INTERNATIONAL JOURNAL OF LEPROSY Volume 50. Number 4Printed in the U.S.A.

Pregnancy and Leprosy: The Consequences ofAlterations of Cell-mediated and HumoralImmunity During Pregnancy and Lactation'M. Elizabeth Duncan, John M. H. Pearson, Dennis S. Ridley,

Reidar Melsom, and Gunnar Bjune 2

Leprosy has at least three propertieswhich make it of particular immunologicalinterest:

a) It is an exceedingly chronic disease.Mycobacterium leprae, the infectingorganisms, have division times of about12 days ( 5"). Thus the incubation pe-riod is about 2-10 years (' 2 ). More-over, because of slow progression ofthe disease, the period from first ap-pearance of symptoms to initiation oftreatment can be several years.

b) M. leprac are almost nontoxic. Pa-tients with active leprosy can show abacteremia of 10 5 AFB per ml and re-main physically healthy ( 11 ). The clin-ical manifestations of the disease arelargely the result of the host responseto the infection.

c) The host parasite relationship in lep-rosy is often unstable, and variationsin both cell-mediated (CMI) and Im-moral immune responses to M. /epraecan cause clinical manifestations(called reactions) which are not di-rectly related to the bacteriologicalprogress or regression of the disease.

Cell-mediated immunity underlies the im-mune response in leprosy. The organismsare killed within macrophages activated bylymphocyte products generated in the im-

' Received for publication on 28 June 1982; acceptedfor publication on 5 August 1982.

M. E. Duncan. M.B.. Ch.B.. F.R.C.O.G.,F.R.C.S.E., National Institute for Medical Research,"Pie Ridgeway, Mill hill. London. NW7 IAA. En-gland. J. M. H. Pearson, D.M., F.R.C.P., DhoolpetLeprosy Research Centre, Hyderabad-500 006, A.P..India. D. S. Ridley, B.Sc.. M.D.. F.R.C.P., Hospitalfor Tropical Diseases, St. Pancras Way, London, NW IOl'E, England. R. Melsom, M.B., Ch.B., D.C.H.(Glasgow); G. Bjune, M.D., Institute for ExperimentalResearch, University of Oslo, Ullevaal Hospital. Oslo.Norway.

mune response to the bacilli. The delayedhypersensitivity inflammatory reactionsfound in leprosy are a manifestation of thecell-mediated response and involve a localaccu mulation of mononuclear cells. Thewide spectrum of leprosy seen clinically andhistologically is due to the level of cell-me-diated immunity and/or delayed hypersen-sitivity (DH) possessed by the individualpatient. In tuberculoid leprosy where theCMI is high there are few skin lesions andrelatively few bacilli, most of which arefound in nerves. In lepromatous leprosy,where the patient's CMI is low, there aremultiple skin lesions and the body tissuesmay harbour as many as 10" bacilli ( 57).Between the two polar forms of tuberculoid(TT) leprosy and lepromatous (LL) leprosythere is the immunologically unstable bor-derline zone: borderline tuberculoid (BT),borderline (BB), and borderline leproma-tous (BL) ( 2 ).

Reactions in leprosy are clinical phenom-ena caused by alterations in the immunestatus of the patient. There are two maintypes of reaction: Type I lepra reaction,which is an example of Coombs and GellType 4 reaction ( 24 ) and Type 2 lepra reac-tion, or erythema nodosum leprosum, whichis an example of Coombs and Gell Type 3reaction ( 75). Type 1 lepra reaction is attrib-uted to factors which alter the patient's DHwith a shift along the classification scale ( .1 ")•Increase in DH will tend to cause upgradingor shift towards the tuberculoid end of theleprosy scale (reversal reaction), which mayinvolve either skin or nerve lesions. De-crease in CMI or downgrading is only oc-casionally associated with a Type I reac-tion, although frequently with worsening ofthe patient's leprosy and increase of the ba-cillary load.

