INTERNATIONAL JOURNAL OF LEPROSY

Page 1

VOLUME 73, NUMBER 2

JUNE 2005

Special Grantors and Sustaining Members

Listed in Contents

INTERNATIONAL

JOURNAL OF LEPROSY

And Other Mycobacterial Diseases

Official Organ of the

INTERNATIONAL LEPROSY ASSOCIATION

(Association Internationale contre la Lèpre)

(Asociación Internacional de la Lepra)

Page 2

Images from the History of Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Original Articles

Hussain, Tahziba, Sinha, Shikha, Kulshreshtha, K. K., Katoch, Kiran, Yadav, V. S., Sengupta, U., and Ka-

toch, V. M. Seroprevalence of HIV Infection among Leprosy Patients in Agra, India: Trends and Perspective -

Gupta, U. D., Katoch, K., Singh, H. B., Natrajan, M., and Katoch, V. M. Persister Studies in Leprosy Pa-

tients after Multi-Drug Treatment - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Narang, Tarun, Kaur, Inderjeet, Kumar, Bhushan, Radotra, Bishan Dass, and Dogra, Sunil. Comparative

Evaluation of Immunotherapeutic Efficacy of BCG and Mw Vaccines in Patients of Borderline Lepromatous

and Lepromatous Leprosy - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Kumar, Anil, Girdhar, Anita, and Girdhar, B. K. Prevalence of Leprosy in Agra District (U.P.) India from 2001

to 2003 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Case Report

Pandhi, Deepika, Mehta, Shilpa, Agrawal, Subhav, and Singal, Archana. Erythema Nodosum Leprosum

Necroticans in a Child—An Unusual Manifestation - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Correspondence

Burdick, Anne E., and Ramirez, Claudia C. The Role of Mycophenolate Mofetil in the Treatment of Leprosy

Reactions - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Asilian, A., Faghihi, G., Momeni, A., Radan, M. R., Meghdadi, M., and Shariati, F. Leprosy Profile in Isfa-

han (A Province of Iran) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Commentaries

Nelson, Kenrad E. Leprosy and HIV Infection (Rarely the Twain Shall Meet?) - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Steinhoff, Ulrich, and Visekruna, Alexander. Leprosy Susceptibility—A Matter of Protein Degradation? The

Role of Proteasomes in Infection and Disease - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Obituary

Diltor Vladmir Araujo Opromolla (1934–2004) by Marcos Virmond - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

African Leprosy Congress - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

News and Notes

Damien-Dutton Award - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Calendar - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

Special Grantors - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -

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INTERNATIONAL JOURNAL OF LEPROSY

and Other Mycobacterial Diseases

CONTENTS

Volume 73, Number 2, June 2005

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INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 2

Printed in the U.S.A.

(ISSN 0148-916X)

INTERNATIONAL

JOURNAL OF LEPROSY

and Other Mycobacterial Diseases

VOLUME 73, NUMBER 2

JUNE 2005

Images from the History of Leprosy

Missionary work in Chitokoloki, Africa, 1935. Mrs. George Suckling and her assistant

are shown with patients at the small, remote hospital in Chitokoloki in what is now Zam-

bia. In this pre-dapsone era, no specific treatment was available and only supportive care

could be offered. The image is electronically reproduced from an original black and white

print measuring 4 × 6 inches, and was made available courtesy of Mrs. Linda Beer-

Kumwenda.

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Page 7

1 Received for publication on 21 September 2004. Accepted for publication on 13 February 2005.

2 T. Hussain, Senior Research Officer; S. Sinha, Senior Research Fellow (CSIR); K. K. Kulshreshtha, Senior

lab. Technician; K. Katoch, Deputy Director (Senior Grade); V. S. Yadav, Statistical Officer; U. Sengupta,

Scientist-Emeritus, and V. M. Katoch, Director Central JALMA Institute for Leprosy and other Mycobacterial

Disease, Tanjganj, Agra, India.

Reprint requests to: Tahziba Hussain, Senior Research Officer, HIV/AIDS UNIT and Clinical Division,

Central JALMA Institute for Leprosy and other Mycobacterial Diseases (Indian Council of Medical Research),

Tajganj, Agra - 282001. INDIA. E-mail: tahziba_hussain@hotmail.com

INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 2

Printed in the U.S.A.

(ISSN 0148-916X)

INTERNATIONAL

JOURNAL OF LEPROSY

and Other Mycobacterial Diseases

VOLUME 73, NUMBER 2

JUNE 2005

Seroprevalence of HIV Infection among Leprosy

Patients in Agra, India: Trends and Perspective1

Tahziba Hussain, Shikha Sinha, K. K. Kulshreshtha, Kiran Katoch,

V. S. Yadav, U. Sengupta, and V. M. Katoch2

ABSTRACT

This study compares the results of HIV seroprevalence, which was carried out in two

phases, i.e., 1989 to 1993 and 1999 to 2004. Although the number of leprosy patients

screened for HIV infection in the second phase is less (2125) as compared to those screened

during the first phase (4025), a rise in HIV infection from 0.12% to 0.37% is certainly dis-

turbing since this area appears to be endemic for both the infections. During the study pe-

riod, the Out Patient department attendance of a few types of leprosy patients like borderline

and borderline lepromatous have risen, whereas others like borderline tuberculoid and polar

tuberculoid have declined in the second phase as compared to that of the first phase. The

trend over a decade suggests that HIV infection is low among the leprosy patients when

compared with other risk groups. Follow-up of these patients at an interval of six months,

revealed that none of them downgraded into a severe form of leprosy nor developed ARC or

AIDS. In this study, it appears that neither infection precipitated the other. The occurrence

of downgradation as well as reversal reactions and neuritis (both chronic and acute) was not

observed among the leprosy patients. None of them developed erythema nodosum leprosum

reactions. Similarly, the HIV-positive leprosy cases did not develop either AIDS related

complex (ARC) or full blown case of AIDS.

RESUME

Cette étude compare les résultats de séroprévalence du VIH, obtenus en 2 phases dis-

tinctes : de 1989 à 1993 et de 1999 à 2004. Bien que le nombre de patients testés pour l’in-

fection par le VIH soit moindre dans la seconde phase (2125) que dans la première (4025),

une augmentation de prévalence de 0.12% à 0.37% est préoccupante puisque la région

étudiée est endémique pour les 2 infections. Pendant la durée de cette étude, si la seconde

phase est comparée à la première, la présentation de patients au service de Consultations Ex-

ternes a augmenté pour quelques types de patients lépreux comme les patients borderline et

borderline lépromateux et diminué pour les patients borderline tuberculoïdes et tubercu-

Page 8

International Journal of Leprosy

2005

loïdes polaires. La tendance dégagée sur une décennie suggère que l’infection par le VIH est

faible chez les patients lépreux, comparés à d’autres groupes à risque. Le suivi tous les 6

mois de ces patients indique qu’aucun d’entre eux n’a rétrogradé en une forme sévère de la

lèpre ou n’a développé le complexe associé au SIDA (ARC) ou le SIDA. Dans cette étude,

il apparaît qu’aucune de ces infections ne précipite l’autre. Il ne fut pas observé de déplace-

ment vers le bas le long du spectre immuno-pathologique ou de réactions inverses ou de

névrites (à la fois chroniques ou aiguës) parmi les patients hanséniens. Aucun n’a développé

de réaction de type érythème noueux lépreux. Concomitamment, les cas de lèpre aussi posi-

tifs au VIH n’ont développé ni de syndrome ARC ni de SIDA terminal.

RESUMEN

Este estudio compara los resultados de una encuesta sobre la prevalencia del VIH en pa-

cientes con lepra, realizada en dos fases, la primera de 1989 a 1993 y la segunda de 1999 a

2004. Aunque el número de pacientes investigados para VIH fue mayor en la primera fase

(4025) que en la segunda (2125), se notó un incremento en la infección por VIH de 0.12% a

0.37%. Esto es preocupante porque sugiere que esta área es endémica para las dos enfer-

medades. En la segunda fase del estudio, se observó un incremento en el número de pa-

cientes BL/LL que acudieron al Instituto y una disminución en el número de los pacientes

BT/TT. Los resultados globales indican que la infección por VIH es baja entre los pacientes

con lepra en comparación con la infección en otros grupos de riesgo. El examen de estos pa-

cientes a los 6 meses de seguimiento reveló que ninguno de ellos “se degradó” a una forma

más severa de la lepra, ni desarrolló los signos del complejo asociado al SIDA, ni la enfer-

medad en si. Además, ninguna de las enfermedades precipitó a la otra. Ninguno de los pa-

cientes desarrolló reacciones reversas (neuritis agudas y crónicas), ni eritema nodos leproso

(ENL).

India has the largest number of known

cases of leprosy and happens to incidentally

be endemic for HIV as well. Some of the

earlier studies done in North and North-

Eastern India did not find any association of

HIV infection with leprosy patients (24). A

few studies from South Indian states

showed a higher prevalence of HIV infec-

tion among leprosy patients, but these stud-

ies alone do not provide any indication of

its association with leprosy (12). Leprosy

caused by Mycobacterium leprae has an un-

usually long incubation period, and infec-

tion with HIV leads to a profound drop in

CD4+ T-lymphocyte count and function

and compromises the cell-mediated im-

mune response, as well (19, 25). Earlier stud-

ies carried out in this center suggested that

1 per thousand (5/4025 : 0.124%) of the lep-

rosy patients harbored HIV infection.

Follow-up of these patients at an interval of

six months, revealed that none of them

downgraded into a severe form of leprosy

nor developed ARC or AIDS (10). Although

this study indicated that leprosy is not a risk

factor for developing HIV-1 infection, the

HIV surveillance studies on this population

was continued with a view to assess the risk

and find out the trend in an area where both

the infections are prevalent. This study

compares the results of HIV seropreva-

lence, which was carried out in two phases;

first, from April, 1989 to March, 1993 when

HIV infection was being detected in India

in different risk group populations to assess

the risk among leprosy patients, and then

from September, 1999 to March, 2004. This

is the first report of a decade of HIV screen-

ing of leprosy patients in this region of the

country and the longest follow-up of HIV-

leprosy co-infected cases.

One of the commonly observed com-

plaints among leprosy patients was pain in

the joints. Many studies have proven that

microbial agents might trigger the autoim-

mune phenomenon and induce rheumatoid

arthritis (1, 5, 8). In order to find out if arthri-

tis is present in the HIV-leprosy co-infected

patients, the sera from these cases were

tested for Rheumatoid arthritis (RA) factor.

Many risk behaviors as well as the routes of

transmission for HIV, Hepatitis B virus

(HBV) and Hepatitis C virus (HCV) in-

fection are identical to those for other sexu-

ally transmitted diseases (STDs) (3). For

this reason, the leprosy sera samples were

tested for HBsAg and VDRL simultane-

ously with HIV.

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Hussain et al.: HIV Infection Among Leprosy Patients

MATERIALS AND METHODS

Leprosy patients, across the spectrum, i.e.,

tuberculoid (TT), borderline-tuberculoid

(BT), mid-borderline (BB), borderline-

lepromatous (BL), lepromatous (LL) and

neuritic (N) types, classified, according to

Ridley-Jopling criteria (23), attending the

Unit-I of the Outpatient’s Department

(OPD) of the Central JALMA Institute for

Leprosy and other Mycobacterial Diseases

(CJILOMD) were included in the study.

The leprosy cases in the study were neither

newly admitted nor untreated patients, al-

though a few were newly detected cases.

For bacteriological determination, the six

skin sites used were the two ear lobes and

four representative active skin sites, i.e.,

hand (right arm and left arm), elbow (right

and left), back, forehead, and the site of the

lesion. In our OPD, four skin sites are rou-

tinely used for determination of the bacteri-

ological index (B.I.). The inclusion criteria

were: adult leprosy patients between the

age group of 16 to 48 yrs. Children and old

patients were excluded from the study as it

was assumed they were not likely to be sex-

ually active. In order to ensure that the pa-

tients were not screened over and over

again, their OPD cards were marked, “HIV-

Screened.” This helped in excluding the re-

peat testing of the patients. Blood was col-

lected asceptically from leprosy patients by

ante-cubital venipuncture after obtaining

pre-informed consent. The sera samples

collected after centrifugation at 2500 g

were stored at –20°C until the assays were

performed. ELISA was done using Genedia

HIV-1/2 EIA kit (Greencross, Korea).

Those found positive were confirmed by

rapid (HIV capillus latex aggregation assay,

Trinity Biotech PLC, Ireland) and Western

blot assays (WesternBlot, BIO-RAD,

NEWLAVBLOT), Nippon Bio-Rad Labo-

ratories, Japan. After post-test counselling,

a report was handed over to those found

HIV-positive and patient was referred to

clinicians for further care and management.

To find out any other co-infections, the

samples were further tested by HBsAg kit,

(Immuno-chromatography test ERBA Hep-

line, Transasia Bio-Medicals Ltd., Mumbai,

India) and VDRL and Rheumatoid Arthritis

kits (Carbogen and Rhelax, RF of Tulip Di-

agnostics (P) Ltd., Bambolim, Goa, India).

RESULTS

The prevalence of HIV-1 infection in lep-

rosy patients was observed in two phases.

In phase one, 4025 patients [30 indetermi-

nate (I), 141 polar tuberculoid (TT), 1888

boderline tuberculoid (BT), 409 borderline

(BB), 600 borderline lepromatous (BL),

751 polar lepromatous (LL), 200 N] were

screened between 1989 and 1993, out of

which only 8 were ELISA positive and 5

were Western Blot reactive. Subsequently,

in the second phase from 1999 to 2004,

2125 patients (21 I, 19 TT, 646 BT, 332 BB,

610 BL, 324 LL, 173 N) were screened, out

of which 8 were ELISA positive and 5 were

Western Blot reactive (Table 1). The varia-

tion in the results of the two tests correlated

well with the titre of HIV-1/2 antibodies in

the sera samples. The strongly positive

samples having a high absorbance value,

ranging between 1.5 and 2.0, measured in

terms of O.D. at 450 nm in an ELISA

reader had an excellent pattern of reactivity

in Western Blot. The samples with weak or

moderate positivity in ELISA, with an O.D.

ranging between 0.5 and 0.7, did not react

with Western Blot. A rise in HIV infection

from 0.124% to 0.376% was observed. Two

samples were reactive to HIV-2 by Western

Blot. Among all the HIV-positive leprosy

patients, there were no other co-infections

like Hepatitis B, Syphilis and RA. Out of

the 8 HIV-leprosy co-infected patients, 2

each were BT and BL types, 3 were BB and

1 was LL type of leprosy.

The predominant clinical features were

hypo-pigmented lesions, clawing of fingers

and toes, pain, and hand muscle atrophy.

Whereas 4 patients had deformity in hands,

only one of them reported acute pain. All

the patients completed a full course of stan-

dard anti-leprosy multi-drug therapy, re-

sponded satisfactorily, and were later clini-

cally and bacteriologically negative. The

initial bacterial index, prior to treatment,

which ranged between 2+ and 3+ became

negative on completion of the treatment.

Two of the 8 HIV-leprosy co-infected pa-

tients (BL, LL) became bacteriologically

negative after 6 months and another 2 (BT,

BL) became negative after 24 months of

treatment (Table 2). We have observed that

following treatment, B.I. became negative

even in BL and LL cases. The HIV-positive

Page 10

TABLE 1. The phase-wise screening of leprosy patients for HIV-1/2 infection.

I Phasea (N = 4025)

HIV status

EIA

Borderline-

Tuberculoid (BT) 1888 (46.90%)

Tuberculoid (BT) 646 (30.48%)

Tuberculoid (TT)

141 (3.50%)

Tuberculoid (TT)

19 (0.89%)

Indeterminate (I)

30 (0.74%)

Indeterminate (I)

21 (0.98%)

Lepromatous-

Leprosy (LL)

751(18.65%)

Leprosy (LL)

324 (15.24%)

Borderline-

Lepromatous(BL) 600 (14.90%)

Lepromatous (BL) 610 (28.70%)

Mid-

Borderline (BB) 415 (10.31%)

Borderline(BB)

332 (15.62%)

Neuritic (N)

200 (4.96%)

Neuritic (N)

173 (8.14%)

a denotes I Phase of HIV screening of the leprosy patients which was from April, 1989 to March, 1993.

b denotes II Phase of HIV screening of the leprosy patients which was from September,1999 to March, 2004.

EIA = ELISA, WB = Western Blot.

International Journal of Leprosy

2005

patients are being followed up at six month

intervals. On follow-up, to date none of the

patients with HIV-1 infection have pro-

gressed into a more severe form of the dis-

ease. None of the co-infected cases have

been lost so far in follow-up. In these co-

infected patients, it is difficult to assess

which infection occurred first. Our results

indicated that HIV-1 infection does not con-

tribute in any way to the precipitation of se-

rious forms of leprosy.

DISCUSSION

It is well recognized that HIV infection

constitutes a major risk factor for tuberculo-

sis (TB) and for other mycobacteria, such

as M. avium and M. intracellulare, but there

are still uncertainties regarding its associa-

tion with leprosy. The association between

the HIV and tuberculosis and certain other

non-tuberculous mycobacterial infections

have been established (20, 21). Potential ef-

fects of HIV infection on leprosy have been

suggested and discussed by several authors

but, despite expectations, little interaction

has been observed uptil now (9, 17, 22). Al-

though an association between HIV and

leprosy has been described in Zambia (18)

and in Tanzania (27, 28), there is some evi-

dence from studies in Mali (15), Ethiopia (6, 7)

and in other African countries that HIV in-

fection is not a risk factor for leprosy (14, 16).

On the contrary, a few studies carried out in

some African countries to determine the as-

sociation between leprosy and HIV infec-

tion suggest that HIV infection is an impor-

tant risk factor for leprosy (4, 18). Some of

these studies had limitations in study design

and some found no association between the

two diseases (2, 13).

The increase in HIV infection as com-

pared to that of the first phase is disturbing

and the mode of transmission appeared to

be heterosexual as revealed during the post-

test counselling session. None of the co-

infected cases admitted to having a homo-

sexual relationship or had a history of blood

transfusion. Two of the males had symp-

toms of STDs at the time of testing.

The trend over a decade suggests that HIV

infection is low among the leprosy patients

when compared with other risk groups, like

TB patients, which is 4.3% (26/600) in Agra

(in press). The prevalence and incidence for

HIV infection in Agra varies in different

groups. Our institute has a Voluntary Con-

fidential, Counselling and Testing Center

(VCCTC), a State body of the National

AIDS Control Organization (NACO), where

screening for HIV infection is carried out

routinely from different groups, namely, Vol-

unteers (individuals opting for voluntary

HIV testing), HIV-suspected cases referred

from different hospitals, female sex work-

ers (FSWs), residents at the Government

Protective Home, and cases referred by

District Jail and District Magistrate, Agra.

The recent annual figures (Jan. through

II Phaseb (N = 2125)

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Hussain et al.: HIV Infection Among Leprosy Patients

Dec., 2004) revealed that the local preva-

lence and incidence of HIV-positivity in the

area is, 40.31% (156/387) among Volun-

teers and 43.39% (46/106) among the Re-

ferred cases (communicated).

In the second phase as compared to that

of the first phase, the OPD attendance of a

few types of leprosy patients has risen dur-

ing the study phase, whereas others have

declined. A striking feature which has

emerged during the second phase of the

study is that there is an increase in the at-

tendance of BB and BL types of leprosy pa-

tients, whereas there is a decrease in the BT

and TT types of leprosy patients as depicted

in Table 1. This could be one of the reasons

for the higher HIV-positivity observed

among the BB and BL cases. Another one

could be attributed to the better control due

to multi-drug therapy (M.D.T.) and de-

creased transmission of M. leprae, with new

cases dominated by a long period of incuba-

tion, in the lepromatous leprosy cases. Al-

though the number of leprosy patients

screened for HIV infection in the second

phase is less as compared to those screened

during the first phase, a rise in HIV infec-

tion is disturbing since this area appears to

be endemic for both the infections.

Expansion of the HIV epidemic could

have a significant effect on the epidemiol-

ogy of leprosy. In this study, it appears that

neither of the infections precipitated the

other. The incidence of downgradation, as

well as reversal reactions and neuritis (both

chronic and acute), was not observed among

the leprosy patients. None of them devel-

oped Erythema Nodosum Leprosum (ENL)

reactions. The total cases of HIV-positive

leprosy patients were only thirteen in both

the phases (5 in phase I, and 8 in phase II),

which have been followed up very carefully

and with special care. We have also ob-

served that reversal reactions and ENL did

not occur among any of the HIV-leprosy co-

infected cases. If the number of cases were

more, then probably one might have noted

some reversal or ENL reactions. To resolve

the issue, a larger study, with longer follow-

up is required. Clinical manifestations of

lepromatous leprosy cases might be im-

munologically mediated and these features

could be abrogated by HIV infection.

Similarly, the HIV-positive leprosy cases

did not develop either AIDS related complex

(ARC) or full blown case of AIDS. None of

the co-infected cases have been lost so far in

the follow-up. This is the first report of a

decade of HIV screening of leprosy patients

in this region of the country and the longest

follow-up of the largest number of HIV-

leprosy co-infected cases. Other studies have

reported follow-up of very less number of

the co-infected cases (11, 26). The underlying

mechanism by virtue of which the severity

of both the diseases is lowered is not known.

The infectious agents and host defences

seem to have co-evolved to reach balanced

states where virus and host survive. While

HIV has not quite yet reached an optimal

balance, tuberculosis (TB), leprosy, HBV,

HCV in humans or lymphocytic chorio-

meningits virus (LCMV) in mice have suc-

cessfully established persistence (29).

TABLE 2. Clinical presentations and bacteriological index among the HIV-leprosy co-

infected patients.

Clinical findings

Skin Lesions Nerves

Pain

Deformity

Pain

Nil

Smear 3+ (Negative after 24 months)

Nil

Smear 2+ (Negative after 6 months)

Nil

Negative

Nil

Negative

Nil

Hand

Smear 3+ (Negative after 6 months)

Nil

Hand

Negative

Nil

Negative

Nil

Hand

Smear 3+ (Negative after 24 months)

Page 12

International Journal of Leprosy

2005

Although the present study does not

show any association between HIV and lep-

rosy, future study is warranted to find out

the reasons for cross-protection, if any, at

the genetic and molecular level.

Acknowledgement. This study was supported by

funds from the Indian Council of Medical Research,

New Delhi. Shikha Sinha is a recipient of Senior Re-

search Fellowship of the Council of Scientific and In-

dustrial Research (CSIR). The authors thank Mr. K. L.

Verma, Mr. M. M. Alam, Mr. Sushil Prasad, Mr. P. N.

Sharma, and Mr. M. S. Tomar of the HIV/AIDS Unit and

the entire staff of OPD for their assistance in the study.

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Page 14

1 Received for publication on 24 May 2004. Accepted for publication on 13 February 2005.

2 U. D. Gupta, Assistant Director, M.Sc., Ph. D.; Dr. Kiran Katoch, Deputy Director (Senior Grade), M.B.B.S.,

M.D.; Dr. Hari Bhan Singh, Research Assistant, M.Sc., Ph.D.; Dr. Mohan Natrajan, Deputy Director, M.B.B.S.,

D.V.D.; Dr. Vishwa Mohan Katoch, Director, M.B.B.S., M.D., Central JALMA Institute for Leprosy and Other

Mycobacterial Diseases (ICMR), Tajganj, Agra – 282001, India.

Reprint requests to: Dr. V. M. Katoch, Director, M.B.B.S., M.D., Central JALMA Institute for Leprosy and

Other Mycobacterial Diseases (ICMR), Tajganj, Agra – 282001, India.

Persister Studies in Leprosy Patients after

Multi-Drug Treatment1

U. D. Gupta, K. Katoch, H. B. Singh, M. Natrajan, and V. M. Katoch2

ABSTRACT

Cutaneous biopsies were collected from leprosy patients who attended the out-patient de-

partment of the Institute for treatment at different intervals, i.e., 12 months, 18 months, 24

months, 36 months, and more after beginning the multi-drug treatment therapy (M.D.T.).

The patients belonged to the two drug regimens; (i) standard multibacillary (MB) M.D.T. af-

ter 12, 24, and 36 months; or (ii) standard M.D.T. + Minocycline 100 mg once a month (su-

pervised) + Ofloxacin 400 mg once a month supervised for 12 months Biopsies were

processed for mouse footpad inoculation and for estimating ATP levels by bioluminescence

assay as per established methods. Viable bacilli were observed in 23.5% up to 1 year, 7.1%

at 2 years, and in 3.84% at 3 years of M.D.T. by MFP and 29.4%, 10.7%, and 3.84% by ATP

assay in the M.D.T. group at the same time period, respectively, but not in M.D.T. + Minocy-

cline + Ofloxacin group after one year. The overall percentage of persisters was 5.55% by

MFP and 7.14% by ATP assay up to 3 years of treatment.

RESUME

Des biopsies cutanées furent prélevées à intervalles successifs (12, 18, 24, 36 mois et

plus) de patients hanséniens traités au service de consultation externe de l’Institut, après

mise en œuvre de la polychimiothérapie (PCT). Les patients furent répartis en 2 types de

PCT : (i) PCT multibacillaire standard après 12, 24 et 36 mois et (ii) PCT standard +

Minocycline 100 mg une fois par mois (prise contrôlée) + Orofloxacine 400 mg une fois par

mois en prise contrôlée pendant 12 mois. Les biopsies furent préparées pour le test d’inocu-

lation à la patte de souris (IPS) et pour l’estimation des niveaux d’ATP par bioluminescence

selon des méthodes bien établies. Des bacilles viables furent observés dans 23,5% des biop-

sies jusqu’à 1 an ; 7,1% après 2 ans et 3,84% après 3 ans de PCT par le test IPS et 29,4% ;

10,7% et 3,84% par test de l’ATP pendant les même temps après PCT, respectivement, mais

pas chez le groupe PCT + Minocycline + Orofloxacine après 1 an. Le pourcentage global de

patients avec bacilles persistants était de 5,55% d’après le test IPS et de 7,14% d’après le test

à l’ATP après 3 années de traitement.

RESUMEN

Se trabajó con pacientes con lepra que acudieron al Instituto para su tratamiento. Los pa-

cientes se asignaron a dos grupos, uno que recibió la poliquimioterapia (PQT) estándar para

lepra multibacilar (MB) y otro que recibió la PQT estándar combinada con Minociclina (100

mg mensuales) y Ofloxacina (400 mg mensuales), ambas drogas administradas de manera

supervisada por 12 meses. De cada paciente se tomaron biopsias de piel a los 12, 18, 24 y 36

meses o más, después de haber iniciado el tratamiento. Las biopsias fueron procesadas para

su inoculación en la almohadilla plantar del ratón (APR) y para la medición de sus niveles

de ATP por bioluminiscencia, de acuerdo a métodos ya establecidos. En el grupo tratado con

PQT se observaron bacilos viables en el 23% de las biopsias a un año del seguimiento, en el

7.1% de las biopsias a los 2 años, y en el 3.8% a los 3 años usando la técnica de la APR, y en el

29.4%, 10.7% y 3.84% de las biopsias usando el ensayo de ATP, a los mismos intervalos de

tiempo. En las biopsias de piel del grupo tratado con PQT + Minociclina + Ofloxacina no se ob-

servaron bacilos después de un año de tratamiento. El porcentaje global de “persistentes” fue de

5.5% por el ensayo de la APR y de 7.14% por el ensayo de ATP a los 3 años del tratamiento.

100

INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 2

Printed in the U.S.A.

(ISSN 0148-916X)

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Gupta, et al.: Persister Studies in Leprosy Patients After M.D.T.

101

In pre-multi-drug therapy (M.D.T.) era,

persistence of drug sensitive Mycabac-

terium leprae and emergence of drug resis-

tant mutants despite prolonged therapy with

DDS was reported to be the cause of treat-

ment failures in lepromatous patients (14, 21).

With the introduction of rifampicin, it was

expected that in addition to a rapid decrease

in the infectivity of multibacillary (MB)

cases, the above problems would also be

taken care of if drugs were used alone (22)

or in combination (13). With the M.D.T. of

leprosy, the results have been satisfactory as

it has been generally effective in reducing

the viable load as well as duration of treat-

ment in MB cases. However, the persis-

tence of drug sensitive viable organisms has

been demonstrated after varying durations

of treatment at different sites by several

workers (6, 8, 9, 11, 16, 20). These persisting

bacilli have special significance as they

have the potential of causing relapse in MB

cases after M.D.T. (8, 12). This study has

been initiated to gain an overview of this

problem and follow the recent trends in

multibacillary cases treated with M.D.T.

