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ATD Report 67-65 29 June 196('-

SurVeys of Foreign Scientific and Technical Literatuie

SOVIET VIROLOGY

ATD Work Assignment A-67-7

This document is subject to special export controlaand each transmittal to foreign governments or for-eign nationals may be made onl wit roalof the Ae _ _o

The pullcation of this report does not constituteapproval by any U. S. Government organization ofthe inferences, findings, and conclusions containedherein. It is published solely for the exchangeand stimulation of ideas.

Aerospace Technology DivisionLibrary of Congress

TABLE OF CONTENT8

introduction .. . .. . . .. . . .* & * I 0 & a iv

I. The Tickborne Encephalitis Complex . . ....

A. Epidemiological Data. . . ... .... . 2B. Behavior of TBE Virus in Cell and

Tissue Culture . .. ... ....... 4. Induced Mutation of TBE Aruses . . . . . .6D. flagnositc Methods for TBE.. ...... .6E. TBE Therapy

1. Vaccines .. .. .. .. ..... * * * & * *2. Challenge . . .... 9

F. Japanese B Encephalitis .... . .13G. Omsk F ,er and Related Diseases . . . . . .13

-1. Hoof-and-Mouth Disease . ....... . . 25

IiI. Rabies.. . . . . . . . . . * * * * * * * 0 a .26

IV. Swtine Plague . . . . . . . . . . . . . . .... 32

V. Venezuelan Equine Encephalomyelitis . . . . . .33

VI. Miscellaneous Diseases - . . * . a . & * . . . .34

VII. Pox-Virus Infections . . . . . . . . . . . . .37

References . . . . . . . . * . * . * * a *40

Appendix I. Supplementary Bibliography . . . . . .70

Appendix II. Conferences on Viral Disease . . . . .82

Appendix III. Some Soviet Virological ResearchInstitutes and Their Personnel . . . . 91

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SOVIET VIROLOGY 1962--1965

WA A-67-7

ITRODUCTION

This report reviews literature on Soviet virologicalresearch published between 1962 and 1965, incluaive, per-taining to the development and administration of vaccinesand other therapeutic preparations designed to protecthumans and animals against virus diseases. It includesdata on preparation and innoculation techniques and chal-lenge tests on laboratory animals to test the effectiveness

of new vaccines. Coverage of related studies in the epidem-

iology, detection, diagnosis, vectors, and infection cycles

of viral diseases is also included. Appendices provide

additional information on virus research personnel and in-

stitutions, and on virological conferences held duringthose years.

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I. THE TICKBORE MMEPHALITIS COMPLEX

Viruses of the tickborne encephalitis complex aregroup B arboviruses and are closely related antigenically,often behaving like distinct strains of a single viralspecies. The Far-Eastern form of the disease is usuallymore virulent than the European form [275). Tickborneencephalitis (TBE, RSSE, Far-Eastern encephalitis,biphasic (two-wave) meningo-encephalitis, etc.) has abroad host range but is usually spread by ixodid or closelyrelated ticks, generally Ixodes persulcatus and Iodesricinus.

Fleas have been implicated as vectors as well [244,281, 111, 282]. In one study, the species composition,host range, and population dynamics of fleas in theKalinin, Perm, and Kemerovo oblasts were studied. It wasfound that fleas transmitted the virus to rodents within6 hours after their birti; this explained the relativelyhigh antibody titers in the rodents and the low numbers ofixodid tick larvae and nymphs found in the vicinity ofburrows. Transmission by fleas was confirmed experiment-ally [110 ].

Virological studies of ticks in epidemic regionsare made regularly, especially during peak infective per-iods [110, 109, 261, 41, 233].

Hundreds of distinct strains have been isolated,including several strains that are antigenically and mor-phologically different from standard strains and areoften highly pathogenic in tissue cultures [109, 41].Birds, rabbits, livestock, hedgehogs, and other wildanimals are also TBE vectors [164, 55]. TBE virus hasbeen isolated from thrushes (Oriocichla daua) carryinglxodes persuZcatua ticks [275, 248] and from hedgehogs,which maintain the virus during hibernation after beinginfected by tick bites or by eating contaminated food[143, 255, 74, 264].

A large-scale survey of virological and serologi-cal data on arboviI-uses isolated in the eastern SovietUrdon revealed TBE, EEE, WE"E, and Chikungunya virus inover 1000 samples from epidemic foci in Siberia, theIrkutsk region, eastern Kazakhstan, and other regions[59, 26]. Secondary examination of insect, bird,animal, and human organs and tissues from eastern

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Kazakhstan yielded data on the first isolation of Casalsgroup A viruses in the eastern USSR [12,93.]. Strains K-10,K-13, and K-16 isolated from~ mosquitoes produced symptomswithin 24~ hours. Strains FT-149, ?T-151, PT-. 61 and PT-182isolated from the birds SturnuB vulaaris, Corvus corona,and Larus ridibundus had Incubation periods lasting from1--8 days (12]. Transovarian transmission of TBE virushas been demonstrated In a sinaP" rcet'ze of' certaintick species. Its, pobential Imnportance is :-hat it en-sures the iLnfection of a large number of larvae and con-I sequently, wide diEremination axnoung the local small-mammal population. The species displaying this trait areIzodes persuZeatua. Ir. rincinus, _T. hexaconi, Dermacentc.silvarum, HacmavhysaZis concinn'a, and H. japonica. Experi-mental infection. -:f i. riCinus showed t- .a t* cialmeans or infect~on could be used. Aiz;c.: tenal es, 3.3%transmitted the virus ,,--. they were infected by feedingon infected mice and 21 % when the virus was inj'ecteddirectly into the bod., navity. Although the lattermethod produced better results, the inoculation processwas often fatal to tr~ticks. The strains did not losetheir cytopathogenic.lty during transovarian passage [249]..

A. aidemiological Da ta -on the Tic cborne Eniceplitis

Ait a conferaiiae on arbovirus infections held in Mos-cow In September 1964, the Eleventh Scientific Session ofthe Insti-tute of Policryelitis and Viruas-Encephalitis Dis-eases of zhe Academy of Medical Se' ences was devoted todiscussion of tickborne encephali1tis, Omsk fever, Kemerovotick fever,, and related diseases [203]. During the fourdays of the session, 85 papers were presented which werelater incorporated Into the published collected papers ofthe meeting. All aspects of these diseases from classifi-cation of the viruses to prophylaxiis and Imimunizationwere discussed. A paper presented by A. M. Butenko andYe. S. Sarmanova on the isolation of new virus strains inKemerovo and Astrakhian oblasts complements the work ofX. P. Cbmnakov et al. on the Isolation of a serologicallydistinc't umber of the TBE complex which was aceomlishedduring the joint Czech-Soviet virologicai expeditionduring the suer of 1962. This exrpedition m~ade virologi-cal examinations of ixodid ticks, suspected human carriers,and healthy persons bitten by ticks In Western Siberia.Both typical and atypical strains were isolat-ed. in one

_'2" ;;elu' .ole&iiy s imiar strains were discoveredwhich produced a febrile type of encephalitis in humans.The new virus strains were cytopathic in chick tissueculture in 48--72 hours, multiplied well in the yolk sacs of7-day chick embryos, were fatal to newborn white mice butgenerally not to adults, and were antigenically distinctfrom the rest of the encephalitis complex although theyp-oitued similar symptoms. Later, 20 similar strains wereisolated which were remarkably pathogenic to Intracere-brally inoculated rats and hamsters, producing brieffever in Rhesus monkeys and having varied effects on tis-sue cultures [40). A report of a test of a new culturalSnactivated vaccine made on a million subjects was givenby D. K. L'vov, and data on its production technology and.uality control were given by A. V. Gagarina and I. M.Rodin. Kemerovo tick fever was discussed at a specialsession. Immunological shifts in humans, the capacity ofthe virus to agglutinate erythrocytes, morphology, and theIsolation of similar viruses In other parts of the SovietUnion were also considered [203].

In typical epidemic foci, sizable percentages ofcaptured ticks carried highly active virus [182, 2322.in some foci the outbreaks have a mosaic pattern which,some Soviet scientists suggest, depends on the variablevirulence of the local strains isolated during epidemics[186]. A high percentage of wild and domestic animals andwild birds usually carry viruses, and humans in suchdistricts usually have complement - fixing antibodies Inhigh titers [155]. At least one case of a patient withrelapsing TEE has been reported [123]. Simultaneous casesof both TBE and Omsk fever have been reported in humansand both diseases usually increases in occurrence withincreases in the rodent and ectoparasite population,pointing to similarities In their mode of distributionsince they are antigenically distinct [263, 59].

A study on comparative natural immunity in r!ptilessusceptible to TBE virus shoved that in reptiles infectedwith TBE by various routes under different temperatureconditions and by different techniques, temperature wasfound to be the most important single factor changingimmune response. No immune response was observed inEremias velox and Agawn caucasia individuals kept at 4*C,whereas the earliest appearance of antibodies and thehighest antibody titers occurred in individuals kept at37 C [273].

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B. The Behavior of TBE Virus in Cell and Tissue Culture

Czech researchers have found that in tissue culturesinoculated with two or more viruses, cell resistanceinvolves formation of interferon-like inhibitors tha- sup-press the invading virus in cultures already adapted toone type of virus [9, 227, 207]. This phenomenon is the"-as! s fcr a method in which TBE virus can be titrated bydetermining cytopathic effect in tissues infected withpolioviruses. In this method, the TBE viruses resisted-he effects of poliovirus, and by some mechanism not yet

nown, but probably involving production of an interferon-&Ke sustance, inhibited the cytopathic effects of polio-

vl-us f8j, Such an interference method can be used toauate the effectiveness of TBE vaccines. A method

reported in 1963 by Al' shteyn et al. was economical and',z'ecise, but was more time-consuming than intracer(bralinoculation of mice [111. A plaque-assay method, on the oth-er hand, depends on the definitive identification of plaques;any condition that interferes with plaque formation is tobe avoideu. Cells, therefore, must not be pretreated withinterferon if plaques are to be clear. This method canalso be used to obtain viral clones by repeated plaqueisolation and subculturing in newborn mouse brain [140].

Many cell and organ cultures have been screened assuitable media for the evaluation of inocula and vaccines.Comparative evaluation of tissue lines by Karaseva andSemenov confirmed the suitability of chick-fibroblast orswine-embryo tissue [13, 14, 15, 92]. Titration inhuman-embryo fibroblasts has yielded results 50 times lesssensitive than the intracerebral inoculation of mice, butwithin its effective range it is clearer, mo.-e precise,and reproducible, and can be used for detecting neutraliz-ing antibody (10, 56]. Tick tissue culture is reportedas the best medium for the early detection of tickborneencephalitis virus since a marked cytopathic effect isproduced by small quantities of virus [189]. In growingvirus in tissue cultures, agitation was shown to aid inthe production of higher titer [75, 137]. Chick-embryotissue was best for work in which gradual and continualrelease of virus from cells without marked cytopathic ef-fect was desired [154]. Several authora report a *partialocytopathic effect in lines that have been chronicallyinfected with the virus, with a reduction In virus multi-plication rate and a consistently low percentage of cell-associated virus (usually 1 % intranuclear) with the restin the culture fluid [138, 16, 19]. Some cell lines are

affected by medium composition with consequent changes incytopathic effect [139], and all cultures of mammalian cellsalso had a resistance to superinfection as discussed above,although long-term culturing could not eliminate persis-tent infections (141).

The effects of long-term culturing on TBE viruseshas been studied at tie Moscow Scen-Iflc Research Insti-tute of Viral Preparations. Culture conditions played animportant role in the properties of some mutant strains,and others maintained their properties unchanged evenunder prolonged culturing and varying temperatures. Somestrains developed the ability to destroy SKH and chickfibroblasts after adaptation [17]. The laboratory ofV. V. Pogodina of the Institute of Poliomyelitis in Moscowhas investigated the variable pathogenicity (virulence) ofTBE and related strains for different laboratory animalsunder varyirg conditions. Various strains of TBE, Langat,Omsk fever, Louping Ill, ?owassan, and Kyasanur forestfever viruses were studied for both intracerebral and peri-pheral pathogenicity in attempts to use neurovirulence asa strain marker. They observed the following types ofneurovirulence: a) high intracerebral and high periphera--Eastern and Western TBE strains, and Omsk fever, Kyasanur,and Powassan viruses; b) low intracerebral and high peri-ph-ral-Khab-9 and Vasenkova strains (EEE); c) highixitmcerebral and low peripheral--Fatayev and Ix-2 (TBE);and d) low introcerebral and low peripheral--Langatstrsin TR-21, recomended as a vaccinal strain . Kice andhamsters were Judged unsuitable for differential diagnosisof the TBE complex since they displayed uniform clinicala mptams with all strains. Lambs were ruled unsuitablebecause of their low susceptibility. While none of theanlnals tested were equally susceptible to all the strains,newborn pigs were the most suitable for differentiatingstrains on the basis of virulence [178, 177).

When a newly isolated TBE strain was injected intoyoung mice and passaged, its virulence decreased. SpecifIcresistance to challenge by the original wild-type viruswas produced by injection with this attenuated strain;de ree of imunIty was affected by virus- dose and time ofiunmfizatlon. The lowered virulence was connected with adecPease in the ability of the attenuated virus to multi-ply in extransuwal tissue [107, 143, 1791. Since titra-tion on the basis of cytapathic effect gave inconclusiveresults [180], the flucrescent-antLbody method (FAM) was

employed in the tissue-culture studies of growth stages, of

the appearance of viral antigen, and of cytopathic effects

of Langat (strain TR-21) virus, a weakly virulent virusdemonstrating antigen visually.

C. Induced Mutation .-f TE Viruses

G. D. Zasukh.na and I. A. Rapoport reported on thechemical mutagenesis of TBE viruses. General studies ofthe variance in hered:.ary characters resulting from treat-ment with various chemical mutagens produced mutant strainsof varying virulence and morphology [2861. Changes incytopatblc effect in tissue culture were not connected withcytopathic effect in cell cultures treated with 5-bromoura-cil, formaldehyde, urethane, and a combined proflavin-urethane preparation [285]. In the work of Zasukhina andRapoport, the effects of some standard mutagens on twogroups of arboviruses with characteristical3y low andhigh mutation rates are compared. Strains of TBE viruswith a characteristically low mutation rate and WVE strainswith a higher mutation rate, better culturing Droperties,and a faster growth rate were treated with: !) 5-bromo-uracil, 2) formaldehyde, 3) 14-bisdiazoacetylbutaneand it) N-ntrosomethylurea. These mutagens producedalkylation of the hereditary material; 1, 2, and 4 yieldeda greater percentage of apathogenic mutants than did 3.A greazer number and variety of mutations were produced byl,4-bisdiazoacetylbutane. These results were highly signi-ficant in explaning "zoological cosmopolitanism, orability of these viruses to survive in dozens of speciesof cold and warmblooded animals. These animals are thereservoirs, carriers, and victims of these viruses, Asecondary aspect of the study was to determine the rangeof artificially induced mutant properties of these viruseswith the intention of creating live vaccine strains fromstrains with induced mutation. Several strains wereselected for further study [287].

D. Diagnostic Methods for Tickborne Encephalitis

The fluorescent-antibody method

The principal advantages of the fluorescent-anti-body method (FAM) in diagnostice are speed, accuracy, and

the saving in reagents [128, 145, 1561. Thds method Xs:

been employed to detect cell-bound and free TBE viral

antigens in sheep-kidney cultures [129], and shows theintracellular distribution of nucleic acids and specificantigen in mouse.-brain and sheep-embryo kidney tissue[220, 219). Thi- method has been used diagnostically and Inthe study of the course of experimental infections. It iseasily and rapidly detectable in the central nervoussystem and lymph nodes soon after infection, usually within24 hours. Viral antigens are easily demonstrable even inanimals showing no clinical symptoms [83, 146).

Complement fixation reactions

Complement fixation is repeatedly cited as one ofthe best methods for diagnosing TBE (though the FAM issuperior) [64, 54, 150, 39]. Its principal disadvan-tages, the length of time required to obtain definitiveresults (as much as 15--30 days) [64, 103] and the rela-tively sophisticated equipment required, make hemagglutlna-tion more acceptable [63]. A method by which driedblood on filter-paper disks is used was ruled unsuitablefor the complement fixation reaction because of the largetiters of anticomplementary substances in the dried blood[54]. However, this system is adaptable to the neutral-ization reaction [54], although in most papers onneutralization, it is carried out in vitro or in tissueculture [255]. The principal advantages of either fastneutralization or complement fixation is the eliminationof mice. Also, since the virus multiplies faster intissue culture than in mice, virus can be obtained,identified, and typed more rapidly r64]. Several papersreport the processes of obtaining and purifying sera forcomplement fixation [150, 266, 58, 38].

Hemagglutination and hemagglutination-inhibition reactions

Hemagglutination and hemagglutination inhibitionhave been used diagnostically in large-scale serologicalsurveys and epidemiological studies both in the fieldand in tissue cultures [276, 95, 126, 200, 171]. Sheep-embryo kidney cultures provide the most suitable mediumfor hemagglutination and for complement fixation, althoughuse of other tissues is reported in the literature [62, 96,223s 47, 53]. TBE hemagglutinating antigens obtained

from viruses grown in various tissue cultures are highlyspecific, requir- no elaborate purification process, andare stable at 40U. They were therefore recommended to

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replace brain-derived antigens for serodiagnosis of TBE.The accumulation of virus in the culture media can bedetermined fairly accurately by hemagglutination and TBEvirus can be detected in experimental mixed infections intissue culture [150]. A modified hemagglutination-inhibi-tion (MI) reaction is widely used in rne Soviet Union insurveys of known and suspected vectors [201, 171, 275, 97].One method, which enables a technician to determinethe presence of TBE and Japanese encephalitis antigenwithout the complement-fixation reaction, involves thesimultaneous performance of the HI test over a wide pHrange, since the Japanese and TBE viruses agglutinate atdifferent pH values [247]. A further modification ofthis test suitable for large-scale work employs paperdiscs and requires minute blood samples [201]. Sinceantigens are plentiful in the blood long before theappearance of clinical symptoms, Gaydamovich and othershave recommended the HI reaction for early detection of

arboviruses and suggest its use in the identification ofvectors [67]. Use of this reaction to demonstrate thepresence of TBE antigen in wild birds and their parasitesis particularly interesting as it enables contacts ofwild birds with epidemic foci to be revealed [171].

