![Page 1: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/1.jpg)
Pediatric Tuberculosis
9/20/2010 1
![Page 2: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/2.jpg)
Definition
Tuberculosis is a disease due to Mycobacterium tuberculosisinfection with systemic spread thus
9/20/2010 2
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
![Page 3: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/3.jpg)
Tuberculosis
The reaction of the tissues of the human host to the presence and multiplication of
9/20/2010 3
human host to the presence and multiplication of Mycobacterium tuberculosis or Mycobacterium bovis
![Page 4: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/4.jpg)
History
• ancient Egypt : gibbus
• 1882, Koch, identification
• management : sanatorium, collapse treatment
9/20/2010 4
treatment
• Chemotherapy :– PAS – 1943 – Lehmann
– Streptomycine – 1945 - Waksman & Schats
– Isoniazid – 1952 – Domagk
– Rifampicine - 1957
![Page 5: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/5.jpg)
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
9/20/2010 5
• 8 million of new cases yearly
• 3 million death yearly
• 20-40% population is infected
• reemergence, global emergency
![Page 6: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/6.jpg)
The secret
Why TB is so strong and robust?
• the secret: specific characters of the bacilli
9/20/2010 6
• special issues:
hematogenic spread
infection vs disease
primary vs post-primary
![Page 7: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/7.jpg)
The main problems
• Diagnosis
– Clinical manifestations : not specific �
both over/under diagnosis & over/under treatment
9/20/2010 7
– diagnostic specimen : difficult to obtain
– TB infection or TB disease ? � no
diagnostic tool to distinguish
• Adherence / compliance
– Drug discontinuation � treatment failure
![Page 8: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/8.jpg)
Etiology
9/20/2010 8
Etiology
![Page 9: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/9.jpg)
The bacilli• Mycobacterium tuberculosis• Mycobacterium bovis
features:
� slender, often slightly curved, rods
9/20/2010 9
� 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)
![Page 10: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/10.jpg)
TB bacilli
9/20/2010 10
TB bacilli
![Page 11: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/11.jpg)
M tuberculosisCharacteristics :
1. live in weeks in dry condition
2. no endotoxins, no exotoxins
3. hematogenic spread
9/20/2010 11
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
![Page 12: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/12.jpg)
Transmission
9/20/2010 12
Transmission
![Page 13: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/13.jpg)
Transmission ...
• airborne human to human transmission by droplet nuclei
• adult pulmonary TB: cough, sneeze, speak, or sing
9/20/2010 13
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
![Page 14: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/14.jpg)
TB droplet nuclei
9/20/2010 14
![Page 15: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/15.jpg)
Transmission factors:
• doses / numbers
• concentration in the air
• virulence
9/20/2010 15
• virulence
• exposure duration
• host immune state
![Page 16: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/16.jpg)
Infection source
• Known source of infection, has
diagnostic value
• Shaw (1954), level of infectiousness :
9/20/2010 16
• Shaw (1954), level of infectiousness :– AFB (+) : 62.5 %
– AFB (-), M tb (+) : 26.8 %
– AFB (-), M tb (-) : 17.6 %
![Page 17: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/17.jpg)
Transmission rate (Shaw ’54)
adultTB patient
9/20/2010 17
AFB(+)AFB(-)
culture(+)culture(-)CXR (+)
65% 26% 17%
![Page 18: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/18.jpg)
Pathogenesis
9/20/2010 18
Pathogenesis
![Page 19: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/19.jpg)
Location of primary focus
in 2,114 cases, 1909-1928
Location %Lung 95.93
Intestine 1.14
Skin 0.14
9/20/2010 19
Skin 0.14
Nose 0.09
Tonsil 0.09
Middle ear (Eustachian tube) 0.09
Parotid 0.05
Conjunctiva 0.05
Undetermined 2.41
![Page 20: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/20.jpg)
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
![Page 21: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/21.jpg)
Incubation period
• first implantation � primary complex
• 4-6 weeks (2-12 weeks) � incubation period
• first weeks: logaritmic growth, : 103-10
4 �
elicit cellular response
9/20/2010 21
elicit cellular response
• end of incubation period:
– primary complex formation
– cell mediated immunity
– tuberculin sensitivity
�������� PrimaryTB infection has established
![Page 22: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/22.jpg)
lymphadenitis
lymphangitis
Pathogenesis ...Pathogenesis ...
