Slide Pediatric Tuberculosis
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Transcript of Slide Pediatric Tuberculosis
Definition
Tuberculosis is a disease due to Mycobacterium tuberculosisinfection with systemic spread thus
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infection with systemic spread thus can affect almost all organs, and the most frequent site is in the lung, which usually as the site of primary infection
Tuberculosis
The reaction of the tissues of the human host to the presence and multiplication of
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human host to the presence and multiplication of Mycobacterium tuberculosis or Mycobacterium bovis
History
• ancient Egypt : gibbus
• 1882, Koch, identification
• management : sanatorium, collapse treatment
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treatment
• Chemotherapy :– PAS – 1943 – Lehmann
– Streptomycine – 1945 - Waksman & Schats
– Isoniazid – 1952 – Domagk
– Rifampicine - 1957
Magnitude of problem
• TB one of the oldest diseases of human
• remains one of the deadliest diseases in the world
• 8 million of new cases yearly
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• 8 million of new cases yearly
• 3 million death yearly
• 20-40% population is infected
• reemergence, global emergency
The secret
Why TB is so strong and robust?
• the secret: specific characters of the bacilli
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• special issues:
hematogenic spread
infection vs disease
primary vs post-primary
The main problems
• Diagnosis
– Clinical manifestations : not specific �
both over/under diagnosis & over/under treatment
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– diagnostic specimen : difficult to obtain
– TB infection or TB disease ? � no
diagnostic tool to distinguish
• Adherence / compliance
– Drug discontinuation � treatment failure
The bacilli• Mycobacterium tuberculosis• Mycobacterium bovis
features:
� slender, often slightly curved, rods
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� aerobic, non-motile, non-spore forming
� acid fail to wash the stain out � acid fast bacilli
�Mycobacteria : found in environments, some strictly human pathogen (M tb, bovis), others animal pathogen and opportunistic pathogens in human (atypical mycobacteria)
M tuberculosisCharacteristics :
1. live in weeks in dry condition
2. no endotoxins, no exotoxins
3. hematogenic spread
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3. hematogenic spread
4. grows slowly (24-32 hr)
5. non specific clinical manifestation
6. aerob, organ predilection - lung
7. wide spectrum of replication: dormant
Transmission ...
• airborne human to human transmission by droplet nuclei
• adult pulmonary TB: cough, sneeze, speak, or sing
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sing
• droplet nuclei : contain 2-3 bacilli, small size (1-5µ) keep in the air for long period
• inhalation, reach alveoli
• middle and lower lobes
Transmission factors:
• doses / numbers
• concentration in the air
• virulence
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• virulence
• exposure duration
• host immune state
Infection source
• Known source of infection, has
diagnostic value
• Shaw (1954), level of infectiousness :
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• Shaw (1954), level of infectiousness :– AFB (+) : 62.5 %
– AFB (-), M tb (+) : 26.8 %
– AFB (-), M tb (-) : 17.6 %
Transmission rate (Shaw ’54)
adultTB patient
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AFB(+)AFB(-)
culture(+)culture(-)CXR (+)
65% 26% 17%
Location of primary focus
in 2,114 cases, 1909-1928
Location %Lung 95.93
Intestine 1.14
Skin 0.14
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Skin 0.14
Nose 0.09
Tonsil 0.09
Middle ear (Eustachian tube) 0.09
Parotid 0.05
Conjunctiva 0.05
Undetermined 2.41
droplet nuclei inhalation
alveoli ingestion by PAM’S
intracellular replicationof bacilli
destructionof bacillidestruction of PAM’S
Tubercle formation Hilar lymph nodesLymphogenic spread
primary focus lymphangitis lymphadenitis
9/20/2010 20Figure. Pathogenesis of primary tuberculosis
hematogenic spread
multiple organs remote focidisseminated primary TB
acute hematogenicspread
occult hematogenicspread
primary
complex
CMI
Incubation period
• first implantation � primary complex
• 4-6 weeks (2-12 weeks) � incubation period
• first weeks: logaritmic growth, : 103-10
4 �
elicit cellular response
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elicit cellular response
• end of incubation period:
– primary complex formation
– cell mediated immunity
– tuberculin sensitivity
�������� PrimaryTB infection has established
Hematogenous spread
• during incubation period, before TB infection establishment:
– lymphogenic spread
– hematogenic spread
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–hematogenic spread
• hematogenic spread (HS):
–occult HS
–acute generalized HS
Occult HS
• most common
• sporadic, small number
• no immediate clinical manifestation
• remote foci in almost every organ
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• remote foci in almost every organ
