EXPERIMENTAL OCULAR SYPHILIS AND NEUROSYPHILIS*t · BRITISH JOURNAL OF VENEREAL DISEASES dosages to keep the monkeys properly sedated. In the rabbits 0 7 to I ml. of pentobarbital

Brit. J. vener. Dis. (1965), 41, 15.

EXPERIMENTAL OCULAR SYPHILIS AND NEUROSYPHILIS*t

BY

J. LAWTON SMITH, JOSEPH A. SINGER, DAVID H. REYNOLDS,

M. BRITTAIN MOORE, JR.,+ ANNE R. YOBS,§ AND JOHN W. CLARK, JR.From the Departments of Ophthalmology and Neurosurgery, University of Miami School of Medicine, Miami, Florida,and the Venereal Disease Research Laboratory, Communicable Disease Center, U.S. Public Health Service, Atlanta,

Georgia.

The challenge in clinical syphilis to-day is thedetection of the disease in the sero-negative patient.The magnitude of this problem is evident when oneconsiders that over 100 cases of ocular syphilis andneurosyphilis have been encountered in this institu-tion within the past year (Smith, 1964; Smith andMoore, 1964; Smith and Taylor, 1965). Ofparamountimportance is the fact that the majority of thesepatients were non-reactive to the standard reagin testsfor syphilis. Diagnosis was established by the follow-ing criteria: (1) history of infection and inadequatetreatment; (2) clinical signs of the disease-as opticatrophy, pupillary changes, and the like-and (3) reac-tive Treponemapallidum immobilization (TPI) and/orfluorescent treponemal antibody absorbed (FTA-ABS) tests on the peripheral blood (Deacon, Falcone,and Harris, 1957; Deacon, Freeman, and Harris,1960; Deacon and Hunter, 1962).A combined clinical and experimental study was

therefore undertaken in collaboration with theVenereal Disease Research Laboratory of the USPublic Health Service in Atlanta, Georgia. Thepurposes of this project were as follows: (1) to studysero-negative syphilis, both in the human and in theexperimental animal; (2) to investigate primaryneurosyphilis (induced by injecting T. pallidumdirectly into the subarachnoid space in the primate);(3) to study ocular syphilis and neurosyphilis in therabbit and monkey-using more recent clinicaltechniques (such as fluorescein fundus photography),and correlated with both standard reagin tests(VDRL) and more exacting (TPI and FTA-ABS)serological methods; (4) to attempt recovery ofvirulent T. pallidum from sero-negative patients and

* Received for publication August 6, 1964.t This work was supported by grants NB 04604-01, NB 0505-01

and 5Tt NB 5277-04, National Institutes of Health; also by grantG-282 National Council to Combat Blindness; and from support fromFlorida Lions Eye Bank, District 35-A.

$ Director, Venereal Disease Research Laboratory.§ Pathologist, and Chief of Medical Research Division, Venereal

Disease Research Laboratory.

animals. This report presents the findings in theexperimental animals noted during the first year ofthis study.

Material and MethodsA primate, the owl monkey (Aotus trivirgatus), was

chosen because of species proximity to man and becauseof previous experience with this animal (Smith andSinger, 1965a, b). The rabbit was also used both as acontrol to assess virulence of treponemes and because ofthe large body of data available in the older literatureconcerning experimental syphilis in this species.

Pigmented and albino rabbits weighing approximately5 lb. (2- 3 kg.) and owl monkeys weighing approximately1 I lb. (0 69 kg.) were housed in rooms at constanttemperature and humidity. They were fed standard rabbitand monkey food and were allowed water as desired.

Rabbits with acute testicular syphilomas were trans-ported from the Venereal Disease Research Laboratoriesat Atlanta, Georgia, to Miami. The syphilomas wereremoved at the height of the inflammatory response foruse in these experiments. The testicular tissue was finelyminced and mixed with a 50-50 serum saline solution(the latter being non-reactive to both VDRL and TPItests). The resulting emulsion was centrifuged to removetissue particles and the supernate was used for inocu-lations.

