issues and technical support. WHO is also involved in advocacy;resource mobilization and utilization through variousmechanisms in collaboration with other UN agencies. NGOs.multilateral and bilateral partn-ers. For the short and mediumterm, WHO supports and encourages the enormouscontributions from international sources but would undertakeefforts to increase mbbilization towards meeting the needsof countries.

References1. Nabarro ON and Tayler EM. The "Roll Back Malaria. campaign. Science 1998; 280:

2067.2068.2. Balter M. Can WHO roll back malaria? Science 2000; 290: 430.3. Africa Malaria Report. 2003. WHo-UNICEF; WHO/COS/MAlJ2003.1093.4. Clinical. behavioural and socio-economic factors related to severe malaria: A multicentre

study in the African Region, WHO 2002. AFR/MAU02.01.5. Narasimhan. V and Attaran A. Roll Back Malaria? The scarcity of international

aid for malaria control. Malaria Journal 2003; 2:8. Article available from:~malariaiournal. com/content/2/ 1 /8

ITNs and encouraging their correct use. Since most Atricangovernments are highly de pendent on external funding forhealth, increased governmental health expenditureswoul~ "ensure greater support for malaria contraI activities. Heavy ~financial investments will be required to strengthen the humah'and institutional capacities to absorb the increased financialin~flows and ensure timely and efficient utilization of resources.ln addition to the traditional malaria contraI personnel. aspecial cadre of malariologists with the appropriate skills mixwill be required, to push the current contraI agenda forward.This would be greatly facilitated by improvement in thetechnical and management abilities of the key actors involvedin this contraI agenda. To sustain impact, funding must notbe sparse and sporadic. but adequate with a long~term focusto meet not only the immediate targets of Abuja but to meetthe MDGs and beyond.

The main Tales of WHO in financing malaria contraIinterventions remain that of providing leadership on health

RESEARCH ARTICLE

Tiendrebéogo A*, Andriamiandrisoa M**, Vololoarinosinjatovg~M ~***, Andrianarisoa S H', Randriamitantsoa J", Bidé L'",,).

IntroductionFurther to the World Health Assembly WHA 44.9

recommendation, 1 Madagascar set up a leprosy elimination

programme in 1992.2 Currently; WHO~recommended MOT isthe cornerstone to eliminating leprosy as a public healthproblem.3 To reach this goal, leprosy programmes in endemiccountries need 10 diagnose and treat with MOT aIl cases ofleprosy. 4,5,6,7 Considering the low health service coverage in

many leprosy~endemic countries, WHO recommended a flexiblesupervision of monthly intakes of Rifampicin in 1995.8 Flexibilityallows giving a patient MOT blister packs for periods of 2, 3,and even 4 months in case of remoteness of the treatmenthealth centre or seasonal inaccessibility. Evaluation of LECs(Leprosy Elimination Campaigns) carried out in districts ofMadagascar showed that 40% of found cases had not receiveda complete treatment. 9 This finding led the LEC's evaluation

team to propose that, for some patients unable to receive acomplete treatment with monthly or flexible supervision ofRifampicin intakes, blister packs for a complete treatment besupplièd after diagnosis.This strategy of treatment withoutsupervision of Rifampicin intakes was called "accompaniedMOT", because a relative of the patient (family member, friend,community leader) is charged to assist and encourage thepatient to take hismedicines until the treatment completion.1O

From 2000 to 2002, AMOT wasadopted for the treatmentof patients unable to attend monthly, supervised intakes ofRifampicin.9 Our study evaluates and compares theeffectiveness in terms of cure rate of AMOT and supervisedMOT (SMOT) strategies applied in 2001 in this country. Generalobjective of our survey was to formulate recommendationsfor using supervised and accompanied MOT consideringleprosy patients' accessibility to treatment health centres.

