joint cb technical data source book on tularemia (sr)

33
h \ b'" Gi AD RDTE Project No. l-X-6-65704-D-112 USATECOM Project No. 5-C0-473-000-020 DTC Project No. DTC-TR-73-Sirz E ,-toi N T S CB TECHNICAL DATA OURC E BOQJ( tUI i'/ /' - .22'/ UME VI Bacterial Diseases (U) Part 0ne: Tul.lremia (U) HEADQUARTERS ' DE5ERET TEST CENTER O FOFT DOUG '/-'t -'.a'i. - - ^1 \, o" II {\ t: -./ UTAH O 241_ /'/ 8+{13 ltli cL'\s$iI h N \ \0 t\ ,.{) 72-L365 copy

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Heavily redacted copy of technical data source book, a review of US biological warfare activity on Tularemia (UL, TT, ZZ) done during Cold War.

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Page 1: Joint CB Technical Data Source Book on Tularemia (SR)

h

\

b'" Gi AD

RDTE Project No. l-X-6-65704-D-112USATECOM Project No. 5-C0-473-000-020

DTC Project No. DTC-TR-73-Sirz

E

,-toi N T

S

CB TECHNICAL DATAOURC E BOQJ( tUI

i'/ /'- .22'/

UME VI

Bacterial Diseases (U)

Part 0ne: Tul.lremia (U)

HEADQUARTERS ' DE5ERET TEST CENTER O FOFT DOUG

'/-'t

-'.a'i. - -

^1\,o"II{\t:

-./UTAH O

241_/'/8+{13

ltli cL'\s$iI

hN\\0t\,.{)

72-L365

copy

Page 2: Joint CB Technical Data Source Book on Tularemia (SR)

I'NCI.^R,SSIFIED

(u) FOREWORD (U)

This document \^/as prepared in compliance with Department of the Armyletter, "Joint Contact Point for Chemical-Biological (CB) Field TesrData," 10 March f967r'nrhich directed Deseret Test Center to publishand maintain a joint CB technical data source book.

The Source Book is organized into a series of volumes, each of whichaddresses an identifiable area of information related to the analysisof CB !./eapons and defensive systems. Areas include agents, generalmodels, weapons systems, assay and data reduction procedures, chemicalsimulants and biological nonpathogens, and knowledge deficiencies.

Parameter values with confidence levels derived from field, laboratoryand chamber test, data are presented. Models and submodels are givenwhich idencify and define Lhe parameters for which numerical values arerequired in esrimating capabilities of weapons systems of the ArmedServices. Weapons systems which have been type classified or are inan advanced stage of development have been included.

The Source Book is designed to be used by the research and develop-ment conmunity as input into design and analysis of weapons systems,defensive techniques, and defensive devices. It may also be used bythose responsible for preparaEion of sysEem performance tables forinclusion in field manuals, firing tables, and oEher presentations ofmunitions expenditure and effectiveness information.

Portions of the information contained in the Source Book were compiledby GEOI{ET, Inc., under contract DAAD-O9-69-C-0078, with the remainderby personneL of DesereE Test CenEer. All inaterial has been subjecEedto review and coordinaEion by selecEed members of Ehe CB communiEy.The conscienEious efforEs expended by Ehese individuals Eo improve,the quality of Ehe finalized. product are gratefully acknowledged andaporeciaEed.

Each part and volume of the Source Book will be updated periodically.Frequency of update will be dependent upon the level of activity inthe research and testing areas covered by the applicable Parl orvolume.

Conrnents and suggestions regarding the adequacy or accuracy of lhematerial presented in this document and any request for assistance inthe use of t.he document should be addressed to:

Conunanding CfficerDeseret Test CenterATTN: STEPD-?S-A(S)iort Dou3las, .'tah EALl3

I]NCIASSIFIED

Page 3: Joint CB Technical Data Source Book on Tularemia (SR)

P as.e

6-r

6-L

7-L

7-1

7-7

8-1

8-2

(-1

Figure

4-L

4-2

5-1

5-2

6-1

6-2

6-3

6-4

7-L

1a

7-3

T'NCI-ASSITTED

(U) ILLUSTMTIONS (U)

TiEle Page

Effecc of Relacive Humidity on Ehe Efficiency ofAerosolizaE,ion of TT aE 75 oF When DisseminaLedby the E2R2 Spray Device 4-L6

Relationship Becween DisseminaE.ion Efficiency ofZZ and RelaEive HumidiEy in Aerosol TesE Chambers

ViabiliEy Decay ConsEanE for Agent ZZ as a FuncEionof Relacive HumidiEy '.

