Pathogenesis TB In Children

HMS Chandra Kusuma Pediatric Departement Of Fac. Med. Brawijaya Univ. Saiful Anwar General Hospital

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

Tuberculosis
The reaction of the tissues of the human host to the presence and multiplication of Mycobacterium tuberculosis or

Mycobacterium bovis

History
ancient Egypt : gibbus 1882, Koch, identification management : sanatorium, collapse 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 3 million death yearly 20-40% population is infected reemergence, global emergency

The secret
Why TB is so strong & robust? the secret: specific characters of the bacilli special issues:
hematogenic spread infection vs disease primary vs post-primary

Etiology

The bacilli
Mycobacterium tuberculosis Mycobacterium bovis
features: slender, often slightly curved, rods 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)

TB bacilli

M tuberculosis
Unique characteristics : 1. live in weeks in dry condition 2. no endotoxins, no exotoxins 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

Transmission ...
airborne human to human transmission by droplet nuclei adult pulmonary TB: cough, sneeze, speak, or sing droplet nuclei : contain 2-3 bacilli, small size (1-5) keep in the air for long period inhalation, reach alveoli middle and lower lobes

TB droplet nuclei

Transmission factors:
doses / numbers concentration in the air virulence exposure duration host immune state

Infection source
Known source of infection, has diagnostic value Shaw (1954), transmission rate:
AFB (+) : 62.5 % AFB (-), M tb (+) : 26.8 % AFB (-), M tb (-) : 17.6 %

Transmission rate (Shaw 54)

adult TB patient
AFB(+)
AFB(-) culture(+) culture(-) CXR (+)

65%

26%

17%

Pathogenesis

Location of primary focus in 2,114 cases, 1909-1928

Location
Lung Intestine Skin Nose Tonsil Middle ear (Eustachian tube) Parotid Conjunctiva Undetermined

%
95.93 1.14 0.14 0.09 0.09 0.09 0.05 0.05 2.41

Pathogenesis
droplet nuclei inhalation

alveoli
intracellular replication of bacilli

ingestion by PAMS

destruction of PAMS
Tubercle formation primary focus Lymphogenic spread lymphangitis

destruction of bacilli

Hilar lymph nodes lymphadenitis

hematogenic spread acute hematogenic spread occult hematogenic spread

multiple organs remote foci

primary complex

CMI

disseminated primary TB

Figure. Pathogenesis of primary tuberculosis

Pathogenesis
M tuberculosis inoculation

M tb destroyed

phagocytocis by PAM

M tb survive, replicate
primary focus formation lymphogenic spread hematogenous spread tuberculin test (+) primary complex CMI (+)

incubation period 2-12weeks

TB disease
complication of: (1)primary complex, (2)lymphogenic and (3)hematogenous spread

TB infection
optimal immunity

primary TB

death

cured

reactivation / reinfection

TB disease

post primary TB

Incubation period
first implantation primary complex 4-6 weeks (2-12 weeks) incubation period 3 4 first weeks: logaritmic growth, : 10 -10 elicit cellular response end of incubation period:
primary complex formation cell mediated immunity tuberculin sensitivity

Primary TB infection has established

Hematogenous spread
during incubation period, before TB infection establishment:
lymphogenic spread 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 rich vascularization: brain, liver, bones & joints, kidney including: lung apex region (Simon focus) CMI (+): silent foci - dormant, potential for reactivation

Pathogenesis ...
Simon focus
lymphadenitis

lymphangitis

primary focus

Ghon focus

TB hematogenous spread

Acute HS
less common large number immediate clinical manifestation: disseminated TB milliary TB, meningitis TB tubercle in same size, special appearance in CXR

Miliary TB

Primary complex
end of incubation period TB infection establishment tuberculin sensitivity (DTH) cell mediated immunity end of hematogenic spread end of TB bacilli proliferation small amount, live dormant in granuloma new exogenous TB bacilli: destroyed / localized

TB infection & TB disease

TB infection: CMI can control infection
primary complex (+) cell mediated immunity (+) tuberculin sensitivity (DTH) (+) limited amount of TB bacilli no clinical or radiological manifestation

TB disease: CMI failed to control TB infection TB infection + clinical and/or radiological manifestation

TB infection

TB

CMI

TB disease

CMI

TB

TB classification (ATS/CDC modified)

Class Contact Infection Disease Treatment

0 1

+
+

2 3

+
+

proph I

proph II?
therapy

TB natural history overview

primary TB infection

primary TB disease post primary TB non respir TB

latent TB infection no disease

respiratory TB new infection

Prognostic factors
A. TB bacilli :
virulence infection dose

B. Patient :
general condition age nutritional state coinfection: morbili, pertussis genetic stress; physically (trauma, surgery) or mentally

Pathology

Pathology
complicated pathogenesis varied pathology clinical manifestation 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, bronchial stenosis, fistula, bronchiectasis Pleura: effusion, fistula, empyema, pneumothorax, hemothorax Blood vessels: milliary, hemorrhage

Pathology jungle
reg lymph node primary focus remote foci
resolution

tubercle formation

milliary seed

calcification

caseation

granuloma

compresses airway

fibrosis
liquefaction

tuberculoma cavity

erodes airway bronchiectasis 2nd lung lesions

rupt to pleura

rupt to airway

br pl fistula

Thank you