IndianJDermatol.2013MarApr58(2):93100.

doi:10.4103/00195154.108029
PMCID:PMC3657276

FixedDurationTherapyinLeprosy:
LimitationsandOpportunities
MunisamyMalathiandDevinderMohanThappa
FromtheDepartmentofDermatologyandSTD,JawaharlalInstituteofPostgraduateMedical
EducationandResearch,Pondicherry,India
Addressforcorrespondence:Dr.DevinderMohanThappa,ProfessorandHead,Departmentof
DermatologyandSTD,JIPMER,Pondicherry605006,India.Email:dmthappa@gmail.com
Received2012SepAccepted2012Sep.
Copyright:IndianJournalofDermatology
ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttribution
NoncommercialShareAlike3.0Unported,whichpermitsunrestricteduse,distribution,and
reproductioninanymedium,providedtheoriginalworkisproperlycited.

Abstract
Leprosyhasbeenconsideredacurablediseaseaftertheimplementationofmultidrugtherapy(MDT),
whichhasbeenproventobesafeandeffective,bybringingaboutasignificantchangeintheglobal
andnationalscenarioofleprosybyupgradingthecontrolofleprosytothenextstageoferadication.
Sinceitsintroduction,theMDTregimensforthetreatmentofleprosyhaveundergoneseveralchanges
especiallywithregardtothedurationoftreatment.Theadvantagesofshorteneddurationoftreatment
needtobebalancedagainsttheriskofrelapseandalotofcontroversiesexistpertainingtothisaspect.
Thefixedduration(FD)therapyisnotpopularamongacademiciansandprivatepractitionerswho
preferprecisediagnosisandtreatmentwithsuperiorMDTregimensandforalongerduration.Onthe
contrary,fromapublichealthcarepointofview,precisediagnosisandalongertreatmentscheduleare
notcosteffectiveandnotfeasibletobeimplementedineliminationprograms.Hence,afinebalance
needstobemaintainedbetweenachievingacureforthepatientandprotectingthesocietyatrisk,and
thisreviewdiscussesthevariouslimitationsandopportunitiesofFDtherapywithanoteonthenewer
MDTregimens.
Keywords:Fixedduration,leprosy,multibacillary,multidrugtherapy,paucibacillary

Introduction
Whatwasknown?
Sinceitsintroduction,themultidrugtherapy(MDT)regimensforthetreatmentofleprosyhave
undergoneseveralchangesespeciallywithregardtothedurationoftreatment.Theadvantagesof
shorteneddurationoftreatmentneedtobebalancedagainsttheriskofrelapseandalotof
controversiesexistpertainingtothisaspect.Thefixedduration(FD)therapyisnotpopularamong

academiciansandprivatepractitionerswhopreferprecisediagnosisandtreatmentwithsuperiorMDT
regimensandforalongerduration.
Leprosy,adiseasewhichhadbeenascourgeofmankindformanydecadeswasconsideredacurable
diseaseaftertheimplementationofmultidrugtherapy(MDT)bytheWorldHealthOrganization
(WHO)in1982.MDThasproveditseffectivenessinbringingaboutasignificantchangeinthe
leprosyscenario,bothattheglobalandnationallevel,bybringingdownthecaseloadstotheextent
thatleprosynolongercontinuestobeadiseaseofpublichealthcareimportance.Inadditiontobeing
effective,ithasalsobeenprovedtobesafeaswellasacceptabletothepatientsaswellasprogram
managers.Inspiteoftheseadvantages,therearesomecontroversiesregardingthecurrentMDT
regimensespeciallyamongacademiciansandprivatepractitionerswhopreferprecisediagnosisand
treatmentwithsuperiorMDTregimensandforlongerduration,butthesearenotcosteffective,
therebynotwarrantingtheirimplementationintheleprosyeliminationprograms.

GlobalandIndianScenario
Theglobalregisteredprevalenceofleprosyinthebeginningof2011aspertheWHOofficialreports
receivedduring2011,from130countriesandterritories,was192,246cases,whereasthenumberof
newcasesdetectedduring2010was228,474andthefigureforIndiawas1,26,800,whichaccounts
foranalarming55.5%.[1,2]PocketsofhighendemicitystillremaininsomeareasofIndia[1]like
BiharandChattisgarhwhichareyettoachieveelimination(withaprevalencerateof1.12and1.94,
respectively).[3]

HistoryofMDT
TheWHOExecutiveBoardreviewedandendorsedthereportsofthestudyGrouponChemotherapy
ofLeprosyforControlProgrammeson17May,1982whichistheofficialdateofbirthofMDT.[4]
MDTwasrecommendedforthefollowingreasons:[5]
Toaddressresistancetodapsoneandtodiscourageresistancetootherdrugstobeused.
Topromotecomplianceandtomoveawayfromlongtermmonotherapysuchasdapsone.
Toretainrifampicininalltherapeuticregimensbecauseofitspowerfulbactericidalactionand
itseffectivenessevenwhentakenonceamonth.
Topromotecomplianceandcosteffectiveness.
TherewerefoursuccessivephasesintheimplementationofMDTwhichwereasfollows:[4]
19821985:IntroductionofMDTonaglobalbasis.
19861990:ExpansionofMDT(intothelessdifficultareas).
19911999:Eliminationstrategy.
2000onward:Afourthperiod,plannedtolastsixyears,designatedfortheIntensive
eliminationstrategyortheFinalpush.
Thechangesintheclassificationofpaucibacillary(PB)andmultibacillary(PB)leprosyandMDT
regimensarepresentedinTable1.[4,69]

