I NT ERNATIONAL JOU RN A L O F LEP ROSY Volume 3:). N u mber 4 Prin/n / hi U .S. A .

~, A Study of Blood Groups and Leprosy in the

Population of Colonia Tovar, 1. ~

Michel F. Lech at, Thomas Bile and Enrico Rasi 3

As a preli min ary trial fo r a larger study ers, ,vho li ve around the church, the popu­ of geneti c polymorphism and leprosy, a lation is scattered in small farms in th e sm vey of ABO blood groups was undertak­ vall ey or foo thills. The households are oft en en among leprosy patients and nonl eproti c constituted by three generati ons, grandpar­ controls in the isolate of Colonia Tovar in ents, parents and children. Venezuela. The German popu lation of the region, however, is not limited to Coloni a Tovar. STUDY AREA As the popul ati on increased over the las t Colonia Tovar is located in a valley cov­ hundred years, a few satellite haml ets de­ ering approxim ately 13 square miles, at an veloped in nearby vall eys beyon d th e altitude of 6,000 feet in th e State of Ar­ mountains. As the years passed, some peo­ agua, in the northern part of Venezuela. ple moved to the nearest Creole villages or The population constitutes a genetic iso­ even to the ci ty of La Victoria. Cultural, late, consistin g almost exclusively of per­ linguistic and breedi ng characteristics have sons of German ancestry, descendants of been diluted progress ively as the distance immigrants who settled in the valley be­ from the center of the settlement in ­ tween 1843 and 1856. It is said that these creased. Recently, with the opening of a settlers numbered 146, representing no road connecting Coloni a Tovar and patronyms. For the mos t part they ori gi­ , important changes have com­ nated from a few villages in the Black menced in the community, which is now Forest, . Since then the population rapidly losin g its earli er characteristics. The has lived in a state of relative isolati on, no village has a health center, with a phys ician road having connected the valley to the in charge, helped by three auxiliary-nurses. rest of the country until the 1950's. Census data are extensive and apparent­ The s urro undin ~ mountainous area is al­ ly close to co mplete, the whole population most unpopulated, except for a few scat­ having been followed up for the last 12 tered families of Creole extraction, born of years by the Servicio de Dermatologia San­ Spanish and/ or Indian ancestry. The result itaria (leprosy service) of State. has been high inbreeding of the group. The data include distribution of the popu­ Apart from shopkeepers and skilled work- lation by household, with information on sex, age and family relationshio for each

1 Received for publica ti on 26 September 1966. member of the household. In 1962 census 2 T h is work was supported in pa rt by the Divi ­ estimates gave a total German population si6n de Dermatologia Sanitaria, Min isterio de San i­ dad y Asistencia Soc ial of VeneI'I ela. and the Leon­ of 1,028 in Colonia Tovar ( 1,107 have left ani Wood Memorial by Train ing Gran t 5 T I AI the isolate and live elsewhere). 220, National Institute of All ergy and In fectious The prevalence of leprosy in the commu­ Di seases, National Instillites of Health, Bethesda, Maryland 200 14. nity is high. It is not known how and when 3 M. F. Lechal. M.D .. P rofessor of Epidemiology, the disease was introduced. A survey made School of Public Health, Lou vai n Un ive rsity, Brus­ in 1942 revealed 32 confirmed cases of sels, Belgium; T. Bi le, M.D.. Medico J efe del Servicio de De rmatologia San itaria del Edo. Aragua. leprosy and 9 suspects among 808 persons Ca ll e Felix Maria Paredes No. 20, Oeste. La Vi c­ examined (H) . Cases were sent to the Cabo toria. Edo. Aragua: E. R as i, M.D., Med ico Adju n to de la Di vision de Derma tologia San ita ria, Luneta Blanco Leprosarium, near Caracas, where a Mercedes, Ed ift cio Catll che, Car a~ a s. Venezp ela. at one tim e 29 pati ents fr om Col onia Tovar 4$8 35, 4 Lechat et. al.: Blood Groups & Leprosy, Colonia Tovar, Venezuela 489

