College, Winston-Salem) (Received for publication August 5, 1946) human beings. It was necessary to select subjects

Transcription

1 TRCHNELLA SKN TESTS N AN ORPHANAGE AND PRSON. COMPARSON WTH SEROLOGC TESTS FOR TRCHNOSS AND WTH THE TUBERCULN REACTON ' BY GEORGE T. HARRELL, S. F. HORNE, JERRY K AKAWA, AND NANCY J. HELSABECK (From the Deprtment of Medicine, Bowmn Gry School of Medicine of Wke Forest College, Winston-Slem) (Received for publiction August 5, 1946) The possibility tht n unrelted disese process my lter the rection to the trichinell skin test ws uncovered in the course of n investigtion on the incidence of trichinosis. A higher percentge of positive skin rections to trichinell ntigen (18.3 per cent) ws obtined in 674 ptients with ctive tuberculosis confined in 3 sntori, thn ws found in 335 ptients without tuberculosis (7.2 per cent) studied in 2 generl hospitls for shorter periods of time (1). On the other hnd, the incidence (18.4 per cent) in 825 ptients without ctive tuberculosis confined in 3 hospitls for mentl diseses ws lmost identicl with tht found in the sntori. This finding suggested tht some fctor connected with residence in n institution might ccount for the high incidence. An nlysis of positive rectors ccording to the durtion of sty in n institution reveled tht the incidence of positive rections reched pek t 18 to 29 months; no history suggesting subclinicl institutionl epidemics ws elicited (1). Experiments were undertken to determine whether positive trichinell skin tests could be produced in the bsence of infection by the ingestion of killed trichine, s in met rendered noninfectious by cooking indequte to denture the protein of the prsite. Sensitiztion ws not induced in the nimls used for these experiments (2). The possibility of biologic cross rection, detectble by skin test, between Mycobcterium tuberculosis nd Trichinell spirlis ws investigted in rbbits infected with trichine nd bovine strin of tubercle bcilli simultneously. No cross rection ws detected in these rbbits by skin tests (3). The present experiments were undertken to determine whether biologic cross rection de- 1 This study ws ided by grnt from the John nd Mry R. Mrkle Foundtion. tectble by skin test might be demonstrted in humn beings. t ws necessry to select subjects for testing who did not hve ctive tuberculosis or cute psychitric disturbnces (1). n order to control dequtely the fctor of ge in institutionlized individuls, it ws desirble to choose one institution in which only children were in residence, nd one institution where only dults were confined for comprble periods of sty. t hd been found tht the incidence of positive skin rections decreses with dvncing ge, wheres the incidence of infection proved t utopsy increses with dvncing ge (1). An orphnge nd prison, both under close medicl supervision, most nerly met the requirements. MATERAL A totl of 526 individuls were subjected to skin tests. Ech person hd been in residence in the institution for t lest one yer; the mjority hd been in residence for 2 to 15 yers (Tble ). n none ws there history of tuberculosis or of recognized mentl disese. No ptient ws known to hve hd trichinosis, nd there hd been no epidemics in either institution which suggested trichinosis. At the Methodist Children's Home, Winston-Slem, N. C., 285 children, vrying in ge from 6 to 19 yers, were tested. The children re ll white nd re housed ccording to ge in groups of 25 to 35 in 13 cottges; every 2 yers they "grdute" from one cottge to nother, so tht the group is firly homogeneous. Though there re kitchens in ech cottge, only 3 re currently used to feed groups of boys included in this study. The reminder of the boys nd ll of the girls et in centrl dining room. Pork obtined from hogs rised on the orphnge frm is served twice weekly from November to Februry; the children et little pork nd prefer beef, which is lso vilble. Routine chest x-rys re not mde, but none of the children found to hve positive tuberculin skin test hd clinicl or roentgenologic evidence of tuberculosis when exmined subsequently. n the North Crolin Centrl Prison, Rleigh, N. C., group of 241 prisoners, vrying in ge from 16 to 77 yers, ws studied. The 58 femle prisoners re housed 64

