Dr Soedarsono

7/23/2019 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

Dr Soedarsono

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