INTERNATIONAL JOURNAL OF LEPROSY^ Volume 62, Number 2

Printed in the U.S.A.

Prospects of Global Elimination of Leprosy as aPublic Health Problem by the Year 2000

The World Health Assembly, in May1991, approved a resolution about the glob-al elimination of leprosy as a public healthproblem by the year 2000, and defined thiselimination as the reduction of prevalenceto 1 case or less per 10,000 inhabitants. Theresolution took into account the consider-able progress achieved with multidrug ther-apy (MDT), with great reduction of preva-lence as well as the substantial support ofnongovernmental organizations and the factthat many countries were giving higher pri-ority to leprosy control.

"The estimative number of leprosy casesworld-wide in 1991 was 5.5 million. Thisfigure shows a marked decline from the 10-12 million cases estimated earlier and sug-gests that it is the success of MDT thatbrought such a drastic reduction."'

Noordeen 2 analyzed in detail the relevantfindings and the justifications for the elim-ination strategy as well as the limitations ofMDT.

The possibility of reaching the elimina-tion goal depends mainly on three factorsand related conditions.

1. Antileprosy drugs and MDTIt is known that the advent of sulfones 3

represented a remarkable progress, withrevolutionary changes in leprosy control:abolishment of leprosaria and shift from in-patient to outpatient care. Early diagnosisand early chemotherapy in dispensaries be-came the most important method of con-trol, supported by health education and rel-evant measures. For more than 30 , yearsInternational Congresses of Leprology andWHO Expert Committees on Leprosy con-sidered sulfone the drug of choice in thetreatment of leprosy. Gradually it was rec-ognized that their main shortcoming wastheir slow effect (clinical, bacteriologic and

' WHO LEP News 1 (1992).2 Noordeen, S. K. Elimination of leprosy as public

health problem. Indian J. Lepr. 63 (1991) 401-409.Faget, G. H., Pogge, R. C., Johansen, F. A., Dinan,

J. F., Prejean, B. M. and Eccles, C. G. The promintreatment of leprosy; progress report. Public Health 58(1943) 1729-1741.

histologic) in the multibacillary forms ofleprosy. Because of the long period of treat-ment required for lepromatous (L) and bor-derline (B) patients, a large proportion ofthem became irregular or lost sight of. Tothis must be added the high proportion ofinactive cases who relapsed, due to the per-sistence of bacilli, and also the developmentof resistant Mycobacterium leprac strains,as confirmed by mouse foot pad inocula-tion.

The WHO/MDT scheme (dapsone + rif-ampin + clofazimine) is at present consid-ered the best one: it increases the efficacy oftreatment and reduces the risk of develop-ment of resistant strains of M. Ieprae.

Attention should be drawn to Dietrich's,et a/. 4 prospective randomized multicentrictrial. They compared monotherapy (dap-sone, DDS) and combined therapy: DDS +rifampin (RMP) and DDS + rifampin +isoniazid (INH) + prothionamide in 307LL and BL patients. After 3 years, treatmentwas stopped and 216 patients finally couldbe evaluated. Several treatment parameterswere adopted including relapses and pa-tients with established DDS resistance inthe mouse foot pad. All of them did notshow any significant differences among thethree treatment regimens.... It is conclud-ed that DDS is very efficient, rifampin orthe combination with rifampin, INH andprothionamide do not add substantially tothe treatment success. . . . However the finalconclusion can only be made after the ter-mination of the 5-year treatment-free pe-riod.

In another trial by Irudayaraj and Asch-holf, 5 132 untreated leprosy patients (77 LL+ 55 BL) were randomized into three dif-ferent regimens: 1) DDS; 2) DDS + RMP

4 Dietrich, M. J., Rangaraj, J., Ganapati, R., De-vanbu, V., Jayakumar, T., Chiang, T., Meyers, W. M.and Gaus, W. Combination therapy/vs monotherapyin BL and LL patient: a prospective randomized multi-center study. (Abstract) Int. J. Lepr. 57 Suppl. (1989)425-426.

Irudayaraj, P. P. and Aschhoff, M. Assessment cri-teria and multidrug therapy. (Abstract) Int. J. Lepr. 57Suppl. (1989) 426.