9/20/2010 22
primary focus
![Page 23: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/23.jpg)
Hematogenous spread
• during incubation period, before TB infection establishment:
– lymphogenic spread
– hematogenic spread
9/20/2010 23
–hematogenic spread
• hematogenic spread (HS):
–occult HS
–acute generalized HS
![Page 24: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/24.jpg)
Occult HS
• most common
• sporadic, small number
• no immediate clinical manifestation
• remote foci in almost every organ
9/20/2010 24
• remote foci in almost every organ
• rich vascularization: brain, liver, bones & joints, kidney
• including: lung – apex region
• CMI (+): silent foci - dormant, potential for reactivation
![Page 25: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/25.jpg)
TB hematogenous spread
9/20/2010 25
![Page 26: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/26.jpg)
Acute HS
• less common
• large number
• immediate clinical manifestation: disseminated TB
9/20/2010 26
disseminated TB
• milliary TB, meningitis TB
• tubercle in same size, special appearance in CXR
![Page 27: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/27.jpg)
Miliary TB
9/20/2010 27
Miliary TB
![Page 28: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/28.jpg)
Primary complex
• end of incubation period
• TB infection establishment
• tuberculin sensitivity (DTH)
• cell mediated immunity
9/20/2010 28
• cell mediated immunity
• end of hematogenic spread
• end of TB bacilli proliferation
• small amount, live dormant in granuloma
• new exogenous TB bacilli: destroyed / localized
![Page 29: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/29.jpg)
Tuberculin skin test
9/20/2010 29
Tuberculin skin test
![Page 30: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/30.jpg)
Tuberculin test
TB infection
cellular immunity
9/20/2010 30
delayed type hypersensitivity
tuberculin reaction
![Page 31: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/31.jpg)
Tuberculin
StrengthPPD S
SeibertPPD RT23
first 1 TU 1 TU
9/20/2010 31
first 1 TU 1 TU
intermediate(standard dose)
5-10 TU 2-5 TU
second 250 TU 100 TU
![Page 32: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/32.jpg)
Tuberculin delivery
1. Mantoux : intradermal injection
2. Multiple puncture :
9/20/2010 32
• Heaf, special apparatus with 6 needles
• Tine, disposable, 4 needles
3. Patch test
![Page 33: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/33.jpg)
Tuberculin
Mantoux 0.1 ml PPD intermediate strength
location : volar lower arm
reading time : 48-72 h post injection
measurement : palpation, marked, measure
9/20/2010 33
report : in millimeter, even ‘0 mm’
Induration diameter :
� 0 - 5 mm : negative
� 5 - 9 mm : doubt
� > 10 mm : positive
![Page 34: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/34.jpg)
Mantoux
tuberculin
9/20/2010 34
tuberculin
skin test
![Page 35: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/35.jpg)
9/20/2010 35
![Page 36: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/36.jpg)
9/20/2010 36
![Page 37: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/37.jpg)
9/20/2010 37
![Page 38: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/38.jpg)
Pengukuran Uji tuberkulin
9/20/2010 38
![Page 39: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/39.jpg)
9/20/2010 39
![Page 40: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/40.jpg)
Tuberculin positive
1. TB infection :
� infection without disease / latent TB infection
� infection and disease
9/20/2010 40
� infection and disease
� disease, post therapy
2. BCG immunization
3. Infection of Mycobacterium atypic
![Page 41: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/41.jpg)
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
9/20/2010 41
• Steroid, long term use
• Certain viral infection: morbili, varicella
• Severe bacterial infection: typhus abdominalis, diphteria, pertussis
• Viral vaccination: morbili, polio
• Malignancy: Hodgkin, leukemia, ...
