 1g)

Kanamycin 15-30 IM/IV OD (max 1g)

Streptomycin 20-40 IM OD (max 1g)

POLYPEPTIDE 15-30 IM OD (max 1g) 15 IM OD (max 1g)

Capreomycin
 Second-line anti-tuberculosis drugs
DRUG RECOMMENDED DOSE
Children (mg/kg/day) Adult
FLUOROQUINOLONES 10-15 OD PO
Ofloxacin <5yo: 15-20 mg/kg/day PO BID

>5yo: 10-15 mg/kg/day PO OD

Levofloxacin 7.5-10 mg/kg/day PO

(max 750 mg/day)

Moxifloxacin 7.5-10 mg/kg/day PO

(max 400 mg/day)
 Second-line anti-tuberculosis drugs
DRUG RECOMMENDED DOSE
Children Adult
Prothionamide 15-20 mg/kg/day 15-20 frequently divided (max 1
2-3 doses (max 1g) g); usually 500-750mg in OD or
BID
Ethionamide 15-20 mg/kg/day PO
(max 750 mg)

Cycloserine 10-20 divided q12H 10-15 usually 500-750 mg/day

(max 1g) BID or OD if tolerated (max 1g)

Para-aminosalicylic acid 150 PO OD 150 PO OD

(PAS) (max 12g) (max 12g)
 APPROACH TO PROPHYLAXIS

TB EXPOSURE

YES
< 5 YEARS Start INH for 3 months
OLD

NO
Radiologic
Repeat
POSITIVE findings YES TB Disease
Mantoux
test after 3
&/or, S/Sx Multiple Drug
suggestive Therapy
months
of TB
NEGATIVE NO

Discontinue H LTBI
If no BCG scar, give BCG Continue > 6H
 PREVENTION
Primary Prophylaxis
• Prevent development of infection among contacts
exposed to active disease

Secondary Prophylaxis
• Prevents progression of latent infection to disease
 MULTI-DRUG RESISTANT TB
DRUGS USED TO TREAT MDR-TB
Group 1- First Line Oral Agents Isoniazid, Rifampicin , Ethambutol , Pyrazinamide
Group 2- Injectables agents Kanamycin, Amikacin , Capreomycin, Streptomycin
Group 3- Fluoroquinolones Moxifloxacin, Levofloxacin, Ofloxacin
Group 4- Oral Bacteriostatic Ethionamide, Prothionamide, Cyclosporine ,
(Second line agents) Terizidone, p-Aminosalicylic acid (PAS)

Group5- Agent with unclear efficacy Clofazimine,Linezolid, Amoxicillin-Clauvalinic acid ,

(not recommended by WHO for Thioacetazone, Imipenem/Cilastatin, Clarithromycn,
routine use in MDR TB patients) High Dose Isoniazid (16-20mkd)
MANAGING SIDE EFFECTS OF ANTI-TB DRUGS
SYMPTOM DRUG MANAGEMENT
Minor GI upset, anorexia, Pyrazinamide, Rifampicin Continue anti-TB drugs
nausea, abdominal pain check doses , give drugs
with small meal or just
before going to bed
Joint pains Pyrazinamide Paracetamol, NSAID
(ibuprofen)
Burning Isoniazid Pyridoxine 10mg per
Sensation/Numbness, 100mg Isoniazid daily
tingling sensation
Orang e/Red Urine Rifampicin Harmless
Discolored Contact Lens Reassurance
Inform the pt at start of
treatment
MANAGING SIDE EFFECTS OF ANTI-TB DRUGS
SYMPTOM DRUG MANAGEMENT
Itching, skin rash Thioacetazone Stop anti- TB drugs
(Streptomycin, Isoniazid, Rifamp,
Pyrazinamide)
Deafness (no earwax on Streptomycin Stop Streptomycin
otoscopy)
Dizziness/ Streptomycin Stop Streptomycin, use
Vertigo/Nystagmus ethambutol
Jaundice( other causes Pyrazinamide, Isoniazid, Stop anti- TB drugs
excluded hepatitis) Rifampicin
Confusion Most anti-TB drugs Stop anti- TB drugs
(suspect liver Failure)
Visual Impairment Ethambutol Stop Ethambutol
Shock Purpura , Acute Rifampicin Stop Rifampicin
Renal failure
APPROACH TO DIAGNOSIS
 THANK
YOU

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