DifferencesinClassificationofLeprosyCasesandMDT
ImplementationinIndia
Until1995,leprosycaseswithmorethan10lesions(countingnumberofskinandnervelesions
involved)wereclassifiedasMB.Inaddition,allcaseswhereskinsmeartestinggavepositiveresults

wereclassifiedasMB,irrespectiveofthenumberofskinandnervelesions.Since1996,theWHO
criterionofsixormoreskinlesionshasbeenusedforMBclassification.[10]Thecriteriaofthe
NationalLeprosyEradicationProgramme(NLEP)toclassifyPBandMBcasesincludesthenumber
ofnervesinvolvedandtheslitskinsmearresultsapartfromthenumberofskinlesionstoincreasethe
sensitivityaswellastoaccountforthepureneuriticcases.[11]Thussince2009,theclassificationof
PBandMBcasesinIndiaaspertherecommendationsoftheNLEPisasfollows:
PB:15skinlesions,nonerveoronlyonenervewithorwithout15skinlesions,slitskin
smearsnegativeatallsites.
MB:6skinlesions,morethanonenerveirrespectiveofthenumberofskinlesions,slitskin
smearspositiveatanysiteirrespectiveofthenumberofskinlesionsornerves.
ThedurationoftreatmentandMDTregimensforMBcasesdifferedfromthoserecommendedbythe
WHOduringtheinitialphases.AtthetimeoftheintroductionofMDTinadistrict,theIndian
AssociationofLeprologistsrecommendedanintensivephaseof21daysofdailyrifampicin600mg
followedbythemonthlypulseddoserecommendedbytheWHOforallprevalentMBcases.Thiswas
modifiedbytheNLEPbyreducingtheintensivephaseto14days.Since1986,basedonthereportsof
theBombayLeprosyProjectStudyindicatingtheequalefficacyoftheWHOregimenandintensive
phaseregimen,theWHOregimenwasfollowed.However,thedurationwasnotrestrictedto24
months,butwascontinueduntilnegativityofsmear.[11,12]NLEPintroduced24monthFDMDTin
1994and12monthFDMDTsince1998.Therehasbeennochangewithregardtothetreatment
regimenordurationofPBcasesfromtheintroductionofMDTin1982.[10]

FDMDTRegimens
Currently,twoFDMDTregimensareinvogue,theWHOregimenfollowedalmostworldwideandthe
PublicHealthServiceregimenfollowedintheUnitedStates.

TheWHOregimen
PB:Rifampicin600mgmonthlyplusdapsone100mgdailysixcyclesinninemonths.[13]
MB:Rifampicin600mgplusclofazimine300mgmonthlyanddapsone100mgplusclofazimine50
mgdaily12cyclesin18months.
TheWHOdoesnotadvocateposttherapysurveillance.Patientsareadvisedtoreportassoonasthey
noteanychangesinskin,eyes,ornerves.

USNationalHansen'sDiseaseProgram(NHDP)treatmentrecommendations
PB:Dapsone100mgdailyplusrifampicin600mgdailyforoneyear.Followupeverysixmonthsfor
fiveyears.[14]
MB:Dapsone100mgdailyplusrifampicin600mgdailyplusclofazimine50mgdailyfortwoyears.
Followupeverysixmonthsfor10years.

AdvantagesofFDMDT
TheeffectivenessofFDMDThasbeenprovedbyitsroleintheeliminationofleprosyandthe
acceptabilitybythepatientsandpublichealthcareadministratorsworldwide.Thevalidityofthe
efficacyofFDtherapyinMBcasescanbeconfirmedbasedonthescientificbasisbywhichthe
durationofthe24monthMDTwasfurthershortenedto12months,whichisasfollows:

