TUBERCUOSIS by Meriah Sembiring,Dr,Sp.

A
Subdivision Respirology of The Pediatric the Ulin Hospital.

INTRODUCTION
TB

one of the oldest diseases of human remains causes of the deadliest diseasesin the wold 8 million of new case yearly 3 million death yearly 20- 40 % population is infected reemergence global emergency Indonesia : numb.1 causes death of the infection diseases.

DEFINITION
Tuberculosis is a disease due to MYCOBACTERIUM tuberculosis infection with systemic spread thus can affect almost all organs ,and the most frequent site in the lung,as the site of primary infection.

M TUBERCULOSIS
CHARACTERISTICS;

1. 2. 3, 4. 5. 6. 7.

Live in weeks in dry condition no endotoxins, exotoxins. hematogenic spread grows slowly (24 32 hr ) no specific clinical manifestation aerob,organ predilection lung wide spectrum of replication:dormant

TRANSMISSION:
. Airborne human to human transmission by DROPLET NUCLEI. . adult pulmonary TB : cough,sneeze,speak,or sing. . Droplet nuclei: cotain 2-3 bacili,small size(1-5U)keep in the air long period . .inhalation, reach alveoli middle and lower lobe.

TRANSMISSION FACTORS
Doses/numbers

.concentration in the air .virulence .exposure duration .host immun state

Infection source
Know

source of infection,has diagnostic

value Shaw ( 1954 ),transmission rate : - AFB ( + ) : 62,5 - AFB ( - ),M tb ( + ) : 26,8 - AFB ( - ),M tb ( - ) : 17,6

PATHOGENESIS
Alveoli
Droplet nucle inhalation

Ingestion by PAMS

Intracellular replication of bacili Destruction of bacili

Destruction of PAMS Tuber formation Primay focus Lymphogenic spread lymphangitis Hematogenic spread Acute hematogenci spread
Disseminated primary TB

Hilar lymph nodes lymphadenitis Primary co mplex

Occult hematogenic spread

Multiple organs remote foci

CMI
Figure,pathogenesis of primary tuberculosis

Incubation period
First

implantation primary complex 4 6 weeks ( 2 12 weeks ) incub.period First weeks : logaritmic growth, : 10 - 104 elicit cellular response End of incubation period : - primary complex formation - cell mediated immunity - tuberculin sensitivity Primary TB infection has eastablished

Hematogenous spread
During incubation peroid,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

Acute HS
Less

common Large number Immediate clinical manifestation : disseminated TB Minilary 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 End of hematogenic spread End of TB bacili proliferetion Small amount,live dormant in granuloma New exogenous TB bacili : 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 Classification
Class
0 1 2 3

( ATS/CDC modifled ) Disease

+

Contact
+ + +

Infetion
+ +

Treatme nt proph I Proph II therapy

Clinical manifestation
General
chronic fever,subfebrille anorexia weight loss malnutrition malaise chronic recurrent cough,think asthma ! chronic reccurrent diarrhea other

Specifik
Respiratory Neurology Orthopedic Lymph

node Gastrointestinal others

: cough,wheezing,dyspnea : convulsion,neck stiffness,SOL manifestation : gibbus,crippled : enlarge,scrofuloderma : chronic diarrhea

Tuberculin agent

Streng
First

PPD S Seiber 1 TU 5 10 TU
250 TU

PPD RT 23
1 TU

Intermedite (standard dose) Second

2 5 TU
100 TU

Tuberculin test
Mantoux 0,1 ml Location Reading time Measurement

PPD intermediate strength : volar lower arm,intradermal : 48 72 h post injection :palpation,marked, measure Report : in milimeter Induration diameter : 0 5 mm : negative 5 9 mm : doubt 10 mm : positive

Microbiology
Culture

( Lowenstein Jensen ) Confirm the diagnosis Negative result do not rule out TB Positive result : 10 62 % ( old method )

Radiographic picture
No

radiographic picture is typical of TB Many lung diseases have similar radiographic appearances mimicking PTB Cannot distinguish active pulmonary TB invactive PTB previously treated TB May not detect early stages of TB disease
Under reading over reading Intra individual inconsistency

Do not always help,particularly in small children at times can be confusing. Some cases : extensive dosease from radiography clinical exam little or nothing. More confusing superadded bacterial pneumonia. Commnoly found : enlargement of hilar / paratracheal nodes sometimes difficult to interpret requires thorax CT with contrast.