284

62, 2^ Editorial^ 285

and 3) RMP + Isoprodian and treated con-tinuously for 3 years. Pre- and post-treat-ment biopsies were inoculated into themouse foot pad. "The BI reduction betweenthe regimens was not significant. The per-centages of bacteriologically negative pa-tients after 3 years period in these regimenswere not different from each other. Eightypatients (63%) remained still BI positive atthe end of the study. About 96% ofthe strainsfrom bacteriologically positive patients af-ter 3 years' treatment did not multiply inthe mouse foot pad, indicating so far a uni-form kill after this period. No relapses havebeen encountered."

In a THELEP trial, in connection withUNDP and WHO (' combined drug regi-mens were studied in 215 previously un-treated patients with lepromatous leprosyin Bamako, Mali, and in Chingleput, India."The regimens—daily RMP, DDS and clo-fazimine (CLOF) or prothionamide (PTH);a single initial large dose of RMP togetherwith daily DDS; and daily CLOF or PTHfor the first 3 months, together with dailyDDS and RMP, either in a single initiallarge dose or 900 mg once weekly—wereadministered for 2 years. During this time,biopsy specimens were obtained, and therecovered Al. lepme were inoculated intothymectomized-irradiated (TR) mice fordetection of persisters. In addition, peri-odically the bacterial index (BI) and loga-rithmic index of biopsies (LIB) were mea-sured, the patients were examined clinicallyand observed for side effects, and a numberof laboratory tests were carried out.

"Despite the widely varying 'strength' ofthe experimental regimens no differenceswere demonstrated among the regimens,with respect to the frequency with whichpersisting M. leprae were detected, clinicalresponse, and adverse reactions, with twoexceptions."

It should be noted that with the regimensof a single initial large dose of RMP togetherwith daily DDS for 2 years the results weresimilar to those of other combinations of

6 Subcommittee on Clinical Trials, Scientific Work-ing Group on the Chemotherapy of Leprosy (THE-LEP). Response of THELEP trial patients to combineddrug regimens. (Abstract) Int. J. Lepr. 57 Suppl. (1989)428.

drugs, including one with daily RMP andCLOF! Side effects should also be taken intoaccount.

Further results of these studies are ex-pected with great interest, mainly regardingrelapses, as well as the findings of other trialsconcerning MDT and new drugs. Ofloxacin,minocycline and clarithromycin are beingtried in pilot studies with promising results,but have lower bactericidal activity than rif-ampin. It is hoped that other MDT schemeswith the new drugs will have greater impacton the disease, shortening the period oftreatment and reducing the rate of relapses.

Notwithstanding the findings of the threetrials, the WHO/MDT as well as other com-binations must be applied because of therisk of development of Al. kprae-resistantstrains with monotherapy. It should be rec-ognized that, in spite of the progressachieved, at present we are far from havingan ideal single drug or combined regimensfor leprosy treatment. The efficacy of MDTmay be improved by replacing CLOF withofloxacin or another drug. CLOF is not ac-cepted by a certain number of' patients dueto the pigmentation it causes.

So far the similarity of findings of variousregimens of MDT and DDS alone does notsuggest that the drastic decline of prevalencesince 1982 is due to the success of MDT.Instead, two other causes should be consid-ered. When MDT was adopted (1982) theduration or treatment was considerablyshortened: 6 months for the paucibacillary(PB) cases, 2 years for the multibacillary(MB) cases. Previously the duration was 3-5 years for the former and 5-10 years ormore for the latter. The anticipated releasefrom control of all cases— PB and MB—automatically caused the decrease of prev-alence. The Figure shows WHO data re-garding mass survey (Myanmar) or randomsample surveys in several countries (Argen-tina, Cameroon, Nigeria, The Philippinesand Thailand) with total prevalence rate aswell as lepromatous (L) + borderline (B),tuberculoid (T) and indeterminate (I). Theseare much higher for T and I cases than Lcases. The considerable shortening of thetreatment period and follow up caused adrastic reduction of total prevalence and foreach form of leprosy. To this should be add-ed that WHO/MDT was implemented with

286^ International .lournal of Leprosy^ 1994

an improvement of the control program ineach area. When this is accomplished, evenwith monotherapy, appreciable results havebeen achieved in several areas of the world.The prevalence was also greatly reduced be-cause patients were released from controlafter long periods of treatment (usually 5-10 years for LL cases).