A modified precipitation reaction was chiefly usedin typing and determining antigenic relationships ratherthan in diagnosis [224].

Neutralization

The chief benefits of neutralizatioL, methods havebeen found to be that clear-cut results could be obtainedwithin 72 hours with freshly isolated strains and withconvalescent sera; even sera contaminated by bacteriacould be used and the tests could be carried out inordinary culture bottles without impairing sensitivity[255, 131, 52]. Disadvantages were such external factorsas season [274]; also, clinical manifestations in a givenindividual affected the neutralization indices so that a

definite hemagglutinin-forming dose could not be determined

accurately [255, 20]. This method could be used to de-

tect infectious RNA in the course of an investigation ofthe properties and functions of TBE virus RNA [49].

A colorimetric test for TBE has been used experi-mentally with success; its only disadvantage is thatdefinite results may be obtained only after 4-5 days.Further research on this test is underway [93].

Plaque formation has been used in the differentialdiagnosis of TBE because its plaques are distinct from thoseformed by other viruses. In one experiment, TBE virusformed large turbid plaques, Omsk fever virus formed smallplaques, and Langat virus (strain TR-21) formed both largeand small transparent plaques, indicating the heterogeneouscomposition of the inoculating strain [122]. Standardiza-tion of conditions is very important since agar Inhibitorsalso alter plaque sizes [51]. Positive identificationmay be made in 3--4 days using a method reported by Logina-Parina in 1964 [121]. The infectivity of TBE infectiveRNA can also be shown by the plaque technique [50].

E. TBE Therapy

1. Vaccines

A 5% brain vaccine against TBE was administered tomice and guinea pigs. This vaccine was prepared fromserum obtained from infected animals two or four days afterinfection, and was administered in two doses 28--32 daysapart. When an allergic reaction appeared, the animalsreceived normal brain suspensions or formol-inactivatedvaccine as desensitizers. In guinea pigs, tissue fromsick.mice and from infected mice which had nct yet dis-played clinical symptoms produced strong anaphylacticreactions. Four-day vaccine caused only a weak response,leading to the conclusion that intermediate antigensappeared between the second and fourth day after injection[13].

A nonallergenic, formolized vaccine was obtained byGagarina et al. by the intracerebral infection of newbornrats. Similar vaccines have been obtained by others [60,83, 115, 260]. Vaccines adsorbed on aluminum hydroxidepossessed greater immunogenicity than native vaccines [115].

Vaccines prepared from tissue cultures were gen-erally more effective and easier to handle and store, andwere areactogenic as compared to inactivated brain vaccines.In general, greater postinfection immunity was observedwith the tissue-culture vaccines [43, 202, 258]. Ratesof antibody accumulation and immunological shift variedduring large--scale trials. High-antibody titers appearedrather early [44] in some previously unvaccinated personsand after considerable delay in others, suggesting to the

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researchers that threee immunizations were optimal. Large-scale trials bore this out, leaving the question of theoptimum intervals to be determined [2591. The immuniza-tions last at least six months [257, 461. In trials withhuman volunteers, Chumakov and his associates found thatmaximum immunogenicity was obtained when shots were given1- 4 days apart followed by a booster after six months,especially in tests of nonadsorbed vaccines [46].

Attenuated vaccines prepared in tissue cultures weremore effective than brain vaccines in almost every case,though their effectiveness was affected by such externalfactors as drugs and hormones [42, 199]. It has been es-tablished that the regional lymph system limits the pene-tration of tilckborne encephalitis virus into the blood-stream under experimental conditions [132]. Cortisonetreatment of mice at the time of immunization did not im-prove the prophylactic effect of the vaccines; on the con-trary, viremia lasted longer in animals receiving corti-sone [98, 253]. X-irradiation speeded the spread of TBEvirus through the regional lymphatic system except in thelungs, where a decrease in virus titers was noted [130].Urethane-barbital preparation had much the same effect ascortisone on experimental TBE infections in mice, withviruses persisting longer and in higher titers [199]. Atissue culture vaccine effective against both eastern andwestern forms of the TBE complex and possibly againstrelated diseases aad which poLesses almost the samevirus-neutralizing capacity 'or all the diseases of theTBE complex was developed at the Institute of Poliomyeli-tis in Moscow by Zaklinskaya and coworkers [283].

Antisera and specific globulins have been found themost suitable for use in epidemic foci because of theirareactogenicity and because they are easily obtainable [57,182]. A-type immune serum against tickbozne encephalitisis specific, shows no anticomplementary activity, and con-tains no antibodies to brain tissue; it can be used as astandard in complement-fixation and hemagglutination-inhi-bitlon tests with TBE antigen [194].

STORAGE PROPERTIES OF TBE VACCINES

Of the wet vaccines, formol-inactivated vaccines werethe most stable, with a shelf life of up to 9 months. Some

batches were kept in rubber-stoppered common glass bottlesup to one year [35, 83, 198]. Dried vaccines kept longest,provided residual moisture did not exceed 1% [125].

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Studies of the properties of viral infection in tis-sue culture have been made in the laboratory of J. Vilcekin Czechoslovakia. Several reports on the formation, anti-viral action, and comparative properties of various inter-ferons have been published. When mice are infected withTBE intraperitoneally or intracerebrally, high interferonlevels are found in the brain of inoculated animals [269).When cells infected with WEE, EEE, vaccinia, NDV, and homo-logous TBE viruses were treated with interferon from TBE-infected cells, their resistance to the other diseases in-creased [2671. The action of TBE-interferon and influenza-interferon was compared; results were found to be similarto those of the previous study, indicating that the speci-fic inducing virus fails to influence the properties of theInterferon formed in a given cell culture [70, 185, 268].

-h ...--_-"c.-cals na Q;fher .oreoarai ors have beer. zoreor less successf Zly tried decansa~nas and t brapeut Ic con ourndsfor viruas ulseases i_ Jhe Sovi-et &-w : actaTs Ind iactones, espec-cially beta-propiolactone, were recommended for generaldisinfection use and for further study [173, 2931.Novembichin and other antibiotics were somewhat effective[28, 73]. Dichloroethylamines showed antiphage action andethyleneimines inhibited the action of many viruses [27,29, 288]. Naturally occurring, interferon-like inhibitorsin both live animals and in tissue cultures have been re-ported in many papers. Most of them are enzymatic andthermolabile [147, 217, 228, 246, 250, 292].

Uniformly satisfactory oesults have been obtainedwith the administration of vaccines, drugs and therapeuticchemicals by means of aerosols [4, 5, 6, 7, 66, 77, 183.187, 270, 271, 289, 290]. In fact, some live, attenuatedvaccines are most effective when administered by aerosol invery small quantities [66).

A killed tissue vaccine prepared from TBE virusstrains Yas-8 and Ix-10 was tested on animals kept in aIVK-2 chamber. Vaccinations were given at 1-, 3-, 5-, 7-and 10-day intervals via an aerosol with particles aver-aging 1--3 microns in diameter. This method produced arapid rise in virus-neutralizing antibody titer and suc-cessfully protected animals challenged with the virus. Thevaccine penetrated the tissue rapidly, enabling smallerdoses to be used, A mixed aerosol conferred immunity toboth viruses (TBE and WEE) [250].

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2. Challenge of Animals Vaccinated Against TickborneEncephalitis

There are numerous reports of challenge tests ofvaccinated animals to determine the efficacy of certainmethods of immunization and the properties of experimentalvaccines. In a study to determine the conditions influ-encing the effectiveness of 3 pr-;,hylaxls in human vol-unteers and the relationship of the immunogenic propertiesof the vaccine and -t'ts immunologic effect, 548 persons, allpreviously unvaccirted, received doses of vaccine at 1--2and 2--3 week intervals. They were revaccinated after 1year. Twelve types of tissue culture vaccine and threetypes of brain vaccine were tested. Conclusions reachedwere that if the first series of shots possessed highlyimmunogenic properties, then a booster possessing diminishedimmunogenocity was effective. The reverse was not true

Some of the standard vaccines, particularly themouse-brain vaccine, are easily contaminated by bacteriaand produce allergic reactions. Thus, tissue-culture mono-layers, especially chick-embryo cultures, are considered asuperior source for vaccines. Formalin or beta-propiolac-tone were used as neutralizers to make the vaccine suitablefor use. Optimum inactivation conditions were determined.A satisfactory vaccine was prepared by inactivation at 40C.(This was necessary because the 370 C temperature of somemethods destroyed the irmunogenicity of the virus). Thisvaccine had a shelf life of approximately 6 months andprotected challenged mice against high concentrations ofvirus. In tests on humans with low or nonexistent serum-antibody titers, 66% of volmnteers developed antibodies insufficiently immunizing titers within 4 weeks after vaccina-tion (84, 1271.

Airborne infection of monkeys with TBE virus pro-duced little CNS involvement, but other symptoms producedwere like those evoked by infection from other routes [23,114]. In two studies the infective dose for aerosol infec-tion was found to be 104--105 i.c. mouse LD50. In bothcases, active immunization with TBE vaccine was the bestway to protect test animals aainst high infectious titers[23, 4 8 ]. Airborne infection is an 'unusual route andoccurs mainly, or perhaps entirely, in the laboratory. Inthese studies animals were kept in a special flow chamberand aerosols were generated by a specially developed appara-

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tus which generated particles with average diameters of0.75--1.5 microns. The dose could be varied by alt-rin.gthe concentration of virus in the carrier fluid or byvarying exposure time. A Formol vaccine offered animalsbetter protection against aerogenic infection than againstinfection by other routes (48].

F. Japanese B Eicephalitis

Virological surveys have shom birds to be an impor-tant factor in the dissemination of Japanese B virus. Asurvey of the southern Primor' ye showed the presence ofhemagglutinating and complement-fixing antibodies in 200wild birds of 36 species [166, 181]. Sheep-embryo kidneytissue culture is the most widely used medium for the eval-uation of cytopathic effect in the diasnosis of the diseasesince no preliminary adaptation is required. The cyto-pathic effect is limited in adult tissue cultures [61, 1651.attempts to culture the virus in guinea-pig tissue Involvethe nece sity of intracranial infection of the initialanimal with a suspension of Infected chick tissue, andintractanial subculturing. This laborious procedure yieldsa preparation with unchanged antigenic properties afterlong passaging [197]. Noninfectious diagnostic sera andhamagglutinins for the HI test have been produced [68, 2371.Uvarov and his associates prepare concentrated hemagglu-tinins by precipitatlon in ammonium sulfate and incubationat pH 3.2--8.5 for 19--24 hr at 0--4°C [264].

G. Omsk Fever and Related Diseases

Osk fever and other renal hemorrhagic fevers pre-sent diagnostic problems similar to those surrounding theidentification of various forms of the tickborne encephali-tis complex. in addition, Omsk fever and Kyasanur forestdisease are antigenically related to tickborne encephalitis.Hemorrhagic nephoso-nephritis (HNN) and Omsk fever areoften misdiagnosed as leptospirosls, tickborne encephali-tis, gastroenteritis and other diseases. The tables com-pare the character'-stics of HNN and related diseases andabdominal conditions for which it is most often mistaken.

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Table I fro.n (216]

CO%-.WRATIV'F Cl.' iCAl CIIARACTERISTICS C* IIMFUaRIAC.;C FEVERS

Herotthiric nc;,lmntre - #trirnean Csntrai Asian hcor- C

nMj'hrits trnigrc fesr I hagac ftt,

PtedowInant clinical syndrorme

Distinct hernrtchzc zai- IPhenomnen: o general ery? severe general I-n- Relatively mild generaland a tAse isrc AI 7 h dir-_ toxicatiOn and distinct intoxication and bmr

genteral toxication a: tiny, h'nonrhaslc severe damiage to the rhagic diathells. Di,.-

the height of the dise ase~ . ao-ea and reli- gaitiointesttna: tracts f d respl.ratory tract

acuernslara~a'.ur jtively mild Wh~rtzz =i-srnaie freet- lesIon.ary exriit :flre. CA lesionS. ly critical bleedizg

lacubatron period

Fromn II to 23 days. on she Fro 2 to 25 days. 3-4 days. Especially 2-4 day;. Especially

aver.Ige 14-IS dys short in intrafm=ral short in inifections Ofho-,pitaZl finections. Personnei caring for

Iinfected laboratory

Prodronal period

Cbsrrrrd rarely. Lasting IProdror-sai perio not IProd*om.? period aom j Rrely observed.

Cycles of develo7met= of the clinical picture of the dimseaa

Fines periods of the disease: 71 Three periodk of tke dis- Three perioks of the dis- jTs-o periods of the .hsC I,

the first geralr feb-ile ease: tfe first Initial ease: the first initial Ithe fIrnt. febrile pert..'

period. jperiod, period

Second perio, - he-.Cr- SecoviJ period - height Second period - khigfl Second period - .pyre xi.*ragic MmsfcstaticrS. Iof th. disease, of tire desc reconvalescence.

Third peritod of rmaxins. Third period - re- TnSperiod - re-injuries to ostanot. cov?escence. j oalscence.

Fosoth period -re- -

Tens petanne often rises rud- Te-rpcratune rises ruzl lAfter:z setere cill! the After a brief chill t,

dtnly to 39-40'C and re- deal) to 33-4CrC and Iternperatur, rises sud- Peratcne rises$ude~Viss high until the 4th- then W.lesb lysis I.ienly to 331-4rC and to 39-4rC. It reJol'5s

7th day of Lt distntr. after 7-9 Sits. A Idro~s ae.hA on the by lysbt 'eturen tL- 9:taut- resol'-i, by lysis in chiacterhstic bd 3rd or 401 dat (stith the Arid 15th day of the jib-

2-3 days d&o' in em prtr begir-nin of trmor- cast..A brief decreaston the lid and! 4th j higic naicttos. on the Wr or 4th dfa,days of th-e J.sease Later it rem-ains at a (oegixin of hemZ-coinciding .rIth the Ilevel :1f 37.-3St to the I titazic =:z' ifer tirsl,

begrnn.n; af the 7th-skb da) of th e lst- is charsctelistic. 1 n;'

hernorhagr.c r-anm- ease and later returns of casts las the sct'.±

fertatour~.to normal hib) is third steea of VCr rvt:

.Arescen period ~I-rJa2 typicaI seCOid~fnt -

notu ,s -thv.-

= Table I continued

woohrak !drt4aA 0=1r~ i~h~ ~r~ he--x -ivc

wrl: 1 hlf k_- ,;, 1e .tIj ere k i.J of -tM bodyf1c eboy!o-t. o!tcb,3y fra= oM oacvcd in SO*; of

fla botm of dw ~fIb of ew C~u from~ the ran

I dift~sle acd =.ti) j-. V!e~ dbe :c TM ofItMc rtc&oaiecer j ecz-'seo .d bgtul tkc . -

Color of Tr, iczI b',ccia T~ykI4 i j Hyve-- a! d* ir~c-niz AZJ jecti1-f

vt~~ble ~ =d inctLti of j~ ~fI~tCi- scrr. Z,e *I ofT c -a of te

ukmst*--es TMc. comp)tCti - ,cic-. cz,3I=- to!! UArolel Civi d±theOn

2l CJrt~y from tsM ties a-d cr4 c~-fty cbic~ etce Ftr:ce.

LitIMbo cc Le ds- izT ikiu pe;,Lf

caw a~d u-of the j d ad i-%&c TM

___~~cme t Po tne __ I _

Lt )ctabdyAz ftojfc~1cbo c P==Cx ritl crum-bdoc tf.~tIe TM~l f %ec ~ tc - ii'hcmce

Tr~i-- TTMz eio.A

D-TM at It I ec-- t-c

S-1c~~,!so-ib ev of I=- e-es:

)bokagic Fso= dw 3.--c day Fro=~ ZTM 3!-41?- day -, ei- ;- =mA zfl ---c±!~y

maniftu- teC Is -a dli&% of en asta tbvoe me- .rzs .4 !ca l & eIs amt *--IT l2 M.

dw peoec&hla r.ua o 4m Issm., bzxci-crJ %- --- to fid of pdz=. in %s Tm

a)GOtaTdi TMe AlId of die ptcc!%Ix =#- te da * f TM - ci eye anfte-meI*AraI mefawc Of TMeIi af c T- iI kf- -,g vll t=ii of TMc bady mmde cbcM1 atdC&ce tell= and I="~a --. TM s~lf2 ct dse U=&- So~-g.e a -

e be.-J ~ dze &aca TMe Cbe= =cslr~i ,Ic of 3jaIC. MkCma rIy Aid %I&I .!bd=,*e.- TL=- tM bcdY -J .i=te Z~eT *T lx a

dzib&g--.e g is =I eal= l~e -a Tb MS = !av~~soed T ert is= ciao 6dg j~a- ztead %

sroeoiA.. raalL j T saz tic~ ar- c:e bo4 -t%i-a .'-11, :ZC4-1 Czcz,.toe of TM

___i$- fag*. ___ _I bet

_eez K=_ _ _ _

Table I continued

I C5p~--C C-CwICia -c 30C !Cc--. a = -c.- C-.ZIRwm"__ __ __ __ __I !i%4C fC-*ffer

=CCC CI & distas d~ asv j 0 b C..)s t It* h;Ci fro=~ -*W. pr.S. utqmil,

the skzcl . It'd Itaera11 50% Cf Cass . amt.fee

Imical aty. a=4 s e d~ !a= -mrse mo =lcjPC 1a!v as :15e ed.e- i 4 dami ci~ I dc ~~

Ce ~ ~ zs :e et.isz:t f th

s:r=ILCO - I I Ine-I s~=*4to-

sc7L- Zd~- I~~dPI iCae

t ow -T Jrscc- pe;* %bC

4 bi s a

Am .1r

L-Ic ~r z-!= ! e - cfd . zCrx a

ck.-~j ~L- w tc=Lc p- ofI t e f :5-s C. detpt c! the~ ea

Z' ZS ! Csc - t~e !Ic~ tb-. !sC*- a w !=:.& a

dw~~~~( tyizi. c--rv %.

