S224^ International Journal of. Leprosy^ 2001

Ch 368CHEMOPROPHYLAXIS :A SYSTEMATICREVIEW OF THE LITERATURE AND META-ANALYSIS

Smith C'.M. on behalf oTMILEP2 Study Group

University of Aberdeen, U.K.

Objective : To quantify the efficacy of chemoprophy-taxis against leprosy based ou a systematic review ofthe literature and meta-analysis of trials.

Method : A literature search identitied 127 publishedpapers relating to the prevention of leprosy and the useof chemotherapy in leprosy was critically appraised.Sixteen trials were selected and grouped into three cat-egories according to the levet of randomisation of thetrial groups. The Relative Risk (RR) with 95% conti-dence intervals was calculated from the raw data usinga random effects moda To estimate the cost effective-ness of chemoprophylaxis treatment, a further analysisof the rates of disease in the trial and control groups wasdone. The numbers needed to be treated ( NNT) to pre-vent une new case of leprosy was then estimated (inci-dence in non-exposed minus incidence in the exposedequals reduced rate, 1 divided by RR equals NNT)

Results : The overall results of the meta-analysisshows that chemoprophylaxis gives 60% protectionagainst leprosy, and when given to dose contacts of in-dex cases, this protection increases to as much as 99%in some studies. The numbers needed to treat werefound to be low in trials of household contacts andhigh in community based stuclies.

Conclusion : The evidence shows that chemoprophy-laxis against leprosy is a feasible and cost-effectiveway to reduce the future incidence of leprosy througha targeted approach. The role of chemoprophylaxisneeds to be re-examined using newer drugs.

Department of Public Health, University of Aberdeen,Foresterhill, Aberdeen AB25 2ZD, U.K.

Phone : 0044-1224-553802 Fax : 0044-1224-662994

Ch 416RELAPSE CASES AMONG THOSE RFT

Miss Kunned Lata Lall, The Leprosy Mission Hospi-tal, Naini, Allahabad, Uttar Pradesh

Objective: To tind out details of relapses among thoseRFT

Design: Retrospective study patients returned with re-lapse during surveillance out of RFT.

Setting: The Leprosy Mission Hospital, a large referralcentre at Naini, Allahabad. Uttar Pradesh, India.

Participants: Records of relapse cases out of surveil-lance

Main Outcome Measures:

Percentage of relapse out^RFT patients.

Conclusion: The trends of relapse of ratio over the past9 years among RFT patients here were evaluated.There was a variation in the percentage of relapseaniong RFT' patients.

The Leprosy Mission Hospital, Naini, Allahabad - 211008, Uttar Pradesh Phone : 0091-532-697267

Fax : 0091-532-697262

Email : thunaini@nde.vsnl.net.in

Oc 279OCULAR COMPL1CATIONS IN LEPROSY :AN EPIDEMIOLOGICAL STUDY OF 219PATIENTS

Ye Fachang, Bao Xin & Mii Hongfiang, GuizhouProvincial Institute Of Dermatology And Venereology,Guizhou, China

One hundred and thirty cases of the 219 patients sur-veyed were founci to have ocular complications, anoverall prevalence rate of 59.36%. The peak preva-lence was seen in hospitalized patients (68.87%,104/151), next in cures after discharge (55.8%, 24/43)and the lowest in newly detected cases (8%, 2/25). Vis-ual disability rate in the study group is 21.6% includ-ing 12.33% blind SIIITerers. The main causes leading tovisual impairments are lieis involvement 1 lagophthal-mos, ectropion) accounted for 24.66%, iris impair-ments 11.4%, corneal diseases 8.6%, and panoph-thalmitis 5.94%.. Adapting measures, such as surgicalcorrection, self-care, functional exercise and topicalmedication, visual acuity of 85 cases (65%) could beimproved or kept unchanged.

126 Gulouxidajie, Beijing - 100009. China Phone0086- 10-649502 16

Fax : 0086-10-64950216

Email : hedaxun@ I63.net

Ne 99ULTRASTRUCTURAL NEUR XL-PATHOLOGYIN LEPROMATOUS LEPROSY

Kumar, Central JALM A Institute For Leprosy, Agra

Involvement of the peripheral nerves is a basic patim-logical phenomenon observed in leprosy whose mani-festation are seen richt from the early stage with hypo-anaesthetic and hypo-pigmented patches to theadvanced forms of the disease with multiple deformi-ties. In the present investigation we have studied theSchwann cell and endothelial edis of endo-neuralblood vessels.

