5ection. of Epibemtiologi anb state f1ebicIne

5ection. of Epibemtiologi anb state f1ebicIne.President-Dr. E. W. GOODALL, O.B.E.

Trench Fever: Its Epidemiology and Endemiology.1

By W. BYAM (Major R.A.M.C.), and LL. LLOYD(Captain R.A.M.C., T.).

THOUGH the title of our paper is " Trench Fever: its Epidemiologyand Endemiology," it will be well to begin by giving you a descriptionof the disease, as its causative organism is at present unknown, andthere is no single sign or test by which it may be recognized withcertainty.

Trench fever has also been known as " five-day fever" and"Wolhynia fever." It is a blood infection communicable from manto man by means of the louse (Pediculus humanus); and is characterizedby recurrent pyrexia, headache, giddiness, pain in the lumbar region,pain in the limbs, chiefly in the legs, and often of considerable severity;conjunctival congestion, sweating, moderate leucocytosis at the heightof the fever, and slight enlargement of the spleen. In some casesa period of irregular fever follows, and eventually a certain percentageof the patients pass into a stage of chronic ill-health. Infection isoften verypersistent, and acute febrile relapses may occur after monthsof quiescence.' The fact that trench fever is not a form of enteric wasclearly proved by the American Red Cross Medical Research Committeeworking under Strong in France during 1918.

Though evidence is forthcoming which shows that trench fever hasbeen known to physicians in Poland as " Febris Wolhynica" for sometime past, it may safely be said that the disease was first recognized asa specific entity during the Great War, when it appeared on all the

' At a meeting of the Section, held October 24, 1919.

N-4

Byam and Lloyd: Trench Fever

European fighting fronts-800,000 being the approximate number ofcases occurring in France among the Allies during four years. If thedifficulties connected with the diagnosis of a disease such as that justdescribed be borne in mind, it will be realized that no reliable statisticsof the incidence of trench fever exist or are likely to be compiled in thefuture.

From Europe the disease was conveyed to Egypt and Mesopotamia,and sporadic infections have been reported among those coming intocontact with returned troops in England and elsewhere; and itis safe to say that the long periods during which the blood of trenchfever patients remains capable of infecting lice make it probable that thedisease will have a far wider distribution in the future, when thoseinfected in Europe have returned to their homes all over the world.In this connexion it is well to point out that the distribution of theother louse-borne diseases by no means corresponds to the distributionof lice, and that a study of the range of typhus and louse-borne relapsingfever is probably our most reliable guide to the future endemic areas oftrench fever, though Australasia will probably become infected as well.

Trench fever being transmitted by lice alone, as far as ourexperimental evidence at present shows, its occurrence depends onthe presence of these insects and of human carriers of the infection.As with other insect-borne diseases, the vector requires to be inconsiderable nurnbers before an epidemic can break out, and closecontact between human beings is necessary to facilitate transferenceof lice.

The spread of lice is due, to some extent, to their own active habits,for when their host is in warm surroundings, so that the temperatureoutside his clothing approximates to that inside, they are liable tomigrate from him and pass on to others in the immediate neighbourhood.This takes place especially in beds where two people are sleepingtogether. To sleep with one who is infested with lice is a certainmeans of becoming verminous. Lice, as we shall see later, are alsoliable to leave their host when he is febrile and his skin becoines toohot for them. They also leave him at his death and cling to hisbedclothes and surrounding objects, and are then very likely to adhereto anyone coming in contact with these bedclothes and surroundings.They may be dislodged by brushing and fall to the ground, and it hasbeen stated that they have been blown off by the wind and carried to adistance. They may also leave discarded garments of their own accord.Lice spread abroad by any of these means may be termed " stray lice,"

