dr soedarsono
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Dr. Hermawan Chrisdiono,
Sp.PRSUD Kabupaten Kediri
Multidrug-Resistant TB:
A Challenge and Its Prevention
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Infection withdrug-susceptible
strain
Exposed toDS-TB
Infection
withdrug resistantstrain
Exposed
toDR-TB
Infection
Drug-susceptibleTuberculosis
Drug-resistanttuberculosis
Disease
Risk factorsRisk factors
Riskfactors
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DOTS accelerationISTC 2006/2009
TB/HIV Collaboration
DOTS-plus DOTS
HIV Epideic
! "D#-TB
TB C$SES
Patient-centered care
approach
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Primary resistance drug resistance among new cases
neer receied TB drugs or receied them for! "month
new terminolog# adopted b# $%& 'Resistanceamong new cases
Secondary (Acquired) resistance drug resistance in a patient who preious
receied atleast " month of TB therap#
new terminolog# adopted b# $%& ' Resistanceamon
WHO/IUATLD Global Project Drug-Resistance Surveillance Reort !o" #
DEFINITION
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e n ons MonoDrug Resistance
against onl# one drug
PolyDrug Resistance against two or more drugs( but not against both % and R(
e)g) against S and %*These are less serious because the# can be e+ectiel# treated with the
cat I and II regimen( using ,rst-line TB drugs
MultiDrug Resistance against at least % and R
ExtensieDrug Resistance *.DR-TB /DR
01D against a 2uoro3uinolone 01D against one or more of the in4ectable drugs'kanam#cin( amikacin( capreom#cin
!om"lete*Totally Drug Resistance
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#ild M. tuberculosisstrain
#ild M. tuberculosisstrain
Dru$%resistant strain
Dru$%resistant strain
Spontaneous mutation
Acquired dru$ resistance
Acquired dru$ resistance
Selectionb# poorregimen( drug suppl# oradherence
Primary dru$ resistance
Primary dru$ resistance
Transmissiondue todiagnostic dela#s(oercrowding andinade3uate infection control
o' Does Dru$%esistant T Deelo
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T+e Marc+ o, esistance
Drug
suscepti
ble TB*
5or limitedresistancemanageablewith 6 drugregimen -D&TS
MD%T
-../
XDR-
TB
2006
Total
DR TB
?
Resistance to%7R
Arises ,rom
mismana$ement o, T
Treata0le 'it+1ndline dru$s
Resistance to %Rand 8ndline drugs
Arises ,rom
mismana$ement o, MDTreatment
Treatmento"tions
seriouslyrestricted
Resistanceto allaailable
drugsNotreatmento"tions
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MD%T causes(,rom "ro$ram
"ers"ectie) Regimen prescription *proiders9
$rong drugs or combination of drugs
$rong duration Drug management
:ualit#
;oose drugs instead of enetration in local marketplace
=ase management *proiders9 1o obseration *D&T
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is2 ,actors MD%T
(,rom "atient +istory) >reious treatment
Relapses
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=auses of Inade3uate antituberculosistreatment
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/agnitude of the /DR-TBproblem
$%& estimates incident cases in8AA 6C)AAA *CF conf limits(
8")AAA-G)AAA /ost /DR TB cases are not
diagnosed 99
>realent cases estimates to betwo or three times higher thanincident cases
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Zignol M, et al. JID2006; 194: 479-85
Estimated gloal in!iden!e and "#o"o#tiono$ M%& among '( !ases, 2004
Estimated Hlobal /DR=ases
2004 TB cases MDR cases %
New Cases 8,897,74) 272,906 2.7
re!iousl"treate# cases
982,6)9 181,408 18.5
Total cases 9,880,)82 424,20) 4.)