69, 2 (Suppl.)^A bstracts of Congress^ S225

Nerve biopsies from four lepromatous leprosy patientswere studied by light and electron-microscopy. The pa-tients (131=6+, Ridley scale ) were on treatment withW.H.O. multidrug therapy for 6 mond] to 1 year. Ultra-structuml examination showed that un-inyelinatedSchwann cell containing many intui bacilli with Elec-troo Transparent Zone. Nlany of the blood vessels en-countered on electron microscopy contirmed the lightmicroscopic observations of intact bacilli in endothelialcolls of endo-neural blood vessels . At the point of thin-ning the endothelial cens appeared rupturing and (tis-charging their contents into lume]] of the vessels. M.lep-rae were seen fioating free in the plasma. The Schwanncells of myelinated aron were not affected in our seriesand M.leprae were not observed. Our observations sug-gest that the Schwann cells of non-myelinated libresprobably have a agreater afiinity for M.leprae thaninyelinated fibres.Whether those two types of Schwanncells are metabolically clifferent, is to be seen.

Central JALMA Institute For Leprosy, Tajganj, Agra -282 001 Phone :0091-562-331751 - Extension 244

Fax : 0091-562-331755

Email : useng@nde.vsnl.net.in

Ne 109PERIPHERAL NERVE SURGERY IN LEPROSY

Dr.G.N.Malariya, Central JALMA Institute For Lep-rosy, Agra

Leprosy is mainly disease of nerves. The skin involve-ment is xvith allprobability, secondary to the neural dam-age at the dermal levei. The involvement of peripheralnerve trunks leads to sensory-motor cleticits in the limbs.

These delicits clinically manifest as (i) deformities re-sulting from adaptive postures conseguem to musclepalsies and (ii) wounds and ulcers due to anaesthesia.Leprosy is feared for its deformities and ulcers whichare also the cause of social ostracism and 511 ma asso-ciateel with the disease.

The neural darnage is 1111111 factorial, intlammatoryneuropathy is initiated by the bacillus to which com-pression neuropathy is also added when the [terveswelling reaches a threshold and can no longer be ac-commodatecl lo the osseofascial tunnels through whichthe nerve trunks have to pass in their course. In theprocess. the nerve trunk is damaged.

Peripheral nerve surgery has a lot to contribute to thewel Iate of a leprosy paliem. First and foremost it canhelp rei leve the compression oh the 'terve trunks andgives good results if steroid therapy is supplementedwith. Thus, it lias a role in preventing the onset of de-formities. Further, if the nerve dainage has become es-tablished, protective sensations can be restored insome patients by simple nerve trunk decompressionbecause nerve libres retain the capacity to regenerate

even in badly thimaged nerves.

Attempts have been made to restore nerve functions bynerve grafting procedures using both (i) autologousand homologous nerve grafts and also (ii) musclebridge grafts of various types. Sensory nerve transfershave been attempted too in certain situations to restoreprotective sensations.

The above concepts will be discussed in some detailalong with their meras and demerits and some likelyfuture approaches will be outlined.

Central J ALMA hist itute For Leprosy, Tajganj, Agra -282 001 Phone : 0091-562-331751

Fax : 0091-562-331755

Ne 164INCIDENCE OF NEURITIS IN A RURALLEPROSY PROJECT OF ORISSA WITH ANINTEGRATED POD PROGRAMME

M.Sathi Ruja,^KEswara Ruo & P.V.PramodSecunderabad

A leprosy project was established in a tribal arca ofOrissa state covering a population of 550 thousands.Routine SET activities were started to detect all thepossible cases in the project arca through surveys. Ad-ditionally prevention of deformity programmes (POD)were initiated as ao integral part of the leprosy serv-ices. The methodology adopted in this component was,examination of patients in a systematic method ofnerve function assessment.

Ali the patients are initially stratified int() 6 risk gradesdepending on their possible risk of developing defor-mity. 36 patients were excluded as not having any riskof developing deformity among 2003 patients. Rest ofthe cases were followed up in the POD programme.

Among patients who had nerve function impairmentand were treated with standardized steroiti therapy andsupportive physiotherapy, 8% had shown improve-ment io nerve function. The patients were further fol-lowed up to monitor the nerve function during surveil-lance period. 4 patients developed new nerve functionimpairments covering the course of MDT programme.

Nerve function assessment is done for ali patients un-der the programme and they also are educated on selfcare practices. The programme also includes i roduc-ing appropriate instruction in the process of treatingTICLIritis.

