INTERNATIONAL JOURNAL OF LEPROSY^ Volume 58, Number 4

Printed in the U.S.A.

Prospective Immunological Follow-up inHousehold Contacts of Mexican Leprosy Patients'

Maria Eugenia Amezcua, Alejandro Escobar-Gutierrez,Josê Barba-Rubio, Jose Victor CAzares, Elvira Mayen,

Miguel ChAvez-NCinez, Rosa C. Pena, Raudel Rodriguez,and Sergio Pastên2

Individual susceptibility to Mycobacte-rium leprae infection and the developmentof leprosy are not concomitant character-istics, and the disease depends on the con-currence of several host and environmentalfactors collectively called "risk factors," suchas certain genetic traits, a continuous con-tact with the bacilli, the immune status ofthe host, the type and magnitude of immuneresponses elicited, etc. Current knowledgeon this subject points out alterations in theimmune responsiveness as the major riskfactors in the shift from an unnoticed M.leprae infection toward its clinical expres-sion (10' '2. 19, 20, 30).

In 1955, Dharmendra and Chatterjee (21 )

investigated the prognostic value of nega-tive lepromin reactions in persons exposedto M. leprae. Further data have demonstrat-ed the limitations of this parameter when itis the only one taken into consideration,mainly because of crossreactivity with othermycobacteria (6.27 ) and the fact that suchskin reaction is under genetic control ( 17 ).The improvement of serological methodsfor leprosy with better specificity and sen-sitivity (33) opened a new approach andprompted several epidemiological surveys

' Received for publication on 17 July 1989; acceptedfor publication in revised form on 20 April 1990.

= M. E. Amezcua, M.Sc., Head, Laboratory for My-cobacterial Research; A. Escobar-Gutierrez, Ph.D.,Head of Department; J. V. Cazares, Biol. Tech.; E.Mayen, B.Sc.; S. Fasten, B.Sc., Departamento de In-vestigaciones InmunolOgicas, Instituto Nacional deDiagnOstico y Referencia EpidemiolOgicos, Secretariade Salud Mexico, Carpio 470, Mexico, D. F. 11340,Mexico. J. Barba-Rubio, M.D., Director; M. Chavez-NUilez, M.D., M.S.P., Epidemiologist; R. C. Pefia, M.D.,Dermatologist; R. Rodriguez, M.D., Dermatologist,Instituto DermatolOgico de Guadalajara, Secretaria deSalud Mexico, Federalismo Norte 202, Atemajac, Za-popan, Jalisco 45190, Mexico.

Reprint requests to Dr. Escobar-Gutierrez.

to be made in order to seek the correlationbetween the risk of developing the diseaseand the specific immune status in leprosyhouseholds. Most of these surveys havebeen carried out looking for either leprominreactivity (21,28,37) or in vitro lymphocytetransformation (25 ' 34 ' 37 ) in the case of theT-dependent response or, similarly, forthe presence of specific antibodies withmethods such as the FLA-ABS test (2 ' 7 ),

radioimmunoassay (5.40 ),) or ELISA(3, 13, 14, 16, 22, 23.35)) Few reports have dealtwith both cellular and humoral responsesevaluated at the same time ( 5 ' 8 ' 9'

38.39) orwith more than one observation in the samepopulation (13, 14, 17,

22 ).) According to thestrategy of the investigation, method ormethods selected and antigen employed, theresults were rather different but all of themsupport the importance of adequate im-munological studies if correct identificationof individuals at risk is intended. Combinedresults of skin and serological tests are betterindications of risk, as has been shown byDharmendra (20 ' 2 ' ) and Bharadwaj, et al. (9),

who recommend the classification of house-holds into four groups where lepromin reac-tivity is interpreted as a relative resistancemarker when specific antibodies are alsopresent.

In our study, the same approach was fol-lowed but the paucibacillary or multibacil-lary character of the index case and changesin antibody levels over time were also con-sidered. After 6 years of observation, a newborderline lepromatous (BL) leprosy casewas found in a household with a leprominunresponsiveness, rising amounts of M. lep-rae-specific antibodies, and extensive con-tact with a bacilliferous index case. How-ever, due to the size of the sample studied,more information will be required before

651

652^ International Journal of Leprosy^ 1990

any definitive conclusion can be reached re-garding the contribution of the multibacil-larity of the index cases as an important riskfactor.