ThemodificationsinthedefinitionsofPB/MBcasesovertimehaveresultedinthe
misclassificationofmanycases.ThereisanincreasedproportionofMBcasesamongnewly
detectedcasesduetotheclassificationofcasesthatwouldotherwisebePBleprosy.Thus,the
bacterialloadofthemajorityofcurrentlydiagnosedMBpatientsissignificantlylesserthan
thoseinthepastasalsoestimatedbytheWHOwhereinthenewlydetectedcaseswithhigh
bacillaryindices(BI3)arelessthan15%.[15]Thenetresultwouldbeadecreaseinthe
overallrequirementsofchemotherapyforMBleprosy.
TheratesofrelapseamongMBcasesafter12monthsofMDT,asestimatedbytheroutine
controlprogramsaswellastheresearchprojectswereverylow,about0.2%annually,similarto
thoseobservedafter24monthsofMDT.[16]Nevertheless,higherratesofrelapsehavebeen
reportedinsomestudies[17,18]involvingMBpatientswithahighinitialbacillaryindex(BI)
(averageBI4+).But,suchpatientsareonlyaminorityinthecurrentscenarioofthe
widespreaduseofMDT,andhencetherelapsescontributedbythemwillbesmall.
Thedapsoneclofaziminecombinationishighlybactericidalasobservedfromnudemouse
experimentsandclinicaltrialswhereindailytreatmentwiththiscombinationkilledmorethan
99.999%ofviableMycobacteriumlepraein36months.Thus,thiscombinationensuresthe
effectiveeliminationofthespontaneouslyoccurringrifampicinresistantmutantswhichare
usuallynotmorethan10[4]organismsinanuntreatedlepromatousleprosy(LL)case.[16]
Accordingtosomestudies[SteeringCommitteeonChemotherapyofMycobacterialDiseases
(THEMYC)andclinicaltrialinMalawi],theresponseofMBcasesreceivingfewerthanthe
standard24dosesofMDTwasaspromisingasthosereceiving24dosesormore.[16,19,20]
AretrospectivestudydoneontheclinicalandbacteriologicalprogressofdefaultedMBcases
revealedthattreatmentwithlessthan12monthsofMDTstillhadfavorabletherapeuticeffects
amongthemajorityofMBpatients.[21]
FourWHOsponsoredstudiestoevaluatetheefficacyofavarietyofdrugcombinationsand
treatmentperiodshavefoundthateventhoughthebacillaryloadwasreduced,apositiveBIwas
stillpresentattheendof24or12months.Butthesebacteriawerenolongerfoundtobeviable
asconfirmedbymousefootpadinoculation.Moreover,astheimmunesystemofMBcasesis
grosslydeficienttomountaneffectivedefenseagainstM.leprae,theclearanceofbacillifrom
thebodybecomesaslowprocess.IthasalsobeenobservedthatalthoughBIsremainedpositive
attheendofthetreatment,theygraduallydeclinedduringfollowup,tendingtoconfirmthat
bacillaryclearanceisnotaffectedbyprolongingtheintakeofdrugs.Consideringthesefacts,it
ispossibletostopMDTsafelydespiteapositiveBIafterafixeddurationof24or12months.
Now,theproblemliesindeterminingtheexactdurationofMDTtoachievemaximumresults
forMBcases.[20,22,23]
Operationally,alongdurationoftreatmentisamajorobstacletosuccessfulimplementationof
MDT.Thus,areductioninthelengthoftreatmentwithoutjeopardizingeffectivenesswould
potentiallyfacilitatepatientcomplianceandnationalprogramactivitiesespeciallyinremote
ruralareaswheremedicalcareisoftenscarceandfrequentlyinaccessibletomostpatients.[20]
ByshorteningthedurationofMDTto12months,thedisadvantagesofreduceddurationare
likelytobeminimalandevenanoccasionalrelapseorfailureoftreatmentcanbetreatedwith
thesameregimen,astherelapseisduetodrugsensitivepersisters.[24]
TheadvantagesofFDMDTinPBcasesarebasedonthefollowingobservations:
Thoughcontinuedvisibilityofclinicallyactivepatchesexistinaproportionofpatientsatthe
endofsixmonthsoftherapy,thispersistingactivityisattributedtothecontinuedinflammatory
responseofthesystemtoclearthepersistingkilledmycobacteria,fragments,orantigens.Ithas
beenobservedthat,onfollowup,in30to80%ofthesepatients,theclinicalactivitygradually
comesdownandthepatientsgetcured.[25]
Basedonthesefacts,wecanconcludethattheFDMDTisadvantageouswhencomparedtoprolonged
treatmentinMBcasesuntilsmearnegativityortillresolutionofclinicalactivityinPBcasesbecause
clearanceofbacterialdebrisorachievementofskinsmearnegativityisnotinfluencedbycontinuance

ofbactericidaldrugsbeyondthepointofbacterialkill.However,therearecertainissuesrelatedtothe
FDMDTinPBcasesandMBcaseswithhighinitialbacterialloadwhichremainunansweredbyFD
MDT.

DisadvantagesofFDMDT
Fromapublichealthcarepointofview,thecurrentMDTregimenhasprovedtobeveryeffectivein
theeliminationofleprosy.However,manyexperienceddermatologistswhoaretherealconsultantsin
theclinicalaspectsofthedisease(astheylookaftertheindividualcases),areskepticalofFDMDT
andfindthattheclinicalcuredoesnotoccurafterFDMDTinallthecasesofleprosy.Clinically
curedpatientsattheendof12monthsofMDTcanstillbebacteriologicallyactiveand
bacteriologicallynegativepatientscanstillbeclinicallyactive.Thusanoverwhelmingnumberof
dermatologistsgiveimportancetoclinicalactivityanddonotfollowtheFDTschedulesassuggested
bytheWHO.