2

Section of Epidemiology and State Medicine

which are in a very helpless condition for finding fresh prey as comparedwith the human flea or the bed-bug. The flea jumps into the air whendisturbed by a sudden draught of wind, such as is caused by a footmoving near it, lights on anything it meets with in its course, and thusfinds its temporary host. The hungry bed-bug hunts down its victim,probably guided by his scent,-often travelling long distances to find him.The stray louse can only wait till a fresh host comes into contactwith it, or wander aimlessly about on its legs which are not very welladapted for travelling on anything except rough cloth or hair. Peacockshowed that it is improbable that lice are attracted to man in any wayby his smell, since they take no notice of a sweat-impregnated shirtplaced near them. They are guided in their movements, to someextent, by a sensitiveness to light. When well fed they creep into darkplaces, but hunger drives them towards the light again. This habit,'however, helps them little in their search. They are very sensitive toheat, being adapted to the temperature which exists between the skinand the clothing-860 to 90 F.-and what guidance they get in findingnew hosts they probably obtain from this faculty alone. Stray lice in abed very quickly find out a man who sleeps in it. The temperature oftheir surroundings has a profound influence upon their movements andvitality. At 104° F. they are extraordinarily active, running roundand round with the rapidity of bed-bugs. At 90° F. they are moderatelyactive, and if unable to feed, digest what food is in them, and die aboutthe second day from starvation. At the temperature of a warm room,about 70° F., their activity is little marked, and their vitality is soreduced that they may survive a week without food. At still lowertemperatures they become moribund and die slowly, some having beenknown to survive ten days at the freezing point, and this is the longestperiod during which lice have been known to live without food. Whilethey remain active the distances that they are able to travel are some-what surprising, their movements, though slow, being fairly persistent.A well-fed female louse was observed to walk along a stretched threadof cotton for a distance of 4 ft. in tbirty minutes, in a warm room, theimpulse to walk being produced by placing- the louse at thetend ofthe thread near the window. Peacock observed that two lice travelleda distance of 5 ft. in an hour in a place where they had apparently noparticular stimulus to guide them. By wpaeans of such wanderings thelouse is no more likely to find a fresh host than by remaining where ithappens to fall. If it is on a smooth s'urface, such as a board, and a clothsurface brushes over it, it immediately attaches itself to the cloth, and

3


we have occasionally availed ourselves of this habit when lice haveaccidentally fallen on the laboratory floor, by passing a turkish towelover the place where they fell and at once recovering them. Again,if the insect is on a cold cloth surface and a warmer one is pressed againstit, the louse will immediately attach itself to the warm cloth. In thisway lice may be picked up in public conveyances with cushioned seats.As these chances do not occur very often, it is certain that the vastmajority of stray lice die without finding a new host. The morecongested the community the more likely are they to be picked up.It follows also that when lice infest a discarded garment the bestchance for them is to remain where they are in the hope of the articlebeing worn again. This is what the majority of them do. A stravlouse, when it finds a new host, can, of course, only multiply if ithappens 'to be a fertilized female. A single louse, however, is enoughto give rise to an attack of any one of the louse-borne diseases, shouldit be an infected one. We have a record of an officer who receiveda single louse upon his skin, scratched himself, and, in due course,developed trench fever, and in like manner we have produced trenchfever experimentally on several occasions by means of a single infectedlouse or its excreta.

An utoccupied dwelling cannot be infested by lice in the manner inwhich it may be infested by bed-bugs or fleas, and the presence of licedenotes recent occupation. Peacock, who ,tudied the disseminationof lice among our troops in France, discusses in detail the reputationwhich certain dug-outs get for being lousy. He comes to the con-clusion that this lousiness is due to the presence of infested mnenand not to any inherent quality of the habitation. The dug-outswith the worst reputation were the largest, those in which most mencongregated.