MATERIALS AND METHODSWorking plan. This study was performed

in families living in the neighborhood of themetropolitan area of Guadalajara, State ofJalisco, Mexico. In this area, there are 1685registered leprosy patients, giving a "cu-mulative" prevalence rate of 92 per 100,000,almost five times the national prevalence of20 per 100,000. Epidemiologically, they areunder the control of the Health Departmentof the State of Jalisco, and the majority aretreated clinically in the Instituto Derma-tolOgico de Guadalajara.

For purposes of the study, families wererandomly chosen on the basis of the iden-tification of an untreated or inadequatelytreated active leprosy patient (index case)and no less than three household contactswho agreed to participate in the study. Inthe first interview, a comprehensive clini-cal, histopathological, and bacteriologicalstudy was made of all members of the fam-ily. Simultaneously, a skin test with lepro-min A was given and a blood sample wastaken from each participant. The follow upconsisted of at least three home visits in aperiod of 5 years, at which time anotherclinical evaluation was made and a newblood sample was obtained from the con-tacts only. After the classification of the in-dex case in the leprosy spectrum, the fam-ilies were divided into two groups: a) onegroup with a lower risk where the index caseswere nonbacilliferous (tuberculoid and in-determinate), and b) the other group with ahigher risk where the index cases were mul-tibacillary (lepromatous).

Index cases. The index cases had a re-corded history of clinical leprosy not lessthan 5 years, had not been treated at all, ortheir chemotherapy was promptly stoppedor followed irregularly. Before the study wasinitiated, the diagnosis and classification ofeach case was confirmed by standard estab-lished methods. The final selection included25 patients: 7 (2 tuberculoid and 5 indeter-minate) were assigned to the lower-riskgroup, and 18 lepromatous leprosy cases

were selected for the higher-risk group. Con-ventional treatment was immediately start-ed and carefully watched in all of the indexcases.

Household contacts. The household con-tacts included persons living in a permanentway in the same house with the index caseat least 1 year before the patient had initi-ated regular treatment, if treated at all. Thecontacts were classified in three degrees: a)type I, the contact lives in the same houseas the index case but sleeps in a differentroom; b) type II, both individuals sleep inthe same room; c) type III, they share thesame bed. Initially, total household contactsnumbered 122 individuals, but only 79completed 5 years of observation. Individ-uals were lost to the study mainly becausethey refused to continue participating or leftthe area permanently because of marriageor migration. The sixth year of this studywas mainly dedicated to locating this groupand looking for new leprosy cases amongthem. The household contacts who com-pleted the survey were in the lower-riskgroup: 19 individuals (6 males, 13 females)with initial ages between 5 and 38 years(mean, 15 years), the majority (17) with typeII contact and only 2 with type III. In thehigher-risk group, there were 60 householdcontacts (30 males, 30 females) between theages of 2 and 68 years (mean, 19 years) whocompleted the survey; 50 lived in type IIcontact and 10 in type III.

Mitsuda test. Lepromin A prepared andstandardized (4 x 10 7 bacilli/ml) at theGWL Hansen's Disease Center, Carville,Louisiana, U.S.A., was used throughout thestudy. The test was given and read by ex-perienced staff using the following scale: 1+= 5 mm to 7 mm in diameter; 2+ = 8 mmto 10 mm; 3+ = 11 mm ( 15).

FLA-ABS test. Specific antibody titersagainst M. leprae were determined with anindirect immunofluorescence method asproposed by Abe, et al. (2), with slight mod-ifications as described in full detail in a pre-vious report (4). A positive result at anytiter was considered enough to qualify thesample as "positive."

Identification of new cases. Minimumcriteria for defining a new leprosy case werethe presence of delimited depigmentationof the skin, with or without sensory loss,

58, 4^Amezcua, et al.: Immunological Follow-up of Contacts^653

where at least one acid-fast bacillus couldbe observed after the bacteriological ex-amination of the corresponding skin biopsy.If most typical lesions were found, theirclassifications in the spectrum of the diseasewere made following the Ridley and Joplingcriteria ( 38) after bacteriological and histo-pathological study of the skin biopsies.