• rich vascularization: brain, liver, bones & joints, kidney
• including: lung – apex region
• CMI (+): silent foci - dormant, potential for reactivation
Acute HS
• less common
• large number
• immediate clinical manifestation: disseminated TB
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disseminated TB
• milliary TB, meningitis TB
• tubercle in same size, special appearance in CXR
Primary complex
• end of incubation period
• TB infection establishment
• tuberculin sensitivity (DTH)
• cell mediated immunity
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• cell mediated immunity
• end of hematogenic spread
• end of TB bacilli proliferation
• small amount, live dormant in granuloma
• new exogenous TB bacilli: destroyed / localized
Tuberculin test
TB infection
cellular immunity
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delayed type hypersensitivity
tuberculin reaction
Tuberculin
StrengthPPD S
SeibertPPD RT23
first 1 TU 1 TU
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first 1 TU 1 TU
intermediate(standard dose)
5-10 TU 2-5 TU
second 250 TU 100 TU
Tuberculin delivery
1. Mantoux : intradermal injection
2. Multiple puncture :
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• Heaf, special apparatus with 6 needles
• Tine, disposable, 4 needles
3. Patch test
Tuberculin
Mantoux 0.1 ml PPD intermediate strength
location : volar lower arm
reading time : 48-72 h post injection
measurement : palpation, marked, measure
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report : in millimeter, even ‘0 mm’
Induration diameter :
� 0 - 5 mm : negative
� 5 - 9 mm : doubt
� > 10 mm : positive
Tuberculin positive
1. TB infection :
� infection without disease / latent TB infection
� infection and disease
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� infection and disease
� disease, post therapy
2. BCG immunization
3. Infection of Mycobacterium atypic
AnergiPatient with primary complex do not give reaction to TST due to supression of CMI :
• Severe TB: miliary TB, TB meningitis
• Severe malnutrition
• Steroid, long term use
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• Steroid, long term use
• Certain viral infection: morbili, varicella
• Severe bacterial infection: typhus abdominalis, diphteria, pertussis
• Viral vaccination: morbili, polio
• Malignancy: Hodgkin, leukemia, ...
TB infection & TB disease
• TB infection: CMI can control infection
– primary complex
– tuberculin sensitivity (DTH)
– cell mediated immunity
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– cell mediated immunity
– no clinical or radiological manifestation
• TB disease: CMI failed to control TB infectionTB infection + clinical and/or radiological manifestation
TB classification (ATS/CDC modified)
Class Contact Infection Disease Manage ment
0 - - - -
1 - -
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1 + - - proph I
2 + + - proph II?
3 + + + therapy
TB Natural history overviewprimary TB infection
primary TB disease latent infection
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no diseasepost primary TB
respiratory TBnon respir TB
new infection
Pathology
• complicated pathogenesis �varied pathology
�clinical manifestation
�radiologic appearance
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�radiologic appearance
• lung represent
• tubercle, granuloma, tuberculoma, fibrosis, fistula, cavity, atelectasis
• complication of primary focus: so many possibilities
Lesions of pulmonary TB
• Parenchym: primary focus, pneumonia, atelectasis, tuberculoma, cavitary
• Lymph node: hilar, paratracheal, mediastinal
• Airway: air trapping, endobronchial TB,
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• Airway: air trapping, endobronchial TB, bronchial stenosis, fistula, bronchiectasis
• Pleura: effusion, fistula, empyema, pneumothorax, hemothorax
• Blood vessels: milliary, hemorrhage
tubercle formationresolution
primary focus
PathologyPathology
remote focireg lymph node
milliary seed
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calcification
2nd lung lesions
caseation
liquefaction
granuloma
tuberculoma
cavity
erodes airway
compresses airway
rupt to pleura rupt to airway bronchiectasis
fibrosis
br pl fistula
Clinical types of pediatric TB
• Infection: TST (+), clinical (-), radiographic (-)
• Disease:– Pulmonary:
• primary pulmonary TB
• milliary TB
• pleuritis TB
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• pleuritis TB
• progr primary pulm TB: pneumonia, endobr TB
– Extrapulmonary:• lymph nodes
• brain & meninges
• bone & joint
• gastrointestinal
• other organs
Clinical manifestation
• vary, wide spectrum
• factors:
– TB bacilli: numbers, virulence
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– TB bacilli: numbers, virulence
– host: age, immune state
• clinical manifestation
– general manifestation
– organ specific manifestation
General manifestation
• chronic fever, subfebrile
• anorexia
• weight loss
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• weight loss
• malnutrition
• malaise
• chronic recurrent cough, think asthma!