It is evident that many of the damaging

425

426^ International Journal of Leprosy^ 1982

complications of leprosy are caused by anunstable host-parasite relationship relatedto changes in the host's immune responsepotential. Diminished CMI can cause in-creased bacillary multiplication, progress ofleprosy and downgrading of classification.Type I reactions can cause neuritis, nervedamage and permanent deformity. Type 2reactions can cause both nerve damage andsystemic illness. Although the triggermechanisms of reactions are not as yetunderstood, conditions causing generaldiminution (or increase) of CMI may initi-ate reactions. Pregnancy is such a condi-tion.

During the course of pregnancy, partu-rition, the puerperium and lactation, thereare profound changes in the immunologicalstatus of the mother. Little information,however, is available on the effect of preg-nancy on leprosy except from retrospectivestudies. A collaborative study was there-fore established to investigate prospective-ly clinical and immunological aspects of theeffects of a) the mother's pregnancy andlactation on her leprosy; b) the mother'sleprosy on her pregnancy and lactation; andc) the mother's leprosy on her child frombirth up to the age of two years. The studywas carried out at the Addis Ababa Lep-rosy Hospital in Ethiopia by the MedicalResearch Council Leprosy Project and theArmauer Hansen Research Institute be-tween December 1975 and May 1978. Thispaper presents the results of the clinical ob-servations on the effect of the mother'spregnancy and first 12 months of lactationon her leprosy.

PATIENTS AND METHODSOne hundred forty-seven women were

studied during 156 pregnancies. There were114 women with leprosy (119 pregnancies)and 33 healthy women (healthy controls:HC, with 37 pregnancies). The women withleprosy were classified initially, on entry tothe study, as follows using the scale of Rid-ley and Jopling ( 52): cured tuberculoid andborderline tuberculoid leprosy (TT and BT/"cured"), 25 women (25 pregnancies); ac-tive tuberculoid and borderline tuberculoidleprosy (TT and BT/"active"), 17 women(18 pregnancies); borderline lepromatousleprosy (BL), 40 women (41 pregnancies);

and lepromatous leprosy (LL), 32 women(35 pregnancies).

Eighty-two patients were receiving dap-sone monotherapy (50 mg-100 mg daily); 26patients (I BL, the rest 13'l' or TT) werebelieved to he cured and had stopped treat-ment. Six patients (2 BL, 4 LL) had devel-oped dapsone-resistant leprosy and werereceiving clofazimine (4 patients all LL, 5pregnancies) or rifampin plus thiambuto-sine and dapsone (2 patients, both BL).

The patients were all Ethiopian womenfrom the low socio-economic class, most ofwhom lived in the villages adjacent to theAddis Ababa Leprosy Hospital. The pa-tients were first seen when they presentedthemselves at the hospital's antenatal clin-ic. Selection of patients was based on theirwillingness to participate in the study, todeliver their babies in the hospital ratherthan at home, and to be seen with their ba-bies for regular assessment, including bloodtests, for a period of up to two years duringlactation.

The patients' hospital case records wereexamined and data were abstracted regard-ing leprosy status (clinical relapse, slit skinsmear results and biopsy reports) and fre-quency and type of reaction prior to admis-sion to the study. Particular attention waspaid to the three-month period immediatelypreceding pregnancy; this was expected toprovide a base line figure for the frequencyof complications in Ethiopian women ofchildbearing age.

Assessment of the patients' leprosy wasmade during pregnancy and after deliveryat six monthly intervals whenever possible.The assessment included full examination,clinical drawings, slit skin smears, biopsiesfor histology and mouse foot pad inocula-tion ( 47), sensory skin testing ( 34) and vol-untary muscle testing ( 23). Full details arereported elsewhere. (I 7)

i) Worsening of the patient's leprosy sta-tus is defined as one or more of thefollowing: conversion from negativeto positive or rise in bacillary con-centration and proportion of solidstained (presumed viable) bacilli in slitskin smears; appearance of new le-sions, extension of existing lesions,erythema of tuberculoid lesions (withno histological evidence of reaction)