WI. -cotJe- II-L= ~o---: t t [_______ _____ _____

waIM f--

(2=4-34-

aviIca I~

Table I continued

rae1 13n fu v--4 f. nw:r .%

ulePIr Tnc0 a I .it - !crT.jo~tn Cr f-I

.A.! a-_ ofC 4esd

; PZ: ' O s~ j,.Cf J.C- :Si :jL sv

a eI

of-_ .7 ,..* a. . xf V_ :. Ta l te ow

g~t~s~g-i o!~. ?e. s. i.. .z' Oz-C 7J Ja Of

_____*=; eIm- the______ ztf &I twjt

f- ~ ~ ~ ~ ~ -V-C-4--,;u t c

04I 1e~ -it 2a D the

ofz~±e .-. e b cIA:-. -

Vofae --- cs ~)~m

is kf m t

Table 2T continued ______

I- In Ile 0' me n o

.3 ~ ~ f1 d ~ ~ e~. &r.e4o -I 4.%If;=

d)o1,o~e taSK ~ t I f S. 3 S~i% af

I L5

Oj tic :v It Wa Z)

_________ I IN.; _jo C7 S 3c fV tt-dtfff iT iaa . -.-i a-.,PS ~ ;4- .lea ~-- z,.s 're ; -c ~~ J,.i- %! g ?s

j t~s tans-;. -~ j seaaa.o 4,,of A!R , t A~.. dnIafx At. zS Istw frea

pau.~i. At ter- vzv a!t ;,c speciofi!= !p-_

ftqi ~ A nd In -. :.aI mC-a C- 4ts-let La-oz! ox C-' I th end, of bta .'~..

ipr~ Tf iaa, jo =43 eas! -- X Adei cta

brSch4 ") dev -.- :-a A ~ "0 ~ b MI of ~ £ ifz- * as3:e f1 -_PIaCsa A" I:. eep ae 5

4c epc a mfsi! i

Ga m r . :5

.C 3c,d_4: pai - _ oft c j-as C! Itr;: _a)4 a-vif 7twt %s 4

iwet~ I jsh. a-wsa p C- j~l dneat -ftr pc Q be--i~ t ber~ . of Se! C

C&c I j SC pZ *.swn ma5-O5J :&: !Idlaz fApu.jfr U1 fIeZ A

P;- i3;zCsrs

rnrOo-! rj fas e athe-tde C~i-~: O~

t-ei zr, bl . I. fr -C~u a~2

M; II I~-16lm t r

zt ema - &h I I I" J'l A zm~a

ezc at Ca 5 s- ~

"-a,~ -.. - - -U-.- -----------

Table I continued

Hemonhagic nephoic- Cr.mean hemorrhag.c Ceieral As-in hemor- Omsk hemorrhagic

nephritsi fever shagic feset fever

into the stomach and

cleat anJ perreal

tissue)

t.'e At the he:h, of th' There is sli;hs en- In the period of In the period of height

-d pieen doee the liver in largenerent of the height of the dis- of the disease the

SO of cases isa be liver and spleen ease the liver is liver is slightly en-

palpardJ a-' a' r-od- daring the period us.aall consider- larged and tender to

cratel) eM e of height of the ably enlarged (pal- palpation. Eniarge-The spleen is r:-el, disease, approxi- pated at 4 cm be- ment of the spleen

enlarged. mae 1 s 331- 'if low the costal Mar- not usual.patients. gin).

ersous ChangeI regular. i From .le frst days From the first dals From the first days of

s)stem Fs-s,. she f,r't da's I tiirre is headache, there is headache, the disease the fol-

lesions I s.c. is a se ere I drosiness. and fdrowsiness and loting signs appear-

headache in al! a sonctimes ins- apathy. Rarely headache, lamb

patients. In 27.5-i pairrnenr of con- there may be a pains. Mansfesta-

of case. from the sciousness, delir- brief loss of con- tions of organic net-

beg;nniig ot the ium and hallucina- sciousness and in %.o system lesions

third period there is tions. and there tevere cases a (pathological re-

a mrked state of mat be brief menin- comatose condition. flexes and meningeal

stupor, mild menin- geal signs and signs .Meningeal pheno- signs) are rare, brief

Zeal symptomrs, and of impa:rment of menzanddiscrderscf and not distinct. Inweak patsological cerebrocras ial in- tendon reflexes are the Bukt.insan var-

reflexes (Babnsht

ner-tation a5rmie- rare and net d-stanct. iant of hemorrhagic

and others). CSF is try of the face, de- fever the injury tousuall) unaltere l, viasion of the the nervous system

the spinal fluid tongue. irregular is more distct.

pressure is ircreased, pupils and patho- The following signs

One may obserse d-s- logical reflexes are very frequents

tinct phenomena of (Babiiskai and brief pslchomotor

serous menan;ia. j o~ners. CSF is excitation, aniso-

Rarely does .ne se, usually not a!- reflexa, appearance

a clinmal picture o' tered. , of pathological re-menirg-encephalitis fleacs. In onhe third

with distinct irnpair of the cases there aremint of conscicu- meningeal signs

nes% - st.por. de!,r-

asaril, psschonio:es:

excitation ar'd ome-

times coma.

-19-

Table I continued

,H emrlih j- C ern'n-ie* C entr. l A sian hem o.- C rrin he no rt~ 4g .cneplirsis is is rhaa-c feser J fe% cr

Metabolic At thec height of the Mectabolic disorders At ti: height of the Change In mctabc-

disorders disease (second and are rare. At Uhe disejic there is a hism nor rc;rlar.

thid er,,, , icgn o te o-1mocrate h~po- At the hcignt offolloisin; e ,cgr~ t ~ ~ ,- U - I ~ -- O

EyrC 2! on. tO I.tst 1:0. C2 0, -ni4fll) dut ient, ani 2a mo-hypoprorciniernia, the recon' zaecn: to ccielte c- I rase hypopiosesin-

ditinct ar:'en~a, period! :tere a; glCrsul-nt an:, fIb- ern.-A a-d sone iNflcfrequee%-l, high ( ceit e rl~e."rnso 202-.Y3rn m o! moerate sA-s-nia s's. ira.. -- e:c i

residual -'.tro;e's irzii*Ann

Ana4()- 00in y o Mota..

of urea). acidos.s hygsC..A Iand decreass! :Al- conside..1b!C si-

xali rc-c.C. of ti-c ee.ent. asblood to helom'0 . A, -chvolamne 1, (some- bloo itc!

times as lo,, as 20vlmI ,moai--

erase chicropenia,

distinct hsypo-cholesteremia,

Co-npii- One rare35 observes lMasiscblteed.-;% \,Iassrse blcedir;s (Fecal pneurtso's-cations niassise herrthages (gasr- irtest na! 1 h Iorn die gastro'- beds ea.:) (,;iril

In the kidney (and P-.iinonar)) very 1intestinal tract are And late (bacteria!)tear of the k:dne; ) rare. Focal very freqaen: and are cej frequent.

and in the epirenal pneumonia oh- arec a dianger so O-Stit, parotitisparenchyma, sith served in 10-16': life. *.. some and peitui de'ekpdeveopmeat of a . f cases, Ins some cares a deep focal rarely.clinical picture of patients parositr.s, pneurnCnrIa de-'acute abdomen". epidelirr.itis and velcps. 0n1 verb

Hem;rrhages in the peritonitis develop. rarel)' ob-servesmesentery and the mu amm~tion ofwall of thie initest ines tesalivary bs;with development of *

an iles tyndere;ichemorrhages into theIstomach arid otherinternal organs; autine l and d eins acency ofe-

velopment Of a

clinkcal picture ofIazotemic uremia.focal pnetumronia.

-20-

Table 11 from (216]

Differential diagnostic signs of IINNN anJ *acute abdomen"

Siiiadcomsbinations Cinical chsaracteristics

of~ 5Ii NN .acute abdoi..en"

torefs o~f abj"I~'ts~'s Abdowtvi.sl pain appears on 3-Stli dayl Sudden onset (A pain - the furst clinicalpain. sign of onset of pithological coniditions

a) rigin (gastrointestinal perforations, auteperitonitis)

b) intcrnsit) Usual) wild pains. nelte Intract- Ver'y acute pains C'1Isssfsn5') frequ4 nIable (-nric strall't I

C) lC-C,4;t IMost frequc:itly kv~al., in efi- Most often in epigatic region, butgastric region but rmay also be may also appear elseishere

8) corcb:nato sit~s Pains usUAIl) precede Omlitln&vomit ig

r) cormbrsstioss with Abdomnial pains usually preceded Pains usually begin while temperature,fever by typicalI hiiji temiperature tco- still notmal , tempetrature later rises

action

Cms'ination 7f ab-an, nAl Abzdoriin,, piins usually comibitned Lumbae pains onij when a gattroducdenailpains w~ith G!!-,- Pains i~tb pains in the lumbar region uker penetrates into the pancreas. in

rsepi-rolishiasis c~olic. or retroperisonealI appendiitts

U-.:, a2nd distresis changeS1 Characteristic Not charactristic, occur rarely~kdchanges ChAractercitti.' (see "ther tables) At the onset of pain attack blood may

be corn.a:, with neutrophil leutcocy-tosis developing later

Cominbnation of pain Abdominal pain .:ots~uned with Abdoias pains dominate clinicalsryndrome vsb other var~oras sympteoms chasracter- picture, often typical clinical nianifts-clinical signs istic of IINN (hemombagic cash, tations of ac..te peritonitis also appear

renal injury etc.) within the first 12-24 hourss

Table 111 from [216]

Ds fere nrsal d.agnostiz signs of I*lsx , squmto-brnJaznec tnccpkits and Isi -b~onc cncgulot.

Signs IINN Mcsquizo-bnero Jaiiiw Tick.-bnre enccphAfizisj ~(autur.n) cepltu (s; rin;-surrner)

PctJof niaxismuni Ma1zwuzz onb:P - .!E v -usSejierrober 1 I,~ly-

Epieic1t "iursnoue. ftc ie otae itc as Tae ftc ie co

CcruCic~isness I e nsr..!--aS parient's M"lc osen impa';1irssct, %\aric'us degrees of cc-

offer corni 5CiC.zir's nsn~piuri'm:cNICIrgcaf -igns !Rares'-.e-r apFoA. lmll r. Ad,'- *Usual obc.end. disr-oz

EncePhAlitis. pisai.ogical Ftzrcil zoserce. :. Obsersej is a ftir, Ecorc vo:ii .2 rule. Veirtfefxc i 3-13 or c0! - u-.- I 'conmIVs5 I.a tz , 4 -: , 'I.Cpclit

ally d~a,~sra1 i) . cecnalj pas neck Ync~cs and shxsc:,c(hersn-.~sc . * rgion, bAft 2 d;sc4. r;.

bulbar J,s -rders s;i-!i. rsreses - fCIS !.e

Cercbrosp.nal fluid IUsual) =Nc -- Appo.. Changes zfss,s obsesses!*inS o - .!ie:t f\:iu 13)-zda rise its ;Cer iquor. ireakd

nr in pore. . piro- cell rsumben, lame-or NC54!t an! ;trimu

cr-os a .-. ) :orl~ r ;nra -CtICCfl t 2%) Clcb,11frn itbloody mcsx(up to 2%.d.ssir.:st actscet, Psst o:e. $e

cytoiii (up- to 200 ce!!% * -I esa.e:e oIper I msn ~5..)C

Blood changes ISee abase (o"he: tab'cs) ?sf.deraze iekeW-s arate leukcytoss.%s.L. a r~urpslshift neutr.cphs.ma. arfeosinzcphslsa

:o the lft. ES% ac - ESR a,:-cfrnaed

Urine and diuresis changes Chfur.cser:;:c changesC =--sne clba- hige ot characmerssic.

(we abo'e a~ters traces io ic- smtrstacsorti

-22-

Table IV Trom [216]

The a important signs of the main foems of viral endemic hemorhatic fe ets (scheme of M.P. Cbsmakov.elaborated on by A.A. Smotodustsev)

f )Hem~orhagic feversCentraKyaxanuw

Main Wears HNN ~Crime In trOs iYss ret..I Asian Forest dsease Aentinlaa

. Properties of the .;rus

Cultlvatio outside the hrn.an body .... + + +

laperimtstal i nfctior La white mice . . +tzpirimental infection (febrile reiction) in

Artigevic relationship to tick-bore cc"

cephalitis vius ......... -

Su3ceFtible animals with clinical (0i) or sub- I

clinical (mbcl) form ........ Vale 7 Rabbit Wbe White Guinea(subel) musk- moute (cl). plg(clJ,

rat el). monkeys white

mckse mo) iuse(ci) (c€.

fi. Epldemiology

Soasoaulity ............. Poly- Spting- Spring- pri g- Sumner- Autuma-senason summer rmmer uminer autumn winter

Role of ixodid tics a carriers and vectors cl

Prtipatio o Gma id mites iz the circu-

Utics of the viL-s in smile-like rodents . .-

Transmi of the vinui to man by rodentscc their *CWP@zaalt es ...... . . -.

!!!. Clinical picture

Ication period Jdays) .. ........ . 11-24 2-4 3-4 3-7 4-8 9-14(M. P.

Chums-kov).7-IO(E.A.G2I'-

Perin,Doask tmperature curve ... .. .. .

V , aaic fevare.... ............ - ". 4 "

Ikel nd uterine bleedig. ......... - - + +

mointesclal bleeding......... .. . ."-

Sevasreeal Pthology-----------------4. .FblWV*A&gic rash ...........Cedsstion deteriorating after decrease i

iperre... ........... .. ." . .

Lauiaocytogis and =rceam In mberTrk's cells. ... ............. .

LacVeuia, shift of blood formua o the left 4 4tahity() . . . ............ 3-S 3 10-30 0.5-3 Is

IV. Main preventive measuree

Vaccinaton . . . ... ...... .- . ..

Der" ion --nd actio ......-23

-23-

Most cases occur in the fall and early winter (October andNovember and blood in the urine has been reported in allcases [11, 278]. Chicken erythrocytes, the aldolase re-action, and special complement-fixing antigens have beentested as diagnostic media. 1. A. Vereta and T. P.Yur'yeva reported on the demonstration of complement-fixing antigen in Omsk-fever patients when convalescentserum was the antibody source. The antigen was detectableup to the twelfth day after infection and could be demon-strated both in vitro and in infected tissue culture fromreactions produced by yellow fever and several simianviruses [265). Since the lytic reaction was clearly demon-strable in only 57--60% of test cases, it was recommendedas an auxiliary test rather than for differential diagno-sis [87, 144]. Results of the aldolase reaction provedentirely satisfactory for the differential diagnosis of HNN[204]. Since viremia was present in animals with an exper-imental infection for 23 days, it was concluded that appar-ently healthy animals or convalescing animals were theprincipal iectors of the disease in an epidemic area [284].Omsk-fever virus produces an extensive cytopathic effect insusceptible swine-embryo kidney cultures; RNA-containinginclusions and viral antigen are easily demonstrated byt:.e FAM [94].

Serotherapy methods were compared by Rodin et al.and were found to be only moderately effective [1901.

In general, diagnosis of HNN Is difficult as theclinical sumptoms are so similar to those of other diseasesand because, when the disease is suspected, comfirmatorydiagnosis is difficult and time consuming. Smorodintsev[216] suggests that, in view of these difficulties, thepatient should be questioned extensively as soon as pcssi-ble so that his contact with vectors may be established ordisproved. Hemorrhagic fevers are naturally focal dis-eases with foci in the Rostov, Bulgarian, Western Siberian,Khabarovsk, Moscow, and Amur regions [18, 30, 88, 172, 277,278]. High humidity and the proximity of the population toswampy areas affects the mortality rate [18]. Mild casesmay be undetected or misdiagnosed, while acute cases may befatal [278]. The red field mouse,rats, other mice, voles, and muskrats have been carriers invarious epidemics and an increase in the forest-mouse popu-lation seems to herald outbreaks. Because of the diagnos-and therapeutic difficulties, extensive prevention involvingfrequent land clearing and vigorous antirodent programs ispracticed [88, 277, 278].

-24-

Ii. HOOF-AND-MOUTH DISEASE

Hoof-and-mcuth virus enters the bloodstream rapidly,penetrates organs, and disrupts normal hematopolesis.Changes in virulence were found to be linked to changes inpenetration properties and multiplication capacity. Viruseswhose virulence has been attuated by passaging penetiratethe blood and organs less easily and multiply with dif-ficulty [78, 2721.

investigations have shown that various tissue cul-'uras are suitable for the cultivation of virus for diag-nostic and vaccinal use. Bovine epithelium [148, 243],swine kidney, and newborn rabbit tissues [102, 206, 235,2U5] have all proven satisfactory for these uses. Foot-and-mouth virus has a complex immunological structure andtherefore, many diagnostic tests for the disease can beused [195); these include complement fixation [155, 215],virus neutralization [242], and diffusion precipitation inagar [166). Skomorokhov [215] recommends complement fixa-tion, which can be used to evaluate vaccine potency.

Techniques for the preparation of virus-containingtissue which the Soviets have found effective are the useof Ascangel [24], chloroform [102, 272], freon [272], andthe mincing of freeze-dried rather than wet tissues [116,1]. A combined treatment with freon, n-butanol, andchloroform removed 98--99% of tissue proteins without low-ering the original virus titer [272]. Adding the purifiedvirus to fat-free milk and spray drying at 30-350C Is aconvenient drying method. When stored, the virus had ashelf life of 1 year at 17--25'C when its residual mois-ture content was 6--9%. No change In storage propertieswas cbserved when the moisture content was reduced to1.3--4.4%. This extra-dry preparation could then be storedat 37°C for 60 days without loss of activity [71, 161].

