INTERNATIONAL JOURNAL OF LEPROSY^ Volume 55, Number 3

Printed in the

Feasibility of Multidrug Therapy (MDT) inHansen's Disease in an Urban Population—Curupaiti

State Hospital, Rio de Janeiro, Brazil'Vera L. G. Andrade, Alfredo B. Marques,

Lucia H. V. da Cunha, and Joäo R. Avelleira 2

Curupaiti State Hospital is located in theurban zone of Rio de Janeiro, Brazil, in theborough of Jacarepagua, and is one of thetwo hospitals specialized in Hansen's dis-ease of the State Health Secretariat. In 1982,the old Curupaiti Colony was divided intothe JacarepaguA Community Institute (700residents) and the Curupaiti State Hospital(150 beds) designated for the treatment ofclinical and surgical problems and severereactions of Hansen's disease patients fromthe health centers and posts from both themunicipality and state of Rio de Janeiro.

A multidrug therapy (MDT) (WHO reg-imen) feasibility study was begun in 1983at the hospital to assess the practicability ofthe WHO recommended regimens (") andto examine the acceptability of the proposedscheme to the patients.

MATERIALS AND METHODSPatients. From September 1983 to De-

cember 1985, 171 multibacillary patientswere put on the WHO regimen-46 of themwere previously untreated patients and 125had previously been treated with rifampin600 mg daily for the first 3 months anddapsone 100 mg daily throughout the reg-imen. There were 22 multibacillary caseswho had previously received dapsonemonotherapy, and these patients were puton an alternative therapeutic scheme usingfour drugs. The 27 paucibacillary patientsincluded in the study received the WHO

' Received for publication on 27 October 1986; ac-cepted for publication in revised form on 19 February1987.

= V. L. G. Andrade, M.D., Director; A. 13. Marques,M.D., Chief Physician; L. H. V. da Cunha, M.D., Ep-idemiologist; J. R. Avelleira, M.D., Physician, Curu-paiti State Hospital, R. Godofrcdo Viana 64, Jacare-pagua, Rio de Janeiro 22700, Brazil.

Reprint requests to Dr. Marques.

regimen; 14 of them were previously un-treated and 13 had previously been underdapsone monotherapy.

Of the 220 patients included in this study,60 arc residents of the Jacarepagwi Com-munity Institute and 160 reside in either themunicipality or the state of Rio de Janeiro.The patients' homes range from 18 to 130kilometers from the outpatient clinic at thehospital where patients come spontaneouslyto receive MDT for Hansen's disease.

Methodology. In the preparatory phase ofthe study a 1-week training course was or-ganized for the health workers responsiblefor the development of the project. To en-sure patient control, it was necessary to in-troduce a data registration system. A tech-nical and administrative reorganization ofthe outpatient clinic was carried out duringthe course of the study.

The basic aspects of Hansen's disease—the names of the drugs; a therapy chart; spe-cial care of hands, feet, and eyes; the like-lihood of reactional episodes; and the im-portance of members of the family comingfor contact screening—were passed on to allof the patients.

The differentiation between multibacil-lary and paucibacillary patients was madein accordance with the following criteria: a)Patients previously untreated and clinicallyclassified as L or B, according to the Madridclassification, showing acid-fast bacilli (AFB)in at least one smear were considered mul-tibacillary. Indeterminate cases with a neg-ative lepromin reaction were also consid-ered multibacillary ( 7 ). b) Paucibacillarycases included tuberculoid and indetermi-nate patients who were lepromin positivewith the absence of AFB in all smears. Lep-romin negativity was defined as :5.5 mmdiameter induration at the skin test sites 4weeks after the intradermal injection of in-

435

436^ International Journal of Leprosy^ 1987

tegral lepromin A, 0.1 ml containing 4.0 x10 6 heat-killed M. leprae. Lepromin posi-tivity was induration >5 mm in diameter.

The 158 multibacillary patients were puton a course of 24 doses in 24 months oruntil becoming bacteriologically negative,using a monthly supervised dose of rilam-pin 600 mg, clofazimine 300 nig, and dap-sone 100 mg plus a daily dose of dapsone100 mg and every other day clofazimine 100mg, self-administered. The paucibacillarycases were given a 6-month treatment withmonthly supervised doses of rifampin 600mg plus dapsone 100 mg daily, self-admin-istered.

A single 100 mg tablet of dapsone wasalso included in the supervised administra-tion of the adopted regimens in an attemptto win back its credibility, in accordancewith the technique used by Rose (Rose, P.,unpublished observations, 1981).