MATERIALS AND METHODS

One hundred twenty six biopsies from

ninety six borderline lepromatous (BL)/polar

lepromatous (LL) patients attending the out-

patient department of Central JALMA Insti-

tute for Leprosy and Other Mycobacterial

Diseases were included in this study. The age

of the patients ranged from 16 to 60 years. All

these patients did not suffer from any chronic

disease like diabetes mellitus, tuberculosis,

hypertension, etc., and showed no clinical ev-

idence of resistance. The patients belonged to

the two drug regimens: (i) standard MB

M.D.T. after 12, 24, and 36 months; (ii) stan-

dard M.D.T. + Minocycline 100mg once a

month (supervised) + Ofloxacin 400mg once

a month (supervised) for 12 months (7). Be-

fore starting the treatment, these patients

were examined in detail, clinical findings

were charted and recorded, and smears were

taken from different sites for calculation of

bacterial index (B.I.). At the start of therapy,

the average B.I. ranged from 2 to 5+ for regi-

men 1 (mean 3.6), and from 1 to 4+ for regi-

men 2 (mean 2.21) on the Ridley scale (15).

The biopsies were processed for mouse foot -

pad inoculation and bacillary ATP assay (5, 11)

as used earlier by us.

Mouse footpad inoculation. The foot-

pads were homogenized and the bacterial

enumeration was done as described by

D’Arcy and Rees (2). A batch of five random

bred BALB/C mice was taken and each hind

mouse footpad was inoculated with 0.03 ml

suspension containing 5000 to 10,000 bacilli.

The bacilli were harvested at six months and

eight months (50% at each stage) after inocu-

lation and acid–fast bacilli (AFB) were

counted (3). The footpad pools were used for

enumeration of the bacilli. The percentage of

viable persisters being low, even a 10-fold in-

crease in the harvest count was taken as evi-

dence for bacillary growth (10).

ATP assay. The biopsies were processed,

bacillary ATP was extracted and assayed as

per the technique standardized in our labo-

ratory (11). ATP levels were estimated and

expressed as pg/million of AFB. Cultures

were set up in the final preparation to rule

out contamination with any cultivable my-

cobacteria or any other organism.

RESULTS

The details of specimens showing viabil-

ity after different durations of M.D.T. by

mouse footpad as well as ATP are presented

in Table 1. Out of 126 biopsies, 71 biopsies

belonged to patients treated with standard

M.D.T. regimen while 55 biopsies belonged

to patients treated with standard M.D.T. +

100 mg of Minocycline + 400 mg of

Ofloxacin once a month (supervised). After

one year of treatment, out of 17 biopsies

(MDT), 4 were found to be positive for vi-

able M. leprae by mouse footpad and 5 by

ATP method while out of 55 biopsies be-

longing to M.D.T. + Minocycline +

Ofloxacin group, none was found to posi-

tive. The range of B.I. of these patients

were 2 to 5+ (average 3.60) and 1 to 4+ (av-

erage 2.2), respectively. By the mouse foot-

pad method, the Fisher exact test of viabil-

ity of M. leprae at one year between regi-

men 1 (4/17) and regimen 2(0/55) is highly

significant (p = 0.002). Similarly, by the

ATP method, the Fisher exact test of viabil-

ity of M. leprae at one year between regi-

men 1 (5/17) and regimen 2 (0/55) is highly

significant. The results from the percentage

of patients with viable bacilli at all time pe-

riods from regimen 1 (7/126) with viable

bacilli from regimen 2 at one year is statis-

tically significant (p = 0.02).

Page 16

TABLE 1. Percentage of biopsies showing positivity for viable M. leprae after different

durations of multi-drug therapy.

Range and

average BI

Duration of

at the time

MFP+(%)

ATP +%

treatment

of biopsy

(1)

(2)

(1)

(2)

(3)

(1)

(2)

(3)

6 months to 1 yr 3.6

2.21

44/17

0/55

4/72

5/17

0/55

5/72

of treatment (2–5+) (1–5+)

(23.5%)

(0%)

(5.55%)

(29.4%)

(0%)

(6.94%)

>1 yr to 2 yrs of 2.55

2/28

3/28

treatment

(1–5+)

(7.1%)

(10.7%)

>2 yrs to 3 yrs of 1.81

1/26

treatment

(1–3+)

(3.84%)

Total

7/126

9/126

(5.55%)

(7.14%)

BI: Bacteriological index; MFP: Mouse Footpad; ATP: Bioluminescence assay; (1) conventional MDT; (2)

Conventional MDT +Minoycline 100 mg once a month supervised + Ofloxacin 400 mg once a month supervised;

(3) Overall.

102

International Journal of Leprosy

2005

Similarly, out of 28 biopsies from patients

who had M.D.T. up to 2 years, 2 biopsies

showed AFB counts by mouse footpad and

3 were positive for bacillary ATP. The mean

B.I. of these biopsies ranged from 1 to 5+

(average 2.6). Further, out of 26 biopsies

from patients who had taken up to 3 years of

M.D.T. or more, 1 biopsy showed positivity

by mouse footpad as well as by ATP assay.

Statistically, the differences between the two

methods were non–significant. The B.I. of

the patients ranged from 1 to 3+ (average

1.81). Overall, out of 126 biopsies included

in this study, 7 (5.55%) showed evidence of

viability by mouse footpad, whereas 9

(7.14%) showed positivity by ATP biolumi-

nescence. The results of quantitative rela-

tionship between bacillary ATP and mouse

footpad showed that when ATP levels were

in the range of 0.36 to 3.59 pg/million, both

techniques were equally good (positives

were 7/126). However, two cases whose

bacillary contents were in the range of 0.039

to 0.04 pg/million bacilli did not show

growth by mouse footpad (Table 2).

The correlation of initial B.I. and M. lep-

rae viability after chemotherapy was ana-

lyzed and is presented in Table 3. At one

year of treatment with standard M.D.T., it

was observed that in biopsies in initial B.I.

up to 2+, no viability was observed by ei-

ther of the method. Further, in biopsies with

initial B.I. of 2 to 3.9+, viability was ob-

served in 4/53 (7.55%) and 5/53 (9.4%)

biopsies by mouse footpad and ATP, respec-

tively. However, in biopsies with initial B.I.

of 4+ and more, higher viability was ob-

served [3/13 (23.1%) by MFP, and 4/13

(30.8%) by ATP]. The differences in viabil-

ity in biopsies between group 2 to 3.9+ and

4+ and more, the differences were signifi-

cant.

DISCUSSION

M.D.T. campaigns have led to a major

decline in the prevalence of leprosy. How-

ever, it continues to be an important public

health problem in many parts of the world.

Despite the regular administration of

M.D.T., live bacilli persist in a section of

leprosy cases. A number of workers have

demonstrated these live persisters by

growth in mouse footpads inoculated by M.

leprae in pre-M.D.T. (13, 14), as well as post-

M.D.T. era (5, 9, 16, 17, 18). W.H.O. and the

some national agencies such as in India

have recently recommended that treatment

in MB cases be stopped after 1 year of

treatment. In this study, 23.5% of the speci-

mens showed growth by mouse footpad

while 29.4% of the specimens showed

growth by ATP assay in patients treated

with conventional M.D.T. after 1 year of

treatment (Table 1). On the other hand,

none of the specimens showed growth by

mouse footpad as well as ATP assay in pa-

tients treated with M.D.T. + Minocycline +

Ofloxacin, clearly indicating that addition

of Minocycline and Ofloxacin in the treat-

ment regimen was quite effective as no vi-

able persisters were detectable after 1 year

of treatment (7). However, in the present

Page 17

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Gupta, et al.: Persister Studies in Leprosy Patients After M.D.T.

103

study as well as in other studies live bacilli

have been demonstrated after one year of

treatment with conventional M.D.T. Out of

the 17 specimens in the up to one year

M.D.T. group, 6 had received M.D.T. for 6

months out of which one showed growth

(having initial B.I. of 5+), and 11 received

M.D.T. for 1 year and growth was seen in 3

patients (having initial B.I. of 4+ and more,

and 3 to 4+ after one year of treatment).

These observations clearly indicate that

there is a potential risk associated with

stopping the therapy at one year mainly in

such patients who are having high initial

B.I. However, the adequacy of one year

treatment in such cases can only be known

after experience of follow-up studies be-

come available. Up to 2 years of M.D.T. (13

to 24 months), 2 out of 28 biopsies (7.1%)

showed growth in mouse footpad and sig-

nificant ATP was detected in 3 out of 28

(10.7%) of the biopsies. In patients who had

taken M.D.T. from 25 to 36 months, 1 out

of 26 (3.84%) biopsies was positive by

both, i.e. mouse footpad as well as ATP as-

say. Overall, 7 out of 126 (5.55 %) and 9

out of 126 (7.14 %) biopsies by mouse foot-

pad and ATP assay were observed to be

positive which are in agreement with earlier

reports where persister rates of 9 to 16%

varying periods of MDT have been reported

(5, 6, 9, 19, 20). On the other hand, much higher

persister rates has also been reported by

Shetty, et al. (16, 17, 18) in nerves and skin of

leprosy patients. There has been good con-

cordance between viability determination

by mouse footpad and ATP when ATP lev-

els were in the range of 0.36 to 3.59 pg/mil-

lion but when ATP levels were lower mouse

footpad failed to detect any positivity as re-

ported earlier by Gupta, et al. (5).

In the present investigation, the patients of

standard M.D.T. were on continuous M.D.T.

until smear negativity (at least 2 years). It is

difficult to foresee how these patients would

have behaved if they had been on one year

fixed duration M.D.T. Persisters have been

reported to be the cause of relapses after 4 to

9 years in well conducted drug trials with ad-

equate follow-up (12). There are reports

which suggest that patients with high pre-

treatment M. leprae loads are at higher risks

of relapse if the treatment is stopped after 2

years W.H.O.-M.D.T./Fixed Duration Ther-

apy compared to patients treated till point of

smear negativity (1, 4). Further, it is apparent

that in biopsies with initial B.I. of 1 to 1.9, the

M.D.T. alone or in combination with minocy-

cline and ofloxacin, no viable organisms

were observed. But when the initial B.I.s

were 2 to 3.9+ or = 4, the percentage of spec-

imens showing viable organisms increased

(7.55% and 22.1% by mouse footpad and

9.4% and 30.8% by ATP). All the specimens

in which viable organisms could be demon-

strated beyond one year had the initial B.I. of

≥ 4+ (Tables 1 and 3). Other studies at our in-

stitute have also shown that highly bacillated

cases dropping out of treatment up to 12 to 18

months had higher relapse rates (8). These

cases are very small proportion of all leprosy

cases as <2% of current cases have B.I. of 3+

or more (unpublished data by Katoch, et al.).

It will be interesting to observe the progress

TABLE 2. Quantitative relationship between ATP content and positive growth in mouse

footpad.

ATP content (pg/million)

Positive by ATP

Positive by MFP

0.36–3.59

7/126

0.04–0.359

1/126

0/126

0.02–0.039

1/126

0/126

Total

9/126

7/126

TABLE 3. Correlation of initial B.I. and M. leprae viability after chemotherapy.

Initial BI

No. of biopsies

MFP+

ATP+

1–1.9+

—

2–3.9+

4(7.55%)

5(9.4%)

4–5+

3(23.1%)

4(30.8%)

126

Page 18

104

International Journal of Leprosy

2005

of such patients after stopping M.D.T. at

other centers where M.D.T. is being given.

Further, there is a need to carry out surveil-

lance studies in larger number BL/LL pa-

tients to know the trends of persisters as well

as the resultant relapses.

Acknowledgment. Authors are thankful to Ishaat

Ali, R. S.Gupta, Asha Ram, V. K. Mathur, Thakur Das,

and Noel Crispin for clinical and technical support.

The gift of some of the reagents from LEPRA, U.K. is

gratefully acknowledged.

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KATOCH, V. M. Clinical and bacteriological

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GUPTA, U., SREEVATSA, SHARMA,V. D., SHIVAN-

NAVAR, C. T., and KATOCH, V. M. Results of a

modified W.H.O. regimen in highly bacillated BL-

LL patients. Int. J. Lepr. Other Mycobact. Dis. 57

(1989) 451–457.

10. KATOCH, K., SREEVATSA, RAMANATHAN, U., and

RAMU, G. Pyrazinamide as a part of combination

therapy for BL and LL patients—a prelimnary re-

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1–9.

11. KATOCH, V. M., KATOCH, K., SHIVANNAVAR, C. T.,

SHARMA,V. D., PATIL, M. A., and BHARADWAJ, V.

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13. PATTYN, S. R., DOCKX, P., ROLLIER, R., and

SAEREDS, I. L. M. leprae persisters after treatment

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biopsy in subsided cases of lepromatous leprosy.

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Sons, Ltd.,1964. pp. 620–622.

16. SHETTY, V. P., SUCHITRA, K., UPLEKAR, M. W., and

ANTIA, N. H. Higher incidence of viable My-

cobacxterium leprae within nerve as compared to

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17. SHETTY,V. P., SUCHITRA, K., UPLEKAR, M. W., and

ANTIA, N. H. Persistence of Mycobacterium lep-

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63 (1992) 329–336.

18. SHETTY,V. P., WAKADE, A., and ANTIA, N. H. A

high incidence of viable Mycobacterium leprae in

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rosy patients. Lepr. Rev. 72 (2001) 337–344.

19. SREEVATSA, GIRDHAR, B. K., and DESIKAN, K. V.

Screening of drug resistant strains of M. leprae in

lepromatous leprosy patients under multi-drug

treatment. Indian J. Med. Res. 87 (1988) 139–143.

20. SUBCOMMITTEE ON CLINICAL TRIALS OF THE CHEMO-

THERAPY OF LEPROSY (THELEP) SCIENTIFIC WORK-

ING GROUP OF THE UNDP/WORLD BANK/WHO

SPECIAL PROGRAM FOR RESEARCH AND TRAINING IN

TROPICAL

DISEASE. Persisting Mycobacterium

leprae among THELEP trial patients in Bamako

and Chingleput. Lepr. Rev. 58 (1987) 325–327.

21. WATERS, M. F. R., REES, R. J. W., PEARSON, J. M.

H., HELMY, H. S., and LIANG, A. B. G. Ten years

of Dapsone in Lepromatous Leprosy: clinical,

bacteriological, and histological assessment and

the finding of viable leprosy bacilli. Lepr. Rev. 45

(1974) 288–294.

22. WATERS, M. F. R., REES, R. J. W., PEARSON, J. M.

H., LIANG, A. B. G., HELMY, H. S., and GELBER, R.

H. Rifampicin for lepromatous leprosy: nine

years experience. Brit. Med. J. 1 (1978) 133–136.

Page 19

1 Received for publication on 15 June 2004. Accepted for publication on 1 October 2004.

2 T. Narang, M.D.; I. Kaur, M.D., M.N.A.M.S.; B. Kumar, M.D., M.N.A.M.S.; B. D. Radotra, M.D., Depart-

ment of Pathology; S. Dogra, M.D., D.N.B., M.N.A.M.S., Department of Dermatology, Venereology & Leprol-

ogy and Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Reprint requests to: Dr. Inderjeet Kaur, Dept. of Dermatology, Venereology & Leprology, Postgraduate Insti-

tute of Medical Education and Research Chandigarh-160 012, India. E-mail: kaur_inderjeet@yahoo.com

Comparative Evaluation of Immunotherapeutic Efficacy

of BCG and Mw Vaccines in Patients of Borderline

Lepromatous and Lepromatous Leprosy1

Tarun Narang, Inderjeet Kaur, Bhushan Kumar,

Bishan Dass Radotra, and Sunil Dogra2

ABSTRACT

Background. Even after 12 months of multi-drug therapy (M.D.T.) multibacillary (MB)

therapy patients with high bacterial index (B.I.) continue to harbor dead bacilli and viable

persisters, which lead to immunological complications such as recurrent reactions and late

relapses, respectively. To achieve faster killing of viable bacilli and clearance of dead bacilli,

various immunotherapeutic agents (vaccines and cytokines) are being evaluated as an ad-

junct to M.D.T.

Aims and objectives. To evaluate the role of BCG and Mw vaccines in the immunother-

apy of leprosy.

Materials and methods. Sixty untreated leprosy patients with a BI = 2 were randomly

allocated to three treatment groups of twenty patients each. Group A patients received World

Health Organization (W.H.O.) (12 months M.D.T.-MBR) and BCG intradermally (105 live

bacilli /per dose). Group B patients were administered 12 months M.D.T.-MBR and Myco-

bacterium w (1 × 108) killed bacilli as first dose and 0.5 × 108 /dose in subsequent doses.

Group C received 12 months M.D.T. MBR with 0.1 ml of normal saline as placebo. All the

groups received 4 doses of vaccine or normal saline repeated at three monthly intervals. The

patients were periodically monitored by clinical (Ramu’s score), bacteriological (slit skin

smear), and histopathological (skin biopsy) parameters, six monthly during and one year af-

ter completion of M.D.T.

Results. The mean reduction in clinical scores in BCG and Mw groups was significantly

more when compared to controls. At 12 and 24 months, the patients in BCG group had sig-

nificantly greater reduction in Ramu’s score as compared to those in the Mw group. BI de-

clined by 2.40 units/year in patients receiving BCG, 2.05 units/year in the Mw group and

0.85 units/year in the control group. Although the incidence of type 1 reactions was appar-

ently more in the BCG and Mw vaccinated groups, the incidence of type 2 reactions, neuri-

tis and development of new deformities was less as compared to the controls.

Conclusions. In our study, BCG exhibited slightly better and faster effect on bacterio-

logical clearance and clinical improvement as compared to Mw vaccine in borderline lepro-

matous (BL)/ polar lepromatous (LL) patients with a high initial B.I., however, their effect

on histopathological (decrease in GF) improvement was comparable. Both the vaccines

were well tolerated. Immunotherapy can be a useful adjunct to the shortened (12 months)

M.D.T. MB regimen to decrease the risk of reactions and relapses in highly bacilliferous

BL/LL patients.

RESUME

Contexte. Même après 12 mois de polychimiothérapie (PCT), des patients multibacil-

laires (MB) avec index bactérioscopique (IB) élevés continuent à avoir des bacilles morts ou

des bacilles viables et persistants, qui mènent fréquemment à des complications im-

munologiques comme des réactions récurrentes ou des rechutes tardives, respectivement.

Afin d’atteindre une éradication plus rapide des bacilles viables et une élimination plus

rapide des bacilles morts, des agents immuno-thérapeutiques variés (vaccins et cytokines)

sont en cours d’évaluation, comme compléments à la PCT.

105

INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 2

Printed in the U.S.A.

(ISSN 0148-916X)

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International Journal of Leprosy

2005

Buts et objectifs. Evaluer le rôle des vaccins BCG et Mw dans l’immunothérapie de la lèpre.

Matériels et méthodes. Soixante patients hanséniens encore non-traités, avec IB de 2,

furent attribués en aveugle à 3 groupes de traitements de 20 patients chacuns. Le groupe A

reçut la PCT pour patients MB de 12 mois recommandée par l’OMS et une injection intra-

dermique de BCG (105 bacilles vivants par dose). Au groupe B fut administré 12 mois de

PCT-MB et Mycobacterium w (1 × 108 bacilles morts en primo-injection et 0,5 × 108 en in-

jections de rappel). Le groupe C reçut PCT-MB pendant 12 mois et 0,1 ml de liquide phys-

iologique comme placebo. Tous les groupes ont reçu, tous le 3 mois, 4 doses de vaccins ou

bien du liquide physiologique normal. Un suivi clinique (score de Ramu), bactériologiques

(test du suc dermique) et histopathologiques (biopsies cutanées) des patients fut effectué

tous les 6 mois pendant le traitement puis 1 an après la fin du traitement par la PCT.

Résultats. La réduction moyenne des scores cliniques des groupes traités au BCG ou à

Mw fut significativement plus importante que celui du groupe contrôle. A 12 et 24 mois, les

patients du groupe BCG avaient une réduction plus importante du score de Ramu que le

groupe Mw. L’IB a diminué de 2,40 unités par an chez les patients ayant reçu le BCG, 2,05

unités par an dans le groupe Mw et de 0,85 unités/an dans le groupe contrôle. Bien que l’in-

cidence des réactions de type 1 fût apparemment plus élevée dans les groupes vaccinés au

BCG et Mw, l’incidence des réactions de type 2, les névrites et le développement de nou-

velles déformations a été moindre chez les vaccinés que chez les contrôles.

Conclusions. Dans cette étude, le BCG a démontré un effet plus rapide et plus important

en terme de clairance bactériologique et d’amélioration des signes cliniques que le vaccin

Mw chez les patients lépromateux borderline (BL) ou les patients lépromateux polarisés

(LL) avec un IB initial élevé. Cependant leurs effets sur l’aspect microscopique (diminution

de la fraction granulomateuse GF) restaient très comparables. Les 2 vaccins furent tous deux

fort bien tolérés. L’immunothérapie peut être très utile comme traitement complémentaire à

la PCT-MB abrégée à 12 mois, pour diminuer le risque de réactions et de rechute(s) parmi

les patients BL/LL fortement infectés par les bacilles de Hansen.

RESUMEN

Panorama. Los pacientes multibacilares (MB) con índices bacterianos (BI) altos siguen

teniendo bacilos muertos y bacilos viables persistentes aún después de 12 meses de

tratamiento con PQT, lo que conduce a complicaciones inmunológicas tales como reac-

ciones recurrentes y recaídas tardías, respectivamente. Para acelerar la muerte de los bacilos

vivos y la eliminación de los bacilos muertos se están evaluando varias vacunas y citocinas

como agentes inmunoterapéuticos.

Metas y objetivos. Evaluar el papel de las vacunas BCG y Mw en la inmunoterapia de la lepra.

Materiales y Métodos. Sesenta pacientes con lepra sin tratamiento y con un BI = 2, se

asignaron, al azar, a 3 grupos de tratamiento de 20 pacientes cada uno. El grupo A recibió la

PQT de la OMS para lepra MB por 12 meses y BCG intradérmicamente (105 bacilos vivos

por dosis). El grupo B recibió la PQT de la OMS para lepra MB y Mw (1×108 bacilos muer-

tos como primera dosis y 0.5 × 108 en las dosis subsecuentes). El grupo C recibió 12 meses

de PQT-OMS-MB y 0.1 ml de solución salina como placebo. Todos los grupos recibieron 4

dosis de vacuna o de salina a intervalos de 3 meses. Los pacientes fueron evaluados per-

iódicamente usando parámetros clínicos (escala de Ramu), bacteriológicos (examen de linfa

cutánea) e histopatológicos (en biopsia de piel).

Resultados. Los grupos tratados con BCG y con Mw evolucionaron mejor que los pa-

cientes del grupo control. Dentro de los pacientes vacunados, los del grupo BCG mostraron

una reducción en la escala de Ramu significativamente mayor que los pacientes del grupo

Mw. El BI mostró una disminución de 2.4 unidades/año en los pacientes con BCG, de 2.05

unidades/ año en el grupo Mw, y de 0.85 unidades/año en el grupo control. Aunque la inci-

dencia de reacciones tipo I fue aparentemente mayor en los grupos vacunados con BCG y

Mw, la incidencia de reacciones tipo 2, neuritis y nuevas deformidades, fue menor que la ob-

servada en el grupo control.

Conclusión. En nuestro estudio, el grupo vacunado con BCG mostró una mejor y más

rápida evolución clínica y bacteriológica que el grupo vacunado con Mw, y esto ocurrió

tanto en los pacientes BL como en los pacientes LL con altos BI; sin embargo, la mejoría

histopatológica (disminución en la fracción granuloma) fue comparable en ambos grupos.

Ambas vacunas fueron bien toleradas. La inmunoterapia puede ser un complemento útil a la

PQT-MB de duración acortada (12 meses) para reducir el riesgo de reacciones y recaídas en

los pacientes BL/LL altamente bacilíferos.

Page 21

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Narang et al.: Immunotherapy with BCG and Mw Vaccines

107

Leprosy continues to be a public health

problem in seventeen endemic countries of

the world. Since the inception of M.D.T. in

1982, there has been 85% reduction in

global prevalence of leprosy. The preva-

lence of leprosy in India has fallen from 57

per 10,000 in 1981 to 3.3 per 10,000 in

2003 (5), but India still accounts for 78% of

all the leprosy cases in the world, and its

elimination program is of major importance

for global leprosy control.

The duration of M.D.T. regimen for MB

leprosy was reduced to 12 months by the

W.H.O. Expert Committee on Leprosy in

1997 (34); however, information regarding

efficacy and safety of shortened MB regi-

men (12 months) is very limited at present.

There are reports of relapses in MB patients

treated with fixed duration treatment (FDT)

from some centers, especially in patients

with higher B.I. (6, 11, 21, 32). Patients in the

lower spectrum, i.e., BL/LL leprosy, have

partial or complete lack of CMI, which is

responsible for persistence of dead as well

as live bacilli even after adequate therapy. A

variety of possible factors which have been

postulated for deficient cell mediated im-

munity are: genetic constitution, primary

fault in T-cells and macrophages, inappro-

priate suppressor cell activity, and abnormal

antigen presentation (26). In these cases the

dead bacilli and their antigens and viable

persisters lead to immunological complica-

tions such as recurrent reactions and late re-

lapses, respectively. To achieve faster

killing of bacilli and clearance of dead

bacilli as well as possible alteration of im-

munological unresponsiveness in these pa-

tients, immunotherapy in the form of vac-

cines and cytokines has been tried.

Antigens of various mycobacteria have

been observed to cross-sensitize the im-

mune response to M. leprae and this might

help in augmenting CMI in leprosy. Promi-

nent among these are BCG (16), BCG plus

killed M. leprae (7), Mycobacterium w

(Mw) (9, 14, 15, 16, 23), and Indian Cancer Re-

search Center (ICRC) bacillus (3). Many

studies have confirmed the immunothera-

peutic efficacy of Mw vaccine, but very few

have evaluated the efficacy of BCG or com-

pared BCG and Mw vaccines. Katoch, et al.

(16) compared the immunotherapeutic effi-

cacy of BCG and Mw vaccines in MB pa-

tients and found both to be effective how-

ever; patients were given M.D.T. until smear

negativity in their study. Present study, was

designed to compare the immunotherapeutic

efficacy of BCG and Mw vaccines in BL/LL

leprosy patients treated with fixed duration

(12 months) W.H.O. M.D.T. MBR.

MATERIALS AND METHODS

Sixty untreated bacteriologically positive

multibacillary leprosy patients (BL, LL)

with a B.I. ≥ 2, age more than 12 years, at-

tending the Leprosy Clinic of Post Graduate

Institute of Medical Education and Research,

Chandigarh, India were randomly allocated

in 3 groups of twenty patients each.

All patients received W.H.O. M.D.T.

(MBR) for one year. In addition, the first

group (group A) was given BCG vaccine

(0.1 ml/dose, containing 105 viable units of

BCG; (BCG vaccine laboratory, Guindy,

Chennai, India). Group B received Mw vac-

cine (1 × 108 killed bacilli in the first dose

and 0.5 × 108/dose in the subsequent doses),

and group C was administered normal

saline 0.1 ml intradermally as control. The

patients in groups A, B, and C received four

doses of BCG, Mw vaccine and normal

saline, respectively, at three month inter-

vals. Informed consent was taken from all

the patients before inducting them into the

study. Patients who were pregnant, in type 1

lepra reaction, and those who had any im-

munodeficiency disorder or were taking im-

munosuppressive therapy, were excluded

from the study.

Patients were classified according to the

Ridley-Jopling classification (10) and diag-

nosis in all patients was confirmed by

histopathology. During and after M.D.T.

treatment, activity of the disease was rou-

tinely assessed clinically by Ramu’s clinical

scoring system (12) (minimum score = 0 and

maximum = 28). A detailed history includ-

ing symptoms and occurrence of reactions

and findings on physical examination were

recorded for all the patients, initially

monthly for one year and every 3 months

later on. Type 1 reaction (reversal reaction)

was diagnosed on noting visible changes in

the existing lesions in the form of erythema,

swelling (edema), presence of subjective

feeling of warmth, tingling sensations and

or local tenderness, or appearance of new

lesions, associated with or without constitu-

tional symptoms. Type 2 reaction was diag-

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108

International Journal of Leprosy

2005

nosed on the basis of presence of constitu-

tional symptoms of varying degree like

fever, aches, joint pains, bony tenderness

with characteristic evanescent lesions of

erythema nodosum leprosum (ENL) associ-

ated with or without specific organ involve-

ment like eye, testis, kidney, etc. Only neu-

ritis was diagnosed by the presence of

persistent and demonstrable tenderness in

the nerves (thickened or not) in the absence

of any evidence of inflammation in the lep-

rosy lesions but with nerve function impair-

ment. Tenderness of nerves in the presence

of inflamed skin lesions of type 1 or type 2

reaction was considered to be part of the re-

action. Patients with deformities were clas-

sified according to W.H.O. grading of

1998(34).

Slit-skin smears were taken initially, and

then every 6 months from the same sites.

Skin biopsy was also repeated from the same

site after 6, 12, and 24 months of starting

treatment for histopathologic evaluation. The

biopsies were graded as LL, BL, borderline

(BB), or borderline tuberculoid (BT) based

on the characteristic distribution of various

types of inflammatory cells as well as the

character, location, and extent of granuloma.

Biopsy was classified as non-specific infil-

trate (NSI) if there was no evidence of a

granuloma, absence of acid-fast bacilli

(AFB) and presence of minimal and scat-

tered peri-appendageal lympho-histiocytic

infiltrate in different parts of dermis. The

results were also compared in respect to

clearance of dermal granuloma(s) by mea-

suring the estimated reduction in granuloma

fraction (GF) (i.e., fraction of dermis occu-

pied by the granuloma(s) and clearance of

acid-fast bacilli) (8).