![Page 42: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/42.jpg)
TB infection & TB disease
• TB infection: CMI can control infection
– primary complex
– tuberculin sensitivity (DTH)
– cell mediated immunity
9/20/2010 42
– cell mediated immunity
– no clinical or radiological manifestation
• TB disease: CMI failed to control TB infectionTB infection + clinical and/or radiological manifestation
![Page 43: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/43.jpg)
TB classification (ATS/CDC modified)
Class Contact Infection Disease Manage ment
0 - - - -
1 - -
9/20/2010 43
1 + - - proph I
2 + + - proph II?
3 + + + therapy
![Page 44: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/44.jpg)
TB Natural history overviewprimary TB infection
primary TB disease latent infection
9/20/2010 44
no diseasepost primary TB
respiratory TBnon respir TB
new infection
![Page 45: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/45.jpg)
Pathology
9/20/2010 45
Pathology
![Page 46: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/46.jpg)
Pathology
• complicated pathogenesis �varied pathology
�clinical manifestation
�radiologic appearance
9/20/2010 46
�radiologic appearance
• lung represent
• tubercle, granuloma, tuberculoma, fibrosis, fistula, cavity, atelectasis
• complication of primary focus: so many possibilities
![Page 47: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/47.jpg)
Lesions of pulmonary TB
• Parenchym: primary focus, pneumonia, atelectasis, tuberculoma, cavitary
• Lymph node: hilar, paratracheal, mediastinal
• Airway: air trapping, endobronchial TB,
9/20/2010 47
• Airway: air trapping, endobronchial TB, bronchial stenosis, fistula, bronchiectasis
• Pleura: effusion, fistula, empyema, pneumothorax, hemothorax
• Blood vessels: milliary, hemorrhage
![Page 48: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/48.jpg)
tubercle formationresolution
primary focus
PathologyPathology
remote focireg lymph node
milliary seed
9/20/2010 48
calcification
2nd lung lesions
caseation
liquefaction
granuloma
tuberculoma
cavity
erodes airway
compresses airway
rupt to pleura rupt to airway bronchiectasis
fibrosis
br pl fistula
![Page 49: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/49.jpg)
Clinical
9/20/2010 49
Clinical
![Page 50: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/50.jpg)
Clinical types of pediatric TB
• Infection: TST (+), clinical (-), radiographic (-)
• Disease:– Pulmonary:
• primary pulmonary TB
• milliary TB
• pleuritis TB
9/20/2010 50
• pleuritis TB
• progr primary pulm TB: pneumonia, endobr TB
– Extrapulmonary:• lymph nodes
• brain & meninges
• bone & joint
• gastrointestinal
• other organs
![Page 51: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/51.jpg)
Clinical manifestation
• vary, wide spectrum
• factors:
– TB bacilli: numbers, virulence
9/20/2010 51
– TB bacilli: numbers, virulence
– host: age, immune state
• clinical manifestation
– general manifestation
– organ specific manifestation
![Page 52: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/52.jpg)
General manifestation
• chronic fever, subfebrile
• anorexia
• weight loss
9/20/2010 52
• weight loss
• malnutrition
• malaise
• chronic recurrent cough, think asthma!