P.B. No. 1518. Krislmapuri Colony, West Marredpally,Sectinderabad - 500 026 Phone : 0091-40-7802139,7807314

Fax : 0091-40-7801391

Email : vrp@lepraindia.org

S226^ International Journal of Leprosy^ 2001

Ne 218ALTERED CHOLINESTERASE LEVELS INLEPROSY NERVES

Lavanya M.Suneetha *, Bhanumathy C.D. #, SamuelSolamo,: @, Sujai Suneetha *, Ravi J.Korula # & Bal-asubtynnanian #, * Lepra India, Hyderabad # ChristianMedical College & Hospital, Vellore, @ SchieffelinLeprosy Research & Training Centre, Karigiri

Cholinesterases are ubiquitous enzymes which play arole in cholinergic transmission, neurogenesis and areimplicated in neurodegeneration and dementia. Verte-brate cholinesterases fali into two categories, Acetyl-cholinesterase (AchE) and Butrylcholinesterase(BchE). These two enzymes differ in substrate speci-ticities and inhibition by selective inhibitors. AchEpreferentially hydrolyses acetylcholine or acetyl-beta-methyl choline while BchE preferentially hydrolysesbutyrylcholine. Work on AchE and BchE in leprosyskin, muscle and serum have been reported. This studyassessed cholinesterase leveis in nerves from patientswith leprosy.

These enzymes were assayed in six normal and 12 lep-rosy nerves in the presence of their selective inhibitors.The mean BchE levet in leprosy nerves was 17.25U/mg (SD 7.37) and

8.35U/mg (SD 6.21) in the normal nerves. The meanAchE levet in leprosy nerves was

21.87 U/mg (SD 6.81) and 16.71 U/mg (SD 5.50) inthe normal nerves. AchE was not significantly altered,but BchE activity was significantly elevated in leprosynerves when compared to normal nerves (P>0.05).

The results show that in leprosy patient nerves there isa significant increase in BchE activity and not in AchEas compared to normal nerves. The possible role ofthese enzymes in leprosy neurodegeneration will bediscussed.

Lepra India, Blue Peter Research Centre, Cherlapally,Hyderabad - 501 301 Phone : 0091-04-7264547

Fax : 0091-40-726257 I

Email : lepindia@hdl.vsnl.net.in

Ne 290TRIPOD TRIAL PREPARATION FOR A CLINI-CAL TRIAL IN A FIELD SETTING Aliso,, M.An-derson

Pokhara, Nepal

The TRIPOD trial is a double blind, placebo con-trolled, multi-centre trial of the use of Predinisolone inthree aspects of leprosy treatment - prophylactic usefor the prevention of nerve function impairment, treat-ment of early sensory nerve function impairment andtreatment of longstanding nerve function impairment.

The trials are run in field clinics of six centres span-ning two countries, with local paramedical staff takingthe primary responsibility for trial patients. In design-ing a trial to run under these contlitions, without com-promising safety and scientific standards, several keyissues were addressed in the design phase, in thepreparation phase and during the trial.

DESIGN - The design conforms to acceptable stand-ards in terms of trial size and randomisation. Ran-domisation and balance of patients between countriesand individual centres needed to accommodate thepossibility of between country/centre differences andearly curtailment.

MANUFACTURE & DRUG DELIVERY - Drugswere locally made for the trial, minimising cost ofmanufacture and cost of importation. Spot checks ofthe manufacturer were made during the process. QCsamples were independently assessed. Drugs werepacked in unique numbered packs under strict supervi-sion.

STANDARDISATION & TRAINING - Between cen-tre differences were minimised by the use of agreed,simplified, standardised entry, exit and outcomeria, and measurement techniques. Centres took part intraining and reliability testing before the iria! started.

SUPERVISION, SAFETY & CONTROL - The trial isintegrated into the routine clinic programme and runby staff in the clinics. Safety is assured through an hi-erarchy of clinic and centre managers, backed up by alocal trial co-ordinator and in-country directors. A su-pervision programme ensures that clinics maintain thestandards set. A co-ordinating committee remote fromthe field provides technical backup, reviews outcomedata and makes safety checks.

Green Pastures Hospital Complex, RO. Box 28,Pokhara -33701, Nepal Phone : 00977-61-21083

Fax : 00977-61-20430

Email : aanderso@inf.org.np

Ne 346LEPROUS NEUROPATHY : MORPHOLOGI-CAL STUDY OF IHOPSIED PERIPHERALNERVES

Takashi Kimura, Kiyoharu Inoue, Shinzo Izaumi,Kazuki Hashimoto & Osamu Yahara, Hokkaido, Japim

Hansen's disease is an infectious disease presenting it-self as neuropathy and skin lesion. Mycohacteri umleprae is the pathogen of leprous neuropathy but themechanism of nerve damage is uncertain. Perineurialthickening and intilteration of M.leprae and/or cell arethe main pathological characteristics of Hansen's dis-ease on nerve biopsy. Here, we report the morphologi-cal study of perineurium in biopsied nerves.

69, 2 (Suppl.)^Ahviracts of. Congress^ S227

Biopsied peripheral nerves from len leprosy patients (6atherculoid patients and 4 lepromatous patients) wereexamine(' from morphological aspeet.

