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NOTE ON ,THE CHARACTERS OF AN ANOMALOUS M'EMBER ' -,OF THE PARATYPHOiD 'GROUP MET WITH'IN MESOPOTAMIA.

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By _ MAJOR F. P. MACKIE. Indian Medical Service;,

, AND

,CAPTAING. J. B0W:EN: Royal Army Medical Corps. ,

Of the Central Laboratory, Baghdad.

-INTRODUCTORY.

.<, ! . . .

\ - IN the courseof-our work in -MesopotamIa we have from time to time, isolat~d from' the'blood: of suspectedentericas; organisms conforming' bib-' , ,chemically to -Bacillus paratypJlOsus B. but failing to respond t'a paratyphoid,-_ B 'serum' (Lister Institute) iri dilutions ~hich would justify, a positi"e diagnosis of that organism. " ';'" --" , ",', _ \

, ! \ The biochemicalproperty'ehieflyrelieclupon iI?-1inkingthes~ -~noniaI6us · types .wit~J3. pg,rf:ttyphosusBhas been the relatively abundant' productic,:m 'of Igas ,in m~dia containing ,'glucose;,mannite and. dulcite, and when'this

property hasbeel1 associated with feeble agglutiIiability in 1,in 100 orl in 200 dilutions of para 'E, serum, it has been customary to ,:return a p~ovisio~al diagnosis,of " i,riagglutinable·p~ra B." , ,

High titre ~era Jor other members of 'the, Gaertner-paratyphoid group hliveinvaria:bly,faileclto 'agglutinate these organisms even in th~' lowest -dilutjons. Fortunately many 'of these anomalous strains have been pre-

__ served, 'and the apparent acquisition by a certain proportion of them (but by no means all) of a ~ definitel.thbughpeculiar response)o para .B' 'serum'

, i~ relatively high dilutions, after_repeated subcul~ure in broth, has merely ;­d~layed)he inve8tig~~ion, which it 'is the object I of this ~paper to descrioe, , and which' in our opini0n'.aem~ms~rat~s the presence of ,a '( new~'para­typhoid organism ,sharply defined' serolpgic!,tlly thbilgh -possessing uil­dou,bted affipities with B. paratyphosus B and possibly with B. s,«ipe~tifer.

, .' ,During t1;le latter part, of, 1918 a series of such strains were recovered · ',ffol)) the blood" arid it\vill h~ well ',at this stage to set, forth brieflY the. 0

clin~calnistory and physical signs of some of th'e~e'casesbef6re'proce'ec1ing . ' i '. with thebacteriologic~l investigation. A paper d~aling with the same

.'. subjecth!l.s, yve i;nidetstand, been submitted for . publication ,by Captain :MacAdam" 'R.A.M;C., .'of 31 B: ,,s .. Hospital, Baghdad,. whose conclusions agree in the Plain withours~ " ' . , ,

Table. I summa~izesthe' main pQints concerning the duration of, ~ ,disease, inocu,lation' history, r~sp~nse 'of the organism to" high titre sera' · atpriinary. isolation, in ,Il; recenkserlesof twelve cases (five British aDd

. seven Indian)iwhich occurred in the last quarter o£}91S. ( , - \', • J " ,I :oJ :.'

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TABLE L-SUlIU,[AI,IY OF. RECENT CASES.

Lahora- -British Organism I Inoculation .tory or iso1a ted day history,'

_~j nUIl,lber ~n«;lian of disea~e T.A:B. / _ Ciinic.al details and place of origin'

--7;- 'in~i:- ---7--1 Feb:ary, N.E. area of operations, in6luding - - 1- 1916 Persian L~ of C. ; no clinical details

709

782

815

825

967

1,059

1,165

1,250

1,251

1,332'

, -

S. B. 72

.1 Marc'h,- ,known; recovered?

British i4 N.E. area; severe septic- type with , _ _ ! 1918 kidney signs and superficial abscesses;

Indian

Indian ,

Iridian

Indian

Indian·

British ,

British'

British

,--""

British'

I -. '

Indian i i

6

8

7

6

20'

5 ,\

8

17

Third week

.'

25 days

, Not inoculated

/' December, ,1916

-

March, 1918 No

record March,

1918 August,'

1915

January, 1918 July,

-1918

recovered _ N.E.a:r:ea; mi.1d case; seven days

fever with diarrhcea ; 'recovered Baghdad area; fifteen days irregular

fever. with congestion of the lungs; recovered

N.E. area; influenza-like type • I

N.E. area; high intermittent fever; . pulmonary involvement ;_ death' Baghdad area; broncho-pneumonia

and irregular fever. Irregular fever; ~rganism isolated

from blood and later from gluteal abscess: septic type •

N,E. area; fever t_en days duration with cerebral symptoms

N. area-Baghdad-Mosul line; fever ten days duration; bronchitis; influenza-like .

N.E. area; temperature and general symptoms those of a paratyphoid

. fever; blood culture on 'ninth and I thirteenth days sterile..; organism

- Signs of liver disease and jaundice;

O~ganism; how. ' , .obtained

Blood culture

, --

" -"

. /-

. " " ,

" !' "

" j,

" " " "

Blood culture and abscess

-Blood culture

" "

- - Urine

Liver, post

. \

f

I

recovered from urine

. fever only the last . seven days before mortem -

*1,298' British 10,

i ..