The prospective of obtaining such a de-crease of prevalence with monotherapy hadbeen indicated by Martinez and I3echelli 7

regarding tropical Africa, in the areas wherethe socioeconomic situation is favorable andthere is an ellixtive control program. Sincethere is, mainly in Africa, a very high pro-portion of tuberculoid cases—in whomspontaneous regression of lesions occurs in60%-80% of cases, 8 ' " and relapses are rarean effective campaign could stabilize andreduce the prevalence to a variable degreein a relatively short period.

Relapses. A high proportion of inactiveL cases treated only with sulfone have re-lapsed. 10-16

Quagliato, Bechclli and Marques 15 ob-served in inactive L patients still on sulfone

7 Martinez, D. V. and Bechelli, L. M. Prospects ofcontrolling leprosy in tropical Africa. Acta Leprol. 66-67 (1977) 19-25.

" Lara, C. B. and Nolasco, J. 0. Self-healing, or abor-tive and residual forms of leprosy and their probablesignificance. Int. J. Lepr. 24 (1956) 245-263.

Dharmendra's communication to WHO, 25 May1964; apud I3echelli and Martinez, WHO Guide toLeprosy Control, 1966, 12.

1 " Erickson, P. T. Relapse following apparent arrestof leprosy by sulfone therapy. Publ. Hlth. Rept. 65(1950) 1147-1157. Reprinted in Int. J. Lepr. 19 (1951)63-74.

" Lowe, J. The late results of sulphone treatment ofleprosy in east Nigeria. Lepr. Rev. 25 (1954) 113-124.

12 Rodriguez, N. J. Relapses after sulfone therapy inleprosy of the lepromatous type. Int. J. Lepr. 26 (1958)305-312.

Price, R. B. Relapse of leprosy in American Sa-moa. Amer. J. Trop. Med. Hyg. 8 (1959) 358-363;apud Int. J. Lepr. 27 (1959) 396.

14 Quagliato, R., Bechelli, L. M. and Marques, R. M.Bacterial negatively and reactivation (relapse) of lep-romatous out patients under sulfone treatment. Int. J.Lepr. 38 (1970) 250-263.

is Noordeen, S. K. Relapse in lepromatous leprosy.Lepr. Rev. 42 (1971) 43-48.

11' Jacobson, R. R. and Trautman, J. R. The treat-ment of leprosy with sulfones. Int. J. Lepr. 10 (1971)726-737.

therapy that up to 3 years after bacterialnegativity and clinical inactivity the num-ber of relapses was small and increased sub-stantially after 5, 9.5 or more years up to30%.

The Marchoux Chemotherapy StudyGroup" studied the frequency of relapsesin MB patients after stopping treatment withrifampin-containing combined regimens. Itwas confirmed that relapses occurred lateafter completion of treatment (ultra-shortcourses, 3 of 6 months duration, 1 of 12months, 2 of 24 months). A great majorityof relapses described in the paper have beenconfirmed by mouse foot pad inoculation.Among 437 eligible patients, 384 have beenseen at least once later than 12 months aftercompleting treatment. Out of these 384, 255had not received antileprosy treatment pre-viously and 129 (33.6%) had received treat-ment.

The overall relapse rate among 384 pa-tients was 17.7%. Among patients followedup for more than I year, relapse was 17.1 0/after 7 years and 25% after 10 years, higheramong those with a BI 5 (21.3%). "Therisk of relapse was significantly smalleramong those which achieved smear nega-tivity (p < 0.01). However achievement ofsmear negativity does not guarantee that thepatients will not relapse." ". . . Because ofthe late appearance of relapse patientsshould be followed-up for at least 7 to 10years after completing chemotherapy. Onlyafter a long period of follow-up may onedraw final conclusions with respect to theefficacy of any RMP-containing combinedregimen, including WHO/MDT. ... There-fore the relative low relapse among patientstreated with WHO/MDT must be inter-preted with caution pending longer follow-up. Because millions of leprosy patients havebeen or currently are being treated with theWHO/MDT regimen, we strongly suggestthat the MB patients, especially those whoseBI is still high after completion of treatment,be closely followed-up."

" Blanc, L., Bobin, P., Daumerie, D., Discamps, G.,Grosset, J., Grossetete, G., Husser, J. A., Jamet, P.,Nebout, M., Pattyn, S. and Traore, I. Relapses in mul-tibacillary leprosy patients after stopping treatment withrifampin-containing combined regimens. Int. J. Lepr.60 (1992) 525-535.

cicpC)

a)35

Cd'H.71

(I) 107.7)

5

30

25

20

15

V, 2^ Editorial^ 287

Total

I

^ T

■L+B

Argent Camer Niger Myanmar Philip Thai!