Light microscopial examinado') showed that lhe per-ineurium was markedly thiekened by inl lume(' cells intuberculoid type and mycobacterium leprae in lepro-matous type. Sehwann eells markedly decreased innumber and nerve libre disappeared without regenera-do') in severe cases. In mild cases, subperineurialedema Wa ti present. The nerve libre density was nor-mal or mildly decreased. Ultrastructural examinado]]showed the abnormalities of basal lamina on perineur-ial edis. The basal lamina of the perineurium com-pletely disappeared in several cases. In mild cases,subperineurizd edema was present. The nerve libredensity was normal or moi Id decreased. Ultrastructuralexamination showed the ahnormalities of basal laminaon perineurial cells. The basal lamina ()I' the perineur-ial disappeared in severa' cases and showed splittingeven the perineurial looked like the normal completestructure in light microscopy. Both types of leprousneuropathy had same changes with regard to abnor-mality of the basal lamina. There are many

M.leprae Schwann edis in libroblasts and perineurialcens ou the nerve of lepromatous patients. althousihfew M.leprae in the nerve of tuberculoid patients. Pre-vious studies indicated that the pathogeneris of leprousneuropathy was doe to destruction of. axon. This studyprov ides that these abnormalities of perineurium arecharacteristic in both types of leprous neuropathy. The

perineurium acts as a barrier between the interior ofthe nerve and extraneural Iluid environment. The dam-aged perineurium light luse the normal function and al-low tissue-damaging l'actors to enter the 'terve result-ing in degeneratine nerve libres.

Hanasaki -7, Asahikawa. Hokkaido - 0788644, JapanPhone :0081-166-513161

Fax : 0081-166-539184

Im 133A STUDY ON THE REPRODUCTIBILITY OFTWO SPECIFIC SEROLOGICAL ASSAYS FORDIA GNOSIS OF LEPROSY

Dr.Om Praka.s.h, Central JALMA Institute For Lep-

rosy, Agra

1)ialtnosis is the first step in the tremulem and controlof any disease, both in the individual as well as in thecommunity. Over the years a variety ()I serological as-says have beco descri bed for diagnosis leprosy.Sean]] antibody competido') test based enzyme I iiikeelimmunosorbent assay (SACT-ELISA) and phenolicglycolipid based enzyme linked immunosorbent assay(PGLELISA) have been reporte(' to be uselul and havebeen studied widely. Que of the important characteris-tics needed for ao immunocliagnostic test, is repro-

dueibility of the results. Regardinu these two assaysthere is no such information available in the literature.Theret6re. ao attempt was made to lind out variations(with-in and between the assays) in the results of Mesetwo tests. 111 the present report. the lindings. in brief,for same have been described.

The reproducibilities ()V Mese two assays were esti-mated using sera with different leveis of anti-Myco-bacteri 11111 leprae antibodies. From the tinding.s it ap-pears that with-in assay reproducibility ofSACT-ELISA is better for sera having low and iniddleleveis of antibodies whereas with PGLEL1SA it \vasbetter with sera having high and low levels of antibod-ies. Between assay variations were 1)01 promising I6rboth the assays. Regarding lhe percent positivities ofboth the assays, the PGL ELISA showed better repro-ducibility that) SACT-ELISA. The results would bepresented and discussed in details.

Central JALMA Instante For Leprosy, Tajganj, Agra -282 001 Phone : 0091-562-331751 - Extension - 203,"")14

Fax :0091-562-33i755

Email : useng@nde.vsnl.net.in

Im 316SCREENING NEW LEPROSY ANTIGENS FORPOTENTIAL AS LEPROSY SKIN TESTS

Parateshwor Amalya *, 1?akesh Manumitia,. *, Kees

Franken #, Toni °malho/1#, Warwick Briaon @ &

Paul Rache , '1' Anandaban Leprosy Hospital, Kath-mandu, Nepal # University Hospital. Leiden. Holland@ University of Sydney, Australia

Elimination of leprosy will require new tools to iden-tify trends in leprosy infection in the community. Aleprosy-specific skin test could answer the critica]question of how MDT programmes impact the trans-mission of leprosy. Present leprosy skin tests com-posed of fractions of the leprosy bacillus do not havethe requisite specilicity to detect leprosy exposure incommunities with high levels of. tuberculosis. We havedemonstratecl that leveis of the cytokine interferon-gamma (IFN- ) produced in a simple overnig.ht wholeblood cultui-e with leprosy antigens are increased inhealthy contacts of leprosy patients. The 35kD zintigen(Triccas, 1996), the 45k1) amigen (Vega-Lopez, 1998)and a newly expressed M. leprzte homologue of theearly secreted antigen of TB of 6k1) (ESAT-6 ML)were employed in overnight whole blooll assays andinterleron-gainina was measured in supernatants.Sion-Herm cultures were compared with longer (5-day) cultue and \vith T-cell proliferation in Nepali lep-rosy patients, leprosy contacts and unexposed subjects.These data indicate the potential of these three rela-tively leprosy-specific antigens for leprosy skin tests.