ThelimitationsoftheFDMDTpertainingtoMBcasesarebasedonthefollowing
observations
Ithasbeenprovedinafewstudiesthatdespitetwoyearsofregulartherapy,10%ofthepatients
continuetoharborviablepersisters.Inaddition,incompletekillingofM.lepraeinpatients
treatedfortwoyearshasbeenconfirmedbythedemonstrationofATPin19%ofthebacterial
suspensionsfromskinbiopsiesandthepresenceofviablebacilliinthenervesofonethirdof
thepatientsastestedbythemousefootpad.Theseobservationssignifythepersistenceofviable
drugsensitivebacilli,probablythedormantbacillithathaveescapedthebactericidaleffectof
drugsincludingrifampicininaproportionofpatients.Thefateoftheseorganismsisofprime
importancebecausethereisnoevidencethatMDTknocksdownpersistersandthereisnodrug
forleprosythatisknowntoactondormantorganisms.Moreover,lepromatouspatientswith
highinitialBIhavenaturallyapoorcellmediatedimmunity(CMI)andpoormacrophage
functioningtodealwiththeseremainingorganisms.Hence,treatmentcannotbestoppedafter
oneortwoyears,aspersistersarelikelytogrow,resultinginrelapse.But,itmaytakeamuch
longertimethantheincubationperiodofdisease,becauseclofazimineremainsinthetissuesfor
alongdurationandmaintainsacheckonthegrowthofM.leprae.[2527]
Higherratesofrelapseofalmost39%havebeenreportedinasubgroupofpatientswithalarge
bacterialload(BI4+)treatedwith24monthsofstandardMDT,duringlateryearsoffollow
upinstudieswherelongfollowuphasbeendone.[28]IthasbeenobservedthathighertheBIor
shorterthedurationoftherapy,thehighertheriskofrelapse.[28]InastudybyGirdhar,etal.,
[29]therateofrelapseinpatientstreatedwithMDTtilltheyweresmearnegativewas1.1per
100personyears,whereaspatientsonFDMDTshowedarelapserateof2.04per100person
years.Similarly,theMarchouxChemotherapyStudyGroupobservedarelapserateof3.4per
100personyearswithFDMDT.[30]
Ithasbeenobservedthatthebacteriologicalrelapsesoccurredearlierthanclinicalworsening
andthiscouldnotbepickedupinmanystudieswithashortfollowupperiodasslitskinsmear
isnotroutinelybeingusedinthefields.[25]
Thereisalsoadifferencenotedintheratesofrelapsebasedonwhethertheywerefieldstudies
orinstitutionalstudies.Thiscouldbeattributedtothefollowingdifferences:InclusionofallMB
casesinthefieldstudiesincontrasttomainlyLL/BL(BL:Borderlinelepromatous)casesinthe
institutionalstudiesandmoreregularaswellaslongdurationfollowupwithperiodicclinical
andskinsmearexaminationininstitutionalstudies.[25]
Theendpointoftreatmentofpureneuriticleprosyisdifficulttoestablishduetothehighly
controversialassessmentandcurecriteria.Ithasbeenshownthatseveralpatientsshow
advanceddiseaseandarepositiveforAFBonhistologybothinthenervesandinskin,even
whenoneorfewnervesareclinicallyaffected.Thissuggeststhatitwouldbebettertoinclude
thesepatientsintheMBgroupandgiveathreedrugcombination.Thenationalprogram

recommendsthatwhenuptoonenervetrunkisthickened,thepatientscouldbetreatedasPB,
whereasthosewithalargenumberofaffectednervesshouldreceiveMBtherapy.These
recommendationsseemjustifiedfromthepointofviewofcontrol,asinthesepatientsbacilliare
deepintheskinornervesandarenotdischargedfortransmission.However,whathappensin
thelongrunisnotclearasalltheorganismsmaynotgetkilledwiththelimitedtreatmentand
mayresultinthedeteriorationofthenervefunction.Further,despiteadequatetreatment,in
somecasesthenervefunctioncanworsenonaccountoffibrosis,causingconcern.[25]
ThecostoftreatingeitheralloratargetedsubpopulationofMBcaseswithMDTfora
prolongedperiodorcarefullyfollowingthesamesortofpatientsforadecademightseemhigh
initially,butmightnotbeexcessive.Nevertheless,thisneedstobeweighedagainstthelower
costsofretreatmentoftherelapseswithasecondcourseofMDT,assumingthatthereisneither
thedevelopmentofdrugresistantdiseasenorthedevelopmentofadditionaldisabilityinrelapse
cases.[28]

ThelimitationsassociatedwithFDPBMDTareasfollows
ThecureorendpointoftreatmentofPBcases(smearnegativepatients)hasbeenmoredifficult
todefineunlikeinMBcaseswhereintheslitskinsmearsareindicatorsofdiseaseactivity.[31]
Continuedvisibilityofaclinicallyactivepatchinaproportionofpatientsattheendofsix
monthsoftherapyhasbeenobservedinalmostallstudiesvaryingfrom10to67%.Studies
conductedintheinstitutionshaveshownalargerproportionofpatientswhoarestillactiveas
comparedtofieldsituations.[25]
Whenthelengthofdurationoftreatmentisnotlongenoughforthebodytoclearoutthe
bacteria,continuedinflammatoryresponseresultsinpersistentclinicalactivityforupto1218
months.Thereisadelayedresolutioninasignificantnumberofpatientswhichsometimesmay
turnouttobefailuresoftreatment.Ithasalsobeenobservedinafewstudiesthatifdiamino
diphenylsulphone(DDS)iscontinuedforafurtherperiodofsixmonthsorMDTis
administeredfor12monthsinsteadoftherecommendedsixmonths,theproportionofpatients
stayingactivecouldbesignificantlyreduced.[25]
Inseveralreports,activegranulomahasbeenfoundinover50%ofthepatientsoncompletion
oftherapyandevensixmonthslater,suggestingpersistingdiseaseactivity.[25]
StudiesattheCentralJALMAInstituteofLeprosy(CJLI),Agra,Indiahaveshownthatagood
numberofpatientsdiagnosedasPBleprosyclinicallywereacidfast(AFB)bacillipositivein
theskinsmear,indicatingtheirchancesofgettinginadequatetreatmentandthesepatientswould
beproneforrelapse.[31]