COUNTRIESTHE FIGURE. Prevalence, L, I and T rates per 1000 in Myanmar (BCG trial area) and in some other areas

of the world (WHO random sample surveys). 2 ' Argent = Argentina; Canter = Cameroon; Niger = Nigeria;Philip = The Philippines; Thail = Thailand.

During the last 15 years Pattyn" and co-workers have been involved in studies onshort MDT regimens for the treatment ofMB leprosy: the duration of treatment var-ied from 104 weeks to 52, 34, 13 and 4weeks. All regimens were triple-drug regi-mens, except for one double-drug regimenand one with four drugs. "Overall, relapsesoccur more frequently among patients witha higher BI at the start of the treatment. . . .The WHO regimen applied to previouslyuntreated, highly bacilliferous patients .. .is followed by a cumulative rate of 10% at5 years."

He concluded that "to evaluate treatmentregimens in MB leprosy it is necessary tofollow-up patients until 9-10 years after theend of treatment . ."; the risk of relapsesincreases with time. Furthermore, "the ab-sence of relapse during the first 3 years doesnot exclude high relapse rates later on." Re-garding the dormant bacilli he adds: "Forthe time being it seems logical to administerto those patients who have been treated in

18 Pattyn, S. R. Search for effective short-course reg-imens for the treatment of leprosy. Int. J. Lepr. 61(1993) 76-81.

the past with whatever combined regimensand who are 'inactive,' a short course of afew days of a bactericidal drug such as RMPonce a year, for 10 years, after the end ofthe treatment to eliminate any possiblebursts of dormant bacilli."

In the 14th International Congress ofLeprosy (1993), the Workshop on Chemo-therapy "suggested the fixed duration regi-men may prove to be inadequate in previ-ously untreated LL patients with a highbacterial load, and counselled caution in thewidespread adoption of 2 years fixed du-ration treatment of WHO/MDT until fur-ther data are available. It also noted thatmany relapses are occurring late and, there-fore, five years' post-treatment follow-upappears to be very inadequate, 8-10 yearsbeing the minimum required."

From the findings mentioned, it appearsthat a significant proportion of MB patientsare expected to have a late relapse after stop-ping the 2-year WHO/MDT. Therefore toreduce to a minimum the relapse rate andthe risk of a late recrudescence of the en-demic, MB cases should be treated until thesubsidence of all signs of activity andachievement of smear negativity. The min-imum period of regular treatment should

288^ International Journal of Leprosy^ 1994

be extended from 2 to 3-5 years, accordingto the severity of the disease and bacterialload. The post-treatment follow up shouldbe of about 10 years.

WHO/MDT in PB leprosy (6-monthtreatment). In PI3 leprosy spontaneous re-gression of the skin lesions occurs in a highproportion of cases, from 53% to 88% 8,9

Although only a certain proportion of P13cases would really need MDT, the impos-sibility of identifying them—unless lepro-min testing is performed—and the risk ofdisabilities render the treatment of all ofthem obligatory.

According to Pattyn," to be effective inP13 leprosy a dose of RMP should be as-sociated with several other doses of RMP,either daily for 6 days or weekly for 8-12weeks or monthly for 6 months, or withdaily DDS for 1 year.

From the studies of Nadkarni, Grugni andKini" and Katoch, et al.' it appears thatPB patients treated for 6 months by WHO/MDT had a lower proportion of inactiva-tion and a higher percentage of deteriora-tion in contrast to a higher proportion ofinactivation and very low rate of deterio-ration with WHO/MDT (6 months) fol-lowed by DDS (6 months). Besides, unfa-vorable evolution occurred mainly in thefirst 2-3 years of follow up. These findingslead to the conclusion that WHO/MDTshould be carried out at least for 1 year andtreatment stopped only when there is nosign of activity. A follow-up period of 2-3years is advisable mainly for patients whoinitially had three or more lesions.

