`
`IOURNAL
`
`of
`
`the
`
`American Veterinary
`
`Medical Association
`
`VOLUME CXII
`
`NOS. 850-855
`
`JANUAR Y-JUNE, 1948
`
`P mil1'3th by
`
`AMERICAN VETERINARY MEDICAL
`ASSOCIATION
`
`600 S. MICHIGAN AVE, CHICAGO, ILL.
`
`Conionfs Copyrighi
`
`I948 by American Veierinary Medical Associafion
`
`—
`
`CEV Exhibit 1021_001
`
`CEV Exhibit 1021_001
`
`

`

`This material may be protected by Copyright law (Title 17 U.S. Code)
`
`lntradermal Foot-and-Mouth Disease Vaccine
`
`Results Obtained from +he First Million Head of Ca’rtle Vaccinated
`
`CARLOS T. ROSENBUSCH. D.V.M.. Ph.D.. ANDRES DECAMPS, M.V., and
`NICOLAS GELORMINI. MN.
`
`Rite-nos .4 tires, A then-lino
`
`A Ni-IW vaccine has been developed by the
`Research Section of the institute de Biol—
`ngia I‘lxperimental of Buenos Aires, Argen-
`tina. A preliminary report on this vaccine
`was given at. the August, 1946, meeting of
`the Associacion Medico Velerinat‘ia Argen—
`tina.
`i‘ormol—
`This vaccine is alum—adsorbed,
`killed and has a high virus concentration
`[513-9. The virus used in its preparation
`is obtained from fresh tongue lesions of
`artificially infected susceptible cattle, and
`it includes the three main types isolated in
`the Argentine Republic.
`Systematic bovine cross immunity studies
`on the viruses isolated from dill‘el'enl cpi~
`entities as well as from varied geographic
`rtones oi'
`the Argentine have permitted us
`to identify the. presence of genetic variants
`approaching the three main standard types
`described in the literature.
`in no case was
`it possible for us to identify a genetically
`pure virus as they all
`included antigenic.
`fractions for at
`least
`two types of virus.
`The most common variation between viruses
`consisted in percentage dilt'erenccs between
`the antigenic fractions.
`These results were obtained through re-
`peated cross immunity tests on different
`strains of the three main types. For that
`purpose the purest strains were used. 0f
`the 3]. strains of virus studied during the
`year 1946-1947. eight corresponded mainly
`to type 0; seven to type (T. and five to type
`A, while eleven could not be classifier] under
`any type, since they proved immunologically
`related to all three of the standard types.
`This l'nilygenetic characteristic was care-
`fully studied and demonstrated not
`to be.
`due to a mixture of viruses by “vital liltra-
`lion” through series of susceptible calves or
`guinea pigs. The predominant virus type
`isolated through the 1946-1947 epizoetic
`
`lieriod were of the (_‘- and 0 types. The
`
`_1’I‘eseiiled before the Section on General Prat:—
`hljt, Jihghty—frnirth Annual Meeting, American Vol-
`-‘t-2l.
`iii-IT.
`tl’mlfll‘i' Medical Association. Cincinnati. Ohio. Aug.
`
`presence of' the A type was found predomi—
`nantly in the eastern provinces which bor-
`der on l-lrazil and Uruguay and which are
`isolated from the rest of the country by the
`large Parana river. The i-niicootic in that
`zone appeared through a period of time.
`while it occurred almost enzootically through
`the whole year in the larger cattle regions
`of the Pampas, involving in some places as
`many as five consecutive outbreaks of the
`disease.
`The strains used in the vaccine were
`chosen to include several strains of each
`standard lype. These strains were especi—
`all.\-' selected for their intradermie immuniz—
`ing capacity, quick action, and Ionicr lasting-
`effects.
`The alum used in the vaccine is prepared
`from commercial sodium alum of tow iron
`content which, after various purification
`steps and further treatment with ammonia,
`shows unusually high adsorbing capacity,
`with titers above 1:100, as measured by the
`neutral red adsorption test.
`The bufi'er used is prepared from gly-
`cocoll,
`is alkaline and highly stable. The
`vaccine is heat
`treated at.
`‘25 (I.
`for
`two
`days, then culture tested in order to insure
`bactel'ioiogic sterility and later controlled
`as to the presence of live virus by freezing—
`elution methods. 'l‘ollowed by massive intra-
`dermolingual
`inoculations into susceptible
`calves. The inoculated animals should not
`show any symptoms of the disease at any
`time.
`Each batch is tested to establish its ini—
`munizing value. by intl'adermic inoculations
`of 2 cc. into susceptible animals. Seven days
`later,
`the animals are tested by tongue
`scarification
`{friction} with an infected
`burlap or cloth. Other animals are tested
`on the fourteenth day by massive intra-
`lingual
`inoculations with the original vi~
`ruses.
`
`If the vaccine has been well applied, as
`judged by the formation and perduration
`ol.‘ a large sized nodule at
`the inoculation
`site, none of the animals should become sick
`
`{45)
`
`CEV Exhibit 1021_002
`
`CEV Exhibit 1021_002
`
`