It was elected to inoculate virulent Treponema pallidumdirectly into the cisterna magna of five owl monkeys andfive rabbits. This was done in order to induce primaryneurosyphilis. Ocular syphilis was investigated byinoculating treponemes into varying ocular sites (anteriorchamber, cornea, vitreous cavity, and optic nerve). Sevenother normal owl monkeys and seven other rabbits wereused for the ocular injections.The monkeys were anaesthetized with subcutaneous

injections of phencyclidine hydrochloride II. It was foundthat 0-2 to 0-4 ml. of a 10 mg./ml. solution of thismedication would induce light anaesthesia with onsetwithir ve minutes after injection and lasting for one totwo hours. It was necessary on occasion to repeat these

11 Supplied as Sernylan (10 mg./ml.) through the courtesy of ParkeDavis and Company.

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dosages to keep the monkeys properly sedated. In therabbits 0 7 to I ml. of pentobarbital (50 mg./ml.) was

given intravenously for anaesthesia. All ocular injectionswere given using tuberculin syringes and short gauge 30needles. Cisternal injections were performed with gauge20 paediatric lumbar puncture needles. The volume of T.palliduni suspension used for ocular injections was

0 01 to 0 05 ml., while 0 2 to 0 4 ml. was used for theintracisternal inoculations. All eyes were examined dailyusing focal illumination and loupes. Biomicroscopic andindirect ophthalmoscopic examinations were performedat appropriate intervals. Significant ocular and physicalchanges were documented by external, fundus, andfluorescein fundus photographs. Pupils were dilated forexamination with 1 per cent. cyclopentolate hydro-chloride*. This drug not only provided better mydriasisthan did atropine in the rabbits, but possessed theadditional advantage of shorter duration of action, so

that pupillary responses could be evaluated within 36hours after ophthalmoscopy.

Sera were submitted from all animiuals for both quanti-tative VDRL and TPI testing. All the serological studieswere performed at the Venereal Disease Research Labora-tories in Atlanta. Proof of infectioni with T. pallidum was

attempted by passive transfer technique on some of the

* Cyclogyl (Schietfelin & Co.).

animals six months after inoculation. This was done byexcising popliteal lymph nodes from selected rabbits andmonkeys, and injecting freshly emulsified suspensions ofthis tissue into the backs of normal rabbits which were thenobserved for the appearance of dark-field positive lesions.

ResultsThe data, first for rabbit and then for monkey,

will be presented as outlined: (1) intracisternalinoculation; (2) ocular routes-cornea, anteriorchamber, vitreous, and optic nerve.

Rabbit(1) Intracisternal Inoculation (Table I)

Five rabbits were inoculated with treponemes inthe cisterna magna. The rabbits appeared healthyand the eyes remained white, quiet, and developed no

lesions during the ensuing two months. In spite ofthese negative findings the serological tests forsyphilis performed two to three months afterinjection showed that all the animals in the group hadreactive VDRL tests.

Hair ancd Skin Findlings.-A consistent findingduring the third month was a change in the texture

TABLE I

RABBIT: INTRACISTERNAL INOCULATION

MonthRabbit ______ ._ ._ _._____ ___- _______

First Second Third Fourth Fi'lth Sixth Seventh Commentand Eighth

R50 Sluggish Alopecia Alopecia Alopecia Dead Generalizedpupils Snuffles Snuffles Snuffles syphilis

Anisocoria Anisocoriai AnisocoriaVDRL R4 VDRL R4

TPI RLymphnode

R51 Alopecia ., Alopecia Alopecia Alopecia GeneralizedSnuffles Snuffles Sniuffles etc. ;yphilisAnisocor-ia Interstitial Iris atrophy Iris atrophy

kerat it isTears dark-

VDRL R2 field 4 VDRL R4TPI RLymphnode

R52 Alopecia .. Alopecia Alopecia Dead GeneralizedSnuffles Snuffles Snuffles syphilisHead tilt Anisocoria Iris atrophyLef't hemi- Uveitisparesis Koeppe

nodulesVDRL R4 VDRL R4

TPI RLymphnode _

R53 Alopecia ,, .. Alopecia Alopecia GeneralizedAnisocoria etc. etc. syphilis

VDRL R8 VDRL R4TPI R

R54 Alopecia Alopecia Dead GeneralizedIris atrophy syphilis

VDRL R32 VDRL R2 Iris atrophyVDRL WR= weaklyreactive;VDRLR4-reactive1 TPI Retc.VDRL WR = weakly reactive; VDRL R4 -reactive 1:4, etc.

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and colour of the fur, giving it an unkempt ap-pearance (Figs 1, 2, and 3). A very typical "moth-eaten" alopecia starting around the eyes and ears andthen involving the back, nape of the neck, and pawswas also noted (Fig. 4). Mucous membrane lesions ofthe nose and conjunctiva were found after three tofour months. These changes were very striking andpresented an almost identical picture in all theanimals inoculated in the cisterna magna. The find-ings were similar to those reported over 40 years agoin the classic study by Brown and Pearce (1920a).

next. In this regard, anisocoria is more difficult toassess in the rabbit with laterally situated eyes thanin the monkey, where both eyes can bo observedsimultaneously.