AbstractBecause of the low cure rate, accompanied multiple drug

therapy (AMDT) was recomtnendedfor treatment of leprosycases unable to attend monthly or flexible intakes of Rifampicinduring supervised multiple drug therapy (SMDT). ln 2003, wecarried out a survey to evaluate and compare the effectivenessof these two treatment strategies (AMDT versus SMDT) withthe objective of formulating recommendations for ~pervisedand accompanied MDT in leprosy~endetnic countries. Thesurvey consisted of cluster sampling of 1,000 patients treatedduring 2001 in Madagascar, either by AMDT or SMDT.Information based on patient interview and clinical examinationwas collected by questionnaires conducted by national leprosyprogramme, health district and basic health centre (BHC) staffin 33 randomly selected districts.

Information from 962 patients, of whom 727 were treatedwith AMDT and 235 with SMDT, showed AMDT was moreeffective than SMDT. The cure rate in AMDT~treated patientswas 98%, whatever the distance between patients' homevillages and BHC. ln SMDT~treated patients, the cure rate was85~86% for those living between 0 and 10 km distance to BHCand 79% for those living more than 10 km from BHC. lnaddition, OUr study did not confirm the advantages of SMDTstrategy in terms of better treatment and care of leprosyreactions and complications occurring during treatment. Basedon those results, we recommend that AMDT should be thetreatment strategy for patients living more than 10 km distancefromhealth centres.

,,'

* Leprosy consuijant, WHO Country OfIiœ in Madagascar, BP 362 Antananarivo 101, lepomS@iris.mg** Director of the Control of Malaria, Leprosy and Tuberculosis, Ministry of Health and Family

Planning, in Madagascar*** Chief, Leprosy Control Central Unit of the Ministry of Health and Family Planning, Madagascar* Medical Officer, in charge of activity foilow up at the Leprosy Control Central Unit, Ministry of

Health and Family Planning, Madagascar** Medical Officer, in charge of logistics at the Leprosy Control Central Unit, Ministry of Health and

Family Planning, Madagascar"* Regional Adviser, Leprosy Elimination Programme, WHO Regional Office in Africa

MethodsThe study consisted of a cross sectional and descriptive

survey involving a random sam pIe of accompanied and

supervised MOT~treated groups of patients (cluster sampling).Leprosy patients treated with MOT during 2001 in Madagascar(around 9,000 people ofwhom 8,599 were new leprosy cases)represented the target population. Sample of patientsto .'retrieve for examination was retained randomly from the listof health districts with cumulative number of new leprosy~j.patients MOT treated during 2001.

By fixing MOT cure rate at 60% and the lowest expected-cure rate at 55% (supervised MpT cure rate during LeprosyElimination Monitoring carried outÏn the country in 199711),the sample sile in a simple random sampling would have been354 witha confidence interval of 95%. Health districts werethe base of sampling. We thus considered a cluster effect of2.5 and put the sample sile at 1,000 patients. Tpe sile of acluster was 25, and we randomly seleçted 40 c1usters fromthe 111 health districts of the country. .

The following survey information was obtained in villages,health centres and- districts randomly selected. Thequestionnaire served to collect information from each caserecruited in the survey. The information forfis were reviewedby the study health districts and centres and at patients'houses: patient clinical file, leprosy treatment booklet, blisterpack stock bin card, health centre 2001 activity monthlyreport, health district 2001 leprosy register, patient's treatmentcard. Retrieved patients were questioned on thecircumstancesof the diagnosis and on treatment go~off. They were thenclinically examined for skin and nerves lesions. We did nottake skin smears for laboratory exam because bacteriologicalexamination has little importance in assessing leprosy cure,particularly when skin smears were not taken at diagnosis ofmost patients and that bacillary index (BI) before treatmentwas unknown.

The survey started in June 2003 and was completed inOecember the saille year. ln each of the six provinces ofMadagascar, Leprosy Programme central unit medical officerand/or WHO leprosy consultant, assisted by ~epro,jyProgramme provincial managers started data collection byvisiting sampled health districts and listing the naines ofpatients to be retrieved for interview and examination.Personnel of basic health centres (BHC) looked for the patientswith the support of community local leaders like village chiefs,local NGO staff members, members of local health committee .and religious leaders. Patients retained for the survey were

examined at basic health centres, and BHC staff visited patientsat home who did not go to the health centre. To ease thecase finding, incentives were allocated to BHC staff and,

-community leaders and patients travelling to health centres.Ali completed questionnaires went to national level forcomputerisedanalysis with Epi~info and Excel software.