SolutionstoOvercomeTheseProblems
ThelimitationsofFDMDTcanbeovercomebyadoptingthefollowingmeasures:
MBcaseswithaninitialaverageBI4+shouldreceiveatleastfouryearsofstandardWHO
MDTasproposedbytheMarchouxchemotherapystudygroup.[30]
ThoughmostofthepatientswithhighBIcontinuetoimproveafterthecompletionofthe12
monthregimen,anadditional12monthsofMDTforMBleprosymayberequiredforpatients
showingevidenceofdeterioration.[32]
TheadditionofimmunotherapybytheBacillusCalmetteGurin(BCG)orMycobacterium
welchiivaccinecanhelptoreducethedurationoftreatmentby50%.[33]
Aregimenofoneyearwiththeadditionofofloxacinandminocyclineatamonthlydosetothe
existingMDTcanbecarriedoutinanattempttoreducethedurationoftherapyasperthetrials
conductedbytheNLEPandCJLI.[34]
RigorousannualfollowupforatleastfiveyearsandevenmoreforPBcasesand10yearsand
evenmoreforMBcasesafterbeingreleasedfromFDMDTisessential.[24]
OfloxacinandminocyclinewithpotentbactericidalactivityagainstM.lepraecanprovidean

effectivesingledosetherapyforPBleprosywhencombinedwithrifampicinasROM(R:
Rimfanpicin,O:Ofloxacin,M:Minocycline)regimen.ForMBleprosy,24monthlydoses
(pulsed)ofsupervisedROMcanbeadvocatedforpatientsrefusingorunabletotakeMDT.
ROMisfoundtobeassafeandeffectiveasMDTduringdosing,causingnoskinpigmentation,
andconferringsimilarclinical,bacteriologic,andhistologicimprovements,withoutincreased
ratesofleprareactions.However,ROMcostsfourtimesmorethanMDTforsimilarduration
regimens,prohibitingmassadministration,butpatientstreatedwithROMmayremain
anonymoustothecommunityandeventheirfamilies.[35]
ThesignificanceofabundantAFBandMBtypehistopathologyinpatientsgroupedasPB
leprosyshouldberesolvedsothatthesepatientscouldbegiventhedrugtherapyandthe
durationoftherapytheywarrant.Thetechniquesthatdirectlyevaluatethetypeandseverityof
leprosyshouldbemaderelevanttothetreatment,especiallyincenterswheretheyareavailable.
[36]
Astheworkloadandfinancialburdenonleprosyorganizationshassignificantlydecreasedover
theyearswithsubstantialdecreaseinthenumberofleprosypatients,slitskinsmearsmayagain
bemadeanintegralpartoftheleprosyprogram.

NewerMDTRegimens
Newerregimensthataremoreeffectiveandoperationallylessdemandingaretheneedofthehour
becauseofcertaindrawbackswiththeexistingMDTregimens,suchas:[3739]
ThelongerdurationoftherapyforMBleprosyisadisadvantagefromtheoperationalpointof
view.
DasponeandclofazimineareonlyweaklybactericidalagainstM.leprae,andastheseweaker
drugsdeterminetheminimaleffectivedurationofthecurrentregimen,furthershorteningofthe
durationoftreatmentmightresultinhigherratesofrelapse.
Dailyadministrationofdapsoneandclofaziminearenotdirectlysupervised.
Sideeffectsofthedrugsinthecurrentregimenlikeclofazimineinduceddisolorationofskin,
hypersensitivitytodapsone,rifampicininducedhepatitis,andsoon.
Emergenceofresistancetodapsoneandrifampicin.
ThevariousnewerMDTregimensincludethefollowing:

MBcases
1.RifampicinsusceptibleMBpatient:[40]
Fullysupervisable,monthlyadministeredregimenrifapentine900mg(orrifampicin600
mg)plusmoxifloxacin400mgplusclarithromycin1000mg(orminocycline200mg)
administeredoncemonthlyundersupervisionfor12months.
2.RifampicinresistantMBpatient:Fullysupervisedregimenintwophases:[41]
Aninitialsixmonthintensivephasefollowedbyan18monthcontinuationphase.The
intensivephase:Moxifloxacin400mgclofazimine50mgclarithromycin500mg
minocycline100mgalltakendaily.
Thecontinuationphase:Moxifloxacin400mgclarithromycin1000mgminocycline
200mgalltakenoncemonthly.
Intensivephase:Dailyadministrationof50mgclofazimine,togetherwithtwoofthe
followingdrugs:400mgofloxacin,100mgminocycline,or500mgclarithromycinfor
sixmonths.
Continuationphase:Dailyadministrationof50mgclofazimine,togetherwith100mg
minocyclineor400mgofloxacinforanadditional18months.
Ifavailable,ofloxacinmaybereplacedbymoxifloxacin400mg,whichhasstronger
bactericidalactivityagainstM.leprae.[42]

