Week 2 BTMC - 6 November 2012

7/26/2019 Week 2 BTMC - 6 November 2012

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Mycobacterium tuberculosis


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HISTORY


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INTRODUCTIONM. tuberculosis , then known as thetubercle bacillus , was frstdescribed on 24 March 1882 byRobert Koch, who s bse! ent"yrecei#ed the $obe" %ri&e in

'hysio"o(y or )edicine *or thisdisco#ery in 1+ -.

The bacteri ) is a"so known as

Koch's bacillus /


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INTRODUCTION0 c"ose"y re"ated 'atho(en,Mycobacterium bovis , in*ects a "ar(e

n )ber o* ani)a" s'ecies chie y catt"e3 o#idae5 and deer 36er#idae57/ ison,ca)e", ""a)a, (ira e, k d , 'i(s andbad(ers can a"" be in*ected/

This bacteri ) a"so occasiona""y in*ectsh )ans, b t this kind o* &oonotictrans)ission is rare today/

T berc "osis sho "d not be re(arded as a&oonosis/


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EPIDEMIOLOGY 9HO : near"y 2 bi""ion 'eo'"e ; one third o* thewor"d


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POPULATIONS AT

GREATEST RISK Ho)e"ess 'ersonsIntra#eno s dr (Aa"coho" ab sers%rison in)ates R ssia and other're#io s states o* the So#ietBnion7Recent i))i(rants to the BnitedStates 0sia, Catin 0)erica7HID@1 in*ectionA0IES


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CLASSIFICATIONSMycobacteria cannot be c"assifedas either FG or F@,

and cannot be deco"ori&ed bya"coho",

t ! ick"y deco"ori&ed by ?

hydroch"oric acid/


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CLASSIFICATIONSMycobacteri ) can be c"assifed intose#era" )a or (ro 's M/ Tuberculosis -95% M/ Bovis -3-5%M.africanum -2-3% .M. leprae .

$ont berc "o s )ycobacteri ) $TM7are a"" the other )ycobacteri ) whichcan ca se ' ")onary diseaserese)b"in( t berc "osis, "y)'hadenitis,

skin disease, or disse)inated disease


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CLASSIFICATIONS0t 'resent there are )ore than Jreco(nised s'ecies o* )ycobacteria

Bs a""y the non@t berc "ar are di#idedinto two "ar(e (ro 's: the *ast@(rowin(and the s"ow@(rowin(/

This na)e re*ers to the s'eed o**or)ation o* #isib"e co"onies on so"idc "t re bases/

ast (rowers 'rod ce co"onies within Jdays, s"ow (rowers in )ore than J days/


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CLASSIFICATIONS The s"ow (rowin( bacteria are di#ided* rther into ? (ro 's de'endin( on'i()entation/R nyon (ro ' I contains the'hotochro)o(ens, (ro ' II contains thescotochro)o(ens and (ro ' III the non@chro)o(ens/ Fro ' ID o* the non@t berc "o s )ycobacteria contains the*ast (rowers/Scotochro)o(en s'ecies 'rod ce ye""ow@oran(e 'i()ent carotinoids7 in the dark/%hotochro)o(en s'ecies 'rod ce their


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CLASSIFICATIONSSo)e bacteria are #ery c"ose"y re"atedto each other: e/(/ Mycobacterium

tuberculosis , M. bovis M. africanum andM. microti the M. tuberculosis co)'"e=7. Mycobacterium avium and M.intracellulare M067/

So)e )ycobacteria cannot as yet bec "t red in #itro M. leprae 7/So)e s'ecies ca se in*ection in h )ans#ery rare"y, b t the co rse o* these

in*ections can be se#ere e/(/Mycobacterium asiaticum 7/


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Pathogenic Mycobacterium spp.