Statistics. The Student's t test was em-ployed to compare the means of the results.Regression lines and coefficients of corre-lation were calculated according by the least-square method. Correlation coefficient sig-nificances were made using Pearson's test.Values of p < 0.05 were considered to bestatistically significant.

RESULTSMitsuda test.The results of the Mitsuda

test in all of the household contacts includedin this study showed that 71.7% were pos-itive to late lepromin reaction. No differ-ences in sex or age were found between pos-itives and negatives. The differentialdistribution of reactors in the lower- andhigher-risk groups are described below.

FLA-ABS test. In order to analyze thehumoral immune response of the wholepopulation studied, only the results in thefirst observation were taken into accountbecause it was the largest of the three sam-ples and, therefore, the most representativeof the serological profile of the inhabitantsstudied. As expected, all 25 index casesshowed positive results regardless of theirleprosy type. In their contacts, 93.6% wereseropositive no matter their sex, age, or typeof leprosy in the patient with whom eachone had contact. When they were separatedin contacts of well-defined bacilliferouscases, on the one hand, and contacts of pau-cibacillary patients on the other, 95.3% werepositive in the former and in the latter 88%were positive, differences which were notstriking.

Lower-risk group. From the 19 house-hold contacts of nonbacilliferous cases, 17showed a positive Mitsuda test (89.5%) withthe following distribution: 7 were 1+ re-actors, 9 gave 2+ reactions, and only 1 hada 3+ result. The remaining two Mitsuda-negative individuals were contacts of dif-ferent indeterminate index cases. The titers

of anti-M. leprae-specific antibodies in allof the cases of this lower-risk group for thethree consecutive samplings are shown inTable 1 and Figure 1A. In the Mitsuda-pos-itive contacts, only two of them showed ini-tial titers of 1:640 or higher which decreasedover time. In subsequent observations, noneof the rest of them had values higher than1:160. When the results in the second sam-ple were compared with findings of the first,no statistical differences were observed inthe rise or fall of the original titers of specificantibodies. When the third sample was takeninto account, only 29% of the sera showeda small increase in titer, always at a lowlevel. The regression line shows a lack ofcorrelation over time (r = 0.25, p > 0.05),which suggests a constant homogeneity inthe antibody response in individuals of thissubgroup. Conversely, in the two Mitsuda-negative individuals the titers showedmarked increases (up to eightfold) from theinitial value. After 6 years of observation,none of the individuals included in thisgroup manifested any sign suggestive of lep-rosy.

Higher-risk group. In the group of 60contacts of active multibacillary patients,38 were positive to the skin reaction withlepromin (61.6%); 21 reached a 1 + reac-tion, 12 gave a 2+ result, and 4 were 3+.FLA-ABS test results were analyzed ac-cording to Mitsuda responsiveness (Table2).

In late reactors to lepromin A skin tests,individual titers of antibodies against M.leprae showed some differences in the upperand lower values they reached in each oneof the three observations made, but in everyone the most frequent titer was 1:160. Re-garding individual variations in titer duringthe study, the majority of the contacts inthis category remained constant or even hada significant decrease, 71% from the first tothe second sample and 81.5% from the sec-ond to the third. Analyzing the data fromeach time point showed no statistical dif-ferences among them and the changes intiter had a negative correlation over time (r= —0.086, p > 0.1; Fig. 1B), quite similarto the Mitsuda-positive contacts in the low-er-risk group.