• chronic recurrent diarrhea
• others
Organ specific
• Respiratory : cough, wheezing, dyspnea
• Neurology : convulsion, neck stiffness,
SOL manifestation
• Orthopedic : gibbus, crippled
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• Orthopedic : gibbus, crippled
• Lymph node : enlarge, scrofuloderma
• Gastrointestinal: chronic diarrhea
• Others
Complications of focus
1. Effusion
2. Cavitation
3. Coin shadow
Complications of nodes
1. Extension to bronchus
2. Consolidation
3. HyperinflationMENINGITIS OR MILIARY
in 4% of children infected
under 5 years of ageLATE COMPLICATIONS
Renal & SkinMost after 5 years
BRONCHIAL EROSION
Most children
become tuberculin
sensitive
3-9 months
9/20/2010 61Miller FJW. Tuberculosis in children, 1982
A minority of children
experience :
1. Febrile illness
2. Erythema Nodosum
3. Phlyctenular Conjunctivitis 1 2 3 4 5 6
BONE LESIONMost within
3 years
24 months
Resistance reduced :
1. Early infection
(esp. in first year)
2. Malnutrition
3. Repeated infections :
measles, whooping cough
streptococcal infections
4. Steroid therapy
infection
12 months
DIMINISHING RISK
But still possible
90% in first 2 yearsGREATEST RISK OF LOCAL & DISEMINATED LESIONS
Development Of Complex
4-8 weeks 3-4 weeks fever of onset
PRIMARY COMPLEXProgressive HealingMost cases
Uncommon under 5 years of age25% of cases within 3 months75% of cases within 6 months
3-9 monthsIncidence decreasesAs age increased
Pemeriksaan mikrobiologis
• Memastikan D/ TB
• Hasil negatif tidak menyingkirkan D/ TB
• Hasil positif : 10 - 62 % (cara lama)
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• Hasil positif : 10 - 62 % (cara lama)
• Cara :
– cara lama,
– radiometrik,
– PCR
Imaging diagnostic
• routine : chest X ray
• on indication : bone, joint, abdomen
• majority of CXR non suggestive TB
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• majority of CXR non suggestive TB
• pitfall in TB diagnostic
Radiographic picture
• primary complex: lymph node enlargement
• milliary
• atelectasis
• cavity
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• cavity
• tuberculoma
• pneumonia
• air trapping - hyperinflation
• pleural effusion
• honeycombs – bronchiectasis
• calcification, fibrosis
do not always help, particularly in small childrenat times can be confusing
some cases: extensive disease from radiography � clinical exam revealed little or nothing
Radiographic picture
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� clinical exam revealed little or nothing
more confusing � superadded bacterial
pneumonia (+)
Osborne CM et.al. Arch Dis Child 1995;72:369-74
• No radiographic picture is typical of TB
• Many lung diseases have similar radiographic appearances mimicking PTB
• Cannot distinguish active pulmonary TB –inactive PTB – previously treated TB
Radiographic picture
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inactive PTB – previously treated TB
• May not detect early stages of TB disease– under-reading
– over-reading
– intra-individual inconsistency
Vijayan VK. Indian J Clin Biochem 2002;17(2):96-100.
Commonly found: enlargement of hilar/paratracheal nodes � sometimes difficult to interpret � requires thorax CT with contrast
Radiographic picture
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Thorax CT reveals enlargement of lymph node in 60% children with TB infection and normal Chest röntgenogram
Delacourt C et.al. Arch Dis Child 1993;69:430-2.
100
60
80
100
Over diagnosis TB by CXR
Over-diagnosis
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32
0
20
40
Diagnosed by X-
ray alone
Actual cases
Sensitivity: 19 – 68%
Specificity: 40 – 98%
Disadvantages
Depends on:Type of antigen usedType of infection
Serology
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Disadvantages
results affected by factors such as
- age
- history of BCG vaccination
- exposure to atypical Mycobacteria
- unable to differentiate between infection and disease
Khan EA and Starke JR. Emerg Infect Dis 1995;1:115-23.