Incidence. To achieve a real decline ofthe endemic it is essential to get a significantand lasting decrease of the incidence. Thistakes a long time, and is not accomplishedunless the rate of MB cases and, conse-quently, the load of infectiousness is sub-stantially reduced. Otherwise, after an ap-parent success of the campaign and a

'' Nadkarni, N. I., Grugni, A. and Kini, M. S. Fixedduration MDT in paucibacillary leprosy (classic andmodified). Int. J. Lepr. 61 (1993) 25-28.

2" Katoch, K., Ramanathan, U., Natarajan, M., Bag-ga, A. J., Bathia, A. S., Saxena, R. K. and Ramu, G.Relapse in paucibacillary patients after treatment withthree short term regimens containing rifampin. Int. J.Lepr. 57 (1989) 458-464.

possible attenuation of the control mea-sures, a reactivation of the endemic wouldoccur in the long term, as observed withtuberculosis in recent years.

According to Noordeen, 2 "AlthoughMDT can drastically reduce prevalence ofexisting cases, its capacity to reduce inci-dence of new cases, at least in the first yearsof MDT implementation, is rather limited."

The decline of incidence takes a relativelylong term, as noted in an excellent controlproject in Central African Republic.Nebout 21 reported the data regarding prev-alence and incidence from 1958 to 1980,before the use of MDT. The population was1,250,000 inhabitants in 1962 and2,050,000 in 1981. The number of regis-tered cases was 65,388 in 1958 (66 per thou-sand), the highest in the world; in 1980 therate was 5.7 per thousand. Almost 50% ofthe patients were regularly treated ( ^ 75%of the dose prescribed was taken), 27.4%intake of 40%-74% and 25.6% less than40%. The rate of new cases per thousandwas 2.37 in 1960, 0.54 in 1970, 0.34 in1978, 0.33 in 1979, and 0.37 in 1980. How-ever, the incidence rates per 1000 of L caseshave slightly increased: 0.025 (1960), 0.028(1970), 0.032 (1978), 0.035 (1979), and0.035 (1980).

WHO/MDT side effects. Taking intoaccount the data concerning MDT in 3507patients in the period between 1986 to 1988,Ramu 22 stated that side effects occur onlyoccasionally. However, a few cases had hep-atotoxicity, oliguria, acute renal failure, flusyndrome, exfoliative dermatitis, methe-moglobinemia, shock, night blindness,lymphadenopathy. Hemolysis occurred in17 cases; red and black pigmentation andichthyosis were common.

Our University Hospital (Hospital dasClinicas) has received some patients withvery serious adverse reactions to MDT:hepatotoxicity, jaundice, renal failure. Oneof them died, and the autopsy showed livernecrosis and hemorrhage, disseminated in-travascular coagulation and gastric ero-sions.

21 Ncbout, M. La lutte anti-lepreuse cn R.C.A. Re-sultats obtenus. Acta Leprol. 86-87 (1982) 15-22.

22 Ramu, G. Problems of multidrug therapy. IndianJ. Lepr. 63 (1991) 435-445.

62, 2^ Editorial^ 289

It is important that staff get adequatetraining to recognize MDT side effects andto take relevant action. Hospital facilitiesarc required to attend the patients with se-rious adverse reactions. It seems that theseoften occur at the third intake of rifampin.

2. Difficulties in implementing MDT andcontrol programs

(This topic is interlinked with section 3.Socio-economic, cultural and other factorsin leprosy endemic areas (discussed later).)

The difficulties may be easily evaluated,considering the table from LEI' News-) Thenumber of registered cases was 3,087,788,including 584,412 new cases. The estimatednumber of leprosy cases worldwide in 1991was 5.5 million. The number of cases onMDT was 1,295,640, roughly 42% of theregistered cases. This means that in spite ofthe WHO, governments and nongovern-mental organizations' praiseworthy efforts,58% of registered patients were not yet re-ceiving MDT nor were the estimated2,400,000 undiagnosed cases.

Marked progress was achieved in 1992. 23

"The proportion of registered cases beingtreated with MDT at the time of this reportis about 49% and the cumulative MDT cov-erage since this strategy was introduced hasreached 22%. More than 5.3 million wereor are being treated with MDT. ..."

From a WHO epidemiological study inan efficient control project in Myanmar 24 itappears that 13% of L cases, 48% of B, 43%of I and 54% of T cases were undiagnosed.The PB patients are less important inspreading the disease but 5%-10% of un-treated I cases could evolve to L or B andbecome contagious. Also a certain propor-tion of undiagnosed and untreated I and Tpatients could develop disabilities.

