Ediciones > Año 1952 > Artículo No. 1 2

Changes in the lepromatous and tuberculin reactions of lepromin-negative leprosy patients after vaccination with BCG
Jacinto Convit
International Journal of Leprosy. 20: 347-354, 1952.
REVISTA: Publicaciones - Dr. Jacinto Convit

NUMERO: Año 1952

TITULO: Variaciones de las reacciones a la lepromina y tuberculina en enfermos de lepra, después de la vacunación BCG

AUTORES: Jacinto Convit; Enrique Rasi; Francisco Canto Rodríguez; Rafael Contreras

RESUMEN:

PALABRAS CLAVE:

International Joruna.l of Leprosy VoL 20 1952 CHANGES lN THE LEPROMIN AND TUBERCULIN REACTTONS Or L8PROMIN-NEGATTVE LEPROSY PATIENTS AFTER VACGJNATION WITH BCG 1 Dn. J i\ C t~ro CON&#39;VJT • Clrief Ph ii~«Ít:Ían, Lepro~ Divi•ion Da. ENRIQCE RAsst f>IJJiaici<Ht F,pidrm ioloo 1.vt. A ntilepro•JI ,s.,roiCHt No . .4 DIL FRAsctsco CANro Rooawuu AII8Úitant · P hl1lficia.11. Cabo 8lo11co Lc:protarisu• 4ND DR. RAP&#39;A.IL CONTRD.U! Phll•icrifl>n, C11ntrnl Di.~ptn~~n.rv. l~IIJI Di\1~ Mini8try of H&#39;oltlr. ond Socilll Wclfa.r• CorlUM, Vo~U.:u.414 IN&#39;I&#39;ROOUCTION The problem of n connection bctween tubereuloeia and lep. rosy has been t he subject of lnvestigation in the laat few y.ean. A series i1f facts which tend to corroborate the hypothesia of ~ interrclationship may ~ summarized briefly u followa: l . Leprosy is a much older disease than tuberculosis. IJa those cDumtrie.s where the epidemiologica&#39;l curve of tubeacu· losis is rising, leprosy is a health problem; whfie in thote countries where that curve is falling, leprosy ls eitber a rela· tiveJy small health problem or none at all. Tuberculosis ia an urba.n d ise.ase, but leprosy is a rural one (6). 2. The change brought about by Mvcoba.ete• *"&#39; ~ • wm in the capacity of an organism to react migbt influence the cout·s-e of anothcr diseasc which, like ·leproay, fs produeed by a cJose ly similar mycobacterium. A primary infection witb tuberculosis might a!fcct thc clínical aspect and courae of leprosy by producing allergic and therefore rélatively berdp forms (8, 6, 8, 11, 16) . 3. St udies of thc Jcpromin reaction in groups of healthy persons in countries where leprosy is not endemic show per&#39;· centages oC lepromin po~itives fluctuating, in dlfferent repor\a, between ~O and 74. It is almost eertain tbat the percentap of pos itivenes~ i ~ dul&#39; to n relat ive eo-immunity fnduced by a prior infection with t he K oc h bacillus (1, &#39;· 7, 12, lt, 17) • . 1 Tranalntion, !l<l m~...,. ha t modi.t1ed, of • papc&#39;l&#39; read at. tbe Thtrd Paa- Amclriean Lcproay C<mt..ren~. Buenoa A1roea, December lt51. 848 1 ntcrru1tional J ou:rna.l o f L eprofly 1952 4. Wben healthy , lepromin -negative pcr sons are inj E.oc t~ with BCG, the r eaction becomes positive in most cases; t hj:i is alBo confirmed by animal tesls (2, s. 9, IS , 1&#39; ). On the basis of theae factg we began an inve~tigati on of the influenc.e of BCG vacc.ination on Mitsuda-negati v<: leprosy ¡iatienta to determine if the lcpromin r enot ion would ~ubsequently become pos itivc. Such an effect would, of course, be o.f unquestionable value with r espect to t hc progu o~ i s of thc disea.se. MATERTAL ANI> METHODS Our first CJC.per imentsl group consisted of llS pútients with lepromatoWI leprosy , tbe lesions of which had disappeared aft er treatment with diasone or promin. but who were all negat ivc to lepromin. The t uberculin rea ction was nt&#39;gati,·e in 5 1. a nd alightly positive (l+) in thP. remaining f)2. A xecond group of 40 patients with the indeterminate form of the ci isea:-;e