All the patients were followed up for two

years. The data was analyzed and the thera-

peutic efficacy of the vaccines compared

using the paired “t” test.

RESULTS

The mean age of the patients in all the

groups was similar. Maximum number of

patients were in the age range of 18 to 40

years. A majority of the patients in all the

groups were males (46/60, 76%). Group A

had 8 (40%) LL, 10(50%) BL, and 2 (10%)

patients of histoid leprosy. In group B there

were 10 (50%) LL, 9 (45%) BL, and 1 pa-

tient with histoid leprosy. Group C had 12

(60%) LL, and 8 (40%) BL patients. The

clinical scores, B.I., and GF were analyzed

and it was observed that the patients in the

three groups were almost comparable by all

these parameters.

All the patients exhibited reduction in

clinical scores with therapy. The mean re-

duction in clinical scores in both groups A

and B was significantly more at 6 and 12

months when compared to group C (p

<0.05). At 24 months the patients in group

A still had significantly greater reduction in

clinical score but the difference between

groups B and C was not statistically signif-

icant (Figs. 1a and 1b). The difference be-

tween groups A and B was not significant at

6 months, but at 12 and 24 months the pa-

tients in group A had significantly greater

reduction in the score as compared to group

B (p <0.05). (Table 1).

The fall in B.I. was significantly more in

groups A and B (p <0.01) at 6, 12, and 24

months when compared to group C. On

comparing the BCG and Mw groups the

mean decrease in B.I. was more in the BCG

FIG. 1(a). Pre-treatment—histoid leprosy with mul-

tiple shiny erythematous nodules in Group A (BCG).

FIG. 1(b). Post-treatment—same patient at 12

months, almost complete resolution of the lesions.

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Narang et al.: Immunotherapy with BCG and Mw Vaccines

109

group (p <0.01) at 12 and 24 months (Table

2). At the end of two years, 14 (70%) pa-

tients in group A were smear negative as

compared to 13 (65%) in group B and 6

(30%) in group C. Almost all the patients

showed a rapid decline in morphological in-

dex (M.I.) during treatment. None of the

patients showed solid staining bacilli at the

end of 12 months.

All the patients showed reduction in GF

but it was more marked in group A when

compared to group C at 12 months (p

<0.05) (Table 3). In relation to the reduction

in GF, the difference between the groups B

and C, as well as the groups A and B, was

not significant (p >0.05) at any time during

the study (Figs. 2a and 2b).

Histological upgrading from LL to BL

was seen in 8/12 (66.6%) patients in the

BCG group, 7/11 (63.6%) patients in Mw

group and 5/12 (41.6%) patients in the con-

trol group. Upgrading from BL to BT dis-

ease was seen only in the vaccine treated

groups. These changes were seen in 1/10

(10%) patient in BCG group and 3/9

(33.3%) patients in Mw group. At 24

months, near complete clearance of granu-

lomas and AFB with histological picture

suggestive of non-specific infiltrate was

seen in 17 (85%) patients in the BCG

group, 12 (60%) in the Mw group, and 6

(30%) in the control group.

A majority of patients in each group had

experienced one or more episodes of reac-

tion before starting antileprosy treatment.

However, only those reactions which oc-

curred in the previous two years (frequency

and degree of severity was also noted) were

considered for comparison in post-treatment

statistical evaluation. History of type 1 re-

actions was present in 4 (20%) patients in

group A, and 3 (15%) patients each in

groups B and C. During the course of study,

the number of patients who experienced

type 1 reaction were 6 (30%), 6 (30%), and

4 (20%) in groups A, B, and C, respectively.

There was an apparent but not statistically

significant increase in the incidence of type

1 reactions in groups A and B, as compared

to group C. However, majority of these re-

actions were mild and were managed with

anti-inflammatory drugs (NSAIDS).

During the period of study, there was a

significant decrease in the incidence of type

2 reactions in group A (p <0.05). The inci-

FIG. 2(a). Pre-treatment LL patient in BCG group

—diffuse granulomatous infiltration in dermis. GF =

80%. (H&E × 55).

FIG. 2(b). Post-treatment (same patient at 12 months)

—almost complete clearance of granulomas. GF = 5%.

(H&E × 55).

TABLE 1. Clinical scores (mean ± S.D.) before and after treatment.

At 6 months

At 12 months

At 24 months

Baseline

Score

Reduction

Score

Reduction

Score

Reduction

16.55 ± 3.60 11.90 ± 2.42

4.65 ± 2.05

8.30 ± 2.70

8.25 ± 2.63

4.60 ± 1.84

11.95 ± 3.20

15.50 ± 3.7

11.8 ± 2.78

3.70 ± 1.92 10.05 ± 2.68

5.45 ± 2.58

6.65 ± 1.66

8.85 ± 2.94

16.20 ± 5.06 14.65 ± 4.92

1.55 ± 1.19 12.60 ± 4.75

3.60 ± 1.46

8.45 ± 2.52

7.75 ± 3.09

Page 24

TABLE 2. Bacteriological index (mean ± S.D.) before, during and after treatment.

At 6 months

At 12 months

At 24 months

Baseline

Score

Reduction

Score

Reduction

Score

Reduction

4.00 ± 0.85

2.35 ± 1.08

1.65 ± 1.18

1.60 ± 0.91

2.40 ± 1.12

0.10 ± 0.30

3.90 ± 0.91

3.80 ± 0.95

2.45 ± 1.25

1.35 ± 0.93

1.75 ± 1.29

2.05 ± 1.09

1.00 ± 1.07

2.80 ± 1.00

3.50 ± 1.05

3.20 ± 0.95

0.30 ± 0.47

2.65 ± 0.87

0.85 ± 0.67

1.70 ± 0.97

1.80 ± 0.89

110

International Journal of Leprosy

2005

dence of type 2 reaction decreased in all the

groups after starting therapy; the decrease

was from 45% (pre-treatment) to 15% (post-

treatment) in group A and from 45% to 20%

in group B, whereas in Group C there was

hardly any change, from 40% to 35%, and 4

(20%) of the patients in group C continued

to have recurrent episodes throughout the

study period. The decrease in the incidence

of type 2 reactions in groups B and C was

not statistically significant.

At the beginning of the study, positive his-

tory of neuritis was present in 8 (40%), 7

(35%), and 9 (45%) patients in groups A, B,

and C, respectively. After starting treatment,

the incidence of neuritis decreased in all the

patients. In group A, 2 (10%); group B, 3

(15%); and in group C, 6 (30%) patients ex-

perienced neuritis as part of reactions. How-

ever, the decrease in the incidence of neuritis

was statistically significant only in group A.

All the patients with neuritis were managed

with systemic steroids, NSAIDS and rest.

Grade 2 deformities like claw hand, foot

drop, and trophic ulcers were present in 4

(20%) patients in group A and 5 (25%) each

in groups B and C. None of the patients in

groups A and B developed any new defor-

mities nor was there any further deteriora-

tion in the deformity status, whereas in

group C, 3 (15%) patients developed new

deformities during the study period, (claw

hand = 2 and foot drop = 1).

All the patients in group A developed an

erythematous papule at the site of BCG vac-

cination, which progressed to shallow ulcer

and healed spontaneously with scarring.

Three patients in this group developed sec-

ondary infection of the ulcer with associated

regional lymphadenopathy and required a

course of antibiotics. Similarly, in the Mw

group as well, all the patients developed

erythema and induration or an inflammatory

papule at the injection site, and in 15 (75%)

of these patients ulceration occurred which

healed spontaneously within 3 to 4 weeks.

No systemic complications were noted fol-

lowing vaccination with BCG or Mw.

All patients tolerated M.D.T. well except

for the occurrence of dapsone syndrome in

three patients (2 in group A and 1 in group

B), who recovered completely following

withdrawal of dapsone.

DISCUSSION

Multidrug therapy (M.D.T.) has been a

very successful development in the treat-

ment of leprosy. However, most of the pa-

tients in the lepromatous spectrum were

still harboring dead bacilli at the end of two

years of treatment with M.D.T., indicating

their poor ability to clear the bacilli. Im-

munotherapy with vaccines, drugs and cy-

tokines could be useful in these patients in

the very specific role of augmenting the

CMI leading to faster killing of M. leprae

and clearance of dead bacilli, thereby re-

ducing the risk of relapse and reactions.

There are many reports in the literature,

which show that the immunological unre-

sponsiveness to bacillary antigens of M.

leprae, in multibacillary patients (BL, LL)

may be altered by various immunological

approaches (3, 7, 9, 13, 14, 15, 16, 22, 23). Although

the precise mechanism of action of these

vaccines is yet unknown, certain assump-

tions can be put forward based on the above

studies and results of other clinical trials.

Mw and BCG vaccines are able to override

the immunological non-responsiveness to

bacillary antigens in multibacillary patients

by generation of cross-reactive Th1 type of

clones and amplification of IFN-γ produc-

tion with a concomitant decrease in levels

of TNF-α and IL-10.

In our study, the reduction in the clinical

scores was significantly more marked in the

BCG and Mw treated groups as compared

to controls (M.D.T. alone) at 6 and 12

months (p <0.05), however, BCG resulted

Page 25

TABLE 3. Granuloma fraction (GF) (mean ± S.D.) at baseline and after treatment.

At 6 months

At 12 months

At 24 months

Baseline

Score

Reduction

Score

Reduction

Score

Reduction

A 55.75 ± 21.04 32.00 ± 18.52 23.75 ± 10.37 10.25 ± 10.81 45.50 ± 16.05 2.00 ± 3.40 53.75 ± 19.18

B 55.00 ± 22.47 29.00 ± 0.04 26.00 ± 13.43 13.75 ± 12.55 41.25 ± 16.69 3.00 ± 4.97 52.00 ± 21.11

C 55.25 ± 23.92 35.00 ± 7.91 20.25 ± 11.41 22.75 ± 14.09 32.50 ± 14.18 10.75 ± 11.15 44.50 ± 19.66

73, 2

Narang et al.: Immunotherapy with BCG and Mw Vaccines

111

in greater reduction in the clinical scores as

compared to the Mw at 12 and 24 months (p

<0.01). All the previous studies on Mw vac-

cine have also reported significant clinical

improvement due to faster clearance of

bacilli (9, 14, 15, 30, 33, 35).

The average decline in B.I. with M.D.T.

has been reported to be 0.57 to 1.01 units/

year (1). In our study, bacterial indices de-

clined by 2.40 units/year in patients receiv-

ing BCG, 2.05 units/year in Mw group, and

0.85 units/year in the control group, the fall

becoming more apparent in immunotherapy

groups at 6, 12, and 24 months. The decline

in B.I. was significantly more in the BCG

treated group when compared to Mw treated

group. The differences between BCG and

Mw vaccine groups observed by us are not in

consonance with the observations made by

Katoch, et al. (16) who found the fall in B.I.

to be significantly more in the Mw-treated

group at 12, 18, and 24 months (p <0.05) as

compared to the BCG group.

Faster reduction in bacterial load and

changes in the cellular composition of the

granuloma(s) from lower to higher spec-

trum and reduction in the granuloma frac-

tion, observed in all of our patients in

groups A and B reflects the upgrading

of CMI following vaccination. Similar

histological/immunological upgrading has

also been reported in all previous studies

(9, 14, 15, 30, 33, 35). Katoch, et al. (16) showed

better histological improvement and im-

munological upgrading with Mw vaccine

when compared to BCG, but in our study

the difference between the two vaccine

groups was not statistically significant for

these parameters.

Leprosy reactions have a great signif-

icance in the course of the disease. Al-

though the incidence of ENL appears to

have fallen with the introduction of M.D.T.,

still a majority of patients with high smear

positivity are tormented by recurrent

episodes of ENL (17, 25). The incidence of

type 2 reactions decreased in all our pa-

tients after starting therapy but it was more

in the BCG treated group. Reduction in the

incidence of type 2 reactions following im-

munotherapy has been observed in other

studies as well. (9, 16, 25, 27, 30, 33).

Incidence of reversal reactions in MB pa-

tients treated with M.D.T. alone is reported

to vary from 9% to 41% in hospitalized pa-

tients (20, 25). In majority of the earlier stud-

ies and as observed by us although there is

an apparent increase in the incidence of re-

versal reactions in patients treated with Mw

/BCG vaccines as compared to the group

given M.D.T. alone, it did not achieve sta-

tistical significance (9, 14, 15, 16, 27, 28).

During the follow-up, it was reassuring to

note that there was a lower incidence of neu-

ritis in the vaccine treated groups [BCG =

2(10%); Mw = 3(15%)] as compared to the

figure of 30% for the control group. This is

in concurrence with an earlier study by Tal-

war, et al. (30) where the control group had

significantly more episodes of neuritis com-

pared to the vaccine group. However, the

decrease in the incidence of neuritis was sta-

tistically significant only in the BCG group.

A steady fall in the deformity rate among

new cases has been observed following the

introduction of M.D.T. since 1980 (4, 28), but

patients can have further deterioration of

their existing deformities during treatment

and thereafter due to increased incidence of

reactions and neuritis (28). In our study none

of the patients in the vaccine treated groups

developed any new deformity or deteriora-

tion of the pre-existing deformity, but in the

control group 3 (15%) patients developed

grade 2 deformities. Similar observations

have been made after immunotherapy with

Mw vaccine by Sharma, et al. (28) and with

BCG + killed M. leprae by Convit, et al. ( 7 ).

The vaccines were well tolerated and

only local complications like ulceration and

Page 26

112

International Journal of Leprosy

2005

mild secondary infection were seen. No

systemic complications developed follow-

ing administration of either of the vaccines.

Development of ulceration and scarring

which were hardly of any consequence

have also been reported in earlier studies

(9, 15, 16, 23, 30, 33). Three patients developed

dapsone syndrome, which is certainly a

very high incidence for dapsone hypersen-

sitivity. This was probably a chance occur-

rence, however such an observation of ris-

ing incidence of dapsone hypersensitivity in

the last two decades has been made by

workers from other parts of India (18, 24).

Dapsone was stopped in all these patients,

they were given the vaccines as per sched-

ule and none of them developed any other

complications.

Ours is the only study after Katoch, et al.

(16) where BCG and Mw have been com-

pared. In the study by Katoch, et al. (16),

M.D.T. and vaccines (at 6 month intervals)

were administered until the patients at-

tained smear negativity whereas in our

study all the patients received M.D.T.

(MBR) for one year and 4 doses of vaccines

at intervals of 3 months.

We observed that BCG combined with

M.D.T. produced better bacteriological

clearance, faster clinical improvement as

well as significant reduction in the inci-

dence of neuritis and type 2 reactions than

Mw, although both the vaccines were al-

most comparable in the histological upgrad-

ing. Katoch, et al. (16) reported better histo-

logical upgrading and bacteriological

clearance with Mw. It is difficult to decide

as to which biological parameters should be

given more significance (bacteriological or

histopathological) in evaluating the im-

munotherapeutic efficacy of a vaccine.

Histopathological improvement seems to

follow bacillary clearance but they can oc-

cur simultaneously and are inter-related but

may not exactly follow each other. Im-

munological investigations like lepromin

test, serology, cytokine assays and lympho-

cyte transformation tests as well as bacil-

lary ATP measurement, macrophage based

assays or DNA/RNA probes which directly

measure the immunological upgrading and

killing of viable bacteria, respectively, may

provide a better answer to some of these

questions; however, the results have not al-

ways been unequivocal.

Although no exact cause can be attrib-

uted to the observed better efficacy of BCG

vaccine in our study, the following hypoth-

esis can be proposed: different immuno-

stimulatory response of BCG in different

groups of people similar to the wide range

of its prophylactic efficacy in different trials

(20% to 80%) (2, 29), shorter interval be-

tween the doses, and the fact that BCG con-

tains live attenuated bacilli (whereas Mw

contains killed bacilli) hence they multiply

and stay for longer period in the patient and

may continue to augment the immunostim-

ulatory/immunomodulatory action of BCG

vaccine. These hypotheses can only be con-

firmed by studying these vaccines in large

number of patients who are followed up for

longer periods and by using a combination

of better investigative immunological tools

as stated above.

At present, based on the results of our

study and the previous similar studies on

BCG and Mw vaccines, we can conclude

that both these can prove to be important im-

muno-therapeutic tools in the management

of BL/LL patients with high smear positivity.

In the present scenario of decentralization of

leprosy services, reduction in the duration of

MB treatment to 12 months, with no strict

slit skin smear monitoring and absence of

rather essential long term follow-up, BCG

appears to be a better option than Mw be-

cause it is cheap and easily available.

Problems in field implementation may be

patient selection; as SSS is not being done so

B.I. cannot be used as a criterion. Studies

have shown that number of lesions/ thick-

ened nerves or extent of disease (number of

body areas involved) may be used to predict

smear positivity (19, 31). Based on these criteria

bacilliferous multibacillary (BL/LL) patients

can be offered benefits of immunotherapy.

Other problem that needs to be addressed is,

training of health workers in diagnosing and

identifying patients with multibacillary dis-

ease. As far as the supply and administration

of vaccine is concerned, BCG vaccine is

freely available in all the health centers in In-

dia (supplied under Universal immunization

program of Government of India), and the

health workers are well trained to administer

the vaccine so there should not be any opera-

tional difficulty to add BCG vaccine to our

ongoing National Leprosy Elimination Pro-

gram (NLEP).

Page 27

73, 2

Narang et al.: Immunotherapy with BCG and Mw Vaccines

113

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Page 29

1 Received for publication on 9 July 2004. Accepted for publication on 22 March 2005.

2 A. Kumar, Biostatistics and Epidemiology Division; A. Girdhar, Clinical Division; B. K. Girdhar, Clinical

Division, Central Jalma Institute for Leprosy and Other Mycobacterial diseases, Taj Ganj, Agra

Reprint requests to: Dr. Anil Kumar, Biostatistics and Epidemiology Division, Central Jalma Institute for Lep-

rosy and Other Mycobacterial diseases, Taj Ganj, Agra 282001; e-mail: biostat@sancharnet.in

Prevalence of Leprosy in Agra District (U.P.)

India from 2001 to 20031

Anil Kumar, Anita Girdhar, and B. K. Girdhar2

ABSTRACT

Leprosy prevalence has reportedly declined all over the world, but six countries, includ-

ing India, are still endemic for the disease. India alone contributes about 60% to the world’s

leprosy case load, with the major share from its northern states. The present study done in

Agra district was based on a randomly-selected sample of over 10% of the population,

spread across 300 villages and 16 urban units of the district. A house-to-house survey was

conducted from July 2001 to July 2003 in all the 26 selected panchayats (300 villages), all

the 11 block headquarters which have an urban component, and 5 (out of 20) localities in

Agra city.

A population of 361,321 persons was examined for leprosy. A total of 592 leprosy cases

[new and cases yet to complete a full course of multi-drug therapy(M.D.T.)] were found,

giving a prevalence rate of 16.4/10,000 population. Although the overall prevalence was

found to be similar in both rural and urban areas, there were pockets with high prevalence.

More cases were detected in the eastern side of Agra (31.4/10,000 in Fatehabad and

28.5/10,000 in Bah Tahsils). Overall, the multibacillary (MB) leprosy rate was 22.3% and

the child leprosy rate 8.4%.

Of the 592 cases, 523 (88.3%) were new untreated cases, giving a new case detection rate

of 14.5/10,000. The MB rate was 17% (89/523), and the child leprosy rate was 8.4%

(44/523) among the new patients. The grade 2 deformity rate was found to be 4.8% (25/523)

among these cases. The duration of disease among new cases was 32.3 months as compared

to 48.1 months among prevalent (registered) cases (i.e., patients who had been diagnosed

earlier and had yet to complete a full course of M.D.T.). The large number of undetected

cases found in this survey suggests the need for continued intensive health education cam-

paigns and case detection activities.

This study highlights the fact that a large number of leprosy cases go undetected in the

present integrated system which is mainly based on voluntary reporting of cases.

RESUME

Il est rapporté que la prévalence de la lèpre est en diminution partout dans le monde.

Cependant six pays, l’Inde y compris, sont encore endémiques pour la maladie. A elle seule,

l’Inde contribue pour environ 60% des nouveaux cas à l’échelle mondiale, avec la partie la

plus importante dans les états du Nord. La présente étude, réalisée dans le district d’Agra, fut

réalisée sur un échantillon pris au hasard de plus de 10% de la population, s’étendant à tra-

vers plus de 300 villages et 16 unités urbaines du district. Une enquête de maison en maison

fut menée entre juillet 2001 et juillet 2003 dans l’ensemble des 26 panchayats sélectionnés

(300 villages), l’ensemble des 11 centres urbains et 5 (parmi 20) localités de la ville d’Agra.

Un échantillon de 361 321 personnes fut examiné pour la présence de la lèpre. Un total

de 592 cas de lèpre [nouveau ou des cas n’ayant pas encore complétés leur PCT] fut détecté,

donnant un taux de prévalence de 16,4 cas pour 10 000 habitants. Bien que la prévalence

globale fut déterminée être similaire entre les zones urbaines et les zones rurales, des poches

de prévalence importante furent découvertes. Plus de cas furent détectés dans les quartiers

Est de la ville d’Agra (31,4/10 000 à Fatehabad et 28,5/10 000 à Bah Tahsils). Globalement,

le taux de lèpre multibacillaire (MB) était de 22,3% et le taux de lèpre pédiatrique de 8,4%.

Parmi les 592 cas, 523 (88,3%) étaient des nouveaux cas n’ayant pas encore été traités, se

traduisant par un taux de détection de nouveaux cas de 14,5/10 000. Le taux de lèpre MB

était de 17% (89/523), celui de lèpre des enfants de 8,4% (44/523) parmi les nouveaux pa-

tients. Parmi ces cas, le taux de déformations de grade 2 était de 4,8% (25/523). La durée de

la maladie parmi ces nouveaux cas était de 32,3 mois, comparé à 48,1 mois parmi les cas

115

INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 2

Printed in the U.S.A.

(ISSN 0148-916X)

Page 30

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International Journal of Leprosy

2005

prévalent déjà enregistrés (c.-à-d. les patients qui ont été diagnostiqués auparavant mais qui

n’ont pas encore terminés leur traitement de PCT). Le nombre important de cas non détec-

tés dans cette étude d’épidémio surveillance suggère qu’il existe encore un besoin important

de campagnes intensives d’éducation sur la santé et la lèpre et d’activités de détections de

nouveaux cas.

Cette étude stresse qu’un grand nombre de cas de lèpre reste non détectés après la mise en

œuvre du système actuel intégré, qui repose principalement sur la déclaration volontaire des cas.

RESUMEN

La prevalencia mundial de la lepra ha disminuido notablemente en los últimos años pero

6 países, incluyendo la India, se mantienen con alta endemia. La India sola contribuye con

cerca del 60% de los casos de lepra en el mundo y su mayor aportación proviene de sus es-

tados norteños. El presente estudio, realizado en el distrito de Agra, se hizo sobre una mues-

tra seleccionada al azar que incluyó a más del 10% de la población de Agra distribuida en

300 poblaciones rurales y 16 comunidades urbanas. La encuesta, casa por casa, se realizó de

julio del 2001 a julio del 2003 en las 300 poblaciones rurales, en 11 municipios y en cinco

(de 20) localidades de la ciudad de Agra.

Se examinaron 361, 321 personas, encontrándose un total de 592 casos de lepra [casos

nuevos y casos que debían completar su tratamiento con PQT-OMS], con una tasa de preva-

lencia de 16.4/ 10,000 habitantes. Las tasas de prevalencia en las regiones rural y urbana

fueron similares pero se detectaron focos de alta prevalencia. La mayoría de los casos se de-

tectaron en el lado oriental de Agra (31.4/ 10,000 habitantes en Fatehabad y 28.5/ 10,000 en

Bah Tahsils). La tasa global de lepra multibacilar (MB) fue del 22.3% y la tasa de lepra en

niños fue del 8.4%. De los 592 casos de lepra, 523 (88.3%) fueron casos nuevos no tratados,

lo que significa una tasa de detección de 14.5/ 10,000. Entre los pacientes nuevos, la tasa de

lepra MB fue del 17% (89/ 523) y la tasa de lepra infantil del 8.4% (44/ 523). También en

estos casos, la tasa de deformidad de grado 2 fue del 4.8% (25/ 253). La duración de la en-

fermedad entre los casos nuevos fue de 32.3 meses en promedio, mientras que en los casos

prevalentes registrados ésta fue de 48.1 meses. El gran número de casos nuevos descubier-

tos en esta encuesta, sugiere la necesidad de continuar con las campañas de educación y de

detección de casos de lepra. Por otro lado, el estudio subraya la baja eficiencia en la detec-

ción de casos del programa integrado actual, el cual se basa principalmente en el reporte vol-

untario de los casos.

Until the 1980s, leprosy continued to af-

fect a major part of the world, especially the

developing and under developed countries.

With the world wide introduction of multi-

drug therapy (M.D.T.) and intensive control

efforts six countries now account for about

90% of the caseload. Of this, India alone

contributes about two-thirds of the leprosy

patients (1, 7). Though there has been consid-

erable decline in the overall prevalence rate

in India, pockets of high endemicity still ex-

ist, especially in the northern states. Our ear-

lier reports (2, 3) had indicated that some ar-

eas in Agra had a high leprosy prevalence,

suggesting a need for proper and statistically

valid estimates. We have undertaken a sys-

tematic survey of the region to get an actual

case load of leprosy in rural and urban areas

of Agra district with an aim to assess if there

was any under-reporting in the present sys-

tem of voluntary case detection as practiced

in the integrated setting.

METHODS AND MATERIALS

Agra district has 6 Tahsils (talukas)—5

predominantly rural and 1 mainly urban.

Each of the rural Tahsils is divided into

blocks. These blocks are subdivided into

nyay panchayats (judicial units) and each

nyay panchayats (referred to as panchayats

in the text) has a cluster of villages under its

jurisdiction. About 65% of the 3.3 million in

the total population of Agra district lives in

the urban areas, while the remaining 35%

live in villages. Of the 65% of the population

living in urban areas, 50% live in Agra city

and the rest 15% reside in smaller towns,

mainly the block headquarters (urban) of the

rural tahsils. Within Agra city, almost three

quarters of the population live in underdevel-

oped or semi-developed crowded colonies

with minimal open space and poor civic

amenities.

The rural part of the Agra district is com-

prised of 94 panchayats spread over 13

Page 31

73, 2

Kumar, et al.: Prevalence of Leprosy in Agra, India

117

blocks in 6 tahsils. For the purpose of this

study, 2 panchayats from each block were

randomly selected and all the villages and

households in the selected panchayats were

included for the survey. In addition, the ur-

ban population from 11 blocks headquarters

(in the remaining 2, there being no town) and

5 (out of 20) localities in Agra City have

likewise been surveyed. In all 361,321 per-

sons—128,819 (35.7%) in rural and 232,502

(64.3%) in urban areas—were examined for

leprosy.

A house-to-house survey was conducted

between July 2001 and July 2003. All the

members present in each of the households

at the time of survey were shown picture

cards and briefed about early symptoms and

signs of leprosy and then physically exam-

ined by a trained paramedical worker

(PMW). The population examined included

all those who were present. Experienced su-

pervisors and medical doctors confirmed

the suspect cases later. The coverage (ex-

amined population) was about 70% of the

total population living in these areas.

Once the patient was diagnosed as having

leprosy, all the skin lesions and thickened

nerves including cutaneous nerves were

counted. Patients were classified as pau-

cibacillary (PB) if they had ≤5 skin patches

with or without 1 to 2 thickened major cuta-

neous nerves (2, 3, 4). Patients were labeled as

single skin lesion (SSL) cases if they had

only one skin lesion with no detectable

nerve thickening. Patients with ≥6 patches

and/or >2 thickened nerves and those with

infiltrations with or without papules or nod-

ules were classified as multibacillary (MB)

(2, 3) cases. Only visible deformity (grade

≥2) was recorded. All the newly detected

patients were put on World Health Orga-

nization (W.H.O.) recommended M.D.T. ac-

cording to the type of disease. A new case

was defined as one “who had not been diag-

nosed earlier and had no history of treatment

for leprosy in the past.” Patients with active

disease found during the survey, with a his-

tory of having received some anti-leprosy

treatment but had not completed the entire

course (defaulters) were recorded as preva-

lent cases. Period prevalence and New Case

Detection Rate (NCDR) were computed per

10,000 population examined. Χ2 test of sig-

nificance (5) was used for comparison.

RESULTS

Period prevalence. Examination of the

361,321 population across the district over

a 2 year survey period (2001 to 2003) re-

vealed 592 patients with active leprosy, giv-

ing an overall prevalence of 16.4/10,000

population. Of the 26 selected Panchayat in

the district, the prevalence rate (PR) varied

from zero in Naya Bans and Kachura in Ki-

raoli Tahsil located in the western part of

the district (see the Figure), to 46.9 in Nagla

THE FIGURE. Map of Agra, India.