Keratitis developed in the right eye of one animal(R5) inoculated in the cisterna magna. The tears ofthis eye were dark-field positive at five months.

Serological Response.-During the third and sixthmonths the VDRL tests were reactive in dilutionsfrom 1:2 to 1:32 on all five animals in this group.

_ X. -FIG. 1.-Rabbit five months after intracisternal inoculation with FIG. 3.-Rabbit three months after intracisternal inoculation with

T. palliclumt. Note unkempt hair, alopecia. T. pallidum1. Note abnormal hair texture.

FIG, 2.-Rabbit three months after intracisternal inoculation withT. pallidlunti.

Ocular Findings.-Iris atrophy, without bio-microscopic evidence of uveitis, was noted in two ofthe five atlimals during the sixth month followinginoculation in the cisterna magna. The iris atrophytended to start in the upper nasal quadrant, spreadin a symmetrical fashion, and involve both eyesequally. In the pigmented animal the iris atrophy wasbest visualized by retro-illumination. The pupils werequite variable in size from one examination to the

FIGi. 4.-Rabbit three months after intracisternal inoculation with T.pall/lumn. Note the periocular alopecia.

TPI tests performed during the sixth month were alsoreactive in these five rabbits. As will be noted later,this was in marked contrast to the serologicalresponse following intra-ocular injections in therabbit and the sero-reactions in monkeys.

Lymph Node Transplants.-Popliteal lymph nodeswere excised at 161 days from three rabbits inocu-lated in the cisterna magna. The nodes were emulsified

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with 50-50 serum saline solution and promptlyinoculated intracutaneously on the backs of normal(VDRL and TPI non-reactive) rabbits. Theserabbits were transported to the Venereal DiseaseResearch Laboratories for observation. Within one

month two out of the three lymph node inoculationsites were dark-field positive for T. pallidum.

(2) Ocular Routes (Table II)Because of interest in interstitial keratitis, uveitis,

chorioretinitis, and optic nerve lesions it was electedto inoculate T. pallidum into the cornea, anteriorchamber, vitreous, and optic nerve.The corneal stroma of both eyes of two rabbits

was injected with treponemes. One animal (R55) diedfour days later. A careful autopsy failed to reveal anysignificant lesions. The other rabbit (R58) began todevelop the typical "moth-eaten" alopecia after fourmonths. The eyes, however, remained normal foreight months. VDRL and TPI tests remained non-

reactive, and one attempt at lymph node transfer wasunsuccessful.The anterior chambers of the eyes of two rabbits

were injected with T. pallidum. One (R56) receivedtreponemes in the anterior chamber of the right eye

and a similar injection of saline in the left. The otheranimal (R57) received treponemes in the anteriorchambers of both. No ocular lesions developed in thefirst rabbit during the next eight months, but thequantitative VDRL titre was 1:2 during the thirdmonth, 1:5 during the sixth month, and 1:2 at eightmonths. In the other rabbit a few tufts of vesselswere seen at the upper limbus of both eyes at sixweeks. By four months, kerato-uveitis with Koeppenodules was apparent in both eyes and the VDRLtest was reactive. The fundi were normal, revealingthat the reaction was primarily an anterior uveitis.One week later the animal developed a head tilt,ataxia, and hemiparesis. The rabbit died on day 133of the experiment. The histo-pathological studies willbe the subject of another report.

Intravitreal inoculations were given to two rabbits.One of these (R59) received treponemes in thevitreous of the right eye and saline in the left. Inthis animal no ocular or systemic lesions developed,and serological tests for syphilis have remained non-

reactive. The other rabbit (R60) was injected with T.pallidum intravitreally in both eyes. By two monthsalopecia was present. In this regard, it is of interestthat at three months the animal was sero-negative but

TABLE IlRABBIT: OCULAR ROUTES

MonthRabbit Route of

Inoculation First Second Third Fourth Fifth Sixth Seventh and CommentEighth

R55 Cornea DeadOU T.palliduni

R56 Anterior No lesionschamberRE T. VDRL R2 VDRL R5 VDRL R2pallidum TPI- TPI-LE saline

R57 Anterior Blood Kerato- Nystagmuschamber vessels at uveitis OU AnisocoriaOU T. upper VDRL R2 Head tilt Hemiparesispallidum limbus OU Dead