In the Mitsuda-negative contacts of LLpatients, the titers of anti-M. leprae anti-

4

3

0

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* •r = —0.086

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1^

1C

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00

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1 A

0

1 B

CO

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654^ International Journal of Leprosy^ 1990

1st^

2nd^

3rd^

1st^

2nd^

3rd^

1st^

2nd^

3rd

SAMPLESFIG. I. Correlation between FLA-ABS anti-M. leprae titer and its change over time. IA = lower-risk group,

Mitsuda-positive contacts; 1B = higher-risk group, Mitsuda-positive contacts; 1C = higher-risk group, Mitsuda-negative contacts. Best fitting regression lines are shown as straight lines; r = coefficient of correlation.

bodies reached levels slightly higher thanthose observed in the Mitsuda-positive con-tacts. Their distribution showed a fiat-typecurve without predominance of any specifictiter, but contrasting with the results in thegroup of reactors, individual antibody lev-els remained constant or increased progres-sively in almost all of the subjects studied;95% from the first to the second sample and82% from the second to the third. The find-ings were statistically significant (p < 0.02),and when the relationship between changesin titer over time was estimated, a weak butsignificant correlation was seen (r = 0.37, p< 0.01; Fig. 1C). Thus, this subgroup be-haves differently from the Mitsuda respond-ers, either from the lower-risk or higher-riskgroups, with a progressive slow exacerba-tion in the antibody response.

A remarkable finding among those indi-viduals belonging to the Mitsuda-negativecontacts of LL patients was the detection ofa new leprosy case. This case was a 13-year-old male, son of an irregularly treated, 50-

year-male LL patient, who maintained along-term type II household contact. In hisinitial evaluation a negative lepromin skintest was observed, and a titer of 1:1280 wasfound in the absence of any clinical sign ofleprosy. The skin lesion identified in thisnew case had features histopathologicallyand bacteriologically compatible with BLleprosy. Until now, he is the only partici-pant in this study who has developed Han-sen's disease.

Lost household contacts. In an attemptto know the rate of new leprosy among thelost household contacts evaluated only onceat the beginning of the study, a deliberateattempt to locate them was made 6 yearslater. This included home visits, the searchfor new addresses, and a careful review ofthe official leprosy records from the last 6years. It was not possible to detect any lep-rosy cases among those individuals located,but it is important to point out that nearly30% are known to be migratory workers whospend most of their time traveling through-

58. 4^Amezcua, et al.: Immunological Follow-up of Contacts^655

TABLE 1. Distribution of anti-M. leprae antibody titers in household contacts of pau-cibacillary (TT and I) leprosy cases.

FLA-ABStiter

Mitsuda positive (N = 17) Mitsuda negative (N = 2)

First sample Second sample Third sample First sample Second sample Third sample

No. % No. No. % No. % No. 0/0 No.

0 2 11.8 0 0 0 0 01:10 3 17.6 2 11.8 0 0 0 01:40 4 23.5 4 23.5 4 23.5 50 0 01:160 6 35.3 11 64.7 13 76.5 50 50 01:640 1 5.9 0 0 0 0 1 501:1280 1 5.9 0 0 0 50 1 501:2560 0 - 0 0 0 0 0

out the country, making difficult their di-agnosis and/or their registration in the lep-rosy surveillance program.

DISCUSSIONThe long-term prospective investigation

of clusters of leprosy bacilli-exposed indi-viduals is the only way to find parameterswhich separate the disease-prone from pro-tected subjects. The field studies involvedcannot be planned unless an adequate in-frastructure of specialized health servicesand, consequently, a high level of opera-tional efficiency is implemented. Guadala-jara, the second largest city in Mexico, pro-vides the facilities and conditions for reliableidentification and recruitment of index casesand their families, as well as an effectivemonitoring system.

A comparison of the results in leprosycontacts with other populations for controlpurposes is not easy because false-positivefindings in leprosy tests are common inhealthy people. If they come from nonen-demic areas probably this positive test re-

sult is the effect of cross-sensitization. Inpopulations from leprosy-endemic areas, inaddition to possible cross-sensitization,there could be unknown specific exposureto Al. leprae (6, 11, 32, 36 , .) For such reasons,in this work healthy families without knowncontact with leprosy cases were ruled out asa control group, and we decided to separatethe contacts of multibacillary (LL or BB)patients from those related to paucibacillary(TT and indeterminate) cases, assuming thatthere are more new leprosy cases in the for-mer (higher-risk group) than in the latter(lower-risk group) as is generally accepted(12, 36, ,) although some doubts still remain(4 '). In selecting the methods for evaluatingspecific immune status, the Mitsuda skintest was chosen, in spite of its inherent op-erational difficulties in performing andreading, because it remains the best avail-able way to look for specific T-lymphocyteresponse (''). Concerning anti-M. leprae an-tibodies, the FLA-ABS test was used due toits high sensitivity throughout the wholespectrum of the disease and its excellentspecificity as has been found in all studied

TABLE 2. Distribution of anti-M. leprae antibody titers in household contacts of mul-tibacillary (LL) leprosy cases.