Page 32

118

International Journal of Leprosy

2005

Patam under Fatehabad Tahsil, and 49.3 in

Karunpura in Bah Tahsil situated in the

astern side of the district (Table 1).

At block level in rural areas, a high preva-

lence (per 10,000) was found in Shamshabad

(41.4), and Jetpur Kalan (40.7), and low

(1.5) in Fatehpur Sikri, and (2.1) in Jagner

blocks. In the urban areas, a high prevalence

of 67.5 was recorded in Jetpur town of Bah

Tahsil, and zero prevalence was recorded in

Kiraoli town (Table 2).

At Tahsil level (rural and urban com-

bined), a prevalence of 31.4/10,000 was

noted in Fatehabad, followed by 28.5 in

Bah. Kiraoli Tahsil, situated on the western

side of Agra, had the lowest PR of 7.2.

Among the rural areas, the highest preva-

lence was recorded in rural parts of Fate-

habad (31.8), and the urban area Bah Town

had the highest prevalence (39.9). Simi-

larly, the lowest prevalence was recorded in

the rural areas of Kiraoli (3.4) and the urban

areas if Kheragad (9.7) (Table 3).

Prevalence of leprosy by age gradually

increased from 4.6/10,000 in 5 to 14 years

age group, to 53.8/10,000 in the age group 45

to 54 years. Age-related prevalence (patients

detected in the age group/10,000 population

examined) in both rural and urban areas

showed similar trends (Table 4). Prevalence

was higher among rural males (17.8 vs. 14.9,

χ2

1 = 9.9, p <0.002), and in the urban females

(18.0 vs. 14.9, χ2

1 = 10.6, p <.001) in com-

parison to their counterparts. However, in the

total population, males and females were

equally afflicted with leprosy (16.8/10,000

in females and 15.9/10,000 in males).

New case detection rate (NCDR). Of

the 592 active leprosy cases detected, 523

(88.3%) patients were detected for the first

time, and had never taken any treatment for

leprosy, giving a NCDR of 14.5/10,000

population in the district (Table 5). The pro-

portion of new cases to total cases found

ranged from 79.5% in Bah to 92.3% in Ki-

raoli Tahsil, indicating a high percentage of

cases having remained undetected.

Duration of disease and deformity grade

TABLE 1. Leprosy prevalence in selected panchayats in Agra district.

Tahsil

(location in

Blocks

Panchayats

Prevalence/10,000

the district)

(cases/population)

1. Kiraoli (West)

1. Fatehpur

1. Samra

2.6 (1/3923)

Sikri

2. Naya Bans

0 (0/2875)

2. Achhnera

1. Kachaura

0 (0/3141)

2. Raibha

8.7 (4/4576)

2. Agra (Central)

1. Akola

1. Malpura

0.9 (1/10,595)

2. Jarua Katra

9.7 (6/6176)

3. Etmadpur

1. Khandoli

1. Hazipur Kheda

14.5 (10/6899)

(North west)

2. Dhaurra

13.6 (13/9569)

2. Etmadpur

1. Chamraula

3.4 (2/5948)

2. Chawli

19.2 (9/4678)

4. Kheragar

1. Jagner

1. BasaiJagner

0 (0/3147)

(South west)

2. Richhauha

6.3 (1/1589)

2. Kheragar

1. Digrauta

4.5 (1/2218)

2. Kheragar

5.3 (1/1885)

3. Saiyan

1. Saiyan

14.3 (8/5616)

2. Iradatnagar

7.0 (2/2848)

5. Fatehabad (East)

1. Shamsabad

1. NaglaPatam

46.9 (31/6611)

2. Siktara

34.8 (19/5454)

2. Fatehabad

1. Nagarchand

14.9 (15/6707)

2. TarauliGujar

13.7 (4/2919)

6. Bah (East)

1. Pinahat

1. Baraura

15.9 (4/2518)

2. Ratauti

10.2 (6/5867)

2. Bah

1. Jarar

21.2 (24/11,308)

2. Bamrauli

28.9 (7/2424)

3. Jetpur kalan

1. Karanpura

49.3 (18/4060)

2. Chitrahat

38.0 (20/5268)

Total

16.1 (207/128,819)

Page 33

TABLE 3. Prevalence (PR) by tahsil and rural/urban status, Agra district.

Rural

Urban

Combined

Tahsil

Population

PR/10,000

Population

PR/10,000

Population

PR/10,000

(cases)

1. Kiraoli

14,515 (5)

3.4

3,511 (8)

22.8

18,026 (13)

7.2

2. Agra

16,771 (7)

4.2

203,261 (301)

14.8

220,032 (308)

14.0

3. Etmadpur 27,094 (34)

12.6

6,295 (19)

30.2

33,389 (53)

15.9

4. Kheragar 17,303 (13)

7.5

5,171 (5)

9.7

22,474 (18)

8.0

5. Fatehabad 21,691 (69)

31.8

4,738 (14)

29.5

26,429 (83)

31.4

6. Bah

31,445 (79)

25.1

9,526 (38)

39.9

40,971 (117)

28.5

Total

128,819 (207)

16.1

232,502 (385)

16.6

361,321 (592)

16.4

73, 2

Kumar, et al.: Prevalence of Leprosy in Agra, India

119

≥2. About a third of the patients had the dis-

ease of recent origin (<1 year), while in 25%,

the initial symptoms had been noticed more

than 4 years earlier. Although the median du-

ration of disease, both in rural and urban ar-

eas, was 24 months; the mean was slightly

higher in rural areas. The duration of disease

in newly detected cases was 32.3 months,

significantly lower that 48.1 months in preva-

lent cases (p <0.05). The difference in median

duration of disease for the two groups was 12

months (Table 6).

Among newly detected cases, the defor-

mity rate of Grade ≥2 was found to be 1.8%

(8/436) in paucibacillary (PB) leprosy, and

19.5% (17/87)—significantly higher—in

the multibacillary (MB) leprosy (p <0.05).

In the district as a whole, it was also found

to be significantly higher in rural popula-

tions, 8% (14/175) against 3.2% (11/348)

among the urban population (χ2

1 = 5.9, p

<0.05). As expected, the deformity rate was

4.8% (25/523) among new cases, signifi-

cantly less than 17.4% in prevalent cases or

defaulters (p <0.05).

DISCUSSION

The findings reveal that the prevalence of

leprosy in the Agra district is 16.4/10,000

(592/361,321), and is nearly equal in the

rural and urban areas (16.1 and 16.6/10,000,

respectively). More than 88% (523/592) of

TABLE 2. Leprosy prevalence in selected rural and urban blocks of Agra district.

Rural Agra

Urban Agra

Tahsil

Blocks

Prevalence*

Prevalence

(No. of Panchayats) (Cases/Population)

Urban unit

(Cases/10,000

Population)

1. Kiraoli

1. Fatehpur Sikri (7)

1.5 (1/6798)

Kiraoli Town

0 (0/863)

2. Achhnera (7)

5.2 (4/7717)

Achhnera Town

30.2 (8/2648)

2. Agra

1. Akola (3)

4.2 (7/16,771)

1. Jamuna Kinara

16.9 (68/40,169)

2. Shah Ganj

23.9 (153/63,910)

3. Lohamandi

13.1 (49/37,547)

4. Taj Ganj

5.0 (25/49,886)

5. Dhanoli

4.7 (6/12,749)

3. Etmadpur

1. Khandoli (8)

14.0 (23/16,468)

Khandoli Town

21.4 (7/3278)

2. Etmadpur (8)

10.4 (11/10,626)

Etmadpur Town

39.8 (12/3017)

4. Kheragar

1. Jagner (5)

2.1 (1/4736)

Jagner Town

18.1 (4/2211)

2. Kheragar (7)

4.9 (2/4103)

Kheragar Town

3.4 (1/2960)

3. Saiyan (9)

11.8 (10/8464)

Nil

5. Fatehabad

1. Shamsabad (8)

41.4 (50/12,065)

Shamsabad Town

22.4 (5/2231)

2. Fatehabad (10)

19.7 (19/9626)

Fatehabad Town

35.9 (9/2507)

6. Bah

1. Pinahat (6)

11.9 (10/8385)

Pinahat Town

23.9 (12/5020)

2. Bah (8)

22.6 (31/13,732)

Bah Town

47.0 (10/2127)

3. Jetpur Kalan (8)

40.7 (38/9328)

Jetpur Town

67.5 (16/2379)

Total

(92)

16.1 (207/128,819)

All Urban

16.6 (385/232,502)

Page 34

120

International Journal of Leprosy

2005

leprosy cases had not received any leprosy

treatment, as they had never been detected

and diagnosed as having the disease earlier.

The observed prevalence in this study is sig-

nificantly higher than the state figure

(0.9/10,000), which is based on the leprosy

elimination campaign (LEC) (6) conducted

in the year 2000. The official prevalence of

leprosy in Agra during 2002 has been re-

ported to be even lower (0.5/10,000) (un-

published report, 2002, District Leprosy Of-

ficer, Agra). The higher prevalence in the

present study is possibly a result of more in-

tensive and supervised work undertaken by

a team, which has resulted in the detection

of large numbers of hidden cases.

As in the case elsewhere in the country,

the distribution of leprosy patients is not

uniform; some areas and tahsils of the dis-

trict have a much higher prevalence than

the others (Table 3). Geographically, Fate-

habad and Bah Tahsil, which have the high-

est leprosy prevalence of almost 30/10,000,

border with Firozabad and Etawa district in

which high endemicity is officially ac-

knowledged (6). Within these tahsils, there

were also pockets (panchayats and villages)

with prevalence as high as 40/10,000 in

rural and 67/10,000 in urban areas, while

some of their adjoining areas had a fairly

low case load. Though age-specific preva-

lence revealed that cases have been de-

tected at all ages and the prevalence in-

creased with age (Table 4), it is significant

that over 8.0% of patients were children

(age ≤ 15). This indicates that active trans-

mission of disease is still occurring. This

correlates well with the observation that

most of the active cases had remained un-

detected for almost 3 years (mean duration

of disease) and may have been the source of

infection. In the present study, more female

patients were detected. This could be due to

examination of larger female populations.

As the survey was done during the daytime,

large number of male members had gone

out to work leaving females at home. On

the whole, there was not much difference in

the prevalence between male and female

(15.9 vs. 16.8, respectively).

Overall, 78% (460/592) of cases had PB

leprosy, with SSL accounting for 24.5%

(145/592), and significant proportion (22%)

TABLE 5. New case detection rate

(NCDR) by tahsil in Agra district;

2001–2003.

New case

Tahsil

Leprosy cases

detection rate

Total New %New (NCDR)/10,000

1. Kiraoli

92.3

6.7

2. Agra

308 282

91.6

12.8

3. Etmadpur 53

86.8

13.8

4. Kheragar

88.9

7.1

5. Fatehabad 83

89.2

28.0

6. Bah

117

79.5

22.7

Total

592 523

88.3

14.5

TABLE 4. Leprosy prevalence by age, sex and clinical type.

Rural (128,819)

Urban (232,502)

Combined (361,321)

Characteristics

Cases Prevalencea

Age: 0–4

0.3

0.2

5–14

5.0

4.4

4.6

15–24

9.2

11.8

11.0

25–34

18.7

25.6

111

23.2

35–44

36.0

30.2

108

32.2

45–54

56.0

52.5

109

53.8

55–64

54.4

60.8

58.0

>64

41.3

63.0

52.3

Gender: Male

17.8

164

14.9

260

15.9

Female

111

14.9

221

18.0

332

16.8

Type: PB

153

11.9

307

13.2

460

12.7

(SSL)

(56)

(4.3)

(89)

(3.8)

(145)

(4.0)

4.2

3.4

132

3.7

ALL

207

16.1

385

16.6

592

16.4

a Per 10,000 population examined.

Page 35

TABLE 6. Duration of disease by case status.

Duration of

New cases (523)

Prevalent cases (69)

disease (months)

Cases

Percent

Cases

Percent

0–6

18.9

2.9

7–12

17.8

4.3

13–24

119

22.8

24.6

25–48

17.0

34.9

49–72

14.5

13.0

>72

9.0

20.3

Mean

32.3

–

48.1

–

Median

24.0

–

36.0

–

73, 2

Kumar, et al.: Prevalence of Leprosy in Agra, India

121

had MB disease. Among the newly detected

patients, a relatively low prevalence of de-

formities of grade ≥2 was noted [4.8%

(25/523), 1.8% among PB and 19.5% in MB

patients). A higher prevalence of deformities

was observed among prevalent patients

(17.4%). The difference appears to be due to

a relatively longer mean duration of disease

in prevalent cases (48.1 vs. 32.3 months)

than in new cases. Of all the patients with

deformities of grade ≥2, about 76% had par-

alytic problems in hands and/or feet (figures

not shown). Since none of the patients com-

plained of any initial symptoms related to

these deformities, the frequency of silent

nerve damage appears to be high.

In conclusion, this survey, representing

all the areas in Agra, indicates that leprosy

continues to be a significant problem in

both rural and urban areas with a larger pa-

tient load in tahsils located on the eastern

side of the district. The undetected pool of

infection has possibly continued to spread

infection in the community as suggested by

the observation of a child leprosy rate of

8.4%. In view of these findings, there is a

need for reappraisal of leprosy elimination

campaign activities to make these more ef-

fective, so that in the future new patients

themselves report at treatment centers on

suspicion of the disease. In addition, contin-

ued case detection activities, throughout the

district, need to be undertaken to detect and

treat hidden cases as this is important for

achieving the goal of eliminating leprosy as

a public health problem.

Acknowledgement. The work has supported by a

internal grant from the institute. Authors like to thank

Dr. V. M. Katoch, Director of the Institute for his sup-

port. Data entry help of Mr. Rajendra Kumar, Mr. V. S.

Yadav for computer assistance, and the help rendered

by 6 PMW and 20 Case searches are also thankfully

acknowledged.

REFERENCES

1. GUPTE, M. D. Leprosy elimination critical issues:

epidemiology—global scenario. In: Leprosy Elimi-

nation: Critical Issues. Ranbaxy Science Founda-

tion, Round Table Conference Series 10 (2002) 3–8.

2. KUMAR, ANIL, GIRDHAR, A., and GIRDHAR, B. K.

Epidemiology of leprosy in urban Agra, India.

Lepr. Rev. 74(1) (2003) 31–34.

3. KUMAR, A. GIRDHAR, A., YADAV, V. S., and GIRD-

HAR, B. K. Some epidemiological observations on

leprosy in Agra (India). Int. J. Lepr. Other My-

cobact. Dis. 69(3) (2001) 234–240.

4. RIDLEY, D. S., and JOPLING, W. H. A classification

of leprosy for research purposes. Lepr. Rev. 33

(1962) 119–128.

5. SNEDECOR, G. W. Statistical Methods. 6th edn.

London: Oxford & IBH Publishing Co. Pvt. Ltd.,

1967. 516–520.

6. STATE LEPROSY OFFICER. Leprosy prevalence rate

in Uttar Pradesh—status as on March 2000 (Post

Mlec 2). Report presented at National level semi-

nar at NIHFW, New Delhi. (2000).

7. W.H.O. The Final Push Strategy to Eliminate

Leprosy As a Public Health Problem. Questions

and Answers. 1st edn. Geneva: World Health Or-

ganization, 2002.

Page 36

Leprosy is a major health problem in In-

dia with a prevalence of 3.22/10,000, affect-

ing all age groups from infancy to old age

(3). Children below 15 years of age consti-

tute about 15% of total cases of leprosy (2).

However, it has generally been observed

that in childhood, indeterminate leprosy is

the most common type, followed by tuber-

culoid variant; borderline lepromatous and

lepromatous leprosy are only occasionally

encountered (18). Various published studies

have consistently described reactions espe-

cially type 2 to be less common in children

than in adults (4, 5, 8, 9, 12, 13, 21).

We describe a 9-year-old boy who pre-

sented primarily with erythema nodosum

leprosum necroticans (ENL) and was sub-

sequently diagnosed as having lepromatous

leprosy.

Case report. A 9-year-old boy presented

to dermatology outpatients with the com-

plaint of multiple red, raised, painful le-

sions over the face and limbs of 4 months

duration. These grouped lesions started

from the chin, followed by similar erup-

tions over his upper and lower limbs, and

subsided with scaling and bruise-like pig-

mentation over the next 2 to 3 weeks. How-

ever, few lesions had ruptured to discharge

pus. He also had episodic fever with each

crop of lesions. There was no evidence of

any systemic focus of infection on history.

There was no history of light colored or

1 Received for publication on 29 September 2004.

Accepted for publication on 31 January 2005.

2 D. Pandhi, M.D.; S. Mehta, M.D.; S. Agrawal,

M.D.; A. Singal, M.D., Department of Dermatology

and STD, University College of Medical Sciences and

Guru, Teg Bahadur Hospital, New Delhi-110095, India.

Reprint requests to: Dr. Archana Singhal, B-16/Fi,

Dilshad Garden, Delhi–11095, India.

E-mail: archanasinghal@rediffmail.com

CASE REPORT

Erythema Nodosum Leprosum Necroticans in a Child—

An Unusual Manifestation1

Deepika Pandhi, Shilpa Mehta, Subhav Agrawal, and Archana Singal2

ABSTRACT

Erythema nodosum leprosum necroticans is an uncommon manifestation of type 2 lepra

reaction, encountered in lepromatous and borderline lepromatous cases of leprosy. We report

an unusual clinical presentation of necrotic erythema nodosum leprosum in a 9-year-old boy

with no pre-existing evidence of leprosy. The lesions resolved completely following multi-

bacilliary multi-drug therapy for 12 months, non-steroidal anti-inflammatory drugs and cor-

ticosteroids.

RESUME

L’érythème noueux lépreux nécrotique est une complication inhabituelle des réactions

lépreuses de type 2. Elle est rencontrée dans les cas de lèpre lépromateuse et lépromateuse bor-

derline. Nous rapportons ici la présentation clinique inhabituelle, chez un garçon de 9 ans, d’un

érythème noueux lépreux nécrotique, sans diagnostic préalable de lèpre. Les lésions

rétrocédèrent complètement après la mise en œuvre d’un traitement incluant une polychimio-

thérapie contre la lèpre multibacillaire, des corticoïdes et des anti-inflammatoires non-stéroï-

diens.

RESUMEN

El eritema nodoso leproso necrotizante es una manifestación poco común de las reacciones

leprosas tipo 2 que aparecen con cierta frecuencia en los pacientes con lepra BL y LL. En esta

comunicación se reporta un caso de esta rara complicación en un niño de 9 años de edad que

no había mostrado evidencias previas de la lepra. Las lesiones se curaron completamente por

tratamiento del paciente con PQT de corta duración (12 meses) acompañada de la adminis-

tración de drogas antiinflamatorias no esteroidales y corticoesteroides.

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Pandhi, et al.: ENL Necroticans in a Child

123

numb lesions, spontaneous blistering or

weakness in any limb. He did not have ocu-

lar, nasal, testicular, joint, or any other sys-

temic complaints. None of the family mem-

ber had leprosy, tuberculosis, or any chronic

ailment.

The patient weighed 22 kg and was febrile

(101°F), with multiple discrete and large sub-

mandibular lymph nodes about 0.5 to 1 cm in

size, non-tender and not attached to the over-

lying skin. On cutaneous examination there

was evidence of facial infiltration along with

multiple erythematous tender nodules and

plaques varying from 0.7 cm to 2 cm were

seen over the cheeks, chin, and right earlobe,

extensor aspect of upper and lower limbs,

lower back, and buttocks (Figs. 1 and 2). Few

lesions had overlying irregular ulcers with

necrotic base (Fig. 2). Multiple hyperpig-

mented bluish macules with well to ill-de-

fined margins were also noted on the bilateral

upper and lower limbs. Bilateral ulnar, lateral

popliteal, and posterior tibial nerves were

symmetrically thickened and non-tender.

There was no evidence of specific glove

and stocking type of sensory loss, or any

motor deficit. Systemic examination did not

reveal any abnormality.

Hemogram revealed mild anemia (Hb =

10.5 gm%), neutrophilic leukocytosis (TLC

= 16,000, DLC = P70L25M3E2), and raised

erythrocyte sedimentation rate (ESR = 81

mm in the first hour). The antistreptolysin

titer was less than 200 and the reports of

throat swab and mantoux test were nega-

tive. Tests for activated partial thrombo-

plastin time (aPTT), kaolin clotting time

(KCT), LE cell and rheumatoid factor were

negative. Other laboratory investigations

including liver and kidney function test,

blood sugar, urine examination, and chest

x-ray were within normal limits. Slit skin

smear revealed a bacteriological index of

5+ along with a morphological index of

10%. Routine histopathology section

stained with hematoxylin and eosin from

the nodule on the left arm demonstrated

neutrophilic abscesses superimposed on a

diffuse infiltrate of foamy macrophages and

plasma cells, along with the evidence of

leucocytoclastic vasculitis, which validated

the diagnosis of lepromatous leprosy with

ENL (Figs. 3 and 4). Fite’s stain showed

clumps of acid-fast bacilli (AFB) in the peri-

neural cells and macrophages.

He was started on World Health Organi-

zation (W.H.O.) recommended multibacil-

lary (MB) multi-drug therapy (M.D.T.),

which included 50 mg of dapsone daily and

300 mg of rifampicin monthly along with

50 mg of clofazimine daily. The patient was

FIG. 1. Hyperpigmented infiltrated plaques with

necrosis present on the extensor aspect of right upper

limb.

FIG. 2. Multiple erythematous to hyperpigmented

nodular swellings on the face and extensor aspect of bi-

lateral arms with few of them showing central necrosis.

Page 38

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International Journal of Leprosy

2005

also started on diclofenac sodium 25 mg

thrice daily along with 30 mg of pred-

nisolone. The lesions subsided in 6 to 8

weeks time, with no evidence of recurrence

or subsequent neural deficit on follow-up.

Prednisolone was gradually tapered over a

period of 6 months and diclofenac sodium

was continued for another 2 months Cur-

rently, he has received MB M.D.T. for 11

months and there is no significant reduction

in the nerve enlargement.

DISCUSSION

Children in leprosy endemic areas are ex-

posed to infection by Mycobacterium lep-

rae. The youngest age reported for the oc-

currence of leprosy is about 3 weeks (15). A

1978, a survey among school children in

Hyderabad showed the prevalence rate to

be 10 to 17 per 1000 (8).

Majority of the pre-pubertal children tend

to have indeterminate or tuberculoid type of

leprosy (18). The children present with

asymptomatic or hypoaesthetic cutaneous

lesions and, less often, with neural manifes-

tations. A single lesion present on exposed

areas of the body was reported to be more

common than multiple lesions of the body.

Leprosy workers have been conservative in

making a diagnosis of multibacilliary or

borderline leprosy in children, despite the

fact that all types of leprosy can occur in

any age group (18). The reported rate of

smear positive leprosy is less than 10% in

pediatric age group (16). This appears to be

a paradoxical situation and runs counter to

the concept that immune responses are

poorly developed in the very young chil-

dren, due to the inability of the immature

lymphoid system to deal with and react

with foreign antigens (6, 19).

Despite the high prevalence of leprosy in

children, the occurrence of both type 1 and

type 2 reaction especially ENL is rare as re-

vealed by an extensive MEDLINE search.

ENL has been reported in 0 to 3.1% of all

the cases of childhood leprosy, which is

much less than the reported incidence of

35% among all the age groups (21) (The

Table). The largest study comprising 1028

leprosy patients has reported 25 cases of pe-

diatric ENL, out of which only 7 patients

were below 10 years of age (5). ENL necrot-

icans, however, has not been reported in pe-

diatric age group to date.

THE TABLE. Studies showing incidence

of erythema nodosum leprosum in pediatric

age group.

Author

Year

No. of

ENL

No.

patients

1 I. Kaur, et al. (12)

1991

132

2 V. N. Sehgal, et al. (19) 1993

161

Not

specified

3 P. V. Prasad (17)

1998

Nil

4 A. Selvesekar, et al. (1) 1999

794

5 X. S. Chen, et al. (5)

2000 1028

6 H. C. Leu, et al. (13)

2000

Nil

7 S. Jain (8)

2002

306

8 K. D. Burman, et al. (4) 2003

Not

specified

FIG. 3. Routine histopathological stained section

from nodular lesion on left arm showing a diffuse in-

filtrate of foamy macrophages along with endothelial

cell swelling, erythrocyte extravasation and polymor-

phonuclear infiltration (H&E ×200).

FIG. 4. Routine histopathological stained section

from nodular lesion on left arm showing a diffuse in-

filtrate of foamy macrophages along with polymor-

phonuclear infiltration (H&E ×1000).

Page 39

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Pandhi, et al.: ENL Necroticans in a Child

125

Hypersenstivity responses are known to

play an important role in the occurrence of

reactions. Reactional episodes and disabil-

ity are less frequently seen in the younger

children, due to the poorly developed im-

munological mechanisms in early child-

hood (6). Therefore, development of disabil-

ities as a consequence of reactions is, more

often encountered in adults and in older

children (5, 19).

Jain, et al. reported the incidence of neu-

ritis to be 24.2% in the cohort of pediatric

leprosy patients, and emphasized the im-

portance of appropriate use of steroids to

prevent deformities (8). Surprisingly, none

of these studies on childhood leprosy have

described the use of systemic steroids in re-

actions, with the exception of the study

conducted by Thirugananam, et al., who re-

ported one child who developed primary fo-

cus of tuberculosis after having received

one and a half years steroid therapy (5, 22, 23).

Digeorge, et al. have described numerous

side effects of systemic corticosteroids in

pediatric conditions, with a special mention

of HPA axis suppression, growth failure and

retarded bone formation, especially when

they are used over a longer period of time

(7). Thus, though we should be aggressive

in using steroids in reactions to prevent se-

quele, the potential serious adverse effects

should be screened for.

Lucio’s phenomena is characterized by

the development of painful, tender, and pur-

puric macules, particularly on the extremi-

ties, with necrotic center which finally de-

velop a black eschar which heals in a few

days to leave superficial atrophic scars (10).

This phenomena is typically seen in pa-

tients with Lucio’s leprosy, which usually

manifests as shiny thickened skin with loss

of body hair (but not scalp hair) and wide-

spread sensory loss. Unlike polar leproma-

tous (LL) there are no skin or ocular le-

sions, motor palsies, and finger contractions

(11). Though this phenomena is character-

ized histopathologically by leucocytoclastic

vasculitis, as seen in the present case, the

usual clinical presentation of Lucio’s lep-

rosy was not observed and thus, the possi-

bility was not considered.

Family contacts with leprosy in the pedi-

atric age group are documented to be a sig-

nificant factor in contracting the disease (8).

Though no such history was found in the

present case, the importance of contact

screening strategies cannot be undermined.

(i) The various factors associated with the

prevalence of ENL include older age group,

bacillary index of more than 4, multiple en-

larged nerves (>5), the presence of nodules

and infiltration, more than 1 year of un-

treated disease and the presence of the anti-

PGL-1 antibodies (14). Our patient had fa-

cial infiltration, high bacillary index, and

multiple thickened nerves though duration

of the disease could not be ascertained.

(ii) In the present case, history of fever

with the eruption of ENL necroticans le-

sions along with thickened nerves pointed

towards a diagnosis of lepromatous leprosy.

Characteristic histopathology, demonstra-

tion of acid-fast bacilli and response to ther-

apy further confirmed the diagnosis and ex-

cluded other possible causes of erythema

nodosum.

(iii) To the best of our knowledge, this re-

port of a nine-year-old boy describes the

first case of necrotic ENL along with lepro-

matous leprosy in a child.

REFERENCES

1. ANONYMOUS. Ministry of Health & Family, Wel-

fare Govt. of India (1982) Annual Report

1981–82, New Delhi.

2. ANONYMOUS. Update on leprosy elimination in

SEAR (November 2003). Regional Health Forum

7(2).

3. BURMAN, K. D., RYALL, A., AGARWAL, S., AGAR-

WALLA, A. Childhood leprosy in eastern Nepal: A

hospital based study. Indian J. Lepr. 75 (2003)

47–52.

4. CHENM X, S,, WEN ZHONG LI, CHANG JIANG, and

GAN-YUN YI. Leprosy in children: a retrospective

study in China. J. Trop. Pediatric. 46 (2000):

207–211.

5. CRUISHANK, R., DUGUID, J. P., MARMIAN, B. P.,

and SWAIN, R. H. A. Natural and acquired immu-

nity. In: Medical Microbiology, 2nd edn. FLAS

Ed, 1973. p. 134.

6. DIGEORGE, A. M., and LEVINE, L. S. Cushing syn-

drome. In: Nelson’s Textbook of Pediatrics, 15th

edn. Bangalore: Prism books pvt. Ltd., 1996. pp.

1623–1624.

7. JAIN, S., REDDY, R. G., NORMANI, S., LOCKWOOD,

D. N. J. Childhood leprosy in an urban clinic, Hy-

derabad, India; clinical presentation and the role

of household contacts. Lepr. Rev. 73 (2002)

248–253

8. JAYAM, S., SEKHAR, K., RAMASEKHAR, K., and

GANAPATHI, R. Childhood leprosy: a study in an

urban slum. Indian Pediatr. 15 (1978) 375–377.