Before WHO/MDT was introduced, thefindings of the WHO Leprosy AdvisoryTeam in Africa (northern Nigeria; north,central and south Cameroon) in a random

sample survey 25 showed that even in coun-tries with fairly good case-finding programsnew cases amounting to 75% of the numberof registered cases were detected.

The difficulties for implementing WHO/MDT and for the development and successof control programs are related to charac-teristics of the disease itself; poor health in-frastructure in many countries, adequate inonly a few; limitations of treatment and pre-ventive methods; education and culturalbackground; socioeconomic and other fac-tors (section 3). Furthermore, in the scaleof priorities leprosy comes after several dis-eases, especially AIDS, malaria, tubercu-losis, trypanosomiasis, cholera, schistoso-miasis, STD and others, depending on thecountries and areas.

According to Nakajima, 26 WHO DirectorGeneral, "AIDS is rapidly becoming a mostserious threat to human existence. WHOestimates that 8.10 million adults may cur-rently be infected with the human immu-nodeficiency virus. More than half of thesewill develop AIDS within ten years and mostwill die.. . . The global malaria situationhas become critical in recent years.... Thedisease is endemic in some 100 coun-tries. . . . In West Africa 18 million peopleare infected with onchocerciasis. . .. Wide-spread malnutrition and improper nutri-tional practices are evident, even in areaswhere food is plentiful. .. ."

In fact, especially where leprosy is highlyprevalent, the health service has to deal alsowith diseases of higher endemicity and/orhigh mortality rates.

Funds available are very often limited andfrequently full advantage of resources is nottaken because of inadequate planning andprogramming. It is difficult or impossible toincrease leprosy budgets proportionately,and the speed of work is thus reduced, tothe great detriment of the development ofthe general program.

2 ' WHO Weekly Epidemiological Record 68 (1993)181-186.

24 Bechelli, L. M., Gallego, G. P., Mg Mg Gyi, Uemu-ra, K., Sundaresan, T., Tamondong, C., Martinez, D.V. and Walter, J. Some epidemiological data on leprosycollected in a mass survey in Burma. Bull. WHO 48(1973) 335-344.

Bechelli, L. M., Martinez Dominguez, V. and Pat-wary, K. M. WHO epidemiological random samplesurveys of leprosy in northern Nigeria (Katsina), Cam-eroon and Thailand (Khon Kaen). Int. J. Lepr. 34 (1966)773- 741.

2" Nakajima, H. Health and development in the1990s. World Health Forum 11 (1990) 355-357.

290^ International Journal of' Leprosy^ 1994

It should be added that in many endemicareas there is a shortage of doctors or mostof them are not interested in working inleprosy control projects. Salaries are usuallylow or not considered high enough to en-courage staff to devote themselves fully totheir work. Furthermore, health campaignshave been hampered by the appointment ofpersonnel, even in supervisory posts, wholacked the necessary technical qualifica-tions.

The above factors have been analyzed indetail by Bechelli 27 ' 28 and Martinez and Be-che111. 8

Millan 29 reported that 10 years after WHOhad recommended MDT, this could be ap-plied only to a minority of patients in Af-rica. However certain countries, membersof OCCGE, have achieved considerableprogress in the last 2 years to improve theMDT coverage. This varies from 8.4% inMali to 97% in Benin. With MDT the prev-alence rate in eight OCCGE countriesdropped from 4.97% in 1982 to 1.09% in1990. However, it seems that in the sameperiod the detection rate continued to bebetween 1.2% and 1.8%.

Millan 29 also stresses that ". . . the appli-cation constraints of MDT raise very diffi-cult operational problems that hinder itsgeneralization. To be effective the MDTcoverage should he preceded, as done in Be-nin and Senegal, by an intense prepara-tion implying the reorganization of duties,actualization of archives and training of rel-evant staff."

In the investigation by the MarchouxChemotherapy Study Group" regarding re-lapses, 50% of their 324 patients had beenlost to follow up 5 years after completionof treatment. It is probable that in routinecampaign work the proportion would hehigher.

In India, according to Ramu 22 ".. . irreg-ularity in intake of self administered clo-fazimine has been occurring due to poorpatient compliance as well as irregular drug

" Bechelli, L. M. Advances in leprosy control in thelast 100 years. Int. J. Lepr. 41 (1973) 285-297.