Prothionamide or ethionamide was addedto the regimens of the 22 multibacillary pa-tients who had been on dapsone mono-therapy for more than 5 years and who werestill bacteriologically positive. The regimenutilized was: rifampin 600 mg/month plusclofazimine 300 mg/month, both taken un-der supervision, plus clofazimine 100 mgon alternate days, ethionamide or prothion-amide 250 mg/day and dapsone 100 mg/day, self-administered. In 13 multibacillarycases, ethionamide or prothionamide wasused to substitute for either clofazimine ordapsone. In four paucibacillary patients itwas necessary to substitute clofazimine fordapsone (Table 1).

The patients came to the outpatient cliniconce a month for a prearranged consulta-tion, to take the supervised doses, to collecttheir month's supply of drugs for self-administration, and to undergo a clinicalcheckup. Patients in reaction and undertreatment with prednisolone underwent aclinical evaluation every week for the firstmonth of therapy and subsequently once amonth. In addition, the patients were ad-vised to come to the clinic should there beany change in their clinical state. After com-pleting the period of supervised therapy, thepatients underwent systematic examinationevery 6 months.

All patients were subjected to slit-skinsmear examination before treatment andsubsequently at 6-month intervals using the

Leiker-McDougall method ( 12 ). Laboratorytests were carried out at the beginning oftreatment and subsequently at 6-month in-tervals or whenever clinically indicated inaccordance with signs or symptoms. Theseexaminations included: transaminases(SGOT/SGPT), bilirubin, alkaline phospha-tase, prothrombin time, urea, creatinine,glucose, cholesterol, hemogram, erythro-cyte sedimentation rate (ESR), fecal para-sitology, urinalysis, and in fertile females,an immunological test for pregnancy.

When during treatment a transaminaseserum level of more than twice the limit ofnormal (SGOT 72 IU and SGPT 64 IU)was found the tests were repeated everymonth. Australian antigen testing was notdone. Liver function tests were performedwith kits from various laboratories.

Patient regularity was measured by ap-pearance at the pre-arranged appointmentsfor supervised medication. Reasons givenfor the failure to appear at these consulta-tions on the arranged date were evaluated,as well as the causes for abandonment oftreatment.

RESULTS

Table 2 shows the main characteristics ofthe study group. Among the 220 patients,13 (5.9%) were under 15 years of age. Therewere 77 women and 143 men whose averageage was 32.7 years. The proportion of malepatients was 2:1.

Two paucibacillary (PB) and 151 multi-bacillary (MB) patients are still under treat-ment, 43 patients (23 PB and 20 MB) com-pleted the prescribed treatment, and 23patients (10.5%) abandoned therapy. Sevenof these 23 patients refused treatment forthe most part due to the high number oftablets and capsules to be taken. Other rea-sons given were: transfer to a health centernearer home = 4; pregnancy = 1; lack offaith in the treatment = 2; refusal withoutciting a reason = 3; family not knowing thewhereabouts of the patient = 1; under treat-ment at a spiritualist center = 1; alcohol-ism = 2; tuberculosis during the course ofMDT = 1; impossibility of transport to andfrom clinic = 1.

There was one death in the group, an el-derly patient on prednisolone. The cause ofdeath given by the autopsy was nccrohem-

55, 3^Andrade, et al.: MDT in HD in Urban Population^437

TABLE 1. Multidrug regimens used.

PatientsRegimens^ Multi-^Pauci-

^Totalbacillary^bacillary

RMP" 600 mg 1CLO' 300 mg id monthly, supervisedDDS' 100 mg

CLO 100 mg every other day 1 self-administeredDDS 100 mg daily

158^158

RMP 600 mg monthly, supervisedDDS 100 mg daily, self-administered

RMP 600 mg monthly, supervisedCLO 100 mg monthly, supervised

3^ETH' 250 mg daily, self-administeredDDS 100 mg daily, self-administeredCLO 100 mg every other day, self-administered

22^ 22

RMP 600 mg monthly, supervised

4^ETH 250 mg daily, self-administered^ 13^ 13

A third drug (dapsone or clofazimine)

23^

23

5 RMP 600 mg monthly, supervisedCLO 100 mg every other day, self-administered 4^4

WHO standard regimens.^ d DDS = dapsone.h RMP = rifampin.^ ETH = ethionamide.CLO = clofazimine.

orrhagic pancreatitis, apparently withoutrelation to Hansen's disease.

Of the 169 patients who started treatmentwith the WHO multibacillary regimen, 8(4.7%) rejected clofazimine due to the cu-taneous hyperpigmentation; 6 of these pa-tients were of mixed race. Of the group, 100(45.4%) were Caucasian and 40 (22.3%) wereNegro.