- -- I .

- 'I death; post mortem showed multiple , necrotic areas in the liver -November, RE. area; a: iJa~e of.P.aratyphoi~ B.

1917· for .comparison; cllUlCally typIcal 0" \ of paratyphoid; -no lung complica-

- -Mon. - .

Frec.es

* B case Included for companson.

,

Bioehemical .-reactiQn

,

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--

'" ", .. '" Ol

'0 -~ .S P=I ~ '0 .c: I'l< :>. .., Ol ..... Ol I'l<

~

'" '" 0 .c: E-I

-i

: -

-

,

Para B Para A'and Gaertner

Strain lost

" -,-L Strain lost.

--

Trace'l in -200 . -

-- -- --

-

1 in 800 -- ,

- --

1 in 400. ---

-, -~ ,

- - ,

1 in 3,200

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156. '\ P~1;atyphoid .Group 'm.et with 'in Mesopotamia I • I'", 'l '

., Of rate we have taken the opportunity of visiting S0me of these' cases , : with the. obj~ct of ascertaining whether the organism' in question was , associated. with .any peculiarity. of clinical syndrome, and'we, therefore,

make no apology' for submitting fuller clinical notes' of eight cases (five , 1 _. . ,

British and three Indian). ' . , '.' / ) ,

I, • [

. C51se967 (Indi~n).-:':E{is conditi;n at the onset is not known accurately" but, :,the disease started with fever and frequent diarrhreac accompanied by griping

pains. No .enlargen'lentof the splEle~ or liver.' Bronchitis was an early symptom, being especially marked .at the bases of the lungs. About the ninth day of the disease the lung condition'was more pronou.nced; a~d the bases are now.described as being congested' and probabILpn'eumonic, and the patient was semi· conscious. The pulse became wea.k, the ,tongue dry and furred, he passeq motions and urin,e in bed. At this stage a blood' culture was sent and ~ para'B-likeorgani~m re­covered in pure culture. The spleen was not enlarged at any stage, J?or were spots found .. Thetempetature'maintained anjrregular course up to the fifty-first day of, the disease,.: when he W~8 evacuated to the base and lost sight of. His' general condition imprqv'edconsiderabiy, though he-was very debilitated' when transferred. ' . '

. Case 'I,059.-'--An Indian who contracted the disease in :Ba~hd~d. He gave a , ' history of fElVer for ten days he fore admission. On admission : he -was found to

have high fever, and an ihtermittimt fever which suggested, malaria. No parasites vyere foun~ in the .blood:", His' pulse and respirations were high, and sign.s., of partial consolidation were' found' at the base of the rightfung. Jaundice supyrvened. Quinine by the mouth and intramuscularly was' in-' effective,aIld he died on the twentieth.d~y of the dise!j.se. On the day of his death a.blood culture was·taken,and'the organism to be' described was, found in pure cultu~e ..

Case' 709.~A British soldier, taken ill tt,tSharaban on August 28, 1918. -Temperature 101'4Q F;,.headache and sore throat .. Transferred to·Baghdad

August 31,1918, as ~.Y.:b. fever,temperature 103° F:, tongu'e .dryltnd furred, throat congested, liver slightly enlarged, spleen much enlarged, , diarrhrea. No 'malarial parasites f<;>Ulld in'the blood, no Klebs.-Loeffier bacilli found in the throat .. E~amination of the' freces showed amrebre of uncertain nature, so he was. put on emetine and quinine.·. General Q6nditio~ very weak and wasted. Septic sores on forehead, back and arms. Blood culture on .the fourteenth' day of the disease', yi~lded a pqre,growth of the. para B-like o~ganismi He' was ina very septic condition, and all ,hypodermicpunct]lres suppurated. On the twenty-eighth day of the disease a petechial rash.was noted on both forearms. 'He was delirious at " .intervals.1 Albumin and pus cells were present in the urine. Septic sores con­tinued to break out ~n~ fresh pustules appeared. The albumin and pus. in,the urine' increased: He was later put .on· urotropine. The' abdomen became dis-

, t-ended and patient developed a cough, and a sudden rise of _tempe~ature 'which ,so.on subsided. His condition began to improve, though ,his temperature re­mained irregular till ,the fortieth day 'of the disease, after whicl;t it fell, and he made an uninterrupted, recovery. , . . Case 1,165.-This patient show'eda loqg-continued irregular fever, which ~as

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F. P. Mackie,'and G~ J,. Bowen ~ 157

,only li~e enteric group~ise~se in the firs,t week or ten days. Blood culture ~n the fifth day gave .a pure' culture of an inagglutinable para B.like organism. Frecal examination on the thirtee'nth, fourteenth, fifteenth and tvv~nty-sixth days

; DAYofOI5. I 2' 3 4 5 6 7 8 9 10 11 12 13 14 15, 16 17 18 19 20' 21 22 23 24 25 26 27 28 29 30 31 ME ME ME M,[ M EM E MEM EME MEM EM EM E MEM E MEM [MEM EM E ME ME ME ME ME ME ME ME ME ME ME F' :

" : : : : : : : : :

104" : : : : : : : : : 1 .'. : : (

: " : .: : . " : : : 103" . ': : ': : : [ : :

1020 : : : : : '.

i, '. 11 V1 11: I), 11 j " ., io I" '. "

V. 1\ : 1 lOO" : " " :

: ri V: : : : i~ '11 11 '. M & : J1 "

99' : : : : : : " : : : : : " : : " : : : : : : : IV. : : II'. : : ~ : : : 'I 9.' "

" ~ : :' 1\ a- II : ~hlW I~ If 97' : " : .1 " :

LI : "

" "

,

CHART I (Gase 709).'

were n,egative;but' about the, thirty"sixth day his temp!'lrat~re rose, and he 'was found to have an abscess in' the buttock. Pus from this grew the same organism

. as that which had been isolated from the blood. A vaecine was made, arid. after two' doses his temperature came down to normal.