R58 Cornea VDRL- Alopecia Alopecia AlopeciaOU T. VDRL- VDRL-pallidum TPI -

Lymphnode-

R59 Vitreous VDRL-- VDRL- VDRL- No lesionsRE T. TPI -pallidum LymphLE saline node-

R60 Vitreous Alopecia Alopecia Alopecia Alopecia Dead No ocularOU T. Snuffles lesionspallidum VDRL- VDRL WR

TPI -Lymphnode-

R61 Optic nerve Dead No lesionsRE T. VDRL- seenpallidumLE saline

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the VDRL test was weakly reactive during the sixthmonth. The animal died on day 166-five days afteran unsuccessful attempt to demonstrate T. pallidumby lymph node transfer.One rabbit (R61) was injected with T. pallidumn in

the optic nerve of the right eye and saline in the left.The serological tests for syphilis remained non-

reactive, and no physical findings had been notedwhen the animal died during the fourth month.

Monkey(1) Intracisternal Inoculation (Table lll)

Five owl monkeys were inoculated with T.pallidumn in the cisterna magna. The animals remained

19

essentially negative to examination for approximately10 weeks when pupillary changes were noted.Anisocoria was a frequent finding, making its

appearance in the second to third months afterinoculation. Pupillary inequalities were extremelyvariable from one examination to the next.At nine weeks one animal (050) developed ptosis

and mydriasis-signs of third nerve paresis (Figs 5

and 6). At 12 weeks alopecia was noted above theright eye and both optic disks were pale. It was notuntil during the sixth month, however, that theserological test for syphilis became reactive. Anotheranimal (052) developed right-sided weakness duringthe second month and died several days later.

FIG. 5.-Owl monkey nine weeks after intracisternal inoculation with FIt. 6.-Owl monkey nine weeks after intracisternal inoculation withT. pallidum. Note dilated right pupil. T. pallidum. Note ptosis of right lid and dilated right pupil.

TABLE I llMONKEY: INTRACISTERNAL INOCULATION

MonthMonkey _ _ ____

First Second Third Fourth Fifth Sixth Seventh Commentand Eighth

050 Ptosis, RE Alopecia Dead Right IttDilated right above RE nervepupil Optic paresis(variable) atrophy OpticVDRL -- VDRL VDRL WR atrophy

051 Cisternal Anisocoria Anisocoria Anisocoria Flame New flame Fundustap- 26 haemorrhage haemorrhage lesionWBC (15% LE White Rising VDRLpolys. 85,% VDRL- VDRL - exudate LE VDRL- VDRL WR titremonos.) TPI R TPI R

052 Right-sided Deadparesis

053 Alopecia onocciput.Dead

054 Vertical Anisocoria Anisocoria Anisocoria Ulcer on Mal perforansnystagmus right heel ulcer

VDRL- VDRL R4 VDRL RI VDRL R4TPI R TPI RLymphnode +



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At five months flame haemorrhages and an exudateappeared in the left eye of one monkey (051) inocu-lated in the cisterna magna. Serological studies fromthis animal revealed non-reactive VDRL tests duringthe third and fourth months. The TPt test wasreactive when tested during the sixth month when theVDRL test was still non-reactive. At seven monthsthe VDRL test became weakly reactive.

Vertical nystagmus was seen in one monkey (054)at two weeks. Anisocoria was seen at three monthsand by six months a mal perforans-like ulcer wasnoted on the right heel. During the third month theVDRL was non-reactive, but during the fourthmonth it was reactive 1:4. In the sixth month theTPI was reactive, and a popliteal lymph nodeinoculated intracutaneously on the back of a rabbitproduced dark-field positive lesions.

(2) Ocular Routes (Table IV)In an attempt to produce interstitial keratitis, T.

pallidum was injected into the corneal stroma of threeeyes in two monkeys. Saline was given as a control inone eye. A small infiltrate around the injection sitescleared during the first two weeks. One monkey (055)remained sero-negative and died in the fourth month.No significant lesions were seen at necropsy. Theother animal (056) showed a weakly reactive VDRLduring the third and ninth months, but was non-reactive during the seventh month. A TPI test duringthe seventh month was non-reactive.