wa~ aelected; they were all negative lo both lepromin Hnd t uberculin. The antt~na u.aed we re: ( 1) Tuberculin (PPD) , 6 un ita per O.l ce. The !Stock eolutlon ot this antigen was r t!cc.ivct.l month!y {rom thc St.atens Serumin.stitut in C..openhngen. Dcnmllrk, while lhc tit tu tinnll w(&#39; r f&#39; ¡m•par{&#39;rl monthly in the NationaJ Inatitute ! or TubcrculORj!l In Co.rl\CM. (2) Wholc leproman, prepared at tho Cabo Blanco Leprosariurn by thc M itsuda · Hayaald t«hnique. (3 ) BCG, prepared in the .B sct.crJOlo~ricn l Uc partrncnl of tbe Nation&J lnatitut~ for T ubcrculo!lill, 0.1 5 mgm. of bactll i ~r 0.2 ce. Eaeh patient wns eimultalle-Ously ¡riv= Lhe l~!prom l n ant.l thc tubt• r culin tena by intradel&#39;mal injccllon of 0.1 ce. M ea~h prcparation on U11• hmer alde of the upper t oreu rm. The resulta of thc tubcrculin t<•st;s wcrc rHd 72 houra alter thc. injectinns, a reactlon of lü3S than 6 mrn. &#39;u~i ng c:on8idued u ne¡rativc nnd one trom 6 to 10 mm. us posith&#39;r ( 1 +) . T h.Mitsuda reaetion waa read ip tho course u! lhe fou ri.h w~k, a nd ih in· terpretation wu that rceom.mendurl by t he Seeond Pan-Amer ican l..cprMy Conferenee (Rio cte Jancir o, October l!HG). Vacclnaüon with BCG was mnde intrarlt&#39;nnally In thP AuprM>cnpul:l&#39;r region with 0.2 ec. o! t he :su.1>pension. Thl11 inj.~ctlou was mnd(&#39; obout 2 weeb after the reading of lhc Mits>Jdo rca~tion. · Two months o!ter the BCG vacclnntion W:lB pí&#39;rformcd, Llw tubcr <·ulin and l~promin testa wcru repcatcd with Lhc ~ mr unlig-cna a1HI 1n lhu snmP ••nner a.e befo~. BESULTS (1). The results of lhc BCG vncci nalion on thc :;;k in reaetiona in the 51 lepromatuus cast:.s which had becn negat.ive to both lepromín and t ube rcul in after the sulfone t rentment an shown in Tnble t. lt wil1 be observed that only la (25.5%) oí the s~ 51 patient. became reactive to lcpromin. the 9thcr 38 rcmaining 20,3 Convit et al.: Mitsuda Reaction after BCG 349 • TABLE 1.-Effects of BCG vaccination in 51 lepromatom caa• Íll wfliM the lepromin and tuberculin reactions were Mgative af t«- e,...tAI u&t · with. sru.lfo!l-6 deri1•atives. - - --- _ ... -- --- - -.. ·-- Lepromin rea.ctioo after va.ccinAtion - -- ·-- Tuberculin renction Positive Negative Total --· - - - alter vaccination No. 1 l:rl No. % No. % 1 10 Positive 12 23.5 23 45.1 35 &8.6 Negative 1 2.0 15 29.4 16 31.4 TOTALC3 13 25.5 38 1 74.5 51 1000 - negative. Of those which gave positive rea<:tions, 12 (28.5%) were one-plus, while only one (2.0 7&#39;o ) was two-plus. As for tuberculin reactivity, 35 of the ·patients (68.6%) became poaitive to that antigen, whilc 16 continued nonr eactive. - In 12 instances (23.5%) both the lepromin and tubercu lin reactions become positive, concordantly, and in 15 cases (29.4%) there was concordance with r espect to continued negativity. Discordance was seen in 23 cases ( -15.1 7o ), with induced tuberculin positivity but no change with r espect to the lepromin r eaction; the reverse discordance was seen in only 1 instance . (2.0%). (2). The resul ts of the vaccination with respect to lepromin reactivity in the 62 lepromatous ca:;es which at the outset were weakly reactive to t uberculin (1 + ) but negat ive to lepromin are shown in Table 2. TABLE 2.- Effecu of BCG vaccination on the lepromin reacti<m ¡,, 81 eca.u m wh.ich the lepromin reaction wa$ negative but the tubereulin ~W. positive ( 1 + ) after treatment with sulf o ne deri11atives. ~=========T=======-=-=·~========== Lepromin reaction Number of caaes after vaccination Positive, 1-plus Pollitivc, 2-pl\18 Positive, total Negative TOTALS --- ------- .. _ - - ,--=== 25 8 33 29 --- -1 62 1 -- - -- Percentage 40.3 12.9 53.2 46.8 100.0 • In 33 of these 62 cases ( 5:3.2 í; ¡ the response to lepromia becamc positive, weakly so (1+) in 25 instances (40.3% ), aDd 360 lnternational J ournal of Lep?