Bedding, however, is a most important source of spread, and it iscourting disaster to sleep in that recently used by an infested person.Most convincing figures in proof of this are quoted by Nuttall. Dr.Hamer, of the London County Council, had the beds examined weeklyin some common lodging-houses, which were largely used by people ofthe tramp class. Throughout one year, in the different months, from12 to 31 per cent. of the beds were found to contain lice; the numberbeing higher in winter and lower in summer. Incidentally, the resultof his inspection over a number of years, was to reduce these percentagesto less than 5, owing to the increased care engendered in the keepers ofthe houses. There is no reason why lice should not lay eggs on blankets,

4


since they do so on the outer garments to which blankets correspondduring the night. Beds unused for several weeks might therefore harbourlice, since the hatching of the eggs may be retarded by cold and theincubation be completed later.

Lice also spread by means of garments, and this is probably themain source of spread in armies, where clothing is largely communalproperty. It has been repeatedly noticed that when lousy garments arediscarded, the lice are liable to congregate outside them, and these liceare very likely to get access to clean clothing which comes in contactwith them. They have also been observed to creep out of the necks ofkitbags and may, in this way, pass on to clean kits. The ordinaryprocesses used in a' laundry do not necessarily kill lice and their eggs,since the water used for washing is often not of the lethal temperature,and soaking in cold or only warm soapy water does them no harmunless the immersion is very prolonged. Garments apparently cleansedfrom dirt may therefore harbour vermin, and those who put them onbecome infested.

Lousiness.-If garments containing lice are worn continually dayand night, the vermin increase and multiply in a remarkable manner.Cases are on record in which single garments 'have held thousands.These are unusual cases, and indicate either extreme helplessness on thepart of the infested person or, what is more likely, utter indifference tothe filthy condition. In attempting to arrive at an average estimate oflousiness in troops, Peacock excluded these extreme cases, and foundthat where 95 per cent. of the men had lice upon them, the, averagenumber was twenty lice per man, the range being from ten to thirty.In another series of men he found about 3 per cent. with more than350 lice each, while one shirt he examined was estimated to contain10,428 lice apd 10,253 eggs.

It is important to remember when inspecting people for lousiness,that the eggs of the louse may be laid on the hair of the body. Inthis position they are very difficult to see, but careful inspection and agood light will often reveal them. It is practically impossible to saywhether isolated eggs found in these positions are those of the body-louse or of the head-louse, the only difference between these two formsof lice being the very elusive one of size. The matter has been thesubject of controversy, as some observers, perhaps unaware that thehead-louse may infest the body-hair, have recorded the nits of thebody-louse in these positions in large numbers. That body-lice do layeggs on the body hair we finally proved in experiments in which men

5


were artificially infested with body lice for a night. In one experimentwe found a dozen freshly laid eggs on the pubic hair of one of themen who was, of course, louse-free before the experiment. To makequite certain that they had been laid during this night, the eggswere incubated, after the hair on which they had been laid was cutoff, and lice emerged from them in due course.

Body-lice are found on man all over the world, and there is prob-ably no tribe free from them. They are, however, less prevalentin tropical than in temperate and cold climates, and in temperateregions are less niimerous in summer than in winter. This is in cor-relation with the different habits of people in the winter. Thenunderclothing is more likely to be of wool than of cotton, and liceprefer wool. It is also the custom with many people in this country,for some reason that is difflcult to understand, to change woollengarments less frequently than cotton ones. Among certain classes inwinter, the day clothing is also worn at night. People also at thistime keep more indoors and crowd together over stoves. All thesehabits are in favour of the spread and increase of lice, and there is nocreature in creation more ready to seize time by the forelock than thelouse.

Soon after the first cases of trench fever were recognized in France,it was realized that they usually occurred in groups, the victims mostfrequently being sleeping companions or persons coming in contactwith one another; the explanation of this being that lice tend tomigrate from a fevered host and so spread infection in the immediateneighbourhood. We were able to prove this by carrying out thefollowing experiments. Some of the soldiers under treatment atthe New End Military Hospital, Hampstead, and the civilians who wereallowing us to infect them with trench fever, offered themselves forthese exceedingly unpleasant experiments, being willing to spend highlyuncomfortable nights in the interest of science. The experimentswere carried out in a small room with distemnpered walls and boardedfloor. It was not artificially heated, and the work was done in Februarywhen the weather was cold and raw. A bed was made up on the floorof the room consisting of two mattresses placed side by side and coveredby a white blanket, with ordinary pillows and pillow-slips, and fourwhite blankets to cover the men. Into this bed the men, clad inflannelette pyjamas, went in pairs, and 200 body-lice were released onthe abdomen of one of them in the region of the umbilicus. The lice-used were, in each case, adults and well-grown nymphs, since young