2 TRCHNELLA TESTS N ORPHANAGE AND PRSON 65 in seprte building with seprte kitchen; hence, this group in effect represents 2 institutions. No prisoner hd roentgenologic evidence of pulmonry. tuberculosis when photo-roentgen survey ws mde few months prior to the initition of this study. Pork rised on the prison frm is served once weekly. The quntity of pork eten t the prison ppers to hve been slightly greter for the 2 yers preceding the test thn tht eten t the orphnge. METHODS n ll instnces, 1: 1, solution of trichinell extrct (Lederle) nd phenolized phosphte buffer sline control solution were used.2 A 1: 1, dilution of tuberculin (Lilly) in distilled wter nd the tuberculin control solution were freshly prepred for use in ech institution. New syringes nd needles were obtined for the skin tests, nd were not used for ny other purpose. One syringe nd needle ws lwys used for ech test solution, nd 2 others for the controls; the syringes nd needles were never interchnged. After being used, they were wshed with distilled wter only, plced in mrked tubes, nd sterilized in n utoclve. An re on the flexor surfce of both forerms ws clened with 7 per cent lcohol, nd 4 workers simultneously injected.2 ml. of the trichinell test nd control solutions in the right rm, nd.1 ml. of the tuberculin test nd control solutions in the left rm. The test solution ws lwys injected proximl to the control solution. The rections were red t 3 minutes nd 24 hours fter injection. The tuberculin rections were grded by the usul scle from 1 to 4 plus. The trichinell rections were lso recorded on scle of 1 to 4 plus, 1 plus denoting n immedite rection which exceeded the dimeter of the injected bleb by 5 mm. or more (1). 2The trichinell ntigen nd control solution used in this study were supplied by Lederle Lbortories, Perl River, N. Y. Ten weeks fter the skin tests were performed, blood serum ws drwn from the ntecubitl vein of the orphns for serologic testing. Serum ws obtined from the prisoners 17 to 19 weeks fter skin-testing. Floccultion tests were performed ccording to the technique described by Suessenguth nd Kline (. The trichine from which the ntigen ws prepred were recovered from rbbits fed 8 weeks previously on rt infected with strin of trichinell prsites obtined from the Ntionl nstitute of Helth (2). Precipitin rections were done with 1:2 dilution of ntigen prepred from the sme dried trichine used for the floccultion test. RESULTS Skin tests Orphnge. Fifty-seven children (2. per cent) gve positive trichinell skin tests; 51 were immedite rections, nd 9 were delyed rections which ppered t 24 hours. Three tests were positive t both 3 minutes nd 24 hours (Tble ). Seven children rected to both the test nd control solution, nd were clculted s negtive in the sttisticl nlysis. Forty children (14. per cent) gve positive tuberculin rections t- 24 hours. The immedite rections to the tuberculin test nd control solution were not thought to be significnt. Six children rected positively to both trichinell extrct nd tuberculin, nd negtively to both controls. One hundred nd ninety-five children gve negtive rections to ll ntigens t both times. Prison. Sixty-five prisoners (27.8 per cent) gve positive rections to trichinell ntigen t some time (Tble ). Fifty-two were immedite nstitution TABLE Summry of trichincu nd tuberculin skin tests Trichi ell Tuberculin 3 minutes 24 hours Totl 3 minutes 24 hours Number tested Test Test Test Test nd nd Posi- Per- nd Per- nd Posi- con- Neg- Posi- con- Neg- tive t centge Posi- con- Neg- Posi- centge con- Negtive trol tive tive trol tive either posi- tive trol tive tive posi- trol tive posi- posi- time tive posi- five postive tive tive tive Orphnge Prison * 53* (mle) Prison (femle) - Totl * Three ptients hd positive rections t both 3 min. nd 24 hrs.