Attenuated and dry hoof-and-mouth vaccines havebeen successful in large-scale use. A dry adsorbed vac-cine which is 99% effective had been tested on 3.5 millionsheep as of 1963. An attenuated vaccine which protects upto 9 months is also in use [215]; the dry vaccines usuallyimmunized for 2-6 months [117]. A dry vaccine preparedfrom strain L-III was tested on cattle. Its preliminarysuccess and low allergenicity have ecommended It forwider use [176].

-25-

III. RABIES, AUJESZKY' S DISEASE, AND POLAR MIADNESS

Rabies and "polar madness" or "rage" (Tundra rabies)of arctic animals, especially foxes, and AuJeszky's diseaseor "pseudorabies" are viral diseases that affect wildanimals primarily. Humans are susceptible to rabies andpossibly to rage virus but not to Aujeszky's disease virus[254]. The table presents criteria for distinguishingrabies from Aujeszky's disease.

Table VDifferential diagnoistic criteria for Rabies and Aujeszky's

disease

DIAGNOSTIC SIGN RABIES AUJESZKY'S DISEASE

Reaction of virus to weakens quite resistantdrying

Locati6n of virus in nerves blood and lymphthe body

Infectivity of sali- always not in the absence cfva nasal discharge

Infectivity cc sometimes yesblood

Behavior of virus on killed in killed in 30-50 minbeing heated to 5-10600 min

Babes-Negri bodies present absent - acidophilicinclusions seen inspinal ganglia ofcattle

Incubation period days to weeks always shortProdromal period several days absent, rapid onset

of diseaseAggressiveness in marked absent

the affectedanimal

Scratching rarely as in swineDrooping of lower often seldom

jawQuick death seldom oftenSusceptibility of yes ro

humansOral infection no yesVirus in the paren- no yas

chymal organsSwallowing inedible yes no

objects

-23-

Table V continued

Means of spreading biting by contact and inthe disease food

Taken ?rom: Orlov, F. M., Comp. Virusnyye boleznJ zhivotnykh(Virus diseases of aniuals) Moskva, 5elidhuzizdaL, 1963,163-16u.

"Rage' has ber orserved in wild and domesticatedpolar foxes [09, 90, i047 105, 106, 235, 236], wolves, dogs,deer, bear, elk, nd lemmings [235]. It is believed thatthe mortality rate is over 90% and that lemmings form anatural reservoir of this eIsease and spread it to foxesduring their migrationu =-35]. These foxes probably infectdomesticated dogs. immunciog,-al and serological testsshow that this virus is similar to but distinct from rabiesand all other neurc~ropic viruses [89, 90, 104, 105, 235].Specific antibodies to "rage" are found in the blood offoxes surviving an asymptomatic form of the disease [89].No Babes-Negri bodies were observed in any case, althoughunidentified intracellular intilueions v-ere found ir foeneural tissue taken from experimentally infected animals[106].

One haman victim has been reported [90]. In theov.--Dec. 1961 outbreak in the Yamal region, a child was

bitten by a fox. The child died 25 days after being bit-ten, despite treatment with antirabies serum. Post-mortemexamination of both the human and fox tissue revealed noBabes-Negri bodies; "rage= was therefore given as thecause of death. Serological methods employing complement-fixation and virus neutralization show that this virus isrelated to Aujeszky's virus and infectious equine encephal-oyelitis virus as well as to rabies virus [235, 236].

No data on any diagnostic methods faster or more accur-ate than those mentioned have been discovered in the litera-ture. Unconfirmed reports of the effectiveness of antirabiesgannaglobulin in neutralizing this virus have been pub-lished; claims that preparations made from this virus willprevent rabies have al: o appeared [235]. Rabies vaccinewill protect foxes aga ;.st rage" virus but no cure isknown for the disease once the symptoms, similar to thoseof rabies, appear. Therefore, prevention of contact be-tween wild and domesticated animals is thb only effective

-27.-

means known for checking the spread of the disease [235].Animals %hose winter rations contain added mineralspossess slightly more resistance than animals fed a stand-ard det [235). Wild and domestic rodents and their ecto-parasites are considered the principal reservoirs andvectors of pseudorabies or AuJeszky's disease, and fleasand ticks are the actual mechanical vectors [254]. Thevarwie. state can las as long as 100-130 days in fleasand the disease can run its full course in 2 days In live-stock, dogs and cats [254]. This shorter incubation periodis one of the signs that differentiates this disease fromrabies (see Table V). The disease is sporadic, usuallyoccurs in the fall, and generally kills young animals [254].73oassay, histology, and diagnosis by clinical symptoms aret ing replaced as diagnostic methods by the more rapid im-mrune reactions, diffusion-precipitation tests and, mostrecently, the fluorescent-antibody method (FAM) [32, 101,170, 2221. The diffusion-precipltation-in-agar reaction israpid, inexpensive, and simple to perform. Its suitabilityfor general use is subject to proof of a lack of additionalnonspecific reactions [22]. To date, the FAM is the fast-est and most accurate method; the appearance of viral anti-gen can be detected 2 hours after infection of a chick-embryo tissue culture [3]. The types of vaccines In useare: a specific gammaglobulin which is obtained by alcoholprecipitation at low temperature [124), to which killedvirus is added, a chick-embryo tissue-culture vaccine inwhich the virulence of the virus is decreased by longpassaging [213, 242], a similar vaccine prepared fromvirus passaged on mouse tissue [242], hyperimmune serum,brain homogenate [2541, and a vaccine prepared in Czecho-slovakia from a weakly virulent, freshly isolated strain[214)]. The last vaccine, still experimental, was announcedin 1964. The virus was suggested as a possible vacclnalstrain; If It is, the need for long passaging [87] to ob-taln sufficiently attenuated virus would be eliminated.Challenging vaccinated laboratory animals with the wild-type virus showed the efficacy of all the vaccines tested.In addition, specific gammaglobulin alone protected new-born pigs with an imunity that lasted for three weeks[124, 4]. Passaged virus was used in large-scale testsand was the most effective among thousands tested. Only afew animals died [213]. "SUC-l," the viral strain iso-lated in Czechoslovakia, protected test animals as well asa passaged strain [214].

Examination of rabies vectors covered rodents,

iA

.I

Fincluding bats, and emphasized canines. Stray dogs are theprincipal vector in civilized areas. Wild foxes are con-sidered the principal reservoir of the disease, spreadingIt to dogs. A survey has shown that pigs and birds alsocarry the disease [157]. Strains of rabies virus isolatedfrom wolves and dogs ar6 the most virulent and the leastvirulent strains come from humans, simians. and livestock[157]. Immunofluorescence and the FAM are used to deter-mine specific antigens for differential diagnosis of rabies.These methods are both faster and more accurate than dia -

nosis by clinical symptoms, his':ology, and bloassay (218].The FAM permits visual localization of antigen and cyto--plasmic inclusion formation in living cells [196], and whenthe dye is bound to hyperimmune donkey serim, it is the mostuseful method for differential diagnosis of rabies [120, 192,221].

Since some of the most effective rabies vaccines aredifficult to prepare and maintain and have dangerous sideeffects, both tissue cultures and various viral strains arebeing screened in the search for suitable replacements forantirables gammaglobulin and braln-tl ssue vaccines. Astudy of rabies virus variants showed that after longpassaging in tissue culture the original wild-type strainacquires a shorter incubation period before causing symp-toms and requires a lower Dim (intracerebral) for infectionof rabbits, but is completely apathogenic in rabbits whenadministered subcutaneously [158]. Variants of standardstrains have been obtained; some of them are more patho-genic than the wildtype, producing svmptoms in 1--2 daysbut with no discernable Babes-Negri blodies, while otherscause atypical clinical forms of the disease. Especiallyinteresting are strains isolated from African dogs suiferinifrom a rabies-like disease related to Arctic "polar madnessor "rage,* strains from cattle suffering from a diseasedescribed as "plague," and miscellaneous atypical strainsfrom human adults [158). When several variants were testedon different arimals' tissues it was shown that homologousimmune sera were the most accurate for diagnostic purposes[192]. These resultz have prompted research into differ-ent virus strains and substrate tis3ues for vaccine prepara-tion.

Since passage In a given animal brain-tissue cul-ture increases the virulence of -.he virus for that particu-lar species and ]essens it for other species, and sinceroute of administration alters the clinical course of thc

disease [153], it is likely that a variety of tissue-cul-ture vaccines will become standard for these reasons andbecause cost and production technology will be simplified.

A specific gammaglobulin obtained frcm vaccinatedhumans was slightly effective but was inferior to horse-serum globulin [76).

Rabies virus has been cultured successfully on chick-embryo fibroblasts and an effectoive vaccine has been pre-pared from this culture [197]. Allergic reactions are oneof the principal disadvantages of rabies vaccines In currentuse and several papers were published between 1962 and 1965on experimental vaccines with reduced allergenic and ana-phylactic proerties [31, 160, 210, 2391. Partial proteo-lytic hydrolysis of crude globulins during production re-duces production volumes with increased vaccine yield [160).Vaccine prepared from newborn ra. and rabbit brain causesfewer allergic reactions than vaccine prepared from adultrat brains [31, 256]. Donkeys have been suggested as asource of antirabies gamma globulin since immune serum canbe obtained from them more rapidly, their ser-um causesfewer reactions in use, and the animals themselves areeasier to maintain and manage than horses [192].

Challenge tests of various vaccines and vaccinationschemes have been reported in the literature. Productionof active-passive immunity in laboratory animals has beenachieved by the administration of a combined dose of anti-rabies gamma-globulin and 0.5% vaccine. Interference wasellmrn'ated by doses of gammaglobulin 4 days before startingthe vaccination program [163]. The injection of cortisoneinterfered with the immune reaction allowing a marked In-crease in virus multiplication [2121. Other experimentsgave similar results [162, 210, 211]. The injection ofstandardized Fermi (formol) vaccine with or without gamma-globulin produced a plasmacytic reation In test animals,intensified RNA synthesis, and increased antibody titer inthe resistant animals [211]. There was a direct relation-ship b-tween the serizi antibody titer and degree of resis-tan-e in the animal which, in turn depended on the po-tency of the vaccine [162, 210, 211].

At a conference on the effectiveness and safety ofnonallergenic rabies vaccines held on the 18th and 19th ofMarch 1965 at the Ivanovskiy Institute of Virology of '-heSoviet Academy of Medical Sciences and sponsored by a com-

-30-

mission of the Ministry of Public Health, all partici- -nts

agreed that nonailergenic vaccines should replace thestandard Fermi vaccine [210]. This special commission wasestablished in 1962 especially to investigate the propertiesof new preparations and to engage in large-scale tests ofthem. Both wet and dried vaccines were tested by variouslaboratorie5 and agencies. Members of the commission were:R. M. Shen, Institute of Virology; 0. G. Andzhaparidze,head of the State Control Institute for Medical and Bio-logical Preparations, Ministry of Public Health; S. S.Unanov, director of the Moscow Viral Preparations ResearchInstitute; M. A. Selimov, head of the Rabies Laboratory atthe Institute of Poliomyelitis and Viral Infections, AMNSSSR; M. A. Khiyenenson, Moscow Municipal Sanitary-Epidemi.-ological Station; A. S. Makaryan, senior inspector of theMinistry of Public Health RSFSR; A. A. Mtvarelidze, TbilisiSanitary-Epidemiologtcal Station, and B. A. Kantorovich,senior scientist of the Institute of Virology. V. M.Zhdanov, director of the Institute of Virology, was incharge of the organization of the work [210]. The commis-sion began its work in January 1963, and made the followingrecommendations to the Ministry of Public Health SSSR in1965: 1) immediate introduction of the nonallergenic vac-cines into medical practice; 2) broader use of the drynonallergenic vaccine; 3) the establishment of a similarcommission to carry out more detailed studies of such vac-cination programs 1210].

IV. SWINE PLAGUE

Swine plague causes extensive damage to the circulatorysystem as s own by extensive septicemia in infected animals.Secondary infections such as paratyphoid, bacterial hemor-rhagic septicemia, diplococcal infections, and listeriosisare the principal dangers of this disease. Differentialdiagnosis is complicated by the lack of really reliablelaboratory tests. Likhachev states in Virus Diseases ofAnimals that the only definite means of differential diag-nosis are analysi- of clinical data, results of bacterio-logical studies, the epidemiological characteristics of thelocal outbreak, and the final isolation of the agent andproduction of the disease in animals [118). Most vaccinesare derived from infected tissue cultures and are concen-trated by treatment with freon and subsequent precipita-tion in acetone [34). Virus passaged in tissue cultures(usually swine embryo) differs in virulence from the origi-nal virus. Several passaged strains retained their viru-lence but were not immunogenic. However, these strainswere used to produce hyperimmune sera and subsequently toinoculate other tissue cultures from which an avirulent dryvaccine was prepared for administraticn by aerosol. Thisaerogenic vaccine required seven days to become effectiveand protected 100% of test animals for two months [33, 152,153, 251).

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I

V. VENYZMAN EQUINE ENCEPHALOMYELITIS

A fluorescent antibody test and a specific hemagglu-tination test based on recent discoverie have been sug-gested as possible diagnostic methods for Venezueiand! equine encephalomyelitis (VEE). in an investigation of

virus reproductive dynamics in 196, Gaydamovich andVagzhanova discovered that a positive hemagglutination re-action can be obtained in tissue culture during the begin-ning of the logarithmic growth phase (6--7 hours afterinfection), and that there is a threshold of infectivitybelow which a positive hemadsorption reaction is not ob-tainable. They suggested that the hemagglutinating proper-ties of the culture fluid would be useful for the earlydiagnosis of the disease and for studi of viral growthdynamics [279].

A diagnostic test for VEE based on the earlyappearance of VEE virus hemagglutinin in tissue cultures

was devised by Gaydamovich and Vagzhanova. A compar-

ison of results showed that neutralization indices were

higher with tissue cultures than with convalescent sera and

that the indices were 0,000 times lower when the cyto-

pathic effet in emine te ned than when neutraliza-tion was per formed with immune rabbit sera. Results could

be obtained within 18 hours, and the method was recommended

for early diagnosis of the disease [691. The fluorescent

antibody method (FAM) is also used in the study of viralreproduction and it has been modified for diagnostic use,

Actinomycin D selectively halts cellular, but not viral,

biosynthesis c280; the acceleration of viral reproduction

in tissue treated with the antibiotic has been reported

[291]. fnce cellular DNA synthesis has ceased, the FAM

is employed to determin te h synthesis site of VEE virus.

RNA precursors and viral antigen can be detected visually

in the cytoplasm by this method [280. In the secondmethod, when viral reproduction in tissue culture is accel-

erated by actinomycn-D, hemmagglutinaton tests can be

used earlier than when the suspected culture is untreated

[291] .

Chemical inhibition of viral attachment to the cell

membrane is reported by N. V. Kaverin. in his study,mouse fibroblasts and human liver cells in culture weretreated with uranyl acetate which inhibited phosphate-

group activity oil the cell membrane. V-EE virus attachedto the cells but was easily removable, suggesting thatphosphate groups are necessary for the firm binding ofVEE virus to cell surfaces [100].

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irT MTr r-" A fMniT T" MlT 4ZA Q VZ' 0~ " Tir..-z-fW'if A .TT MI M4hQ

Insects and contairninated food and water are theprincipal sources of vesicular stomatitis, a disease whichinfects cattle, swine, and humans (the latter under labora-tory conditions). Scme of the principal mechanical vectorsare: -' m':' r, u C_., r: S tr Lndmiscellaneous flying insects. Complement-fixation reactionsare commonly used for differential d~agnosis. Survivinganimals are immune for one year after recovery. No specifictherapy was reported in the literature studied and the mostcommon treatment is symptomatic [1321.

In the Soviet Union, irfectious equine encephalomye-litis is spread by ticks, flies, and mosquitos. The mor-tality rate is often 100% and Babes-Negri bodies are fre-quently seen in brain tissue of dead animals. Severalpapers have been published investigating its connectionwith rabies [206]. The two most common diagnostic methodsare bioassay and serodiagnosis (complement-fixation).Although therapeutic use of immune serum has been success-ful, the resuitant protection is only transitory; thismethod has been replaced by vaccination with a chick-embryovaccine (used on at least 45,000 horses as of 1963) or byan attenuated live vaccine obtained from rabbit brain [206).

Infecttous equine anemia is spread in a variety ofways, generally from infected to uninfected horses via con-taminated food or by Diptera Transmission by intestinalparasitea is also suspected. After recovery, an animalcan carry the infection up to 6 years. Differential diag-nosis is difficult since there are several diseases withsimilar symptoms, and chemical diagnostic methods are oftenunreliable. Diagnosis is mainly based on observation ofsymptoms and on the fact that outbreaks usually occur inlate summer--early fail. Formol and aluminum hudroxidevaccines are often unsatisfactory; quarantine is thus theonly really effectivea preventive measure [191].

Japanese infectious equine encephalomyelitis, adisease usually called "Japanese-B"encephalitis when ob-served in humans, also displays seasonality. It is mostcomon near swampy areas during the summer, when it isspread by infected horses.Transovarial transmlssion has

been demonstrated in the following tickr -hich are the prin-cipa1 vector z durirg the winter months 7P,'¢'

R'. .;-)u S -s - r:l As1-4 .-rp i -I

-34-

_.208]. Complement-fixation

with specific antigen is the most common diagnostic method.Recovery confers immunity in animals. Administration offormol vaccine (in three shots) each year before the startof the epidemic season, is effective as a vaccinationprogram, although insect eradication is considered to bethe most effective control measure [208].

Contagious pustulant dermatitis of sheep and goats(contagious ecthyma) has been reported in humans, includingvolunteers for experimental Infection and individuals in-fected by a diseased animal. The disease affects mainlyyoung sheep and goats, is spread by contaminated food andwater, and has an incubation period of 8--10 days. It maybe diagnosed by clinical observation, by the agglutina-tion, precipitation, and complement-fixation reactions, byneutralization, and by bioassay. A dried vaccine, adminis-tered in saline, has been developed which protects againstexperimental and natural infections. Sheep are immunefollowing recovery from natural infection. In the limitedstudies involving humans, little or no immunity existedafter recovery and the vaccine gave limited protection [2341.