6


larvae might have proved difficult to retrieve. The men were instructednot to get out of bed; not to touch the insects; to avoid scratchingif possible; to interfere in no way with their roaming. They werealso asked to note when and where they were bitten.

Every two hours the temperatures of both men were taken, andnotes were made as to the condition of their skins, whether moist or dry.Sometimes a brief observation was made as to the scattering of the liceat the time of our visits, and the men were questioned as to the biting.The experiments were allowed to proceed for varying periods, generallyabout sixteen hours, and the lice were then again collected and theirdistribution on the men and blankets noted. It was found necessary,in each case, to rip along the tape holes of the pyjama trousers and toopen any seams into which the lice might have obtained access. Inthis way complete data of the migrations of the lice were obtained. Sixof these experiments were carried out, in three of which the man uponwhom the lice were released, called the primary host, was febrile; andin three he was normal. His bed fellow, the secondary host, was normalin each case. The febrile man was in each case suffering from trenchfever. There was a very marked difference in the behaviour of the licein the two series of experiments, there being an increased migrationfrom the primary host when he was febrile. When both men wereafebrile, 62 per cent. of the lice remained on or near the primary host,35.5 per cent. being inside his pyjamas; while only 20 per cent. passedon to or near the secondary host, 9.5 per cent. of these being inside thepyjamas. When the primary host was febrile, only 44 per cent. of thelice remained on or near him, 15'5 per cent. as opposed to 35'5 percent. being inside his pyjamas, while 38'5 per cent. instead of 20 percent. passed on to or near the secondary host, 12'5 per cent. being insidehis pyjamas. It is therefore seen that the febrile condition of the primaryhost nearly doubled the migration. When the primary host was febrile,the second man felt the biting of the lice very much earlier than in theother cases-in the first, second and third hour respectively, whereas inthe afebrile series the secondary host was never bitten within fivehours from the commencement of the experiment- so soon in factthat it is indicated that some of the lice migrated either before theyfed on the febrile man, or, any rate, before they had obtained a fullmeal. Where the first man was normal the interval before thesecond was bitten was such as to have allowed the lice to be readyfor a second meal after having fed to temporary repletion when theywere first released.

7

Byam and Lloyd: ITrench Fever

CHART I.

Illustrating the migration of lice from an afebrile man (P. H.)to an afebrile bedfellow (S. H.).'

' The charts, tables, and illustrations accompanying this paper are reproducedby permission of Messrs. Henry Frowde, Hodder and Stoughton.

8


CHART II.

Illustrating the migration of lice from a febrile man (P. H.to an afebrile bedfellow (S. H.).


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The temperatures attained by the sufferers from the three diseasescarried by lice and characterized by a febrile condition are: in thecase of typhus fever 1030 to 1040 F., sometimes 105' F.; in that ofrelapsing fever 104° to 1050 F. usually; and in that of trench fevercommonly 1030 F., often 104° F. It may therefore be taken as proventhat the fevers of these maladies tend greatly to increase the sheddingof the lice from the patients, quite apart from their deaths, and thatthis phenomenon is partly accountable for the rapidity with whichlouse-borne epidemics spread.

The conditions of war or famine greatly favour the multiplication oflice, and at such times epidemics of trench fever are likely to occur;but over-crowding, dirt, and other depressing circumstances all reducethe inclination and opportunities for disinfestation, and provide conditionssuitable to the transmission of the disease. It is easy, therefore, to seehow " louse-borne" diseases have usually been regarded as "dirt-borne"in the past.

