Rev. Inst- Med. tro|. São paulo 2g(5) t276-2E3, seteñhrò-outubro. lg87

PREDICTIVE VALUE OF SEROTOGIC IESTS IN THE DIAGNOSÍS AND FOLLOI¡V.UP OF PATIENTS W|TH PARAGOCCIDIOIDOMYCOSIS tr)

Luz EIeD¡ CIINO & Á[getÐ BESTA,RO

SUMMABY

A serologic study was undertaken in a gtoup of 4A patients with active pe lacoscidioidomycosis who were treated in the same foÍm (ketoconazole). fo¡ identicaJ. periods of time (6 months), and followed-up for valious periods post. therapy. The tests employed w€re agar gel iÌnrnunodiffusion (.A,GID) and, com: plement fixation (FC). AIso studied were S0 seta from patients ,with proven and pulmonary aspergilloma, B0 patients rwith culturaly proven as \¡¡¡ell as 92 specimens from healthy individuals, residents in thg endemic a.rea for pamcoccidioidornlrcosis, A single lot of yea,st filtpàte antigen wâs used throwhout the stud¡r, ltre va,lue of each tÆst was measuted acsording to GAIEN a¡rd GAMBINO 6. Both tests v¡ere highly sensi¿ive, gg aÃd. gtVo rcs. tæctively. Regarding their specificity, the AGID was totally specific S¿hile the CI' edúbited 96.6Vo and 97qo specificiþ in front of tuberculosis patients and healthy individuals respectively and. 82% in comperison ï'ith patients with other mJ¡coses. The concElt of predlctive value, that is, Ûre certainty one ha.s in accepting a positive test ås diagnostic of , favored tbe ,q.GID proædure (70OVo) ov4-r the CF test. The lattet coutd sort out vnllr- 9t7o ceftainty a patient with patacoccidioidomycosis among a group of healthy indi. viduals a,nd willf, 97.5% in the sase of TB patients; when the group in question was composed by individuals with other deep Í\ycoses, sucTì certBinty was lower (877a). T'he above results indicâte that both the .4,GID and the CF iests fumish results of high sonfidenc€; one should not telay, howevel, in the CF alone as a means to establish the specific diagnosis of pamcoccidioidomycosis.

KEI¿ WORD,S: Predictive values; Serologic tests; pamsoccidoidorlycosis; Cros$ rea.ctions; Systemic lr¡ycoses,

INIT,ODUGTION

ParacoccidÍoidomycosis irs a polylno4lhio This being so, it worrld bs highly deslrâble to disease and its varying clùúcal manifestations attempt standatdization of the various tests oft€n delay promp¿ consideration by the trea- currently available and of the reegents ting physical of its erE, real etiology. In tffs con_ ployed in such tests s,7. text serologic tests play an important role in diagnosist"2,11,u,17,19,25, FΡrthermore and due cenetally, in o¡der to achieve standardlza, to the ch¡onic nature of paracoccidioidoh.vcG tion, it is necessårf,r to r¡ndertake the-statist¡ca¡ sis, such tests are also cruciâl in evatuating anâlysis of the most p¡omising tests 6,2,10. Ihg the patient's 2.as,2,8p4, respo¡ìse to treatme¡;it first step towards this goal is to evaluate tho (') s¿udy ges€ntod durj¡s the rslt¡M rr¡temãtlotrsl cou(ql¡IuE on psrêcocclauoidomycosis, Ileb¡1¡sry t986, M€de¡ü¡, eo- loÍrbiB. cotpo¡ación lnvestlgactones Blológic5s (cIB), qoslitÀt p¿blo !3¡a l¡obóà urtbe, Mectellin, cotombts, south ¡t¡¡rer¡cs.