Regression Line Showing MO Decay RaEe as a FuncEionof Relative Humidity

Downwind Dosage Under the Conditions Indicated inthe Legend for Stabilized TT or JT (l^Iind speed, 3meEers per second)

Downwind Dosage Under t,he Conditions Indicated inche Legend for SEabilized TT or JT (Wind speed, 6

met,ers per second)

Downwind Dosage Under Ehe Conditions Indicated inEhe Legend for ZZ (Wind speed, 3 meters Per second)

Downwind Dosage Under Ehe CondiEions IndicaE,ed inthe Legend for ZZ (Wind speed, 6 rneters Per second)

Response of Noninrnune IndChaIIenge with Agenc SR

ividuals t.o Aerogenic

4-22

5-5

5-9

6-2

o-J

6-4

5-5

7-2

7-3

7-5

Response of MuIEipLeChaLlenge wirh Agenr

Response of Aerogenic VacChallenge with Agenc, SR

Puncture Vaccinees Eo AerogenicSR

cinees to Aerogenic

TINCI.ASSIFIED

Page 4: Joint CB Technical Data Source Book on Tularemia (SR)

l-I.}i ili. ,1 ,i,$f irts

'}Il,

'{rir

.lI't

I

#GT'i

H$!I

j,

3

I.gfrtt'1

.t

*ti

Number

< -/,

5-5

5-6

6-1

7-L

7-2

7-3

7-4

7-5

7-6

A-1

Summary of Total Decay Rates of Aerosols of ZZ LnCirambers aL Three Relative Humidities

Total Decay Parameters for Agent JT for TesE ChamberTrials

EstimaEes of Total MO Decay aL Selected Rel-ativeHumidities and 75 oF TemPerature from Test ChamberData .

Estimated Ef fective Dor.rnwind Distances for StabilizedTT, ZZ, and JT Released from an Aerial Line Source

Efficacy of Aerogenic Vaccination with LVS AgainstRespiratory Infection with EIEncisella. tularensis 425

Tetracycline Prophylaxis of Human Airborne Tularemia

Tetracycline Therapy of Human Airborne Tularemia

Formaldehyde Gas SEerilization of f'acilities'Materiats and Equipment . 7-10

Characteristics of Selected Decontaninants 7-Il

Amounts of Beta-propiolactone (BPL) Released in ShipExperiments. 7-11

sR Field Trials. . . A-1

P"g.

5-6

5-7

5-8

6-7

7-e

7-7

7-7

,r." : i" .:-i-

'-!i;_: rtvr:\i..:,1r":.1'*l :"j. li.:s

Page 5: Joint CB Technical Data Source Book on Tularemia (SR)

.i {l,lll"l:t'e,. :... ....: I tl-.{l

IIIIII

5-8

6-7

7-0

7-7

7-7

7 -LO

7 -1r

CFJPTER 1

(s) SLDftlARY (U)

General

Incub at.ion Period

t.o 5 days, de:enciing on dose.

Eo 10 days, d:pe:rC:.ng on dose.

fever rvith I F crg3nisms; at a dose of lOe organisms,

I 7-1r

A-1

l^_,

1-,

l-'o

III

( -)

(-),'-\

^(,,_gvCl orL=- J

eD-?

a

I10 - Nociays.

'ri

Page 6: Joint CB Technical Data Source Book on Tularemia (SR)

'{t,tI

II

ItII

{

0

ru,, :.!,gr;: i iJrilil tffi

d. (U) Morbidirv RaEe '(r) SR - wirhouE vaccinat.ion, l0o percent; wirh vaccinaEion,

20 Eo 40 percenE.

(2) JT - wichouE vaccinaEion, 100 percent; wirh vaccinaEion,to 20 percenE.

(3) MO - without vaccinaEion, 90 percenE.irrnunological respon:hriEh vaccinat,ton, 0.

e. (U) Morr,aliEy RaEe

(i) SR - withouE vaccination or therapy, 30 percenc; wiEhvaccination, less Ehan 5 percenE.; wich early Eherapy, ress Ehan 5percenE.

(2) JT - wiEhouc vaccination or Eherapy, less chan I percenE;with vaccinaEion or Eherapy.

(3) MO - none.

t.. (U) DuraEion of Illness

for 3

I-3.

to

t

(1) SR - To death, 2-4 weeksi for survivors, 4 tro 8 weeks.

(2) JT - 4 to L2 weeks depending on dose.

(3) HO - AfLer,massive dose (lOe organisms), ni_nor symproms4 days with liEEle or no incapaciEaEion.

Source ParameEers

\

-

; i,- il 1-' :^,'i11.",T1

',. ;.-;', -: i, :- i:..-:))

Page 7: Joint CB Technical Data Source Book on Tularemia (SR)

{i1..?

disease in vaccinaEed volunceers but 25,000 cells resulced in overt il1-ness. Good prot.ection of vaccinaced volunteers was provided against20,000 inhaled cells of JT.

d. (U) TheraPv.

SEreptomycin is Ehe drug of choicescrains of F. Eularensis. For sErepEomycinor EeCracycline are effecEive.

for nonsErepcomycin resiscancresisE,anc strains, kanamycin

I

I

I

IIII'lIIIIII

large

L-7 .

e. (U) DeconEaminaE,ion

Beta-propiolactone is the most effectiveenclosed areas. Ethylene oxide and formalin

O Knowledge GaPs

va por deconcaminant f c.rare also effective.