were isolated. In 1950 COllvit (3) foulld the Servicio de Dermatologia Sanitaria in 113 cases among 1,126 persons examined, La Victoria for conditions other than lep­ who constituted nearly all the population at rosy. that time. The prevalence, therefore was Characteristics of the sample. The age 100.4/ 1,000, a figure in sharp contrast to the distribution of cases and controls is given in prevalence in the rest of the State of Ar­ Table 1 by ethnic groups, disease status, agua, 1.35/ 1,000. and sex. Among the , 58.0 per cent After 1950, several surveys were made of the individuals were under 40 years of again by Convit et al. (1 ,2.4) , in con­ age, in .contrast to 65.2 per cent among the nection with studies of lepromin-reactivity Creoles. The patients were on the av e r a~e in the population. Thirty- two more cases older than the controls, 48.1 per cent of the were found, some of which had escaped patients being under 40, in con tras t to 64.9 detection in earlier surveys. In 1962 an per cent of th e controls. examination of the German population of The sample consisted of 448 individuals, Colonia Tovar revealed only two cases not including 174 males (38.8%), of whom 52 yet registered (r;). (29.9%) were cases of leprosy, and 274 females (61.2%), of whom 29 ( 10.6%) were SAMPLING AND TECHNICS affected by the disease. Among the 81 Sampling methods. Although random cases, 54 (66.7%) were of German extrac­ sampling from lists prepared beforehand tion, 16 (19.8%) of Crevle extraction, and from the registers of leprosy in the Division 11 ( 13.6%) of mixed extraction. Among de Dermatologia Sanitaria of th e Ministerio the 367 controls, 179 (48.8%) were of Ger· de Sanidad y Asistencia Social ill Caracas, man extraction, 165 (45.0%) of Creole ex was intended, the procedure soon ap­ traction, and 23 (6,3%) of mixed extraction. peared to be unworkable for practical and As far as possible, multiple sibs were psychologic reasons. Although the cooper­ excluded from the sample, through precise ation given by the personnel of the local instructions given to the health inspectors health center, as well as by the sanitary screening the individuals for blood tes ting. inspectors of the Servicio de Dermatologia Although it is believed that this purpose Sanitaria (leprosy service) was excell ent has been fulfilled to a major extent for and dedicated, summons of the selected those sibs sharing the same household, individuals yielded few attendances. It mostl y children, this goal probably was not should be remembered in this conn ection, achieved for old sibs living in different that this population had been subjected to households. Moreover, in the German pop­ numerous surveys, especially skin testing, ulation, the high degree of inbreeding im­ over the past few years. plies some degree of family relationship Cases and controls in the German isolate among all members of the population. were therefore included in the sample as The diagnosis of leprosy was ascertained volunteers. The population was invited to from the records of the Servicio de Derma­ cooperate in the survey. In addition, blood tologia Sanitaria (leprosy service) of Ar­ specimens were taken from individuals at­ agua State, which for the last few years was tending the local health center. Advantage in charge of leprosy surveillance in this was taken also of a local survey of the area. No attempt was made to classify handicapped for rehabilitation, conducted patients with respect to the type of leprosy, concurrently among the leprosy patients. since most of them were residual cases. Specimens from the Creole population Technics. The typing was performed im­ were obtained as opportunity arose in mediately after blood withdrawal, with use Colonia Tovar and the nearby city of La of grouping cards developed by Becton and Victoria. The sample consisted of mothers Dickinson Co., Baltimore, Maryland. Be­ attending the well-baby clinics at the local cause of djffi culties encountered in health center, persons submitted to serolog­ drawing blood from leprosy patients with ic test for syphilis on the occasion of re­ anesthetic hands, and from rural individu­ ques t for travel authorization, and persons als used to hard work, with call ous hands, attending the dispensary of E1 Consejo an

..,;

,,-0 N 1- 0> o ~ I '".<;) -""" .-:0 00~ M .Q N 1~O>~ ­ _NC'l-- -- RESULTS -----:-1 ...... C'l lC C"I M 0 U":I 1 -I< Y. N -.j< M M"'l - ~ ABO blood grouping was determined for