276 CÁNO, f,. E. & RESTREPO, A. - Èedictive value of se¡orogic tests in the diaglþsis and fotlo\¡¡-u! of pEtionts ìrith pa¡âcoccidìoidomycoE:s. Rev. IDst. M€d. irolr. São P¿u¡o, 29t 276-2A3, 1987. tests results obtained when studying series of were 33 cases with histoplasmosis and 17 vrith patients ând of control individuals. We be- pulmonary aspergilloma. lieve that various points should be empha,si- Group C: patients z,ed here as follqws: Constituted by 30 with culturally-proven tuberculosis by M. tubercu. losls var, hominis. 1. The group(s) ur¡del study should be as homogeneous a,s possible and cons- Group D: Composed by 92 healthy indivi. tituted by p€$ons twith simila¡ charâÆ- duâls, all resident in endemic a¡eas for par€" teristics. Ideauy, Û1 the case of pa. coccldioido[rj¡cosis and v¡ho had been previou& tients - rwho should have been prc. ly skin-tested with paxacoccidioidin and for¡nd perly diagnosed tåey should be acti- reactive æ. ve ât time of filst- testing, be treated with the same drug and for similar Concefnturg group A, tftese patients were periods of time, q'ith bleedings ta,lring exarniried at various periods. All 43 v/ere tes- place at identical pe¡iods during and ted at time of diagnosis, when their disease after therapy. Healthy controls should was active. They v¡¡ere all treated vrith keto- be chosen among persons living in the conazole (200 mg,/dey) for a period of 6 mon- known endemic areas for the disease ths; during this time, 42 patients wet€ bled urder study. Patients with ot¡rer fi¡n- at montl¡ 3 of thempy and 4l at 6 months, gal diseases should also be studied Upon determination of therapy, 31 patients once their diagnosis has been propedy were available for testi.ng 12 months after fi- established. nishir¡g drug inta,he, 16 patients after 24 - 2. Identica'l tÆsts should be applied to aü and I after 36 - months. specimeru! and the methods sl¡ould be Patients with paxa.coccidioidom¡¡cosis wer€ carefully controlled, avoiding modifica, classified as having pulmonary diseas€ with tions to the teshniques during the pe dissemination to othet organs (29, 67 -ïEo, ot Iiod of study7 6. as presenting involsement lestricted to the 3. It would be highly desirable to use a (14, 32-5Vo) - Concwrcîf, pulmona"rJ¡ tu- single lot ot antigen for all tests but berculosis was found in 5 patients (11.07¿). if this is not feasÍble, one should em- Regarding other parameterc, most patients (42) ploy antigens potencyT'16. of comparable wele males and âIl were adults, ages 35-62 yeals. Ihe above steps twould, eliminat€ va,riables and would peamit a more precise statistical Sera were collected before breakfast f¡om evalu&tion. all individuâls (groups A, B, C, D), prese¡ved 1:10.000 meÉhiolate bu.ffer solution 8, IÌ¡ring the pa.st 6 years rwe have had tl¡e \trith in and kept the æfdgerato¡ oppofiunity to perform serologic tests to a in at 4'C until time series of patients and healthy coDtfol groups of testing; this rwas done before 15 days of who present optimal conditions for standardi- collection date. obtained the ba. zation. The results we form The serologic t€sts evaluated ï'ere com. sis of tllis publication. plement fixation (CF), the 50ø¿ hemo$¡sis mi- MATEßIAL ÄND METIIODS crGtest recoûlmeded by the CDC Laboratorl¡ Brar¡ch e, and tfie âgar gel immunodiffusion Sera obtained from 4 grol¡ps of percons techrique (AGID) suggested by the Panameri. were studied" as follows: ca'n Health Organization serolog¡¡ study 8. G¡oup À: Composed ttJr 43 pa,tients \trith grou¡x laboretory proven parasoccidioidornycosls as Both tÆsts employed .a yeast filtrate ánti- described elsewhet e T'n þE, gen obtained according to techniques alleady 23, Group B: Fo'rmed þy 50 patients vrith othe¡ descdbed from P. b¡adliensls isoþte 8339. deep mycoses, lwhose diagnosis had allso been A large batch wâs plElarcd and utilized aU established b¡¡ laboratory þro¿€dures. There throughont tlre study pefiod.