Polymerase chain reaction
• PCRPCRPCRPCRfrom gastric aspirate ���� diagnosis of TB in children Sensitivity: 44 – 90%Specificity: 94 – 96,8%Compared to MTB culture
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Compared to MTB cultureLodha R et.al. Indian J Pediatr 2004;71:221-7.
PCR technique using primer containing IS6110 ����better results
Khan EA and Starke JR. Emerg Infect Dis 1995;1:115-23.
May help in early detection of resistant strain of MTBLodha R et.al. Indian J Pediatr 2004;71:221-7.
• Detection of interferon- γ (QuantiFERON-TB)
comparable with TST to detect latent TB infection
Advantages- less affected by BCG vaccination- can discriminates responses due to nontuberculous
Interferon γ
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- can discriminates responses due to nontuberculous mycobacteria
- avoids variability and subjectivity associated with placing and reading TST
The utility of QFT in predicting the progression to active TB has not been evaluated
Mazurek GH et.al. MMWR Dispatch 2002;51.
Prognostic factors
A. TB bacilli :– virulence
– infection dose
B. Patient :– general condition
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– general condition
– age
– nutritional state
– coinfection: morbili, pertussis
– genetic
– stress; physically (trauma, surgery) or mentally
The main problems
• Diagnosis– Clinical manifestations : not specific �both over/under diagnosis & over/under treatment
– diagnostic specimen : difficult to obtain
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– diagnostic specimen : difficult to obtain
– No other definitive diagnostic tools
– TB infection or TB disease ? � no diagnostic tool to distinguish
• Adherence / compliance– Drug discontinuation � treatment failure
Diagnosis1. Tuberculin skin test
2. Chest X ray
3. Clinical manifestation
4. Microbiologic
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5. Pathology
6. Hematological
7. Known infection source
8. Others : serologic, lung function, bronchoscopy
Clinical setting management
Suspect TB
proveTB
Mantoux test
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proveTB infection positive negative
not TB
Seek other etiologies
completed: Ro, labDiagnosis TB
treatment
Practical clinical approach to Ped TB
• Scoring system
�Stegen, 1969
�Smith, Marquis, 1981
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�Migliori dkk, 1992
�WHO, 1994
• Algorithm
�IDAI, 1998, 2002
Algorithm for Early Detection and Referral for Childhood
Tuberculosis in Indonesia
Suspected TB:• Close contact with adult with AFB sputum (+) • Early reaction of BCG (in 3-7 days)• Weight loss with no apparent cause, or underweight with no
improvement in 1 month with adequate nutritional support (failure to thrive)
• Prolonged/recurrent fever with no apparent cause• Cough more than 3 weeks
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• Cough more than 3 weeks• Specific enlargement of superficial lymph node• Scrofuloderma• Flychten conjunctivitis• Tuberculin test positive (> 10 mm)• Radiological findings suggestive TB
If > 3 positive Next page
Considered TB
Give anti-TB therapyObservation in 2 months
Clinical response (+) No clinical response/worsening
TB
Continue anti-TB therapy
Not TB MDR TB
Refer to hospital
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Continue anti-TB therapy Refer to hospital
Reevaluation in Referral Hospital:Clinical signsTuberculin testRadiological findingsMicrobiology and serology examinationHistopatology examinationDiagnostic procedure and therapy according to each hospital’s protocol
ATTENTIONPresence of any dangerous signs:• Seizure• Decreased level of consciousness• Neck stiffnessOr signs such as:• Spinal tumor/lump• Limping • Dam board phenomenon � Send to hospital UKK Pulmonologi –IDAI. Jakarta;2002.
Encountered problem
• Increasing demands of TB drugs for Pediatric TB
• Increasing diagnosis of Pediatric
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TB using the IDAI algorhitm
• Over diagnosis ?