During the louse-borne epidemics in Roumania, which occurred in1916 and 1917, it was noted that the assemblage of large numbers ofpersons at the centres established for vaccination and prophylacticinoculation led to an increase in the number of cases of typhus andrelapsing fever, and there is every reason to. suppose that there mightbe a like increase in cases of trench fever under similar circumstances.

A large number of cases of trench fever resulted among troops inthe field from the use of bedding and clothing discarded by the sickand issued to healthy men before being thoroughly disinfested anddisinfected. Even when measures to destroy the lice have beenthoroughly carried out, such articles may still remain a source ofdanger. The excreta of the lice are infective and remain so afterexposure to dry heat at 80° C. for twenty minutes-moist heat atconsiderably lower temperatures (600 C. for twenty minutes) is capableof sterilizing them. In addition, sunlight, prolonged keeping (fourmonths and possibly longer), and exposure to soap and hot water,as used when clothes are washed by hand, have been proved, experi-mentally, to have no effect on the infectivity of the virus as containedin louse exereta. Such droppings of lice adhere to fabrics, and it iseasy to understand how the blankets and garments of the sick arecapable of transmitting trench fever when issued to other men. Theexcreta become detached when the article is again taken into use, andmay enter cuts, scratches, open wounds, or even the conjunctival sac,and infection is the result.

11


The contamination of food by louse excreta is not a source of danger,as infection in man cannot be produced by the mouth; neither caninfection take place by inhalation-a point of importance when werealize the ease with which the light dust, derived from louse excreta isblown about.

The prevalence of scabies may be an epidemiological factor ofimportance, for lesions of the skin result from this *disease, and constantscratching ensures inoculation if infective louse excreta are present.

Now to turn to " seasonal incidence." Cold weather, in that it leadsto the wearing of underclothing for long periods, and keeps peopleindoors and in close contact when fuel is scarce, is an epidemiologicalfactor under the conditions already discussed. Atmospheric conditions,per se, do not appear to have any influence on the spread of thedisease. The effects of atmospheric conditions on the prevalence oflice is too big a subject to consider here.

Fragment of sewing-cotton fouled by louse exereta. (x 30.)

The chief epidemiological factors are therefore: (a) human carriersof trench fever; (b) lice; (c) close association between the sickand the healthy; and (d) garments and bedding which have beendiscarded by the sick and then taken into use before being properlytreated. The endemiological factors cannot be said to be known withcertainty. Hereditary transmission of the disease in lice does not occur.The excreta of lice, though infective for four months after being passed,and possibly somewhat longer, have failed, to produce infection when keptin the dry state for nine months or more. The human carrier casealone remains.

It having become evident that a lirge proportion of the cases oftrench fever invalided home showed a tendency to pass through asubacute stage into a chronic condition, with symptoms of disorderedaction of the heart, and also, in some cases, of neurasthenia, two seriesof experiments were performed by us for the War Office Trench FeverInvestigation Committee in order to obtain some further information asto the duration of these infections. The results, we think, establish the

.12

Section of Epidemiology and State Medicine 13

fact that the sequelm of trench fever are but a continuance of the diseaseand evidence of a persistence of infection-a finding that must have afar wider bearing on the field of medicine generally than on that oftrench fever alone when other neurasthenic conditions are considered-and a finding that explains how an epidemic may be started anlew.