`

`(16
`
`
`lttlfil‘lNliilStfl l—lill-It '.A M PS Gupoau INI
`
`.iHT'Il.
`
`.-\.\'.ll..-\.
`
`lesion,
`tongue
`slightest,
`the
`or develop
`while all, or most, of the unvarcinaied cou~
`truls should become sick.
`A great. deal
`ot’
`importance has been
`placed on the applicatiou ot
`the vaccine.
`since it
`involved the generaliaml adoption
`of a new and somewhat complex technique.
`In addition, the thickness of the individual
`skins and the varying working facilities
`liustallations)
`required that
`specific
`in—
`structions be e‘iven. Following are the. con-
`clusions after a prolonged study ol"
`the
`problem:
`The vaccine should be applied intruder-
`micallv in the dose of 2 cc. after careful
`shaving and disinfection of the vaccination
`area. For
`that purpose appropriate 2-cc.
`syringes should be used with needles 5 to
`7 mm.
`long and with a gauge of 0.7 to 0.9
`mm.
`
`The imuculation site should be preferably
`to =1
`linger breadths behind the base of
`:3
`the ear, and in bulls between the base of the
`ear and the poll.
`In animals with a Very
`thin skin.
`the inoculation site should be
`modified, choosing for that. purpose the side
`of the face (masseter region}.
`These places have been selected through
`cruuitless trials and are based on the longest
`perduration ot' the nodule which, according
`to our own experience. should last at least
`a year. The selection of other inoculation
`points is not advised on the basis of the
`more irregular results in the perdul‘ation of
`the original nodule due to such factors as
`tenseness ot' the skin, sensitiveness of the
`animal (scratching), and possibility of in-
`t‘ections.
`The vaccine should be injected careful];r
`in order to insure its thorough intradermie
`application. For that purpose the needle
`should not be inserted too superficially or
`too deep in the skin, because either of the
`two procedures is dangerous, causing the
`formation of
`:‘ibscesses
`by
`compression
`necrosis when too superficial, which later
`open and permit. the loss of part of the vac-
`cine, or by the passage of part of
`the
`vaccine to the subcutaneous tissues, which
`is equall).r ineffective.
`A good application of the vaccine is as-
`sured by the appearance and permanence
`ol‘ a nodule, the size of a “half-nut".
`II‘ the
`vaccine does not. produce the characteristic.
`nodule, or
`if an abscess should he formed
`as the result
`ot." an inadequate technique,
`the animals should be rm-‘accinatml.
`
`the
`that
`olriservz'itions point out
`Our
`presence and length of the immunity is in
`direct relation lo the poi-duration ot' a largo
`nodule.
`'l‘he immunity produced by the vaccine
`appears within the first
`six days and is
`definitely established by the Fourteenth day.
`The. length of the complete polyvalent
`im-
`munity is of six months. After the sixth
`month, the immunity is still evident toward
`some viruses while it appears definitely re-
`duced
`toward others. Experimental
`im—
`munity tests, performed at varying intervals
`is, (i.
`it, and 12 months; by tongue scarifica-
`tion methods with the ditlferent:
`types of
`virus, demonstrated a complete protection
`towards our
`three standard types on the
`third- and sixth—month tests and a complete
`protection towards two types on the ninth-
`and twelfth—month tests. New virus strains
`are being tested to obtain a complete poly-
`valent
`immunity which should last
`for
`twelve months.
`The statistical results obtained by com-
`pilation of data gathered throughout:
`the
`first year of vaccination, including 2 million
`head of cattle, of which close to 1 million
`reached the sis—month immunity period,
`demonstrated highly satisfactory results,
`even
`though it
`involved
`the wholesale
`adoption of a new and somewhat complex
`method of application, of which an appre-
`ciable amount has been applied by laymen
`due to the shortage of veterinarians.
`and
`Notwithstanding these
`difiiculties
`the fact
`that,
`in most. cases
`the animals
`were repeatedly in direct contact. with the
`disease through the intense enaoiitic which
`reigned in the country during,r that. period.
`there were on];r 7 per cent partial or total
`failures of all
`the lots vaccinated in that
`time.
`These failures included :3 per cent. due to
`incorrect application as judged by visual
`inspections made by our veterinarians. The
`l‘en’iaininpr 2 per cent were caused by pos-
`sible deficiencies in the vaccine either in its
`preparation or maintenance because of the
`delicate nature of the product. The vaccine
`has an effective duration of
`thirty days
`when maintained at a temperature of :5
`to
`10 C. If maintained at higher temperatures
`the duration is shortened, depending on the
`degree of exposure.
`The success obtained by the use of thifi
`method has encouraged us to test it in other
`countries (t‘hile, Uruguay. Porn. Paraguay,
`
`CEV Exhibit 1021_003
`
`CEV Exhibit 1021_003
`
`