• Need improvement � IDAI scoring system
Proposed IDAI scoring system
Feature 0 1 2 3 Score
Contact not clear reported, AFB(-)
- AFB(+)
TST - - - positive
BW (KMS) - <red line, BW�
severe malnutrition
-
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BW� malnutrition
Fever - unexplained - -
Cough <3weeks >3weeks - -
Node enlargemnt
- >1 node, >1cm,painless
- -
Bone,joint - swelling - -
CXR normal sugestive - -
Notes for IDAI scoring system• Diagnosis by doctor
• BW assessement at present
• Fever & cough no respons to standard tx
• CXR is NOT a main diagnostic tool in children
• All accelerated BCG reaction should be evaluated
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• All accelerated BCG reaction should be evaluated with scoring system
• TB diagnosis total score >5
• Score 4 in under5 child or strong suspicion, refer to hospital
• INH prophylaxis for AFB(+) contact with score <5
Diagnosis of TB in children
• If you find the diagnosis of TB in children easy, you probably overdiagnosing TB
• If you find the diagnosis of TB in children difficult, you are not alone
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difficult, you are not alone
• It is easy to over-diagnose TB in children
• It is also easy to miss TB in children
• Carefully assess all the evidence, before making the diagnosis
Anthony Harries & Dermot Maher, 1997
Objectives of treatment
• Rapid reduction of the number
of bacilli
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• Preventing acquired drug
resistance
• Sterilization to prevent relapses
Treatment principles
• Drug combination, not single drug
• Two phases :
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� Initial phase (2 months) – intensive, bactericidal effect
� Maintenance phase (4 months / more) – ‘sterilizing’ effect, prevent relaps
Smear +Culture +
108
107
106
105
Sensitive organisms Resistant organisms
Nu
mb
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of
bacil
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ml
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sp
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m
The ‘fall and rise’ phenomenon
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Smear -Culture +
Smear -Culture -
104
103
102
101
100
Start of treatment(isoniazid alone)
Weeks of treatment
0 3 6 9 12 15 18 WHO 78351
Nu
mb
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of
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ml
of
sp
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Toman K, Tuberculosis, WHO, 1979
Treatment principles
• Long duration � problem of
adherence (compliance)
• Other aspects :
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• Other aspects :
�Nutrition improvement
� prevent / search & treat other disease
Hypothetical model of TB therapy
A
B
Pop A = rapidly multiplying (caseum)
Pop B = slowly multiplying (acidic)
Pop C = sporadically multiplying
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B
C
Bacteridal activity & ‘sterilizing’ effect
0 1 2 3 4 5 6
Pop C = sporadically multiplying
Months of therapy
DrugsDaily dose
(mg/Kg/day)Adverse reactions
2 Time/week
dose
(mg/Kg/dose))
Isoniazid(INH)
5-15
(300 mg))Hepatitis, peripheral neuritis,
hypersensitivity
15-40
(900 mg))
Rifampicin(RIF)
10-15
(600 mg))
Gastrointestinal upset,skin reaction,hepatitis, thrombocytopenia,
hepatic enzymes, including orangediscolouraution of secretions
10-20
(600 mg)
Dosage of antituberculosis drug
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discolouraution of secretions
Pyrazinamide(PZA)
15 - 40
(2 g)Hepatotoxicity, hyperuricamia,
arthralgia, gastrointestinal upset
50-70
(4 g)
Ethambutol(EMB)
15-25
(2,5 g)
Optic neuritis, decreased visualacuity, decreased red-green colour
discrimination, hypersensitivity,gastrointestinal upset
50
(2,5 g)
Streptomycin(SM)
15 - 40
(1 g)Ototoxicity nephrotoxicity
25-40
(1,5 g)
When INH and RIF are used concurrently, the daily doses of the drugs are reduced
National consensus of tuberculosis in children, 2001
Populasi basil TB pada pasien
Kavitas,ekstrasel
Massa kijuDalam makrofag
(intrasel)
Jumlah populasi 107 - 109 104 - 105 104 - 105
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RIF, INH
Netral
Metabolisme danperkembang biak
AktifLambat atauintermiten
Lambat
pH Netral/basa Asam
Obat paling efektif(berturut-turut)
INH, RIF,STREP
PZA, RIF, INH
Drug activities upon TB pop
TB Population
Multiplying rate
Drug
activities
A rapidly INH>>SM>
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A rapidly INH>>SM>
RIF>EMB
B slowly PZA>>RIF>>
INH
C sporadically RIF>>INH
Corticosteroid
• Anti inflammation
• prednison : 1 - 3 mg/kg BB/hari, 3x/hari oral 2 - 4 minggu, tapering off
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tapering off
• Indications :
– TB milier
– Meningitis TB
– Pleuritis TB with effusion
Treatment evaluation
• Clear improvement in clinical and supporting examination, especially in the first 2 month
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especially in the first 2 month
• Main : clinical
• supporting exam as adjuvant
Treatment evaluation
• Clinical improvement :– Increased body weight
– Increased appetite
– Diminished / reduced symptoms (fever,
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– Diminished / reduced symptoms (fever, cough, etc)
• Supporting examination : – Chest X rays : 2 / 6 month (on indication)
– Blood : BSR
– Tuberculin test : once positive, do not needed to repeat !