II

l-5

I

-

.:t[lf(GEf-

Page 8: Joint CB Technical Data Source Book on Tularemia (SR)

tlil

CHAPTER 3

I AGENT AND DISEASE .HAM.TERISTI.S (U)

3-L. (U) Biological NaEure of the Organism

In 1911, a bacillus isolated from ground squirrels in TulareCouncy, Californ!a, was designated BacEerium Eularense. SubsequenEly,Jtn"r-nar'es have been used: rr.rcel@ -tulirensis,and pasteurella tularensis. iE;tit rE h?s-Edn profiCa' Ehat Ehisorganism be placed in a new genus and designaE,ed Francisella tularensis.ir-tr"s been indicated that this name will be .ts.dE-Tfrfficffii-of Bergeyts Manual of DeterminaEive BacEeriology.(r) The lacter willbe used in this book. F. Eularensis is in Ehe family Brucellaceae.Cells of I. Eularensis o""G-IrrEErre in approximaEely equal numbersas cocci and shorE, rods 0.2 by 0.2 to 0.7 microns in slze, and theyoccur singly raLher Ehan in clumps or chains.(z) The cells are highlypleomorphic, nonmoEile, usually noncapsulaEed, sEain gram negaEive andnay show bipolar sEaining. The organism can be gro\.rn in Ehe laboraEoryon culEure media conEaining glucose and whole blood or serum. Cystineis ofEen included in Ehe media as well as proEein digescs. On agarmedia conEaining blood, small gray colonies form afLer 2 co 5 days ofincubacion aE Ehe opEimum growch temperature of 37 oC. Cells are killedby heat with a Ehermal death poinc of 56 oC. for 10 minuEes. AlEhoughthe organism is very fragile and fascidious in culcure, ic will survivein naEure aE low EemperaE,ures for long periods. To some exc.enc, vari-aEion in che infecEiviEy of F. tularensis has been associat.ed wichcolonial characEeristics in EhaE variant,s producing rough coloniesare usually avirulenr. However, variaEion in infecciviEy is alsoassociaEed wich smooEh colonial types, and colony characEerisEicsanong smooEh colonies are noE indicaEive of a degree of infecEiviEy.Changes in infecEiviEy occur in the microbial populacion during res-idence in various species of animals. In parEicular, low virulenEsErains have been obcained from birds and frou Eicks. Also, strainsobcained from waEer rodents such as the muskraE, are of lower virulenceEhan those from rabbits and hares.

ain SelecEion and Devel

3-1

I

I

II

t:tltr

III

$

IiI

1-: - " ::!i'--:..,

;; ;..l:::, ildi;

Page 9: Joint CB Technical Data Source Book on Tularemia (SR)

1j

IIIII

3-3. f an"."cterisEics of the Disease

a. (U) Nomenclature. The present dqsignalion of the disease

caused Uy p._.*f.il""i" i" tulaiemia and was used in 1921 by Francis'(l)iio tt." t""tri.U"t.a extensively to the knowledge of the disease and

the organism. other narnes that have been used for the disease are

raUbit-fever, deerfly fever, glandular fever, and Oharars disease'

b. (u) Transmission. Tularemia is primarily a disease oflagomorph" (i"UUit"-t" ""a-tares)

and rodents, though it has probably

the greatesE variety of susceptible hosts of any bacterial disease

k"o".. These include birds, reptiles, and a large number of manrnalian

,fu"i.". Also, it is unique in its ability to reProduce and to sur-

vive in arthropods. It has been knovrn to be transmitted from the

mature female tick to the young through the egg. The disease can be

transmiEted from the infecEed to the noninfected host by a great

.r.ii"ay of arthropod veetors, including ticks, flies, lice, fleas,mites, and mosquilos. Bedbugs and spiders were found to carry the

organism, but lransmission was not demonsErated. Transmission may

occur by most of the known modes--such as contact \./iCh (or handling of)infectei animals, consumption of or contact with infected food or

vraEer, the bite of an infected animal, or inhalation of infected dust

or .r"ty small parEiculate materrial. Direct infection from man to nan

has not been demonstrated.(1)

c.(U)Svrnptoms.TheSymPcomsoft'hediseasearevariedanddepend t,o some ."t""t on the source of infection, the portal of enEry

into the host, and the form and locat.ion of the disease in the body'

The forns of the disease and the parts affected in human infecsionhave been described as -follows '(e)

(1)Ulceroglandularorcutaneous.Theprimarylesion,apapuleformed aE the "Tt"

of GiioductG" of tne agent' Progresses to an ulcerand is accompanied by an enlargemenL of the regional lyoph nodes'

These initial lesions may be due to direct contact with the infectedsraEerial or co the bite of an arEhroPod'

(() oculoglandular or.ophthalnic. This begins as a conjuncti-vitis follotred les on the upper eye lid and

ulceration of thl conjunctiva. It is often accompanied by an enlarge-ment of the lynph noals of the scalp, salivary glands, and,axilla' Itprobably ,""rrit" from the introduction of the agent by hands soiledwith P. tularensis or the splashing of infected liquids inEo the eye'

(3) Glandular. In this forrn the portal of entry cannot be

determinea, "iffiere is no local lesion, but enlargemeng of the

regional lyoPh nodes occurs.