Bechelli, L M. Futurology of leprosy. Aussatz. Le-pra. Hansen-Krankheit, Teill II. Herausgegeben von J.H. Wolf; Wiirzburg, 1986, 409-414.

29 Millan, J. Le VIII' Congres des Leprologues deLangue Francaise. Acta Leprol. 8 (1992) 1-3.

supply .... Patients who are taking self-administered drugs irregularly would be onrifampicin monotherapy. There is a greatdanger of emergence of rifampicin resis-tance in them and rifampicin resistance hasalready been documented in 39 cases re-lapsing under rifampicin monotherapy."(Grosset, et al. 1989)

Languillon" considers that MDT is "rel-atively possible" in urban areas but not inrural zones. In the French-speaking coun-tries good roads among villages allow themobile teams to treat and control the pa-tients. However, after 6-8 months of treat-ment they improve and become irregular orstop the drugs. This does not happen in thepilot areas where MDT has a special sur-veillance. It is also noted that during theperiod of agricultural activities patients donot attend regularly. Languillon mentionsthe I LEP programs, 620 in 88 countries: outof 831,000 patients only 32% were receivingMDT.

When only dapsone was used Laviron"reported that in French-speaking Africa,10% to 60% of the patients were under reg-ular treatment, around 60% were not yetdetected, and about 50% were out of control("lost sight on.

With WHO/MDT what is the proportionof MB cases that in fact have taken the drugsirregularly over 2 years? Probably a signif-icant proportion of them are taking self-ad-ministered drugs irregularly. For decadesthis has been a constant difficulty in leprosyprojects and also in the control of otherchronic diseases. Thus the efficacy of treat-ment would be reduced while the risk ofrelapse would be increased.

3. Socioeconomic, cultural, education,demographic, political and relatedfactors in leprosy-endemic areas

There is an intimate relationship betweenthe health situation and the economic levelwhich, in its turn, depends on very differentecological, demographic, historical, culturaland sociological factors. A leprosy endemicis present in developing countries or areas.

'" Languillon, J. Polychimiotherapie de la lepre enzone rurale. Acta Leprol. 6 (1988) 67-71.

Laviron, P. Lepre; rapport sur un seminaire (Kam-pala), Bureau Regional de l'Afrique. AFRO 0218, 1970.

6 2 , 2^Editorial^ 291

In the highly industrialized countries lep-rosy had disappeared or is practically ab-sent, even before the advent of sulfones. Inaddition, in these countries "imported"cases have not disseminated the disease.This spreads where the inhabitants face un-favorable socioeconomic and related con-ditions: penury, hunger, malnutrition, highinfantile mortality, unemployment, lowminimal salary, inflation, recession, poorhousing, slums ("favelas"), promiscuity, lackof hygiene, illiteracy, no family planning,ecological degradation, corruption, politicalinstability, rebellion, internal war, etc.

In an editorial in the I l'orld Health Fo-rum, the WHO Director General Nakajima 26

analyzes health and development in the1990s: "In spite of improvements in theworld health situation, the disparity be-tween developed and developing countriesand even between population groups in somecountries remains great. The high rate ofavoidable maternal mortality in many de-veloping countries, and the difference in theexpectancy between the rich and the poor,are unacceptable. . . . Notwithstanding somesocial indicators show that even at low-in-come levels, impressive human develop-ment can be achieved. Yet we still have along way to go to realize the goal of healthfor all people, everywhere. . . . The issue ishow to stem the rising tide of socio-eco-nomic conditions that deprive millions offellow human beings of the basic conditionsfor health, and for leading a decent and pro-ductive life. . . . Accompanied by the lackof economic growth, rising unemployment,diminishing expenditure on other health-related sectors (such as education, watersupply and sanitation) and the natural dis-asters that beset certain countries andregions, this means that millions of peopleremain critically vulnerable at the start ofthe new decade. . ."

The above facts and considerations givethe picture of the difficulties that WHO andgovernments are facing and have to over-come in order to reach the objectives ofdifferent health campaigns, including theelimination goal ofleprosy by the year 2000.Tuberculosis may be mentioned as an ex-ample. With BCG and the advent of newdrugs since the 1950s, the disease was undercontrol. However, due to adverse condi-

tions, including the spreading of AIDS, therehas been a significant increase in the inci-dence and number of deaths. 32

Taking into account what was consideredin sections 1, 2 and 3, it does not seempossible to achieve the global eliminationof leprosy as a public health problem by theyear 2000. In the next 7 years it will beextremely difficult, if not impossible, for allof the endemic countries to reach the de-sirable socioeconomic level and overcomeall the unfavorable conditions. The alter-native would be the availability in the verynear future of an efficient vaccine and/or avery effective and easily administered drug,as much as possible cheap and free fromserious side effects, capable of reducing toa very short period the duration of treat-ment.