BCG

AIDSpatients


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CHARACTERISTICSM. tuberculosis is an ob"i(ateaerobe weak"y Fra)@'ositi#e

)ycobacteri ) , hence Lieh"@$ee"sen stainin( , or acid@*aststainin(, is sed7/9hi"e )ycobacteri ) do not see)to ft the Fra)@'ositi#e cate(ory*ro) an e)'irica" stand'oint i/e/,they do not retain the crysta" #io"et

stain7, they are c"assifed as acid@@


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CHARACTERISTICSMe)ber o* the Mycobacterium tuberculosis co)'"e= which inc" des M/

tuberculosis , M/ bovis , M/ bovis 6F, M/africanum , M/ ulcerans0n ob"i(ate aerobe6e"" wa"" "i'id rich 2-@> dry wei(ht o*the or(anis)7Dir "ence *actors @@@ 6ord *actor, s "*atides


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CHARACTERISTICS0"" Mycobacterium s'ecies share acharacteristic ce"" wa"" , thicker thanin )any other bacteria, which ishydro'hobic , wa=y, and rich in)yco"ic acidsA)yco"ates /

The ce"" wa"" consists o* thehydro'hobic )yco"ate "ayer and a'e'tido("ycan "ayer he"d to(ether by

a 'o"ysaccharide, arabino(a"actan


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Lipid-Rich Cell Wall of MycobacteriumMycolic acids

CMN Group:Unusual cell walllipids (mycolicacids,etc.)

(P urified P rotein Derivative)


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CHARACTERISTICS

M. tuberculosis (row #ery s"ow"yM. tuberculosis di#ides e#ery 1-@2ho rs, which is e=tre)e"y s"owco)'ared to other bacteria, whichtend to ha#e di#ision ti)es)eas red in )in tes !. coli 7 candi#ide ro (h"y e#ery 2 )in tes7/Iso"ation o* the s"ow@(rowin(or(anis)s can re! ire ? to 8 weeks

o* inc bation


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CHARACTERISTICS

It is a s)a"" baci"" s that can withstandweak disin*ectants and can s r#i#e in a

dry state *or weeks/ Its n s a" ce""wa"", rich in "i'ids e/(/, )yco"ic acid 7, is"ike"y res'onsib"e *or this resistanceand is a key #ir "ence *actor

They are n s a""y resistant to ki""in(by 'ha(ocytes/ They are a"so hi("y resistant to dryin(,b t they are ki""ed d rin('aste ri&ation o* )i"k heatin( to > 6


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CHARACTERISTICS

The s"ow (rowth res "ts *ro)inabi"ity to trans'ort n trients

ra'id"y across the wa= "ayer/S"ow (rowth ca ses de"ay india(nosis by "aboratory

6 "t res o* c"inica" )ateria" areinc bated *or ' to 8 weeks/ Thedo b"in( ti)e o* t berc"e baci""i isabo t 18 ho rs


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%atho(enesis o* T berc "osis

Inha"ation o* s)a"" 1@- )7 dro'"etn c"ei containin( M/ tuberculosise='e""ed by co (hin(, snee&in(, orta"kin( o* another indi#id a" withca#itary t berc "osis

%ri)ary in*ection by M/ tuberculosis o* non@i)) ne a"#eo"ar)acro'ha(es with nrestrained

'ro"i*eration within the in*ected


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Eisse)ination o* in*ected)acro'ha(es thro (h the drainin("y)'hatics into the circ "ationEe#e"o')ent within ?@8 weeks o* a6E4G T ce"" de'endent ce""@

)ediated i)) ne res'onse with(ran "o)a *or)ation and)acro'ha(e acti#ation at sites o*

in*ection


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0cti#e in*ection s a""ytrans*or)ed into "atent in*ection

e=ce'tions: in*ants, 0IES79ith decre)ent in T@ce""de'endent ce"" )ediated i)) nity

years "ater7 in*ection reacti#atedwith de#e"o')ent o* t berc "osis

HID in*ection, diabetes )e""it s,

rena" disease, cancer, ad#anced


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6"inica" eat res o* T berc "osis