FLA-ABStiter

Mitsuda positive (N = 38) Mitsuda negative (N = 23)

First sample Second sample Third sample First sample Second sample Third sample

No. No. No. No. 0/0 No. No. 0/0

0 2 5.3 3 7.9 5.3 2.... 8.7 0 - 01:10 3 7.9 11 29.0 4 10.5 3 13.0 2 9.1 01:40 12 31.4 20 52.6 8 21.1 5 21.7 12 54.6 I 4.61:160 11 29.0 4 10.5 24 63.1 7 30.6 5 22.6 7 31.81:640 6 15.8 0 0 2 8.7 2 9.1 7 31.81:1280 2 5.3 0 0 3 13.0 1 4.6 7 31.81:2560 5.3 0 0 1 4.3 0 - 0

656^ International Journal of Leprosy^ 1990

populations (2, 7, 24, 26, 31 ) , including MexicanMestizos ( 4).

Before discussing our findings in both riskgroups, it is important to consider the stud-ied population as a whole. The proportionof Mitsuda reactors was similar to that insome other reports (21 . 28 ), but not all ( 1 . 3 ').Also, the FLA-ABS test gave results in ac-cordance with other reports (2, 79, 26 ) exceptone ( 39). Disagreements in both cases areprobably the consequence of the genetic,cultural, and socioeconomic differencesamong such populations. The presence of ahigh number of leprosy contacts with de-tectable amounts of specific antibodies bythe FLA-ABS test was independent of thecloseness or extent of the relationship withhousehold contacts with heavy loads of ba-cilli. This suggests an efficient circulation ofM. leprae, an almost universal susceptibilityto be colonized with them, a long persis-tence of antibodies once sensitization hasbeen acquired, and frequent events of re-stimulation by the bacillus. Thus, with theFLA-ABS test it is easy to demonstrate con-tact with the bacteria but its positivity is notenough to identify an infection in progressor to estimate the risk of developing thedisease.

The lower-risk group studied here wassmall and definitive conclusions could notbe made. Nevertheless, in all but two in-dividual's responses were as expected in animmune situation, that is, a good T-cellreactivity and relatively low stabilized lev-els of specific antibodies. It is worth point-ing out that the remaining two Mitsuda-negative household contacts seem to be inan adverse condition if our previous sup-position was correct. Both were contacts andclose relatives of independent indetermi-nate cases and their immunological behav-iors could be the result of the presence ofhigh-risk factors shared with their indexcases and common sources of infection.

The higher-risk group comprised two well-defined populations separated according toMitsuda test results. The first population areresponders, and they display quite a ho-mogeneous pattern in their humoral re-sponses, resembling Mitsuda-positive con-tacts in the lower-risk group. The secondpopulation do not show a late response tothe lepromin skin test, which may not nec-essarily be the result of a leprosy-associated

anergy because other causes, such as the ef-fect of certain genetic traits, insufficient sen-sitization, secondary immunodeficiencies,or some other nonimmunological factors,could account for the same result. As wasmentioned, specific as differentiated fromnonspecific causes could be assumed if anti-Al. leprae antibodies were present simulta-neously. Although all of these Mitsuda-neg-ative household contacts had such antibodies,analysis of their titers showed a general ten-dency to reach greater levels than did Mit-suda-positive contacts and, in most of them,there was an increase over time. It is verylikely that such results really reflect the pres-ence of an active subclinical leprosy infec-tion as has been reported (8, 9, 13, 14, 17, 22) , atleast in the case of unusual levels of specificantibodies.