ResultsFrom the sample of 1,000 people treated with MDT in 2001

within the 33 randomly selected health districts visited forthe survey, 962 completed questionnaires were sent foranalysis. 1\1/0 districts did not send back their questionnaires,and four districts recruited more cases than scheduled.Recruitment rate was 96% of the expectedsize of patients'sample.

Of the study sample 57% were males, 89% were older than14 years of age, 88% were from rural areas and 97% were notliterate (Table 1). Of the total, 24% lived more than 10 kmfrom the health centre providing MDT treatment, 56% hadmultibacilary form of leprosy (MB) and Il % were disabled(with grade 2 disability in WHO scale).

For ail those parameters, the two groups treated with AMDTand SMDT were different. AMDT group (76% of the studiedsample) had relatively more female cases. more children (lessthac 15 years old), more illiterate people working in ruralareas, living more than 10 km from health centres, affectedby paucibacillary form of leprosy and having more grade 2disabilities at diagnosis.

Due to the applied treatment strategy, each group hadspecific characteristics. Thus, in the AMDT group, 451 people(62%) retumed to the basic health centre for the end~of~treatment examination. Of 693 people interviewed, 340 (49%)had an a,ccompanying person for their AMDT treatment. Finall~675 of 693 (97%) of people interviewed said they took thetotality of given blister packs after diagnosis.

ln SMDT group, treatment adequacy rate (PB patient havingtaken the 6 PB blister packs in a period less or equal to 9months or MB pat.ient having taken the 12 MB blister packsin a period less or equal to 18 months) was 18% (43 casesout of 235 evaluated patients). Defaulter patients (interruptionof treatment for more than 12 consecutive months) were 60,equalling 26% of SMDT group.

Figure 1: Cure rate and occurring or worsening grade 2 disabilitiesalter the diagnosis, Madagascar, 2003

100

the treatment health centre was higher than that of patientsliving more than 10 km away (79%). Theobserved differencewas statistically significant. ln ail distances, AMDT cure ratewas always higher than SMDT (Figure 2).

ln both treatment groups, some patients did not completethe treatment. ln AMDT group, 17 interviewed patientsdisrupted their treatment because of side effects, because

~'"' -they found themselves cured after the first intakes of MDT0 Grade 2 disability 1 blister packs or did not accept thediagnosis of leprosy for

=urringorworsening ~t.' their condition.,In SMDT group, 43 patients defaultedafterf~ a treatment disruption of more than 12 consecutive months..;;,,;.,t, The cure rate in PQtients with incomplete treatment was 57%,

"Tf"'" ,,: 88% in AMDT group and 43% in SMDT group. The differenceLl.3 ",~ff_~ 'c of observed cure rates between the two groups.was statistically

significant.

~ Cure rate.,10~010-'

..

AMDT SMDT TOTAL

Other information from the survey

Allergic reactions to MDT medicines, mainly to Dapsone..occurred in 14 cases, equal to 1 % of the studied group. lnAMDT group, the allergic reaction rate was 1 %, while in SMDTgroup this rate was 2%. The observed difference was notstatistically Significant.

Leprosy reactions were observed during patients' treatmentor during the assessment clinical examination. Duringtreatment, 34 leprosy reactions occurred in patients (4% ofthe study group). Percentages of patients with reaction duringtreatment were 3% in AMDT group and 5% in SMDT group.The observed difference was not statistically significant.Leprosy reactions at the assessment examination were notedin 11'patients (1 % of the study woup). These reactions occurredin 1 % of AMDT patients and 3% of SMDT patients. Theobserved difference was not statistically significant.

Figure 2: Cure rate according to access distance between patients'home and MDT treatment health centre and treatment strategy (AMDTor SMDT), Madagascar, 2003

œ AMDT cure rate

[J SMDT cure rate

.Total cure rate

Comparison of the two strategies' effectiveness

Of the 962 p~tients of the sample whose questionnaireswere available for analyse, 845 cases (88%) were~trieved forèlinical examination to assess the cure efter MDT treatment;693 patients were tram the AMDT group (95%) and 152 tramthe SMDT group (65%). For the whole sample of examinedpeople, the cure rate reached 96%. AMDT group cure ratewas 98%, with no statistical significant difference betweenpatients who came back for the end~of~treatment examinationand those who did notor between patients having had or notan açcompanying persan. SMDT group cure rate was 85%,with no statistical significant difference between patientsadequately treated or not. The observed difference betweenthe two groups of treatment (98% for AMDT and 85% forSMDT) was statistically significant (Table 2 and Figure 1).