3.Fullysupervisable,monthlyadministeredregimens:
ROMcombination:Rifampicin600mg,ofloxacin400mg,andminocycline100mgfor
12months.[43]
PMMcombination:Rifapentin600mg,moxifloxacin400mg,minocycline100mg
(PMM)for12months.[40]
4.Sixweekquadrupleregimen:Rifampicin600mgplusofloxacin400mgplusclofazimine100
mgplusminocycline100mgonceaweekforsixweeks.[44]
5.Onceamonth,supervisedrifampicin600mgplusofloxacin400mgplusminocycline100mg
inadditiontoselfadministereddapsone100mgplusclofazimine50mgdailyfor12months.
[45]
6.Dailyrifampicin600mgplussparfloxacin200mgplusclarithromycin500mgplus
minocycline100mgfor12weeks.[46]

PBcases
SingledoseofROMorRMMforallPBcases.[11,43]
Fourweek,ofloxacincontainingregimen:Rifampicin600mgandofloxacin400mggivenin
superviseddosesdailyforfourweeks.
OnceamonthROMforsixmonths.

AccompaniedMDT
ThepatientisprovidedtheentiresupplyofMDTdrugsatthetimeofdiagnosis,whilesomeoneclose
toorimportanttothepatientassumestheresponsibilityofhelpinghimorhercompleteafullcourseof
treatment.[47]Itisasimplebutawrongsolutionforimplementingsupervisedtherapybecauseof
confusedoperationaldifficultieswithtechnicaljustificationsitignoresthefactsofpooradherenceof
leprosypatientstoselfmedicationcompletely,lacksevidencebasedjustification,andneglectsthe
importanceofregularcontactsbetweenhealthcareworkersandpatients,whichiscrucialforthe
preventionofimpairment.

UniformMDT
Advantages
TheuniformMDT(UMDT)regimencouldbeeffectiveandoperationallyconvenientinthe
contextoftheintegrationofleprosyintogeneralhealthcareservices.[48]
DrugcompliancewithashorterdurationcanmakeitanacceptableregimenforMBpatients.
ClofaziminerelatedpigmentationoftheskinisusuallyshortlivedandacceptabletoPB
patients.
Ascontinuedinflammatoryresponseresultsinpersistentactivityinleprosy,additionof
clofaziminecanhelpinPBpatients.
GranulomasregressedfasterifclofaziminewasaddedtothePBregimen.

Disadvantages
UMDTwillovertreatPBleprosypatientsandundertreatMBpatients,especiallythosewitha
highinitialBI.

Conclusions
TheMDTregimensforthetreatmentofleprosyhaveundergoneseveralchangesespeciallywith

regardtothedurationoftreatment.Theadvantagesofashorteneddurationoftreatmentneedtobe
balancedagainsttheriskofrelapse.Inaddition,thefactthatcompletionofMDTandremovalofthe
detailsofthepatientfromtheregistermaynotbeequivalenttothecureofleprosyshouldbebornein
mindwhiletreatingleprosypatients.Thus,thedurationofMDTrequireddependsontheaim,
resources,motivationoftheindividual,andhisavailabilityforfollowup.Inthefieldsetup,wherethe
aimistointerruptthetransmissionofleprosy,afixeddurationof24or12monthswiththreedrug
MDTforMBpatientsislikelytodothejob.Thisisbecauseinthefields,duetoextensivescreening,
thepatientsarepickedupatanearlystageandhence,therearenottoomanypatientswithlarge
bacterialloadwhoposeathreattorelapse.Moreover,theoperationallyfeasiblesixmonthPBtherapy
willalsohelpinreducingtheactivecaseload.Nevertheless,thesepatientsaretobekeptunderregular
followupforvaryingperiodstolookforevidenceofdeteriorationespeciallyMBpatientswithhigh
BIorPBpatientswithinvolvementofthenervetrunk.RetreatmentwithMBtherapyshouldbe
institutedifthereisworseningorevidenceofrelapse,asallstudieshaveshownthattherelapsesare
duetodrugsensitivepersisters.Ontheotherhand,fortheinstitutionalpatients,wheretheaimisthe
cureoftheindividualpatientinadditiontotheinterruptionoftransmission,anextendedtreatmentof
fouryearsoruntilsmearnegativityisdesirableforallhighlybacillatedpatientswithBI4+.Ethical
issuesalsoneedtobeconsideredandafinebalanceneedstobemaintainedbetweenachievingacure
forthepatientandprotectingthesocietyatrisk.Thiswouldbepossibleonlywhenthetreatmentofan
individualisensuredtillattainmentofcompletecure,atleastwhereverfeasible.
Whatisnew?
ThedurationofMDTrequireddependsontheaim,resources,motivationoftheindividual,andhis
availabilityforfollowup.Inthefieldsetup,wheretheaimistointerruptthetransmissionofleprosy,a
fixeddurationof24or12monthswiththreedrugMDTforMBpatientsislikelytodothejob.Onthe
otherhand,fortheinstitutionalpatients,wheretheaimisthecureoftheindividualpatientinaddition
totheinterruptionoftransmission,anextendedtreatmentoffouryearsoruntilsmearnegativityis
desirableforallhighlybacillatedpatientswithBI>4+.

Footnotes
Sourceofsupport:Nil
ConflictofInterest:Nil.