277 c'aNo' L' E & RESTREPo A Pre'lictivs Yslue of serotoglc tests pâEcoccidioidomycos:s. - tn the diasÐosis sn¿r folloey..up of lauênts with Rev. IDst. Med. tlop. São p¿uro, 29: }?6-283. I9B?.

For comparison putf)oses, a single ¡ot of 30 TB patients GsVo) as well as B Histoplasl¡La capsulatum of the nor- whole yeast oells a.n mal controls (3.37¿), tumed out positive. tigen \Ã'as prel)âted ¡5 and used in the CI' tests. When the IL capsulatum whole yeast CF results cells werc considered positive when antigen was used in tfìe C¡' test (Fig. the titer was > qrere 1), at¡ 1:8; IDGA results DG histopla.smosis sel6r reâcted; a high proportion Êitive when band 1 either alone or accompa. G7 or 86Eo) of the para,coccidloidomlrcosis ca, nied by bands 2 and g, q'as detected 1?,1s. ses also tecogn¿ed ttre heteÌo,logous antigen. S€ven serum St¿tistical analS¡sis eacompassed thè deter_ samples from aspergilloma pa. tients ( mination of sensitivity, especificitr anal pæatic. þqo), one of the TB patients (8.32¿) and I from the tive velue as defined by GALEN and. GAM- healthy control group (9.8%) g1¡9 werc also positive. o, and ITOZINN and TASCIIDIIÂN r0 (Table 1). Tlre Student test t was used to de_ ïhe sensitivity of botll serologia tests was temine statistical significance. determined in trmtients witf¡ para4occid.ioido- myoGsis, a¿ every one of the study perioals (Fig. ?ÅBLE 1 D€f¡nitioÌì of teIÃls (+) 2). At time of diagnosis both AGID ar¡d CF proved highlt sensitive (Bg ând g0Z¿) æsDecti- Equation ooncePt D€ftnftioE employed to vely. lherapy caused. a certain loss oi sen- meâsure vhtue of test sitivity with â trend towards loweÌ figures ráith time of thempy. At the end yeâ.ß Sensitiyttt percentage of J ot T,P. ' alter cessation of treatment, dlse8se i¡dtir4aluah AEE, of. lhe ca,- ses could still detected qriüh positivo test T.P.+IlN... be by AGID and 85Zo æsults by the CF: IIowever, ¿here were no statistical differences betrween the two tests. Speclftcitj' percenktge of T.N. r.' non-diseased ---_x100 The sf,ecifìcity was determined in the con- individuåls T.N. + P. trol gÎoups (8, C and Ì\¡ith D). .q,s eai] be seen in negative Fig._3 ¿est results. the AGID test was totally specific, ,ì¡,iû¡ no false positive reactions being recorded for k€dicttye percen¿Bge of T,P. pati€nts with other myoosis, tuberculosis or v¿Iue of s lositive reactols _--X¡OO positive healtl¡Jr controlË. .A,s it lærtains the CF test test having disease T.P. +FP. *i.* (Fig. 3), only 3 false positive reætions (g7Eo (+) TaI€n from cât€n ânat Gambioq ^ ,.rìar r

274 CANO, 1,, E, REST.REPO. p¿tieÈts & .{. -¡P¡edictive value of serologic t€€ts in tho di8g[osls a¡d fol¡ow-up ot vltD p€¡8¿occtaltotaloE¡¡cosis. Bee, IDsÉ. Mert- tÉp. São Pd¡lo, â. nÈW, 198î . '

Groups

m Porococcidioidomycosis I7-- H¡stoplosmosis I Pulmonory Aspergillomo Ef:f:tl TB If Heolthy controls

tÈ5tJ ì Agor gel Complemenl Fixofion (CF) irnmunodiff usion (AGID) with porococcidio¡d¡n vr¡lh U:ggplglgrul! whole w¡th porûcocc¡d¡oidin teost cells Fig. 1 - Semrogic test¡¡g with P. Dmsulensls arld lI. cslFul¡tum ÂDttgenE in patients with systemic Eycosês, tubercutosis and nolmal pe¡soDs.