• chronic recurrent diarrhea
• others
![Page 53: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/53.jpg)
Organ specific
• Respiratory : cough, wheezing, dyspnea
• Neurology : convulsion, neck stiffness,
SOL manifestation
• Orthopedic : gibbus, crippled
9/20/2010 53
• Orthopedic : gibbus, crippled
• Lymph node : enlarge, scrofuloderma
• Gastrointestinal: chronic diarrhea
• Others
![Page 54: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/54.jpg)
9/20/2010 54
![Page 55: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/55.jpg)
9/20/2010 55
![Page 56: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/56.jpg)
9/20/2010 56
![Page 57: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/57.jpg)
9/20/2010 57
![Page 58: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/58.jpg)
9/20/2010 58
![Page 59: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/59.jpg)
9/20/2010 59
![Page 60: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/60.jpg)
9/20/2010 60
![Page 61: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/61.jpg)
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
![Page 62: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/62.jpg)
Pemeriksaan mikrobiologis
• Memastikan D/ TB
• Hasil negatif tidak menyingkirkan D/ TB
• Hasil positif : 10 - 62 % (cara lama)
9/20/2010 62
• Hasil positif : 10 - 62 % (cara lama)
• Cara :
– cara lama,
– radiometrik,
– PCR
![Page 63: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/63.jpg)
Radiology, serology , ...
9/20/2010 63
Radiology, serology , ...
![Page 64: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/64.jpg)
Imaging diagnostic
• routine : chest X ray
• on indication : bone, joint, abdomen
• majority of CXR non suggestive TB
9/20/2010 64
• majority of CXR non suggestive TB
• pitfall in TB diagnostic
![Page 65: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/65.jpg)
Radiographic picture
• primary complex: lymph node enlargement
• milliary
• atelectasis
• cavity
9/20/2010 65
• cavity
• tuberculoma
• pneumonia
• air trapping - hyperinflation
• pleural effusion
• honeycombs – bronchiectasis
• calcification, fibrosis
![Page 66: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/66.jpg)
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
9/20/2010 66
� clinical exam revealed little or nothing
more confusing � superadded bacterial
pneumonia (+)
Osborne CM et.al. Arch Dis Child 1995;72:369-74
![Page 67: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/67.jpg)
• 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
9/20/2010 67
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.
![Page 68: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/68.jpg)
Commonly found: enlargement of hilar/paratracheal nodes � sometimes difficult to interpret � requires thorax CT with contrast
Radiographic picture
9/20/2010 68
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.
![Page 69: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/69.jpg)
100
60
80
100
Over diagnosis TB by CXR
Over-diagnosis
9/20/2010 69
32
0
20
40
Diagnosed by X-
ray alone
Actual cases
![Page 70: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/70.jpg)
Sensitivity: 19 – 68%
Specificity: 40 – 98%
Disadvantages
Depends on:Type of antigen usedType of infection
Serology
9/20/2010 70
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.
![Page 71: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/71.jpg)
Polymerase chain reaction
• PCRPCRPCRPCRfrom gastric aspirate ���� diagnosis of TB in children Sensitivity: 44 – 90%Specificity: 94 – 96,8%Compared to MTB culture
9/20/2010 71
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.
![Page 72: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/72.jpg)
• 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
9/20/2010 72
- 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.
![Page 73: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/73.jpg)
Diagnosis
9/20/2010 73
Diagnosis
![Page 74: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/74.jpg)
Prognostic factors
A. TB bacilli :– virulence
– infection dose
B. Patient :– general condition
9/20/2010 74
– general condition
– age
– nutritional state
– coinfection: morbili, pertussis
– genetic
– stress; physically (trauma, surgery) or mentally
![Page 75: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/75.jpg)
The main problems
• Diagnosis– Clinical manifestations : not specific �both over/under diagnosis & over/under treatment
– diagnostic specimen : difficult to obtain
9/20/2010 75
– 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
![Page 76: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/76.jpg)
Diagnosis1. Tuberculin skin test
2. Chest X ray
3. Clinical manifestation
4. Microbiologic
9/20/2010 76
5. Pathology
6. Hematological
7. Known infection source
8. Others : serologic, lung function, bronchoscopy
![Page 77: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/77.jpg)
Clinical setting management
Suspect TB
proveTB
Mantoux test
9/20/2010 77
proveTB infection positive negative
not TB
Seek other etiologies
completed: Ro, labDiagnosis TB
treatment
![Page 78: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/78.jpg)
Practical clinical approach to Ped TB
• Scoring system
�Stegen, 1969
�Smith, Marquis, 1981
9/20/2010 78
�Migliori dkk, 1992
�WHO, 1994
• Algorithm
�IDAI, 1998, 2002
![Page 79: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/79.jpg)
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
9/20/2010 79
• 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
![Page 80: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/80.jpg)
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
9/20/2010 80
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.