·osy 1952 more strongly (2+) in only 8 i nstances (12.9 ~&#39;( ) . Almost onehalf of. tbe total, 29 cases (46.8%), r emained ncgative . (3). The resulta of the vaccination in the 40 cases of the indetenninate form, all negative to both ~sts before vaccination, a.re shown in Tablea 3 and 4. T .. r& 8.-Effects of BCG vaccina.tion in 1,0 cases of the indetermina.te form tÜl negative to both the lepromin and tuberculin tests after treatment with sulfone derivatives. -- -- Lepromin reaction after vacrination - Tubercuün reaction Positive Negative Total -- --- alter vat.:cination 1 No. % No. 1 (&#39;"o No. % Po~ntive 18 45.0 1 2.5 1\) 47.5 Neptive 17 42.5 4 10.0 21 ., 52.5 TOTAL..~ 35 87.5 5 12.5 40 100.0 1 - - - - -- - ------ T.A•.w: •.- A n.alysis of the responses to lepro-min in the .40 cases of the indeter-m·inate form after BCG vaccin.ation. -- -- . -- - ~ree oí reactivity to lcpromin Number of cases Percentage - . N~tive 5 12.5 P081livP. !-plus 20 65.0 POIIltive. 2-plus fl 15.0 Pociti V(&#39; 3-plus 3 7.5 .. TOTAL 40 !OO. O . ---- ---. ----- - ·-- - It is seen that no less than 35 vf these 40 cases (87.5%) becarne positive to lepromin, only 5 remaining nonreactive. Of the positives, 26 ( 65 &#39;. é of the total group) were weakly so, one-plus ; 6 (15%) were two-plus, and 3 (7.5 7o ) gave st rorig r eact ions, thr ee-plus. With respect to the tuberculin test, ba rely one-half- 19 ( 47.5&#39;/o ) - became r eactive, 21 rernaining n ~gxtive In 18 of these cases (45 &#39;ié> ) there was coucordance 111 tht development of reactiv ity to both antígena, while 4 (1 ll . ) n mained negative to both of them. In 17 (...12.5%) th.-rt! wa· discordance in the development of positivity only to l ,· ~romit only 1 patient (2.5%) became positive to tuberculin ., ·t•ne . • 20,3 Convit et a. Mitsuda Reaction alter BCG 861 COMMENTS Tite results, which show that the Mitsuda reaction beeame positive in 46 ( 40.7%) of the 113 lepromatous cases included in Tablea 1 and 2, are rather encouraging from our point of view. The problem of responsibility in discharging patients from the leprosaria is partly solved when it is known that, in an important percentage of those who become bacteriologically negative, the reactivity to the Mitsuda test can be changed to positive by BCG vaccination. The observations a~ regards the cases . of the indeterminate form which were negative to lepromin, we are inclined to &#39; ~elieve, almost solve the problem of preventing the hitherto frequent transformation of these cases to the lepromatous type. . For the purpose of studying the type of tissue reaction ··evoked by BCG, we subjected several of the positive Mitsudareaction lesiona to biopsy and found that they were also strueturally positive, i.e., of . tuberculoid aspect. Subsequent observations of sorne of the patients in our records show that the use of larger doses of BCG, given either in a single injection or by revaccination, improves the resulta. Not only are the percentages of positivity increased, but the Mitsuda reactions obtained are stronger. By comparing the findings of the so-called discordant reactions, it is noticed in Table 1 that 45 per cent became tuberculin positive compared with only 2.5 per cent in Table 3, while in the latter group 42.5 per cent became lepromin positive