There was cutaneous allergic reaction todapsone in 6 patients; in 3 multibacillarypatients ethionamide was used in place ofdapsone, and in 3 paucibacillary patients wesubstituted clofazimine. One paucibacillarypatient was found to have methemoglobi-nemia, and continued the treatment withclofazimine.

Of the 196 (89%) patients under control,3 paucibacillary patients experienced type1 reaction; 2 during the therapeutic courseand 1 began treatment in reaction. Of themultibacillary patients, 56 (32.7%) com-menced treatment with a reactional epi-sode, while 55 (32.1%) experienced reac-tional episodes during treatment (Table 3).

Of the total of 57 patients who began MDTin a reactional state and the 57 who expe-

rienced reactions during MDT, the per-centages of old cases were 79% and 80.7%,respectively.

The side effects of therapy among the totalnumber of patients in the group includedfive complaints of epigastralgia and 12 ep-

TABLE 2. Main characteristics of casesincluded in IIDT studs' group.

PatientsCategory Multi-

bacillaryPauci-

bacillaryTotal

No. patients atstart 193 27 220Males

No. 131 12 143Age mean 33.9 27.4

(median) (39) (27)Females

No. 62 15 77Age mean 32.4 28.1

(median) (32.5) (27)Completed treat-

ment 20 23 43Excluded from

study

Includes one death.

Regular'^Irregular'' Excluded'^TotalClassification

438^ International Journal of Leprosy^ 1987

TABLE 3. Patients with reactions.

Began MDT^

Ilad reaction^Ilad noClassification

^with reaction^during MDT^reaction^Total

No. % No. To No. % No.

Pa uei baci I lary 4.0 8.0 88.0 25 12.8Multibacillary 56 32.7 55 32.1 60 35.0 171 87.2

Totals 57 29.0 57 29.0 82 41.8 196 100.0

isodes of nausea and/or heartburn. Therewas no indication for the withdrawal or thesubstitution of any one drug, and all of theseproblems were solved by symptomatictreatment.

Of the 196 patients, 54 (27.6%) showedalterations in their liver function tests. Oth-er than 8 (4.1%) who presented with jaun-dice, the values were never found to be morethan twice the standard norms, and the ther-apeutic regimen was maintained in a ma-jority or cases ( 2 ), results of subsequent testsbeing within normal parameters.

Patient regularity on the WHO regimens(Table 4) was greater than 80% for bothmultibacillary and paucibacillary patients.

It is worthwhile pointing out the impor-tance of contact examinations through which21 (35%) of the total of new cases were di-agnosed. Two cases came to the clinic as aresult of the health education program.

DISCUSSIONThe experience of the Curupaiti State

Hospital demonstrates that in practice theintroduction of multidrug therapy in Han-sen's disease does not only involve the in-troduction in itself of a therapeutic regimen.Other strategic elements must comprise ba-sic control activities ("), such as: completeupgrading of medical personnel and healthworkers; standardization of bacilloscopic

examination; establishment of a service ofprevention of deformities by simple tech-niques; provisions, availability, and sys-tems of distribution and storage of drugsutilized; an organized data reporting sys-tem; implementation of health educationactivities; and rigorous post-therapeutic fol-low-up of patients—all of which are essen-tial for the successful outcome of the pro-posed program.

We believe that the supervised dose notonly guarantees the monthly return of thepatients but also acts as a direct incentivefor their commitment to the treatment.

In the official therapeutic regimen in thiscountry, rifampin is self-administered. Aswell as guaranteeing its efficiency (' 3 ), theuse of rifampin in a supervised dose has theadvantage of avoiding the emergence of ri-fampin-resistant pockets ( 4-6 ) and avoids itsimproper use for other pathologies, a com-mon occurrence in our services.

The acceptability of MDT, as measuredby patient regularity in attendance for pre-viously arranged supervised doses, was ex-cellent for a metropolis such as Rio de Ja-neiro. These results are similar to those ob-tained by Rose (unpublished observations,1981), Keeler ( 10), Birch ('), and Kaur, et al.(9 ).

The acceptance of the treatment is duemainly to the support of activities such as

TABLE 4. Regularity to WHO MDT scheme.

No. To^No. To^No. No.

PaucibacillaryMultibacillary

Totals

24162186

88.884.084.5

19

10

3.74.64.5 24

7.411.311.0

27193220

100100100

Regular = patients who took >90% of prescribed supervised doses.b Irregular = patients who took 50%-89% of prescribed supervised doses.Excluded = patients who took <50% of prescribed doses.

d Includes one death.

55, 3^Andrade, et al.: MDT in HD in Urban Population^439

prevention and treatment of disabilities.This is because the Hansen's disease pa-tients consider "treatment" as the resolu-tion of these problems and the mere inges-tion of drugs does not put to rest theseconcerns.