Diagnosis
1.Clinical manifestation 2.Tuberculin skin test 3.Chest X ray 4.Microbiologhy 5.Pathology 6.Hematology 7.Know infection soure 8.Others : serologic,lung function,bronchoscopy

Proposed IDAI scoing system

Featur Contact TST
BW (KMS)

0
Not clear

1
Reported, AFB ( - )

2 Severe -

3
AFB (+)

Score

Fever Cough
Node enlargement

< 3 weeks

<red line

+
3 weeks

Normal

+
sweeling

+ -

Bone,join

CXR

 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 with scoring system TB diagnosis total score 5 Score 4 in under 5 child or strong suspicion,refer to hospital INH prophylaxix for AFB (+) contact with score <5

Treatment
Objectives:
Rapid

reduction of the bacilli numbers,to cure the patient Sterillization, to prevent relapses
To achieve two phases : Initial phase ( 2 months) intensive,baci.eradication Maintenance(4 months /more)-sterillizing.
Prevention

of acquired drug resistance

 Principles

Multi drug ,not single drug ( monotherapy ) Long term,continue,uninterruptedproblem The drug is taken daily and regularly

TB bacilli population
Location TB population TB amount Metabolism & replication Acidity (pH) Most effective drug (conscly) Cavity,extra cell A Active/rapidly Active / rapidly Neutral/base INH,RIF,ETB Intra macrophage B Slowly Slowly Acid PZA,RIF,INH Caseous mass C Sporadic/intermit tent Sproradic/intermi ttent Neutral RIF,INH

TB therapy regimen
2 mo 6 mo 9 mo 12 mo INH -------------------------------------------------------RIF -------------------------------------------------------PZA --------ETB --------SM --------PRED ---- -- --

Dosage of antituberculosis drug

Drugs Isoniazid (INH) Rifampicin (RIF) Dally dose (mg/kg/day) 5 -15 2 time/week dose (mg/kg/dose)) 15 40 (900 mg)) 10 20 (500 mg) Adeverse reactions Hepatitis,perippheral neuritis,hypersensitivity Gastrointestinal upset,skin reaction,hepatitis,thrombocytop ania,hepatic enzymes,including orange discolouraution of secretions Hepatotoxicity,hyperuricamia,ar thralgia,gastrointestinal upset Optic neuritis,decreassed redgreen colour discrimination,hypersensitivity,g astrointestinal upset Ototoxicity nephrotoxicity (300

mg))

10 15 (600 mg))

Pyrazinamide (PZA) Ethambutol (EMB)

15 40 (2 kg) 15 25 (2,5 g)

50 -70 (4 kg) 50 (2,5 g)

Streptomycin (SM)

15 40 (1 g)

25 40 (1,5 g)

Corticosteroid
Anti

inflammation Prednison : oral,1 2 mg/kg BW/day,tid 2- 4 weeks,tap off Indications :

Miliary TB Meningitis TB Pleuritis TB with effusion

THERAPY EVALUATION
Clinical

evaluation

Increased body weight Increased appetite Diminished /reducesymtoms ( fever,cought,etc)

Supporting

examination

Chest X ray :2/6 month Blood : BSR TST : once positif,do not repeat !

THERAPY FAILURE
Inadequate

therapy :

response, despite adequate

Review the diagnosis, not a TB case ? Review other aspects : nutrition, other disease MDR rarely in children
Treatment

discontinuation

THANK YOU

PATHOGENESIS
Alveoli
Droplet nucle inhalation

Ingestion by PAMS

Intracellular replication of bacili Destruction of bacili

Destruction of PAMS Tuber formation Primay focus Lymphogenic spread lymphangitis Hematogenic spread Acute hematogenci spread
Disseminated primary TB

Hilar lymph nodes lymphadenitis Primary complex

Occult hematogenic spread

Multiple organs remote foci

CMI
Figure,pathogenesis of primary tuberculosis