![Page 81: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/81.jpg)
Encountered problem
• Increasing demands of TB drugs for Pediatric TB
• Increasing diagnosis of Pediatric
9/20/2010 81
TB using the IDAI algorhitm
• Over diagnosis ?
• Need improvement � IDAI scoring system
![Page 82: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/82.jpg)
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
-
9/20/2010 82
BW� malnutrition
Fever - unexplained - -
Cough <3weeks >3weeks - -
Node enlargemnt
- >1 node, >1cm,painless
- -
Bone,joint - swelling - -
CXR normal sugestive - -
![Page 83: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/83.jpg)
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
9/20/2010 83
• 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
![Page 84: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/84.jpg)
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
9/20/2010 84
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
![Page 85: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/85.jpg)
Treatment
9/20/2010 85
Treatment
![Page 86: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/86.jpg)
Objectives of treatment
• Rapid reduction of the number
of bacilli
9/20/2010 86
• Preventing acquired drug
resistance
• Sterilization to prevent relapses
![Page 87: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/87.jpg)
Treatment principles
• Drug combination, not single drug
• Two phases :
9/20/2010 87
� Initial phase (2 months) – intensive, bactericidal effect
� Maintenance phase (4 months / more) – ‘sterilizing’ effect, prevent relaps
![Page 88: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/88.jpg)
Smear +Culture +
108
107
106
105
Sensitive organisms Resistant organisms
Nu
mb
er
of
bacil
li p
er
ml
of
sp
utu
m
The ‘fall and rise’ phenomenon
9/20/2010 88
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
er
of
bacil
li p
er
ml
of
sp
utu
m
Toman K, Tuberculosis, WHO, 1979
![Page 89: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/89.jpg)
Treatment principles
• Long duration � problem of
adherence (compliance)
• Other aspects :
9/20/2010 89
• Other aspects :
�Nutrition improvement
� prevent / search & treat other disease
![Page 90: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/90.jpg)
Hypothetical model of TB therapy
A
B
Pop A = rapidly multiplying (caseum)
Pop B = slowly multiplying (acidic)
Pop C = sporadically multiplying
9/20/2010 90
B
C
Bacteridal activity & ‘sterilizing’ effect
0 1 2 3 4 5 6
Pop C = sporadically multiplying
Months of therapy
![Page 91: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/91.jpg)
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
9/20/2010 91
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
![Page 92: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/92.jpg)
Populasi basil TB pada pasien
Kavitas,ekstrasel
Massa kijuDalam makrofag
(intrasel)
Jumlah populasi 107 - 109 104 - 105 104 - 105
9/20/2010 92
RIF, INH
Netral
Metabolisme danperkembang biak
AktifLambat atauintermiten
Lambat
pH Netral/basa Asam
Obat paling efektif(berturut-turut)
INH, RIF,STREP
PZA, RIF, INH
![Page 93: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/93.jpg)
Drug activities upon TB pop
TB Population
Multiplying rate
Drug
activities
A rapidly INH>>SM>
9/20/2010 93
A rapidly INH>>SM>
RIF>EMB
B slowly PZA>>RIF>>
INH
C sporadically RIF>>INH
![Page 94: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/94.jpg)
TB therapy regimen
2 mo 6 mo 9 mo 12mo
INHRIF
9/20/2010 94
RIFPZA
EMBSM
PREDDOT.S !