Di t ib ti f /DR 1 > i
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Distribution of /DR' 1o >rior
Treatment
Zignol M, et al. JID2006; 194: 479-85
%ist#i*tion o$ M%& #ates among ne+ !ases "#eio*sl *nt#eated/
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Zignol M, et al. JID2006; 194: 479-85
Distribution of /DR' >riorTreatment
%ist#i*tion o$ M%& #ates among "#eio*sl t#eated !ases
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>roblem anal#sis /DR inIndonesia
&nl# 8AF of hospitals 7 ! CF of priateproiders are currentl# inoled in D&TS
1o data on TB drug resistance( except for
few small studies *$est Jaa /DR' CF 999) Some second line drugs are free aailable on
the market and currentl# used in ,rst lineregimens9
1eglect to take treatment histor# causesKLmiss- classi,cation and LLunder-treatmentLL))
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Therapeutic KLchaosLL ' prescription of inade3uatedoses ? combinations of drugs
/an# TB patients are treated b# priate proiders(
not following D&TS
unsuperised treatment( no monitoring no registration( no reporting high costs to the patients *fees Mn-controlled use of second-line drugs in hospitals
and priate sector *3uinolones( kanam#cin etc >oor treatment performance in most hospitals'
low conersion rate 7 low cure rate because man#
patients drop-out from treatment) inade3uate drug supplies and distribution
MDin Indonesia (-)
i 2 , t , i d
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is2 ,actors ,or increasedMD
in Indonesia (1) =urrentl# the chronic TB cases
cannot be treated *no D&TS plus
aailable
These chronic cases continue to
transmit drug resistant TB
TB- %I@ is loomingN
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O
T+e real
MD%T34D%T inIndonesia
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MD%T5 A !+allen$e to&ealt+ System
ase identi$i!ation o$ M%&-'( #e*i#es culture,
s"e!ies identi$i!ation, and #rug susceptibilit"
testing
o+ man *alit ass*#ed lao#ato# to e
estalis3ed to ens*#e a!!essiilit, taing into
a!!o*nt t3e sie o$ "o"*lation, geog#a"3i!!3a#a!te#isti!s and t3e e"idemi! o$ t*e#!*losis
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MD is More !ostly to !ure(Peru)
/
1/
6/
7/
8/
-//
All T e%treatment MD T
Treatmentsuccess(9) :1/%6/ :;/ %
6//:-
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0
20
40
60
80
100
Russia Dominican
Rep.
Korea Peru Hong Kong
Tre
atmentsuccess
(%)
all T MD%T
Espinal MA et al. JAMA 2000 2!":2#"$-2#%#
MD%T is +arder to cureMD%T is +arder to cure
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Indiidual Impact of /DR
0erage direct medical costs percase in the MS' P8Q(QC8 Burgos( et al) CID8AAC 6A' G-QC
;ong treatment duration *"-86mos)( often diUcult and toxic
;ong periods of isolation ma# be
necessar# Depression is common
Disease ma# be incurable *chronic
%igher rate of death
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&istory
"6 Hlobal drug resistance sureillance pro4ect launched
" Stop TB $orking Hroup on D&TS->lus for /DR-TB
" 1egotiations with pharmaceutical industries
8AAA Hreen ;ight =ommittee Initiatie launched
8AAA lus pro4ect launched
8AA8 The Hlobal lan to Stop TB(
1ew Stop TB Strateg# *DR-TB component 8
8AAG 1ew funding Initiaties M1IT0ID 8AA $%0 recommended tool for scaling up /DR-TB
management
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DOTS%Plus scale u" o, t+rou$+ t+e =>!
Se"tem0er 1//; ? @; "roects
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GLC approved projects through June 2009
Mncertaindemand
%igher
price
=>!%a""roed "roects in 77 countriesB ;6C;;/ atients a roed ,or
- an$lades+1 +utan@ India6 Indonesia; Myanmar7 Ne"al Sri >an2a8 Timor%>este
- ur2ina Faso1 !ameroon@ D !on$o6 Et+io"ia
; =uinea7 enya >esot+o8 >i0eria. MoGam0ique-/ 'anda-- Sene$al-1 S'aGiland-@ H$anda-6 TanGania
- eliGe1 oliia@ !osta ica6 Dominican e"u0lic; Ecuador7 El Salador =uatemala8 &aiti. &onduras-/ Mexico-- Nicara$ua-1 Para$uay-@ Peru-6 Hru$uay
- E$y"t1 ordan@ >e0anon6 Pa2istan; Syria
7 Tunisia
- AGer0aian1 Armenia@ elarus
6 ul$aria; Estonia7 =eor$ia aGa2+stan8 yr$yGstan. >atia-/ >it+uania-- Moldoa-1 omania-@ ussia-6 Ser0ia-; Tai2istan-7 H2raine- HG0e2istan
- !am0odia
1 !+ina@ Micronesi
a6 Mon$olia; P+ili""in
es7 Samoa Jietnam
Parameters to consider
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Parameters to consider'+en desi$nin$ a DOTS%
Plus strate$y &overn'ent and (TP )o''it'ent *ell per+or'ing ,asi) T/ Progra' is a,le to i'ple'ent the # )o'ponents o+
T/-Plus Rational )ase-+inding strateg using 1ualit assured
s'ear )ulture and /T 3 )on)ordan)e 4ith a /R56 Representative R/ data +or rational )ountr7area-
spe)i+i) treat'ent design and planning o+ pro)ure'ent Relia,le T throughout treat'ent 8ree e++e)tive side-e++e)t 'anage'ent Regular suppl o+ A55 drugs involved9
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Assessment o, sites5 Issues t+atneed to 0e addressed in all sites
;ack of E:0 assured lab capacit#
Inade3uate use of aailable second
line drugs *inade3uate regimens(,nancial barriers( no S;-DST
1o experience with 6 t#pes of S;D