6o (h one o* the ear"iest si(ns with'rod ction o* s' t ) as tiss e necrosis

'ro(ressesEys'nea a "ater sy)'to) indicatin(e=tensi#e in#o"#e)ent o* ' ")onary'arenchy)a

e#er and wei(ht "oss re ectin(syste)ic actions o* IC@1 and T$ @

cachectin7 secreted by acti#ated)acro'ha(es


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LABORATORY INVESTIGATION

FOR MYCOBACTERIOSIS

MICROSCOPIC

DIRECT

CONCENTRATED

CULTUR & DSTANTIBODY DETECTION

CYTOKINE MEASUREMENT

MOLECULAR

PCR LCR

HIBRIDIZATION


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SPECIMEN

Process ASAP, some is contaminated b norma! "!ora

A##ro#iate $o!%me

Mornin& s#%t%m and %rine is better

A$oid s'ab

T #e o" s#ecimen de#end %#on in"ection site

Ed%cate #atient on #ro#er met(od o" e)#ectoration


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SPUTUM SPECIMEN

NATIONAL CONTROL PROGRAM !

*+ S#ecimens in - $isits, at time o" $isit,ne)t mornin& and attime o" re$isit+ Intermittent bacteria! s(eddin&

-+ ./ m! in scre' ca#,'ide mo%t( container

+ Co!!ected at o#en air or s#ecia! room

0+ Ind%ction 1 a+ G! ceri! &%aico!ate -22 m& at ni&(t

b+ Mi!d e)ercise "o!!o' b dee# ins#iration

c+ P( sio!o&ica! sa!ine in(a!ation

Pre#are smear "rom #%r%!ent, caseo%s or necrotic #ortion

Add e3%a! $o!%me o" / 4 sodi%m ( #oc(!orite #rior to smear #re#aration, %n!ess "or c%!t%re


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MICROSCOPY

5IE6L NEELSEN 76OT 8

MO9IFIE9.5IE6L NEELSEN 7 6OT 8:INYO;N 7 COL9 8:INYO;N.GABBETT 7 TAN T6IAM 6O: 8 7 COL9 8A;RAMINE FL;OROC6ROME 7 COL9 8

Dia"#o$i$ co#%rmatio#

Treatme#t e&a'uatio#Do #ot (i)ere#tiate 'i&i#" a#( (ea(

bacteria

A'' mycobacteria*#ocar(ia a#(r+o(ococcu$ are AF,Cut o) &a'ue -.///01/./// bacteria

2er m'


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Aci(0Fa$t Or"a#i$m$

%ri)ary stain binds ce"" wa"")yco"ic acids

Intense deco"ori&ation does notre"ease 'ri)ary stain *ro) the ce""wa"" o* 06o"or o* 0 @based on 'ri)arystain6o nterstain 'ro#ides contrastin(back ro nd


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9HOAIB0TCE reco))ended)ethod

Aci( Fa$t ,aci''i AF,! a22ear re( or 2i#3 co'ore( ro( a#(t+e bac3"rou#( i$ $tai#e( i# b'ue co'our

More t+a# 1/ AF, 2er %e'( i# 4/ %e'($ 555 !

1 6 1/ AF, 2er %e'( i# -/ %e'($ 55 !

1/ 6 77 AF, 2er 1// %e'($ 5 !

1 6 7 AF, 2er 1// %e'($ E8act #umber

Re9ue$tre2eat $2ecime#

No AF, :ou#( i# at 'ea$t 1// %e'($ 0 !

Ne&er re2ort a$ M. tuberculosis by $mear re$u't o#'y!


