Professional Documents
Culture Documents
Ridwan M Daulay
Wisman Dalimunthe
Rini Savitri Daulay
12/26/2018 1
Definition
Tuberculosis is a disease due to
Mycobacterium tuberculosis 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
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Pathogenesis
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Droplet nuclei Alveoli Ingestion by PAM’S
inhalation
Intracellular replication
of bacilli
Destruction
Destruction of PAM’S of bacilli
Hematogenic spread
Primary
Acute hematogenic Occult hematogenic
complex
spread spread
Multiple organs
CMI
Disseminated primary TB remote foci
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Figure. Pathogenesis of primary tuberculosis
Pathogenesis ...
Simon focus Lymphadenitis
Lymphangitis
Primary focus
(Ghon focus)
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Transmission rate (Shaw ’54)
Adult
TB patient
AFB(-) Culture(-)
AFB(+) Culture(+) CXR (+)
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Diagnosis
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Diagnosis
1. Known infection source
2. Clinical manifestation
3. Tuberculin skin test
4. Chest X ray
5. Microbiology
6. Pathology
7. Others : serologic
Critical Analysis
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Clinical Manifestation
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Systemic Manifestation
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Spesific Manifestation
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Tuberculin Skin Test
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Tuberculin test
TB infection
Cellular immunity
Tuberculin reaction
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Tuberculin
PPD S
Strength PPD RT23
Seibert
first 1 TU 1 TU
intermediate
5-10 TU 2-5 TU
(standard dose)
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Tuberculin delivery
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Tuberculin
Mantoux 0.1 ml PPD intermediate strength
Location : volar lower arm
Reading time : 48-72 h post injection
Measurement : palpation, marked, measure
Report : in millimeter, even ‘0 mm’
Induration diameter :
0 - 5 mm : negative
5 - 9 mm : doubt
> 10 mm : positive
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Mantoux
test
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Pengukuran Uji Tuberkulin
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Tuberculin positive
1. TB infection :
Infection without disease / latent TB infection
Infection AND disease
Disease, post therapy
2. BCG immunization
3. Infection of Mycobacterium atypic
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Tuberculin negative
1. No TB infection
2. Anergy
3. Incubation period
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Anergy
Patient 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
• Certain viral infection: morbili, varicella
• Severe bacterial infection: typhus abdominalis,
diphteria, pertussis
• Viral vaccination: morbili, polio
• Malignancy: Hodgkin, leukemia
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Microbiology
• Culture (Lowenstein Jensen)
• Confirm the diagnosis
• Negative result do not rule out TB
• Positive result : 10 - 62 % (old method)
• Methods:
– Old method
– Radiometric (Bactec)
– PCR
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Polymerase chain reaction
From gastric aspirate diagnosis of TB in children
Sensitivity: 44 – 90%
Specificity: 94 – 96,8%
compared to MTB culture
Lodha R et.al. Indian J Pediatr 2004;71:221-7.
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Radiology
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Imaging diagnostic
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Radiographic picture
• 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
• May not detect early stages of TB disease
– under-reading
– over-reading
– intra-individual inconsistency
20
0
Diagnosed by X- Actual cases
ray alone
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Serology
Depends on:
Sensitivity: 19 – 68%
-Type of antigen used
Specificity: 40 – 98% -Type of infection
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.
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Interferon γ
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
mycobacteria
- Avoids variability and subjectivity associated with
placing and reading TST
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Clinical setting
management
Suspect TB
Positive Negative
Completed: Not TB
Diagnosis TB
Ro, lab
Seek other
Therapy
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etiologies 37
Therapy
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Objectives of TB therapy
• Rapid reduction of the bacilli number, to cure
the patient
• ‘Sterilization’ to prevent relapses
to achieve two phases:
Initial phase (2 months) – intensive, bacilli eradication
Maintenance phase (4 months / more) – ‘sterilizing’ effect,
prevent relapse
• Prevention of acquired drug resistance,
to achieve: principles of therapy
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Ped TB therapy principles
106
Smear +
Culture +
105
104
Smear -
Culture +
103
102
101 Smear -
Culture -
100
0 3 6 9 12 15 18 WHO 78351
Start of treatment Weeks of treatment
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Toman K, Tuberculosis, WHO, 1979
TB therapy regimen
2 mo 6 mo 9 mo 12mo
INH
RIF
PZA
ETB
SM
PRED
DOT.S !