10

mown:,

20

10

. I I 1 ■

11^II I 1!3-o^0-3^4-6^7-9^0PREGNANCY

1. 4-6^7-9^10-12LACTATION

50, 4^Duncan, et al.: Pregnancy and Leprosy^ 427

or increased activity of the lesion as i)

diagnosed histopathologically.30

ii) 'I'ype 1 lepra reaction was diagnosedby the occurrence of one or more ofthe following: erythema and edema 20

(sometimes with ulceration) of skinlesions; tender enlargement of nerves Iwith or without loss of nerve functionand often of abrupt onset; loss of

10

nerve function without tender nerves ICin patients with tuberculoid or bor-derline^leprosy^(")^("silent^neuri- ■ tis"); tenosynovitis, especially of theextensor tendons over the back of thewrist ( 7"); or histopathologically ( 5).

iii) Type 2 lepra reaction was diagnosedby the occurrence of one or more ofthe following: the appearance in theskin of crops of shiny, painful rednodules, either superficial or deep,and lasting from 3-5 days (these werefrequently accompanied by a system-ic upset with fever, malaise, lymph-adenopathy and tender, enlargedperipheral nerves); iridocyclitis; dac-tylitis; or histopathologically ( 5 ').

RESULTSi) Worsening of the patient's leprosy status

Table 1 and Figure 1(i) show the num-ber of cases and timing of the worseningof the leprosy status in the women inthe study by three-month intervals fromthree months prior to conception to 12months postpartum. Two of the 155women (one LL, one BL) had shownincreased activity of slit skin smearsprior to conception. By comparison 55(35.5%) showed worsening of their lep-rosy status in association with pregnan-cy or the first 12 months of lactation. In43 of the 55 women the deteriorationoccurred during the second half of preg-nancy or the first three months of lac-tation, most commonly (31 cases) dur-ing the third trimester.

In 19 cases the deterioration wastransient with increased activity (in skinlesions, slit skin smears or biopsy) mostoften in the third trimester, which dis-appeared during lactation. However, inthe remaining 36 cases (23% of thosestudied) the deterioration was signifi-cant and progressive.

FIG. I. Time of first occurrence of complicationsof leprosy prior to conception and during pregnancyand lactation.

(i) Worsening of leprosy status(ii) Type I lepra reaction

(iii) Type 2 lepra reaction

ii) Type 1 lepra reactionThe number of patients who were di-

agnosed as having type 1 lepra reactionand the timing of the first episode in re-lation to pregnancy/lactation is shownin Table 2 and Figure 1(ii). Two womendeveloped the reactions shortly after aprevious pregnancy and within threemonths of the pregnancy under study.After an initial increase in the numbersof women with reaction in the firsttrimester, the number of new casesdropped during the second and thirdtrimesters and then increased sharplyafter delivery, decreasing only gradu-ally within the first year of lactation.Type 1 lepra reaction often continuedfor many months. Figure 2(i) shows thenumber of patients who showed evi-dence of reaction in each three-monthperiod, and demonstrates the magni-

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428^ International .1(nirmel of Lepro.sy^ 1982

.I II I I I I 10

1 I I I I I I I MONTHS^3-0^0-1^1.-6^7-9^0-3^4-6^7-9^10-12

PRiLNANCY^ LACTATION

FIG. 2. Time of occurrence of all episodes of leprareactions prior to conception and during pregnancyand lactation.

(i) Type I lepra reaction(ii) Type 2 lepra reaction

0

tude of the problem during lactation. Itshould be noted, however, that this fig-ure includes patients with "silent neu-ritis — ; this is probably caused by TypeI lepra reaction, but histological proofof the etiology has not as yet been ob-tained (I").

