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Recent Advance
Treatment of Tuberculosis from WHO guidelines 2010
. 1, ..
2, ..
2
1,
2
WHO2010
4
3
2003
2050
- Casedefinition
- Standardtreatmentregimens
- Monitoringduringtreatment
- Co-managementofHIVandactiveTB
case
- Supervisionandpatientsupport
- Treatmentofdrug-resistanttuberculosis
- TreatmentofextrapulmonaryTBand
TBinspecialsituations
Case definition
TB suspected case: productivecough>2weeksandotherrespiratorysymptoms(shortness
ofbreath,chestpain,hemoptysis)and/orconsti-
tutionalsymptoms(lossofappetite,weightloss,
fever,night
Case of TB: definite case of TB anddecidedtotreat
Definite case of TB: oneormoresputumsmearpositiveAFBorM.tuberculosis identified
fromclinicalspecimen,eitherbycultureormo-lecularlineprobeassay
Pulmonary TB (PTB): TB involvinglungparenchymaorpatientwithbothpulmonary
andextrapulmonaryTB
Extrapulmonary TB (EPTB): TB in-volvingorgansotherthanlungparenchyma,e.g.
pleura,lymphnodes,abdomen,genitourinarytract,
skin,jointsandbone,meninges
Smear positive case: onlyone sputumspecimensmearpositiveAFB
Smear negative case: 2 specimens aresmearnegativeAFB(at leastoneearly-morning
specimen) in awell functional external quality
assurance(EQA)system
Smear not done: pulmonaryTBcaseswithoutsmearresults
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Registration group: neworpreviouslytreated patients, in previously treated patients
consideredoutcomeofmostrecentTBtreatment
astable1(NoTBtreatmentcategoryIIV)
Table 1TBregistrationgroupbyoutcomeofmostrecentTBtreatment
2
Smear positive case: only one sputum specimen smear positive AFB Smear negative case: 2 specimens are smear negative AFB (at least one early-morning specimen) in a well functional external quality assurance (EQA) system Smear not done: pulmonary TB cases without smear results Registration group: new or previously treated patients, in previously treated patients considered outcome of most recent TB treatment as table 1 (No TB treatment category I IV)
Table 1 TB registration group by outcome of most recent TB treatment
HIV status: TB register include date of HIV testing, starting co-trimoxazole, and starting ART Standard treatment regimens
HIV status: TBregisterincludedateofHIVtesting,startingco-trimoxazole,andstarting
ART
Standard treatment regimens
2fixed-dose
combinations (FDCs)
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Table 2 Recommendeddosesoffirst-lineantituberculosisdrugsforadults
3
2 fixed-dose combinations (FDCs)
Table 2 Recommended doses of first-line antituberculosis drugs for adults
New patients isoniazid rifampicin 6 2HRZE/4HR 2HRZE/6HE 2HRZE/4HR extrapulmonary TB streptomycin ethambutol 2HRZ/4HR (CAT III) guideline 2HRZE/4HR intensive phase continuation phase 3 2HRZE/4(HR)3 (directly observed) 3 intensive continuation phase 2(HRZE)3/4(HR)3 HIV
New patients
isoniazid
rifampicin 6
2HRZE/4HR
2HRZE/6HE
2HRZE/4HR
extrapulmonaryTB
streptomycin ethambutol
2HRZ/4HR(CATIII)guideline
2HRZE/4HR
intensive
phasecontinuationphase
3 2HRZE/4(HR)3
(directlyobserved)3
intensivecontinuationphase
2(HRZE)3/4(HR)3
HIV
HIV
2
intensivecontinuationphase
HIV
HIVHIV
1
HIV
5
intensivephase
HIV
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isonia-zid2HRZE/4HRE
3
intensivecontinuationphase
isoniazid7.4
Previously treated patients
13
MDR-TB155
MDR-TB
(MDR-TB
3)10
(default)
(relapse)MDR-TB32
(Failure)MDR-TB
49rifampicin
6
MDR-TB5094
(drug
susceptibility testing, DST)
rapidmolecular-basedDST(lineprobeassays)
rifampicin/isoniazid
12 conventional
DST(
10) liquidmedia
(2842)solidmedia
conventionalDST
empiricalregimenDST
(failure)
empiricalMDR regimen
(default)(relapse)
regimen first-line drugs
2HRZES/1HRZE/5HRE
HIV
MDR-TB
DST HIV-
infectedTB CD4 counts 200 /