"'; 'Q",," oooo N 0 444 (Table 2) and D-typing for 377 per­ 'l! ",,"oo_MO>Moo 0 sons (Table 3). "9 ...... ,C'\IC\I...... 0 z With respect to leprosy, the results sug­ g MO>

G.l M I'-MMNO> O Gene frequencies were derived for the N I ::: M

DISCUSSION No differences are readily apparent in the distribution of ABO phenotypes in rela­ tion to leprosy, either in the total sample, or in either one of the two ethnic groups fo rming the study population. If the difficulties of interpretation raised by the small size of the sample, which was insufficient to reveal sli ght differences in the proportions of phenotypes according to 35, 4 Leclwt et. d.: Blood Croups & Leprosy, Colonia Tooar, Venezuela 491

TA BLI'; :2 . Distribution IIf ABO 7Jli enotypes in leprosy cases and controls, by ethnic (f 1·OU/I . ------Ppr tpnl pht'1lo1."pp,; Etli1li(' ------group Disease ~ l aL u :; T utal A I B AB 0 I Leprosy case,.; 16 25 .0 '12 .5 0.0 62.5 Creole ConlTols I 165 33 .9 I 10 .3 3.0 52 .7 Tot a l 181 33 .1 10 .5 2.8 53 .6 \ Leprosy cases 54 48 . 1 5 .6 0 .0 46 .3 German Controls 178 48 .3 3.9 1.7 46 .1 Total I 232 48 .3 4 .3 1.3 46. 1 Lepro,.;." ease,.; I 10 30.0 20 .0 0 .0 50 .0 :\Iixed Co ntrob 21 38. 1 0.0 0.0 61.9 I Total I 31 35.5 6.5 0.0 58 .1 Leprosy cases 80 41 .2 8. 7 0 .0 50 .0 Total Control,.; 364 41 .2 6.6 2.2 I 50 .0 Total 444 41 .2 7.0 1. 8 50 .0 I I I

TABLE 3. Proportion of aa ph enotypes 1:n cases and controls, by ethnic (frau)).

Leprosy e a ~e,.; Control:; Total

Ethnic group No. tested % No. tested % No. tested %

Creole 16 0.0 163 6.7 179 6. 1 German 53 3.8 123 5 .7 176 5 . 1. Mixed 9 0 .0 13 0 .0 22 0 .0 Total 78 2.6 299 6.0 I 377 5.3

TABLE 4. A BO (fene frequencies in th e cording to the type of leprosy, i.e., lepro­ German and Creole (froups , 1'rrespect1've of matous vs tuberculoid cases, and between disease status. lepromatous cases and controls. This is not unexpected, sin ce the lepromatous and Gene frequencies German,.; Creole,; tuberculoid types of the disease present contrasting differences with respect to th e 0 0.679 0.732 host-parasite relationship between M. leJJ­ A 0.293 0 . 199 B 0031 0 .069 rae and the human organism. It is possible to conceive of host fa ctors, for example, genetic on es, whose role is restricted to or disease status or ethnic group, are disre­ apparent only in lepromatolls leprosy. The garded, the followin g remarks can be made pooling of leprosy cases without respect to in the light of the pilot trial. the type of leprosy w.ould readil y dilute The type of the disease should be taken associations between lepromatous leprosy into account. Differences are more likely to and genetic characteristics. This require­ be observed between cases classified ac- ment calls for a larger sample. 492 International JoumaZ of Leprosy 1961