Page 40

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International Journal of Leprosy

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9. JOPLING, W. H., and MCDOUGALL, A. C. Leprosy

reactions. In: Handbook of Leprosy, 5th edn. New

Delhi: CBS publishers, 1996. pp. 82–91.

10. JOPLING, W. H., and MCDOUGALL, A. C. The dis-

ease. In: Handbook of Leprosy, 5th edn. New

Delhi: CBS publishers, 1996. pp. 10–53.

11. KAUR, I., KAUR, S., SHARMA, V. K., and KUMAR,

B. Childhood leprosy in Northern India. Pedi-

atric. Dermatol. 8 (1991) 21–24.

12. LEU, H. C., CHEN, J. C., CHAO, J. Y., CHAO, P., ET

AL. Epidemiology of leprosy in Taiwan; its pat-

tern in children. Int. J. Lepr. Other Mycobact. Dis.

68 (2000) 57–62.

13. MANANDHAR, R., LE MASTER, J. W., and ROCHE,

P. W. Risk factors for ENL. Int. J. Lepr. Other

Mycobact. Dis. 67 (1999) 270–278.

14. NOORDEN, S. K. The epidemiology of leprosy. In:

Leprosy, 2nd edn. Edinburgh: Churchill Living-

stone, 1994. pp. 29–48.

15. NOUSSITOU, F. M., and SANSARRICA, H. Leprosy in

Children. Geneva: World Health Organization,

1976. pp. 11–28.

16. PRASAD, P. V. Childhood leprosy in an endemic

area. Indian J. Pediatrics. 65 (1997) 751–754.

17. SAMUEL, N. M., SAMUEL, S., and ABIGA, R. B.

Borderline leprosy in a 3-year-old child. Indian J.

Lepr. 57 (1985) 628–631.

18. SEHGAL, V. N., and CHAUDHARY, A. Leprosy in

children: a prospective study. Int. J. Dermatol. 32

(1993) 194–197.

19. SEHGAL, V. N., REGE, V. L., MASCARENHAS, M. F.,

AND REYS, M. The prevalence and pattern of lep-

rosy in a school survey. Int. J. Lepr. Other My-

cobact. Dis. 45 (1977) 360–363.

20. SELVESKAR, A., GEETHA, J., NISHA, K., and MANI-

MOZHI, N. Childhood leprosy in an endemic area.

70 (1999) 21–27.

21. SHARMA, P., KAR, H. K., MISRA, R. S., MUKHERJEE,

A., KAUR, H., MUKHERJEE, R., AND RANI, R. Reac-

tional states and neuritis in multibacilliary leprosy

patients following M.D.T. with/without immuno-

therapy with Mycobacterium w anti-leprosy vac-

cine. Lepr. Rev. 71 (2000) 193–205.

22. THIRUGANANAM, T., and RAJAN, M. A. Borderline

reactions treated with clofazimine and cortico-

steroids. Indian J. Lepr. 57 (1985) 164–171.

Page 41

TO THE EDITOR:

Leprosy or Hansen’s disease (HD) is of-

ten complicated by immune-mediated reac-

tions. Reversal reaction (RR), a delayed

type hypersensitivity response, can occur in

borderline tuberculoid (BT), borderline bor-

derline (BB) and borderline lepromatous

(BL) patients. Erythema nodosum leprosum

(ENL) is an antibody immune complex re-

action that occurs in BL and lepromatous

(LL) patients. The standard treatment for

RR is systemic corticosteroids, whereas

thalidomide is the most effective drug for

ENL (2, 5, 10). While steroids provide rapid

control of ENL symptoms, long term use

often results in the associated adverse ef-

fects (11). Three patients with leprosy reac-

tions and thalidomide or steroid toxicities

were treated with mycophenolate mofetil

(MMF) as a steroid sparing agent and their

outcomes described below.

Case 1.A 29-year-old Hispanic male was

diagnosed with BL (slit smear average of

4.5) and started on daily rifampin 600 mg,

dapsone 100 mg, and clofazimine 100 mg.

He developed ENL and RR with a signifi-

cant neuritis 4 months after treatment was

initiated. Daily thalidomide 100 mg and

prednisone 60 mg (1 mg/kg) were started

and rifampin was changed to minocycline

100 mg daily with moderate improvement

of symptoms. Prednisone was slowly ta-

pered to doses ranging from 35 mg to 15

mg daily, and 18 months after the first

episode of ENL the patient developed an

ENL flare. Thalidomide was increased to

200 mg daily for 1 week and then to 300

mg daily. Symptoms improved. After 2

months of being on high doses of thalido-

mide and prednisone (30 mg to 40 mg

daily), MMF was added as a steroid sparing

agent initially at 50 mg twice daily and then

at 1000 mg twice daily.

Thalidomide was lowered to 250 mg

nightly and several attempts to taper the

dose below 40 mg were unsuccessful. Three

moths later, the patient complained of per-

sistent burning pain in his hands and feet,

mostly at night. Due to this burning pain,

thalidomide was stopped. Nerve conduction

studies demonstrated slowing of ulnar and

median motor conduction and a sensory pe-

ripheral neuropathy consistent with thalido-

mide neuropathy. The patient was referred

to the U.S. National HD Program where he

was diagnosed with a probable thalidomide

neuropathy. The recommendation was to

restart thalidomide in order to lower the

prednisone dose. While on thalidomide 200

mg and prednisone 40 mg, his ENL recurred

and the patient developed acute orchitis re-

quiring prednisone 80 mg daily for adequate

ENL control. Despite 10 months of MMF 2

grams daily, in addition thalidomide 200 mg

and clofazimine 100 mg daily, his pred-

nisone could not be lowered due to flares of

lesions and symptoms.

Case 2. A 29-year-old Burmese man with

BL HD (slit smear average of 4.3) on Octo-

ber 2001 presented with bilaterally enlarged

tender greater auricular and ulnar nerves and

pink annular plaques on elbows, knees, and

the periorbital region. His RR was treated

CORRESPONDENCE

This department is for the publication of informal communications that are of interest

because they are informative and stimulating, and for the discussion of controversial

matters. The mandate of the JOURNAL is to disseminate information relating to leprosy in

particular and also other mycobacterial diseases. Dissident comment or interpretation on

published research is of course valid, but personality attacks on individuals would seem

unnecessary. Political comments, valid or not, also are unwelcome. They might result in

interference with the distribution of the JOURNAL and thus interfere with its prime purpose.

The Role of Mycophenolate Mofetil

in the Treatment of Leprosy Reactions

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with prednisone (1 mg/kg/day) with mini-

mal improvement noted after 2 months.

MMF 500 mg twice daily was started at 500

mg twice daily and later increased to 1000

mg twice daily. During the 7 months he was

on MMF, several attempts were made to

lower the prednisone dose. Each taper re-

sulted in an exacerbation of symptoms. The

MMF was discontinued.

Case 3. A 51-year-old Hispanic female on

treatment for BL (slit smear average of 1.1)

for 5 months developed a severe RR which

was treated with prednisone 40 mg daily

and had a good response. After several

months, when prednisone was tapered to 5

mg daily, she developed a new RR. Pred-

nisone was increased to 80 mg daily with a

subsequent worsening of her diabetes melli-

tus. MMF 500 mg twice daily was started

and then increased to 1000 mg twice daily.

The patient had improved signs and symp-

toms. However, she developed severe gas-

trointestinal distress which resolved when

MMF was discontinued 3 months later.

DISCUSSION

Several drugs are available for the treat-

ment of HD reactions, most are used in com-

bination. Prednisone, which remains the gold

standard therapy for the acute symptoms of

both reactions, is fraught with numerous side

effects since these leprosy reactions require

many months to years of immunosuppressive

therapy. Thalidomide, which is the most ef-

fective drug in the treatment of ENL, is also

related to toxicities including periphereal

neuropathy. Other effective drugs for ENL in-

clude high dose clofazimine, which has an

anti-inflammatory effect, and pentoxifylline,

which like thalidomide inhibits tumor necro-

sis factor-alpha (TNF-α) production.

Mycophenolate mofetil (MMF), an im-

munosuppressant agent, has been used in

transplanted patients (3, 7), and also as a

steroid sparing immunosuppressive in in-

flammatory skin diseases such as pemphigus

vulgaris (6). MMF is a reversible inhibitor of

inosine monophosphate dehydrogenase (IM-

PDH), an enzyme that is critical in the de

novo synthesis of purines. Lymphocytes, in

contrast to most other cells, depend more on

the de novo pathway for purine synthesis

than the salvage pathway. Therefore, MMF

affects both B and T lymphocyte synthesis.

RR is thought to be caused by increased T-

cell reactivity to Mycobacterium leprae (4)

although recent data suggests that humoral

immunity may also be involved (8). ENL

pathogenesis has been attributed to an in-

crease of TNF-α syntheis which is induced

by T cells (1, 9). These mechanisms suggested

that MMF would be useful in treating RR

and ENL; however, this was not observed

during MMF treatment in these patients.

—Anne E. Burdick, M.D., M.P.H

Professor of Dermatology,

University of Miami and Medical Director,

University of Miami/Jackson Memorial

Hospital Hansen’s Disease Program

—Claudia C. Ramirez, M.D.

Research Fellow,

Department of Dermatology

and Cutaneous Surgery,

University of Miami, Miami, Florida

REFERENCES

1. BARNES, P. F., CHATTERJEE, D., BRENNAN, P. J.,

REA, T. H., and MODLIN, R. L. Tumor necrosis

factor production in patients with leprosy. Infect.

Immun. 60(4) (1992) 1441–1446.

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mide: use and possible mode of action in reactional

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tions. J. Am. Acad. Dermatol. 7(3) (1982) 317–323.

3. BEHREND, M. Mycophenolate mofetil: suggested

guidelines for use in kidney transplantation.

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4. BRITTON, W. J. The management of leprosy rever-

sal reactions. Lepr. Rev. 69(3) (1998) 225–234.

5. CRAWFORD, C. L. Use of thalidomide in leprosy. Ad-

verse Drug React. Toxicol. Rev. 13(4) (1994) 177–192.

6. ENK, A. H., and KNOP, J. Mycophenolate is effec-

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SARNO, E. N., NERY, J. A., and SAMPAIO, E. P.

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73, 2

Correspondence

129

Leprosy Profile in Isfahan (A Province of Iran)

ABSTRACT

In Iran, there have been a few cases of leprosy in several provinces, however, native

physicians believe that leprosy is not present primarily in an Isfahan endemic area. We per-

formed an investigation either to approve or rule out this idea.

We found 25 lepra patients who were registered and followed in Isfahan Leprosy Health

Registeration Center, all of whom were infected in other regions and migrated to Isfahan

city at a later time.

Final analysis proved that there are not any cases of leprosy by itself in Isfahan as an en-

demic region at the time of this study (1975 to 2002) .

TO THE EDITOR:

In Iran, there have been a few well-known

cases of leprosy in the provinces such as

Azarbayjan, Khorasan, Lorestan, Khouses-

tan, Boushehr, Hormozgan, and Baluchestan

in itself (1). In Isfahan, however, there has

been a common belief among medical per-

sonnel that there are not any endemic cases

of leprosy in the native population of this

province area. According to this proposed

idea, we decided either to attempt to prove

or disprove it by an overall survey on this

disease.

MATERIALS AND METHODS

In this descriptive retrospective cross-

sectional study, we took the registered

records of all lepra cases from Isfahan Med-

ical Health Center, between 1975 and 2002,

in whom leprosy as a diagnosis was sug-

gested and confirmed through a skin smear

and skin biopsy.

We studied the documents and searched

for items such as sex, age, nationality, type

of the disease, residential area, and the

mode of treatment. We found 25 registered

patients from the above period.

RESULTS

From the 25 Lepra patients who had been

registered bewteen 1975 and 2002 in Isfahan,

the youngest patient was 14 and the oldest

was 67 (mean age = 40 years). Twenty of

them were in the lepromatous spectrum, and

5 were in the tuberculoid spectrum of leprosy.

In respect to the nationality, 19 were

Afghani, 4 were Iranian who had migrated

to Isfahan after being infected in other

provinces, and 2 were Iraqi. According to

the patients’ residential area, the highest

numbers belonged to Isfahan city and

GRAPH 1. The comparative evaluation of the

prevalence of leprosy patients in different parts of Is-

fahan province.

Khomeinishahr city, respectively (Graph 1).

The sex distribution of the patients showed

80% males and 20% females.

Finally, we did not find any lepra patients

originally from Isfahan.

DISCUSSION

Leprosy is a worldwide disease, particu-

larly prevalent in tropical underdeveloped

countries. Leprosy is endemic in 24 coun-

tries (2, 3).

Mycobacterium leprae bacilli live in

colder areas of the body such as skin, mu-

cous membranes, nerves, or scrotum (4, 5).

At the beginning of 2004, the number of

leprosy patients undergoing treatment in the

world was around 460,000. About 515,000

new cases were detected during 2003. Among

them, 43% were multibacillary (MB) cases,

12% were children, and 3% were diagnosed

with severe disabilities. During the past two

years, the global number of new cases de-

Page 44

130

International Journal of Leprosy

2005

tected continued to decrease dramatically (a

reduction of about 20% per year) (6, 7).

New cases are reported annually from

many provinces in north east, north west,

west, and south of the country. It was esti-

mated that the total number of lepric pa-

tients in Iran until 1982 was 16,500. Ac-

cording to the World Health Organization

there are approximately 30,000 to 45,000

lepra patients in Iran (1, 7). Iran is not con-

sidered as an endemic area for leprosy (1).

CONCLUSION

There was an idea that there were not any

cases of leprosy among the native population

of Isfahan province in Iran, and the results of

the study confirmed this. In Iran, no study

has been carried out to determine the pre-

dominant clinical forms, and further studies

and research in this area are required.

Acknowledgment. We are very grateful to health

workers in the Leprosy Registration Center in Isfahan

who helped us a lot.

—A. Asilian1, Professor, Dermatology,

—G. Faghihi, Assistant Professor

Dermatology,

—A. Momeni, M.D. Dermatology,

—M. R. Radan, M.D., General Practitioner

—M. Meghdadi, Professor

Dermatology,

—F. Shariati, Assistant Professor

Dermatology

1Reprint requests to: A. Asilian, Depart-

ment of Dermatology, Alzahra Hospital,

Mail Box 897, Isfahan University School of

Medicine, Isfahan, Iran.

E-mail 1: g_faghihi@med.mui.ac.ir

E-mail 2: yaldarad22@yahoo.com

Page 45

In this issue of the JOURNAL, Hussein and

colleagues report data from a long term

seroprevalence study to evaluate the associ-

ation of HIV infection and leprosy among

patients seen at their clinic in Agra, India

(8). In the period from 1989 to 1993, 5 of

4025 leprosy patients (0.12%) were HIV

positive, whereas in the period from 1999

to 2004, 5 of 2125 (0.38%) were HIV posi-

tive. This increase is not significant despite

the apparent major increase in HIV infec-

tions among subjects screened at the same

clinic. In 2004, among 387 persons who

were “voluntarily” screened at their request,

the HIV prevalence was 40.3%, and it was

43.4% among 106 persons referred for

screening (8). From this it appears that the

prevalence of HIV infection has not in-

creased in patients with leprosy despite ev-

idence of a substantial HIV epidemic

among the population served by the clinic.

So why hasn’t the HIV prevalence in-

creased in a comparable fashion among lep-

rosy patients? Are they resistant or immune

to HIV infection? In the past few years some

individuals have been identified who are im-

mune to HIV infection despite repeated ex-

posure to the virus. One such group are per-

sons who are homozygous for a 32 base pair

deletion in the CCR5 gene that renders them

completely resistant to infection with HIV-1

viruses that require attachment to the CCR5

co-receptor to enter the target CD4+ lym-

phocyte and replicate (3, 11). Individuals who

are heterozygous for the CCR5 deletion are

partially resistant to HIV-1 infection and

progress more slowly after infection (14).

Also persons with genetic mutations in the

CCR2 and SDF-1 genes progress more

slowly after acquiring an HIV-1 infection

(16). These critically important discoveries

have had major ramifications in our under-

standing of the biology of HIV-1 infections

in humans.

Another group of individuals who are par-

tially resistant to HIV-1 infection are those

who are heterozygous for HLA alleles (9).

Also, subjects who are heterozygous for

HLA-B or DR alleles when compared to

their HIV-1 positive sex partner appear to be

less readily infected than persons who are

homozygous with their partner for these ge-

netic loci. However, this resistance to trans-

mission is only relative, not absolute like

homozygozity for the 32 base pair deletion

in the CCR5 receptor (3, 6).

In addition, some patients appear to ac-

quire relative resistance to HIV infection or

progression of HIV. Persons who are co-

infected with GB virus C, a retrovirus that

also infects macrophages and lymphocytes,

appear to have slower progression of HIV,

and lower HIV viral loads during their GB

virus viremia, which is often chronic (7, 19, 20).

Whether or not they are resistant to HIV-1

transmission, as well, has not been deter-

mined. Other infections, which have been

reported to slow or delay the progression of

HIV, and decrease the HIV-1 viral load in

infected individuals, include scrub typhus

(O. tsutsugamushi), Dengue, and measles

(13, 17, 15). The proposed mechanism for the

negative interaction between these infec-

tions and HIV-1 also involve the CCR5 co-

receptor, which is also the receptor for the

Beta chemokines, MIP-1 alpha, MIP-1 beta,

SDF-1 and RANTES. These chemokines

regulate the immune response and attach to

receptors on CD4+ lymphocytes blocking

the ability of HIV-1 to attach to and enter

CD4+ lymphocytes to produce more viral

copies.

Could M. leprae infection also interfere

with HIV-1 attachment and entry into CD4+

lymphocytes by attaching to the chemokine

receptor? This seems very doubtful for a

number of reasons. Whereas untreated pa-

tients with polar or borderline lepromatous

COMMENTARY

Leprosy and HIV Infection

(Rarely the Twain Shall Meet?)

131

INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 2

Printed in the U.S.A.

(ISSN 0148-916X)

Page 46

132

International Journal of Leprosy

2005

leprosy may have high levels of bacteremia,

mid-borderline or tuberculoid patients do

not. Chemokines are often increased as an

acute phase reaction to a systemic infection.

But this is probably not characteristic of lep-

rosy patients. However, I am not aware that a

systematic study of chemokine levels in un-

treated leprosy patients has been done. If not,

it might provide some useful information.

It seems much more likely that the low

rates of HIV-1 co-infection in leprosy pa-

tients living in HIV-endemic areas in Africa

and Asia, which have been reported in sev-

eral studies (1, 4, 10, 12, 15), can be best ex-

plained on the basis of the epidemiology of

the two infections. Clearly, tuberculosis and

Mycobacterium avium complex infections

have increased dramatically in areas having

major AIDS epidemics. Indeed, both of

these mycobacterial infections can be clas-

sified as “AIDS-related opportunistic infec-

tions.” In fact, worldwide the major cause

of death among AIDS patients is tuberculo-

sis, so it is the most important opportunistic

infection in AIDS patients globally.

Why is leprosy so different? Despite the

pandemic of AIDS with over 40 million

people infected and living with HIV/AIDS

and over 30 million deaths, the virus is quite

difficult to transmit. It requires sexual con-

tact or parenteral exposure through injection

drug use or a transfusion, or perinatal trans-

mission from an infected mother to her in-

fant. Even sexual transmission through un-

protected sex is quite inefficient, varying

from a transmission rate of 2 to 3/1,000

episodes of unprotected sexual intercourse

in the absence of an active STD to as high as

5 to 6/100 such exposures when one or both

partners have an active STD. Injection drug

use may be somewhat more effective in

transmitting HIV-1 but the prevalence rates

are seldom above 25% to 50% among daily

injectors in a city with an active AIDS epi-

demic.

Although many seroprevalence studies of

HIV-1 infection have been reported among

leprosy patients in several African countries

experiencing major HIV/AIDS epidemics

(1, 4, 10, 12, 15), these studies have not been ac-

companied by behavioral data, so that one

cannot gauge whether the patient population

studied was actually exposed to a source of

HIV-1 infection or how frequently exposure

had occurred. Since HIV-1 is not casually

transmitted, the HIV-1 prevalence in the

area where the leprosy patients are being

treated is somewhat irrelevant. It would be

important for a leprosy researcher working

in an AIDS endemic area to screen the sex

partners of the leprosy patients for HIV to

determine whether the leprosy patients have

actually been exposed or how many have

been exposed. As far as I am aware, such

data have not been reported.

Why then is there such a major difference

between the TB/HIV co-infection rate and

the leprosy/HIV co-infection rate in AIDS

epidemic areas. Clearly the data suggest that

a much higher proportion of the population

has a latent tuberculosis infection than has a

latent or incubating an infection with M.

leprae. Tuberculin skin test surveys suggest

that 30% of the world’s population, or about

1 billion persons, have a latent tuberculosis

infection. When a major HIV epidemic in-

fects a population, the rates of TB reactiva-

tion increase dramatically as cellular immu-

nity is abrogated by the HIV-1 infection. In

addition, an HIV-1 infected person who ac-

quires a new M. tuberculosis infection has a

30 to 40% chance of developing clinical tu-

berculosis within a year or two of infection

with M. tuberculosis, compared to a 5%

chance of active tuberculosis in an HIV-1

uninfected person.

It seems very likely that latent M. leprae

infections are not too common, even in en-

demic countries. Many such latent M. leprae

infections may have been suppressed, or per-

haps cured, with exposure to antibiotics like

Rifampin, a Macrolide antibiotic or to BCG.

So when a person develops an HIV-1 infec-

tion in these countries, leprosy does not fol-

low. These ideas are only speculation. It is

not possible to reliably measure latent M.

leprae as effectively as latent TB can be di-

agnosed using the tuberculin test. Some in-

vestigators have tested for phenolic glycol-

ipid-1 in sera from HIV-1 infected persons

and controls to estimate the prevalence of M.

leprae infection (5). One intriguing study

from Cuba found that 14.9% of 437 HIV in-

fected patients compared to 1.3% of blood

donors had antibodies to PGL-1 (5). How-

ever, this test may not be completely specific

in HIV-1 infected persons. The specificity

could be studied by testing sera from HIV

positive population in which leprosy is rare

or absent. Furthermore, a positive PGL-1

Page 47

73, 2

Commentary

133

antibody test may not indicate an active M.

leprae infection compared to a previous in-

fection that has been cured. Clearly, newer

methods are needed to detect latent M. lep-

rae infections. Such data together with care-

ful epidemiological studies of the rates of

exposure to HIV-1 among leprosy patients

might clarify why leprosy seems not to be

an AIDS-related opportunistic infection or

whether leprosy patients are relatively resis-

tant to HIV-1 infection.

—Kenrad E. Nelson, M.D., Professor

Departments of Epidemiology,

International Health and Medicine

Johns Hopkins University

Bloomberg School of Public Health and

School of Medicine

Baltimore, Maryland 21205, USA

E-mail: kenelson@jhsph.edu

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Page 49

A recent study conducted in Vietnam and

Brazil revealed a significant association of

leprosy susceptibility with the Parkinson´s

disease (PD) gene PARK2 and PARKG.

Variants in the regulatory region shared by

these genes turned out to be a major risk

factor for leprosy (9). Although the mutation

of the PARK2 (Parkin) gene responsible for

familial early onset of PD is not identical

with the nucleotide polymorphism found in

leprosy patients, it is not surprising that

malfunction of a central enzyme results in

disease or enhanced disease susceptibility.

Parkin is a ubiquitin-protein ligase that

controls—together with other ubiquitin-

conjugating enzymes—the degradation of

proteins by proteasomes. In the last years, it

became clear that the ubiquitin-proteasome

complex is a hot topic in biological science,

because a breakdown of this central catabolic

system is associated with severe human dis-

eases, including neurological disorders, in-

flammation, cancer, and susceptibility of in-

fection.

Proteasomes are the enzymatic heart

of the cells. Protein synthesis and degrada-

tion are metabolic processes equally essen-

tial for prokaryotic and eukaryotic cells. As

for the catalytic pathway, lysosomes and

proteasomes are two major proteolytic ma-

chineries that are involved in protein degra-

dation. While extracellular and cell-surface

membrane proteins are mainly targeted to

lysosomes, the vast majority of cytoplasmic

proteins are degraded by proteasomes.

The enzymatic activity of proteasomes is

strictly regulated and acts in concert with

the ubiquitin pathway, which primarily tags

proteins for degradation (1). Proteasomes

are found in archaebacteria, some eubacte-

ria (e.g., Actiomycetes) and eukaryotes.

While their role in prokaryotes is not fully

understood, they perform multiple func-

tions in eukaryotic cells: degradation of

damaged and abnormal proteins into small

peptides and processing of proteins thereby

yielding proteins of different biological ac-

tivity including cell-cycle regulators, onco-

gens, tumor suppressors and transcription

factors. Finally, MHC class I restricted cy-

tolytic CD8+ T cells recognize peptides

from self- and non-self proteins that are

generated by proteasomes. This enables

CD8+ T cells to control for and eliminate al-

tered and infected cells. All this crucially

depends on the precise function of the

ubiquitin-proteasome system and thus, it is

not surprising that aberrations lead to

pathological reactions and disease (2).

The first step in the substrate selection for

proteasomal degradation is mediated by the

addition of poly-ubiquitin chains. This “kiss

of death” is triggered by the successive ac-

tion of several enzymes including the Ub-

activating enzyme (E1), Ub-conjugating or

carrier enzyme (E2), and Ub-protein ligase

(E3). Ubiquitin tagged proteins are then rec-

ognized and digested by the proteasome, a

multiprotein complex (10). The catalytic ac-

tive sites of the eukaryotic proteasome is

housed in a barrel shaped 20S core complex,

which is composed of 28 subunits arranged

in 4 stacked heptameric rings. The outer

rings contain the a-subunits which shape the

gates of substrate entry and product release.

The two inner rings harbor the β subunits

(β1–β7) of which the β1, β2, and β5 sub-

units are catalytically active. In contrast,

proteasomes of prokaryotes encode only

one type of α-subunit and one type of β-

subunit. Despite this difference the overall

architecture of these complexes is con-

served. It seems that in eubacteria, protea-

somes are not necessary for intracellular

proteolysis as most bacteria rely on other

cytosolic proteases for protein turnover.

COMMENTARY

Leprosy Susceptibility—A Matter of Protein Degradation?

The Role of Proteasomes in Infection and Disease

135

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International Journal of Leprosy

2005

Interestingly, the only eubacteria

known to contain proteasomes are the

family of actinomycetes to which M. tu-

berculosis and M. leprae belong. M. tuber-

culosis is unusual for a bacterium because it

lacks two proteases of the HslUV and Lon

family (3). Both mycobacteria are intracel-

lular pathogens that spend most of their life

inside cells, primarily macrophages. A re-

cent study by Darwin, et al. provides an ex-

planation of the strategy used by M. tuber-

culosis to avoid killing in the phagosome

(4). They could demonstrate that transposon

mutants with insertions in proteasome asso-

ciated genes of M. tuberculosis are highly

sensitive to reactive nitrogen intermediates

which are produced as major defense mech-

anism by infected host cells. However, the

type of damage that would target a protein

for proteasomal degradation is not well un-

derstood, yet. Perhaps modifications such

as nitrosylation are recognized by the eu-

karyotic ubiquitin-proteasome system as

suggested for proteins with oxidative dam-

age (5). Since the gene products of noxR1

and noxR3 have also been implicated in re-

sistance to nitric oxide it is unclear whether

proteasome associated mutations directly

affect the degradation of modified proteins

or whether the proteasome is needed to con-

vert precursors into active forms of noxR

proteins. Moreover, the mycobacterial pro-

teasome is essential for the refolding of pro-

teins that have been damaged by reactive

nitrogen intermediates (RNIs) as demon-

strated in vitro.

The coevolution of host cells and

pathogens involves also the ubiqutin-

proteasome system. Many viruses need the

ubiqutin-proteasome in order to form cor-

rect virus particles (Ros), express compo-

nents of this system as virulence factor

(ubiquitin ligase) (6), or modulate the pro-

teasomal activity by directly interacting

with defined proteasome subunits (7). On the

other hand the ubiquitin-proteasome system

is also crucial for infected host cells to fight

against invaders by processing and present-

ing their antigens to cytolytic T cells (8).

At first glance this seems to be paradoxical

but taking into account that the ubiquitin-

proteasome pathway acts on proteins, a cen-

tral component of life, it adds up that this

system evolved and is used beyond the bar-

rier of species and even different phyli.

CONCLUSION

The ubiquitin-proteasome system plays a

key role in a broad array of basic cellular

processes with protein quality control as

central function. Loss or impairment of this

function is associated with many different

types of diseases. Although we currently do

not understand the molecular mechanisms

of mutated PARK2 and PACRG and en-

hanced susceptibility to leprosy, it is inter-

esting to note that PD and leprosy are dis-

eases that both affect the nervous system

which seems to be extremely sensitive to

aberrations in the ubiquitin-proteasome sys-

tem. Although accumulation of ubiquitin

conjugates and/or inclusion bodies is char-

acteristic for many neurodegenerative dis-

eases, a firm and direct pathogenetic linkage

to aberrations in the ubiquitin-proteasome

system has not been established yet. So far,

we can only speculate how mutations in

PARK genes relate to leprosy susceptibility.