Anterior chamber inoculations were made in two

monkeys. One animal (057) was injected withtreponemes in the right eye and with saline in theleft. The other animal (058) received treponemes inthe anterior chambers of both eyes. Anisocoria wasnoted during the second month in both animals. TPIand VDRL tests remained non-reactive for sevenmonths. Although no anterior uveitis was observed,at six months the first animal (057) developed a sub-hyaloid haemorrhage and a large exudate in thecontrol eye (Figs 7, 8, and 9). This occurred on day

FIG. 8.-Owl monkey (057). Fluorescein fundus photograph of sub-hyaloid haemorrhage. Animal held upside down.

FIG. 7.-Owl monkey (057). Left (control) eye 162 days after injectionof T. pallidum in anterior chamber of right eye. Note sub-hyaloid FIG. 9.-Owl monkey (057). Taken three weeks after Fig. 8. Notehaemorrhage and exudate. absorption of sub-hyaloid haemorrhage.

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162, a week after a diagnostic intracisternal tap.During the sixth month a popliteal lymph node wasexcised and inoculated intracutaneously on the backof a rabbit. Virulent T. pallida were subsequentlydemonstrated in the lesion that developed from thenode of this sero-negative monkey.The other monkey (058) is also of great interest.

During the sixth month a few small haemorrhagesdeveloped in the fundus around the posterior pole ofthe right eye. Although this monkey remained sero-negative to VDRL and TPI tests for over six months,a popliteal lymph node excised during the sixthmonth and inoculated on the back of a rabbitcontained virulent treponemes. Both of these sero-negative monkeys had active infection as shown bylymph node transplant.Two monkeys inoculated with T. pallidum in the

vitreous developed endophthalmitis and died duringthe first week. This was apparently due to a secondarypyogenic organism.

Onemonkey (061) was inoculated with treponemesin the optic nerves of both eyes. Both disks becamepale during the first month (Figs 10 and 1 1). VDRLand TPI tests remained non-reactive for over sevenmonths. An attempt at lymph node transfer duringthe sixth month was unsuccessful. It is difficult todifferentiate the effects of trauma from syphilis as thecause of this optic atrophy.

DiscussionThe number of reported cases of primary and

secondary syphilis in the USA has risen from 6,323in 1957 to 20,540 in 1962 (USPHS, 1963). Thenumber of cases of syphilis of all stages reportedduring 1962 was about 124,000 (Moore, 1963). Ifadded to this are the unreported cases and those thatremain undetected because ofnon-reactive serologicaltests, the total number becomes alarming. Thisrising incidence prompted a renewed interest inexperimental syphilis.

TABLE IVMONKEY: OCULAR ROUTES

MonthMonkey Route of

Inoculation First Second Third Fourth Fifth Sixth Seventh Commentand Eighth

055 Cornea RE Infiltrate at VDRL- AlopeciaT. pallidum injection aboveLE saline site both eyes

Dead

056 Cornea OU VDRL WR- VDRL WR- VDRL-T. pallidum TPI-

057 Anterior Anisocoria Anisocoria Anisocoria Anisocoria Sub-hyaloid Negativechamber haemor- serologyRE T. rhage andpallidum exudate PositiveLE saline LE transfer

VDRL- VDRL- VDRL- VDRL-TPI -Lymph-node +

058 Anterior .. Small Deadchamber haemor-OU T. rhage REpallidum VDRL-

TPI-Lymphnode +

059 Vitreous Endo- SecondaryRE T. phthal- infectionpallidumn mitisLE saline Dead

060 VitreousOU T.pallidum

061 Optic nerve Pale disks Pale disks Pale disks Pale disks Pale disks Pale disks Pale disks Trauma vs.OU T. Sluggish Sluggish T. pallidumpallidum pupils pupils as cause of

pale disksVDRL- VDRL- VDRL- VDRL-

TPI-Lymphnode-

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FIG. 10.-Owl monkey (061). Right eye third month after injection ofT. pallidumJ in optic nerve. Note pale optic disks.

T. pallidumn was identified as the causative agent ofsyphilis by Schaudinn and Hoffmann (1905). Thefollowing year Bertarelli (1906) successfully inocu-lated the rabbit with T. pallidum. The natural course

of experimental syphilis in this animal was beautifullydelineated by Brown and Pearce (1920a-f, 1921a, b)The rabbit has retained its position as the principallaboratory animal for the study of syphilis. Since our

interest in this study was mainly in syphilis of the eye

and nervous system of the primate, we elected toinoculate T. pallidum directly in the central nervous

system and eye in both monkeys and rabbits. All therabbits inoculated intracisternally developed clinicalsigns of generalized syphilis as manifested byalopecia, anisocoria, and reactive VDRL and TPItests. Iris atrophy without uveitis was quite common.The rabbit developing the most marked interstitialkeratitis was inoculated in the cisternal magna, notthe cornea. In the monkey, optic atrophy, third nerve

paresis, anisocoria, and retinal haemorrhages andexudates were produced. In general, serologicalresponse in the owl monkey is much less marked thanin the rabbit.One of the most striking findings and the one with

the greatest clinical significance is the successfuldemonstration of dark-field positive lesions in rabbitsinoculated with popliteal lymph nodes from monkeyspreviously injected with T. pallidum yet non-reactiveto both VDRL and TPI tests.