In this study, the highest most commonFLA-ABS titers in the lower-risk groups(Mitsuda-positive contacts of any leprosycase) were 1:40 and 1:160, hence an eight-fold or greater value could arbitrarily betaken as evidence of an active infection.However, we must question the feasibilityof this conclusion due to the size of the sam-ple studied. Additional support for theimportance of detecting a high titer of anti-bodies associated with lepromin unrespon-siveness is the fact that the new leprosy casereported here fulfills such characteristics.However, it will be necessary to undertakea prospective study of larger groups fromother endemic areas before we can reach anydefinite conclusion.

The increment of antibody titers foundin part of the Mitsuda-negative contacts,their weak but significant correlation overtime, could be interpreted as being the resultof a constant antigenic stimulation and,consequently, the existence of subclinicalleprosy. This is an approach which routinelyhas been used in the serodiagnosis of severalacute viral and microbial infections and sel-dom used in chronic infectious diseases. Thepreliminary data presented here suggest itsapplication in the case of leprosy. Surely theinterval between each serological determi-nation must be in terms of years apart, andthis involves serious operational difficultieswhich can limit its practice on a wider scalein many endemic areas. When possible, wefeel this procedure could be worthwhile ifit could eventually be adequately validated.

58, 4^Amezcua, et al.: Immunological Follow-up of Contacts^657

In conclusion, our results clearly supportthe role of the immune response as a riskfactor in the development of leprosy, butnot the close and extensive contact with anactive multibacilliferous case. Moreover, ourlower- and higher-risk groups seem to bevery similar in their immunological behav-ior, regardless of the bateriologic nature oftheir index cases. Such a situation fits verywell with the proposition made and devel-oped by Dharmendra (20,21) and Bharadwaj,et al. (8 ' 9 ) as already mentioned. Therefore,it will be necessary to continue the surveil-lance of this study group for a longer timein order to find conclusive answers. Thisand other similar studies should provideuseful data for the identification of personsat risk of developing leprosy.

SUMMARYA 6-year prospective study of 79 house-

hold contacts of leprosy cases was made inorder to correlate the development of thedisease with their specific T-cell immunity,measured by the Mitsuda test, and levels ofanti -Mycobacterium leprae antibodies de-termined in three consecutive observationswith the FLA-ABS test. Overall in the con-tacts, 71.7% were Mitsuda positive and93.6% showed seropositivity, without re-gard to their age, sex, or leprosy type of theirindex case. Households were divided intolower-risk and higher-risk groups accordingto either the paucibacillary or multibacillarycharacter of their index case. The lower-riskgroup consisted of 19 contacts of 2 tuber-culoid (TT) and 5 indeterminate cases. Thehigher-risk group was made up of 60 house-hold contacts of 18 active lepromatous (LL)cases. All but two contacts in the formergroup had a positive Mitsuda reaction; themost common antibody titer was 1:160, witha tendency to stabilize or decrease over time.In the two Mitsuda-negative contacts, in-creased antibody levels were observed. Inthe higher-risk group, 61.6% were Mitsudapositive and showed a humoral profile sim-ilar to those Mitsuda positive in the lower-risk group. In most of the Mitsuda-negativeLL contacts, the antibody levels remainedconstant or progressively increased, sug-gesting a high probability of active subclin-ical infection. This assumption was partiallysupported by the finding of a new borderlinelepromatous (BL) leprosy case in the Mit-

suda-negative LL contact group. Neverthe-less, the contribution of the close and ex-tensive contact with a multibacilliferous caseas a risk factor was difficult to evalute be-cause of the small size of the sample studied.