(4) fvphoidal or crvptogenic' The symPtoms of this rype closelyresemble those of tvphoia t".,r"f-lHe organism may gain access throug:i

the skir. , bu t :here "r" ,,o local les ioas or regional lyir'ph r:oce en-

Largenei:s. SePt,icemia occurs.

l:IIIIIIIII

Page 10: Joint CB Technical Data Source Book on Tularemia (SR)

{'it,'

a resulE of the ingestion of conE ed foodviolenE local process that takes the form of aor angina. There may be absesses on Ehe upperpharyn-x or nasopharynx. IE is accompanied byof vomit,ing, Dain, and diarrhea.

ominal. In Ehis form, asor \^/ater, Ehere may be anecrot,izing pharyngitispalate and ulcers in the

gas troinEes E,inal symp Eoms

lo

(6) Pneumonic or pleuropulmonary. The sympEorus are variableand may occur as a result of inhalaLion of Ehe F. tularensis organism orfrom its hemaEogenous E,ransfer from a primary focus on Ehe skin or else-where Eo Ehe lungs. Priu'rary. E,ularemic pneumonia has been described.

(7) MeningiEic. This Eype of involvemenE. is rather rar-e inEhe UniEed Seates buE under cerEain condiEions of arthropod Eransmissionhas been observed in che USSR. Development of the infecEion is accom-panied by high fever, headache,prosEraEion, and frequenEly incoherenceand lack of responsiveness. Fever may undulaLe markedly, rising rapidlyto high cerdperaEures.

(8) The nnnifestation of Ehe disease resulting frorn theulcerogland,ular, oculoglandular, and che glandular is sinilar and theseforms could conveniencly be termed glandular. Pneurnonic Eularemia mayrepresenc a special forin of typhoidal Eularemia and ic is quite f.ikelythac the principle route of infection for cyphoidal tularemia is respira-Eory. (ro;

3-4

Page 11: Joint CB Technical Data Source Book on Tularemia (SR)

IIIIIIIIIIIIIII

t

tfi

i:' l i:,-Li

e. (U) Susceptibilitv/Severicv. f. Lularensis is highly in-fect.ive and pathogenic as eviienced by the wide range of hosEs, cheinvasiveness of ghe organism, and the exEensiveness of manl' recordedout,breaks. (abbits, horses, and a number of rodents are highlysuscepc:ble co che disease. )1an, also, is highly suscentibLe. No

eviience is reporLed of differences in susceptibility wiEh regard Eo

sex or socioeconomic variatioa. There is some indication ofincreased severit.y with age. Severity may be greater for blacksthan fc: whites.(s) Occurrence of che di.sease is occupation-orienEedani so a grea:er number of cases are reporEed anong nen than wornen and

Page 12: Joint CB Technical Data Source Book on Tularemia (SR)

also among Ehose who work with animals or animal producEs. A11 individ-uals when exposed do noE necessarily become infecEed or clinically ill.fn a recenE outbreak of 47 cases, where a number were hospiLalized,seven showed no clinical sympt.oms, buE Ehey did have changes in aggluE-inaLion EiEer indicaLing infect,ion.(e) The relaEive severit,y of thedisease is dependenE, to some degree, uPon the form it takes, the modeof enEry of rhe infecEion, and Ehe source of the infecEive agent.Thus, the oculoglandular, the Eyphoidal, the abdominal, and the pneumonicare more severe Ehan the oEher forms of the disease. The abdominal andoculoglandular forms are associated with rather specific modes of entry.Apparenely the ryphoidal and pneumonic may resulE from several modes ofentry, buc Ehere is some evidence thaE they frequently are associaEedwith respirat,ory inhalaeion of infecEed parEiculace maEerials. InAmerica, Ehe severity of Ehe disease in humans is greaEer Ehan thatobserved in Europe, whereas the incidence and magniEude of major out-breaks in Europe, particularly Ehe steppe areas, are greaEer Ehan inAmerica. IE is thoughc thaE sone differences in reservoir hosts may beresponsible for these differences. In the United SCaEes, Ehe cotLonE,ailrabbie is the EpsE conmon source of infection, whereas, in Europe, andpart,icularly in Russia, Ehe principal source of infecLion is srna1l rodenEs,mainly wat,er rodenLs. IE appears that nrhere the coEconE,ail rabbiE isEhe principal- reservoir of the disease, Ehe organism is mainEained ina more virulent and infecEive condition Ehan when the waEer rodenE isthe principal reservoir hosE. There is evidence that some degree ofsErain selectivity with regard Eo Ehe organism occurs wit,h these differenthosEs. The less severe naEure of Ehe disease, as iE occurs in wat.errodent,s (as conpared Eo tabbiLs), has been observed in Ehis country.(e)IE is probabLe thac this shifE in number of cases may be associaced wichchanges in occupaEional populacion densiE,ies and with ureEhods of Creat-ment, prirnarily Ehe exEensive use of antibiotics wiEhouE specificidenEiii.cation of the cause of Ehe illness, rather Lhan a change insuscepeibility of the population or severiEy of the disease.