DISCUSSION test ånd applied It to paracoccidioidoÍSrcosis. ï1lis concept advanced by GALEN and cAM- Itre results of tÌ¡e prcsent study confim BINO ó, furrishes a more precise inforD¿tio¡ lrevious indications conceming the adequate concerning the possibility tbât a¡¡ individual sensitiviw of both tåe .6.GID and the CF tests who has rea€ted in t,lle test, truly has pam, for the dt8€nosis of pamÆoccidioido4lrcosis coccldioÍdom!¡cosis. Ibe results iDdicate tbat s 1,34;6).1,,12,t314,17'23,27. Concernlng tl¡e specifici. serum reactive in the AGID fest should come W of such tests, our results offer statisticaüJr f¡om a patient who has - ot has had paÊ supported datå for the AGID, former¡J¡ shown mcoccldioidomycosis, The certainty comes- to be highly specific 3¡,8,ú,13.2¡. In ttris ægar4 ffom the 1007¿ prcdictive values exhibited by the cF test atthough l¡ighly spec;fic (g'IEo) in this technique eitheÌ at the tllne of diagnosis front of healthy controls, tsas shoen to be less or et var¡ous pelioals dur¡¡g and after thera. preûise nrhen cornpBred to patlents wÍth his py. In tl¡e case of the CF test, a posiuve te toplasmosis and aspergiUom¿ (82øo). îress silrt in arl und¡agûosed pati€Dt inaUcates tbøt tEo mycotic dlso¡ders are collrmon in the en in comparison witf¡ hestt\y inauviduals in the demic ar€as for pamcoccldioidomõ¡cosis 5r6gt eDdehlc aleas, tl¡is patient has 937¿ possibl- and, itr consequence, one may rim lnto düfi- lilies of llaving paÍacoccitlioidorqycosis; this is culties !Íhen &tt€mpting a defiDite d¡agnoslg also a meaningful flgure. tlowever, a¡nong â l¡r a pafticular pattent, polrulation Of patients \tr¡tlx suspected ll]ycoses, Se8rching for Ê mef,hod to cledry the abo tåe Ofs pÉdict¡ve value. is lower @!qo) etrtd vo problem, we have utillzed a ststigtical coD- althóugh not yet €xtrcmety ùnþofta.nt, there cept, tbat of tha p¡edlctive ìsatue of a positlve ¿lo ¡rossibilitfes of misdiagnosiDg the pBtient's

279 CATYO, L. E. & R;ESTREPO, A. - P¡€dictive v¡ilue of seÌoloAic tests ir the aüâglosis a¡d fottow-up of pati€nts wtth pamcoccidioialoevcosjs. Rev. IDst. Med. trop. São Psr¡lo, z9t 276-283, 19A7. t,

i. a¡ararrrìotl I

;'õ ô- AGID

àe

L J I Diogno.i. ond rtreropy Post - Th eropy

L Perio¿. of Observot¡on ( Months) J ¡'ig 2 - Sensit¡vity oI s€¡ologic tests with P. brasiließis súige¡s t¡ patieDts with paÈcoccictioiatomycosis þeto¡e, duliûB s,nd afteÈ slecific the¡e?y.