RESUMENEn un estudio prospectivo de 6 afios de 79 contactos

convivientes con casos de lepra, se intentO correlacio-nar el desarrollo de la enfermedad con la respucstainmune celular especifica (reacciOn de Mitsuda) y conlos niveles de anticuerpos anti-Mycobacterium leprae(prueba FLA-ABS, tres observaciones consecutivas).El 71.7% de los contactos fueron Mitsuda positivos yel 93.6% mostraron seropositividad independiente-mente de la edad, sexo o tipo de lepra del caso indicerespectivo. Los convivientes se dividieron en gruposde bajo- y de alto-riesgo de acuerdo al caracter pau-cibacilar o multibacilar de su caso indice. El grupo debajo riesgo consisti6 de 19 contactos de 2 pacientestuberculoides (TT) y de 5 casos indeterminados. Elgrupo de alto riesgo estuvo formado por 60 convi-vientes de 18 casos lepromatosos (LL) activos. Excepto2, todos los contactos en el primer grupo tuvieron unareacciOn de Mitsuda positiva; el titulo mds comUn deanticuerpos fue de 1:160, con tendencia a estabilizarseo a decrecer con el tiempo. En los 2 contactos Mitsuda-negativos se observaron niveles aumentados de anti-cuerpos. En el grupo de mayor riesgo, el 61.6% de losconvivientes fueron Mitsuda positivos y mostraron unperfil humoral similar a los Mitsuda positivos en elgrupo de menor riesgo. En la mayoria de los contactosMitsuda negativos los niveles de anticuerpo perma-necieron constantes o aumentaron progresivamente,sugiriendo una alta probabilidad de infecciOn subcli-nica activa. Esta suposiciOn fue parcialmente apoyadapor el hallazgo de un caso nuevo de lepra lepromatosalimitrofe (BL) en el grupo de contactos (de LL) Mitsudanegativos. La contribuciOn del contacto intimo y pro-longado con un caso multibacilifero como un factor deriesgo fue dificil de evaluar debido al pequeno tamafiode la muestra estudiada.

RESUME

Une etude prospective d'une duree de 6 ans fut rea-lisee parmi 79 contacts domiciliaires de malades de lalepre afin d'etudier la relation entre lc developpementde la maladie et l'immunité cellulaire specifique, me-suree par le test de Mitsuda, et les taux d'anticorpsanti-Mycobacterium leprae determines par trois ob-servations consecutives avec le test FLA-ABS. Parmi('ensemble des contacts, 71.7% etaient positifs au Mit-suda, et 93.6% ont montre une seropositivite, sans tenircompte de Page, du sexe, ou du type de lepre du casindex. Les maisonnees furent divisees en groupesfaible risque et a risque eleve en fonction du caracterepauci- ou multibacillaire du cas index. Le groupe

658^ International Journal of Leprosy^ 1990

faible risque etait constitu& de 19 contacts de 2 maladestuberculoides (TT) et de 5 malades indetermines. Legroupe A risque eleve emit constitu& de 60 contactsdomiciliaires de 18 cas lepromateux actifs (LL). DansIc premier groupe, tous les contacts sauf deux avaientune reaction de Mitsuda positive; le titre d'anticorpsle plus frequent etait 1:60, avec une tendance A la sta-bilisation ou a la diminution au cours du temps. Des^7.taux Cleves d'anticorps ont etc observes chez les deuxcontacts negatifs au Mitsuda. Dans le groupe a risqueCleve, 61.6% etaient positifs au Mitsuda, et montraientun profil serologique similaire A celui des contacts Mit-^8.suda positifs du groupe A faible risque. Cher la plupartdes contacts de LL A Mitsuda n&gatif, les taux d'anti-corps resterent constants ou augmenterent progressive-^9.ment, suggerant une grande probabilite d'in fection sub-clinique active. Cette hypothese emit partiellementetayee par la decouverte d'un nouveau cas de lepreborderline lepromateuse (BL) dans Ic groupe des con-^10.tacts de malades LL A Mitsuda negatif. Neanmoins lacontribution comme facteur de risque du contact rap-proche et prolong& avec un cas multibacillifere fut dif-^11.ficile A evaluer du fait de la petite taille de l'echantillon&tudie.

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Acknowledgments. This work was partially sup-ported by grants nos. PCSABNA-21649 and PCSAC-NA-050625 from Consejo Nacional de Ciencia y Tec-nologia (CONACyt), Mexico. We are most grateful toDr. Eleanor Storrs for supplying the armadillo liverinfected with M. leprae. We are also grateful to Dr.Victor Manuel Ruiz Godoy for his helpful advice, sup-port and guidance throughout this work. We are thank-ful to Mrs. Socorro Sandoval for her cooperation. Ourthanks also go to Dr. Ethel Garcia for her helpful com-ments on and revision of the manuscript, and to Mrs.Silvia Diaz for her excellent secretarial assistance.

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