Cattle are most susceptible to Rift Valley feverand are infected by insects which carry the virus from itsrodent reservoirs to its principal hosts. Humans usuallyacquire the infection from infected cattie,and the mosquitoesAeies cabal7us and Culex fleiier. Other vectors are the flyEretraDoidites chryscoasterand the Rhipzecehaius spD. tick[2313. Standard serological reactions are used diagnosti-cally ana several experimental live-virus vaccines havebeen tested [231].

Livestock, particularly cattle and their wild rela-tives, are the most susceptible to rinderpest. The domes-tic animals acquire it from contact with wild carrierswhich include rodents, wild birds, 1sects, and pigs, aswell as dogs and cats. The suslik C "te s Y0 r C1 cus

is the principal reservoir and carrier [21]. There arenumerous papers reporting the results of studies on theserological relationships of this virus to various simianand swine-plague viruses. In the Soviet Union, complement-fixation 'T:ploying specific hyperimmune serum or viralantigen -I.jrations is used for early diagnosis. Thediffus: jr~cipitation-in-agar reaction is commonly usedfor difi.'>ential diagnosis [21].

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I

Most current research published deals with studiesof various viral vaccines.A formol-aluminum hydroxide v*.:cinehas been reported to be more e'rtective than the tissue vac-cines used previously, and a live-virus vaccine (attenuated)produces an immune response within 24 hours [21]. The useof ultrasound does not inactivate lapinized vaccines unlessapplication is prolonged (60--120 min); small doses are use-ful in separating the lapinized virus from the tissue cul-ture [167]. A dry vaccine prepared from stabilizedNakamura-III (L-III) strain proved as effective as thestandard formol vaccine; however, its peak immunizationtiter required 20 days to appear (24]].

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VII,* POX-VIRUS INFECTIONS AN4D THE DEVETAOPMEN OF EFFECTIVEVACCINES

Pox viruses grown In tissue culture have been employedin vaccine reserch and in studies of' the synthesis and in-tracellular localization of' DNA. The reactivation of' heat-killed viruses of' this group by closely related strains hasbeen studied and the results of' one such study are shownin Table 6.

Table VI f'rom [33].Renettva betw~eu wm=m vuet a"d aeftiemei vim

Tested in

aptved esti e I I I chick Mie '

lin ____.. I rabbit

Va(ab (Vatiooa Planter. Iuatvtd0 0-

iVariola. active 0 VAVaaaINV iNV+ALI

vaccinic.

0 AL0

Ectromelis, active EC ECAiastri. active AL * 0

A0im Ectca"ai AL+ECj

Ea~lasrin activei AL o !

EtJomTelia. active - ' EC E

xniaasctia -aei~s ; N:V a C

Ecrnla cie I E I E

Vwinans "v NV V 0

vaccinia,inactivated 0 1 0 I

Ectrornelia. active, 0C

NbV - lesions characteriatic of "'accnis, (netuovaccinia "rin)VA - lesions chaiacteristic of v'ariols.

AL-lesions characteristic of astrimW- lesions characteristic of ectromoelis,

0-80 ons

-37-

In thi3 study [36], the authors demonstrated reactivationusing vaccinia, variola, alastrim, and ectromelia viruses.Results published in later papers indicated that reactiva-tion of a heat-killed virus depends on the integrity ofits DNA and part of its protein component [37], and thatthe factor causing deproteination of viral neucleocapsidsis coded in the cell genome rather than that of the virusand that effects of this factor are observable within 2--2 1/2 hours after infection [151]. Reacitvation does notoccur in cell cultures lacking this factor. Autoradio-graphy and the FAM (fluorescent antibody method) have beenused extensively in the study of cell-virus interaction andfor differential diagnosis [80, 149], and autoradiographyhas been employed in studies of early viral DNA and antigensynthesis [175]. The FAM detects specific viral antigensin tissue cultures within 6 hours and has been used todistinguish vaccinia, var'iola, alastrim, varicella, cowpox,Herres z:s=', and H -es szzOx viruses. The chiefadvantages of the FAM are its specificity and simplicity[80]. Using cytopathic effect in tissue culture as part ofthe diagnostic procedure was complicated in one case bylack of temperature control; the importance of controlled,optimum temperatures during culture incubation was stressedas cytopathic effects often were not observed at tempera-tures higher or lower than optimum [79]. Because of theirsensitivily, standard tissue-culture methods were generallyrecommended for confirming diagnosis and for diagnosis ofasymptomatlc carriers [133]. The two variants of vacciniavirus most commonly used in the preparation of vaccineshave been called "red" and "white" because of the pockmarksthey produce on chick chorioallantoic membranes. Differ-entiation is therefore done visually and confirmed by thediffering hemagglutlnation activity of the two variants[133].

Antiviral ccmpounds such as 6- azauracil ribosideand urethane delay mortality in mice infected with vacciniavirus intranasally and intracerebrally, but do not lowermortality rate [861.

Tissue cultures are used to evaluate the activityof strains being screened and the potency of viral prepara-tions, and to select mutants for further screening [81].The plaque-forming properties of vaccinia virus in chicktissue culture have rendered it useful for a rapid, accur-ate, and economical procedure for determining vaccinepotency. The method employs test-tube cultures and giveseasily interpreted results in 48 hours [81].

-38-

Clonal mutant vaccines have been prepared in tissue

culture and those vaccines have successfully immunizedtest antmals and children [.>1, although they possessatypical properties in compaZ'lson to the parent strains andthe heterogeneous virus population from which they wereisolated [1351. Heterogeneous vaccines displayed propertiesdependent upon the proerties of their most common component[135]. The interference of inactivated virus with the multi-plication of live virus in tissue culture has been tracedto an as-yet-unidentified factor lonated In or on the inacti-vated virus. One of the principal factors governing theeffect of the inactivated virus on live virus multi l.cationis the time between the injection of each type [174].

The Immune mechanism involves plasmacytic response.In a series of papers [136, 225, 226, 229] the authors demon-strate the important role of phaocytosis the significanceof the site of inoculation and the innoculum dosefIntra-venous and intranasal are the most effective rou.es andIntranasal is most economical inoculation method), and thedegree of antibody synthesis in Immunologically competentcells of the lymphatic organs. Antibody titers are highestafter intravenous inoculation. The duration of immunitydepends on the degree of plasmacytic response over a periodof time and not necessarily on the initial degree o re-sponse [2253. Data from an experiment performed in 1962confirm the above conclusions. In this experiment, animalsirradiated with sublethal doses of gammaradiation wereimmunized with a dry live-virus vaccine 6--10 days afterirradiation. In most cases the radiation slowed the de-velo:)ment but not the degree of immunity. These resultsdiffer from those obtained with killed vaccines and fromthose obtained in experiments in which previously immunize&canimals were exposed to Ionizing radiation [56].

AA.- A Th d -41- - I A

ate antigens of a brain vaccine against tickborneencephalitis. Voprosy virusologli, no. 5,1965,577-583.

2. Afanaslyeva, C. V., and Yu. F. Sapozhenkov. Data on theixodid ticks (parasi'tformes, Ixodlidae) infesting Tolalhares in the 'Turlien SSR. IN: AN Turkmen SSR. Izvest-

ya, Seriya blologichesklkh nauk, no. 4, 16,9-2

3. Albrecht, P., et al. Pseudorabies virus in chick-embryo cell cultures and in infected animals demnon-strated by the fluorescent-antibody technicue. Atctavirologica, v. 7, no. 4, July 1963,. 289-296.

aL. Aleksandrov. N. I., et al. Aerosol immunization usingdry, powdered vaccines and toxld. Reot0Clinical studies of postvaccinal reactions to 1Immuni-zation with a dry brucellosis vaccine. ahurnalmila'obiolo ii, epidemiologl i I mmunobiologi, v * 33,no. 11, 1962, 31-3..

5.Aleksandrov, N. I., et al. Aerosol inmunization usingdry, powdered vaccines and toxoids. Report 8.Aerogenic immunization of large numbers of peoplewith a dry plague vaccine. Zhurnal miicrobiologii,epid~miologii I immunobiologli, v. 33, no. 7, 1962,46-50.

6. Aleksandrov, N. I., et al. Aerosol immunization withdry powdered vaccines and toxoids. Report 9. Re-active and inmunological effectiveness of theaerogenic method of brucellosis vaccination.Zhurnal miIrobiologil, epiderniologil I immunobiologli,v. 33. no. 12, 1962, 95-102.

7. Aleksandrov, N. I., etL al. Experience in mass aerosolimmunization of man with powdered tularemia vaccine.Zhurnal microbiologii, epidemiologil I iunnunobiologii,no. 2, 1964, 38-43.

8. Altstein, A. D., et al. Interference between tickborneencephalitis and poliomyelitis viruses in tissueculture. I. Resistance of cells infected with t ck-borne encephalitis to cyvtopathic efffet of poliovirus. Acta virologica, v. 6, no. 5, 1962, 421-427.

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9. Altstein, A. D. interference betwenn tickborne encephal-Itis and po]aomyelitls viruses in tissue culture. II.Mechanism of cell resistance to pollovirus of tissuecultures infected with tickborne encephalitis virus.Acta virologica, ,. 6, no. 6, 196P, 481-u86.

10. Al'tshteyn, A. D. Titrating TBE virus and virus-neutralizing antibodies in human-embryo fibroblaststo investigate interference with polio virus.Voprosy virusologii, no. 5, 1962, 529-534.

i1. Al'tshteyn, A. D., et al. A method for serologicalstudies based on interference between TBE and poliovirus in human tissue culture. Voprosy virusologil,no. a, 1963, 392-397.

12. Ananyan, S. A. Prelimirary serological and virologicaldata on the isolation of arbo-A viruses in theeastern Soviet Union. Acta vlrologica, v. 8, no. 1,1964, 93.

13. Andzhaparidze, 0. G., and N. N. Bogomolova. Interactionof TBE virus and receptive cells in vitro. Report 4.Developmental phases of viruses In a monolayer cellculture. Voprosy virusolcgii, no. 1, 1962, 35-39.

14. Andzhaparidze, 0. G., et al. Reaction of TBE viruswith receptive cells in vitro. Report 5. Viraldevelopment in an infected cell and infective RNA.Voprosy virusologil, no. 4, 1962, 28.

15. Andzhaparldze, 0. G., et al. Comparative sensitivityof various primary tissue culture lines (swineembryo) to destruction by TBE virus. Voprosyvirusologil, no. 5, 1962, 534-536.

16. Andzhaparidze, 0. G., et al. Chronic infection of cellswith TBE virus. Report I. Properties of chronicallyinfected cell cultures. Voprosy virusologii, no. 6, 1962,650.

17. Andzhaparidze, 0. G., et al. Variability of tickborneencephalitis virus. Report 2.. Voprosy virusologii,nc. 2, !9:5, i6-67 MPS 31,!43

18. Anokhinn, i. T. Spread of hemorrhagic nephroso-nephrlt-sin Amur oblast. Zhurnal mikroblologii, epldemiologlii I4 muncbiologli, no. 4, 1965, 147. JPRS 33724

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19. Avaicyan, A. A., et a!. Acute and chronic infectionscaused by TBE virus in tissue culture. Voprosyvirusologii, no. 6, 1963, 713-719.

20. Barkova, E. A.,and A. P. Ierusalimskiy. Dynamics of theappearance of virus-neutralizing antibodies inlpatients with various clinical forms of TBE. Voprosyvirusologii, no. 2, 1962, 189-193.

21. Bazylev, P. M. Rinderpest. IN: Orlov. F. M., comp.Virusnyye bolezni zhivotnykh (Virus diseases ofanimals). Noskva, Sel' khozizdat, 1963. 20-231.

22. Bazylev, P. M., and Yu.V. Fonin. Diagnosis of Aujeszky'sdisease by the diffusion precipitation In gel method.Veterinariya, no. 7, 1965, 16-19.

23. Benda, R., et al. Eperimental airborne infection ofmonkeys with tickborne encephalitis. Acta virologica,v. 6, no, 1, 1962, 46-52.

24. Berulava, S. N. Using Ascangel to purify foot-and-mouth virus. IN: Voprosy veterinarno virusologii(Problems of veterinary virology). Moskva, Kolos,1964. 203-208.

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26. Bigovskiy, A. I. Viral characteristics of TBE inWestern Ukraine. Voprosy virusologii, ito. 6, 1964,733.

27. Borisov, L. B. Comparative characteristics of theantiphage activity of dichiorethylamines. Mikro-biologiya, v. 33, no. 1, 1964, 79-84.

28. Borisov, L. B., and G. S. Yakovieva. Inhibitory effectof novoembichin on bacteriophages and viruses.Voprosy virusologii, no,. 2, 1962, 148.

29. Borisov, L. B., and N. B. Rumell. Antiviral activity ofethyleneimines. Voprosy virusologii, no. 6, 1963,728.

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30. Bratovanov, D., et al. Epidemiology of renal hemor-rhagic fever in Bulgaria. Zhurnal mikrobiologii,epidemiclogii i immunobi/!ogii, V. 33, no. 1, 1962,122-126.

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40. Chumakov, M. P. Isolation of a virus differing fromthe agent of tickborne encephalitis from Ixodespersulcators ticks and humans in Western Siberia.Acta virologica, v. 7, no. 1. 1963, 82-83.

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51. Desyatkova, R. G., and 0. 0. Andzhaparidze. Effect ofsome factors on plaque formation in cell culturesinfected with TBE virus and its RNA. Voprosy viruso-logii, no. 3, 1964, 339-344,

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59. Feoktistov, A. Z., and Z. N. Kondrashova. Study of thehemaglutinating capacity and the inhibition sensi-tivity of TBE virus strains from the Khabarovskregion. Voprosy virusologli, no. 6, 1964, 741.

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62. Gaydamovich, S. Ya., and N. G. Titova. Accumulationdynamics or infectious virus particles and hemag-glutinating and compleanent-fixing antigens oftickborne encephalitis virus In an infected tissueculture. Acta virologica, v. 6, no. 2, 1962, 151-158.

63. Gaydamovich, S. Ya., and Yu. M. Tsirkin. Improvedlaboratory diagnosis of ticlcborne spring-summerencephalitis. Report I. Ileragglutination andcomplement-fixation typing of viruses with tissueculture antigens. Acta virologica, v. 8, no. 3,1964, 243-248.

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66. Gaydamovich, S. Ya., and V. V. Vlodavets. Observationof the minimal concentration of influenza virus inthe vapor phase of an aerosol. Voprosy virusologiiL,no. 3, 1963, 34~9-353.

67. Gaydamovich, S. Ya., and V. A. Vagzhanova. Early detec-tion of arboviruses in tL-issue culture by hemaggluti-nation. Voprosy virusologli, no. 6, 1964, 712-714.

68. Gaydamovich, S. Ya., and Duan Suan Myou. An HI diag-nosticum for Japanese encephalitis virus. Voprosyvirusologii, no. 1, 1965, 105-110.

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82. Han Shi-gie, and V. V. Pogodina. Fluorescent-antibodytechnique in the s-tudy of Far-Eastern tickborneencephalitis in mice, hamsters, and pigs. Actavirologica, v. 8, no. 1, 1964~, 22-29.

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APPENDIX I.SUPPLEHENTARY BIBLIOGRAPHY OF ARTICLES AND BOOKS CONCERN-ING DLAGNOSIS, THERAPY, EPIDEI-OLOGY AND HISCELLANREOUSSTUDIES OF VIRAL DISEASES PUBLISHED BETUE-E-F4 1962 AND 1ba.LISTED ALPHAB-TICALLY BY AUTHOR.

1. Arlkhipov, N. I. Morphological changes in swine plaguevirus-infected spleen cultures. IN: Voprosy veter-inarnoy virusologii (Problems of veterinary7 virology)Moskva, Kolos, 1964. 253-256.

2. Arldipov, N. I. changes in capillary permeability inacute swine plague. IN: Voprosy veterinarnoy vir-usologii (Problems of veterinary virology). Mloskva,Kolos, 1964. 291-297.

3. Avakyan, A. A., F. M. Kirillova, I. B. Pavlova, A. D.Al tshteyn, and L. N. Kats.Idaterials pertaining tothe study of etiology of hemorrhagic fever with arenal syndrome. Zhurnal mlkroblologii, epidemiologiiI immunobiologii, no. 7, 1964, 129-134.

4. Bazhedomova, M. A., and S. F. Zakirova. Hemagglutinincharacteristics of TBE viruses during repeatedpassages on SMH cells and human-embryo kidney cultures.Voprosy virusologii, no. 6, 1964, 730.

5. Bektemirov, T. A. Interference between vaccinia, andvariola viruses in chick embryos. Acta virologica,v. 9, no. 6, 1965, 541-550.

6. Beladi, I., and 14. Bakay. Persistent pseudorabies virusinfection in calf cells. Acta virologica, v. 7, no.5, 1963, 477.

7. Belkov, G. P. The Fourteenth All-Union Conference ofEpidemiologists and Microbiologists and Infection-ists held in Moscow on June 29 to July 4 1964.Zhurnal mikroblologii, epidemiologi.i immunobiologii,no. 1, 1965, 150-152.

8. Borodina, T. A. Keratcgenic properties of TBE virus.Voprosy virusologii, no. 3, 1964, 354-357.

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0. Bukrisaa A. G.,. I. Yershov, and V. Ki. Zhdanov.Luminescent microscopy study off tissue-culture cellsduring- the initial phase of' their interaction withSendai virus. Voprosy virusologii, no. 1, 1962,1'3-220. JFRS 10401

10. Chistova, Z. Ya. and~ V. 11. Syrurin. INutantz off av-1anlar'Yngotracheitis virus. IN: Voprosyr veterinarnoyvirusologii (Problems off veterinary .0virology).

,~sv, K los 0, 1964. 413-425.

11. Chumakov, 11. P. Classiffication and nomenclature offviruses in the TBE antigenic subgroup. Voprosyvirusologii, no. 3, 1965, 376-'30.

12. Danielova, V. Multiplication dynamics off Taleynavirus in diffferent body parts off Aedee vexanemosquitos. Acta virologica, v. o, no. 3:1962227-:230.