Site of reaction. Reaction in skin, or skinand nerve, was a feature of pregnancy andearly lactation (especially with regard to thefirst occurrence). Reaction in nerve alonewas a marked feature of lactation and oc-c.curred in only two patients during the sec-ond half of pregnancy (Table 3). Where Type

—E^1 lepra reaction occurred in skin during late5 17;^lactation it was always in association withu worsening of the patient's leprosy status.C)^Downgrading and upgrading. These were

o5 5 diagnosed histologically in all cases. Down-E^grading from BL to LL occurred in five pa-

- tients. In 3 the phenomenon was observedV c^during the third trimester, in I immediatelyu' 0 postpartum, and in 1 at six months post-

L!E-!^partum in association with worsening of the5.3^leprosy status. Upgrading reaction was ob-.a^served in six patients after delivery, in four

of whom there was concomitant clinicalevidence of reaction in skin or nerve.

iii) Type 2 lepra reactionThe number of patients diagnosed as

having Type 2 lepra reaction and thetiming of the first episode in relation to

10

TT and BT "cured"and "active" 40 41

BL 44 45LL 32 35

II (27%)19 (42%)10 (29%)

0

3 (7%)2 (6%)

50, 4^Duncan, et al.: Pre,gnancy and Leprosy^ 429

TABLE 2. Incidence of Type I and Type 2 lepra reaction according to classification ofleprosy.

No. of patients developing reactions

Finalclassificationof leprosy"

No. ofpatients"

No. ofpregnancies

studied"Type 1 lepra^Type 2 lepra

reaction^reaction

Type I andType 2reaction

concurrently

" The initial classification and grouping of patients has been revised to include new cases (previously healthycontrols) and relapse cases (previously TT and BT "cured") under appropriate classifications.

pregnancy/lactation are shown in Table2 and Figure l(iii), respectively. Threewomen had reaction during the threemonths preceding the pregnancy underinvestigation; in two cases the reactionfollowed a previous pregnancy. Therewas a rise in incidence of reactionthroughout pregnancy and the first sixmonths of lactation. Figure 2(ii) showsthe timing of the recurrent episodes ofType 2 lepra reaction; most of them oc-curred during the third trimester and thefirst nine months of lactation.

Mixed reactions. Type 1 and Type 2 re-actions occurred concurrently in five pa-tients, all of whom were upgrading duringlactation. One patient had previouslydowngraded during pregnancy. In four casesthere was also some evidence of worseningof the leprosy status.

DISCUSSIONIn certain diseases natural remission oc-

curs with the advance of pregnancy fol-lowed by deterioration after delivery. Suchdiseases include rheumatoid arthritis(27,28,44 , ,) ulcerative colitis (I 5), and sarcoid-osis ( 5"). Systemic lupus erythematosus fre-quently presents for the first time immedi-ately postpartum ( 5"), as does rheumatoidarthritis (''). Transient hypothyroidism andtransient hyperthyroidism have been ob-served following delivery of patients withHashimoto's and Graves' disease, respec-tively (I 2). In poliomyelitis ("), tuberculo-sis ( 48 . 72), and leprosy ( 2 "• 53) the disease hasbeen shown to become overt or to progressrapidly during pregnancy, especially thethird trimester and immediately postpar-tum. The high fatality and unusual severityof viral hepatitis in malnourished women

TABLE 3. Number of patients developing Type I lepra reaction in pregnancy andlactation—site of reaction.

3 monthsprecedingpregnancy

Pregnancy (trimester) Lactation (months) Total^Totalpatients episodes3 0-3 4-6 7-9 10-12

Skin only 1 I 4 12(I)" (I) (2) (I) (2) (I)

Skin and nerve I 3 1 6 10(I) (I) (I) (I) (I)

Nerve only 4 II 14 14 II 28 59(1) (2) (8) (1(1) (8)

Upgrading" 1 2 2

Total 1 6 4 6 16 18 18 13 40 83(2) (3) (5) (9) (13) (10)

" Figures in parentheses ( ) denote the number of patients developing recurrent episodes of Type I reaction.'' Upgrading was diagnosed histologically with no clinical evidence of Type I reaction.

430^ International Journal of Leprosy^ 1982

during late pregnancy is well known ( 8).Possible explanations for these observa-tions have been:

a) Raised hormone levels during pregnan-cy. Increased levels of free cortisol and17-hydroxycorticosteroid explain theremissions of rheumatoid arthritis andulcerative colitis (' 5 : 5"). Increase inendogenous corticosterone causingsuppression of host resistance may inpart explain the exacerbation of tu-berculosis and leprosy during preg-nancy. In mouse experiments nochange was observed in the rate ofmultiplication of M. leprac, but ahigher count of viable bacilli wasachieved in foot pads of mice fed ona diet containing hydrocortisone ( 58).Similar results have been obtained inexperiments using M. tuberculosis ( 5).