Even if the elimination goal establishedby the World Health Assembly in May 1991is not reached, the praiseworthy efforts ofWHO, governments, nongovernmental or-ganizations and specialists shall be of greatbenefit to countries and populations.

In light of the data presented, the follow-ing conclusions can be drawn:

• In randomized trials MDT regimenswere not significantly superior to DDS alone.Furthermore, a significant proportion of laterelapses have been observed in MB patients.The present findings do not confirm that thedrastic reduction ofleprosy prevalence, from10-12 million to 5.5 million since 1982,was due to the success of WHO/MDT. Whenthis was adopted the duration of treatmentwas considerably shortened. The anticipat-ed release from control of all treated casescaused, automatically, a considerable re-duction of prevalence.

• Late relapses have been observed in asignificant proportion of MB patients, es-pecially those with a high BI when stoppingMDT. To reduce to a minimum the relapserate and the risk of recrudescence of theendemic, MB cases should be treated untilthe subsidence of all signs of activity andthe achievement of smear negativity. Theminimum period of regular treatmentshould, therefore, be extended from 2 to 3—

WHO Working Group Meeting. Tuberculosis re-search and development. WHO/TB/91.162.

292^ International Journal of Leprosy^ 1994

5 years, according to the severity of the dis-ease and bacterial load. The post-treatmentfollow up should be about 10 years.

• Unfavorable evolution was more oftenobserved in P13 patients submitted to only6 months of WHO/MDT. Thus, it is nec-essary to carry out regular treatment withMDT for at least 1 year, and the treatmentshould be stopped only when there is nosign of activity. A follow up of 2-3 years isthen required, mainly for patients who ini-tially had three or more lesions.

• Considerable progress has beenachieved in the therapy of leprosy and itscontrol in the last 50 years, and the WHO/MDT and other MDT regimens are rec-ommended because of the risk of the de-velopment of resistant strains of M. lepraewith monotherapy. However, the presentsituation regarding the control of leprosywith WHO/MDT is similar to that of syph-ilis treated by arsenical + bismuth + mer-cury until 1943 when penicillin was intro-duced. So far there is not an ideal singledrug or combined regimen for leprosy ther-apy.

• Many unfavorable conditions in en-demic areas hinder the implementation ofWHO/MDT and the control of leprosy andother diseases.

• In view of the above, it does not seempossible to achieve the global eliminationof leprosy as a public health problem by theyear 2000, unless an ideal drug and/or vac-cine becomes available in the very near fu-ture. With BCG and effective drugs, tuber-

culosis was under control for a long periodbut, in recent years, its morbidity and num-ber of deaths have increased significantly.Syphilis has not yet been eradicated in halfa century in spite of the effective and simpletreatment with penicillin.

It is expected that the endeavors of WHOand institutions and scientists concernedwith the problem may lead, in the near fu-ture, to the discovery of the ideal drug and/or vaccine, the only way of controlling lep-rosy in a relatively short period, as yawswas practically eradicated and smallpoxeradicated, in the most adverse conditions,in two remarkable WHO programs.

—Luis Marino Bechelli, M.D., Ph.D.Prgfessor of DermatologyFaculdade de Aledicina

de Rtheirilo PretoUniversity of Silo Paulo, BrazilFormer Chief . Medical OfficerLeprosy Unit11'orld Health OrganizationGenera, Switzerland

Reprint requests to Dr. L. M. Bechelli,Rua Prudente de Morais 767/111, 14015-100 Ribeirdo Preto, SP, Brazil.

Acknowledgment. The author wishes to thank Dr.

Paulo M. G. Pagnano for his comments on the manu-

script, Drs. Ana M. F. Roselino and Ana N. Almeidafor the graphic, J. C. Masotti Filho for the data on side

effects, and Miss Marisa T. Hayashi and Mrs. Regina

II. 11. Benatim, secretaries of the Department of In-

ternal Medicine.