3-6

Page 13: Joint CB Technical Data Source Book on Tularemia (SR)

Table- 3 -1 (-). Infe-ctivitY of Strains of E'Pigs, anC Rabbics

tularensis for )iice, Guinea

tularensis Strain Ilous e

SCHU S)Nev lr-/+25 F3 ^ G425 F.- =G425 F. G

425 r:c (rt),alntraperiEoreal injection; all ot ers are su

Number of Organisms Constituting One LD=^

Rabbit

II

103>lu'"

l0e10e

utane ulls

Guinea Pig

L

II1

II

II

10101r r'€

t0

J-O

Page 14: Joint CB Technical Data Source Book on Tularemia (SR)

'xtttr'1

\

I ..* : : i',i" .'.. ;,; r. ^,.-Ir;--=-

Table 3-3 (U). Incapacitating Tularenia in }lan Caused by Inhalation ofFrancisella Eularensis 425 (ts)

AverageItaximalD6

(or

I

s p ira tor!Dose I

ganisms) 1

NumberVolunteers

Exposed

Average NoDays Oral

Temp >100oFal Temp.,o- r\ r/

rlll

80200800

7 ,500l2 ,000t5 ,0oo30 ,00086 ,000

astrepton"zcincure was 103

b StrepEon;;cinter,lPera ture

8

7

9

B()7

26

thereapy was begu:n.-; *c:I r rr!-rre4, r

1

Jlt

3

5

7

26

1t q

37.5r00100t00100

was begun inF, or higher,

l0

7 .56

5

4.64.5

B

2.56

5

4.65R

"6.5b6.3

102 .8101.5103r03.1LAz.6L02.6

' 104. Ib to3 .3

Iboth volunteers r^rhen oral tempera-hou:s .

rwo of six volunt.eers when oralfor 36 hours.

thereapywas 103 o

Ill

tlIlIIIIII

VolunEeersi Averageebrile I Incubation

Period (days

Page 15: Joint CB Technical Data Source Book on Tularemia (SR)

II

{ in'l i.l . ,'1"$,;q,i

Table 3-4 (U). Relationship BeLween Respiratory Dose of FrancisellaEularensis 425 and Time to Illness'

Nr:mberOrganisms

ApproxinateEquivalent No.Median Febrile

Doses

Time to Illnessor Incubation Period

(days )

Con fidenceLirnit , 957"

(days )

7.86-11.087 .29-L0,4L6. 14- 9. rl5.56- 8.47s.37 - 8.274.96- 7 .834.58- 7.444.L4- 6.993.96- 6.823.80- 6.653.53- 6.382.93- 5.792.53- 5.4L2 . l0- 5.002.O3- 4.941.89- 4.81

Estimated IllnessProbabilicy (%)"

100200800

1 ,6002 ,0003,2005 ,0008,200

10,00012 ,00016,40032 ,00050,00080 ,00086 ,000

t00 ,000

rSelecEed data from Printout.

Table 3-5 (U). Illness Probability as a Function of Respiratory Dose

of Francisella Eularens Ls 425

lA

WNtunber MedianFebrile Doses

(rBo)

0.51.05.0

r0.0

ZJ508794

820I ,6408,200

16,400

F\:_.: l

Fif*l

9.468.8s7 .637 .016.826.40( ao

5.575.393.234.954,353,973.553 .483 .35

0.51

2

5

1020

50

60

Number Organisms

aLog normal (probit) relationship statistic'

3-L2

Page 16: Joint CB Technical Data Source Book on Tularemia (SR)

I

II

Table 3-6 (U). ResponseLevels of

r r \t f i ,t il iri lr i'l'E)l + ./.t.:-'1

--

of l'lan Following Aerogenic Expo-sure Eo-ivS

ut..d on Agglutinin Ticer(1e)

Do se(org)

ofExpos ed

NumberVolunteers

NumberResPonding

ProPorEionRespondinC &)

1

11

2

12

4

3444444

!l\,

200450560600700

1, 2oo1,330

33 .325 .025.050.025.050.0

100.0

3-13

Page 17: Joint CB Technical Data Source Book on Tularemia (SR)

tjli'il[,AS;tIFIEH]

Table 3-7 ,(U). Response in Man to LVS Dose Levels

LVS Dose(No. org)

1.0 x lG1.0 x 1058.5 x 1065.0 x 1065.0 x 10"7.0 x 1071.0 x 108

Ind ividualsChallenged

(Nunber)

FebrileResPonse

(% ot challenge)

Sys EemicResponse

of challenge)("/"

0000

5980

42t+2

8B

92942

III

307980BO

1009090

I

lPersonal corrnunication with Dr. H. T. Eigelsbach, U. S. Army BiologicalLaboratories.

3 -14

Page 18: Joint CB Technical Data Source Book on Tularemia (SR)

II

tI

IIIIItIIIIIIIII

CIJAPTER 4

f ror*.E PAMITETERS AND,IToDELS (u)

4-1. (U) General

Source DaraneCers associaced wilh tne effecE,iveness of a biologicalweapon are the concenEration of Ehe agent maEerial produced, Ehe sLoragesEabiliCy cf the agent producE in storage, and the efficiency of diss-eminaEion cf Che agenE maEerial. These are the agent-related parameE,ersChaE influ€rce source scrength of Ene agent as iE is disseminated by a

municion. Through research and testing over Ehe pasE several years,informacio:: has been acquired on Ehe production, scorage and disseminationof agenE p:eparaLion of F. Eularensis. NaEional policy now bans thedeveloproenc. of biological weapo". a.d Ehose \^/eapons thaE were developedand Ehe iniormation regarding thenr lnay now be considereC "obso1ere."However, Er:e general informaEion, as well as the parameEer values ob-t,ained, re:ain of rnajor imporcance in assessing the Ehreat thaL biologicalwarfare may pose for this naEion or it,s allies and in developing defen-sive capa'ciliLy againsE biological atEack.