compáred with only 2.0 per cent in the former one. These facts demonstrate clearly that the respective phenomena of the tuberculin and lepromin reactions evoked by BCG are completely different, and it seems certain that they depend upon different mechanisms. lf we compare the percentages of positivity of the Mitsuda reaction obtained after BCG vaccination in the two groups of . patients, we find th.at the anergy of the indeterminate cases is Il\UCh less profound than that of the ·le}>romatous ones. Worthy of special mention are two cases oí the indetenninate form in which the diffusion of lesiona, as well as tbe strongly positive bact.E>riolo&&#39;ical findings and their negative • reactions to lepromin, madt· ••~ ~U~tJ.W>Ct that a transformation to the lepromatous ty~ was takin-i! olace. After revaceination with BCG these two cases b~amt iepromin J?OSitive and the elinical and bacteriologkal picture •as completely modifled. I1tternational Journal of Leprosy 1962 SUMMARY A atady has been made of the changes brought about, with rwpeet to reactivity to the Mitsuda test, by BCG vaccination of 118 leprosy patients of the lepromatous type whose lesione had disappeared after treatment with sulfone derivatives and who were all negative to lepromin prior to vaccination. Of th ese patients, 51 were negative to tuberculin and 62 were weakly (1+) positive. Of the 51 cases negative to both tests, 13, or 25.4 per cent, 1 beeame positive to lepromin. Among the 62 p~tients who were negative to lepromin but poeitive to tuberculin (l +), there were 33, or 53.2 per cent, whose Mitsuda reactions became positive. In a group of 40 patients with the indeterminate form of the dieeaae who were negative to both tests, the Mitsuda reaetion beeame positive in 35, or 87.5 per cent. . The results as ·shown by our case records lead us to thf! conclusion that BCG vaccination should be of value in solving the problem of discharge from the leprosaria, and that it should help to reduce the high incidence of transformation of cases of the indetenninate fonn, negative to lepromin, to the lepromatous type. T.he hiatopathological examinations which were made of some of the poeitive Mitsuda reactions obtained, proved them to be structuraJiy positive. RESÚMEN • Se estudió el cambio de la reacción de Mitsuda, después de la vacuna· ei6n BCG en 118 enfermos de lepra de tipo lepromatoso, lepromino negativos, cuJU !~iones habfan desaparecido después de tratamiento con derivados aullónicos. De este grupo ele pacientes 61 fueron negativoa a la tuberC!\llina 1 62 debilmente posit ivos (una +). · De loa 51 casos negativos para ambas pruebas, 13 o sea 25.4% viró la reacción de Mitsuda a positiva. De loa 62 pacientes negativos a la lepromina pero positivos a la tuberculina (una +) 33 o sea 63.2%; la reacción de Mitsuda viró a positin. En el grupo de 40 pacientes de forma indeterminada, negativos a anbu pruebas, la reacción de Mitsuda viró a positiva en 36 o sea 87.5"&#39;- Loe resultados obtenidos son una prueba de que la vacunación BCG ee ele iwaportancia en la solución del problema de las altas hospitalarias, ·uf como tambien en la reducción de la alta incidencia de transform&clÓil haeia el tipo lepromatoso del grupo indeterminado Mitsuda negativo. J:1 examen histopatológico hecho en algu!las de la reaccione• de Mit~ suda o~tenidas, demostró que eran estructuralmente nositivu. 20. 3 REFEIU::NCES l . A ZUt.AY, R. l J, 1111(1 CONVl&#39;r. J. A ln tt1\de!&#39;mtrn:.a&#39;>&l d~ Wtt.ud.a am pe.::~:sol\S 4fi.t t&#39;IM pnla nñ<J • ru.lcnuC&#39;Q de lcprll. Arq . Serv. Nac. Lepra <1 ( Hl46) L.