. This case is of interest in showing a pyremic deposit of the organism, uDde~., ' discuBsion.· ' . . .

.r ' OAy.,rOIS I 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 16 19 20 21 22 23 24 25 2& 27 28 29 30 31

'MEMEMEMEMEMEMEMEMEMEMEMEMEM£MEMEM~MEMEM-EMEMEMEMEM'EM EMEMEyEMEM£ F~ \ • :i ',~ ~ ~ " . 1 ~ :. : ~ _: :

32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 OAy.,rOIS, ME ME ME MEM EME M EM EME ME MEM EM E MEM E ME ME M E M EM EM E MEMEM E ME ME ME ME ME ME ME

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10'"

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U L~ IV: .. :/ 1 ,~ ~l 1 ~ -' :1 1 99'" " 11: 11 : : : : " : :), : : .1 : : I-&. .,. : If. IV. : I 'Iv. V. : J Ill": 11 .. ' , Ir; ~ II ~ .~ I'! ~ ~,~ , ,

.7'

'. 0' : :' ., " " : :. 0.,

" . C,HART II (Case 1;165).

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" , ) , " Case l,2-50.-This case' sho~ed 'a short ~harp f~~er of nine days' duration,fol~ Jowed by recovery. He, was verydrowsy,and almost comatos~ at the height of

, the attack, so that he wa~ suspected to ,be suffering from cerebral malaria.. Splee~ , enlarged, no lung' signs, no spots, no ~bdominal sighs, but liver eplarged.' Blood 'cul~ure was positive on the eighth day.\ '

DAY of 015, I 2 3 4 5 G 7 8 9 10 " 12 13 ME

> IME ME MEME MEMEM E M.E MEM E M EM E

I F " : i,

I05Q

11: \: :'. 1040

-:-r\ 1 "

r03° . , ..

f : : " " : '. .. .' f 020

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'01 0

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. CH~RTIII (Case: 1,250). ; !

cdse 1,251.-This patient ,was taken ill on th~ march, to' Mosul at' the) end of' operations. The first and chje'(symptom was bronchitis. lrifluen,za was ,at first suspected, and then,m;:tlaria; so he,w3:s giveJ1 oral and intrap'tuscular'quinine. No parasites were, however, found ih 'the blood. The spleen was enlarged, but no

,- other abdomin,al signs. ,The fe~erlasted forte'n days, and V\i"as -xery sImilar to.the \ last mise, "though not ,quite so severe. A hI'ood culture taken on the sixth day of 'the rise (or' t,he seven,te~nth day from the, onset of the illness), gave 'a pure culture ot an 1nagglutinable para J?·like organism. . "

. .. . \

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t?~YofDIS. 5 6 7 6 9 10 11 12 13 14 15 16 17 16 19 20 21 22 23 24- 25 26 \'" M,E ME ME .. , EM E r" E M EM E ME M , M E M , M , M E M E M E M E M EM , M EM M f. 1 • FO

"

': i "

.104° .' t 030 .: IX " ~

, '. '"

102" \: ., V t tl -' :1 ~

101.° :. f lJ. H " .-,. " " :li

loo" f' .' 11 I.: .11i' M '~ ..:. : . " -'

99' : : : f I1 : 1 : : : : : .' : I: I/, : : : : : " ,

! 98' " "V' r\ -, " :' : . ~ ~ 7" I ::

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"CHART IV(Cas~ 1,251).

Case 1,332.-;-A British soldier, working'in the refugee camp at Baquba. He was ill fqur or fiv{3 day's before goIng to hospital. His chart shows an irregular

; feye~, like tha~ met with in, paratyphoid fever. Slight _ bronchitis, abdomen dis-·

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" ten'dea" spots' not, present. Trace of~lbumin i~ the urine.: Spl!=lenand liver' : ~lOt felt. Has the appearan~e of a~mild enteric. He suf(ered from nephritis when " III France,' " - , ,,' " " , '"

Blood cuItu~es takelil 'on the ninth, and'thir,teenth days, proved' sterile.! ; ,Para B in,agglu~inable wasreco,vered froln the urine 'on the' twenty-fourth day ,

of ,the, disease.' " . ,

OAVofOIS, 6 ,7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 M M£M£M £ M E M £ MEM EME M,E MEM EM E ME ME ME ME ME ME ME ME ME ,

f" 0'

! ",

103" " o.

i~ r V- i , :1 : : :. :t .. 1020

if ~ !J1 ~' ~I JII..~j " \ .' " 1,01.0

IV: 'M lI~ IV: .,

f ~ '. " 100° '. ,

IV: V: Kj . V: Ir: " 0,

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" \ CHART V, (C;ase -1,332).

Case 72.--;-This case is, remarkable becaus~ his symptoms; tiil the l~st week, were almost entirery hepatic.