13. Degryatkova, R. G. Role off TBE virus iFNA in experi-mental inf'ections in mice. Voprosy virusologii,no. 3, 1963, 275-273.

154. Dyadichev, N. R. Defining the concept of epidemicprocess. Zhuz'nal uikrobiologni, epideiologil iiMmunobologii,, no. 6, 1965, 14~5.

15. flzhivanyan, T. I.,,and G,, D. Zasukhina. Investigationoff pathogenic prc-3exti.es of two variants or onestrain of HEE virus.* IN: A!&tual' nyye problemyvirusnykh inrelk;tsiy, 1965, 177.

~6.Galbo, S., n'd 1. Ga~Gov. Atteupts at cultivatingcertain viruses cof the myxogroup in -Acrobe sus-pensions treated with ultrasound and untreated.INl: Bull'.arska aikademliya na nauite. Do.0-ady, v. 18,no. 11, 1965, 103-9-1042.

17. Gala-tt, I. B. Z-xperiients ,.L V, I, il en'K and 0. A.Pcksrovskaya wiith inoculation --f mnky with tick-borne encephalitis. Zhurnal nevropatolo~ii ipaildiiatrii, v. 64~, no. 1, 19614, 158-159.

13. Galegov., 0. P., zud V. KC. 2;hdanov, Inclusion ofcarbon'1 uridine into cell cultue i k'etewith poultry pseudoplague virus and inhibition ofthe syinthesis ol' v ra]aiionucleic acid. IN~:A -adewiya flauk SSSR. Dolady, v. 165,:. no. 3, l6:z

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19. Gaycdamovich, 3 . Ya., and Duan-Suan Iiyosu. 0hoacgraphic fractionation ofL Japanese enc epialit isvirus on cpalciu;,, phnosphate coluw.nr.. Vopros3T

vi-nuolgi, no. 2, 19,!-:

20. Gaydamovich, S. Ya., and V. R. O'cu~izova. Hi~arlutin-atiIn. antif.enC -Eror. TFLE- -.'iruz 2ror.- tizzue cultures.Vo;ProZ' vi"U-10:-i, !'o. 3, 136u5, 362.

21. Grigoryeva, L. V., and T. V. Starovoytova. Thefrequency of recovery of certain enterovirusesand bacteria in water basins and sewage.Gigiyena I sanitariya, no. 7, 1965, 108-109.

'?2. Hoptm-an, J. ; edical virology in the USSR. 1. C. R. S.M~edical Rleports. M4onograph- 3n Soviet 1tledical Sci-ences, no. 1. Fordhamn University 'Press. 1962.

23. israelyan, A. A., and G. D. Zasukhina. Variability cl-virus during passage through various organismis.Voprosy virusologii, no. 3, 1965,, 23-it7.

24. Ivanisova, S. , Ri. Skoda, V. ilayerad. Sokol.Inactivation of Aujeszky's disease (Pseudorabies)virus by nitrous acid. Act'a virologica, v. 7, no.1, 1963, 7-15.

25. Kaulen, D. P. Fourth interinstitute confer7ence onproblems of radiation microbiology and irmuno-y.IMeditsinskaya radiologiya, no. 7,j 1964, 68-71.

26. Kereyev, N. 1. Materials on the geography of endemicInfections in Xazakhstan. IN: Akademdya naukKAzakhakoy SSR. Vestnik, no. 2, 1965, 7-11.

27. Kislyakova, L. IT., G. S. Tseraidis, V. M, Zhdanov,.M. G. Bogdanova, and M. I. Limarenko. A study ofviral etiology of chr-onic pemphigus. Voprosyvirusologii, no. 3, 1964, 320-324.

28. laimenko, S. N., et al. Features of VEE virus structure.voprosy virusologii, no. 5, 1965, 520-5925.

29. KolOSov, V. MI. Adaptation of fowl-plague virus topigeon embryos. IN: Voprosy veterinarnoy virusologi.(Problems of veterinary virology), Nos-Ava, -Kolos,,1_964. 371-376.

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30 .:iravchenko-.,A. TO$ and A. D. All'"Vshteyn. ?r.1 lc:.is olfoncogenic sal'ety of live virus vaccines. Tcoros5Zvirusc)ooii-, n~o. 5, 1964, 527-5-2. jPRS 27714,

I)J.. Lx-is1k±:, A S. Viruses and their nositi=n innature. Priroda, no. 10, 1:964,

32. i~ltA. F.* S~crapf.e. !Ni: Orlov, F. K.,. coraip,vrirusnyy e bolezni zhivotn!kh (Virus diseases ofanimials). 1-1o sAkva, Sell'khozizdat, 1963. 307-320.

33. Kulik, D. 1*1. Catannesia of patients with psychic dis-'Lurbances caused by antirabies vaccine. Zhurnalnevr^oato.lcogxi i psikchiyatrii, v. 65, no. 6, 1965,913-0917.

34. ezhvaG. A.,and A. Ya. Urushadze. Biological prc-perties of avian 1aryn,otraceitis virus. T14:Vo-prOsy veterinarnoy virusologii1 (Problems ofveterinary virology), iHcsk-va, iOO,1964. 401-412.

35. Libikora, H., V. Smidova, and N. Valentova. Neutraliza-tion tests with a cytopatYLic variant of tickborneencephalitis virus in stable cell lines. Actavirologica, v. 6, no. 1, 1962, 91.

36. Libikova, H. Assay of TBE virus in Hela Cells III.Selection and properties of virus antigens for anin vitro neutralization test. Acta virologica,v. 7, no. 6, no. 6, 1963, 516-524.

37'. Likhac!ev, 11. V. Cowpox. 1-K: Crlov,,, F. EI., com.p.Viruanyye bolezni zhivotnykb (Virus diseases Ofanimals3). MIoskva, Sel'khozizdat, 1-0,3. 45-77.

3.Likhachev, N. V. African swine plague. IN: Orlov,F. -1., comip. Virusnyye bolezni zhivotnykh (Virusdiseases of animals), fioskva, Se:1'khczizdat, 1963.497-506.

3.lyks, S. I. Mechanism of the formation of noninfectious3Acridinic" polio antigen. Voprosy virusologik, no. 6,1964, 652-656.

40. Llvov D. K., V. A. Zaklinskaya,aad K. V. Fokilna.Dys-anics o1- sero-.logical indicators of' immunity inaninals immunized writh TBE vaccine. Vopposy viruso-logii, no. 4. 1363, 420-427.

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41. Ltvowv, Do r., V. A. Zalainskaya~and M4. P. Chuuax'a*ov.Serologic al immunity indicat11ors in humans afterinjection of a TBE vaccine. Voprosy virusolc-3ii,no. 4., 1:963,s 42743-5

42. L' vov, D. K... et al. Spectrum of antihemmagglutinatingantibod'-ies af'ter exper-imantal immunization withviruses -.'L the TBE cciiplex. Voprosy v.irusologii,no. 6, 1-65, 657 w-663-

43. Nlarenni~ova, S. S., and N. N. IF.1altseva. Ccuiparativestudy of some vaccinia virus strains. Cc,unication2. Pathogenicity for laboratory animals. VOprosyvirusologii, no. 3, 1064, 237-291.

44~. Flarrennikova, S. S., N. N. 1vlalltseva,and N~. A. Yumasheva.Origin.9 of' vaccinia virus. Voprosy virusolcgii, no.6, 1905 71779

45. Nlastyukcva, Yu. N.,. A. A. Symarokov, and N. T.Sarayeva. Mechanism of antismallpox immunity.Communication 2. Role of leucocytes in smallpoximmunity. Investigation of organ homogenates frominfected animals. Vopros-_ vfrusolcgii, no. 1, 1964,90-95.

46. MaYer, V. Virulence of tickbox'ne encepalitis virus.III. Bloevaluation of large and small plaque variL-ants of the TE virus complex. Acta, virologica, v.8., no. 6, 1964, 507-520.

47. Kayer, V., and R. Skoda. Behavior of modified andvirulent strains of Paeudorabies (Aujeszky' dis-ease) viruises at different temperatures, Actavirologica, v. 6. no. 1, 1962, 95.

48. IMoroz, A. G. Effect of ionizing radiation on the repro-duction of epidemic parotitis virus in white miceand guinea pigs. Voprosy virusologii, v. 9., no. 1,1964, 6672 PRS 23,956

49. Orlov, F. I., Equine influenza. IN: Orlov, F. Iicomp.Virusnyye boleznI zhi~votnykh (Virus disease ofanimls). Hoskva, Sel' kbozizdat, 19634. 422-427.

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50). Par'anevich, I .,, and H. i"1. SzoI:z1ov. I-nteracti on ofnucleic aceids with speci "ic intracell ular antigensin iied infeections. a-1eport One. eipoearance anddistribution of nucleic acids in mixed InfectionseCuseciIa heroes and TEE vir-uses. Vcprorsy virus-

loino. ~5 41.

51. F.a 1anovic*h%, L. I.,and ia. 114'. 3okol0ov. Itheractionnucleic acids ivith specific intracellular antigensin =ixed virus I.niections, iilepcrt 2. Vcprcsy

virusologi-2, no. 2, &,22

52. Pavlovskiy, Ye. N., A. A. Pchelkina, and F. F.Talyzin. Cross-neutralization with the aid ofsera of animals affected with snake venom ofencephalitis virus. IN: Akademiya nauk SSSR.Dokiady, v. 156, no. 5, 1964~, 1239-1240.

z 3- fav-1vchiy~ Ye. !, 1. I. V10 -- in, and Xli. Kotlyarova.Ziaural --ocal oint of transuidtted diseases in

connection with the tpoo~ical epidemiolq~y ofZooant5hroponcziz. Zhurnal mi',-bio~logii, epideiido-logii1 i i=-runobologli, no. 6, 1-01"5, 156-157.,

54. ?ille, E~. R. Viruses ofmonkeys. Voprosy virusc-logii, no. 2, 1965, 131-138. JRS 31143

55. Pfrog, P. P. Viral pneumonia of pigs. 111: Orlov., F. M4.comn. Virusnyye bolezni zhivotnyldi (Virus diseases

o"*animals), K.cshva, Sell kliozizdat, 1963. 513-522.

56. Piros, P. P. Viral sastroenteritils of suine. IN4:Orlov, 1.. comp. VTirusnyye bolezni zlhvo,,tnykhI(Virus diseases or1 animals), iiosk7.a, Sel' ihoziAzdat4-,1963,: 522-531.

57. ?isars1U, -4., and 1R. Pruszynshi. Important data r-e-gardirng the prevention of rabies. Pzeglad epidemic-logiczny, v. 19-, no. 2, 1965, 1'112

53. PogZ-odina, V. V., and S. S. 1igznn H atural iiun-ty_U~aIive and clinical cPo -flaen E.Vp::

vucoi .2, l_:,$2, 243-2174.

59. Pogodina, V. V. Ccparative study of viruses of thetickborne encephalitis complex with respect toviremia. Acta virologica, v. 8. no. 2, 1964!,113-122.

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60. Popova, 0. M., and 0. N. Berezina. The effect of pre-liminary roentgen Irradiation on the susceptibilityof white mice to the ornithosis virus, upon infee-tioD with an aerosol of the virus. Voprosy viruso-logl, no. 2, 1964, 213-216.

61. Pospelova-Shtron, M. V., and It. L. Wumov. Case ofcarlring into the USSR of Rfaeve7nhysaZli o03',th-phi a Hoag. et Kohis, tick (Ixodoldea, Ixodldea) bythe migratory bird Tuzdus a~u=a Lath. Zoologiche-skl shurnal, v. ig4, no. 9, 1965, 11411-11412. JPRS

62. Poteiyevskiy, E. G., at' L. A. Vereta. ,o-oDlement-fixa-tion dynamics of TBE antigen in sera cf Infectedanimals. Vop-osy virusologk1, lj, 196 , 494,

63. Priymyagi, L. S. Efffect of interferon on RES cell linesinfezted with TBE v.-rus. Voprosy vfrusCi 1, no. 2,1965, 225-226.

64. PrOt&5, I. I., and V. I. Notyakov. Clinical fonm ofalte and tick encephalitis In Belorssia. Zhuraalnevr tolo 1. psikhiatrII, v. 65, no. 3, 1965,

65. Romanova, L. N., A. T. Kravchenkoand I. G. Vasil'yeva.Pathogenesis of allergic complications due to viruses.Report 1. Development of infection In mice givenrepeated sublethal doses of fixed rables virus.Voprosy virusologii, no. 4, 1965, 430-435.

66. Salganik, R. N., and A. A. Trukhachev. Effect of DNA-as* on the aultiplication of adenoviruses in tissueculture. IN: Akademiya nauk SSSR. Sibirioeotdelenlye. Izvestlya. Seriya biologo-meditsinskikhnauk, no. 8, v. 2, 1963, 99-101.

67. Savenko, S. N. Relation of multiple sclerosis andacute encephalomyelitis epidemics. Zhurnal nevro-patologii I pslkhlatrii, v. 64, no. 3, 1964, 360.

68. Semenov, B. F. Multiplicat on of TBE-type viruses inchick-fibroblast cultures. Voprosy vIrusologil,v no. 2, 1964, 169-173.

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69. Serov, i.;. 2. Abortion virus of sheep. IN: Orlov,F.M1., comp. Virusnyye bolezni zhivotny!kh (Virusdiseases of animals). Moskva, Sel'lkhozizdat, !963.

70. Shashayev, M. A. Biological characteristics of plaguebacteriophages. IN: Zhurnal mikrobiologilepidemiologii I immunobiologii, no. 12, 1964, 32-35.

71. Schramek, S., V. Mayer, and S. Zemla. Oxygen uptakeand aerobic glycolsis of human cells persistantlyinfected with tickborne encephalitis. Acta viro-logica, v. 6, no. 3, 1962, 295.

72. Semenov, B. F., G. i. Stepanov, E. E. Rozina, Yu. Z.Gendon, B. I. Chernos, and Ya. Ye. Khesin. Viruseswhich effect albino mice similar to TBE virus.Voprosy virusologii, no. 2, 1964, 169-173.

73. Sergeyev, V. A. Effect of various conditions on repro-duction of virus in trypsinized swine spleencultures. IN: Voprosy veterinarnoy virusologii(Problems of veterinary virology). 14oskva, Kolos,1964, 242-247.

74. Sergeyev, V. A. Infectious rhinotracheitis of cattle.IN: Orlov, F. M., comp. Virusnyye boleznizhivotnykh (Virus diseases of animals). Moskva,Sel'khozizdat, 1963. 264-275.

75. Sergeyev, V. A. Mucous-membrane diseases of cattle.IN: Orlov, F. M., comp. Virusnyye boleznizhivotnykh (Virus diseases of animals). Moskva,Sel'khozizdat, 1963. 275-285.

76. Segeyev, V. A. Viral diarrhea of cattle. IN: Orlov,F. M., comp. Virusnyye bolezni zhivotnykh (Virusdiseases of animals). Moskva, Sel'khozizdat,1963. 285-293.

77. Shcherbatykh, P. Ya. American infectious equineencephalomyelitis. IN: Orlov, F. M., comp.Virusnyye bolezni zhivotnykh (Virus diseases ofanimals). Moskva, Sel'khozizdat, 1963. 169-175.

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73. $htanni:.v, Ye. V. PUrification of virus-cont-aminatedI-,ate-, L-~ neans- of o-::L' o1~es Gir f:'enai scnitajvi.-a, no.1, ,

79. Shukeyr, A. A. Pathomorphology of experimental rabiesin laboratory animqals infected with a Fleury strainadapted to chick embryos. Voprosy virusologii, no.5, 1963, 568-574.

80. Shvarev, A. I. Spinal and radicular forms of lympho-cytaric choriomenerigitis. Zhurnal nevropatologiii psikhiat:,.ii, no. 9, 1964, 1290-1294.

81. Skalinsi'd-, Ye. I. Subricroscopi%- nhanges caused bypigeon-pox virus. * ;7: Vopros y vet erinarnol:virusol-n-ii (Problei s c1 veterinary virology).lios'.tita, iZolos, 1064. 431 44.

82. Smorodintsev, A. A. First page in virus study. Naukai zhizn', no. 12, 1964 52

8.. Solov'yev, V. D. So~ne results ofstudies in antiviralimmunity of tissue. Vop~rosy, virus-Ologii, no. 5,.1964, 580-587. JP.RS 27714

84. Solov yev., V. D. Transformation capacity of wild andlaboratory strains of vaccinia.Voprosy virusologii,[. no. 3, 1965, _307-315.

85. Stancek, D. Relationship of tickborne encephalitisvirus to L-cells. Acta. virologica, vt. 7, no. 3,1963, 225-232.

86. Strogot, A. K. Epizootic cattle fevers (bovineinfluenza). IN: Orbit, F. M., comp. Virusnyyetolezni zhivot-lykh (Virus diseases of animals).Moskva, Sellkhozizdat, 1963. 242-246.

87. Strogov, A. K. Blue tongue ofT sheep. IN: Orlov,iF. N., conip. Virusn-yye bolezni zhivotnyldh (Virusdiseases of animals), lMoskva, Sel'khozizdat, 1963,,2 46-264.

8.Sushkov, F. V., V. I. Ry abcv, n .I1 apvK Response of tissue cultures to X-rays followingviral infection. IN': Vo1prosy veterinarnov viruso-losii (Problems of vete-rinary vircloE-y.m~os1Kva,Kolos, 19'4. -67-71,

: 89. Svet-Moldavsi~ly, G. Ya. Historical study of Far-EastTBE. Voprosy virusoloGii, no. I, 1965, 9_0 .

90. Terskikh, I. I., anC G. D6. Zairov. Comparative studyof trachoua and ornithosis viruses. Voprosy viruso-logii, no. 6, 1964, 674-677.

91. Tsion, R. A. Scotland sheep encephalomiyelitis. IN:Orlov, F. I.I., corip. Virusnyye bolezni zhivotny:.hkVirus diseases of animals). Moskva, Sell IhozizCit,1963. 293-300.