References
1.WHO.Leprosytoday.[Lastassessedon2012Aug05].Availablefrom:http://www.who.int/lep/en/
2.India'salarmingshareofglobalnewleprosycases.[Lastassessedon2012Aug05].Availablefrom:
http://www.thehindu.com/scitech/science/article2995018.ece.
3.DesikanKV.Eliminationofleprosyandpossibilityoferadication:TheIndianscenario.IndianJ
MedRes.2012135:35.[PMCID:PMC3307180][PubMed:22382174]
4.DaumerieD.ImplementationofMDTSuccessivesteps.In:SansarricqH,editor.Multidrugtherapy
againstleprosy:Developmentandimplementationoverthepast25years.Geneva:WHOLibrary
CataloguinginPublicationData2004.pp.4557.
5.WHOStudyGroup.WHOTechnicalReportSeriesno.847.Geneva:WorldHealthOrganization
1994.Chemotherapyofleprosy.
6.SansarricqH.TheStudyGroup.In:SansarricqH,editor.Multidrugtherapyagainstleprosy:
Developmentandimplementationoverthepast25years.Geneva:WHOLibraryCataloguingin
PublicationData2004.pp.4557.
7.JoplingWH,McDougallAC.5thed.NewDelhi:CBSPublishersandDistributors1996.Handbook
ofleprosypp.10117.

8.HastingsRC,OpromollaDVA,editors.Leprosy.2nded.Edinburgh:ChurchillLivingstone1994.
Dharmendra.Classificationsofleprosypp.17990.
9.JacobsonRR.Treatmentofleprosy.In:HastingsRC,OpromollaDV,editors.Leprosy.2nded.
Edinburgh:ChurchillLivingstone1994.pp.31749.
10.RaoCK.ImplementationofWHOMDTinIndia19822001.In:SansarricqH,editor.Multidrug
therapyagainstleprosy:Developmentandimplementationoverthepast25years.Geneva:WHO
LibraryCataloguinginPublicationData2004.pp.92105.
11.PaiVV,GanapathiR,RaoR.DevelopmentandevolutionofWHOMDTandnewertreatment
regimens.In:KarHK,KumarB,editors.IALtextbookofleprosy.NewDelhi:JaypeeBrothers
MedicalPublishers(P)Ltd2010.pp.35367.
12.MishraRS,KumarJ.Classification.In:KarHK,KumarB,editors.IALtextbookofleprosy.New
Delhi:JaypeeBrothersMedicalPublishers(P)Ltd2010.pp.14451.
13.WHOrecommendedMDTregimens.[Lastassessedon2012Aug05].Availablefrom:
http://www.who.int/lep/mdt/regimens/en/index.html.
14.WorobecSM.Treatmentofleprosy/Hansen'sdiseaseintheearly21stcentury.DermatolTher.
200922:51837.[PubMed:19889136]
15.MDT:DurationoftreatmentFAQ.[Lastassessedon2012Aug05].Availablefrom:
http://www.who.int/lep/mdt/duration/en/inde2.html.
16.JiB.Whymultidrugtherapyformultibacillaryleprosycanbeshortenedto12months.LeprRev.
199869:1069.[PubMed:9715593]
17.ShawIN,ChristianM,JesudasanK,KurianN,RaoGS.Effectivenessofmultidrugtherapyin
multibacillaryleprosy:Alongtermfollowupof34multibacillaryleprosypatientstreatedwith
multidrugregimenstillskinsmearnegativity.LeprRev.200374:1417.[PubMed:12862255]
18.GirdharBK,GirdharA,KumarA.Relapsesinmultibacillaryleprosypatients:Effectoflengthof
therapy.LeprRev.200071:14453.[PubMed:10920610]
19.PnnighausJM,BoerrigterG.Are18dosesofWHO/MDTsufficientformultibacillaryleprosy
resultsofatrialinMalawi.IntJLeprOtherMycobactDis.199563:17.[PubMed:7730703]
20.SalesAM,SabrozaPC,NeryJA,DupprNC,SarnoEN.Nodifferenceinleprosytreatment
outcomescomparing12and24dosemultidrugregimens:Apreliminarystudy.CadSaudePublica.
200723:81522.[PubMed:17435879]
21.ShettyVP,WakadeAV,GhateSD,PaiVV,GanapatiRR,AntiaNH.Clinical,histopathological
andbacteriologicalstudyof52referralMBcasesrelapsingafterMDT.LeprRev.200576:24152.
[PubMed:16248211]
22.PattynSR,BourlandJ,GrilloneS,GroenenG,GhysP.Combinedregimensofoneyearduration
inthetreatmentofmultibacillaryleprosyCombinedregimenswithrifampicinadministeredduring
oneyear.LeprRev.198960:10917.[PubMed:2671559]
23.PattynSR.Efficacyofdifferentregimensinmultibacillaryleprosy.LeprRev.198657:26571.
[PubMed:3553815]
24.PaiVV.Chemotherapyofleprosyfurtherchallenges.[Lastassessedon2012Aug05].Available
from:http://medind.nic.in/haa/t06/i2/haat06i2p72.pdf.
25.GirdharBK,GirdharA.Shortcoursetreatmentofleprosy:Presentstatus.[Lastassessedon2012
Aug05].Availablefrom:http://icmr.nic.in/bufeb02.pdf.
26.AnonymousPersistingMycobacteriumlepraeamongTHELEPtrialpatientsinBamakoand
Chingleput.SubcommitteeonClinicalTrialsoftheChemotherapyofLeprosy(THELEP)Scientific
WorkingGroupoftheUNDP/WorldBank/WHOSpecialProgrammeforResearchandTrainingin
TropicalDiseases.LeprRev.198758:32537.[PubMed:3323750]
27.SharmaA,SharmaVK,RajwanshiA,DasA,KaurI,KumarB.PresenceofM.lepraeintissuesin
slitskinsmearnegativemultibacillary(MB)patientsafterWHOMBR.LeprRev.199970:2816.
[PubMed:10603717]
28.LemasterJW,ShweT,ButlinCR,RochePW.Predictionofhighlyskinsmearpositivecases
amongMBleprosypatientsusingclinicalparameters.LeprRev.200172:238.[PubMed:11355514]
29.GirdharBK,GirdharA,KumarA.Relapsesinmultibacillaryleprosypatients:Effectoflengthof
therapy.LeprRev.200071:14453.[PubMed:10920610]
30.JametP,JiB.RelapseafterlongtermfollowupofmultibacillarypatientstreatedbyWHO