Questioning retrieved cases showed that 25 of them (3%of the interviewed group), 15 in AMDT group and lOin SMDTgroup, had received MDT treatment before or after 2001treatment. Mer excluding those recycled cases, the cure rateof AMDT group(98%) remained higher than SMDT group one(85%) and the observed difference was still statisticallysignificant. Among patients examined to assess the treatmenteffectiveness, 542 people did not have any disability at thetime of the diagnosis or at most had a grade 1 disability,consisting of a sensory loss without visible lesion ol\.han~,feet or eyes. Grade 2 disability, occurring or worseI1ing ofgrade 1 disability. among these people has been 2% in generaland 1 % and 3% in AMDT and SMDT groups, respectively(Figure 1).

AMDT group patients' cure rate remained at98% whateverthe distance between patients' village ~nd the treatment .health centre. However, in SMDT groups, the cure rate of

1to10km

During assessment clinical examination, still visibl~\Jeprosypatches were observed in 308 cases (36% of the study grt>up).Those visible patches were present in 36% of AMDT patient~and 39% of SMDT group. The gbserved difference was I:lptstatistically significant. 1

Our study results did not confirm advantages of supervisedMDT strategy; neither performing nerves' examination duringpatients' monthly visits to health centres to detect, treat andprevent neuritis and impairments nor better treatment andcare of leprosy reactions and complications occurring duringtreatment. There was no statistically significant differencebetween the two groups foroccurring leprosy reactions ormedicine allergy, or for occurring or worsening grade 2disabilities. This absence of difference could be explainedbecause: most disabilities happen after silent neuritis or severeleprosy reactions hitting the patients at home and impossibleto prevent by periodic examination at health centres; inpractice, leprosy patients treated with SMDT are not properlyand systematically examined for neuritis during monthly visitsto health centres; peripheral health centre workers are usuallynot trained to carry out nerve examination with sensory andmuscle testing on hands and feet.

Finally, the idea that SMDT permits better follow~up ofleprosypatients, mainly to detect and treat leprosy reactionsand neuritis, is not verified. Indeed, a SMDT~treated patientwhose leprosy reaction would occur a few days after her/hismonthly visit to the health centre for supervised treatment,would not go back to the health centre for consultation.A treated patient, weil informed to refer to the health centrein case of reaction, would do so either treated by SMDT orAMDT. Not supporting the costs of monthly visits to the healthcentre, the AMDT~treated one would be more able, financiallyspeaking, to travel to the health centre for the treatment ofhis/her reaction than one treated with SMDT.

DiscussionHeterogeneousness of the two treatment groups

The difference in sile of the two treatment groups does notreflect the real repartition of 2001 treated leprosy cases.Based on wrong information that ailleprosy patients in 2001were treated With AMDT, the sampling did not tare into accountthe need to recruit two representative groups for comparisonof the two treatment strategies. The larger number of peoplerecruited in the AMDT group is attributable more to therandomisation of the clusters that selected the country'smost~endemic districts. These districts, most of themlandlocked and with the most difficult access to patients,were in the majority of those retained for AMDT strategy.

Heterogeneousness of the groups is also linked to the factthat AMDT particularly addressed patients living in remoteareas. It is then easy to understand that women, with legsmobility compared to men, are more present in this group.Children for whom an accompanying persan is easy to findin their family (parentaJ.are also and logically more representedin the AMDT group of treatment. Other criteria (remoteness,living in rural area, lower literacy rate, leprosy disability) arealso attached to AMDT group, meaning legs accessibilitY't9 .."'health services for patients of that group. For the type ofleprosy (PB or MB), the shorter treatment of paucibacilla~. '..cases probably influenced the frequent choice of AMDT forPB patients. MDT blister packs were put in lots of six in plasticbags, and many MB patients received their full treatment in-two parts, collecting a bag of six blister packs at each visit tothe treatment health centre. Those cases were considered astreated by SMDT, with flexible sem ester supervision ofRifampicin intakes.