92. Tsion, R. A. St:ine influenza. IN: Orlov, F. M., comp.Virusny-e bolezni zhivotnykh (Virus diseases ofanimals). Moskva, Sel'khczizdat, 1963. 506-513.

93. Vasilenko, V. A., and P. N. Kosyakov. Is there a rela-tionship between inherent and acquired immunereactions of the organism to a virus infection?Voprosy virusologii, no. 1, 1964, 78-82.

94- Vigovskiy, A. I. The isolation of a TBE group virusfrom a patient in the west Ukraine. Voprosyvirusologii, no. 2, 1964, 163-166.

95. Votyakov, V. I., and T. I. Lemeshevskaya. TBE in Belo-russia. Comunication 2. Cultivation of Belo-russian strains in cell cultures. Voprosy viruso-logii, no. 5, 1964,, 6o8-614.

96. Yelkin, I. I., and V. K. Yashkul'. Zhurnal mikro-biologii, epidemiologii I immunobiologii, no. 1,1965, 91.

97. Yelkin, I. I., and V. K. Yashkul'. Problems of epidemio-logical geography. Report four. Zonal regional andresidual nosological areas of disease. Zhurnalm1krobiologii, epidemiologli I immunobologii, no. 2,1965, 73-80.

98. Yelkin, I. I., and V. K. Yashkul'. Epidemiologicalgeography problems. Report five. Factors condition-ing the geographical distribution of causative agentsof natural focus zoonozes. Zhurnal mikrobiologii,epidemiologli I Immunobiologil, no. 10, 1965, 116-124.

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99. Yelkin, 1. 1., and V. K. Yashkul. Problems of epidemio-logical geography. Part four. Formation of noso-logical areas of the zoonoses with natural nidality.Zhurnal mikrobiologii, epidemiologii i irniunobio-logii, no. 12, 1965, 70-78.

100. Yershov, F. I., V. M. Zdanov, and A. A. Tsarenva.Reproduction of Venezuelan equine encephalomye-litis virus in cells treated with actinomycin.Antibiotiki, no. 3, 1965, 250-255.

101. Zalkind,, S. Ya., et al.. Morphological and cytochemi-cal studies of the effects of tickborne encephali-tis virus on tissue culture cells. Acta virologica,v. 6, no. 5, 1962, 447-4~51.

102. Zasukhina, G. D,, and I. A. Rapoport. Effect of chemi-cal mutagenic fLlactors on the TBE virus. Communica-tioui I. Variability of TBE virus under the influ-ence of 5-tromouracil and l,4-bis-diazoacc-tylbutane.IN: Materialy II nauchnoy sessii Instituta. polio-miyelita i viruanykh entsefalitov ANN SSSR, Moscow,1964, 46.

103. Zhdanov, V. M., N. B. Azadova, and A. G. Bukrinskaya.Study of interaction of Sendai virus with tissuecultures by the fluorescent-antibody method.Voprosy virusologii, no. 2, 1962, 162-167. JPRs19625

104. ZI:Qarov, M ±.,I. A. Li-i;i,.a ... m.e~:,zncL.Ya, --itell s1a:-a. Sci..e p ar ar e'1erz -C.endai

virus nucleocaspici. Vcjp;o y viuoo iG. l 4,

Pcl1';::trcnic Ccvo.~ C~a 2~ Yp.-Csyvirus1. 1 i. ,~

106. Zhdanov, V. M., and F. I. Yershov. Actinomycin D as anin vitro dye and fluorochrome. IN: Alcademiya naukSSSR. Doklady, v. 162, no. 4, 1965, 932-933.

107. Zhdanov, V. M., L. A. Mel'nikova, I. A. Kozlova, 1. G.Balandin, 0. P. Peterson, and L. Masharina. Sup-pression of synthesis of smallpox vaccine virus byhistone. IN: Akademiya nauk SSSR. Doklady, v.165, no. 5, 1965, 1182-1183.

108. Zhimatov, Kh. Zh. Problems of biosynthesis of viruses.IN: Akademiya naul Kazaknsicoy SSR. Vestnik, no. 5,1962, 10-19. JPRS 15188

109. Zhumatov, Kh. Zh. Contemporary data on the molecularstructure of viruses. IN: Akademiya naukKazakhskoy SSR. Vestnik, no. 3, 1965, 28-39.

110. Zinshenko, A. P. The problem of the role of rabiesvirus in the etiology of multiple sclerosis andencephalomyelitis. Zhurnal nevropatologii ipsikhiatrii, v. 65, no. 11, 1965, 1634-1641.

111. Zubshitskiy, Yu. N. Study of the distribution of pro-eins of alien origin in a human nonimmune organismand the possible duration of their stay by the lum-inescent-antibody method. IN: Akademiya nauk SSSR.Doklady, v. 155, no. 1, 1964, 234-237.

112. Zverev, P. I. Malignant catarrhal diseases of cattle.IN: Orlov, F. M., comp. Virusnyye boleznizhivotnykh (Virus diseases of animals). Moskva,Sel'khozizdat, 1963. 231-241.

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AP>EJDTx ii.REPORTS OF CONFERENCES ON VIRAL DISEASES HELD BETWEEN 1962AN]) 1965 AND THEIR PARTICIPANs

±.Baroya:, 0. V. Summary report of the Presidium of theAcademy of Medical Sciences, USSR. IN: Akademiyameditsinskikh nauk SSSR. Vestnik, no. 4~, 1964, 6.

2. Selikov, G. P. Local application of antibiotics.Subject discussed at the Conference on the Use ofAntibiotics held in Moscow 1963. Antibiotiki, no.5, 1964, 471.

3. Belikov, G. P. Conferenee of the Presidium of the I. I.Mechnikov All-Un,-ion Scientific Medical Society ofEpidemiologists Microbiolo ists and InfectiousDiseases Specialists held 8 October 1965. IN:Akademiya nauk Kazakhakoy SSR. Veatnik, no. 9, 1966,150.

4. Bychlcova, M. V. Seventh Joint Scientific Session of thePoliomyelitis and Viral Encephalitis Institute of theSoviet Academy of Medical Sciences and the Byelo-russian Institute of Epidemiology Microbiology andHygiene devoted to a discussion of the problem oftickborie encephalitis. IN: Akademiya meditsinskikhnauk SSSR. Veatnik, no. 1, 1964, 89.

Pariciants Chuinakov, M. P., Gilmanova, G. Kh.,Gocacosya N. N., Karpov, S. P., KarpovicPanov, A. G., Pivanova, G. P., Robinson, I. A.,Rzhakhova, 0. Ye., Sarmanova, Ye. S., Serjeyeva, G. 1.Shalunova, N. V., Smorodintsev, A. A., Stepanova,Le G., Vereta, L. A., Votyakcov, V. I., Zasukhina, G. D.

5. Kats, L. N. Problems of biology and medicine discussedat the Thirteenth All-Union Conference on Lumines-cence held in Kharkcov from 25 June to 1 July 1964.IN: Akademiya nauk SSSR. Izvest±ya. Seriya bio-logicheskaya, no. 2, 1965, 319.

6. Kats, L. N. The Sixth Session of the Inter-departmentalScientific Methodological Commission on AnthraxControl held In Moscow 12--14 March 1964. Zhurnalmikrobiologii, epidemiologiLi I immunobiologii, no.2, 1965, 156.

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7. Veber, L. G. Proceedings of the Second ScientificPractices Conference devoted to the activities ofsanitary epidemiologic centers of Sverdlovsk and itsenvirons. Gigiyena i sanitariya, no. 7, 1964, 124-125.

8. Yerkhov, I. S. Joint Scientific Session on Vascular andinfectious Diseases of the Nervous System held 9--12December 1964 In Sverdlovsk. Zhurnal nevrcpatologiiI psikhiyatrii, v. 66, no. 5, 1966, 791-792.

9. Fourteenth All-Union Conference of Epidemiologists andMicrobiologists and infectious Disease Specialistsheld in Moscow from 29 June to 4 July 1964. Zhurnalmikrobiologil, epidemiologii I immunobiologii, no. 12,1964, 3.

Participants: Alisov, P. A., Belikov, G. P., Sokolov,M.7., TimaIkov, V. D., Vashkov, V. I., Yelkin, I. I.

10. Ninth Scientific Session of the Poliomyelitis Institute.Voprosy Virusolcgii, no. 1, 1965, 121-'26.

11. Seventeenth Scientific Session of the Institute ofVirology im. D. I. Ivanovskiy of the Academy ofMedical Sciences, USSR. Voprosy virusologii, no.1, 1965, 119-121.

12. Zeytlenok, N. A. Poliomyelitis and other enterovirusdiseases. IN: Akademiya meditsinskikh nauk SSSR.Vestnik, no. 3, 1964, 94-96.

In 1963, the Eighth Scientific Session of theInstitute of Poliomyelitis and Virus Encephalitis ofthe Academy of Medical Sciences, USSR, was held inMoscow. Four hundred and thirty-nine scientistsfrom 45 cities in 14 Soviet republics, 21 scientistsfrom seven Communist countries, and two Americanvirologists participated in the session.

The conference dealt with problems of eliminatingpoliomyelitis, poliomyelitis-like diseases, non-pollomyelitic enteroviruses, latent oncogercviruses, the Impro ement of live pcliomyelitisvaccine, the nature of viruses, and their relation-ships with the cell. Twenty-six reports and talkswere given on the study of the nature of diseases

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observed after mass immunization similar to themild forms of poliomyelitis and expressed in theform of a brief paresis of the lower extremity, notuncommonly reco:rded under the clinical diagnosis of"poliomyelitis" or "myelitis." The Session indicatedthe need for investigators to concentrate theirattention on determining the nature of the flaccidpareses of undetermined etiology from the viewpointof the possible role of Coxsackie A viruses,adenoviruses, new, still unknown viruses, as well asagents or factors which are not viruses. Serologi-cal studies with Coxsackie A virus strains adaptedto tissue cultures, with antigens of other entero-viruses as well as adenoviruses, should be carriedout on a broader scale and, depaending on theresults of the investigation of paired sera, methodsof isolating the viruses in suckling white miceshould be used.

The Session recommended that the Ministry of Health,USSR, record and take into consideration the polylo-myelitis-like cases as "flaccid paresis of undeter-mined etiology." It is essential that in the caseof these diseases as well as in cases suspicious ofpoliomyelitis, clarification of the diagnosis witha final recording of the diagnosis be made by commis-sions of authoritative specialists consisting ofneuropathologists, specialists on infectious dis-eases, virologists, and epidemiologists. The Sessionalso considered it necessary to organize qualifiedvirological and serological studies in every caseof a disease suspicious of poliomyelitis as well asof all cases of flacid paresis of undeterminedetiology.

The Session indicated the expediency of 1) deter-mining the list of laboratories which can performthe necessary and adequately qualified virologisaland serological studies for poliomyelitis, the ECHOviruses, and Coxsackie viruses; 2) dividing theterritory of the USSR into regions, assigning themto the nearest virological laboratories accordingto the list mentioned, and in the absence of suchlaboratories, assigning them locally to the labora-tories of large central institutes; 3) giving aid tothe laboratories in the matter of equipment, and thecreation of the required conditions for carrying outthe work on the necessary scale.

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At the Session. 48 reports were presented on theproblem of nonpoliomyelitis enteroviruses and thediseases which they cause. A study was made ofdifferent types of interaction of enteroviruseswith one another and in combination with infectiousdiseases In human beings and animals, and processesof variation of Coxsackie A viruses on their adapta-tion to different tissue cultures.

Seventeen reports presented the results of a complexstudy of iatent tumor viruses, chiefly the OV40virus (simian vacuolating), which can be found invirus vaccines. Frequent infection of Macacusrhesus monkeys with the OV40 virus was determinedand frequent infection of monkeys of other specieswas also found when they were kept together withMacacus rhesus.

Twenty-six reports and talks were given over to theimprovement of live poliomyelitis vaccine, and 24reports on new data were presented and discussed onthe nature of the viruses and their interrelationswith the cells. The other reports were on problemssuch as the study of distinctive inhibitors of virusactivity, formed in cultures of transplantablestrains of cells free of viruses. These reportsaroused great interest.

The Conference noted the great importance of theo-retical studies presented in the field of geneticsand physiology of viruses and experimental chemo-therapy and recommended the further development ofwork along these lines, particularly on the studyof the intracellular processes of virus multiplica-tion and the biosynthesis of their components.

13. Levkovich, Ye. N. Seventh Joint Scientific Session ofthe Institute of Poliomyelitis and Virus Encephali-tides of the Academy of Medical Sciences, USSR, andthe Belor-issian Institute of Epidemiology, Micro-biology and Hygiene on tickborne encephalitis andother arbovirus diseases. IN: Academiya meditsin-skilkh nauk SSSR. Vestnik, no. 1, i964, 89-90.

In 1963 the Seventh Joint Scientific Session ofr the

Poliomyelitis and Viral Encephalitis Institute ofEpidemiology, Microbiology, and Hygiene sponsored adiscussion of the pioblem of tickborne encephalitis

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and other arbovirus diseases which was held InMinsk. Representatives of scientific Institutionsof 28 cities in the USSR as well as scientlists fromCzechoslovakia, a total of 181 participants, tookpart in the Session. One hundred and twenty-fourreports were given on problems of differentiationand classification of viruses of the tickborneencephalitis group, new methods of studying arbo-virus diseases and problems of epidemic-controlmeasures, as well as data on the distribution ofother arboviruses on the territory of the SovietUnion.

Reports of the following Soviet scientis were pre-sented: M. P. Chumakov, L. G. Karpovich., Ye. S.Sarmanova, G. I. Sergeyeva, M. V. Bychkova, V. 0.Tapupere; and from Bratislava, Czechoslovakianscientists Ye. 0. Libkova, V. Mayer, R. Rzegacek,0. Kozukh, and E. Eriek concerning the isolation ofvirus strains different from the viruses of the tick-borne encephalitis isolated in Kemerovskaya oblast'from ixodes persulcatus ticks from sick persons withsymptoms of an undetermined fevrile illness. It wasdetermined that these strains are distinctly differ-ent from the viruses of the tickborne encephalitisgroup with respect to their behavior in tissue cul-tures, their range of pathogenicity for animals, andin their antigenic structure. The fact that thestrains isolated were arboviruses was substantiated.On a comparative study of these strains with differ-ent serological groups of other arboviruses, thecharacteristics of the isolated virus, which theauthors called the "Kemerovskiy virus," were demon-strated. The finding of antibodies to this virus inthe blood sera of human beings and animals in theregion where the virus was isolated makes it pos-sible to suppose that it has a possible role inhuman pathology and that it circulates in nature.

In reports of Ye. N. Levkovich, V. I. Votyakova,V. V. Pogodina, 0. Ye. Rzhakhova, I. A. Robinzon,and others, the possibility was shown of isolating,as individual species, the viruses of Far Easternand Central Europeam encephalitides, Scotish encep-halitis, Povassan, Omsk hemorrhagic fever, Kyasanurforest disease, and the Malayan virus (Langat).

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On problems of the selection of attenuated strainsof tickborne encephalitis, a number of reports andcommunications were given by L. G. Stepanova, G. D.Zasukhina, V. I. Mayer, Ye. 0. Libikova, P. I.Al' brekht, and M. K. Tyushnyakova. Data were pre-sented on obtaining strains off the tickborne encep-halitis virus with attenuated nervous system viru-lence. A lively discussion revolved about thecriteria characterizing attenuation of strains andpossibiolities of utilizing the latter as a livingvaccine. V. i. Il'yenko and A. A. Smorodintsevreported preliminary data on the testing of theimmunogenic characteristics and side-effects pro-duced by the live vaccine against tickborne encep-halitis, prepared from the Malayan virus (Langat).

In the reports of V. I. Il'yenko, A. D. Al'tshteyn,N. V. Shalunova, A. G. Karpovich, Ye. N. Levkovich,and others, on the topic, "New Methods of Studyingtickborne encephalitis," the studies dealt withthe phenomenon of interference, the use of culturesand tissue, the hemagglutination-inhibition test,and others. It was shown that the interferencephenomenon can be used for the demonstration intissue culture of viruses which do not exert a cyto-pathogenic effect, for the titration of viruses, andfor the determination of antibodies in blood sera.The accumulation of interferon in the tissue culturewas noted.

A series of reports was given on the utilization ofthe cytopathogenic effect of the virus, immunofluo-reacence, the diffusion-in-gel test, plaque forma-tion, and the hemagglutination-inhibition teat byV. I. Votyakov, G. I. Sergeyeva, P. K. Al'brekht,Han Shih-Tse, P. S. Karaseva, N. V. Loginova, R. G.Desyatskaya, G. P. Pivanova, S. P. Karpov, L. A.Vereta, L. G. Karpovich, 0. Ye. Rzhakhova, andothers. Achievements in the field of applying tis-sue cultures to the study of tickborne encephalitiswere presented. New serological methods, particu-larly the hemaglutination-inhibition test, havebecome extensively used in the practice of labora-tory, clinical, and epidemiological research. Theimprovement of antigens for the hemagglutination-Inhibition test as well as methods for eliminatingnonspecific Inhibition from them have been suggested.

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A. A. Smorodintsev and S. A. A. Ananyan reportedthe use of the hemagglutination-inhibition test forthe serological demonstration of arbovirus diseases,which made it possible to detect the existence ofpreviously unknown foci of arthropod-borne diseasesof group A, C, and Buniamwer (after Casals) in theterritory of the USSR.

A comprehensive s l ;udy was made of the mechanism ofthe circulation of the virus during the period ofactivity of ixodial ticks and outside of the periodor the blocoenotic relationships of the tilckborneencephalitis virus by zoologists, parasitologists,and virologists L. P. Nikiforov, Yu. A. Morozov,V. A. Bouko, L. A. Vereta, and others. Successfulwork was accomplished in controlling tickborneencephalitis through the utilization of the char-acteristic features of landscape types of foci forepizootological and epidemiological prognoses. Dataon the study of the natural foci of tickborne encep-halItis in various geographic regions of the SovietUnion were obrained for Belorussia, the Ukraine, theUrals, Siberia, the Far la.t, Tatarskaya ASSR,Udmurtskaya ASSR, and others by V. I. Votyakov, L. V.Gromashevskly, G. I. Netskiy, L. G. Tatarinova,G. Kh. Gil'manova, A. V. Mishin, V. I. Chabovskiy,and others.