/, -,) Agent. ProCucE,ion and Storage

Page 19: Joint CB Technical Data Source Book on Tularemia (SR)

CHAP]ER 5

f aouu*cE 'ARAI'{E'ER'

AND MoDELs (u)

5-1. (U) General

The atmospheric transfer model for biological agents involves a

consideration of gas/aerosol transport and attenuation effects. The

particle size range of interest is equal to or less Chan 5 microns inii"*"ter so t,hat deposition and irnpaction of particles are not signif-icant. The atmospheric transfer model describes the transPort. of thesource cloud(s) by the wind as Ehe cloud diffuses, and also thosefactors which aEtenuate the biological effectiveness of the cloud.

t-r. I

Attenuat,ion

a. (U) Loss of viabilitv with Aerosol Age

(r) The source cloud of biological agents is subjecEed to a

decrease in the biological effectiveness of the cloud as it is trans-ported and as it ages. One reason for this lessening of biologicaleffect:-veness is a decrease (with cime) in t,he viable cell concentra-tion of the agent cloud. This decrease rnay be affected by such con-ditions as relative humidity, temPeraEure' solar radiation, and

atmospheric pollutants. One of Ehe widely used mathematical models Eo

quantify viable agenr decay is the exponengial decay model:

Q(t) = Qs exp(-Kt) (s.l)

where Q(t) = number of organisms in agent cloud aE time t, oEB.,

Qo = source sLrength (i.e., number of organisms in agent- cloud at E = o)

K = exponenrial decaY

E = aerosol age after

cons tant rl

dissemination, min.

(2) The Eime at which Ehe number of viable organisms in theagent cloud has decreased to one-half. the initial number (sourcesirength) is defined as the viable agent half-life. The viable agenthalf-life, Qo, is given bY:

to = '693/K (s.2)

decay rate in Percent per minute for

5-r

to Eireless.

t'I

I l00K is nearlv equalvalues of K ='O.I or

Page 20: Joint CB Technical Data Source Book on Tularemia (SR)

(3) The simple e:<ponential cecay nodeL is riidel,v used but i-'has long been argued that this model does not adequately quantiiy theviable agent cecay nor does it describe the biological Ioss process.Nunerous other models have been proposed to quantify ciecay of thebiological aercsol cLoud.(5e) A joint working group of llLJCOl{ ORG andForE Detrick personnel, while noc proPosing the use of this model, hasindicated the need for a modification of the model which will reflectvarious values of K cnanging with sequentially increasing time incre-nents.(5e) A recent Deseret Test Center special study on biologicaLaerosol decaf in test chamber experiments(6o) has determined thaEdespite its i:'ladequacies, the widespread use and reasonable f it codata of the sinple exponential model justify its continued use unliLfurther data tndicate that other mocels offer sorne significant improve-nenE.

ir -:

II

!

I

Page 21: Joint CB Technical Data Source Book on Tularemia (SR)

I\

IIIIItIIIII

e. (U) Viabilitv Decay ?araneters for l1O

( f ) The mater:-aI presented is orienEed Cowari the use of \10 as

a s i:nula::t f or agencs S3. anC JT i.n f ield ies ts . Paraneter value con-parisons of che agent.s r.ri-ll be used as a basis for deiernining wheEle:or not ):a wil! be a gco<i sii-.rulan: ior agents SR. and JT.

(2) Six aerr:sc1 Ees:s coi:ducted. a: Fort Detrick (Ces c chanbers95 anc 9:) were poolec :o deternine the tcE:,1 decay ra!e ior llO. T::esees:lna::s, as wel-l- as tIe irdividuaL tesC rcPCr: means, are prese::rcCll

II

ct

Page 22: Joint CB Technical Data Source Book on Tularemia (SR)

l-l i \ \etir: :'-- ''-

DaE,a from Eescs in oEher chambers or wiEh oEher dissemin-q/as noE used because it. unnecessarily ineroduces bias inEo

\l

lII

lin Table 5-6.aEion devicesEhe escimaEes

Table 5-6 (U) EstimaEesHumidit,iesDaca( 23 ,eo

RelativeHumidity

(%)TeS I

NumberNumber of

Repl ications

ObservationTimes(min)

Decay Rate100k) ("L/nLn

Mean95% Confidence

Leve 1

30il;*ri

50

B5

138 7L4s6

L456

1456L6521 768L77 62346

J

r6b

T2

4

4-184-LB-32

Pooled mean

4-L8-32

Pooled mean

4-L8-324-LB-32

a

4-LB-324-L8-32

Pooled mean

19.0L6.6

18 .3

L4.3

14.3

8 .335. 70

d 5.418. 66

7 .5L

L6 ,2-2L.8a

a

4.50- 6.894,52- 5.954.03- 6.793.76-r3.6

aBecause of interaction wiEhin the variables, confidence limits werenot determined frorn Test 6l-tE-L456.

bNo data available." Test ieport 63-TE-1768 vras not obt,ained. These daLa were exEracEed

from Deseret Test Center's report.(eo) This mean was not used incalculating the pooled mean because the number of replications per-formed in the test \"ras unknown.

dThe mean reported here was obtained from daEa in test tank 95. Datafrorn test tanks 96 and 97 were too variable to be reliable.