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LA,ORATORYDIAGNOSIS

0cid@*ast s)ear and c "t re o* asedi)ent obtained by $aOH

deconta)ination and centri* (a"concentration o* ?@- ear"y )ornin(s' t ) s'eci)ens0cid@*ast stains 6arbo"* chsin

Kinyo n7, a ra)ine@rhoda)ine%o"y)erase chain reaction %6R7 o* frst@ti)e s)ear 'ositi#e res'iratorys'eci)ensEr/ Nohn R/ 9arren, Ee'art)ent o* %atho"o(y, $orthwestern Bni#ersity

einber( Schoo" o* Medicine, N ne 2 J


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LA,ORATORYDIAGNOSIS

6 "t re o* acid@*ast baci""i(( based )edi ) Cowenstein@

Nensen70(ar and broth based )edi )

Midd"ebrook7

Er/ Nohn R/ 9arren, Ee'art)ent o* %atho"o(y, $orthwestern Bni#ersityeinber( Schoo" o* Medicine, N ne 2 J


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S' t ) stained by Lieh"@$ie"sen


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S' t ) stained by a ra)ine


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Lo;e#$tei#0


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Er/ Nohn R/ 9arren, Ee'art)ent o* %atho"o(y, $orthwestern Bni#ersityeinber( Schoo" o* Medicine, N ne 2 J


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co"onies o*)ycobacteri )


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6o"onies o* )ycobacteri )


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MEDIA FOR T, CULTURE

Se)isyntethic 0(ar Media e(Midd"ebrook JH1 , JH117 : contain

defned sa"ts, #ita)ins, co*actor,o"eic acid, a"b )in, cata"ase,("ycero"Ins'issated (( Media e(Cowenstein Nensen7 contain defnedsa"ts, co)'"e= or(anic s bstances

roth Media )idd"ebrook JH+,

JH127 Nawet&, Me"nick 0de"ber(


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,ioc+emica Te$t$ :or t+eI(e#ti%catio# o:Mycobacteria

$iacin acc ) "ation$itrate red ction

%yri&ina)idase Tween 8 hydro"ysisBrease

0ry"s "*ataseIron 'take


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"i#erential $haracteristics of

$ommonly solate&Mycobacterium spp.


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T+a# Tubercu'o$i$MOTT!

In*ections ac! ired *ro) anen#iron)enta" reser#oir o* or(anis)s

H )an 'atho(enicity #aries *ordi erent s'eciesReco#ery in c "t re indicates'resence o* conta)inants,sa'ro'hytes, or 'atho(ens

corre"ation with c"inica" 'resentationcritica"7


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Ru#yo# C'a$$i%catio# o:MOTT Or"a#i$m$

%hotochro)o(ensScotochro)o(ens$onchro)o(ensRa'id Frowers


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%hotochro)o(ens R nyon Fro ' I7Mycobacterium ansasii

Mycobacterium marinumScotochro)o(ens R nyon Fro ' II7

Mycobacterium scrofulaceum

Mycobacterium (enopiMycobacterium s)ul*aiMycobacterium *or&onae


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$on@%hotochro)o(ensMycobacterium avium co)'"e=

Ra'id FrowersMycobacterium fortuitum (ro 'Mycobacterium chelonaeMycobacterium abscessus


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MOTT I#:ectio#$ =Mo$t Commo# Cau$e$ 1

6hronic broncho' ")onary disease ad "ts, cystic fbrosis'atients7

Mycobacterium ansasiiM. avium co)'"e=

M. abscessusM. (enopi "ess *re! ent7M. s)ul*ai "ess *re! ent7

6er#ica" or other "y)'hadenitis es'ecia""y chi"dren7Mycobacterium avium co)'"e=

M. scrofulaceum "ess *re! ent7Skin and so*t tiss e disease

Mycobacterium marinumM. fortuitumM. chelonae

M. abscessus1 rown@ ""iott and 9a""ace, Nr/, Mande"", Eo ("as, and ennett 2 -


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MOTT I#:ectio#$ =Mo$t Commo# Cau$e$ 1

Eisse)inated in*ection HID@'ositi#e7Mycobacterium avium co)'"e=M. ansasii

Eisse)inated in*ection HID@ne(ati#e7Mycobacterium abscessusMycobacterium chelonae