newpreviouslytreatedcases
sputum smear positiveAFB
intensive phase
smearpositiveAFBDST
5
Monitoring during treatment AFBstaining
intensivetreatment
2smear
positiveAFB 3
smearpositiveAFBDST
MDR-TBtreatmentfailure
regimen
8(2HRZES/1HRZE/5HRE)
3smearpositiveAFB
DSTMDR-TB
treatmentfailure
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sputumsmearAFB2,56
2sputumsmearpositiveAFB
3DST56
sputumsmearpositiveAFBDST
regimen8(2HRZES/1HRZE/5HRE)
sputumsmearAFB3,58
3sputumsmearpositiveAFBDST
58sputumsmearpositiveAFB
DST
intensive
treatmentpositiveAFB
relapse, failure pretreat-ment isoniazid resistance
intensivetreatmentpositiveAFB
- intensivephase
-
-
-
(extensivecavitation)
-
- MDR-TB
first-linetreatment
- smear positiveAFB
regimen rifampicin6
intensive treat-mentpositiveAFBguideline
extensionintensivephase
3 positive
AFBMDR-TB
AFB
cohortanalysisoftreatmentout-comes 3
new pulmonary
smear-positivepatients
(pro-gramme quality)
3 cure
sputum smear
intensive phase
continuationphase
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Table 3 Definitionoftreatmentoutcome
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- - MDR-TB first-line treatment - smear positive AFB regimen rifampicin 6 intensive treatment positive AFB guideline extension intensive phase 3 positive AFB MDR-TB
AFB cohort analysis of treatment outcomes 3 new pulmonary smear-positive patients (programme quality) 3 cure sputum smear intensive phase continuation phase
Table 3 Definition of treatment outcome
pyridoxine10mg/day
isoniazid-
inducedperipheralneuropathy
(symptom-base approach)
minoradverseeffect
majoradverseeffect
4
5
- Cutaneous reaction
antihis-
tamineskinmoisturizing
challenge
isoniazidrifampicin
doseisoniazid50
3
- Drug-inducedhepatitisfirst-
lineanti-TBdrugshepatitisisonia-zid,pyrazinamiderifampicin
jaundicerifampicinhepatitis
intensivecontinua-tionphase
LFT
streptomycin, ethambutol,
fluoroquinoloneLFT
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2challenge
rifampicinhepatotoxicity
isoniazid pyrazinamide
rifampicin
challengerifam-picin37challengeiso-niazid
challengerifampicinisoniazid
challengepyrazinamide
pyrazinamide
hepatitisintensivephase
2HRES/6HR pyrazinamide
hepatitis continuation phase
2HRZE/4HR
isoniazidRZE69
rifampicinpyracinamide
2HES/10HEisoniazid
rifamicin streptomycin,
ethambutolfluoroquinolone18
24
Table 4 Symptom-basedapproachtomanagingminorside-effectsofanti-TBdrugs
8
2HES/10HE isoniazid rifamicin streptomycin, ethambutol fluoroquinolone 18 24
Table 4 Symptom-based approach to managing minor side-effects of anti-TB drugs
Table 5 Symptom-based approach to managing major side-effects of anti-TB drugs
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2HES/10HE isoniazid rifamicin streptomycin, ethambutol fluoroquinolone 18 24
Table 4 Symptom-based approach to managing minor side-effects of anti-TB drugs
Table 5 Symptom-based approach to managing major side-effects of anti-TB drugs
Table 5 Symptom-basedapproachtomanagingmajorside-effectsofanti-TBdrugs
Co-management of HIV and active TB case
HIV testing antiretroviral
therapy (ART) 8
starting anti-TB drugs
survival
TB recurrence rate first-
lineARTstandard-doseefavirenz(EFV)
2 nucleoside reverse transcriptase inhibitors
(NRTIs)AZT (TDF)+ 3TC
(FTC)+EFV
efavirenzteratogeniceffect
nevirapine (NVP)
AZT(TDF)+3TC(FTC)+NVP
cotrimoxazoleprophylaxis
Pneumocystisjirovecii
drugsusceptibil-
ity testing (DST)
HIV
MDR-TB
HIV-positiveTBpatients
intermittentTBtherapyintensive
phaserelapsefailure
dailyintensivephase23
threetimesweekly
short-course intermittent regimen
acquiredrifampicinresistance
2HRZE/4HR
HIV positive HIV negative
rifampicin-containingregimen
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8relapse
6