3 66 G. T.' HARRELL, S. P. HORNSE. 3. R. AXAWA, ANt) N. J. :LSABECC rections, nd 16 were delyed. Three were positive t both 3 minutes nd 24 hours. Thirteen prisoners gve positive rections to both the test nd control solution t 3 minutes. Seventeen prisoners (7.1 per cent) hd delyed rections to tuberculin. Two prisoners rected to both tuberculin nd trichinell ntigen, nd did not rect to the control solutions. One prisoner gve positive rection to both tuberculin nd the tuberculin control solution t 24 hours. One hundred nd sixty-three prisoners rected negtively to ll ntigens t both times. TABLE Comprison of tuberculin nd trichinell skin tests nstitution Trichinell Tuberculin (24 hrs.) positive (either time) Orphnge Prison (mle) o Prison 2+ 2 (femle) Since the interprettion of immedite nd delyed rections to trichinell ntigen is still in doubt, positive rections t either period were compred with lte tuberculin rections (Tble ). No correltion between positive rections to tuberculin nd trichinell ntigen ws found. The dt were tbulted ccording to the extent of the trichinell rection nd the durtion of sty in ech institution (Tble ). The durtion of sty in n institution did not pper to ffect the extent of the trichinell rection. When the percentge of positive trichinell rections ws tbulted ccording to yers of institutionliztion, the incidence ws found to be highest in the orphnge t the second nd fifth yers, with secondry pek t the ninth yer. n the prison, the pek incidence ws reched t the sixth yer. co.4 -d C A4 v Pz - *@ V-,vel tzu 6 ui L41 LX.*.. ** mow _ romu () "o" - 4C Sno 44" o * C equ - Jmw ut reo, Uo)m -it t- mr# 4eq r.+t. W-4 u)to-noo O i w4 son4 Rt %Om ocoo oooooooooooo o + o + ooooo-oj + ot4-c~4ooo U- 1m -eqc4-1 eqc4 vooroooson<o O Wo4 A, vl o6c-ilr-6clii- oumouo+o6 X c c4"e4m.'tm "",d e > t it,~ o m m oo o! 4- z +,,ooooooooooo 7 + m + +1 re) l e U)c % eq C)oo"o q-4c -t_t ) -'. -. e-4 - V-'4c.'4f C4 t-- -OM ~to tnc,4 - eq C4 U) ~~~~~~~~~~~~~~~~~1 - V- +~~~~~~~~~~~~~~~1 O4 m ed" " -..W4-4 U) e e U)Ve -..% v-4.14.) q 4-h oh ; C) Ce 4-). l Ce oh - *; o C). Cis 'e ' Ce '.

4 TRCHNELLA TESTS N ORPHANAGE AND PRSON 67 TABLE V Comprison of serologic rections for trichinosis with skin tests Positive tichinell sin tet Positive tuberculin ln test Negtive trichinell nd tuberculin skin test nstitution Totl Floccultion Precipitin Floccultion Precipitin Floccultion Precipitin Porn- --tive ttive t2 either TetdPosi- N TetdPosi- N hour Tete roni- Ne TetePoni- Ne Tete Poni- Ne TetePoni- Negtim Test tiive t ttive hov T tive Te+ ttiveti est tive i e tive tive Orhnge Pries () 4 2 2* (mle) prison (4i) 8 4 4" 3 2 2(-)* * (femle) 2(3+) f Totl * Ser with doubtful (±) floccultion gve negtive precipitin test. ** Ser with 3+ floccultion gve negtive precipitin test. Serologic rections Orphnge. Floccultion tests for trichinosis were performed on serum from 38 children with positive trichinell skin tests, from 2 children with positive tuberculin nd negtive trichinell skin tests; nd from 2 who rected negtively to ll ntigens. All floccultion tests were negtive (Tble V). No precipitin tests were done on the children. Prison. Floccultion tests were performed on serum from 53 prisoners with positive rections to trichinell ntigen, from 5 with positive delyed tuberculin rections, nd from 51 who rected negtively to ll ntigens (Tble V). Five ser from the group with positive trichinell skin tests, nd 2 from the group negtive to both ntigens, gve doubtful floccultion rections; 2 of the ltter group gve strongly positive floccultion rections. Precipitin tests were performed on serum from 2 prisoners with positive trichinell rections, from 5 with positive tuberculin rections, nd from 18 who were negtive to ll ntigens; none were positive. Serum hd been collected from the other prisoners fter mel nd ws too cloudy for performnce of ccurte precipitin tests. Precipitin tests on serum from rbbits known to be infected with trichine were strongly positive; these tests served s control on the technique nd the potency of the ntigen. DSCUSSON No correltion hs been found between the tuberculin nd trichinell skin rections; this clinicl observtion grees with the results of experimentl investigtions in rbbits (3). No biologic cross rection detectble by skin test ppers to exist; the incresed incidence of positive trichinell skin tests in tuberculous ptients is still unexplined. Whether the pprent increse in the incidence of positive trichinell skin tests mong ptients confined to ny institution is connected with subclinicl institutionl epidemics, cnnot be ctegoriclly stted. The fct tht the flocculting ntibodies nd precipitins pper to