illness, .As it pertains tuberculosis, the pre- spesificibt,ó,21. Cleârly there is need to studJ¡ dictive va.lue was lrigh (925/or, tnùcatì¡lg *øt the antigenio make up of P. brrs ieDsis and of the t€st is capable of discrird¡ating wilh high other mycotic agents causing deeÞseated Í\y- efficienclr bef,ween this drsotder and paracocci. cosis in otder to isolate specific antigenio moi- dioidorqycosisr. ff treatment for tho mycoses ties. fn this folm., it B'ould be possiblo to is offered, the prcdictive velue deüeases anal prcduce specific ant¡gens whic.l¡ would ft,srilt after 36 months of therapy cessation, the pos- tn t€sts ü¡ith higlrer predictlve values a,ûd j¡ sibiuties of colTectly deternjning tlre etiolosr a more prccise diàgnosis for the patient l¡ paat. of the illness is only 5080. need of ploE¡tt, specific theraly s,?8. fn some diagnostic centers, it has b€€[¡ costumary to perform botl¡ the AGID and tlþ RÐST'MEN CF tests because the fonrer, ¿lthough much pledisffvo simpler to perform, does not vaqr enterisivelJr Valor de las Inuebas serofodcss duaing the follow-up studies, while Ure latterr Irara el dlagnosdco y seguimtento de Ia procedu¡e lenals itseLf to adequ¿te quantitifica" Ila¡æorcialtoidomicosls. túon. Ibe rcsults we p¡esent hero indicate th¿t Con el objeto de determinar p¡a it is stiu sowrd to proceed atong such lùres. el vdlor dictivo ale las pn¡ebas serológicas (F¡jacióD do Cross reactivibr amoDg varior¡s n¡rcotio Complemento, trE, e fnmunodlfusió¡ e[ cel antigens has been exteÐsivet!' docum¡9nted ü¡ de Agar, IDGA), utilizaalas ¡egulaFmente €r¡ tåe past 35.13,15¡BÆ,28, with tlre llore sensitivê nuestro laboratorir ¡)ara el diagnóstico y el teshniques caflryiag the lerger burden of noû. segul¡rdento de la parâcoccidioldonrlcosis, so

280 SANO, !. E. & R.ESTR¡IPO, A. - Preillctive value ot s€rologio teÁhs in the drãgaostB a¡d follow-üp of pstr€nts sith Bev. LEst, lvled. trop. Sio Pr{o, Æt È18.2æ, 19A7.

Groups

æl Heolthy cmtrols

Ø Polienls with hisloplqsmos¡s ond osperg¡llomo

I Poti€nls with TB

.;

à!

rEsr _____J Fig. S!êcificity or ¡ - se¡orogic t€sts reith P. brl¡ rersû ÀntigeDs in fhlee ditte¡ent controt smups_ Grougs

AGID .'.'. Heollhy conlrols

r¡rl TB pol¡€nts

Pqtionts other CF - mycoseS 60 .: = fL ^40

036 72 24 36

L During f."ot."nt J L- Post-Tr€otmenl .J

L Pêriod of Obs€rvol¡on ( Uont¡slJ Eig. 4 - Pr€diclive calue ol ð positùe serologic test tn p¿tients with para{occldioidoll¡¡¡coâis atrd ià t¡æe d¡tfeft'at conü¡oI Bror¡ls, acco¡ating to tine of t¡rerapy.

281 cÂNO, I t & RESTREPO, Pr€dlctive A - lalue of se¡ologic tests iE the altBglosis å¡at fotloF-r4r of Þsti€ûts wità pâmcoccidioidonycos:s. nev. IDst. Med. trop. Sio Psuto, nr y¡6-Z&3,79A7,