He reported sick on November, 4, \1.918, complaining of pain in the upper , abq6menand vOll1iting after f?od'~ Thy tongue was foul and ,the bowels con- "

stipated;, LivElr e~larged ,thre,e fingers below-the costal margin and, tender., 'This c'Ontinlied,l,and laterjaundicie supervened;' Entamce,ba histolytica cysts

" wyre found ,in the stool, and ~e was notedtobe ,ve'r:yanremic. On November 18 'hit] liver :w~sexplored, qn the supposition of abscess,but no' pU8 was found. , On November 23 he developed. fev,er, Iwhich cqntinued 'till ,he died on Noverri~e,r29.His liversymptOlps incr~ased, ,and hf:Bmapemesis and meloona preceded death. , . " ~ , ' ' ' . ,'" 0 ' " '

post1r'nortefn exam'i'i:lation showed the, prese~ce ,or' free. fluid in the peri- ' toneum,' gre~t,enlargement' of; the liver, which was dotted with yellowi~h a~eas . and nodules like new growths; and ,multiple absc'esse,s. N 9 primary growth' was, found. Some signs of <;>ld 9-ysentery but no ulcer,atiort in the small gut. Spleen

'was enlarged. Portions of the li~er were: sent to' us by Oaptain, Pasley, R.A.M.d . • ' \ c" • , • \ ••• \" '

, (to whom .we'are indebted f9r these notes), and the bacillus referred' to was isolategfromthe D€lcirotic areas present in the liver. , . . , . Sections 'of tl:ie~ liver' shovyed that th~ nodules referred to were'necrotic

. ,in' character, characterized by. centraL areas of complete cell ~destruction with su;roundingln~ense infiltration of small ce~ls, that is,they were !n, effect

, multiple abscesses.. ~heseareas contained numerou\:l GraIri-nega~ive coliform i!

'bacilli. " ~

REMARKS ON ,THE' CLINIC,AL NOTES,' ETC.

Th.is side-of 'the investigatioI}, is not as COinplet.e' as we should wish, but the situation and the relation. of the Central LabOratory do. not off~r such facilities for the close observation ofcase~ as. the' pathologists of

, ' , ',' ,'.' I hospitals, enjoy. The ear:lier cases had all been, sent down tht;l line before

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'160 " ,

Paratyp"hoid, G;oup:me( wzth in Mesopota}hia

the laboratory investigations were \ sufficiently iJ.dyanced to' suggest special" attention being paid to their clinical state; Latterly all cases have peen' 'seen, and we are i~debted to~~riou8 medical officers for providing notes'

.> and charts and ,forgiving~s access to the cases. " ~ It will be seen that the majority of ,the case~cap:1~ from or near the

railhead of th~ Persian lines' of communication; and especially \ from· the Jelus ,refugees ,or those who have been brought into contact with them,

i This is of interest in view of recent reports (reviewed, in the Tropical Diseases Bulletin) of investigators working in Armenia and the Caucasus' who" have 'des9ribed anomalous' organisms ,of the: same kind~ ,and ,which were. considered by' them to have-affinities, with B. 'suipestifer or B. aertrYQke ,(B. Erzindjian).- ", '

·Se~eral pat'ients,however, have apparently contracted the dIsease in, I}aghdad; one app3;rently was infected,On the Baghdad-Mosulline, and one . culture wasrecehtly sent. to the .laboratory, from Nasariyeh on the South, Euph~ates. .Samples of ,high tihe ",C "serum have been sent out from the laboratory to all first-class laboratories in Mesopotamia, and further evidence of theocGurrence of this strain will probably be available, later.", "', ,,'" - , ~, "" "

or the 11 cases of which we 'ha:ve some clinical details, 6 ,were inoculated with T.A.B.' vaccine 'within a ye!},r;2.longer: ,~han a year"and ' in 3 there was no record; 5 were British and',6 were Iridian. '

l'he organism was recoveredfrohl bl90d cultures in \a pure st~tein'10' ~nd from the urine in lease (21st day). '.'. "

The days oil which blood cultures were ,positive were as ,follows: ·5, 6 \ 6,7,7,8,8,14, 17; 20. - , '

\ ' 'SUMMARY OF CLINICAL, SYMPTOMS. ',. I

, As regards th~ ~ll~ical symptomSiti~ e~identthat in general they ar~ suggestiv:e of the en~eric group of disea~es, as ,biopd cultures have been sent

. on that· supposition. In the charts which are available it appears that the course of the fever isvariab1'e.. . , '

In two cas~s<ther,e were clear-cut attacks of, fever Jasting.aboutten ' days, whilst in others the fever was of a-long continued remittent nature ~. wbichhad some of the characters,but !was by 'no me,ans typical of, the' other varieties of paratyphoid fever.: In sevE3ralcases there 'were well

'marked:,pulfuonary,symptoms, varying from ,bronchitis to congesti~n of the bases,:and inone, case to consolidation oftbe Icing, so that a diagnosis

',0£ pneumonia was arrived at. l '" . , , ,: ' •

. ' The Case 72, is ,remarkable in that well defined necrotic areas were found in the liveI';artd it was from these that the bacillus was isolated. bas~ ,1;165 gave a; p~sitive ,blood~ulture;and ,later the organism was'