Treatment with stilbestrol and thy-roid hormones has been considered afactor in the sudden appearance of skinlesions of leprosy ( 32• "8) (W. H. Jop-ling, 1979, personal communication).Conversely, treatment with drugswhich have anti-thyroid activity hasbeen successful in murine leprosy ("").

b) Metabolic disturbances. General mal-nutrition and protein deficiency areprobable etiological factors in leprosy( 3 ."") and have been reported as com-mon in pregnant women in Ethiopia( 2 '). The rapid worsening of leprosyand disappearance of reactions underconditions of near starvation has beenrecorded ( 55). It is likely that depres-sion of CMI associated with severemalnutrition (") is responsible for thesephenomena.

c) Alteration in CMI during pregnancy.Recent publications have report-ed varying results regarding altera-tions in CMI during pregnancy( 0. 10. 14, 21, 29, 30. 43. 01, 70) . Some of thedifferences in results are due to vari-ations in methodology, concentrationsof lymphocytes in tissue culture, useof autologous plasma rather than stan-dard serum and choice and dosage ofmitogens and/or antigens used. Sincethese tests are all carried out in vitroand isolated from the intact immunesystem, the results may bear little re-semblance to what really happens iu

vivo. It is generally agreed that thereis some suppression of CMI probablydue to serum factor(s). Cell-mediatedsuppressor mechanisms, however,may also be involved (' 2), in particularcausing an impaired response to PPDwhich reverts to normal shortly afterdelivery.

Attempts to explain this suppression ofCMI in terms of endocrine levels have beenmade by assessing the icr vitro response tophytohemagglutinin and other mitogens inwomen taking contraceptive pills, with con-flicting results ( 3 : 2"). However, the immu-nosuppressive properties of pregnancy as-sociated a-macroglobulin (PAM) which risesdramatically in pregnancy and then dropsto insignificant levels within six to nineweeks postpartum has been demonstrated(""•"'). PAM has been identified on the sur-face of peripheral leukocytes in both preg-nant women and in women taking oral con-traceptives, and is present in some womenuntil six months postpartum. Estrogen hasbeen shown to trigger the rise in levels ofPAM (later renamed pregnancy associateda-glycoprotein: PAG) both in women tak-ing oral contraceptives and in men takingstilbestrol for prostatic carcinoma (""). It islikely that the estrogen-induced immuno-regulation is mediated through the thymus(9. While PAM (PAG) was shown to mod-ify cellular transformation most when elec-tive stimulators of T cells were used, theexact role of PAM (PAG) in the impairmentof the immune response in pregnancy hasnot been ascertained since other factors areknown to be involved. In leprosy in partic-ular it is very likely that plasma from preg-nant leprosy patients contains increasedsuppressive factors, since plasma frommothers with leprosy had a greater inhibi-tory effect on their babies' lymphocytetransformation than plasma from healthymothers ( 7).

The presence of immune complexes dur-ing normal pregnancy is controversial ( 23 . 39).The discrepancies in results may be due todifferences in methodology, and the role ofimmune complexes in human pregnancy re-mains unknown ( 38).

The diseases mentioned above show apattern of amelioration during pregnancyand rebound deterioration postpartum.Leprosy, however, shows what may be

50, 4^Duncan, et al.: Pregnancy and Leprosy^ 431

called a biphasic adverse effect, with de-terioration of the leprosy status duringpregnancy and prolonged Type 1 lepra re-action following delivery. While variousfactors as mentioned may influence the pa-tient's leprosy status, we feel that the mostlikely explanation for this biphasic effect issuppression of the mother's CMI duringpregnancy and recovery of CMI postpar-tum.

i) Worsening of the patient's leprosy statusPrevious reports indicate that preg-

nancy is apt to precipitate the appear-ance of overt leprosy ( 13, 26. 37, 53.6'.1). Ourresults fully confirm this. Six percent(2/33) of the "control" patients devel-oped leprosy during the study, and 32%(8/25) of the apparently cured cases re-lapsed.