Controlled degradation of proteins derived

either from the pathogen M. leprae or in-

fected host cells might be fundamental for

the integrity of infected cells as well as in-

duction of immunity against leprosy. As

consequence, the failure of ubiquitination

may result in accumulation of toxic proteins

in highly sensitive nerve cells which, once

damaged, cause paralysis and disfiguration

typical for leprosy patients.

—Ulrich Steinhoff

—Alexander Visekruna

Max-Planck Institute of Infection Biology,

Berlin, Germany

Reprint request to: Ulrich Steinhoff, Max-

Planck Institute of Infection Biology, Schu-

mannstr. 21/22, 10117 Berlin, Germany.

E-mail: steinhoff@mpiib-berlin.mpg.de

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73, 2

Commentary

137

Page 52

Prof. Diltor V. A. Opromolla passed away

last December, 2004 at age 70. He studied

medicine at the Pontifical Catholic Univer-

sity of São Paulo where he graduated in

1957, and took his Ph.D. in dermatology in

1973 at the University of São Paulo (USP).

Soon after, he started his studies on leprosy

at the State Department of Leprosy Prophy-

laxis where he met two other important

names in Brazilian leprology, Dr. Abraham

Rotberg and Luiz Marino Bechelli. In 1958,

Prof. Opromolla moved to Bauru where he

joined government health services as a lep-

rologist in the local leprosarium, which

later become the Instituto Lauro de Souza

Lima. He soon started to approach patients

with a wide view, including, at that time,

prevention of disabilities. Apart from the

standard treatment, Prof. Opromolla had a

particular concern for disabilities, and he in-

augurated a special clinic named “The

Healthy Foot Room” where patients could

have full examination of feet, treatment of

foot ulcers and talks on prevention of ulcers

and self-care. It was a tremendous success

and the “room” was further expanded in the

late 1970s with the visit of Prof. Arvello,

from Venezuela, who was introducing the

concept of prevention of disabilities by

simple techniques in the Americas. The visit

of Dr. Arvello and the commitment of Prof.

Opromolla was the beginning of a deep

modification in the institution and how it re-

gards P.O.D. and rehabilitation for leprosy-

affected persons. In the clinical side, Prof.

Opromolla was introducing new drug treat-

ments and led the studies on the use of ri-

fampicin in the treatment of leprosy. At that

period, compulsory internation was discon-

tinued in Brazil and the old leprosarium

was becoming an unstable institution. One

of the outstanding contributions of Prof.

Opromolla was to make a clear diagnosis of

this situation and to lead a group of doctors

and scientist to transform the old leprosar-

ium of Bauru in to a modern and solid re-

search and training institution. He suc-

ceeded in this regard. Today Instituto Lauro

de Souza Lima is a leading institution in

leprosy in Brazil and is acknowledged in

the international community. The scientific

production and the massive number of

trainees each year earned the Institute the

position of Leprosy National Referral Cen-

ter for the Ministry of Health and for the

World Health Organization—and this is a

concrete result of the continuous and dedi-

cated work of Prof. Opromolla and his abili-

ties to gather people of different areas to

form a real multidisciplinary institution to

serve leprosy-affected persons. He served

also as consultant leprologist for the Min-

istry of Health and was a leading member of

the W.H.O. Leprosy Expert Committee for

several years. Prof. Opromolla took as his re-

sponsibility the renovation and up-dating of

Hansenologia Internationalis, the only regu-

lar leprosy periodical published in the Amer-

icas, serving as editor from 1989 until his

death. He fought hard to improve the quality

of the published articles, to produce bilingual

issues and to obtain funds to publish and dis-

tribute the journal. His personal scientific

production was remarkable, with more than

200 articles published and several chapters

in books, apart from his own book on clini-

cal leprosy. One of his personal prides in this

field was the invitation to write the preface to

the 2nd edition of Hastings’Leprosy.

OBITUARY

DILTOR VLADMIR ARAUJO OPROMOLLA

1934–2004

138

INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 2

Printed in the U.S.A.

(ISSN 0148-916X)

Page 53

In April 2004, he was compulsorily re-

tired as he reached 70 years of age, but he

kept the same routine at the Institute, partic-

ipating in the clinical rounds, lecturing, and

actively attending scientific meetings. Al-

though fragile due to the illness that took

him, he continued to accept engagements

on behalf of leprosy and leprosy-affected

persons. A few days before his death he was

visiting Rio Branco, in the State of Acre, to

discuss further research on Lobos’s Dis-

ease. It was also opportune that, just one

month before his death, the Ministry of

Health awarded him one of the top prizes in

the field of public health in Brazil.

One week after his death, a ceremony

was held in the Saint Judas Thadeu Church

in Bauru, which was packed with those who

had known or worked with Prof. Opro-

molla. It was an opportunity to remember

again past experiences. It was also a mov-

ing occasion and a celebration of his work

and life in the cause of science and the

leprosy-affected person.

—Marcos Virmond, M.D., Ph.D.

73, 2

Obituary

139

Page 54

AFRICAN LEPROSY CONGRESS

Scientific Program1

Eskom Convention Center,

Johannesburg (Midrand), South Africa

31 January to 3 February 2005

140

INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 2

Printed in the U.S.A.

(ISSN 0148-916X)

1The list of Congress attendees will be posted on the

ILA web-site, and keynote presentations will be

published in subsequent issues of the JOURNAL.

Opening Ceremony.

Dignitaries participating in the Opening

Ceremonies included:

Dr. Manto Tshabalala-Msimang, Minister

of Health, Republic of South Africa

Dr. Asomou Baah, Assistant Secretary

General, W.H.O

Mr. Yohei Sasakawa, W.H.O. Goodwill

Ambassador for the Elimination of Leprosy

Dr Antoine Kaboré, Director of Commu-

nicable Diseases, W.H.O, AFRO

Dr. Bide Landry, Regional Advisor, Africa,

W.H.O Leprosy Elimination Program

Dr. Gopal, President, IDEA

Dr. Deepack, President of ILEP

Dr. Noordeen, President of ILA

Page 55

Remarks on the opening of the Congress.

Dr. Manto Tshabalala-Msimang.

Minister of Health, Republic of South

Africa

It is a great pleasure for me to welcome

you to South Africa for this second confer-

ence of the International Leprosy Associa-

tion to be held on the African continent.

This Congress coincides with the celebra-

tion of the World Leprosy Day. The World

Leprosy Day was founded by Count Raoul

Follereau, who was deeply involved in the

fight against leprosy, particularly in Africa.

Count Follereau campaigned to reverse the

negative images associated with leprosy, as

did Mahatma Gandhi. The ideals of Gandhi

and his willingness to personally care for

people affected by leprosy did much to

change public perceptions of this disease.

One cannot think of leprosy without being re-

minded of banishment and exile. Of course in

the South African context, the prison of

Robben Island comes to mind. Robben Island

was for about 80 years a home to leprosy pa-

tients before it was made a prison that is now

synonymous with the triumph of human

rights and freedom. I am delighted that many

of you will be visiting Robben Island after

this congress and that you will have the op-

portunity to see this place that is of historical

significant to the ideals of freedom and de-

mocracy in this country and across the world.

Great strides have been made against lep-

rosy in Africa and the rest of the world since

the first meeting of the International Leprosy

Association was held on the African soil in

Cairo in 1938.

Leprosy treatment has developed signifi-

cantly during the past decades. We are espe-

cially proud that African researchers have

played a leading role in developing new

interventions against this disease. We in

Africa can also boast of our own leprosy

research facility, namely ALERT based in

Addis Ababa. We can mention Davey’s tri-

als with oral Dapsone in 1948 in Nigeria,

Browne’s introduction of clofazamine in

1960 in Nigeria and the vaccine trials of

Karonga in Malawi in the 1980s as just

three of the many significant investigations

into leprosy that have taken place in Africa.

These studies have made a global contribu-

tion to the armory against leprosy.

We have seen many successes in the fight

against leprosy in Africa. These have been

due to developments such as the introduc-

tion of multi-drug therapy and the very high

success rates associated with it. The simpli-

fication of various procedures has enabled

workers with limited skills to undertake

leprosy work successfully and civil society

participation in the efforts against leprosy

has improved significantly.

African countries have demonstrated de-

termination to work towards the elimination

of leprosy as defined in the resolution of the

World Health Assembly of 1991 and signif-

icant progress is being made towards the re-

alization of this goal.

In South Africa we are proud of the con-

tribution made by our specialists who have

published their findings in the International

Journal of Leprosy and Other Mycobacte-

rial Diseases and Leprosy Review. Their

work should contribute in enhancing the

knowledge of the international health com-

munity charged with the treatment of lep-

rosy. I am pleased that at this Congress you

will be hearing a presentation by one of our

dermatologists on South Africa’s experi-

ence in providing leprosy treatment at a

general hospital following the closure of the

last of our specialized leprosy facilities.

Until 1977, hospitalization for leprosy

treatment was compulsory in South Africa.

FIG. 1. Opening Ceremonies: front, from left: Dr.

Sunil Deepak, President, ILEP; Mr. Yohei Sasakawa,

W.H.O. Goodwill Ambassador for the Elimination of

Leprosy; Dr. Manto Tshabalala-Msimang, Minister of

Health, Republic of South Africa; Dr. S. K. Noordeen,

President, International Leprosy Association. Rear,

Ms. Hoshino, translator.

73, 2

News and Notes

141

“. . . much needs to be done to ensure

that leprosy patients benefit fully from

the advances in treatment seen in recent

years”

Page 56

142

International Journal of Leprosy

2005

Specialized leprosy institutions began to close

during the 1980s and in 1997, the remaining

institution, Westfort Hospital, was closed.

We are pleased that leprosy has been re-

duced to very low levels in South Africa.

About 50 new patients are detected each

year. However, 40% of our newly diagnosed

patients suffer from Grade 2 (W.H.O.) dis-

abilities. This indicates that a large percent-

age of our patients are only being diagnosed

after having suffered from the disease for

some time. There are about 160 patients

that are registered for treatment. At least

3000 people have disabilities related to lep-

rosy amongst the economically active age

groups in the country.

Despite the fact that new patient detection

levels have reached very low numbers as

both a percentage of the population and in ab-

solute numbers, we are intensifying the im-

plementation of our leprosy control policy.

The goal of the leprosy program is to de-

crease the current prevalence of leprosy in

order to work toward the eradication of lep-

rosy. The objectives of the program are to:

“Develop standard guidelines for the early

diagnosis and management of patients

“Prevent disability and rehabilitate dis-

abled patients

“Establish a central register and measure

treatment outcomes

“Ensure that there is at least one medical

doctor with leprosy expertise in each

teaching hospital to which leprosy pa-

tients can be referred

“Ensure that early diagnosis of leprosy is

included in the PHC training material

of health professionals.”

Our aims are to:

“Increase awareness of the continuing

existence of leprosy

“Promote the early treatment of patients

with multi-drug therapy

“Promote community involvement in

case detection

“Ensure that that multi-drug blister packs

are made available at the treatment

points used by leprosy patients

“Improve the knowledge of health staff

supervising leprosy treatment to enable

them to help patients and avoid disabil-

ities.”

In South Africa, leprosy treatment has

come a long way, from the darkness and iso-

lation of Robben Island to the bustle of PHC

clinics in our modern facilities. However,

we acknowledge that much needs to be done

to ensure that leprosy patients benefit fully

form the advances in treatment seen in re-

cent years.

This conference provides us with a oppor-

tunity to celebrate the progress that has al-

ready been made on our continent towards

providing treatment for all patients. It also

reminds us of many patients who have not

yet received treatment and the many people

who have had leprosy and who suffer from

disabilities. All these people need our help.

We have an excellent opportunity here of

learning from each other. I am particularly

pleased to see that the conference program

has sessions dealing with “reaching the Un-

reached” and “Community Based Rehabili-

tation” which should facilitate the sharing of

best practices.

FIG. 3. Delegates in plenary Session.

FIG. 2. Opening Ceremonies: Presentation of

Banners of Honor by IDEA delegates.

Page 57

73, 2

News and Notes

143

Most of you have had first hand experi-

ence of the harsh attitudes towards this ill-

ness. We all have an important role to play

in changing perceptions of leprosy and pro-

moting the rights of leprosy patients. I am

glad that this congress will also discuss the

factors that impact on our interventions

against this disease.

Many of you work in difficult conditions,

providing care for your patients in innova-

tive ways and for that I salute you. I wish

you well during this congress and trust that

you will be able to return to your work-

areas refreshed with a deeper understanding

of leprosy and better equipped to serve

those whose health depend on you.

It is my pleasure to declare the African

Leprosy Congress of 2005 open.

Docteur Antoine B. Kaboré,

Directeur Régional de l’OMS pour l’Afrique

Le Docteur Luís Gomes Sambo, le nou-

veau Directeur régional de l’OMS pour

l’Afrique, aurait souhaité être en personne

parmi vous à ce congrès qu’il qualifie lui-

même d’historique parce que:

(i) c’est le premier congrès de l’Association

Internationale de la lèpre (ILA) dans un

pays de la Région africaine de l’OMS,

(ii)le congrès a lieu en 2005, terme fixé

pour l’élimination de la lèpre en tant

que problème de santé publique au

niveau national dans tous les pays,

Malheureusement, ce congrès coïncide avec

sa prise de fonction. Il a dû se résigner à

nous désigner pour le représenter et vous

transmettre son message.

En son nom, je voudrais tout d’abord re-

mercier le Gouvernement de l’Afrique du

Sud et en particulier le Président de la

République et La Ministre de la Santé pour

toutes les facilités qu’ils ont offertes pour

que ce congrès soit une réussite. Nous con-

naissons l’hospitalité légendaire de l’Afrique

du Sud et nous sommes émerveillés par la

qualité de l’organisation et la disponibilité

de nos frères sud-africains chaque fois que

nous avons l’occasion de participer à une

réunion dans ce beau et grand pays.

Je voudrais remercier tous les respons-

ables de l’Association Internationale de la

Lèpre pour les efforts qu’ils ont consenti

pour organiser ce congrès en Afrique car, de

mémoire, il s’agit des premières assises sur

le continent.

Je voudrais aussi remercier toutes les

organisations non gouvernementales re-

groupées ou non au sein de la Fédération

Internationale des Associations contre la

Lèpre (ILEP) pour leur dévouement à la

cause des malades de la lèpre et pour tous

les efforts qu’ils ne cessent de déployer

pour faire de l’élimination de la lèpre une

réalité visible en Afrique.

Enfin, je voudrais remercier tous les par-

ticipants à ce congrès pour leur implication

dans les programmes d’élimination de la

lèpre et leur contribution à l’organisation de

la lutte contre la lèpre dans la Région

africaine de l’OMS.

(Résultat des programmes d’élimina-

tion de la lèpre). Grâce à vous tous, le pro-

gramme d’élimination de la lèpre est un des

programmes les plus réussis de la Région.

La détermination des pays à combattre la

lèpre a été la clé de tous les succès que nous

avons eus. Grâce à l’engagement politique

au plus haut niveau des Etats membres, et

grâce au dynamisme des responsables na-

tionaux, la lèpre a été considérée comme

une priorité nationale et les services de

santé se sont focalisés sur les activités

d’élimination. Ainsi, plus d’un million et

demi de cas de lèpre ont été détectés et

guéris dans la Région au cours des dix

dernières années. L’importance de la mal-

adie a été considérablement réduite. La pré-

valence est passée de 1.500.000 malades en

1990 à 45.000 en 2003. L’élimination de la

lèpre a été réalisée au niveau régional où le

taux de prévalence est actuellement à 0,80

cas pour 10 000 habitants. Dans les pays, la

FIG. 4. Mr. Yohei Sasakawa (L) and Dr. Gopal,

President, IDEA.

Page 58

144

International Journal of Leprosy

2005

situation s’est inversée. En 1990, nous

avions 42 pays très endémiques dans la Ré-

gion. Aujourd’hui seuls trois pays présen-

tent la lèpre comme un problème de santé

publique majeur et je peux vous assurer que

ces pays sont à pied d’œuvre pour atteindre

le seuil de l’élimination de la lèpre.

(Résumé de l’histoire de l’élimination

de la lèpre). Qui pouvait croire en un tel

succès?

La découverte de la Dapsone dans les an-

nées 40 avait suscité un vif espoir de vain-

cre la maladie, mais l’apparition des résis-

tances dans les années 60 avait vite fait de

transformer cet espoir en rêve.

Avec l’adoption de la polychimiothérapie

dans les années 80, l’espoir renaissait de

nouveau mais les doutes persistaient dans

les esprits face à l’expérience de la Dap-

sone. En 1991, lorsque l’Assemblée mondi-

ale prenait la résolution d’éliminer la lèpre

(Résolution WHA44.9), nombres de parte-

naires n’y croyaient pas vraiment. Aujour-

d’hui, grâce aux efforts déployés par tous

les pays et l’enthousiasme que l’élimination

de la lèpre a suscité dans le monde, cette ré-

solution s’est traduite en réalité.

Dans la Région africaine de l’OMS, la

couverture géographique des services de

santé par la poly chimiothérapie anti-lèpre

(PCT) est à plus de 90% au niveau des dis-

tricts sanitaires et dans tous les pays. La qual-

ité de la prise en charge des cas de lèpre a été

nettement améliorée et les taux de guérison

sont supérieurs à 85%. L’intégration du

dépistage et du traitement de la lèpre dans

les soins de santé primaires se poursuit et

rassure sur la pérennisation des activités.

Dans tous les pays de la Région, la décentral-

isation du diagnostic et du traitement est dev-

enue effective. La souplesse introduite dans

le traitement des malades a été un moyen

pratique et opérationnel pour assurer leur

régularité au traitement et améliorer les taux

de guérison. D’un pays à un autre, cette sou-

plesse dans le traitement varie selon les réal-

ités locales et l’organisation en place. Elle

va de la prise mensuelle sous le contrôle de

l’agent de santé à la remise de tout le traite-

ment au malade ou à sa famille pour en as-

sumer la responsabilité. Elle a permis au

cours des campagnes lèpre dans les villages

d’améliorer le taux de complétion des traite-

ments qui est actuellement supérieur à 85%.

Au-delà de la souplesse dans la délivrance

des traitements, c’est surtout à la mise en

œuvre de la stratégie d’élimination de la

lèpre que nous devons tous les succès enreg-

istrés. Ses principaux éléments tels :

• le renforcement de l’accessibilité géo-

graphique, financière et culturelle des

services de diagnostic et de traitement

la lèpre,

• la disponibilité des médicaments et la

gratuité des traitements pour les malades,

• la mobilisation sociale en faveur de

l’élimination de la lèpre,

• la prise en charge précoce et correcte

des malades,

• le suivi régulier des programmes et la

mise en œuvre rapide des interventions

correctrices,

• l’organisation des activités de soutien

telles la formation, la supervision régu-

lière et la sensibilisation des populations.

ont été extrêmement utiles pour l’atteint des

résultats.

Je voudrais ici remercier les responsables

des programmes nationaux d’élimination de

la lèpre, les membres du groupe de l’Al-

liance mondiale pour l’élimination de la

lèpre et tous les partenaires qui ont con-

tribué à ce succès, plus particulièrement la

Nippon Fondation et Sasakawa Memorial

Health fondation, la fondation Novartis

pour un développement durable, l’Agence

internationale danoise de développement

(DANIDA), la Banque mondiale et toutes

les Organisations Non Gouvernementales

membres de la Fédération internationale

des associations contre la lèpre (l’ILEP).

(Défis actuels). Malgré les efforts dé-

ployés et en dépit des bons résultats

obtenus, l’élimination de la lèpre est encore

fragile et beaucoup de choses restent à faire

pour la consolider à tous les niveaux: ré-

gional, national, intermédiaire et district

dans les pays.

• Plusieurs pays vacillent encore autour

du seuil de l’élimination et d’une année

à une autre, se retrouvent tantôt en

deçà, tantôt au-delà du seuil d’un cas

pour 10.000 habitants.

• Plusieurs pays ont des districts encore

très endémiques à cause du stigmate de

la maladie, du manque d’information et

Page 59

73, 2

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145

de l’absence des services de prise en

charge des cas.

• La détection est encore élevée. Plus de

40.000 nouveaux cas sont dépistés

chaque année. Cette détection témoigne

du succès des campagnes et des projets

d’action spéciale. Elle constitue aussi

un indicateur de la persistance de la

transmission de la maladie dans les

communautés.

• Le stigmate social de la lèpre est encore

présent. La maladie continue de faire

peur et les malades sont toujours vic-

times de rejet que seule l’ignorance jus-

tifie. C’est dire que dans le domaine de

l’information et de la sensibilisation sur

la lèpre, nous avons encore beaucoup à

faire. La réhabilitation sociale des

malades et leur intégration dans les com-

munautés doivent se poursuivre en col-

laboration avec les autres secteurs.

Nous savons tous que la Région africaine

est à un tournant critique de son histoire. Les

défis qu’elle doit relever sont nombreux. La

pauvreté et la misère persistantes dans les

populations nous préoccupent. Les maladies

émergentes et ré-émergentes s’ajoutent aux

épidémies et ne facilitent pas le développe-

ment harmonieux des programmes de santé.

En dépit de ces conditions difficiles et de la

précarité des services de santé, les Etats

africains ont engagé des efforts pour élim-

iner la lèpre. Nous devons les encourager à

poursuivre cet engagement et à maintenir la

lèpre dans la liste des priorités nationales des

services de santé.

Face aux défis actuels, la responsabilité

des pays et surtout des programmes na-

tionaux est grande. Sans une volonté na-

tionale, rien ne peut se faire. La responsabil-

ité du bureau régional de l’OMS pour

l’Afrique est aussi importante mais elle est

conditionnée par la détermination des pays.

Toutefois, l’OMS poursuivra ses efforts pour

aider les pays à s’approprier les programmes,

assurer la pérennisation des activités et

obtenir plus de résultats en espérant que nous

réaliserons un monde sans lèpre. Pour y par-

venir, les partenaires doivent aussi tout met-

tre en œuvre pour poursuivre leurs appuis fi-

nanciers et logistiques aux programmes.

(Orientations futures et perspectives).

Tous, ici présents à ce congrès, nous savons

que la mise en œuvre de la stratégie d’élim-

ination de la lèpre a été faite dans un climat

difficile où l’absence de définition claire des

rôles et des responsabilités entre les parte-

naires ainsi que l’absence d’un mécanisme

efficace de coordination n’ont pas facilité la

collaboration. Cette situation n’a pas permis

aux pays de bénéficier pleinement de l’appui

que nous devions leur apporter.

Dans l’intérêt des nations et au regard de

nos engagements, nous invitons toutes les

structures et les organismes (scientifiques,

responsables de programmes, partenaires

publics et privés, Organisations non gou-

vernementales nationale et internationale

passionnés par la cause des malades de la

lèpre) à tourner la page et regarder vers

l’horizon sous un angle d’espérance et avec

une volonté d’ouverture pour une améliora-

tion de la collaboration et de la coordination

des interventions dans les pays. Nous pen-

sons qu’il s’agit là d’une condition essen-

tielle pour réaliser un monde sans lèpre.

L’OMS poursuivra ses efforts. Une nou-

velle stratégie qui prendra en compte la

situation épidémiologique actuelle dans

laquelle la lèpre devient de plus en plus rare

sera proposée. La contribution de tous les

partenaires à l’élaboration de cette stratégie

permettra de mettre en place le cadre et les

conditions d’une meilleure collaboration.

Dans cette nouvelle stratégie qui sera essen-

tiellement orientée vers la consolidation des

acquis des programmes nationaux, la prior-

ité au niveau inter-pays et régional sera le

renforcement de la coordination et de la col-

laboration entre les partenaires. La création

d’un cadre de concertation pour retrouver

l’harmonie tant nécessaire au bon déroule-

ment des programmes nationaux occupera

une place prépondérante. J’ai la ferme con-

viction que nous aurons l’adhésion de tous.

Je finirai mon propos en vous rassurant

une fois encore que dans le cadre du rôle

que les Etats membres ont confié au Bureau

régional l’OMS, l’Organisation s’engage à

poursuivre son appui aux pays pour l’élim-

ination de la lèpre.

Je souhaite beaucoup de succès à votre

congrès et vous remercie pour votre attention.

Page 60

146

International Journal of Leprosy

2005

Mr. Yohei Sasakawa,

W.H.O. Goodwill Ambassador for the Elim-

ination of Leprosy.

I would like to begin by expressing my

sincere gratitude to Her Excellency Dr. Man-

tombazana Tshabalala-Msimang, Minister of

Health of the Republic of South Africa, for

opening this Congress with such a wonderful

song. I also had the opportunity to speak

with her before the meeting. I was highly en-

couraged to hear from her that, although the

issue of leprosy has not been addressed ex-

tensively so far during her term, she realized

that there is a need to do more to inform the

media and general public about the disease,

and that she would do her best to adjust her

schedule so that she can attend the upcoming

workshop on Robben Island.

This Congress has been organized by ILA

under the leadership of Dr. Noordeen, who

always been at the forefront of the medical

battle against leprosy. The results he has

achieved to date have been outstanding. I

would like to express my deepest admira-

tion for Dr. Noordeen for bringing together

here today a diverse group of people from

ILA, ILEP, IDEA and other organizations

dedicated to the battle against leprosy, as

well as program managers and field workers

from many of Africa’s English-, French- and

Portuguese-speaking countries. I firmly be-

lieve that we are all gathered for a common

purpose: to create a world free of leprosy

and a world free of discrimination.

As you know, W.H.O. has been working

toward the goal of reducing the prevalence

rate of leprosy to less than one case in

10,000 people in every country in the world

by the end of 2005. Drugs have been made

available free of charge everywhere in the

world in hopes of achieving this. While the

achievement of this goal will by no means

mark the end of the battle against leprosy,

there is no doubt that it is a very important

milestone, and one that I hope we will all

work for together.

Before arriving in South Africa, I visited

India, where I was heartened by the steady

progress being made toward elimination,

which has seen the prevalence rate come

down to 1.98. I am confident that India will

achieve elimination by the end of 2005.

Following India’s example, I believe that it

is important to set specific goals, and set

them high.

Fortunately, thanks to the concerted ef-

forts of individuals and organizations

around the world, we have come a long way

in the medical battle against leprosy. Since

the 1980s, 14 million people have been lib-

erated from the disease. As W.H.O. Good-

will Ambassador for Leprosy Elimination, I

have been traveling the world to spread cor-

rect knowledge about the disease, repeating

our three simple but important messages

tens of thousands of times: Leprosy is cur-

able. Free treatment is available. Social dis-

crimination has no place.

Unfortunately, these messages have yet

to reach many people. We need to do more.

Although the medical battle against lep-

rosy is progressing smoothly, there is an-

other important question that we must face.

That is the question whether the 14 million

people who have been cured of leprosy have

been able to assimilate back into society in

the way that people cured of other diseases

such as tuberculosis or malaria have. I am

afraid that this has not been the case.

The medical advances that have been

made to date in the treatment of leprosy are

truly remarkable. On the other hand, deter-

mined efforts to root out discrimination and

stigma are only just beginning. Faced with

this issue, I visited the Office of United Na-

tions High Commissioner for Human Rights

for the first time two years ago. I was truly

surprised to find that such a serious human

rights issue as discrimination against people

affected by leprosy had never before been

brought before the UN Commission on Human

Rights. Together with the members of IDEA,

who are also here today, I convinced its Sub

Commission on Promotion and Protection of

Human Rights to investigate the issue, and sub-

sequently the Sub Commission unanimously

adopted to further study the state of discrimi-

nation against leprosy affected people and

their families. As a result, we are very fortu-

nate to have with us today, Prof. Yozo Yokota,

the Japanese member of the UN Sub Com-

mission on Human Rights. Prof. Yokota is

here to listen to all you have to say, so that he

can go back and share your thoughts with the

other members of the Sub Commission.

“Leprosy is curable. Free treatment is

available. Social Discrimination has no

place.”

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147

I believe that this meeting is a truly his-

toric occasion in the long history of leprosy.

It has brought together people from around

the world who have personally experienced

and overcome the disease. They have come

to share their stories, voice their opinions

and serve as partners in leprosy elimination.

Their stories are more powerful and reveal-

ing than anything I can say here at this

podium. I cannot stress enough the impor-

tant role they have to play.

I have already remarked already on the di-

versity of those present. I believe it is the in-

tention of Dr. Noordeen and his team that we

debate the issues more widely, more deeply

and more vigorously than ever. This diver-

sity also represents the best way for the three

messages — Leprosy is curable. Free treat-

ment is available. Social Discrimination has

no place —to reach as many people as possi-

ble. I hope you will join me in this effort.

Dr. Bidé Landry,

Coordonnateur régional du programme

d’élimination de la lèpre pour la Région

Africaine de l’OMS

First, I wish to thank the organizers for the

privilege of being part of this historic meet-

ing, and for the opportunity to be here to lis-

ten and to learn from men and women who

have been working in leprosy for many years.