0lternatie for famil# member D&T
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#+y s+ould Indonesia considerto use t+e =>! mec+anism *
0ccess to a complex market of3ualit# assured second line
drugs >referential prices *pooled
procurement
Technical assistance bene,tingfrom H;= experiences worldwide
Re3uirement of the H i
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>reparation>rogrammatic management of DR-TB *D&TS->lus
0ssesment ? Situation 0nal#sis D&TS progress 7 capacit# *case management( ;ab
capacit#
/agnitude of /DR-TB *DRS( Treatment
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$ow to #etectMDR-TB
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M(4)D%T Sus"ects (-)
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Diarrhoea'
malabsorption ofdrugs
%I@ in some
areas associatedwith /DR-TB
M(4)D%T Sus"ects (@)
>o'probabilit# of resistance
MD T sus"ects in
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MD%T sus"ects inIndonesia =hronic cases
>roen with preious patientscard and from histor#
>atients failing re-treatment *categor# 8 >roen with information from the TB register
>atients reporting preious TB treatment Including second line drugs such as 3uinolones and
kanam#cin *in hospital( priate sector >atients failing ,rst line *categor# " treatment >atient still smear positie at month of ,rst line
*categor# " treatment Relapse cases >atients who return after default
0fter categor# " and?or categor# 8 treatment
S#mptomatic TB suspects reporting close contactwith con,rmed /DR-TB patients
Including health care workers in the /DR-TB ward
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&o' to Desi$nin$MD%T e$imen
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Princi"les o, MD treatment
0t least 6 drugs with *almost certaine+ectieness
1o drugs from failing regimen)
Initial phase G months( at least G da#sper week
Smears and culture monthl# till cultureconersion
=ontinuation *after conersion for atleast " months
D&T throughout
DST guiding treatment
=rou"in$ o, anti T dru$s
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=rou"in$ o, anti T dru$s=rou"in$ Dru$s
=rou" - 5 frst%line oral
anti T dru$s
IN& (&)< i, ()< Et+am0utol
(E)< PyraGinamide (K)=rou" 1 5 inecta0le antiT a$ents
Stre"tomycin (S)< anamycin(m)< Ami2acin (Am)
!y"ro (c,x)< oLo (o,x)< leo(l,x)< moxiLoxacin (m,x)alloo H= et alecent Adances in t+e Medical Sur$ical Treatment o, MD%T
!urr O"in Pulm Med (1//6)
ou !annot !ure MD%T
As Fast As ou !an !reate
ItQ
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Isolateuntil three consecutiesputum 0rinciples
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Mse dail# patient-centered D&Tthroughout entire treatment course
Record drugs gien( bacteriologicalresults( chest radiographic ,ndings(and the occurrence of toxicities
&ptimiVe management of underl#ingmedical conditions and nutritionalstatus
/anagement >rinciples *8
Frame'or2 !om"onent @5
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%ou &ust 'a(e to ta)e t'e
pills and t'at*s it+
E. a#amillo, 2006
Frame'or2 !om"onent @5A""ro"riate treatment strate$ies t+at utiliGe S>Dsunder "ro"er mana$ement conditions
Management of
adversedrug reactions and
co-morbidities Health education
and
counseling rovision of
enablers
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/onitoring
=ollect sputum specimens for smear andculture periodicall# during treatment onceculture negatie
&btain end-of-treatment sputum specimenfor smear and culture
>erform chest radiograph periodicall#during treatment and at end of treatment
Resources permitting( monitor minimum oftwo #ears following treatment *3uarterl#during ,rst #ear( eer# six months during
second #ear
$ow #o we respo to t1e
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$ow #o we respo to t1e
MDR-TB8XDR-TBproble)?
Prior to starting an MDR-TB project, it is mandatory to address
adequately all thesefactors
To implement
a good DOTS
Programme,ith quality
e &ee# to a##ress t1e +&ow& (actorsco&tributi&g to #rug-resista&ce
!" #o super$ised treatment
%" Bad adherence & super$ision
'" #o standard treatments
(" )requent drug stoc*-outs
+" nti-TB drugs ofpoor quality
" #on-programmatic management
." #o hospital infection control
J !aminero
u))ar"
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Treatment of /DR TB' Ynot coste+ectieZ
Technicall# diUcult and#ields low cure rates
Expensie( drawingresources awa# from the
treatment of pan-susceptible disease
Treatment of drug-resistant strains( when
improperl# monitored(gie rise to een moreresistant organisms
Decreased irulence andtransmissibilit# of /DR
TB strains
u))ar"
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D&TS9 Nand nothing else9 TB is being defeated
b# model D&TSprogram)
D&TS is our besthope of preentingthe emergence ofresistance to anti-TB
drugs
u))ar" 92:
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TOP MANAGEMENT
PREVENTION
DOTS STRATEGY
MDR-TB
ISTC2!"2#
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Thank You
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