6atheter associated in*ectionsMycobacterium fortuitumM. abscessusM. chelonae

1 rown@ ""iott and 9a""ace, Nr/, Mande"", Eo ("as, and ennett 2 -


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0ntit berc "ar Er (s

irst "ine dr (sRi*a)'icinroad s'ectr ), bactericida"

Mechanis) o* action :bindin( bacteria" R$0 'o"y)erase inter*eres

R$0 synthesistha)b to"Inhibits biosynthesis o* arabino(a"actan )a or'o"ysaccharide o* ce"" wa""7

Isonia&idInhibits )yco"ic acid biosynthesis acti#ated byKat F (en7

Stre'to)ycin0)ino("ycosideMechanis) o* action

Inter*eres 'rotein synthesis, da)a(e o* ce""

)e)brane, )isreadin(A)iscodin( (eneticcode


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M "tidr ( resistant t berc "osisMER T 7

Resistant *or 2 )ain dr (sRi*a)'icin I$H7 wA or wAo other

T dr (sIncidence increase 2 'erann ) 9HO Se't 2 > 42-/ MER new cases79or"d MER 're#a"ence MER 4/?Indonesia : QQERS dr ( resistance s r#ei"ance7 :


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XDR = MDR-TB plus resistance to

at least 3 of the 6 availableclasses of second line drugs

Of 1 !6"# isolates in 16 countriesduring $###-$##% &b' (D( ) *+O,!

$# .ere MDR and $ .ere XDR

XDR found in/0 2/ % of MDR

atvia/ 1" of MDR

4orea/ 15 of MDR

XDR-TB/

7tensive DrugResistant TB

ro) : T Caborator trainin co rse *or 0sia@%asifc he"d b 9HO ei in


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B'aya %enan(( "an(an T0wa" th 1++ @an 9HO dan IB0CTEte"ah )en(e)ban(kan strate(i'enan(( "an(an T yan( dikena"seba(ai $trate"i DOTS "irectly+bserve& Treatment ,hort-course 7dan te"ah terb kti seba(ai strate(i

yan( secara ekono)is 'a"in( e*ekti*cost-e#ective 7


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Strate(i EOTS1/ Ko)it)en %o"itis2/ %e)eriksaaan Eahak Mikrosko'is yan(

Ter a)in M t nya?/ %en(obatan Nan(ka %endek yan( standar

ba(i se) a kas s T den(an tata"aksanakas s yan( te'at, ter)as k 'en(awasan"an(s n( 'en(obatan

4/ Na)inan ketersediaan O0T yan( ber) t

-/ Siste) 'encatatan dan 'e"a'oran yan()a)' )e)berikan 'eni"aian terhada'hasi" 'en(obatan 'asien dan kiner a'ro(ra) secara kese" r han


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%edo)an $asiona"%enan(( "an(an T 2 87

Tata"aksana %asien T berk "osis1/ %ene) an 'asien T

2/ Eia(nosis T 'ar dan T ekstra 'ar?/ K"asifkasi %enyakit dan Ti'e %asien4/ %en(obatan T-/

Tata"aksana T 0nak>/ %en(awasan Mene"an ObatJ/ %e)anta an dan Hasi" %en(obatan T8/ %en(obatan T 'ada Keadaan Kh s s


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Nenis, Si*at dan Eosis O0T

Jenis OAT Sifat Dosis harian(m !" )

Dosis min uan(m !" )

#sonia$id (%) &a"terisid ' ( *) + (- + )

/ifampicin (/) &a"terisid + (- + ) + (- + )

0ira$inamid(1)

&a"terisid ' ( 2 ) 2' (2 )

Streptomycin(S)

&a"terisid +' (+ +-) 33

4tham5utol(4)

&a"teriostati" +' (+' ) 2 ( 2')


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Week 2 BTMC - 6 November 2012

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