It has also been shown previouslythat pregnancy is associated with theexacerbation of existing leprosy(13. 26, 33, 35, 37, :A, 69) .

study confirm this; 20% of the patientsreceiving treatment showed transientworsening of their leprosy during thestudy period despite apparently effec-tive chemotherapy.

A novel and hitherto unrecorded find-ing was the high proportion of patients(38% of those receiving treatment) whoshowed significant and apparently pro-gressive deterioration almost certainlycaused by the emergence of dapsone-resistant leprosy (proven in all sevencases where mouse foot pad tests wereundertaken). This high figure may be re-lated to the high proportion of new casesin Ethiopia (about 50%) showing pri-mary low-grade dapsone resistance ( 43).

The immunosuppression of pregnancymay well afford the opportunity for drug-resistant bacilli to multiply and causeovert disease unusually rapidly. Thesefindings have been fully reported else-where ('").

The phenomenon of downgrading wasobserved particularly during pregnancy andmight be expected in any condition whereCMI is suppressed. Within the LL group anumber of patients showed a shift from sub-polar lepromatous leprosy (LL s) to polarlepromatous leprosy (LL„) (I in associa-tion with exacerbation of the infection.

ii) Type 1 lepra reactionSince this is usually due to an in-

crease in CMI or DH it is not surprisingthat it occurs immediately after deliv-ery and our study confirmed the find-ings of others ( 12 ' 33 ' 33). However, theclassical appearance of reversal reac-tion with erythema and edema of skinlesions was not a prominent feature inour patients, except in those who alsorelapsed with active leprosy or who hadvery recently started treatment. Thepicture described by Rose and Mc-Dougall ( 33) may reflect the natural evo-lution of the disease in untreated pa-tients. We did, however, observe thatreaction in skin or skin and nerve wasa feature of pregnancy and early lacta-tion; whereas reaction in nerve alonewas a feature of the lactation period.This may reflect predominant exposureof the surface antigens of actively mul-tiplying M. leprae during pregnancy andrelatively increased uncovering of cy-toplasmic antigens postpartum (. 1), ifpostpartum recovery of CMI leads tobacillary destruction. Reversal reactionwas sometimes unusual in that it wasseen coincidentally with Type 2 lepra re-action.

While the peak incidence of new cases ofType I lepra reaction occurred immediatelyafter delivery, new and recurrent episodesalso occurred late in lactation, suggestingthat residual Schwann cells in the nervetrunks contained small numbers of bacilliwhich previously went unrecognized ( 7.1 ),but with recovery of CMI were recognizedand attacked. Alternatively, late reactionmay be caused by the release of sensitizedlymphocytes which can be trapped in thespleen for prolonged periods (").

iii) Type 2 lepra reactionOur observations confirmed other re-

ports of an increase in Type 2 lepra re-action during pregnancy (33.40' 71 ) andduring lactation (33.37). The reaction wasassociated with exacerbation of leprosyand occurred throughout pregnancy witha peak in the third trimester [Fig. 2(11)],gradually decreasing during the first yearof lactation. The incidence is higher thanwould be expected in non-pregnant pa-tients on treatment, particularly in the

The results of this

432^ International Journal of Leprosy^ 1982

BL group, and is probably associatedwith the suppression of CMI, increasedmultiplication of bacilli and hence in-creased antigen load, and a tendency toshift towards the lepromatous pole ( 7").