I have always been intrigued by the devo-

tion and dedication of people working in

leprosy and I am hoping that by being asso-

ciated with you, I will also be affected with

your passion and compassion.

An uncle of mine, a Roman catholic

Bishop, many years ago educated me that to

be involved in leprosy, one must have at

least one of the three Ms. You must either be

a Missionary, a Mercenary or Mad. In my

short life, I have seen a few people who have

been able to combine all the three qualities.

Distinguished Ladies and gentlemen, we

have a lot to be proud of. Within the last 20

years; the number of countries, where lep-

rosy is a major public health problem has

fallen from 122 to 9.

Over 14 million people have been cured

of leprosy. In place of despair, there is now

hope that future generations will not have to

deal with leprosy that way our generation

has had to struggle with leprosy.

This historic congress, therefore repre-

sent a period of celebration. We are here to

celebrate not only our achievements. But

also the lives of those who have sacrificed

their lives to ensure that leprosy does not

destroy lives. We are also here to celebrate

the lives of all those who have and continue

to suffer the disease in silence.

But the congress is also an opportunity

for reflection. Our top priority should re-

main to support the 9 remaining countries

to reach the elimination target.

It is worth remembering that our ultimate

aim is not elimination but a world free of

leprosy. We talk about 14 million of people

cured from leprosy. This is not completely

true. People might have been cured physi-

cally but not emotionally, mentally and

spiritually. This is because the biggest so-

ciety is still not cured from the stigma of the

disease. And as long as the society is not

cured, no one will be completely cured.

Curing the society of the stigma of leprosy

is a very big and long-term agenda.

I have no doubt that the post elimination

era will be as challenging as the pre elimi-

nation agenda. We will need even more

support and resources. We need to be more

creative, so that leprosy control moves from

the margins to the mainstream of health

policy, health strategies, health service de-

livery and health budget.

We have been successful so far because

of the collective action of national govern-

ments, NGOs (both local and international)

foundations, the private sector, (especially

the pharmaceutical sectors, researches and

scientific community) and through the vi-

sion foresight, leadership efforts of a num-

ber of special individuals. Some of whom

are here with us.

The key of our future success is partner-

ship. We have no option but to work together.

I know that W.H.O. has not always been a

good partner and occasionally we have been

part of problem rather than being part of the

solution. We have not always adequately

recognized the special role NGOs play. We

are keen to learn from our past mistakes and

not to repeat our old mistakes. We ask the

same from our partners. We will not always

agree. Occasionally one may disagree but we

should always reach a consensus.

“We have no option but to work to-

gether.”

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International Journal of Leprosy

2005

If ever there was a just war, the war against

leprosy is one such war.

On behalf of the millions who have bene-

fited and will benefit from your work, I salute

you and wish you a very fruitful congress.

Working Together For A World Without

Leprosy

Dr. Sunil Deepak

President International Anti-Leprosy Feder-

ation (ILEP)

Honorable Minister, distinguished guests,

dear friends and colleagues,

ILEP is honored to be associated with this

historic Africa congress of ILA. ILEP has

chosen its mission as “Working together for

a world without leprosy”.

When we say “working together”, we

mean 15 autonomous members of ILEP that

are together since 1966 and that support ac-

tivities in 94 countries of the world. As ILEP

members, we recognize that the combined ef-

forts of ILEP members as a federation is

greater than the sum of their individual ef-

forts. “Working together” also means the high

quality technical expertise from the ILEP’s

Technical Commission and its support for re-

search, scientific journals and teaching mate-

rials. Finally, it also means our national and

local partners including Governments and

national programmes at different levels, na-

tional and local non-governmental organiza-

tions and families and associations of per-

sons affected with leprosy.

For reaching the goal of a world without

leprosy, the support provided by ILEP

member associations has an operational di-

mension that includes financial support,

technical advice, training and human re-

sources, teaching materials, equipment,

drugs, etc. This support from ILEP mem-

bers is based on a holistic view of leprosy

that means attention towards diagnosis and

treatment of the disease, prevention of dis-

abilities, community education, care and re-

habilitation and the human rights approach.

For achieving this goal of a world with-

out leprosy, ILEP members promote inte-

grated and sustainable approaches to the

fight against leprosy that include combined

programmes and general health services,

strengthening of referral services, training

of personnel in general health services and

promotion of community-based rehabilita-

tion and socio-economic rehabilitation pro-

grammes.

In this scenario, we see many challenges

for continuing the fight against leprosy in-

cluding:

• Ensuring adequate attention towards

leprosy in primary health care settings

and in combined programmes

•Networking with organisations in-

volved in non-leprosy related activities

and promoting their attention towards

needs of leprosy affected persons.

• Strengthening the coverage of general

health services.

• Sustainable and effective strategies for

the fight against leprosy in the post

2005 period.

In conclusion I would like to reaffirm that

ILEP members are committed to work to-

gether with Governments and all stake-hold-

ers and partners in Africa to ensure the pro-

vision of sustainable, quality services for

treatment and care of persons affected with

leprosy for as long as these are needed. I also

wish the participants of the African congress

of ILA for fruitful discussions that will con-

tribute to the realisation of our goal for a

world without leprosy one day. Thank you.

Page 63

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News and Notes

149

Introduction. Dr. J. P. Bréchet and

Dr. Alexandre Tiendrebeogo

The elimination strategy is based on 2

key elements: Early diagnosis of leprosy

and effective Treatment with a standard

M.D.T. treatment.

However the implementation of these

key elements is fraught with many difficul-

ties such as:

• Problems in training and communica-

tion due in part to the low level of skills

at the periphery where health centers

constitute the front line in contact with

the population, and also where exists

low awareness of leprosy about symp-

toms, access to treatment and gratuity

of M.D.T.

• Problems of Organizing activities at the

Health Unit level where detection and

treatment are often part of a vertical

program, and where treatment is either

prolonged or cases recycled due to de-

formity or reaction.

• Problems of Access to detection and

treatment centers due to low geograph-

ical coverage, financial constraints

(transport cost and loss of salary while

going to Health center)and social

stigma.

This symposium looks at operational as-

pects of detection and treatment through the

shared experience of different approaches

in Africa, which is the continent with the

greatest number of countries having a high

prevalence of leprosy.

Detection of Leprosy.

a) Active and passive detection by Dr.

Alexandre Tiendrebeogo Passive detection

is examination of suspected cases present-

ing themselves spontaneously, it needs to

be supported by health education cam-

paigns and availability of free M.D.T. The

advantage is that it facilitates integration of

leprosy into general health services, is

cheap and is appropriate in areas with good

health coverage.

In Active detection, suspected cases are

gathered in a village and examined during a

visit in the village, it needs to be accompa-

nied by flexible distribution of M.D.T. and a

repeated visit after 2-3 months. The advan-

tage is that hidden cases are more easily

found and community participation helps to

reduce stigma of leprosy in isolated areas or

those with poor health coverage.

Treatment likewise can be adapted to

monthly supervised M.D.T. distribution,

flexible M.D.T. distribution for 2 to 3

months and Accompanied M.D.T. distribu-

tion of the whole course of treatment.

A good combination of all these strate-

gies will ensure a high success rate of de-

tection and treatment adapted to the preva-

lence, health coverage and context of lep-

rosy in the area.

b) Active and passive detection in Mali

by Dr. Samba O. Sow

Comparing 2 strategies of leprosy cases

finding it was found that active case finding

is more efficient but expensive, allows early

detection, treatment and prevention of dis-

abilities, should be repeated for 2 to 3 years

in remote areas according to the prevalence,

while Passive case finding should be ac-

companied by education sessions in order

to be more efficient.

The 2 strategies need to be combined in

most endemic countries for leprosy elimi-

nation

c) Urban leprosy and detection in Mada-

gascar by Dr. Claude Rattrimoarivony

The case of Antananarivo, capital of

ILA African Congress

Johannesburg 31 January–3 February 2005

SYMPOSIA

Operational Issues of Leprosy Case Finding

and Treatment

Page 64

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International Journal of Leprosy

2005

Madagascar with a rapidly growing popula-

tion coming from the rural areas. Although

the Prevalence rate is low (0,14 /10 000) the

number of new cases detected is constant

and is mainly constituted by MB cases

(94%) . Reaction appear in 20% of cases.

This may be due to having only one Derma-

tology reference center for Confirmation of

Diagnosis. To improve detection staff need

to be trained in active case finding and fol-

low-up in the suburbs as well as to raise

awareness of the indifferent population.

The case for social assistance in the urban

context is made so as to look for defaulters

and improve the cure rate.

Quality of Diagnosis.

a) Results of ULR in Cameroon – Dr.

Charles Nsom Mba

Updating of Leprosy Registers was per-

formed in 10 Provinces over 2 years and re-

sulted in a marked reduction of the Rate of

Prevalence from 0.82 to 0.46 per 10 000.

The main lessons learned were that detec-

tion depended on the information about lep-

rosy and level of awareness of the commu-

nity. The health workers required updating

about leprosy and improvement in M.D.T.

coverage in order to achieve the reduction

in Prevalence. Hence the recommendation

to pursue this activity as a routine supervi-

sion activity.

b) Validation of diagnosis in Angola –

Dr. J. P. Brechet

With an increase in case detection and

Prevalence, justification to validate the di-

agnosis of leprosy became obvious. First

high endemic Provinces were visited, regis-

ters updated, patients examined and staff

assessed in their skill to diagnose Leprosy.

The impact of previous training was poor

and a new strategy of in service training

during supervision visits was introduced.

The validation included 3 elements: Patient

examination, validation of information sup-

port (charts and Register) and validation of

statistical reports.

Thus the main elements to confirm diag-

nosis include: patient examination by 2

trained technicians, systematic review of

nerve assessment (sensitivity, muscle

strength testing, deformity grade) and clini-

cal diagnosis In Angola only 60 % of cases

were confirmed, 6% were wrong diagnosis

and 34 % were non leprosy cases disap-

peared due to migration of population and

poor follow-up. It is recommended to ex-

pand the confirmation of diagnosis by in-

volving dermatologists and medical doctors

as well as to strengthen formative supervi-

sion visits.

Strategy in Leprosy Treatment.

a) Accompanied M.D.T. in Madagascar.

Assessment by Dr. A. Tiendrebeogo

Due to a low cure rate (55%) in Mada-

gascar and in an effort to improve the treat-

ment completion rate, accompanied M.D.T.

was introduced in 2000. Over a 3 year pe-

riod up to 21,000 new cases of leprosy were

treated. An assessment of this strategy was

performed by taking a sample of 962 cases

treated in 2001 in 32 districts and examin-

ing them in 2003, after completing treat-

ment. The results showed a high cure rate

(98%) against a lower cure rate for super-

vised M.D.T. distribution (86%). Patients

living more than 10 km from the health

Center showed lower cure rate with super-

vised M.D.T. It is therefore recommended

to pursue Accompanied M.D.T. distribution

for people living more than 10 km from the

Health centers and to continue supervised

M.D.T. distribution to those living near the

Health Unit.

b) Comments about Leprosy Treatment

by Dr. V. Pannikar

The current M.D.T. blister packs is still

the main form of treatment and W.H.O. will

continue to provide free M.D.T. to all coun-

tries treating leprosy patients up to the year

2010. Other treatment schedules are being

studied and the results will not be published

until 2010.(ROM and Uniform M.D.T., 5

year prospective study to assess relapse rate)

The key points are Flexibility in M.D.T.

distribution (how and when to adapt distri-

bution to where patients are living), elabo-

rating joint guidelines for finding default-

ers, developing tools to diagnose relapse

and to be aware of the risk of Rifampycine

drug resistance.

c) Strategy for Leprosy Control in a low

endemic country –case of Sudan by Dr. E.

Tanyons

In Sudan Master clinics were developed

in each Province according to population

Page 65

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News and Notes

151

density and accessibility. These clinics con-

firm diagnosis of suspected cases and start

M.D.T. treatment. This is a method to facil-

itating supervision and makes good use of

scarce medicines and Human resources.

The Seminars for increasing awareness of

leprosy are undertaken for health staff and

community leaders. The expected result is

reliable and valid reports.

These topics raised some very practical

issues such as active versus passive detec-

tion, financial aspects involved in these

strategies, despite the fact that pockets of

leprosy exist and require to be detected, in

any case and by any means available.

Diagnosis of leprosy can be improved by

careful examination and confirming the di-

agnosis by 2 examiners, including where

possible dermatologists and performing for-

mative supervision visits of Health workers.

Treatment schedules need to be flexible

and adapted to the patients taking into ac-

count distance, follow-up and community

participation, so as to minimize defaulters

and obtain a high cure rate.

Dr. J. P. Bréchet

Dr. A. Tienderébéogo

Symposium on

REACHING THE UNREACHED

Preamble. As an introduction to the sym-

posium, the moderator made the following

remarks:

• The current strategy for Leprosy Elimi-

nation centres on early detection and

prompt treatment with M.D.T.

• For many years it was recognized that

in some countries and regions, there

were pockets of patients that could not

be easily accessed through the conven-

tional leprosy elimination programs.

• This situation continued to persist in spite

of claims of high geographical coverage

and the integration of leprosy services

into the Primary Health care package.

• Innovative approaches spearheaded by

W.H.O. namely Special Action Projects

for Elimination of Leprosy (SAPEL)

and Leprosy Elimination Campaigns

(LEC) were implemented by several

countries leading to significant suc-

cesses in reaching underserved and de-

tecting and treating hitherto hidden lep-

rosy cases.

• In spite of the efforts, new leprosy

cases continue to be detected in num-

bers and with established deformities.

This suggests that leprosy cases con-

tinue to occur in the community but are

not detected in time.

• The possible explanations include factors

that prevent the cases from accessing the

health services, e.g. long distances, cost

and stigma.

• Some patients with suspect symptoms

do present to health facilities but are

not detected due to the lack of relevant

knowledge and skills among the health

workers.

• This symposium was meant to review

the achievements made through the

previous innovative approaches, to de-

cide if some aspects are still relevant.

Country presentations, especially from

high prevalence countries, would high-

light the problem of unreached patients

and the measures taken to reach them.

The overall output would be a collec-

tion of recommendations and possible

approaches to reaching the unreached.

Presenters. The symposium was moder-

ated by Dr. H. Joseph Kawuma (Uganda),

and the country presentations chaired by

Dr. J. Chwuku (Nigeria).

There were brief presentations by: Dr. L.

Bide (W.H.O./AFRO); Dr. B. Njako (Tanza-

nia); Mr. Mitiku Ensermu (Ethiopia); Dr. J.

Mputu (DRC); Dr. Samuel Hermas (Mada-

gascar); Dr. Ndeve A. (Mozambique).

Synopsis of presentations. The World

Health Organization (W.H.O.) Medical Of-

ficer reiterated the contribution of Africa to

the global leprosy burden referring back to

his key note address on Leprosy Elimina-

tion in African Region of W.H.O.

Describing the successes achieved with

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International Journal of Leprosy

2005

LEC and SAPEL projects in the past, he in-

dicated how these were no longer appropri-

ate in the form used then but that innovative

approaches could still be used to address

the yet unreached patients.

The presentation from Tanzania de-

scribed factors behind the uneven distribu-

tion of leprosy cases in the country. While

some areas were simply high prevalence

pockets, the distribution was also influ-

enced by: geographical coverage by the Na-

tional Elimination Programme due to,

among others, bad terrain and lack of train-

ing of health workers. Dr. Njako listed the

measures taken to overcome some of the

problems with particular emphasis on the

gains made through increasing the skills of

health workers in over 80% of health units

and promoting functional integration.

A presentation from Ethiopia described

the current leprosy elimination status. There

are no apparent high endemic pockets or

hard to reach areas. This leads to the opti-

mism that, if the present strategy is sus-

tained, the leprosy burden will continue to

show a downward trend. The current PHC

strategy in the country is focusing on im-

proving health in the home or household.

The challenge to the NLEP is to ensure that

aspects relevant to early detection and treat-

ment of leprosy will be integrated in this

strategy.

The Leprosy Programme Manager of

DRC justified the thinking that there are

still many unreached cases. There is an in-

creasing number of newly detected cases in

spite of poor geographical coverage as re-

sult of war and a poor road communication

network. Attempts to use community vol-

unteers especially in the underserved areas

were frustrated by unforeseen demands for

remuneration (for would be volunteers).

The strategy will continue to be pursued but

engaging volunteers identified by the com-

munity.

Madagascar has, perhaps, the most se-

vere leprosy burden in the region. The

country presentation reported that the

strategy to reach yet unreached cases was

based on intensified community mobiliza-

tion and education.

Mozambique’s health services in general

were affected by the protracted war. The

brief country presentation described a grad-

ual improvement of the elimination pro-

gramme between 1994 and 2003. Preva-

lence rate at the end of 2003 was 2.2 per

10,000. To reach unreached cases, they in-

vested mostly in training of staff in govern-

ment and private health services, social mo-

bilization and health education. Coupled

with a systematic updating of registers, they

are optimistic that the leprosy burden will

continue to go down.

Comments, conclusions and recom-

mendations. The contents, recommenda-

tions and discussion points arising from the

various presentations can be summarized as

follows:

(i) Deliberate efforts should be made by

National Programmes and their partners to

continue the search for underserved areas

and populations in order to reach the yet un-

reached leprosy cases and to provide them

with M.D.T. services.

(ii) “Reaching the unreached” is a Pri-

mary Health Care strategy aimed at ensur-

ing equity in health care. Leprosy control

strategies should aim at improving access

of underserved populations to general

health services including M.D.T. services

and should target equal not greater access.

(iii) Particular attention should be paid to

strategies to increase access of women to

health services, and ensure coverage of ur-

ban and peri-urban areas including slums in

view of increasing urbanization in the dif-

ferent countries.

(iv) Efforts to Increase geographical cov-

erage should be sustained. This could be by

using volunteers in areas in which basic

health infrastructure does not exist. Experi-

ence shows that it is essential that the vol-

unteers are identified by the communities

served and that, as a pre requisite, adequate

training is carried out, logistics ensured and

a referral system put in place.

(v) Existing organized groups should be

used for sensitization and mobilization. Ex-

amples: School Children to identify sus-

pects and direct them to volunteers; Reli-

gious Groups that are active in the hard to

reach areas for communication, advocacy

and social mobilization; and Ex-Patients for

mobilization.

(vi) The following general measures may

be taken to ensure that leprosy related pri-

orities remain in the correct places.

• To ensure that leprosy continues to be

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153

given deserving emphasis in country

health strategies e.g. the focus on fami-

lies and households in Ethiopia.

• Services for diagnosis and treatment ,

training and re-training of existing staff

must be sustained.

• Intensify use of dermatological services

as an entry point to identify leprosy

suspects.

• Ensuring inclusion of leprosy in the

curricula of medical schools and other

health training institutions.

• Organizing operational research in the

suspect pockets.

• While LECs and SAPELs are no longer

appropriate in their original design, it is

possible to apply selected, sustainable ele-

ments of LECs in the known pocket areas.

• Community Rehabilitation and Social

Economic Rehabilitation Programmes

should be maintained on the agenda for

their primary purposes but also because

they present good opportunities for

community mobilization.

• It is important for leprosy related bilat-

eral and multi-lateral agencies (refer-

ring to the particular case of W.H.O.

and the ILEP Organizations) to im-

prove their internal coordination in or-

der to avoid sending conflicting mes-

sages to countries.

H. Joseph Kawuma

GLRA

P.O. Box 3017 Kampala, Uganda

Kawuma@infocom.co.ug

Symposium on

COMMUNITY-BASED REHABILITATION (CBR) FOR

PEOPLE AFFECTED BY LEPROSY

Introduction. Many people affected by

leprosy live with the long-term physical and

psychosocial consequences of the disease.

In 1998, the number of people living with

leprosy-related visible impairments was es-

timated to be 2 million. Social problems re-

sulting from stigma are often not restricted

to the person who has had leprosy him or

herself, but affect whole families. Therefore

the number of people indirectly affected by

leprosy will be much larger than this. The

physical impairments may lead to contin-

ued risk of further disability and to limita-

tions in activities of daily living. Visible im-

pairments (deformities), activity limitations

and/or stigma may lead restrictions in social

participation, such as problems in family

relations, marriage, education or employ-

ment. A substantial proportion of people

who suffer such adverse circumstances will

learn to cope and overcome their disadvan-

tages. Yet others may require assistance to

restore or optimize their functioning and so-

cial integration. Services offering a wide

variety of rehabilitation interventions to

meet such needs have traditionally been of-

fered in and through institutions. Else-

where, specialized socio-economic rehabil-

itation outreach programmes have at-

tempted to improve the social participation

of people affected by leprosy. However, the

coverage of both institutes and outreach

programmes is small compared to the

global need for such services.

The same is true for people with other

disability. An estimated 600 million people

worldwide live with one or more disabili-

ties. Only a fraction of these have access to

rehabilitation services. The reasons include

poor geographical coverage of existing

services and the high cost involved in spe-

cialised, particularly institution-based serv-

ices. Community-based rehabilitation

(CBR) has been devised as a strategy to

make basic rehabilitation services widely

available to all people with disability. CBR

is defined as “A strategy within community

development for the rehabilitation, equal-

ization of opportunities, and social integra-

tion of all people with disabilities. CBR is

implemented through the combined efforts

of disabled people themselves, their fami-

lies and communities, and the appropriate

health, education, vocational and social

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International Journal of Leprosy

2005

services.” (UN, W.H.O., and ILO. Joint po-

sition paper, 1994)

It is important to realize that CBR and

institution-based rehabilitation are comple-

mentary. For many people, CBR services

may be sufficient to meet their needs. How-

ever, an estimated one third of people with

disability will require specialist services

(e.g. reconstructive surgery) at one point or

other during their rehabilitation. Another

important point to realise is that there is no

one “method of doing CBR.” Essential

characteristics of CBR are that programs or

services are participatory, involving the

client and his or her family as key stake-

holders, and that the services empower the

people concerned to take control of their

own lives and optimize their abilities. Of-

ten, CBR programs are multi-disciplinary

and multi-sectoral, including staff, services

and/or skills from medical, paramedical, so-

cial, educational and vocational disciplines.

Since CBR is a community-based service,

often people with many types of disability

are included. However, traditionally, this

has not included people affected by leprosy,

either because separate rehabilitation serv-

ices catered for their needs or because

stigma against leprosy was and is still pre-

sent within CBR programs also.

Because the needs of people affected by

leprosy are very varied, ranging from phys-

ical prevention of disability activities to ed-

ucation and vocational training, these can

be addressed well within the context of a

general CBR program. Leprosy programs

should therefore aim at integration of the

rehabilitation needs of people affected by

leprosy into general CBR programmes.

This is also called “mainstreaming” of lep-

rosy rehabilitation.

Stigma and discrimination by Dr. Wim

van Brakel. A major factor leading to social

exclusion of people affected by leprosy is

the stigma against leprosy found in most so-

cieties around the world. Stigma has major

impact on psychosocial life of individuals,

families and communities, it leads to viola-

tion of human rights, has strong negative

consequences for public health pro-

grammes. Currently, there is no widely ac-

cepted intervention model or even a stan-

dard definition of stigma and a comprehen-

sive, strategic approach to interventions is

missing. In principle, many of the negative

consequences of stigma can be addressed

through CBR. There is also an indication

that the empowerment that results from

client-participation in CBR activities re-

duces stigma. However, the impact of such

activities is often not measured and, as a

consequence, the effectiveness of CBR in

reducing stigma is not known.

Stigma measurement is usually frag-

mented and often condition-specific, e.g.,

only community attitudes to leprosy are as-

sessed. This is partly because there is no

generic set of instruments available for a

comprehensive assessment of stigma.

In November 2004, the Royal Tropical

Institute Leprosy Unit in the Netherlands

organised an international research work-

shop on health-related stigma. Seventy re-

searchers, experts and people affected by

stigmatized conditions discussed their con-

cepts, findings and experiences regarding

stigma related to leprosy, HIV/AIDS, tuber-

culosis, Buruli Ulcer, mental illness,

epilepsy and physical disability. A striking

finding was that, despite marked differences

in determinants of stigma, the experiences

and consequences of stigma appeared very

similar across different health conditions

and cultures. Because of this, common con-

ceptual frameworks, strategies for stigma

reduction and stigma measurement tools

appear feasible. A new consortium, the In-

ternational Consortium for Research and

Action Against health-related Stigma

(ICRAAS), was launched to reduce health-

related stigma and its harmful conse-

quences, including discrimination and so-

cial exclusion.

The role of self help groups in commu-

nity-based rehabilitation of people af-

fected by leprosy by Ms. Jannine Ebenso.

In Nigeria, the planning cycle is used in

the management of CBR programs.

Planning. Needs analysis. SHG can help

them to analyse their own problems and

brainstorm strategies. SHG can have an im-

portant role in identifying the real needs in

a community. In Nigeria, we have been in-

volved with groups in various communities.

We have seen the value of sharing the local

knowledge and personal experience of

groups of people with disabilities (not all as

a result of leprosy) in the planning process

of our projects.

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Implementation. Groups can decide the

duration, standard, quality, and quantity etc

of all aspects of the CBR project. Group

members should be the prime movers, not

outside “experts.”

Monitoring progress. Are we on track?

Will we achieve this year’s objectives? Any

minor amendments needed? Are resources

sufficient / allocated wisely? Need re-allo-

cating?

Evaluating impact. Have the aims and

objectives been achieved?

The Gwada Community Development

Association in Nigeria has built itself up

over the last 3 years. Meeting monthly, the

groups discuss and plan for their develop-

ment. Even though most are affected by

leprosy, there are also interested members

of the community in the group. To date the

group have planned prevention of disability

activities including a successful eye care

screening programs in an onchocerciasis

endemic area by the eye team attached to

the leprosy program and distribution of pro-

tective footwear to people with plantar

anaesthesia. They also organized socio-eco-

nomic rehabilitation activities like micro-

credit schemes, where the members are re-

sponsible for setting up criteria and limits,

deciding on the beneficiaries, monitoring

repayments, tracing defaulters and setting

interest rates.

Self-help groups can be review using the

criteria presented by Cornielje, et al.

(2000), which were developed for the eval-

uation of CBR projects.

(i) Restoration of quality of life. Self-care

groups (SCG) in Ethiopia have seen bene-

fits of their activities in terms of reduction

of ulcers and improvement in the skin care

of the hands and feet. Group members men-

tioned feelings of “belonging to a group,”

improved self-respect and dignity and con-

fidence to participate socially. In Nigeria,

SCGs are just coming up, but the initial

feedback is very encouraging, with neigh-

bours and friends assisting one another in

finding solutions to the problem of recur-

rent ulcers. Small cooperatives have devel-

oped that are concentrating on improving

the socio-economic status of the group

members. IDEA Nigeria was launched in

December 2003. A National Committee has

been formed and each state is being encour-

aged to form their own branches and com-

mittees. Already letters of introduction have

gone to the Federal Government of Nigeria

informing them about the needs of people

affected by leprosy.

(ii) Locus of power. Effective empower-

ment requires that clients participate in all

aspects of the process so that ownership is

achieved and benefits are sustainable.

Equality of access to local resources and

services is a common objective. In many in-

stances empowerment is realized through

(in-)formal education, (vocational) training

and paid employment, but it may equally

take place through participation in self-help

groups, community-based organizations

and through processes of active participa-

tion in the development of co-operatives. A

successful example of empowerment is the

community development group in Kuta Vil-

lage, Niger State, Nigeria. After they had

voiced their needs and started to get organ-

ized, they managed to meet several of the

main needs by themselves.

(iii) Involvement of others. Integrating

previously stigmatized or excluded individ-

uals in the community demands a level of

community involvement, though this may

vary from acknowledgement or mere toler-

ance through to active encouragement, par-

ticipation and ownership. Community par-

ticipation is seen as indispensable to em-

powerment since only through such

participation social, economic and political

changes will take place. These changes are

imperative in the process of enabling

people with disabilities to become inte-

grated into mainstream society. CBR may

be defined as a system that uses existing re-

sources of manpower and material within

the community to promote integration of

disabled people in all spheres of life.

(iv) Range of activities. Often, the focus

of rehabilitation is only on specific dis-

abling conditions that require (specific

forms of) rehabilitation, e.g. the improve-

ment of locomotion through physical ther-

apy, or the prevention of disabilities by

making appropriate footwear available. In

Nigeria, the Joint National Association of

Disabled People (JNADP) is a self-help

group for people with all manners of dis-

ability from many different of causes.

People affected by leprosy are represented

on the National Committee. At the JNADP

annual meeting in May 2004, representa-

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International Journal of Leprosy

2005

tives of the Federal Government of Nigeria

were present. A national policy on rehabili-

tation of the disabled is being put in place.

As people affected by leprosy were in atten-

dance, their needs will also be taken into

account. In Kebbi State, the people affected

by leprosy have joined this group and have

brought about an increase in the number of

services offered by the rehabilitation serv-

ices. Partnerships have been developed be-

tween government, NGOs and community

associations as well as the group members

and there is good collaboration and infor-

mation and resource sharing in the three

groups that are members so far.