Turner and Hollander (1957) reported similarfindings with Macaccus rhesus and Cerpethecus

FIG. 11.-Normal owl monkey. Compare disks with Fig. 10.

aetheopis (African green) monkeys. One of hismonkeys remained sero-negative for 361 days, yetsuspensions of liver and blood yielded positiveresults on transfer to rabbits. Another monkey neverdeveloped a primary lesion at the inoculation site,remained sero-negative for 219 days, and yet bloodand lymph node suspensions yielded positive resultson transfer to rabbits. Sero-negative infectiousrelapse has been produced in rabbits as well. Nelson(1952) treated a group of syphilitic rabbits with smalldoses of penicillin one month after inoculation. TheVDRL titres fell to zero within three months aftertreatment. In marked contrast, the TPI tests, althoughinitially falling, again rose to pre-treatment levels.Moreover, treponemes were demonstrated bypositive lymph node transfer in these VDRLnegative animals after five months. A study of sero-negative syphilis in humans is now in progress.

SummaryThe natural course of experimental primary

ocular syphilis and neurosyphilis in the rabbit and inthe owl monkey is presented. Virulent treponemeshave been recovered from the lymph nodes of sero-negative primates previously inoculated intra-ocularly with T. pallidum.

Grateful acknowledgement is here given to Mr JohnnyJustice, Jr., photographer of the Bascom Palmer EyeInstitute.

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REFERENCESBertarelli, E. (1906). Zbl. Bakt., 1. Abt. Orig., 41, 320.Brown, W. H., and Pearce, L. (1920a). J. exp. Med., 31,

475.(1920b). Ibid., 31, 709, 729.(1920c). Ibid., 31, 749.(1920d). Ibid., 32, 445.(1920e). Ibid., 32, 473.(1920f). Ibid., 32, 497.(1921a). Ibid., 33, 495, 515, 525.(1921 b). Ibid., 34, 167.

Deacon, W. E., and Hunter, E. F. (1962). Proc. Soc. exp.Biol. (N. Y.), 110, 352.

Falcone, V. H., and Harris, A. (1957). Ibid., 96,477.-, Freeman, E. M., and Harris, A. (1960). Ibid., 103,

827.Moore, M. B., Jr. (1963). J. Amer. med. Ass., 186, 831.Nelson, R. A., Jr. (1952). Brit. J. vener. Dis., 28, 160.Schaudinn, F., and Hoffmann, E. (1905). Dtsch. med.

Wschr., 31, 711.Smith, J. L. (1964). Amer. J. Ophthal., 57, 973.

and Moore, M. B. (1964). "Recent Advances in theSerodiagnosis of Ocular and Neurosyphilis",

chap. 12, pp. 321-334. University of Miami Neuro-ophthalmology Symposium. Thomas, Springfield,Ill.

--and Singer, J. A. (1965a). Anter. J. Ophthal., in press.(1965b). Ibid., in press.

and Taylor, W. H. (1965), Ibid., in press.Turner, T. B., and Hollander, D. H. (1957). Biology of

Treponematoses.WHO Monogr. Ser. No. 35. World Health Organization,

Geneva.US Department of Health, Education, and Welfare,

Public Health Service (1963). VD Fact Sheet-1962, p. 9.

Syphilis oculaire et neurosyphilis experimentales

RESUME

On decrit l'evolution naturelle d'une syphilis oculaire etd'une neurosyphilis experimentales chez le lapin et lesinge "chouette". On trouva des treponemes virulentsdans les ganglions lymphatiques de primates auparavantinocules avec le treponeme pallidum par voie oculaire.

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Documents

EXPERIMENTAL OCULAR SYPHILIS AND NEUROSYPHILIS*t · BRITISH JOURNAL OF VENEREAL DISEASES dosages to keep the monkeys properly sedated. In the rabbits 0 7 to I ml. of pentobarbital