multidrugregimen.MarchouxChemotherapyStudyGroup.IntJLeprOtherMycobactDis.
199563:195201.[PubMed:7602214]
31.PrasadPV,BabuA,KaviarasanPK,ViswanathanP,TippooR.MDTMBtherapyinpaucibacillary
leprosy:Aclinicopathologicalassessment.IndianJDermatolVenereolLeprol.200571:2425.
[PubMed:16394431]
32.Leprosyelimination:MDT:DurationoftreatmentFAQ.[Lastassessedon2012Aug05].
Availablefrom:http://www.who.int/lep/mdt/duration/en/inde1.html.
33.SehgalVN,SardanaK.Immunoprophylaxisofleprosy:Currentstatusandfutureprospects.Indian
JDermatolVenereolLeprol.200773:712.[PubMed:17456909]
34.KatochK,KatochVM,NatarajanM,GuptaUD,SharmaVD,SinghHB.Longtermfollowup
resultsof1yearMDTinMBleprosypatientstreatedwithstandardMDT+onceamonthMinocycline
andOfloxacin.IndianJLepr.200880:33144.[PubMed:20329382]
35.VillahermosaLG,FajardoTT,Jr,AbalosRM,CellonaRV,BalagonMV,DelaCruzEC,etal.
Parallelassessmentof24monthlydosesofrifampin,ofloxacin,andminocyclineversustwoyearsof
WorldHealthOrganizationmultidrugtherapyformultibacillaryleprosy.AmJTropMedHyg.
200470:197200.[PubMed:14993633]
36.RaoPN,PratapD,RamanaReddyAV,SujaiS.Evaluationofleprosypatientswith1to5skin
lesionswithrelevancetotheirgroupingintopaucibacillaryormultibacillarydisease.IndianJ
DermatolVenereolLeprol.200672:20710.[PubMed:16766835]
37.PrasadP,KaviarasanPK.Leprosytherapy,pastandpresent:Canwehopetoeliminateit?IndianJ
Dermatol.201055:31624.[PMCID:PMC3051288][PubMed:21430881]
38.BanditC.RecentAdvancesinLeprosyChemotherapy.JTropMedParasitol.200629:6876.
39.JiB.Chemotherapyandchemoprophylaxisofleprosy.[Lastassessedon2012Aug05].Available
from:http://www.tropika.net/review/020226Leprosy_Chemotherapy/article.pdf.
40.JiB,GrossetJ.Combinationofrifapentinemoxifloxacinminocycline(PMM)forthetreatmentof
leprosy.LeprRev.200071:S817.[PubMed:11201894]
41.ReportoftheninthmeetingoftheWHOtechnicaladvisorygrouponleprosycontrol.World
HealthOrganization,RegionalOfficeforSouthEastAsia.2008
42.WHOExpertCommitteeonLeprosy.WHOTechnicalReportSeries968.2012
43.LEPROSYNEWDRUGREGIMENS.[Lastaccessedon2012Aug05].Availablefrom:
http://www.who.int/tdr/research/progress/9900/methods_treatment/en/inde5.html.
44.PattynS,GrilloneS.Relapseratesanda10yearfollowupofa6weekquadrupledrugregimen
formultibacillaryleprosy.LeprRev.200273:2457.[PubMed:12449889]
45.KatochK,KatochVM,NatrajanM,SharmaVD,SinghHB,GuptaUD.Chemotherapytrialsin
MBleprosyusingconventionalandnewerdrugspefloxacinandminocycline.IndianJDermatol
VenereolLeprol.200066:1825.[PubMed:20877014]
46.TejasviT,KhaitanBK,KhannaN,PandhiRK,SinghMK.Evaluationofanewfixedduration(12
weeks)multidrugregimenofbactericidaldrugsinmultibacillaryleprosy.IndianJLepr.
200678:32937.[PubMed:17402345]
47.JiB.AccompaniedMDT(AMDT)morequestionsthananswers.LeprRev.200273:3017.
[PubMed:12549837]
48.JiB,SaundersonP.UniformMDT(UMDT)regimenforallleprosypatientsanotherexampleof
wishfulthinking.LeprRev.200374:26.[PubMed:12669926]

FiguresandTables

Table1

ClassificationofpaucibacillaryandmultibacillaryleprosyandMDTregimens:Changesovertime
ArticlesfromIndianJournalofDermatologyareprovidedherecourtesyofMedknow
Publications