. • \1 ,

1 Capt~in MacAdam's c~sesbring outthi~ point still mor~ strongly.

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. F. P. Mackie. and G. i J: Bowen, 161

. isolated 'from. an abscess in the buttock. Tholl:gh we h'ave not 'studied the clinical side ~ufficiently .to point out any distinction between infec· tiori from t~is organism and the paratyphoids A and B,' it seems a~ if f'. Para C" had a particular lia,bility to. produce visceral infections especi· ally in the lungs. ,The slowing. of, the pulse, so markeq a feqture in ,the paratyphoid fevers, seems' to .. be less, evident in these cases .. The othe~' strains referred to" in this' paper are devoid o~ any detailed clipical history. I

" 782, 707, 20, 41, and· 44 are all strains' from Baquba (near'the rail·" .... head for the ,Persian Lines of Communications). The 'last three of these were isolated by one of,· us (G. J. -B~), dJlring an investigation into an epi5J.emic of malaria and dysentery amongst the J elus refugees, who came from the, rieigh.bourhoodof, Lake Van:' .

. The remaining strairis=-viz., 5,297; 4,443, 7,776, 8,021, 4,364, 3,414, were all" para B inagg'lutinables," which have been met with from time to time in,Amara and Baghdad (1917-18), and had~ been set aside for further ,examination. ' , . ! ,

DESCRIPTION' OF TIIE ORGANISM. I

A motile Gram-negative coliform organism, growing freely on agar, and on MacConkey plates as, a' semitransparent, lactose ~on-fermente;r, of medium size: Nb odour is t producbd by the growth on .agar. The sugar reaCtions in such sugars a.s: ate at our disposal are ident.ical "'ith those,of para B.

Lactose •• Glucose .• Mannite ., 'Dulcite ... Maltose' •• 8accharose

'lndol , ..

•• No change A. G.

,A. G. t

A;G. A.G.

•• ,No change

Litinus Milk.

Acid for one or tW9 days. Turns alkaline from third to s;venth day. -

The ,reactions of all the organisms which are the subject of this paper IJire id~ntical in the above . characters, land re~ain constant ~after repeatedsubculture;'This organism will be referred to hereafter as pa'ra P

. for purposes ,of convenience. '

SEltUM REACTIONS. OF' DIFFERENT. STRAINS iMMEDIATELY AFTER

, 'ISOLATION' FROM· T~E PATIENTS.

On ~ccoU:nt qf its biochemical relations to the Gaertner (para B group) it was generally put up with Gaertner high titre sera, but as the ,results show, it,was never ag'glutinated by this serum .

. It, was evident from ,these reactions that we had to deal with an, " anomalous organism, and at first we thought the aggl~tina;ting power would . , be 're?overed by rep~ated subcuhures. '.. ' ' " .

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162 .. Par.atyphoid ~ aroup rnet,with in MesopotamiaJ

,

Sera

, Strains T A -B -----O;;rt~~r :100 200 200 ,

\ 707 709 815 -825 .. 967 +

1,059 ' " 1,165, \ .. (from blood) 1,165 (from abscess)

782 t;250 , + 1,251 1,332 +

, . Fiye strains were accordi'ngiy,pa.s~aged thirty times from broth to broth over a period of about three weeks; They ~ere then tested in se~eral dilutions of stock high titre paratyphoid B serum (Lister Institute, of November 28),

" \ with the following results :-, , ' ",

Strain of Dilutions of B serum', ba0,llus '100 ' 200 400, 800 .1,600 3,200, 6,~00 12,800

815 '825

967 -++ ++ ++ + + ' + 1,059 +

. 131'B.S.H.*' ,-Stock para. B (ROyal} , , Army Medical ++++ ++++ ++-f+ +++ +++ ++

College) , , ' . ' '. • I

, ',* A strain obtained from Captain MacAdam, R.A.M.C ... ,,". -,

, The result snowed that the'lack 'of agglutinating power was not an accidental feature, in that it could not be recovered b~ repeated subculture .

. I ,THE PRODUCTION ,OF A HIGH-TITRE SERUM, TO PAR;A C. , , If .-' •

The ,first two experiments' failed, in that both rabbits died in fr.oin three to f~ur days Of a virulent septic:;emia, caused by,the bacillus with which they were inoculated. 'The vaccine had-),>'eim heated to 56°,C. for twenty minutes, but the bacteria. were evidently not ,killed by this treatrnent. .

For the next experiment the v(1ccines were heated' to 60° C. for forty minutes. Rabbits 782 and ,1,059 were given intravenous injection 9f killed culture beginning at' on~-tenth of a loopful, and ending with one loopful of· living culture: .. 'One rabbit (1,059) died 'in four days after the living dose,

-', and' Its 'se:fum withdrawn post mortem and thatofihe living rabbit,were then tested. The signs ,in the rabbit which died were those of a toxic septi­cremia~The peritoneum'alid pleurre were dotted with small hremorrhages,

. and bloody serous effusi9ns were found in these sacs. I' Rabbit 1,059.shQwed. purple hffimorrhagic inflammation cif the appendix. Annexed are shown the interactions of 'these tw,o sera and st~ains .