`

`.J.\s'l:.\|:r
`
`III-ls
`
`I“oo'1‘—AND~h'IUU'J‘i-i DISsase Mouse
`
`47
`
`and Bolivia), amounting to a total of almost.
`100,000 animals. The results obtained in
`these countries have agreed with those of
`the Argentine.
`The same vaccine has been applied to
`about 100,000 sheep with excellent results.
`The only difficulties observed were related
`to cases of incorrect t‘lpplicatitm.
`The dose of the vaccine for sheep is ]. or.
`The inoculation site 1-e:.-.ommended is
`the
`side of the face (below the eye). the elbow.
`or the medial
`'l‘ace ot'
`the thigh, choosing
`always regions free of wool.
`This vaccine has not given the desired re-
`sults in swine. At present we are carrying
`on research on a different vaccine prepared
`solely with swine virus strains. The pre-
`liminary
`results
`obtained
`are
`highly
`promising.
`scale experiments have
`lenige
`Further
`been performed through the last six months
`on a new vaccine based on a predmninanee
`ot' quick-acting virus strains which has ell-
`abled us
`to obtain a complete polyve‘dcnt
`quick-acting immunity within the
`first
`t.i\-'clit'.j.-'-t'onr to thirty-six hours of the appli—
`cation. The immunity which is established
`is ol‘ shorter duration til to .1 months).
`This vaccine is enabling us at. present to
`obtain the desired results in livestock 't'airs.
`at weaning, in transi'iorts or livestock move:
`meats, or even to limit beginning outln'eaks
`of the disease, providing that not many ani-
`mals are incubating the virus.
`Very good results have been obtained in
`large lots oi"
`livestock. building a vaccinav
`tion ring,r or barrier
`immediately around
`the disease outbreak. These results could
`not be obtained with the regular vaccine
`because it. requires generally fourteen days
`for the establishment of complete immunity.
`Comparative field immunity tests between
`the
`subcutaneous
`t‘il’aldmann or Silvio
`Torres types) and the.
`int'.radei'mic. vaccine
`have demonstrated that
`the immunity es-
`tablished in the case of
`the subcutaneous
`vaccines is generally slower in its onset and
`of a shorter duration.
`in addition, the im-
`munity cited in young animals is much
`greater with the inlradi-ermie vaccine, pro~
`vided [here is a peril-cl nodule ]Jl.'l‘lt1l1'£ti'lull.
`The immunity produced by the inlriuier-
`Iuie vaccine is slrielly ol‘ :1
`lissno type and
`ease ol‘
`not
`immoral. as
`in
`the
`the.
`filth-
`cutaneous vaccine. This is proved by the
`complete lack of
`formation of blood anti-
`bodies as tested by selfllI‘Ii-Vil‘ils neutraliza-
`tion lesls.
`
`the. intra-
`this new vaccine,
`Concluding.
`dermie vaccine. because of
`its decidedly
`lower cost, quicker immunity cll‘ect, stronger
`action, and longer duration should supplant
`in the very near future all
`the present-day
`subcutaneous vaccines.
`
`Human Epilepsy and Canine Hysteria
`Related
`
`In an article describing the part. played
`by chemi‘ally treated wheat
`llour
`in the.
`etiology of human epilepsy. Silver,
`Joini—
`sou, Kai-k, Klein, and Zevin f.}.A-iu..ll.i-t.
`Nov. 22, 1947: 757-760) make a strong
`case against
`the use of gaseous nitrogen
`trichlm'ide to make white bread tine. silky.
`and more appealing to the palate, for, when
`fed to dogs it causes “canine epilepsy",
`the
`name preferred for “running tits,” ”va—
`nine hysteria,”
`or
`“fright. disease.”
`ol‘
`veterinary literature, which bears a close
`resemblance to idiopathic epilepsy ot'
`the.
`human being. Electroencephalograms of ex-
`perimentally stricken dogs
`justified the
`authors to use the word “epilepsy" for the
`canine ailment. In short, some of the white.
`llour of the United States and a few l‘ill-
`ropean countries is toxic. Instead of being
`the stall of tile, it is the stail' ot' a grave.
`cerebral disorder manifested ill man and
`dogs. The investigatimial work of Meinick
`and (Jogwell and of Arnold and Elvehjem
`in this country and that of Johnson and
`Kark et- at.
`in England is cited, and the
`references where the curious may read the
`details are given. The relation of farina-
`ceous food to the disease we call canine
`hysteria.
`is well known in the small animal
`clinic, but
`its definite connection with the
`human epileptic is news.
`
`(i. Rosen—
`l’l'ruenlirm.— -l.)i'. A.
`It‘oot—RH!
`berger
`[WASH ’08), senior
`lield veteri-
`narian of the (.‘-ali.t'ornia State Department.
`of Agriculture,
`takes care of the foot-rot
`problem in sheep by automatic immersion
`of their feet. in copper sulfate solution at a
`specially constructed salt
`lick. The sheep
`approach the sail
`trough by walking over
`wooden lanks Ill
`l'l. wide and a few inches
`deep.
`“'rlit‘tl
`tllt' Wet, or
`lituatnl'nl. Henson
`arrives, water is l'n'sl put
`into line shallmv
`tanks and later llle copper solution.
`l“or a
`short
`time.
`the sheep must be guarded
`against drinking the solution—From.
`the.
`('niifw'nio ll’rmi fi'i'un'f'i'.
`
`CEV Exhibit 1021_004
`
`CEV Exhibit 1021_004
`
`