When a household consists of blood -rela ­ diferencia aparente, sin embargo, e ll relaci6n tives, which is generally the case, the gene­ con la enfermedad. tic constitution of anyone individual in the EI grupo aleman mos tr6 un exceso signifi­ household is probably related to the genet­ cante del gene A. ic constitution of the others. Moreover, for a communicable disease where household transmission is important, as was shown to RESUME he the case in leprosy, the risk of anyone in Vne etude des groupes sanguins a ete the household developing leprosy is likely menee chez 80 malades de la lepre et 364 to be associated with the disease status of temoins appartenant aux populations alleman­ the others. Therefore, with multiple sam­ des et creoles de Colonia Tovar et des environs, pling in the same household, the distribu­ au Venezuela. La prevalence de la lepre dans tion of ·genetic factors and the risk of dis­ ceUe region es t de 100 pour mille dans la pop­ ease might show a spurious association. ul ation d'origine all emande et de 1.3 pour Although multiple household sampling mille dans la population creole. has been avoided in this study, the basis for La dimension de l'echantillon n'a pas ete exclusion has been only the household exist­ suffisante pou r qu'une analyse statistique puisse ing at the time of study. Nothing is known etre pratiquee sur les distributions des divers phenotypes. Toutefois, a premiere vue, il ne of the past structure of the households. semble pas exister de difference en relation Because of the social structure of this com­ avec la maladie. munity, it is probable that any blood rela­ Le groupe d'origine allemande temoignait tives living at present in different house­ d'un exccs sign ifi catif du gene A. holds have shared common households in the past, where they might have been exposed to a common risk of contraction of Acknowlcdgmcnts. The authors wish to ac­ the disease. knowledge th e cooperation of Hynson, West­ cott and Dunning, Inc., Baltimore, Maryland, SUMMARY and Becton, Dickinson and Co., Rutherford, New Jers ey, for providing the blood grouping A study of blood groups was conducted cards used for this study. among 80 leprosy patients and 364 controls The assistance of the staff and personnel of in the German and Creole populations of the Medicatura Rural of Colonia Tovar and Colonia Tovar and vicinity, Venezuela. The the Servicio de Dermatologia Sanitaria of prevalence of leprosy in the area is 100/ Aragua State in La Victoria in carrying out 1,000 in the German population and 1.3/ this study is gratefully acknowledged. 1,000 in the Creole population. The data were processed on an IBM sorter The sample size was too small to permit in the Department of Epidemiology, Johns statistical analysis of the phenotypic dis­ Hopkins School of Hygiene and Public Health, tribution. No difference related to the dis­ Baltimore, Maryland, by Mrs. Loretta Permutt, ease, however, was readily apparent. Research Associate. The German group showed a significant excess of gene A. REFERENCES 1. CONVIT, J. An investigation of leprosy ill RESUMEN the German ethnic group of Colonia Tovar, Se hizo un estudio de grupos sanguineos Venezuela. IV. Clinical findings and varia­ en 80 enfermos de lepra y 364 conh'oles en la tions in the Mantoux and Mitsuda reac­ poblaci6n alemana y creole de colonia Tovar tions observed during five years after BCG y sus alrededores, en Venezuela. La prevalen­ vaccination of Mitsuda-negative contacts. cia de la lepra en el area es de 100/1,000 en Internat. J. Leprosy 2 4 ( 1956) 38-44. la poblaci6n alemana y de 1.3/1,000 en la 2. CONVIT, J. Studies of leprosy in the German poblaci6n creole. ethnic group of Colonia Tovar, Venezuela. EI tamano de la muestra fue demasiado pe­ V. The morbidity rates in BCG-vaccinated queno para permitir el analisis estadistico de and unvaccinated groups during five years. destribuci6n de los fenotipos. No se encontr6 Internat. J. Leprosy 24 (1956) 269-274. 35,4 Lechat et. al .: Hl ood GrOlillS & Leproslj , Colonia Tovar, Venezuela 493

3. CONV1T, J., Gm,;zALEs, C. L . and RA SI, E. de lepra. Mem. VI Congr. Internac. Lep­ Estudios sobre lepra en el grupo aleman ro l. , Madrid, 1953, pp. 529-534. Abstract de la Colon ia Tovar, Venezuela. Intern at. ill Intern a t. J. Leprosy 21 -(1953) 587. J. Leprosy 20 (1952) 185-193. 5. SISJH UCA, C. and RASI, E. Inform acion epi­ demiologica so bre el fo co leprogeno de la 4. CONV IT, .T ., GONZALES, C. L., RASI, E. and Colonia Tova r, Est. Aragua. VIlIth Intemat. SlsmucA, C. Estudios sobre lepra en el Congr. Leprol., Rio de Janeiro, September grupo etnico alelll