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F. P. Mackie and. G. J. ·Bowen 163

Serum from , "" r~~~~ ~~~u- Strain 59 160 D~g~ions of hiito-titre se~u~OO 1,600 3,200 6,400

Btrain782 V • . 782 ++++ ++++ ++++ ++++ ++++ ++++ ++ + 782 v. 1,059 ++++ ++++ ~+++ ++++ +++ / +++ ++ +

" 1,059 v. 1,059 ++++ ++++ ++++ ++-++ ++++ .;J-++ I ++ + 1,059 v. 782 ++++ ++++ ++++ ++++ ++++ ++++ +++ ++

*++++ =, Strong 'agglutination with sedimentation and complete clearjng of supernatant fluid. . . ' ,

',+++ ++ +

=' The same reactions not complete in every particular~ , = Partial agglutination with some opalescence of supernatant fluid.

, ~ Distinct but incomplete agglutination. = No reaction. . -

, '. Cpntrols w'ere' always done and, unless otherwise stated, were negative."

Rabbit 782 was - then ,bled out and its serum USfld' as a'" H;igh-titre C serum" (titre about 3,290). This C serum was then tested against all the .available strains of those hitherto called "para B inagglutiIiable." The results are, s~ol'Vn in Table. II. , '

TABLE H.-PURE PARA" 0 ~ STRAINS' (TYPE "M ")., High- Dilutions 1 in ' ,

'. " Strain titre; 100 200 400 . 800 1,600 3,200 6;400 12,800' sera I

815' "C" ++++ ++++ ++++ ++++ ++++ +++ ++ + *"B" -

825 "C" +++-:+- ++++ ++++ ++++ ++++ +++ ++ + "B" - .' -

1,059 " O"~ ++++ ++++ ++++ +++.+ . +++ ++ + "E" Trace -'

1,251 "C" ++++ ++++ ++++ ++++ ++++ ++++ ++ ++ '~B"· .

;relfis "0" ++7-+'++++ ++++ ++++ ++++ + Trace 20 "E" 31 "C" ++++ ++++ '++++ ++++ -P++ +' Trace

ItS.H: "B'.' \ . ~,~43 " 0" ++++ ++++ ++++ ++++ +++ +++ +

~'B n

J,776 "C," ++++ ++:+-+ ++++- '+++ ++ Trace, ,--"B" --:

\ ~~ace 8,021 ,~C " ++++ ++++ ++++ ++ T ~' B" - "- -'-

3,414 - "0" ++++ ++++ +\~++ ++++ ++++ +++ ++ "B"

72 "0" ++++ ++++ ++++ "B ;,

* Paratyphoid B serum from Lister Institut~.

TABLE H (continued).-PA!lA "0" STRAINS WHICH REACTED ,·ALSOTO A 00-- AGGLUTININ IN PARA "B" HIGH-TITRE.SERA (TYPE HN").(

High: Dilution~ 1 ,in Strain titre

sera 100 200 " 400' 800 1,600 3,200 6,100 12,80(}

782 "0" ++++ ++++ ++++ ++++ ++++ ++ +' "B". ++, + + +

++++ 967 "C" ++++ +++t· +'+++ ++++ ++++ ++ + "B" ++ ++ ++ +. + +

'1,250 ,~c " ++++ ++++ ++++ ++++ ++++ +++ ++ Trace "B" ++ ++ ++ ,+ - -.'

. Jelus' "0" ++++ ++++ ++++ ++++ ++++ +'+++ +++', + n ",B" \ + + ++ :i- + + +

Jelus " C'" ++++ ++++ ++++ ++++ +++ +++ ++ + 44 "E" +++ +++ I ++. ++ ++ +

5,297 ",0," ++++ ++++ +4-+ +++ ++ ih+ .,.. -'-

"·B ". +++. +' + + 4,364 " C .. " ++++ ++++ .++++ +++ .+++ +++ -+

"B". + + + -'- '

1,332 "0" ++++ ++++ ++++ .++++ +++ ,++ Tra.ce "B" + + ++ Trace

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164 Paratyphoid Group mrz,.t with in Mesopotamia

THE AG~LtJTINATION REACTI~NS OF PATIENTS' SERA TO VARIOUS

I I STRAINS OF PARA "C" BACILLI.

Experiment I.~ Serum of Case 1,250. (Inoculated with'T.A.B. vaccine nine months' previously.) .

v. . Bacillus 1,250 ", Para" 0" (782), ' Stock Para B

1125

++++ ++++

++

1/50 ++

+++ +

1/125 '± +

1/250 l/GOO

Experiment II.-Serumof Case 1,251. (Inoculated with T.A.B. vaccin:e about four months previously.) ,

v. 1/251/50 1/125 1/250 1/500 Strain 1,251 _" ++++ ++ + Para "0 "(782),,·' ++++ ++++ ++ + ± Sto~k para B '," ++ ' ++ + +

Experiment lll.-Serum of Case 1,332. (In this case the bacillus was cultivated from 'the urine in the third week of the disease.' There was no history of anti typhoid inoculatiqn.) ,

v. Strain 1,332

. Para;" 0 "(782) •• Para B •• ,~

1/25 ,++++

+++

1/50

+++-+:

+++

1/125 ++++

-+

1/250

++++

+

1/000 ++++

+ Floc: soft , and ,

, . dispersable

Experiment IV.-Seruinof Case i,165.· (In this case the 1:)~cilius ,had been isolated first by blood culture and later from a'-subcutaneous abscess. ' The patient had had two doses of autogenous vaccine. He had received typhoid vaccine 'three and a half years previously.)' . "

, '. '. ' _. v.