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Dosage of antituberculosis drug
2 Time/week
Daily dose
Drugs (mg/Kg/day)
dose Adverse reactions
(mg/Kg/dose))
Isoniazid 5-15 15-40 Hepatitis, peripheral neuritis,
(INH) (300 mg)) (900 mg)) hypersensitivity
Gastrointestinal upset,skin reaction,
Rifampicin 10-15 10-20 hepatitis, thrombocytopenia,
(RIF) (600 mg)) (600 mg) hepatic enzymes, including orange
discolouraution of secretions
Streptomycin 15 - 40 25-40
Ototoxicity nephrotoxicity
(SM) (1 g) (1,5 g)
When INH and RIF are used concurrently, the daily doses of the drugs are reduced
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National consensus of tuberculosis in children, 2001
Corticosteroid
• Anti inflammation
• prednisone : oral, 1-2mg/kgBW/day, tid
2-4 weeks, tap off
• Indications :
– Miliary TB
– Meningitis TB
– Pleuritis TB with effusion
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Treatment problems
• The main : compliance / adherence
• The factors :
– Long duration
– Drug side effect
– Initial improvement – misinterpreted by
patients / parents
– Inconvenient health service
– Socio-economic-cultural factors
• The following : drug resistance
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Treament problem solution:
FDC
Rifampicin (R)
combi-packs
Pyrazinamide (Z)
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Combipack drugs
two or more separate drugs put in one pack
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FDC with IDAI formulation
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WHO FDC (H/R/Z:30/60/150 & H/R:30/60)
BW Intensive, 2 mo Continuation, 4 mo
(kg) (tablet) (tablet)
<7 1 1
8-9 1,5 1,5
10-14 2 2
15-19 3 3
20-24 4 4
25-29 5 5
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IDAI FDC (H/R/Z:50/75/150 & H/R:50/75)
BW Intensive, 2 mo Continuation, 4 mo
(kg) (tablet) (tablet)
5-9 1 1
10-14 2 2
15-19 3 3
20-33 4 4
Note: BW < 5kg should be referred and need tailored dosing
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fixed dose combination
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Therapy evaluation
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Therapy evaluation
• Clinical improvement :
– Increased body weight
– Increased appetite
– Diminished / reduced symptoms (fever, cough,
etc)
• Supporting examination :
– Chest X rays : 2 / 6 months (on indication)
– Blood : ESR
– Tuberculin test : once positive, should not be
repeated
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TB classification (ATS/CDC modified)
0 - - - -
1 + - - proph I
2 + + - proph II?
3 + + + therapy
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Primary prophylaxis
• To prevent TB infection in TB Class 1 person
• Exposure (+), infection (-) tuberculin negative
• Drug: INH 5 - 10 mg/kgBW/day
• As long as contact take place, the source should
be treated
• At least for 3 months
• Repeat TST:
– Negative: success, stop INH
– Positive: fail, become TB Class 2 continue as 2nd proph
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Secondary prophylaxis
• To prevent TB disease in TB Class 2 person
(exposure (+), infection (+), disease (-)
• High risk population
– Under five, puberty
– Long term use of steroid
– Malignancy
– Viral infection: morbili, pertussis
– Conversion of tuberculin test
• Drug: INH 5 - 10 mg/kgBW/day 6-12 month
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Prevention
• Socio-economic improvement
• BCG immunization
• Chemoprophylaxis (1st & 2nd)
• ‘Therapy’
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BCG immunization
• Mimicking the TB pathogenesis with attenuated
TB bacilli
• Without hematogenic spread and/or without
establishment of remote foci
• CMI (+) DTH (+) TST (+)
• Older neonate (>2 month not vaccinated) TST
first
• Mass immunization : BCG without TST first
• Accelerated BCG reaction: help the screening
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Diagnosis of TB in
children
If you find the diagnosis of TB in children easy,
you probably overdiagnosing TB
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