(3) The pooled means were calculated by averaging Ehe weighEedmeans from each EesE. Because no measure of dispersion was calculaEedfor Tesc 61-TE-1456(ezl, Ehe 95 percenc confidence limics cannoc be given.When each of Ehe percenE recovery points for Ehe 30 and 50 percenE rela-Eive humidities was fiEted direcEly Eo EquaEion (5.1) by leasc squares'a differenE pooled mean was generaEed. InformaEion on some of chisvariaE.ion is lacking.

(4) The effecc which relative humidiEy has on decay can be

of Total MO Decay aE Selected Relaciveand 75 oF Turp"taEure from TesE Chamber

,66 ,6? ,58)

5-8

Page 23: Joint CB Technical Data Source Book on Tularemia (SR)

shown when t:ie individual- test:neans in Tabie 5-6 are assuned to be (andare treated as) inciepencienE rando: variables. Because of rhe differentnumber of replicaEions conducted fc: each tesl, this assunption is ncIentirely Erue. Figure 5-2 shows the resulti-ng regression line whenrelacive hu:j-City is createi as tha independent variable. Because inthe Fort Decrick chamber tes:s Cer:,)erature was not signiiicantly variei,the ef fect cf f emperature on llO iccav cannot be ascerEai-;recl .

l

J

Page 24: Joint CB Technical Data Source Book on Tularemia (SR)

I

CA{PTER. 6

AGENT EFFECTiIENESS PREDICTIONS (U)

6-1. (U) Casuaity Predictions

The ge;reral casualty prediction model for biological agents ispresented in '.'clume X of the Source Book. The paraneter values(presenced in this book) for area coverage and dose response in humansr,ray be used rv:-th this mociel for casualcy prediction and threat assess-nent fcr F. t:l-arensis. Casualty predictions are not presented in thisbook because cf the r,rultitude of pararneEer combinations that rvould needto be presented and because other publications, such as the JointIlunitions Ef f ectiveness }lanual, are designed to provide that inforr,ra-tion. Doi"nr.ri:-.d dosage es t j::raLes are presented here for one dissemina-Eion model to r-..

I

I

I

I

I

Il;

Il.

II

6-i

Page 25: Joint CB Technical Data Source Book on Tularemia (SR)

tI

NeuEraI(BeEa = 0.88 Inversion

(Beta = 0.66)

Wind speed (m/sec)- 3.00Biological decAy rate (7"/min) - 3.00Source StrengEh (org/m) - 2.36xl0lo

l50n release hf..

2

E roaI

lroC}co(!68 rot

t;

iil,

li

li?:

li

f

i{

l0 -r

l0 -z

10 -1

Figure 5-1 (U).

r,--- \

100 101Distance Downwtnd (km)

Downwind Dosage Lrnder che CondlElons Indj-caced infor SCabilizec Ti or JT (i.iind speed, 3 meters per

Ehe Legendsecond) (U)

Page 26: Joint CB Technical Data Source Book on Tularemia (SR)

{ Tl.l l1 l[ i, {: ''i i I-'if ni i i: "* .. I .. ' .. '-: ' .1 i, j s. tt-r';r

TINCLASSIFIED

l:\t

2) to'

I

tJo

CJ

(!qQ IO2c

I

IIII

10 -1

I0 -1

! rgure o -3

1Oo I01 102 103

Dlscance Downwind (km)

(U). Downwind Dosage Under che Condicions Indicaced in che Legend forSEablllzed TT or Jl (:Jir.d speed, 6 mecers per s:ccnd)(U)

o-J

UNCLASSIFTED

Invers ion(Beca = .66)Neutral

(Beca = .88)

Wind speed (m/sec)- 6.U0Biological Decay Race (%/min) -

3 .00Source StrengEh (org/m) - 2.35xlOo

l50m release ht.

Page 27: Joint CB Technical Data Source Book on Tularemia (SR)

-t

IEd

EIo0

o

q,b0o.t)o

tJlYVLf\.).)rr LLJU

10 -r

Figure 6-3 (U). Downwind Dosage Under the CondiEions IndicaE.ed in Ehe Legendfor ZZ (Wind speed' 3 meEers per second) (U)

6-4

I]NCI.A,SSIFIED

II

III

101lgJ

nvers !on(Beca = 0.66)

NeuEral(Beca = 0.88)

Wind speed (m/sec) - 3.00Bio Decay Race (7./rnin) - 5.00Source Screngch (org/m) - 5.40xl0rr

release

50m release hE.

DisEance Downwind (km)

Page 28: Joint CB Technical Data Source Book on Tularemia (SR)

tili ci,- &'

I@

IIIIIIIIItIIItII

104e

EIcotro

cr 103

ooA

10 -1

Figure 6-4 (U).

l@ ro1

DisEance Downwind (km)

Downwlnd Dosage Under che Conditions Indlcatedfor ZZ (Wind speed, 6 mecers Per second) (U)

in Ehe Legend

(Beca = 0.88)

Inversion(Bera = 0.66)

Wind speed (m/sec) - 6.00Bio Decay nace (%/nin) - 5.00Source SErength (org/m) - 6.40x10rr

l50m release hc.

Page 29: Joint CB Technical Data Source Book on Tularemia (SR)

7 -L.