anaJizaron los datos Þrovenientes de 43 pacien- P. bm€lue¡¡si,e lÌEeu¡odiJtusioD test an geE. J. cüi. tes son la enfermedad. Tales pacient€s fueron Mic¡ol¡lol., 19: 40+407, lSa4. tratados en forma identica (Ketoconazol, 200 4. FAVA-NETTO, C. - trlùnu¡ologia da para¿occidioido- mg/dia por 6 meses); además ambas pruebâs micose. Rêv. IreÉ. l}f€at'. 1rop. S. p¿ûIo, lE: 42,53, 1926. serológicas utilizaron un mismo lote de antig+ no, eliminando asl posibles variables. FU€ra 5. IEAiRETIIÌA-CI¿UZ, M. F.; GAI,VÁO_C¡îSTRO. B. & 'WÁNù(E, B. PÐdução ê de los sueros provenientes pacientes - f,âdronização dos anttgenos de los 43 ¿lo P. b¡âsilieÉ¡s, II. c¿psulðtum, A, f¡utg¡tus per con paracoccidioidomicosis (¡{), se estudiaron uso no tmúroaliagróstico. Mem. IDst. Osw. Cruz, t¡: 50 suercs de pacientes con otrâs micosis pro- 301.305, 1985. fundas (B) y 92 sueros de personas sar¡as (C). 6. GALEN, R.. S, & GÁMBINO, S. R., ed; Beyond Empleamos las fórmula,s dadas por y - GALEN noÌrÌ¿tity. Tlrc prcdÍctive f¿tue and efflci€ú(t of me- ó GAMBINO y hallamos que la sensibiltdad de atic¿l diagnosis. New Yorik, J. Witey ê!a! SoILs, 19?5, ambas pruebas serológicas era comparable, sin p. 10-14. djferencia estadísticamente significativa entre 7. EITEPEET, M.; ell8s (FC SUN, S. H, & VUKOVICII, K. &. = E7,IæA = 88AVo). Dicha seû Stanai,a,rdÞâtlon of Сrcotodcat rcagents! In: INTffi-- sibilidad tend.Ía a disminuir con el tratamien- NATIONA¡. CON¡EEENCE IN STA¡ID¡IR,DIZI\TION.O¡' io, siendo más marc¿da su baja du-rante las DL{GNOSTIC MATBIAL. proc€ed¡¡€!, A a¡ta, C€dteß obseúsaciones post-terâpia. .Al a'nalizar la eg fo¡ D¡s€asè Coltml, 1974. p. 1A7-794, pocifibialad se enconttó que la IDGA era to- 8, KÅT'FnlÂN, L.; HÛPPER,T, M.; FAVA.NSITO, C,; NE. talmente esp€cífica, no encontrandqse falsos GRONI, R,, & IIESTREFO, A. - ltanual of stanat¡¡dized positivos en las poblaciones controles estudia, serodiatnostic pmcedües foI systêrEtc ûycosis. part I: Agar gel iEEu¡oaliffuston tests. Washt¡gtÐn, D. pa- dâs (B y C). La F'C mostró w S6.7Eo de C., aÀnêdcar¡ H€etth OrgaÀizstion, 19?2¡ especificidqd frente a la poblaciód C y un 82Eo trenl,ø a la B, siendo estedistisarnente sig- ¡{AIrIllf¡ArN, L.; EUPPEET, M.; FAVA-NSI:IO, C.; NE- nificativa la diferencia entre ambas. Basados GI¿oM, R,. & RESTRPO, Â. MarìÌ¡sl of stêndâdized - pa¡t en los datos ariterior€s, se buscó et valof pte serodlagnostic procedu¡es lor syst€mic . I]: €oEplêmert fixation test. Wasrdngtôn, D. C,, pâ¡s- dictivo, hallaridose que la IDGA d¿ seguddâd mericrü H€slth Organizetion, 1072. completa para el diagnóstiso en cualquiera de los perfodos evaluados no asi la Fc, la que ¡

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282 CÀNO, L. E, & RES'I?EPO, A. - Ptecllctive value ol a€Eologlc tests tr¡ the di¿g¡osls and follqw.up of trlati€ûls \rttb ps.r3¿occidioidor¡J'côsiE, Rev. IDst, Med. trolr. São Pe[lo, nr nÈn3, rß87.