¡&-1 48 ; ( \&#39; e>l. 1, S«únd Pun-Amcrican LcpTW}&#39; Conl«f&#39;cncc); l nterllJ\t.. J . Leprot•}&#39; 15 11947) 264-266 (in Eo.gli.ah). 2. Azuw. Y, R. D. A n~iio do) 8 (&#39;(; !>Obre il rt:\\M lepromfnlca. ArQ.. &rv. K11c • .L~J•· 6 {1948) 81-I:H.i; O. lh •~p . t Rio du Jnnci ro) 34 (1948) 8ó3..sfot&#39;l; Mom. V Congr. l nLt:rnuc. L~: pru, Ha.vEma, 19t8; Huvana, 1049, Pf&#39;· J lt12-U46. 3. Bo:LINO, R. M ~:dicino y Quím t c l~ . Alergia y curao de ll\ lnfeecl61\. Ed. : Rev. Tnionnací6n Terapéunca ( Luverk l~. Gerllll\ny) , 1036, pp. 1 ~200. • 4. BOl&#39;CilH:U.I, U. Ric<!r che ~~~ o!SSI!rVlU_Íoni Bulla r~tt.iv i~ cubt.nea dei 16bbrosi alle conldNl<- &#39;&#39;lt•prom ine." G!or . iW3ano Dano. ~ Slt. 11 ( 1937) G29-630. · 5. C HAUSSlNA~n. R. Lo tubcrcuh)!ie ¡;t l11 lt&#39;lpr\&#39;., ma ladiea anta¡onlquu.. r!;vict,JOO de In lllp ro ¡p.ur lo tuburculoBe. Intcrnat. J . Ltpro-r t~ ( 1948) .:3 1 -4:!~ . 6. Cos vrT, J .. A WlAY. R. D •• B r.n ~wotz. D. and SAJ..oAOO, P. The lepr<>mín test in tuberculous pc!&#39;OOHB in a non-f!ndclllic ILrt&#39;L I nterna t. J. L<lpro.sy 12 ( 1944) 60-64. 7. CUMMI NI:l, S. L. unrJ Wn.Lt.\IIIS. B. M.. Cutnncous r>eTUrlUvity to lkcldfMt b:H·illl la l3U!í[ll:nsion. Britlnh 1\led. J. 1 ( 1&84) 702·708. 8. FOtNANIH:?., J . M. M. E:~tu di o com¡H\raLivo de 11\ r&#39;l&#39;:1\.ccl6n do "Míbsuda con ln.s resc~i()Ol&#39;tl tutx:rcullntdlll. Rcv. a rgentinA Dllt:matoa.lf. D ( 1939) ·125-4&3. 9. FLOCH. H. nnd 0 E:STO!>Hll:S, P. Allorgi" ot para-allergie d1J1.1 la l~pre. R.<:action de Mltsuda ; allerg-•c lóprouoo et a.llel:g:io tubcrculolde. vaccinniion par lt&#39; BCG. lnternat. J . Lopros-y 11 (1960) 177-l&a. LO. RABXW..O. JR. Sobt·e n co-·ínfc<:\&#39;ño tuoorculosa dos doe.ntas do lep¡-&. F otha M.Micll ( lfl35) (Msn:h 25) . ll. RAD~t..o •• IP.. Novrus ob:l<ll"&#39;\&#39;n&#39;oe!) S(Jbre a ln!cc~iio tobel:-cu lo.e· na ~rL Rcv. brns.ile1rn LeproL 5 (1937) 465-479. 1..2.. RAD:O:A, R. N o t~ sur In re.<\c tion de Mit!suda ehex de<~ snjet.a lnd$xnnea de lópre; de l&#39;lnflucnce du tnitcmcnt de la lep ~ w r la buDJ6mio l(:prcuse ct sur les ln b.&#39;lcillumic l6prc:use et sur les résultat.a de la réac:tion de MiMudn. Ann. Soc. bnlgo Méd . Trop. 18 (1938) 6&-7!. lH. Ros•;r•fBEnG, J., SouzA CAMr·os., N. ami .AUN, J. N. Da rela~ lmunobiol6g ic.a. ClllTC tuberculo¡¡c u lepr a.. I. Ac;i.o poaítin.nte do BCG &obre n lepromi.no- rca~. Rev. bra.alle!ra Lcprol. lt ( 1960) 8-.28. l4. RoSt.:.MBt:Jl.O, J .. AUI&#39;l, J . N. Cind Sou7..A C AMl"&#39;S, N. Da rel~lo lmooobiot61{ lea untrc tubcTc-utose e lcpm. liT. A leprom.ino-ra~lo era m iUlCU rlt&#39; ri l•JIC&#39;C&#39;ndc-ncil\ nilo 1 <-p r.)~A vacunAdas oom BCG po1" vía oral. Dlssocia¡;ívl C&#39; l&#39;lt r,. -r ~rg1a tulx-rcullniea a rea,io do Mit.uda. Re&#39;&#39;· brlltul.,,n &#39;-•&#39;1" "&#39;- 11 1 tV51J } t28-143. t6. ROTtii!RC, A. ancl ¡rLY.I.:RY 0·1: O !.lYI.tlll \ n. J . A reo~ño da lcprowna na tulw.rculDS4-&#39;. 1~<·~· br~UJ;il•• • r u. Lc prl•l 6 (19$7) Spec. No. , ¡¡p. 2~7- 291. 364 l ntcrnatronal Jourrw.l o/ Lcprosy 1962 16. &#39;RoTBl:P..O, A., Bt.nAr.LL.I, L... M. ttod l{lm., H. A ren.~ño de Mit.sud l\ cm p&ia t iÁO )fiJU()jt ~nu:a di! lepra. Mom. V C:lu~. Intcrnnc. Lepra. HaTIVllll l~tl; ¡iavnna, 19~9, pp. ó86·(19d; r tJpr i11lcd i11 InternA:... J. Loproay ti (1950) 2il9-220 (in 8ngliah). 17. SOU&#39;t~ Lnu, M. .E:ílJ.udo c;dt:ico de jtta11t&#39;&#39; lepromina (R. de M !Lauda) . · Rev. brulllllra Leprol • .S ( 1.938) 448-4\.49.
  Ediciones > Año 1952 > Artículo No. 1 2
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