![Page 95: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/95.jpg)
Corticosteroid
• Anti inflammation
• prednison : 1 - 3 mg/kg BB/hari, 3x/hari oral 2 - 4 minggu, tapering off
9/20/2010 95
tapering off
• Indications :
– TB milier
– Meningitis TB
– Pleuritis TB with effusion
![Page 96: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/96.jpg)
Treatment evaluation
• Clear improvement in clinical and supporting examination, especially in the first 2 month
9/20/2010 96
especially in the first 2 month
• Main : clinical
• supporting exam as adjuvant
![Page 97: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/97.jpg)
Treatment evaluation
• Clinical improvement :– Increased body weight
– Increased appetite
– Diminished / reduced symptoms (fever,
9/20/2010 97
– 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 !
![Page 98: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/98.jpg)
Treatment failure
• Inadequate response, despite adequate therapy :
– Review the diagnosis, not a TB case ?
9/20/2010 98
– Review the diagnosis, not a TB case ?
– Review other aspects : nutrition, other
disease
– MDR – rarely in children
• Treatment discontinuation
![Page 99: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/99.jpg)
Treatment problems
• The main : compliance / adherence
• The factors :
– Long duration
9/20/2010 99
– Drug side effect
– Initial improvement – misinterpreted by patients /
parents
– Inconvenient health service
– Socio-economic-cultural factors
• The following : drug resistance
![Page 100: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/100.jpg)
DOTS with a SMILE
S : Supervised
M : Medication
S : Supervised
M : Medication
9/20/2010 100
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)
![Page 101: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/101.jpg)
Treament problem solution: FDC
Fixed dose combination: >2 drugs in one tablet in a fixed dose formulation
• simple dosing
• patient friendly, doctor friendly
9/20/2010 101
• patient friendly, doctor friendly
• increase adherence
• reduce MDR
• easier drug supplying
• easier drug monitoring
![Page 102: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/102.jpg)
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
![Page 103: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/103.jpg)
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
![Page 104: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/104.jpg)
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
![Page 105: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/105.jpg)
WHO vs IDAI fdc formulation
• WHO:
– INH: 4-6 mg/kgBW
– BW grouping: too many
– not practical
– hard to remember
9/20/2010 105
– 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
![Page 106: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/106.jpg)
TraceTraceTraceTrace
Adult TB patient centri-
fugal
9/20/2010 106
Child TBpatient
centri-petal
![Page 107: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/107.jpg)
case finding
centripetal
• trace the source
• adult people
centrifugal
• trace other ‘victims’
9/20/2010 107
• adult people
• close contact
• by chest X ray
‘victims’
• children
• close contact
• by tuberculin
![Page 108: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/108.jpg)
Pencegahan
• Perbaikan sosio ekonomi
• Kemoprofilaksis
• Imunisasi BCG
9/20/2010 108
• Imunisasi BCG
![Page 109: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/109.jpg)
Kemoprofilaksis primer
• Mencegah infeksi
• Anak kontak dengan pasien TB aktif, tetapi
belum terinfeksi (uji tuberkulin negatif)
9/20/2010 109
• Obat : INH 5 - 10 mg/kg BB/hari
![Page 110: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/110.jpg)
Kemoprofilaksis sekunder
Mencegah penyakit TB pada anak yang terinfeksi :
1. Mantoux (+), Rö (-), klinis (-) :• Umur < 5 th
9/20/2010 110
• 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
![Page 111: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/111.jpg)
Imunisasi BCG
• Imunitas spesifik
• Uji tuberkulinmenjadi (+)
• Mt (-) baru BCG
9/20/2010 111
• Mt (-) baru BCG
• Masal : langsung BCG tanpa Mt
• Reaksi lokal : membantu screening
![Page 112: Pediatric TB.ppt [Read-Only]ocw.usu.ac.id/course/download/1125-respirologi/mk_res_slide_pediatric_tuberculosis.pdfDefinition Tuberculosis is a disease due to Mycobacterium tuberculosis](https://reader030.vdocuments.us/reader030/viewer/2022040721/5e2e2442787f592bc114cc64/html5/thumbnails/112.jpg)
Thank you
9/20/2010 112
Thank you