¡oloFr. lErashingtoD. Soclety fo! Microbiology, .á.. Post-theBpt¡ st¿fuE of p$acocciauoidorrycosig ^4rûêrlcan - 19Ì6, p. 9i)6.910. patiênts tæated with &etocor¡åzole. Áûer. J. llle¡l., !l (18): 53-5?, 1983. l7- RESIREPO, Â. & MONCAÐÄ, L. E. SercIogic pro. ceduEs ln tlìe aüagrosis of ps,mcoccidioialomycosis.- I¡: 8. a.ESTREPO,4. Procedimie¡tos serclógicos eÈ ¡a I¡['rmN,[fiON¡I SYMPOSIUM ON i\rtYCOSES. Proc€êd- pùacoccialloidoEicosis.- Aal€tmtos Microblol. E¡le!û. ings. Wa.Ebi¡gton, P¿HO, 1970, p. lol'110. (Scient. P¡¡til. lnl€o. 3: l834ll, 1984. No.205). . ROBLEDO, I\[. A.; GOMEZ, I.; GI'IIE&REZ, F.; CÁNC. MONcÄDA, L. E. & &ESTR.trO, A. tvaluación s l¡go plauo R.ESTRE?O. Ä. & L. E. - Chaúcbâlzation - of thê pÌectpltià trallals aletected iû the iEmu¡odliffusloÀ de pacie¡bes con paÉcoccr¿Uoidlo¡dlcoa¡s batÂdos cor tests fo! paracoccia¡¡oido¡lycoÂLs: Äppl. nflc¡oblol., i¿,8: &etoconarol, Aot¡ Eed. oolomb., ü: 155-160, 1985. 138.144, 19?4. 25. RUBINSÌEIN, P, & NEGRONI, R,, €d. - Micosig bro¡coI)ulrnoùa¡es del adr¡lto y del Diño. Buenoa á,i!eÉ, 19. &ESTR.EPO, ,4.; RESTÞEO, M.; RESTBEPO, F.; ÂRI$ Editolial BetÈ, 1981. p. 1%.150;193-221. TIZAB¡J¿ L-t MONCÂDA, !. E. & I¡ELEZ, E. - 26. WHEAT, FRENCH, V,; KåMEL, & tu]mü¡e rcsponse iD p8,lacocci¿holdoDrycogla: a con J.; M. L, S, Tglr9¡ÌI, R. P- EvaluâtloÈ oI crosÊ.rcactioDs ià R. ÈoUed study o¡ 16 p¿tielts befo¡ô aD¿l afte? tl€€lment. calÉ!t¡3!E selologic tesis. J, cII¡. Mlclobiol., 23: 493- S¿boulsudiå. 16: 151-103, 19??. 499, 1986. RESTR@O, A. & C,AÌ'IO, L- E. A comparison ol n. YARZ,IBAL, L. .4.; ALBORI{OZ, CABRÁL, myceual fllbate and lysÊte- ps¡acoccidioidin in M.; lf. tt ¡ t€âsü S.A¡ÍrIÁGO, A. R. Specülc double dlftussioD ûlcro wiüh ps,ÉcoccldioldoÈrycosis. MJcolrÃthologl¡ ¡)atfents t€chnique fü the diagnæts- of Àspe¡glllosls snd pBrs- (De¡ u8.¿r), 84: 49-54, 1983. coccidroidomycosis usiDg üonospecütc aDttseE. Ssbou. lauaua, 16: 55-62, 19?8. R,ESTREPO, A.; GOMEZ, I.; C,åNO, L. E.; -ARANGO, M. D.; GIIIIEEREZ, P.; SANIN, A. & ROBLEDO, M. YÁRzllL¡iL, I". - Composición aÃtigé[ics de P. h!¡. Ä. - Îleatment of pÂracocclodioidomycosis çlth keto. sili€Dsls, In: DEL NEGBO, G.i L.LCAZ, C. S. & F'IG conåzole. A thlee-yea! erped€Ece. ame!. J. M€d,, 7iI RILI,o, A. }I., ed. Blâstù (18): 48-52, 1983. f¡r¡cose srd-aEeÌic€nB.- Sáo Psdo, SaÍior; ÐUSP, 1982. p. 59-67. EESIEEO, GO\EZ, I.; CÄNO, L, E-; 'AR¡NGO, M. D.; cmItRREz,^.i F.; SANIN, ¿{. & RoBLÐo, M. R€cebido para pl'lbllcadãô ú. 21/7/86-

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