CHAPTER 7

(C) DEFENSE (U)

(U) DeEection and Physical Prot.ectionsrl{IT

!It{aEild

iId

1, 1

III

Because of rhe number of poEent.ial biological agenEs, deEeccion andphysical proEecEion capabilicies are developed E,o be applicable co allagenLs racher Ehan for specific agenEs. A detailed discussion ofdecection equiprnent and developments is presenEed in Volume XIII of EheSource Book. This wiIl include rapid agent idencification concepts.ProtecEive equipmenE and pracEices are discussed in Volume XI of cheSource Book.

7-) ts iolog ic a1 Countermeasures (U)

Effective biological countermeasures consisc ofa. (Lr) General.the following:

IIIIT

IItIII

(f) ImmunizaEiont.ularens is .

uEilizing a live vaccine sErain of Francisella

(2) Ancibiocic Eherapy usedabort illness.

as a posc-exposure prophylaxis to

3) Antibiocic Eherapy pronpEly used as a curaEive treacmenE

I

t

Page 30: Joint CB Technical Data Source Book on Tularemia (SR)

t: rfra:r.\ ': l i :i.! .l . 4

7 -2 (u) Tetracycline Prophylaxis of Human Airborne Tularemia

sDivided inEo morning and.evening doses; treaEnent instituEed 24 hoursafter exposure to 25,000 organisms or 250 human infectious doses.

Table 7-3 (U). Tetracycline Therapy of Human Airborne Tularemia

Table

DailyDosea(grams ) Frequency

Duration(days)

Number ofSubj ec ts

Number I11During

TteatmenE

Number 111AfEer

Treafment

1

1

21

DailyDailyDailyEveryother day

1528L419

10B

8

B

0002

2

008

Daily Dose"(grams )

22I

Days of Therap;r

10L4l5

Number ofgubj ec ts

11bzo

8

Number withRelapse

502

I

l

I

rVolunteers exposed to 25,000 organisms or 250 human infectious doses;all men received 4 grams of drug the first day of therapy. Daily dosewas given in incremenEs at 6 hour intervals.

btvelve men infected with the SCHU-S4 strain and eight with the SCHU-

55 (streptomycin resistant) strain of Francisetla Lularensis.

(3) freaunent of volunteers,exposed to aerosolized strain 425,with streptomycin resulted in dramatic therapeuEic resPonse similarto that seen with treatment of infection with SCHU-S4.(rs) The thera-peutic efficacy of tetracycline against strain 425 has not beenevaluated in humans, hcrvrever, it is reasonable Eo assune that it wouldbe effective.

7-3- ta.

Decont.aloinaEion

General (U)

Page 31: Joint CB Technical Data Source Book on Tularemia (SR)

Table 7-4 (U). Forrnaldehyde Gas Sterilizacion of Facilities, Materials,and Equipment(zs)

VolumeTestCondition

LaboratoryRooms

Large lioom

MoblLeLaboratory

Surfaces

FiIler MediaClass ICabinet

LaboratoryEquiprnent

Vaccine Tubes

Amount ofParaforma

685L379

20165

330

7.5

12.6

3 0- 150

0.6

ft3

22504598

67216

2200

ViableecoverLes^

B.S.

B.

B.

subtilLsmarcescens

sub t 11 is

subtills

sub ti1 is

subtills

subtilis

sub tilismareescens

0/s0/s

0lL

0/s

o/s

o/s

25

42

\|I

tsO

100-200 0/10

0/2o/2

aNumber of vlable recoverles/total tests conduct,edb 106 per patch.

Concentration

1062x101 o

1F

106

10?

b loe

(rt-_Vi,a'

[.ttll:

F,'Lft

Page 32: Joint CB Technical Data Source Book on Tularemia (SR)

1

Itj

Ii

Ii

:

iI

,

II

/

IIIIItItIIIIIII

Table 7-5 (U). Characteristics of Selected Deconganinsngs(2.4)

Decontarninant

Beta-propiolac tone(BPL)

Formalin (377.formaldehyde inwater )

Ethylene oxide

DecontaminantRequirements

Environmen talLimi cations

RH not lessthan 70%; min-imum effectivetempera ture24 oc (75 oF)

RH: 85% bes t;cemperacure 2L-2l oc (70-80 oE) best(not less than16 oc (60 oF)

Ilinimum effec-tive temperaEuret6 oc (60 oF)

'- :{ r-':

' 7:1I

Physical Statefor Use

Vapor oraeros o1

Vapor oraerosol

2 hr contacttime; 24 houraera tion

16 hr contacttime; 24 hraeration

6-8 hr conEacEar 2l oc (70of) 12 hr con-tact at 16 oC

(60 oF) 12 hraeration

Page 33: Joint CB Technical Data Source Book on Tularemia (SR)

c. (u) Decontamination of Small ArEicles

(i) Because of the inability of BPL t,o peneErat.e exEensively, itwas found <iuring Ehe experi-ment.s cited above EhaL contarninated materialsin smaII inclosed spaces were noE decontaminaEed.(ze) As indicated inTabIe 7-5, 6 to L2 hours of cont.act, depending on tempelature, shouldadequaEell' eliminat.e the hazard.

Conc lus ions (u)