Strain 1,165 Para" 0" ParaB ••

I 1/25

++++ ++++

1/50 ++++ ++++

1/125

++++ ++++

1/250 +++ +++

1/500

+ ++

, Experi1n~nt V.--,-A control experiment, w~th the serum of a patient

'(No .. l,298) from wh~m a true para B had ~een isolated from the stools. v. 1/25 1/50 1/.125 1/250 1/500

Strain 1,298 ++++ I +++ ++ ++ Para "0" ' Para B .•• ++++ ++++ ++++ ++++ ++++

Experiment VI.-,-Theserum of one of the patients (No. 1,251) put up .' .~ against ~ 'number of differ:ent " C " strains isolated from other patieIlts~ ,

v. Bloo4 serum of~ase 1,2~4. - 'u

," '0 " strains etc. 1/25 1/50 1/12. 1/250'

782 +++ +++ + + 1,251 .. ++++ ++++ ++++ ! ++++ 3,414 " •• ++++ .++++ ** ." ++++ 7,776 ' ". ++++ ++++ ++++, ++++ Jelus 20 +++-t: ++++. ++++ ++++ 31 ++tr-+ ++++ ++++ , ++++ G.-pig Aertrycke. ++ + Para. B (No. 7,115) +++ ++ ++ +

* Not carried further, -* * Accident:

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. , F. P/ Mackie and G. J. Bowen 165

Remarks.,-It is evident from the abo~e' results that the~ blood of patients . suffering from '" para, C", infection shows well-marked 'agglutinating"

properties when tested against the homologous organism and also against, othe:r "para C" strains. rrhe power of" agglutinating paraB was, in every case much less marked ; this may have been9:ue to the presence of a

\' 'co':agglutinin or in some cases, more probably'to the effect of recent T.A:B. inoculation. ' ,

·ABSORPTioNExPERIMENTS.

From 'the fo~egoing' data in Table II it will be apparent that of the strains grouped under the" para C " category, eleven ,are agglutinated in ,very hig1;t dilution by "C" serum 'alone and not at all influenced by para B se'rum ,; whilst eight strains are influenced by both sera.

In the latter, however, th~ reactions with" C " serum exhibit a degree and type of agglutination which of. themselves would suggest a very much ~ closer serological affi~ity t() the" C," group ,than' to, pa~a B; An attempt was, therefore, made to determine whether representatives 'of the two types, Type "M" (agglutinated by "c" serum only) a,nd Type "N" (agglutin\1ted by "C " serum 'and' B serum, though in different degrees and of different type, ,as expla~ned above) could ,remove tqe specific B

, agglutinins from ,a ,B serum. I,

/ The strains used were No. 31 and No. 44. Experiment I.-Absorption of 13, serum b'y ",C" strain No. 31

(M. type). ;I!efore Absorption.

Dilution 1 in: 'lOO 200 400 ' 800

B serum v. BIBacillus ... ++++ ++++ ++++ +++ , v. Strain 31

1,600 3,200 6,400

Superuatant v. B_ " ' ~ 'v. 31 I

"

+++ ++'

, After Absorpt~n with Strain 31.

++++ ++++ ++++++++ +++++++ \

Rema~ks.-As might, be' expected, no removal, of B agglutinins occurred after absorption with strain No. 31~ which' is uninflul'lnced by B serum. ' '

Experiment- Ii."':"":Absorption of B serum with" C '.' strain No. 44 Jelus, C" N " -type).' " ' ,

Before Absorption. , \/ ,I pilntion 1 in : \100 200, 400

B serum v. B bacillus ;+-+++ ++++ +:+++ v. Strain 44.. +++ +++' +++

800 ,

+++ ++'

Superuatant v. B , v.44

" After Absorption with Strain 44.

++++ ++++ +++* +++~ ++ ,+, I - -,

I

1,600 3,200

+++ ++ ++ +

++++ +++

6,400

Remarks.-Absorption' of B serum: with No.' 44. has not effected, the removal of specific B agglutinins Ibut has simply removed the

. .' co-agglutinin.. in B ,serum for strain No. 44. '

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-, ' .. 166" ,Paratyphoid Group met with ~n 'Mesopotq,mia

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Experirnent IiI.~A c~ntrolabsorption e~periment. B serum absorbed ',' . with a n strain, No.- ,7,115. "~

, f' .

Before Absorption. Dilution I in: 100 200 ,', ,400 800· "

B serum v. B bacillus .. ++++ +++4- ++++ +++ ;~ v. Strain 7,115 +'+++ ++++ ++++ \ ++++

After Absorption with No. 7,115.' ' Bupernatant v. B· .•. , +++ +' .

" v. 7,115 •. ++ \ +

1,600 3,200

+++ .++ +++' " +++

6,490

Remq:rks.- Shows nearly complete removal of. specific B agglutinins by absorption' withN·o. 7,115 (a recently- isolated B ,'strainj. " \ It has not bee~ po~sible to multiply e~periments of this kind. owing' to technical difficulties and accumulation of other work, but it is hoped that opportunity may be afforded at the List,er Institute, London, for a, more complete study of the strains from ,the absorption point of view. The question whether these" C" strains may be allied to B. aertrycke has'. been' borne in, mind but owing.to the lack of a classical strain of B. a.ertrycke and an anti-aertiycke' serum this matter has' only been partially undertaken in Baghdad. .'