The large number of patients who ac-cepted clofazimine does not agree with thefindings of several specialists in this coun-try. We believe that the relationship estab-lished between the patients and the healthprofessionals and the emphasis on the im-portance of effectiveness on both their partsis one of the crucial factors in avoiding therejection of the hyperpigmentation broughtabout by the clofazimine.

As far as the presentation of reactionalepisodes during MDT is concerned, our ob-servations would seem to indicate that thetherapeutic regimen did not contribute totheir occurrence: We did not observe anyaggravation of episodes, which is similar tothe findings in Trinidad and Tobago by Kee-ler (m).

When WHO presented the proposals forMDT in 1982, we asked: Will the Hansen'sdisease patient accept being medicated un-der monthly supervision? The results ob-tained to date respond to this question inthe affirmative.

SUMMARYThe acceptance of the WHO regimen in

a group of 220 patients was approximately84.5%. Only 11% abandoned the treatment,and the substitution of ethionamide or pro-th ionam ide for clofazimine due to excessivehyperpigmentation was necessary in onlyeight cases.

The WHO regimens adopted provided amore frequent (monthly) relationship be-tween the patients and their health service.It was necessary to: a) reorganize the tech-nical-administrative infrastructure, with theintention of providing an improved serviceto the patients for treatment and control;and b) pay more attention to the problemof deformities and health education activ-ities.

As for the side effects of the drugs, 54patients showed alterations in their liverfunction tests, which were usually mild andwhich resolved despite continuation of thetreatment.

Of the reactional episodes observed dur-

ing MDT, it would not appear that the ther-apeutic regimens contributed to their oc-currence or aggravation.

RESUMENLa aceptaciOn del esquema de tratamiento propuesto

por la OMS en un grupo de 220 pacientes fue de aproxi-madamente el 84.5%. Solo 11% de los pacientes

abandonaron el tratamicnto y la substituciOn de la clo-fazimina por etionamida o protionamida solo fue ne-

cesaria en 8 casos debido a una hiperpigmentaciOnexcesiva.

El esquema de la OMS adoptado, permitiet una re-

laciOn mas frecuente (mensual) entre los pacientes y

sus Servicios de Sahli!. Para el estudio, fue necesario:(a) reorganizar la infracstructura tecnica-administra-

Pva con objcto de mejorar el tratamicnto y control delos pacientes, y (b) poncr mas atenciOn al problema de

las cleformidades y a las actividades de educaciOn sa-

nitaria.En cuanto a los efectos colaterales de las drogas, 54

pacientes mostraron alteraciones en sus pruebas defunciOn hepatica, pero estas fucron moderadas y seresolvicron no obstantc la continuation del tratamicn-

to.De los episodios reaccionales obscrvados durante el

estudio, no hubieron evidencias de quc los regimenes

terapeihicos contribuyeran a su ocurrcncia o agrava-miento.

RESUMELe schema de traitement prescrit par l'OMS s'est

revel& acceptable chez 80,5%, parmi 220 malades. Onze

pour cent seulement ont abandonne ce traitement. Chezhuit cas seulernent on a du rernplacer la clofazimine

par l'ethionamide ou la prothionamide, par suite d'unc

hyperpygmentation excessive.Les schemas de l'OMS qui avaicnt etc adoptes ont

perm is un contact plus frequent. mensual, entre lesmalades et les services de sante. 11 a cependant etcnecessaire d'abord de reorganiser ('infrastructure tech-

nique et administrative, aim de proposer un service

ameliore aux malades en ce qui concerns la traitementet la lutte contrc la lepre. De plus. it a fallu accordcrplus d'attention au problems des dilformites, ainsiqu'aux activites d'education pour la sante.

En cc qui regards Its efjets secondaires des medi-caments, 54 malades ont montre des alterations dans

les epreuves fonctionnelles hepatiques. Ces alterations

etaient habituellement legeres; tiles se sont estompees,et ccci meme alors que la traitement etait poursuivi.

Quant aux episodes reactionncls observes au coursde la polychimiotherapie, it ne semble pas quc les sche-

Inas therapeutiques aient contribue a Icur apparitionet a Icur aggravation.

Acknowledgments. We wish to thank the State Health

Secretariat of Rio de Janeiro, the Raoul FollereauFoundation, the Evangelical Commission for the Re-

440^ International Journal (?I . Leprosy^ 1987

9.

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Brant, Ocilla Reis. Arle/ienne Rosa, Ruth Reis doAmaral, Marlene Barroso; and Dr. Cello de Paula Nlot-

ta for his guidance.

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