anti-TB drugs,ART
cotrimoxazole
compliance
Supervision and patient support
(supervi-sion)
(directlyobservedtherapy,DOT)
(patient-centred care)
newsmear-positivecases
DOTS2006default5
Treatment of drug-resistant tuber-culosis standard treatment
MDR-TB
standard
empiricMDR-TB
(functionalequivalentofonlyonedrug
treatment)1
DST
4
cross-resistance
64smear
culturenegative
18culturenegative
24
MDR-TBsputumsmear
culture negative
smearculture3
sputumconversion
smearculturenegative2
30
MDR-TB5
Group 1: First-line oral agents pyrazinamide(Z),ethambutol(E),rifabutin
(Rfb)
DST
DST
rifabutin cross-resistance
rifampicin
Group 2: Injectable agents kana-mycin(Km),amikacin(Am),capreomycin(Cm),
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strepyomycin (S) MDR-TB
aminoglycosides
aminoglycosides
kanamycinamikacinstreptomy-cin
kanamycinamikacin
ototoxicitystreptomycin
kanamycin amikacin
cross-resistance
kanamycinamikacin
capreomycin
Group 3: Fluoroquinolones le-vofloxacin (Lfx),moxifloxacin (Mfx),ofloxacin
(Ofx)
MDR-TB levofloxacinmoxifloxacin
ofloxacin ciprofloxacin
drug-suscep-tibledrug-resistantTB
Group 4: Oral bacteriostatic second-line agents para-aminosclicylicacid(PAS),
cycloserine (Cs), terizidone (Trd), ethionamide
(Eto),protionamide(Pto)ethionamide
MDR-TB
para-
aminosalicylicacidenteric-coated
cross-
resistance 2
para-aminosalicylicacid
cycloserinepara-aminosalicylicacid
ethionamideGIside-effect
hypothyroidism
3
ethionamide,cycloserinepara-aminosalicylic
acidterizidonecycloserine
Group 5: Agents with unclear role in treatment of drug resistant-TBclofazimine
(Cfz), linezolid (Lzd), amoxicillin/clavulanate
(Amx/Clv),thioacetazone(Thz),imipenem/cilas-tatin(Ipm/Cln),high-doseisoniazid(16-20mg/kg/
day),clarithromycin(Clr)WHO
MDR-TB
1
4XDR-TB
Treatment of extrapulmonary TB and TB in special situations extrapulmonary TB
20 25
extrapulmonaryTB
HIV testing
extrapulmonaryTBex-trapulmonaryTBregimenpulmonary
TB2HRZE/4HR
912
disabil-itymortality9
corticosteroid
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streptomycin
ethambutol
latecomplication
hydrocephalus, obstructive uropathy,
constrictivepericarditis,neurologicalinvolve-mentPottsdisease
fluctuationaspiration
incisiondrainage
druginteractionsrifam-picinmetabolize
anti-infectives(proteaseinhibitor,
mefloquine,azoleantifungalagents,clarithromycin,
erythromycin,doxycycline,atovaquone,chloram-phenicol),hormonetherapy(ethinylestradiol,nore-hindrone,tamoxifen,levothyroxine),methadone,
warfarin,cyclosporine,corticosteroids,anticonvul-sants(phenytopn),cardiovascularagents(digoxin,
digitoxin, verapamil, nifedipine, diltiazem, pro-pranolol,metoprorol,enarapril,losartan,quinidine,
mexiletine,tocainide,propafenone),theophylline,
sulfonylureahypoglycemicdrug,hypolipidaemic
drugs(simvastatin,fluvastatin),nortriptyline,halo-peridol, quetiapine, benzodiazepines (diazepam,
triazolam), zolpidem, buspirone
rifampicin
higherdoseestrogen(50g)
rifampicinmetab-olism-inducingrifampicin2
rifampicin
rifampicin
2HRZE/4HR
first-line anti-TBdrugs
streptomycin
ototoxic
activeTBactiveTB
isoniazidprophylaxis6
BCGvaccination
isoniazid regimen
pyridoxine
supplement
LFTserum
alanineaminotransferaselevel3
LFT
regimen
- hepatotoxic drug 2
hepatotoxicdrugs3standard
regimen regimen 9HRE
2HRSE/6HR6-9RZE
-hepatotoxicdrugs1
regimen2HES/10HE
- hepatotoxicdrugsregimen
regimen18
24 streptomycin, ethambutol
fluoroquinolone
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2HRZE/4HR
isoniazidrifampicin
ethambutolpyrazinamide
3
pyrazinamide 25//
ethambutol 15//
3
isoniazid regimen
pyridoxine peripheral
neuropathy
streptomycinneph-rotoxicity ototoxicity
streptomycin 15/
/23
serumlevel
streptomycin
1. WorldHealthOrganization. Treatment of
tuberculosisguidelines.4thed.,2010.