Whilst the above work was in' progress an epidemic of gastro-enteritis', accompanied by' very high mortality,' occurred amongst young calves at, the" Military Dairy Farm, Amara. This outbreak wa~ investigated by Capt~in Laurence, R:A.V.C., the veterinary bacteriologist, who recovere~ from 'the blood of some of th~calves' strains which he, in conjunction with officers of the Central Laboratory, 'Baghdad, was able to demonstrate a~ belonging to the Gaertner-paratyphoid group .. ,This investigation will be duly reported upon by the officers concerned. These ,calf 'strains are agglutinated well by B serum and also to some extent by'" C" 'serum and n<,lt at all by ~ Gaertilerserum, and in all pr()bability they will: be found to ,be genuine B, aertrycke. '

At the same time II:~ epizootic occurred also among the guinea-pigs ~t the ,Central Laboratory; A~aia. Strains of a similar organism were isolated ~Y Major T,H. Gloster, 1.1\1.S" and these like the calf strains have been used as presumed B. aertrycke strains in the experiments which .follOw :.:.....,. , . ' . ' '. ,

Experiment IV.-Absorption of " C" serum with calf strain No. 4 . . ' Be/ore -A bsorption. '

Dilutioh 1 in: 'lOO '. 200 . 400 ' 800 '

" 0" serum v. Oalf No. 4 '+'++ . ++++++ ,+++ 1,600 " ,3,200

.+++ ++ 6,400

Trace

"" ,v. B +++ .++ ++ +. After Absorptio~ with Calf NO., 4.

+ + '" . 'SuP'lrnatant v. No. 4

. v. "C ", ++++ ++++ +++ +++ +++ "

v. B

EXp'eri~ent' V.--.:.Absol:'ption ~f. " C ., serum with calf strain, No. 6. I I,

. Before Absorption. Dilution 1 in: '200 400 800 I 1,600 3,200 6,400' 12,800 25,600

" "0" serum'v. OalfN().6 +++ +++ +++ +++ +t+ +++ +++ , :B serum v. Oalf 6 .. ++++ ++++ .:++t+' ++++ ++++ +++ +'++ '

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F:' P. Mackie and a. J. l?owen

After Absorption oI" 0" serum with No. 6. Supernatant v. No. 6 , ,

, v. "0"++++ ++++ ++ + + + +' " v. B .. I. , _. _. ,,', ,_

Remm·ks.,The, ab6ve two expe~iments show that the specific "-C" , aggh~tinins are not affected l?y absorption with either of, the calf, strains. The absorption simply removes the co-agglutinins in " C" seru'm for the' calf strains and for paraB. '. ' .

A further series of 'exp~riments (not here detailed) in.which" C " serum was absorbed with the presum'ed B: a'e1·trycke (B. suipestifer) isolated from the guinea-pig epizootic yielded a similar result-viz .• no' removal of the sp'ecific" C" agglutinin but only that of the co~agglutinin in " C " serum for the guinea-pig strains, the calf strains and B. paratyp~osus B. ,

It is hoped that opportunities "will be afforded for multiplying and repeating' experiments of· this nature, but at p~esent it would -appear fairly clear~hat the "C" strains can' be serologically differentiated both from true para 13 and from the 'presumed \ aE)rtrycke strains,.recovered from 'the calf and guinea-pig epid,emics. . '. ' ,

We wish. to' ,acknowledge. the help, and guid~nce which has been 'given us.in ,this investigation by Lieutenapt-Colonel J. C. G. Ledingham, C.M.G.,' R.A,M.C. ' He has also, .kindly agreed to take some of the strains back to London and test them, against classical strains of )3. suipestifer: We also wish to ~cknowledge' ~he help of Serjt. Tr:asler, ·Royal Army. Medical ,Corps, and Pte. Bull, Royal· Army Medical Corps.

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ADDENDUM. -

Whilst this paper was' awaiting publication a communication has appeared in the Lancet, of February 22, 1919, p: 396, by Dr.'L. Hirschfeld, entitle'd "A New Germ of Paratyphoid." From his description it appears 'that Dr. Hirschfeld has met with' an organism similar to, if not ~dentical with that described by us in this paper. He nas '-met with the organism we describe at intervals during the years 1916,11917 and 1918, and the paper'descrIbing it was read before the Inter-Allied' Medical' Society in' Salonika on December io, 19H3. .'

~he organism we describe has been met with from time to time. during 1917 and 1918,but it was only in September 1918 that' we began 'to carry out the experiments wrich led us to the conclusion that we were dealing with a specific entity. ,1 ".' " •

, ,N'OT~ BY i." C. G. ,LEDWGHAM, ,LISTEB INSTITUTE. \ ,

, The" C" strains labOve described .have beenretested in this Institute ;with results entirely confirmat~ry of those detailed . by Mackie anp. Bowen. -' 1/

:Further, the Hirschfeld strain, obtaiJ;led through' the kindness of Colonel Ha~vey, Army 'Medical Servipe, of' the Royal Army Medical College, behaves ex~ctly like the' Mesopotamian," q" strains a:tiq',is, agglutinated

'to t~tre by the Baghdad" C " serU}ll. ,The strains jSoli!.ted from the~alf ,ap~, guinea-pig epizootics at .Baghdad and ~mara prove ; 'to be 'typ~s of B. suipestifer,. ' ,

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