(v) Benefits of small groups in CBR.

They provide an opportunity to share expe-

riences, develop new attitudes and acquire

new life skills.They create a public voice

for the rehabilitation process and encourage

participation.They develop confidence as

individuals “go public” about the impact of

leprosy. They provide a powerful voice

when confronting officialdom.

The Ethiopian National Association of

Ex-Leprosy Patients (ENAELP) by

Ms. Birke Nigatu.

The ENAELP is an association legally

established by leprosy-affected persons to

advocate their rights and create awareness

in the society about leprosy, which is badly

misunderstood and unnecessarily feared. In

addition, the ENAELP is committed to so-

cio-economic rehabilitation of its members

to enable them to regain dignity and self-es-

teem. Currently, the association has 20,000

members in 54 local associations in the

seven regions of Ethiopia. To achieve its

objective, the ENAELP has been imple-

menting awareness, advocacy and socio-

economic rehabilitation projects, in partner-

ship with national and international agen-

cies.

The awareness and advocacy work of

ENAELP ranges from publishing a bilin-

gual annual magazine called the “Truth” to

printing of posters, brochures and caps and

radio broadcasting using the government

media. Commemoration of World Leprosy

Day, which was started by ENAELP in

2000, has been also an important event to

advocate the rights of persons affected by

leprosy. ENAELP also lobbies the govern-

ment and all others concerned for equal par-

ticipation and equal opportunities of per-

sons affected by leprosy. So far the associa-

tion has protected and averted the displace-

ment of members from their settlements

and it is doing its level best in advocating

the availability of quality treatment and

POD for affected persons. ENAELP is the

founder and an active member of the

Ethiopian Federation of Persons with Dis-

abilities. ENAELP has a good relationship

with the Ministries of Labour, Social Af-

fairs and Health, who assist the association

through a steering committee established

together with the ENAELP.

Parallel to the awareness and advocacy

work, ENAELP carries out socio-economic

rehabilitation activities for its members.

They belong to the most disadvantaged

groups because of stigma and poverty. To

speed up integration, it is essential to em-

power persons affected by leprosy socially

and economically. This will demonstrate

that they have the potential and the skill to

be productive like any other citizen. To this

end, ENAELP works with revolving fund

schemes for members to enable them to en-

gage in dignified income generating activi-

ties. The association also provides primary

and higher education opportunities for chil-

dren of members, empowering families to

break the cycle of stigma and accompanied

poverty. With the same aim, ENAELP or-

ganises self-help groups for women af-

fected by leprosy, providing training in

handcraft production. So far, these strate-

gies have proved very successful.

A Key to success in CBR: Designing

an appropriate program using a partici-

patory approach by Dr. Denis Byomungu.

There are many who are in need of reha-

bilitation. There are many patterns of CBR

conducted in Africa. There is an urgent

need to evaluate CBR programs in order to

identify the most effective CBR approach.

This paper reports lessons learnt by The

Leprosy Mission in the DR Congo in de-

signing a CBR program using a participa-

tory approach.

The following questions were asked:

(i) What is the community? People af-

fected by leprosy vs. all community: in

DRC rural areas: community in a defined

area and in urban areas: members of self

help group.

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157

(ii) How does the community participate?

All the community, through representatives

or beneficiaries: Rural areas: through reha-

bilitation committee members and in urban:

through members of self-help group.

(iii) Expected level of participation: full

community-led vs. provision of services

within the community: The programs in DRC

was community-led with some guidance.

(iv) Beneficiaries: People physically dis-

abled by leprosy vs. community affected by

leprosy, other disabled in or excluded. In

DRC, people with leprosy-related disability

and their household and people with other

disability were considered (up to 15% of

the budget).

(v) Depth of outreach: how to deal with

the poorest (destitute). ignore there special

needs vs. welfare: Targeting the helper

(usually family member), breaking the cy-

cle of poverty through scholarship com-

bined with income generating activities ,

assisting the community to care for their

poor through communal projects and using

services from other organizations caring for

the poor.

(vii) Meaning of rehabilitation: welfare

vs. development: micro-credit schemes,

community awareness and advocacy work.

(viii) Program against stigma: commu-

nity awareness and advocacy.

(ix) End point of rehabilitation: approxi-

mately 3 years or 3 loan cycles.

(x) Long term goals: Client: Re-inser-

tion, respected role, self-esteem, earning

and supporting the family, personal learning

and development. Community: CBR and

Community Development and Project: Sus-

tainability through Revolving Loan.

Conclusion. For sustainable transforma-

tion to happen, we need to see in our pro-

jects the principles described in an old Chi-

nese poem on community development:

“Not a showcase, but a pattern; Not odds

and ends but a system and Not relief but re-

lease.” This starts by designing an appropri-

ate CBR program with full participation of

all stakeholders, including beneficiaries and

communities where they live.

Issues related to integration of rehabil-

itation activities related to leprosy in

CBR programs by Sunil Deepak, Jayanth

Kumar, and M.V. Jose

The progressive integration of vertical

leprosy control programs into primary

health care services, has been accompanied

with calls for integration of rehabilitation

activities related to leprosy affected persons

in community-based rehabilitation (CBR)

programmes. Keeping this in mind, during

the last twelve years, AIFO/Italy through its

partner organization AIFO/India has organ-

ized a series of workshops and training

courses in India to promote the conversion

of vertical leprosy control programs in CBR

programmes and integration of persons

with leprosy-related disabilities in these

CBR programmes. At the same time, CBR

projects targeting all people with disability,

including persons with leprosy-related dis-

abilities, were initiated.

Recently a participatory evaluation exer-

cise was carried out in three AIFO-sup-

ported CBR projects in Karnataka state of

India: SRMAB project in four sub-districts

of Mandya district; MOB project in three

sub-districts of Mandya district; and AMSK

project in Bhalki sub-district of Bidar dis-

trict. This evaluation, carried out through

focus group discussions, looked at two spe-

cific aspects.

Integration of persons with leprosy-re-

lated disabilities in CBR activities. CBR

projects have many components including

medical, educational, social, etc. Integra-

tion of leprosy-affected persons in CBR

was evaluated mainly by looking at their

participation in heterogeneous self-help

groups (SHG). Implications for change in

role from vertical leprosy workers to CBR

workers: the feelings of ex-leprosy work-

ers, who were now working as CBR work-

ers, need to be carefully considered.

• Regarding inclusion of leprosy affected

persons in SHGs, the discussions

brought up the following issues:

(i) CBR workers, people with disability

and leprosy-affected persons all agree that

integration of persons with leprosy disabili-

ties in SHGs is problematic and requires

proper planning and follow-up.

(ii) Persons with more visible deformi-

ties face more problems.

(iii) Self-stigma or perceived stigma among

leprosy-affected persons, their fear that they

will not be accepted, is a big obstacle.

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International Journal of Leprosy

2005

(iv) Other disabled persons may express

negative feelings about integration of lep-

rosy-affected persons, but usually this ob-

stacle can be overcome through awareness

and discussions.

(v) The integration was gradual over a

period of many years – examples of lep-

rosy-affected persons active in a SHG stim-

ulate more persons to join.

• Regarding the feelings of ex-leprosy

workers, the discussions showed that

the change of role from leprosy worker

to CBR worker is perceived as a big

problem, especially by persons with

long-standing experience as leprosy

workers. Some of the issues that came

out included:

(i) Higher workload: “before we just dis-

tributed drugs and explained a few things,

now the work is never over…”

(ii) Loss of expertise: “before we had

clear cut competence, now we have to facil-

itate but problems are more difficult to

solve…”

(iii) Closer contact with persons and

their families by home visits: “earlier,

people had to come to the ambulance, now

we have to go to homes…”

For these reasons, for contemplating any

change in (vertical) leprosy programs to

start CBR activities, the ex-leprosy workers

made the following recommendations:

• The role-change of the health workers

from prescriber to facilitator is a key is-

sue and needs to be tackled by suffi-

cient plan ning and discussions.

• Workers need support in the transition

period through training, dialogue, shar-

ing of experiences and opportunities to

talk about problems.

• Change must be planned and gradual.

In conclusion, integration of leprosy-re-

lated rehabilitation services and CBR is fea-

sible and it improves the sustainability of

the project activities. The CBR approach

has a great deal to offer for integration and

rehabilitation of leprosy-affected persons.

However, both these aspects require careful

planning, preparation, support and training

and a gradual implementation process.

Dr. Wim van Brakel

Ms. Jannine Ebenso

Ms. Birke Nigatu

Dr. Denis Byamungu

Dr. Sunil Deepak

Symposium on

PREVENTION OF BLINDNESS IN LEPROSY

IN AFRICA

The problem of eye involvement as a

cause of disability in leprosy is well recog-

nized. (3) Often, however, the focus is on

the unique pathology, rather than the signif-

icant impact on the stigma associated with

leprosy and on the quality of life of people

affected by leprosy. Lagophthalmos, be-

sides being a condition that is potentially

blinding, is also disfiguring and disabling,

perpetuating the stigma associated with lep-

rosy. Vision loss, whether due to cataract or

corneal disease secondary to lagophthal-

mos, significantly decreases quality of life.

As life expectancy is increasing worldwide,

the prevalence of visual impairment and

blindness, associated with aging, is also in-

creasing. For these reasons we must con-

tinue to address the problem of eye disease

in leprosy in Africa.

Recently, the primary shift in the discus-

sion of ocular leprosy has been from the

clinical conditions found in patients affected

by leprosy to a discussion of the best ap-

proaches to integrating eye care and leprosy

control activities to increase awareness, ac-

cess to, and acceptance of eye care services

by people with leprosy. In Africa it is rec-

ognized that there are deficits in the number

of eye care professionals; in some countries

there are fewer than one ophthalmologist

per one million population. Consequently, it

should be recognized that access to and the

quality of service delivery received by lep-

rosy patients will only be as good as that

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159

which is available to the general popula-

tion. Nevertheless, with the recent launch of

the VISION 2020 Initiative (9) to achieve

elimination of avoidable blindness by the

year 2020 there have been significant im-

provements in planning for eye care deliv-

ery in Africa. Clearly, blindness cannot be

eliminated; the initiative focuses on those

causes of blindness that either can be pre-

vented (e.g., trachoma, onchocerciasis) or

cured (e.g., cataract). By putting systems

into place in Africa it is hoped that utilisa-

tion of services such as cataract surgery can

be high enough in a defined population that

no one becomes blind due to cataract. It is

critical that leprosy patients be integrated

into these national and district VISION

2020 programmes to ensure that avoidable

blindness is eliminated in leprosy patients at

the same level as in the general population.

Burden of potentially blinding eye dis-

ease in leprosy patients in Africa. Find-

ings from the Longitudinal Study of Ocular

Leprosy (LOSOL) has indicated that ap-

proximately 11% of newly diagnosed MB

patients will have potentially blinding ocu-

lar pathology at the time of their disease di-

agnosis. (2) Findings suggest that there is

little difference in the prevalence of ocular

pathology between different countries, once

age and other demographic factors are con-

trolled for in the analysis. Older patients

have a considerably higher risk of having

eye disease, probably due to a wide-range

of reasons, than younger patients at the time

of their disease diagnosis.

Work carried out among Tanzanian pa-

tients currently on M.D.T. (n = 371), sam-

pled from regions listed as endemic, sug-

gest that 13.5% have some form of leprosy

related ocular disease and that 9.4% have

potentially blinding pathology. Blindness

(<6/60 in the better eye) was recognized in

6% of the study population. Similar to the

LOSOL study, old age was associated with

potentially blinding pathology, as was the

duration between recognition of clinical

signs (by the patient) and enrollment in

M.D.T. Cataract was the leading cause of

vision loss and few of the patients had

sought eye care services. Separately, a

study carried out in Nigerian leprosy vil-

lages (8) demonstrated a three-fold higher

prevalence of potentially blinding pathol-

ogy and a three-fold higher prevalence of

blindness (17.9%). In both settings it was

noted that these patients were not part of

any routine, integrated eye care service.

Guidelines for the management of eye

disease in leprosy and for integrating lep-

rosy patients into general eye care serv-

ices. In 2001 ILEP sponsored a workshop

of leprosy control program managers, oph-

thalmologists, epidemiologists, and others

to develop guidelines for the management

of eye disease in leprosy and on integration

of leprosy patients into general eye care

services (5). Key components of these

guidelines include:

(i) Creating a strong collaborative rela-

tionship between the national leprosy con-

trol program and the national prevention of

blindness committee.

(ii) Establishment of 4 key signs to be

detected at the time of leprosy diagnosis to

guide eye care management and disability

prevention. At the time of leprosy diagnosis

all patients should be examined for lagoph-

thalmos (any gap in mild closure), visual

acuity, the red eye, and presence of a facial

patch. All people with lagophthalmos, de-

creased vision (<6/18), persistent red eye

(2+ weeks in duration), and/or a facial

patch in reaction should be referred by the

basic health worker to a higher level for

clinical evaluation, or as per guidelines in

the national leprosy control and prevention

of blindness programs. It is estimated that

approximately 20% of newly diagnosed

leprosy patients will require referral to a su-

pervisor or an eye care professional.

(iii) Steps to be taken at the time of dis-

charge from anti-leprosy treatment At the

end of anti-leprosy treatment all patients

must be educated regarding the risk of eye

disease and informed that they should re-

turn for examination if they develop

lagophthalmos, diminished vision, a red

eye, or a facial patch in reaction. Explicit

instructions regarding referral must be

given to each discharged patient. All pa-

tients with lagophthalmos should receive

continued periodic follow-up.

(iv) Suggested revisions to the current

W.H.O. disability grading system for eye

disabilities (see below).

(v) Strong encouragement to provide

cataract surgery with implantation of an in-

traocular lens, when feasible.

(vi) Adoption of different procedures,

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International Journal of Leprosy

2005

other than simple tarsorrhaphy, for the cor-

rection of lagophthalmos.

These guidelines serve as a basis for the

integration of leprosy patients into the gen-

eral eye care infrastructure in leprosy en-

demic countries. Nevertheless, it is recog-

nized that a failure to operationalize the

guidelines will lead to the continued poor

access to eye care services and continued

stigma, poor quality of life, and blindness in

leprosy.

Disability grading of the eye in lep-

rosy. Recent research carried out in Tanza-

nia showed significant discordance in the

grading of eye disability when done by an

eye care professional compared to an inte-

grated health worker (IHW). IHWs recog-

nized 3 people with grade 2 disability while

the eye care professional recognized 13

people; similarly the IHW recognized 8

people with grade 1 disability while the eye

care professional recognized 60. Improved

training could assist with assessment of

lagophthalmos and testing of vision, how-

ever, without significant efforts and training

and provision of instruments, IHW are not

going to be able to assess iridocyclitis and

corneal opacities. The current disability

grading system for the eyes is impractical

for most programmes. Accordingly, it is

recommended that visual acuity (either vis-

ual impairment [visual acuity <6/18] or

blindness [visual acuity <6/60], depending

upon the setting) and lagophthalmos should

become the primary indicators for monitor-

ing disability (grade 2) and that corneal hy-

poesthesia, corneal opacities, and uveitis

should be removed from the leprosy dis-

ability-grading scheme.

Lagophthalmos surgery. Lagophthal-

mos surgery should be provided to patients

who need it. Evaluation of the need for

lagophthalmos surgery should be based on

one or more of the following conditions:

size of lid gap, corneal exposure, corneal

hypoaesthesia, visual acuity, and/or cos-

metic difficulties. Research in Egypt (over

300 surgeries) has shown that the modified

lateral tarsal strip procedure (1, 6) had excel-

lent success; over 80% showed a reduction

of lid gap of more than 3 millimeters and

complete lid closure was achieved in 50%

of eyes. Lid closure was associated with

during of lagophthalmos; the longer the du-

ration the less degree of closure. Less clo-

sure was also found in patients with severe

lagophthalmos and of an older age. The ad-

vantages of the modified lateral tarsal strip

procedure were that it was simple, could be

carried out in one stage (yet, repeated later,

if necessary), it does not require long term

follow up or physiotherapy, corrects ectro-

pion and entropion, is cost-effective, and

has a cosmetically appealing result. The

“Prevention of Blindness” manual (4) will

have a section on this procedure. Simple tar-

sorrhaphy should be discontinued, expect in

emergency cases. There are many barriers

that prevent patients from accepting

lagophthalmos surgery, one of which is the

poor cosmetic result of tarsorrhaphy. With

the adoption of better surgical techniques,

programmes need to be developed to in-

crease the uptake of lagophthalmos surgery.

Cataract and cataract surgery.

Cataract related vision loss is higher in lep-

rosy patients than in the general (age-

matched) population. Cataract is the lead-

ing cause of blindness in leprosy affected

persons and many do not have access to

general eye care services. Experience in

Nigeria has shown that the cataract surgical

coverage (% of people receiving surgery

among those who need surgery) is generally

quite low in leprosy patients. (7) Many pa-

tients had opted to have couching per-

formed by itinerant traditional healers; out-

comes of this procedure (using a thorn to

puncture the cornea and dislodge the lens to

the back of the eye) are very poor. The bar-

riers to use of service noted in Nigeria, a

similar throughout Africa fall under the

headings of awareness (of the service, of

where to go, of the expected outcome) , ac-

cess (high cost of surgery, inadequate trans-

portation network), and acceptance (fear of

poor outcome, fear of discrimination by

hospital staff, and social support in the

family). Improving uptake of surgery re-

quires that surgical management should be

carried out in base hospitals rather than as

an outreach activity in order to assure high

quality of surgery and to manage any surgi-

cal complications. This will also, with time,

reduce the stigmatization of leprosy. Simi-

lar to the general population, in which

“bridging strategies” are successful in in-

creasing access to surgical services leprosy

patients need to be brought to the base hos-

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73, 2

News and Notes

161

pital for surgery. Clear policies regarding

subsidies for surgery need to be developed

and implemented.

Surgical experience from both Asia and

Africa has shown that leprosy patients,

even with complicated cataract, can gener-

ally benefit from implantation of an intraoc-

ular lens. There is no evidence to suggest

that post-operative inflammation is more

common in patients with a history of

chronic uveitis. Not implanting an intraocu-

lar lens will, in most cases, result in a pa-

tient that is still blind.

Integration of leprosy patients into

VISION 2020 at the national and district

level in Africa. Integration of leprosy pa-

tients into general eye care services can best

be accomplished through the development

and implementation of national and district

VISION 2020 plans. There are a number of

steps recommended to achieve integration.

(i) Assessment of needs and capacities.

Evidence in Africa would suggest that ap-

proximately 10% of newly diagnosed lep-

rosy patients and three times this number of

leprosy settlement patients have potentially

blinding pathology. These figures can be

used to calculate the needs in most African

settings. Assessment of capacity for eye

care should include listing of ophthalmolo-

gists and cataract surgeons by region and

compilation of information on routinely

used referral practices, in particular the use

of “bridging strategies” to identify and get

patients to hospital. Skills of integrated

health workers in the 4 key signs of ocular

leprosy and the skills of eye care providers

in lateral tarsal strip procedure for lagoph-

thalmos and implantation of IOL for

cataract surgery should also be determined.

(ii) Establishing a national strategy and

national policies. Most every African coun-

try has a national prevention of blindness

committee (NPBC), comprising the Min-

istry of Health, NGOs, service groups, and

others. The Leprosy Control programme

and the NPBC should meet and review the

needs assessment and capacities in the

country. Together the two should develop

strategies for integrating leprosy patients

into general eye care services in the coun-

try. Policy decisions regarding such issues

as the cost of cataract surgery for leprosy

patients and the potential for subsidy and

waivers should be determined.

(iii) Clearly defining the training needs

required for integrated health workers, su-

pervisory personnel, and the referral eye

care providers. It is anticipated that inte-

grated health workers will need to upgrade

training. Also, supervisory personnel, and

eye care workers (ophthalmic clinical offi-

cers, cataract surgeons, and ophthalmolo-

gists) will likely require some upgrade

training regarding lagophthalmos surgery.

Training should also cover procedures for

monitoring uptake of eye care services (pri-

marily cataract and lagophthalmos serv-

ices), and the outcome of services received.

(iv) Implementing integration at the VI-

SION 2020 planning level. VISION 2020

implementation planning occurs at the dis-

trict level; a district being defined as having

a catchment population of between 1 and 2

million people. At this level there is ex-

pected to be at least one ophthalmologist or

cataract surgeon and a team supporting

these individuals. Each district should have

a VISION 2020 Task Force. The district

leprosy control officer should meet with the

Task Force to plan out and implement the

integration strategy. The aim is to integrate

leprosy patients into the routine system for

service delivery, eliminating the need for

special structures and personnel for leprosy

patients.

(v) Program monitoring. Monitoring

should be built into the district VISION

2020 plan whereby the district leprosy con-

trol officer can verify eye care coverage and

outcome of services.

Strategic planning and implementation are

critical tools for leprosy control and preven-

tion of blindness to ensure that persons af-

fected by leprosy are fully integrated into

general eye care services in Africa. By do-

ing so it is possible to eliminate avoidable

blindness by the year 2020.

Prepared by: Paul Courtright (1), Swapan

Samanta (2), Essam el Toukhy (3), Hemed

Kilima (4), Caleb Mpyet (5), and Muthiah

Arokia Rajan (6)

1. Kilimanjaro Centre for Community Ophthal-

mology, Tumaini University, Moshi, Tanzania (pcour-

tright@kcco.net)

2. Gouripore State Leprosy Hospital, Bankura, West

Bengal, India (swapan_samanta1@rediffmail.com)

Page 76

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International Journal of Leprosy

2005

3. Cairo University, Cairo, Egypt (eeltoukhy@

yahoo.com)

4. Department of Ophthalmology, KCMC/Tumaini

University, Moshi, Tanzania (drkilima@yahoo.com)

5. Department of Ophthalmology, Jos University

Teaching Hospital, Jos, Nigeria (mpyetc@yahoo.com)

6. Sacred Heart Leprosy Centre, Kumbakonam,

Tamil Nadu, India (pratheepa_rajan@hotmail.com)

References

1. ANDERSON, R. L., and GORDY, D. D. The tarsal strip

procedure. Archives of Ophthalmology. 97 (1979)

2192–2196.

2. COURTRIGHT, P., DANIEL, E., RAO, S., RAVANES, J.,

MENGISTU, F., BELACHEW, M., CELLONA, RV., and

FFYTCHE, T. Eye disease in multibacillary leprosy

patients at the time of their leprosy diagnosis: Find-

ings from the Longitudinal Study of Ocular Lep-

rosy (LOSOL) in India, the Philippines and

Ethiopia. Lepr. Rev. 73 (2002) 225–238 .

3. COURTRIGHT, P., and LEWALLEN, S. Ocular manifes-

tations of leprosy. In: The Epidemiology of Eye

Disease, 2nd Edition. Chapman & Hall Medical,

2002.

4. COURTRIGHT, P., and LEWALLEN, S. (eds). Prevention

of Blindness in Leprosy, 3rd Edition. Singapore:

World Scientific Publishing Co. Pte. Ltd., 2000.

5. COURTRIGHT, P., and TAMPLIN, M. Guidelines for

the management of eye care in leprosy: Recom-

mendations from ILEP-supported meeting. IAPB

News. 2002: 8–9.

6. JORDAN, D. R., and ANDERSON, R. L. The lateral

tarsal strip revisited: The enhanced tarsal strip.

Arch. Ophthalmol. 107 (1989) 604–606.

7. MPYET, C., DINEEN, B. P., and SOLOMON, A. W.

Cataract surgical coverage and barriers to uptake of

cataract surgery in leprosy patients in north-eastern

Nigeria. Brit. J. Ophthalmol. (in press).

8. MPYET, C., and SOLOMON, A. W. Prevalence and

causes of blindness and low vision in leprosy pa-

tients in north-eastern Nigeria. Brit. J. Ophthalmol.

(in press).

9. www.VISION2020.org

Damien-Dutton Award

Photo: Dr. Waters (right) and Dr. Meyers

The 2004 Damien-Dutton Award was

presented to Dr. Michael F. R. Waters,

OBE, FRC P, by Trevor Durston of the Lep-

rosy Mission International of London and

Dr. Wayne Myers of the American Leprosy

Mission, at a ceremony held in London,

England on Tuesday, November 30, 2004.

Dr. Waters has a wide knowledge and expe-

rience on leprosy and is well known for his

demonstrations and lectures. He served

from 1959 to 1976 as the Director of Lep-

rosy Research in Malaysia. He has pub-

lished numerous papers on leprosy and its

treatment. His ability to communicate with

enthusiasm and lucidity to non-medical

workers has earned him the praise of many

throughout the world. He received numer-

ous honors throughout his lifetime.

Dr. Waters wrote, “I am both very hon-

ored and humbled by the kindness of the

Damien-Dutton Society on being named as

the recipient of the Damien-Dutton Award

for 2004. Although the leprosy world has

changed drastically since I first started my

work in 1959, we all continue to pray that

the love and compassion of Christ may con-

tinue to be shown to all of those suffering

from leprosy just as it was shown so re-

markably by Father Damien.”

NEWS and NOTES

Page 77

73, 2

News and Notes

163

Calendar of Meetings and Events

Day

mm/yy

Location

Details

Contact

e-mail

28–30 Jul-05

Sheraton Hotel,

US-Japan Cooperative

Gail G. Jacobs,

gg6z@nih.gov

Seattle, USA

Medical Science Program

Program Officer

Tuberculosis/Leprosy Panel

NIAID/NIH

12–30 Sep-05

ALERT, Addis Abbaba, Clinical leprosy & tropical

ALERT Training

leprosytb@elecom.net.et

Ethiopia

dermatology for Physicians

Division

www.telecom.net.et/tdalert

3–28 Oct-05

ALERT, Addis Abbaba, Management of combined

ALERT Training

leprosytb@elecom.net.et

Ethiopia

leprosy and tuberculosis,

Division

HIV/AIDS control programmes

www.telecom.net.et/tdalert

for physicians and operational

research methods in epidemiology

7–16 Nov–Dec 05 ALERT, Addis Abbaba, Clinical leprosy and management

ALERT Training

leprosytb@elecom.net.et

Ethiopia

of combined leprosy,

Division

www.telecom.net.et/tdalert

tuberculosis, and HIV/AIDS

control programmes for senior

field staff

tba

Nov-05

Joao Pessoa

10th Brazilian Congress

Francisca Estrela

of Hansenology

Notice. From Carville, U.S.A., Ceremonies

were held on Feb. 12, 2005, to mark the de-

parture of the Daughters of Charity from their

service to the National Hansen’s Disease

Hospital at Carville, LA. Sr. Marie ThJrPse

Sedgwick, Provincial, West Central Province,

St. Louis, presided over the ceremonies, de-

scribing Carville as “a place of miracles.”

Appreciation was also expressed by Bishop

Robert Muench, Diocese of Baton Rouge,

Capt. Charles Stanley, Director, National

Hansen’s Disease Programs, and Colonel

Herbert Oliver on behalf of Louisiana Gov.

Katherine Blanco. Beginning in 1896, 116

Sisters of the Daughters of Charity have

served at Carville in 109 years of continuous

service. The NHDP continues to provide care

to new and previously diagnosed patients

from its facilities in Baton Rouge, and several

patients who are retired but able to live inde-

pendently still reside at Carville.

Page 78

*Aide aux Lepreux Emmaus-Suisse, Spi-

talgasse, CH-3011 Berne, Switzerland.

*American Leprosy Missions, One ALM

Way, Greenville, South Carolina 29601,

U.S.A.

*Amici dei Lebbrosi, Foundazione Italiana

Raoul Follereau, Via Borselli 4, 40135

Bologna, Italy.

Damien-Dutton Society, 616 Bedford Ave-

nue, Bellmore, New York 11710, U.S.A.

*Damien Foundation (DF/APD), 16 Rue

Stevin, B-1040 Bruxelles, Belgium.

*Deutsches Aussatzigen-Hilfswerk e. V.,

Postfach 9062, D-97090 Würzberg 11,

Germany.

*Le Secours aux Lépreux (Canada), 1275

Rue Hodge Bureau 12, Montreal H4N

3H4, Canada

*Netherlands Leprosy Relief, Wibaut-

straat 137K, 1097 DN Ansterdam, The

Netherlands.

*Pacific Leprosy Foundation, 115 Sher-

borne Street, Bag 4730, Christchurch,

New Zealand.

*Sasakawa Memorial Health Founda-

tion, Senpaku Shinko Bldg., 1-15-16

Toranomon, Minato-ku, Tokyo 105,

Japan.

ACKNOWLEDGMENT

The Board of Directors of the INTERNATIONAL JOURNAL OF LEPROSY gratefully ac-

knowledges the financial assistance from special grantors and sustaining members

which, with the special donations of certain members, has made possible the con-

tinuation of publication of the JOURNAL directly by the International Leprosy Asso-

ciation. Without this assistance the official organ of the ILS, so essential to leprosy

workers everywhere, could not be published.

SPECIAL GRANTORS

164

INTERNATIONAL JOURNAL OF LEPROSY

Volume 73, Number 2

Printed in the U.S.A.

(ISSN 0148-916X)