Treatment failure
• Inadequate response, despite adequate therapy :
– Review the diagnosis, not a TB case ?
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– Review the diagnosis, not a TB case ?
– Review other aspects : nutrition, other
disease
– MDR – rarely in children
• Treatment discontinuation
Treatment problems
• The main : compliance / adherence
• The factors :
– Long duration
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– Drug side effect
– Initial improvement – misinterpreted by patients /
parents
– Inconvenient health service
– Socio-economic-cultural factors
• The following : drug resistance
DOTS with a SMILE
S : Supervised
M : Medication
S : Supervised
M : Medication
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I : In
L : a Loving
E : Environment
(Grange JM, Int J Tuberc Lung Dis 1999; 3:360-362)
I : In
L : a Loving
E : Environment
(Grange JM, Int J Tuberc Lung Dis 1999; 3:360-362)
Treament problem solution: FDC
Fixed dose combination: >2 drugs in one tablet in a fixed dose formulation
• simple dosing
• patient friendly, doctor friendly
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• patient friendly, doctor friendly
• increase adherence
• reduce MDR
• easier drug supplying
• easier drug monitoring
FDC tablet formulation
WHO
• H : 30 mg
• R : 60 mg
IDAI
• H : 50 mg
• R : 75 mg
9/20/2010 102
• R : 60 mg
• Z : 150 mg
• R : 75 mg
• Z : 150 mg
WHO FDC (H/R/Z:30/60/150 & H/R:30/60)
BW
(kg)
Intensive, 2 mo
(tablet)
Continuation, 4 mo
(tablet)
<7 1 1
9/20/2010 103
8-9 1,5 1,5
10-14 2 2
15-19 3 3
20-24 4 4
25-29 5 5
IDAI FDC (H/R/Z:50/75/150 & H/R:50/75)
BW
(kg)
Intensive, 2 mo
(tablet)
Continuation, 4 mo
(tablet)
5-9 1 1
9/20/2010 104
5-9 1 1
10-19 2 2
20-33 4 4
Note: BW < 5kg should be referred and need tailored dosing
WHO vs IDAI fdc formulation
• WHO:
– INH: 4-6 mg/kgBW
– BW grouping: too many
– not practical
– hard to remember
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– hard to remember
– a gap for BW 30-33 kg
• IDAI
– INH: 5-10 mg/kgBW
– simple BW grouping
– more friendly both for doctor and patient
case finding
centripetal
• trace the source
• adult people
centrifugal
• trace other ‘victims’
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• adult people
• close contact
• by chest X ray
‘victims’
• children
• close contact
• by tuberculin
Pencegahan
• Perbaikan sosio ekonomi
• Kemoprofilaksis
• Imunisasi BCG
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• Imunisasi BCG
Kemoprofilaksis primer
• Mencegah infeksi
• Anak kontak dengan pasien TB aktif, tetapi
belum terinfeksi (uji tuberkulin negatif)
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• Obat : INH 5 - 10 mg/kg BB/hari
Kemoprofilaksis sekunder
Mencegah penyakit TB pada anak yang terinfeksi :
1. Mantoux (+), Rö (-), klinis (-) :• Umur < 5 th
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• Umur < 5 th
• Kortikosteroid lama
• Limfoma, Hodgkin, lekemi
• Morbili, pertusis
• Akil baliq
2. Konversi Mt (-) menjadi (+) dalam 12 bl, Rö (-), klinis (-)
Obat INH 5 - 10 mg/kg BB/hari
Imunisasi BCG
• Imunitas spesifik
• Uji tuberkulinmenjadi (+)
• Mt (-) baru BCG
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• Mt (-) baru BCG
• Masal : langsung BCG tanpa Mt
• Reaksi lokal : membantu screening