ConclusionWith increased MDT service coverage owing to ~he integration

of leprosy programme in basic health centres and bettermanagement of MDT blister packs. combinations of SMDTand AMDT in 2001 resulted in improved leprosy patients' curerate in Madagascar, up to more than 90% whatever the leprosyform (PB or MB). By giving patients the totality of requiredblister packs for a complete treatment at diagnosis, AMDTstrategy showed a higher cure rate than SMDT. Furthermore,our survey did not confirrn advantages of supervised treatmentin terrns of better case holding, prevention and care of leprosyreactions and complications. Considering MDT~service coveragein the count~ whichwas 80% of basic health centres accordingto 2003 Leprosy Programme annual report. accompanied MDTstrategy should be continued in Madagascar. ln this case.during leprosy active case finding, new cases in villages situatedmore than 10 km of a health centre should be treated withAMDT.

The observed cure rates ,-'.ln the studied sample. the observed cure rate was very high,

whatever the type of leprosy and even in patients withincomplete treatment. This confirms the great effectivenessof WHO~recommended MOT regimens. This cure rate is farhigher than that observed in 1999 among leprosy casesdiagnosed during 1997 and 1998 LECs and during LeprosyElimination Monitoring in 1997. which showed a cure rate of55%.12 AMDT, however. was not the only factor improving thecure rate in the country. Among other favouring factors werethe increase in health service coverage and better managementand supply of blister packs, namely packing them in lots ofsix plastic bags before sending them to basic health centres.

The superiority of AMDT cure rateAMDT treatment strategy obtained a higher cure rate thanSMDT.

This is probably because a case of leprosy able tocomplete MDT treatment with monthly supervision. whengiven the treatment in AMDT. would surely complete themedicine intake. even without an accompanying persan.A patient treated with AMDT. having ail the blister packs withhim/her at home and unable to take the medici~es uq,tiltreatment completion, however. would not complete hisihertre~tment if proposed for supervised MDT. Unlike'SMDT.distance does not influence AMDT effectiveness. In.terms ofcure rate. AMDT appears the most appropriate strategy inareas with poor health service coverage and difficult accessto health centres for geographical or financial reasons.

References1 v.Iorid Health Assembl~ Elimination of leprosy. Resolution 44.9. 13 May 1991. Handbook

of resolutions and decisions of the WHA and the Executive Board. 3 Vol. III. 19851992. 3rded. Geneva: WHO. 1993; 117-118.

2. Madagascar Ministry of Health. Nationalleprosy control programme. 1992.3. WHO. Leprosy Elimination Group. The final push towards elimination of leprosy-

Strategic plan 2000-2005. Geneva. 2000.4. WHO. A guide to leprosy controi. Geneva: OMS. 2nd ed.. 1989.5. WHO. Shortening duration of treatment for multibacilary leprosy. WER. May 1997.6. WHO. Chemotherapyof leprosy for control programmes: report of a WHO study group.

WHO technical report series. no. 675. 1982.7. WHO. Chemotherapy of leprosy: report of WHO study group. WHO technical report

series. no. 847.1994.8. WHO. A guide to eliminating leprosy as a public health problem. Geneva: WHO.

WHO/LEP/95.1.1995.9. Madagascar Ministry of Health. Report of joint mission. Ministry of Health. WHO and

Raoul Follereau French Association. on the evaluation of leprosy elimination campaignsin high endemic districts of Madagascar. April 1999.

10. WHO. Guide to eliminate leprosy as a public health problem. Geneva: WHO. 2000.Il. WHO. Risk of relapse in leprosy. Geneva: WHO/CTD/lEP/94.1. 1994.12. Madagascar Ministry of Health. Report on leprosy elimination monitoring in Madagascar

by Ministry of Health and WHO externat monitor. May 1997.

Communicable Diseases Bulletin for the African Region .Volume 2 No. 3