ber no reltion to positive skin rections would rgue ginst subclinicl institutionl epidemics. However, precipitins re known to persist for 2½ yers fter proven infection in humn beings (5). The length of time for which flocculting ntibodies persist in humn beings is not known, but in swine the test remins positive for 1 months (. t is possible tht different ntigens re involved in the production of the skin test nd the serum rections (6). The increse in the incidence of positive skin rections previously noted fter 2 yers' residence in n institution ws confirmed t the orphnge; t the prison the pek ws lter, but in generl the reltion of positive skin tests to length of institutionliztion followed the dt previously reported (1). The explntion for this reltionship is still obscure. The wide vrition in the incidence of positive rections obtined in the 9 institutions which hve now been studied cnnot yet be explined. While positive tuberculin skin rection does

5 68 G. T. HARRELL, S. F. HORNE, J. K. AKAWA, AND N. J. HELSABECK not indicte the presence of ctive tuberculosis, it does indicte tht the individul hs been infected t some time nd is llergic to some frction of the orgnism. t would be resonble to expect some degree of correltion between the skin rections to tuberculin nd trichinell ntigen if one disese ffects the severity of the other, s ws suggested by the experiments in guine pigs previously reported (7). Perhps ctive tuberculosis is necessry for the infection with trichine to be enhnced; the present study cnnot nswer this question. Tht tuberculosis my ffect the course of trichinosis ws shown lso by studies of the eosinophil response of guine pigs (8). The injection of live virulent M. tuberculosis depressed the number of circulting eosinophils in trichinous nimls. Since rpid rise in eosinophils is the most frequent nd esily detected erly lbortory evidence of uncomplicted trichinosis, the bsence of eosinophili in tuberculous ptient with positive trichinell skin test could cuse confusion in dignosis. t is known tht the electricl resistnce of the skin of disturbed mentl ptients my vry mrkedly from tht of the sme ptient fter recovery (9). Previous studies with trichinell ntigen in one mentl hospitl suggested tht the rectivity to biologic products my be ltered in the sme wy (1). Though none of the prisoners or orphns gve history of ctive mentl disese, it is true tht ll prisoners hve committed n offense nd my justly be suspected of hving psychitric disturbnce. Mny orphns my likewise hve some mild psychitric mnifesttions. None of the individuls studied ws cutely disturbed, however, nd hence would not be expected to hve n ltered skin rection. SUMMARY 1. No correltion between the trichinell skin test nd the tuberculin rection ws found in 526 individuls confined in n orphnge or prison. The incidence of positive trichinell skin tests in 241 prisoners ws 27.8 per cent; the incidence in 285 orphns ws 2. per cent. 2. Positive serologic rections to the floccultion or precipitin tests were not found in persons with positive trichinell skin rections. 3. The durtion of sty in n institution is pprently fctor in determining the incidence of positive trichinell skin tests. The explntion for this finding is obscure. BBLOGRAPHY 1. Hrrell, G. T., nd Home, S. F., Trichinell skin tests in tuberculosis sntoriums, hospitls for mentl diseses, nd generl hospitls. A comprison of results in tuberculous nd non-tuberculous ptients. Am. J. Trop. Med., 1945, 25, Aver, John W., Yow, E. M., Hrrell, G. T., nd Fowler, E. B., An ttempt by feeding to induce in nimls rectivity to Trichinell spirlis in the bsence of infection. Am. J. Trop. Med., 1946, 26, Hrrell, G. T., nd Helsbeck, N. J., The effect on the trichinell skin test of simultneous infection with bovine tuberculosis in trichinous rbbits. J. Clin. nvest., 1947, 26, Suessenguth, H., nd Kline, B. S., A simple rpid floccultion slide test for trichinosis in mn nd in swine. Am. J. Clin. Pth., 1944, 14, ; Gould, S. E., Trichinosis. Chrles C. Thoms, Springfield, llinois, 1945, p Aikw, J. K., Hrrell, G. T., nd Helsbeck, N. J., The effect of peptic nd tryptic digestion on the ntigenicity of Trichinell spirlis. J. Clin. nvest., 1947, 26, Dvis,. T., Hrrell, G. T., nd King, E. S., The effect of simultneous tuberculous infection on experimentl trichinell infesttions in guine pigs. Am. J. M. Sc., 1945, 29, Spink, W. W., Effects of vccines nd bcteril nd prsitic infections on eosinophili in trichinous nimls. Arch. nt. Med., 1934, 54, Brnell, A., Correltions between epiderml impednce nd the clinicl course in certin psychoses. Proc. Soc. Exper. Biol. nd Med., 1939, 42, 839.