The clinical aspect of the problem of tickborneencephalitis and the tendency toward tickborneencephalitis evolution as a clinical phenomenon waspresented in a review report by A. G. Parov, aswell as in reports of A. I. Shapoval, K. G. Umanskly,R. N. G.xariy, and ,thers. The differentiation ofEastern and Western variants of tilckborne encephal-itis, reflecting the clinical characteristics andcharacteristics of the course of the disease, wasconsidered sufficiently substantiated. It wasrecommended that the route of Infection - arthropod-borne or alimentary - be formulated in the diagno-sis. Attention was called to the need for seekingout new, more effective methods and means of therapy.

In a report by D. K. L'vcv and others, data on theextensive testing of cultured, inactivated vaccineagainst tLickborne encephalitis were presented,

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Epidemiological observations and serological exper-iments have shown that it produces no aide effectsand that It is highly effective immunologically.

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APPENDIX III.SOME SOVIET VIROLOGICAL RESEARCH INSTITUTES AND THEIRPERSONNEL

Introduction

The numerous Soviet institutions involved in viro-logical research range from small stations or field hospitalsdealing with specific problems to institutes covering theentire field. The latter perform the important researchand publish most of the scientific materials on the subject.All-Union institutes also carry out studies directed towardpolicymaking and serve as advisory bodies to the Ministryof Health, USSR; the main virological institute in eachSoviet Republic performs a similar function. Usually thecentral institute dces research work and coordinates thestudies of sanitation stations, public-health centers, andfield hospitals. Among the leading institutes in Moscoware the D. I. Ivanovskly Institute of Virology; Academy ofMedical Sciences, USSR; the Institute of Poliomyelitis andViral Encephalitis, Academy of Medical Sciences, USSR; theInstitute of Epidemiology and Microbiology, Ministry ofHealth, RSFSR; and the Scientific Research Institute ofViral Preparations. Institutes in Leningrad include theInstitute of Experimental Medicine, Academy of MedicalSciences, USSR, and the Medical Institute of Sanitation-Hygiene; the Institute of Medicine and the Institute forthe Advanced Training of Physicians are located in Kiev.

The following is a list of institutions which areengaged in virological or closely related research.Affiliated scientists are listed under each insticution,along with any available information on their professionalqualifications, positions, and honors conferred itpon them.

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SOME SOVTr VTROT/)GTCAT. RESFARCH TNS'PTMT FES A"D T ETPERSONNEL

All-Union Scientific Research Chemical2-PharaceuticalTnstitute im. . Ko Ordzhonikidze

Relikov, fl. P. Katunina, V. T.JDaniyelyan, N. M. Pershin, n. w.

All-Union Scientific Research Tnstitute of Railroad Wy-giene, Ministry of Railroads, USSR

Ametirova, M.N. Kozina, '. P.Dubrovina, .. Kulinkova, W. X.Fayershteyn, S. G. Parkhomenko, T. M.Kazakovtseva, Ye. T). Sokolova, N. N.Koral'nik, B. P.

All-71nion Scientific Research Tnstitute of VeterinaryVirology and Microbiology Ministry of Agriculture,TTSSR

"1olosov, V. M. Sergeyev, V. A.Nikitin, Ye. Ye. Syurin, V. N.Pozdnvakov, A. A. Vladimirov, A. 4.

Belorussian Scientific Research Tnstitute of Epidemiologyand Microbiology

Dirt Votyakov, Veniamin Tosifovich (specialty:virology). Doctor of Medical Sciences; Professor;Director of the Belorussian Scientific ResearchTnstitute of ERidemiology and Microbiology. Nomi-

nated for corresponding mebership in the Academy ofMedical Sciences, TTSSP by the academic councils ofthe Aelorussian Institute of T'idemiology and micro-biology: the Relorussian Society of Epidemiologists,Microbiologists, and Tnfectious nisease Specialists;the ministry of lTealth, Relorussian SSR, and theAll-Union Scientific Medical Society of Eoidemiolo-gists, Microbiologists, and Infectious DiseaseSpecialists im. I. I. Mechnikov.

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Protas, T. 7.

Central Asian Scientific Research Antiplague Tnstitute,Alma-Ata

Shashayev, m. A.

"ientral Trnstitute for Advanced 'Praining of Physicians ofthe Academy of Medical Sciences, TTSSR

TBektimirov, r". A. Sarayeva, 'N. T.*autikina, A. V. Sokicar, T. *4Vatyukova, vui. N. Varoslavskaya, N.Sumarokov, A. A.

Central Scientific Research Tnstitute of Epidemiology,ministry of Realth, UJSSR

Pille, E. R.

Control Institute for medical and 'Riological Preparationsim. L, A. Tarasevich.

Al'tshteyn, A. D. Kravchenko, A. T.

Donetsk Province Sanitary Epidemiological Station

Anishchenko, G. A.

norki Scientific Research Tnstitute of Boidemiology andmicrobiology

flir- 1. N. Blokhina

ivogicheva, M. A.

Institute for Advanced Training of Physicians. Kiev.7 halko-Titarenko, V. P.

C C'

Insti.tute of Fdemiology and Microbiology. Kiev.

Dyadichev, N. R.

institute of Eoidemiology and Microbiology im. N. F.Canalei of the Academy of Meuical Sciences, USSR

Al'tshteyn, A. D. Ketiladze, Ye. S.Ava:n, A. A. Kirillova, F. M.Fedorov, Yu. B. Mayorova, G. G.Kats, L. N. Mirolyubova, L. V.Kaulen, D. P. Pavlova, I. B.

Solov'yev, Valientin Dmitriyevich (speci-alty: virology). Corresponding Member of the Aca-demy of Medical Sciences, USSR; Docto2 of MedicalSciences; Professor; State Prize Winner; Head ofthe Section of Virology, Institute of Epidemiologyand Microbiology im. N. F. Gamaley of the Academyof 1edical Sciences, USSR; Head of the Chair ofVirology, Central Institute for Advanced Training

of Physicians. Nominated for active members'hipin the Academy of Medical Sciences, USSR, by theacademic councils of the Institute of Epidemiologyim. N. F. Gh.aaley of the Academy of Medical Sciences,USSR, Central Institute for Advanced Training ofPhysicians of the Academy of Medical Sciences, USSR,Institute of Poliomyelitis and Viral Encephalitisof the Academy of Medical Sciences, USSR, Instituteof Virology im. D. I. Ivanovskiy of the Academy ofMedical Sciences, USSR, and the Board of the All-Russian Society of Epidemiologists, Microbiologists,and Infectious Disease Specialists.

Institute of Experimental and Clinical Oncology, Academy

of Medical Sciences, USSR

Dir: A. I. Serebnov

azurenko, Nikolay Petrovich (specialty: virology)Doctor of Medical Sciences; Head of the Laboratoryfor Pathology of Leukoses, Institute of Experimentaland Clinical Oncology of the Academy of MedicalSciences, USSR. Nominated for corresponding mem-bership in the Academy of Medical Sciences, USSR,by the academic councils of the Institute of Exper-

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irnental and Clinical Oncology of the Academy cf INeci-ical Sciences, USSR and the Board of' the All-UnionScientific Medical Society of Epidemiologists, '.ic-

roiloit, ana Infectious Disease Specialists 4m.I. I. Mechnilkov.

Institute or Medical Parasitolg-,y and Tropical Medicine,Ministry of Health,, USSR

Naumov, R. L. Pospelcva-Shtcrm, M.. V.

Institute or Medical Radiolomy of the Academy or Medical

Sciences, USSR

Dir: G. A. Zedgenidze

Cherkasov, V. F. - Manager or Scientific MethodsDepartment

Chermyakhovskaya, A. K.Filatcv, P. P.Yelashov, Yu. G.

Institute or Zoolo-y and ParasitologyAaeyo cecs

Uzbek SSR

Lakhanov, Zh. L.

Institute or Poliomyelitis and Viral Encephalitis or theAcademy or Medical Sciences, USSR

Dir: Chumakov, M. P.

Agol, V. I. Karxiysheva, V. Ya.Al'tshteyn, A. D. Karpovich, L. G.Avakyan, A. A. Khanina, M4. K.Bannova, a. G. Khan Shi-tszeBychkova, 11. V. Levina, L. S.Gnuni, 1. 1.. Levkovich, Ye. N.Qagarina, A. V. L'vov, D. K.Gavrilovskaya, I. N. Malygina, I. G.Gol'dfarb, L. G. Pistsov, N. G.Iyks, S. R. Pogodina, V. V.Kalinina, L. I. Rodini, I. M.

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Sarmanova, Ye. S. Shoshiyev, ..Selimov, M. A. Svet-IMoldavskayat, I. A.Sergeyev, N. N. Svet-l',oldavskNiy,, G. Ya.Shaluno-a, 1. V. Tsilinskiy, Ya. Ya.Shirman, G. D. Vil Iner,. L. N

Volorshiiova, Marina Konstanti~iovna (speci-alty: virology) Doctor of' 1Nedical Sciences; Professor;Head of' the Section of Poliomyelities and EntervoviralInfections, Institute of' Poliomyelitis and Viral En-cephalitis of' the Academy of Medical Sciences, USSR.Nominated for corresponding membership in the Academyof' Medical Sciences, USSR, by the Council of- the In-stitute off Poliomyelities and Viral Encephalitis ofthe Academy of Medical Sciences, USSR.Yan Zhu su Zaklinskaya, V. 1

Institute of Virology, Czechoslovak Academy of' Sciences.Bratislava.

Albrecht, P. Link, F.Blaskovic, D Mayer, V.Brawler, I. Hada, B.Jakubik, J. Sadecky, E.Jasinska, St. SktOda, RI.Lesso, J.

Institute of Virology im. D. I. Ivanovskdy of the Academyof Medical. Sciences, USSR

Dir: V. M. Zhdanov - Corresponding Member of theAcademy-of Medical Sciences.. USSR

Bekieshova, A. Yu. Gaydamovich, S. Ya.Beletskiy, V. D. Gltel man, A. K.Berezina, 0. N. Gorshunova,. L. P.Bukainskayal A. G. Gromykov, A. I.flurducheva, 0. KantoroviCh, R. A.Buzinov, 1. A. Kareva, 1M. 11.1Bycbkova, Ye. N. Kaverin, N. V.Chervonskiy, V. I. Ketiladze, Ye. S.

Thitriyeva, R. A. laisenko, G. A.Dox-midcntov, R. V. Konovalov, G. V.Preyzin, R. S. Kosyakov, P. N.Feklisova, L. V. Kozlova, 1. A.

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Kozlykova,~ 1.Parfanovich, Il. I.Kurbanov, 1. A. Peterson, 0. P.L. Y u -, Popova, 0. A..Lip::ind, I.I. A'. Posevaya, T. A.E*ariaryan, it. G. Priyr.,a:-j, L. S.iEecvedeva, G. 1. Razularahcva, E~. B.iie:ler, L. B. ovnova, Z. l.iMelni.cva, L. A.* Ryutova, V. P.iioroz, A. G. Sergeyenko, A. D.Naumlova, V.* K. Shen, A.Obukhovskaya, N. 11.

Shubladze, Antonina Konstantancvna (speci-alty: virology) Doctor of- Medical Sciences; Professor;State Prize !-,.'nner; Head of the Laboratory of Coin-p :rative Virol:)gy, Institute of Virology in. D. 1.Ivanovskiy of the "'ca6e-l.Y of Mecf-cal Sciences, USSR.io-minated for corresooneinc, membership in the Academy

of: iNedical Sciences, USSR~, by the academic councilsof the Institute o41 Virology in. D. I. Ivanovskiy of,tE.he Acadeui~v of edical Sciences, USS.D, of the InstCi-tute of Eoidemiologyr and 1-licrbiology im. N. F.Garmal ey of the Aca-demy of Medical Sciences, USSR,and by the Board ofL the All-Union Scientific MedicalSciety of Epide:.niologists, Microbiologists,, andInfcectious Disease Specialists im. I. 1. Mechnikov.Shuk.eyr, A. A. Sivoshinskiy, D. S.

Sokolov, M~ikhail Ignat yevich (specialty:virology) Dcoctor of Medical Sciences; Professor;Head of the Section for Flu Prevention; Head of theLaboratory of Viral Genetics, Institute of Virologyim. D. I. Ivanovskiy of" the AcademY of iledical Sci-ences, USSR. Nominated fLor corresponding member-shipin the Academy of Vledical Sciences, USSR, by theacademic councils of the institute of Virology i.D. 1. -,vanovs*-iy of the Academ~y of' Medical Sciences,

USS, of the Kazakh Institute of Epidemiology, Micro-biology, and Hygience, and b-. the Boards of the All-Union and Kazak~h S-cientific Societies of Eoidemiolo-gists, IMicrobiologpists, and Infectio-us Disease Speci-alists. Also nominated by P. G. Sergiyev, V. D.Ti-makov, P. F. Zdrodovskiy, and A. A. Smorodintsev(Active M.,ember of the Acadeway of Medical Sciences,USSR, and !Gi. £Clh. Zhumatov (Corresponding I'ein'cer ofthe Academy of Medical Sciences, USSR). CSpitsyna, L. N. Titiova, N. G.SIta kha nova, V. 1k;. Tsareva, A. A.Te.-skikh, I. 1. Tsi T'-'.an I -ma o

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Vagzhanova, V. A. Yankevich, 0. D.Vanag, K. A. Yershov, F. I.Vasilenko, V. A. Zairov, G. KVlodavets, V. V. Zakstel'sllaya, L. Ya.Vorkunova, G. K. Zhantyueva, Ye. M.

Kaluga Province Division of Public Health

Kobzar', I. S. Yavrumov, V. A.

Khabraovsk Antiplague Station

Kalmykova, A. D. Vasilenko, 0. G.Kraminskaya, N. N.

Khabarovsk Scientific Research Institute of Epidemiologyand Microbiology

Vereta, L. A. Yur'yeva, T. P.

Kiev Institute of Medicine

Dir: V. D. Bratus'

Suchkov, B. P.

Krasnodarsk Institute of Medicine

Babkin, P. S. L'vov, D. K.Lopatin, A. N.

Kuybyshev Institute of Epidemiology, Microbiology, andHygiene

Bukovskaya, S. N.

Leningrad Institute of Experimental Medicine of the Aca-demy of Medical Sciences, USSR

Smorodintsev, A. A. - Head Department of Virology

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Leningrad Sanitary Hygiene Medical Institute

Borisov, L. B. Yakovieva, G. S.

L'vov Institute of -Epidemniology, Microbiology, and Hygiene

Dir: A. I. StolniakOva

Urin, A. 1. i~ishko, Ya. G.Ionov, L. I. Lipkin, M4. Ye.Kolotilova, L. V.

Moscow Order of Lenin M*edical Institute irn. I. I'l. Sechenov

Ya~qhkul', V. K. Yellin, -I. -

-'-scow Provincial Sanitary BjxIdeniological Station

Spotarenko, S. S.

Moscow Scientific Research Institute of Viral Preparations

Dir: 0. Go Andzhaparidze

Bogonolova, N. N. Iilushin., V. N.Desyatskova, R. Go Neustroyev, V. DoDosser, Y. M. Rapoport, R. I.Gendon, Yu. Z. Rozina, N. Ye.Genkina. F. B. Semenov, V. F.Gurvich, E. B. Stepanova, L. G.Karaseva, P. S. Shutov, A. V.Kokovikhina, K. I* Unanov, S. S.Kolosov, V. 1. Varshaver, N. B.Levchnko, V. Do Yermakova, M. N.

Ma'sea N .Zalkind, So Ya.Marennmikova, S. S.

Odessa Set~entific Research Institute olf Epidemiology andMicrobiology im. I. I. Mechnikov

Diri "U. Zh. Zhumatov

Feoktisto?_, A. Z. Tokar', R. Go

Kondrashova, Z. N.

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Onsj% S~ientifkc Research institute of~ NaturallY Focalinf'ections, Ministry of Health, RSFSR

Fedorcva, T. N. Yegorova, L. S.Korsh, ?. V. Zakorkidna, T. f..Ravdcfisikas, 0. V.

Order of LUenin ilitary i.7edical Acade-iy jul. S. 1-1.. rv

Bashmakov, G. A. Tarascv, V. 14.

Perm Scientific Research Institute of 'Vaccines and Sera

I-11namyeva, V. 11,. Starodubt-seva, G. I.?zhenichncv, A. V.

?rimcr'e Territory Antiplague Station

SotUnikora, A. N.

Riga Republic Sanitary Epidemiological Station

Gromnova., Z. V. Marder, V. LoHarder,, B. B.

Rostov Sanitary EpidemiiologicaL Station

Perelatov., V, D.

Rostov Scientific Research Institute of Medical Parasi-tology

Kemarova, 0. N. Kvashnina, A. S.

Scienti1fic Research Institute of Epidemiology, Micro-biology and Hygiene. Kazan.

Gil'manova, G. o Livanova, I. A.Lapshina, G. N. Tuisheva, R. 1 1

Scientific -iesearch Inst1*Uute of" Epidemiiology and 41:icro-bioz-, of tL-he instrv of' 'Health*i, R&'-SR

Chernos, Gondon, Yu. ZGenni:ina, F. L.

Scientific_ -'esearch Ins.-tute of Vaccines and~ Sera -,;L.'T . iiechnikocv

1) r in sc GI ti Y;u masheva, .. A.RuEldtenko, A. A.

Turmenian Ean tiplague S3tation, institute of Zoology and?arasitolo&g.-, Academy off Sciences, Tauen SSR

Bel I shaya, G. S. Zagniborodcva, Ye. N.

Ukrainian Scientific Research Derratcvenereoogical, Institute

Bogdanova, 1-1. G. Liiiarenko, If.. I.K-1slyakova, L. rt. Tseraidis, G. S.

Vladivostok Institute of Epidemiology, M~icrobiology andHygiene

Somov, G. P. SoldatUov-, G. M.

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