This study highlights the risks to whichleprosy patients are exposed when they be-come pregnant. Their disease may relapseor deteriorate, and they are liable to devel-op reactions or neuritis for many monthsafter delivery. Moreover, there may be re-luctance to use either additional chemo-therapy or corticosteroids during preg-nancy and lactation; thus the medicalmanagement of these patients is made moredifficult. There is clearly a place for healtheducation in this situation. Patients shouldbe made aware of the risks they undergoand encouraged to plan their pregnancies totake place only when their leprosy is fullycontrolled by chemotherapy. Careful med-ical supervision during and after pregnancyshould, however, reduce the consequences(if not the incidence) of leprosy complica-tions associated with pregnancy. Aware-ness on the part of the obstetrician of po-tential leprosy problems may play a criticalpart in their early recognition and correctmanagement.

SUMMARYOne hundred fourteen Ethiopian women

with leprosy and 33 healthy women with-out leprosy were studied prospectivelythroughout 119 and 37 pregnancies, respec-tively, and followed up during lactation.Fifty-five women showed worsening of theirleprosy status; in 31 (56%) this was ob-served during the third trimester of preg-nancy. Forty women were diagnosed ashaving Type I lepra reaction; in 20 (50%)the first occurrence was during the first sixmonths of lactation. Twenty-eight womenhad Type 2 lepra reaction, which in 19 (68%)first occurred during the third trimester ofpregnancy or the first six months of lacta-tion. These adverse effects of pregnancy onleprosy are thought to be associated withsuppression of maternal cell-mediated im-munity during gestation and recovery post-partum. Implications for the obstetrician,physician and leprosy health worker arediscussed.

RESUMENSe hizo tin estudio prospectivo de 114 mujeres con

lepra y de 33 mujeres sanas a traves de 119 y 37 em-barazos, respectivamente. El estudio se continuo has-tit Ia lactancia. Cincuentit y cinco mujeres mostrarontin agravamiento de su enfermedad: en 31 mujeres (56%)

est° se observ(i durante el tercer trimestre del emba-

razo. Cuarenta mujeres presentaron reacciones lepro-sas del Tipo I; en 20 de ellas la primer aparicitin de

reaction leprosa ocurrni durante los primeros 6 meses

de la lactancia. Veintiocho mujeres tuvieron reaction

leprosa del Tipo 2 la caul, en 19 (68%) apareciti durante

el tercer trimestre del embarazo o durante los primeros

6 meses de lactancia.Se piensa que estos efectos adversos del embarazo

en lepra estiin asociados con supresion de Ia inmuni-

dad celular materna durante la gestaciOn y durante la

rectiperaciOn post-parto. Se discuten las implicacionespant el obstetra, el medico y el leprOlogo.

RESUMEOn a mene tine etude prospective de la grossesse et

de Ia lactation chez cent quartorze femmes ethipiennessouffrant de lepre (119 grossesses) et chez trente-trois

femmes temoins indemnes de lepre (37 grossesses).

Chez cinquante-cinq femmes malades, on a observe

one deterioration de Ia situation de Ia maladie. Chez31 &entre Liles (56%) cette deterioration a etc obser-

vee au cours du troisieme trimestre de la grossesse.

Une reaction lepreuse de Type I a etc diagnostiqueechez quarante femmes: chez 20 (50%), le premier epi-

sode se situait au cours des six premiers mois de Ia

lactation. Une reaction lepreuse de Type 2 a etc noteechez vingt-huit femmes, dont 19 (68%) ont presente lepremier episode an emirs du troisiéme trimestre de la

grossesse ou durant les six premiers mois de Ia lac-tation. On estime que les effets adverses qu'cxerce lit

grossesse stir Ia lepre sont associes a tine suppressionde l'immunite a mediation cellulaire chez Ia mere aucours de la grossesse et du post-partum. Les impli-cations pour l'obstetricien, le medecin et le travailleur

de lepre sont discutees.

Acknowledgments. We are most grateful to the staff

and patients of the Addis Ababa Leprosy Hospital,

particularly Ato Moges Mend and Ato Wondemageg-nchu Mekuria, without whose help and cooperationthis study would not have been possible. We also thankProfessor A. E. Beer and Doctors D. A. Seaton and

W. H. Stimson for helpful comments during the prep-aration of the manuscript.

M. E. Duncan was supported for part of the study

by a research grant from the British Leprosy ReliefAssociation (LEPRA).

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