Series I.-Chart III is that of a patient said to be suffering fromneurasthenia, who complained of indefinite pains in the limbs, atendency to excessive sweating, the symptoms of disordered action ofthe heart, and who was nervous, depressed, and much below his usualweight. Lice were fed on him from the two hundred and ninety-eighthto the three hundred and thirty-ninth day from the onset of his trenchfever attack-that is to say, nine months from the commencement of

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Patient said to be a neurasthenic. Lice were ied upon him from the twohundred and ninety-eighth to the three hundred and thirty-ninth day from theonset of his trench fever attack. During this period he was only febrile asshown. The exereta from these lice produced the infection shown on Chart IV.

his illness, the patient having been in England and under our observa-tion from, the early febrile stage of his disease, which was contractedunder natural conditions in France. During the period the lice continuedto feed he was only febrile as shown. The excreta collected from theselice, on inoculation into a healthy volunteer, produced an infection, thefever of which is shown on Chart IV. During this fever period, licewere fed on the volunteer and excreta from them inoculated into asecond healthy man: Chart V shows the resuilt. It can only besupposed, therefore, that this case of neurasthenia was really one oftrench fever, in a form capable of infecting lice, and a danger to those

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14 Byarn and Lloyd: Trench Fever-

around him. The fact that the lice themselves were non-infective beforebeing used in the experiment was proved by inoculation of their excretainto two healthy volunteers, who showed no apparent change as theresult-of this inoculation.

Series 11.-A case similar to the one first described had been infectedwith trench fever in France, under natural conditions, fifteen monthspreviously, and had been under observation in England for thirteenmonths when the experiment began. Two hundred and fifty lice,obtained by the kindness of Mr. Bacot, from the same clean stock asthat used for the experiments in Series I, were fed on this man twicedaily from the four hundred and forty-third day of his disease onwards,for a period of twenty-eight days. The excreta passed by these lice

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The result of infection with excreta from lice fed on the neurasthenicpatient whose chart (III) is shown above.

were collected and 40 mgm. were emulsified in normal saline solution,and injected subcutaneously into a healthy volunteer. Fifteen dayslater an acute- febrile illness (temperature 1030 F.) began, with frontalheadache, pains in the loins, and pains in the knees. On the followingday the eyes were pink, the tongue -slightly furred, and rose spotsappeared on the trunk-chiefly the abdomen. There was tenderness ofthe knee cartilages and of the lower portion of the left shin. Pain inthe head and in the calves and lumbar region became so severe thatmorphia had to be administered. The area over the spleen. was sotender that it was- impossible to determnine whether this organ was.enlarged. Four days from the onset of illness, the volunteer was free


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Byam and Lloyd : Trench Fever

of all symptoms, and no enlargement of the spleen could then bedetected. On the following day severe frontal headache returned, therewas extensive herpes labialis, and the temperature rose rapidly to 102° F.No further febrile relapses occurred, but convalescence was prolonged.Lice were fed on this volunteer from the fourth to the thirty-third day.of his febrile attack, and their excreta, in turn, when inoculated intothe skin of a healthy man, caused an acute attack of trench fever afteran incubation period of seven days.

It is obvious, therefore, that the correct diagnosis of these late andpersistent cases is of the greatest importance, both for the sake of thepatients themselves, whose sufferings at present are little understood,and for the sake of those with whom they come in contact and whoare, therefore, liable to be infected should lice be present. And wemay say, when considering the endemiology of trench fever, thatchronic carrier cases are the most important factor.

Finally, it may be well to summarize our present knowledge of the,mode of transmission of the disease. Trench fever is conveyed fromman to man by means of the louse (Pediculus humanus), both thebody-louse and the head-louse being capable of transmitting infection.Such experiments as have been carried out suggest that fleas, bed-bugs,ticks, and mosquitoes are incapable of passing on the disease from manto man, and as the usual laboratory animals, including birds, have provedimmune to infection, it is probable that no other intermediate hostthan the louse plays any part in the spread of trench fever.

The exact part that lice play in the transmission of the disease hasbeen the subject of much discussion, but the main facts to be deducedfrom our experimental work and that published by other observers maybe summarized as follows:

(1) Lice that have fed on a trench fever patient become infective tohealthy men after a period varying from five to eight days from the-first infecting blood feed.

(2) Conversely, lice that have fed only on healthy men are incapableof causing trench fever.

(3) Lice once infected probably remain so for the rest of theirlives, and certainly up to the twenty-third day of their infection.Such lice, however, do not pass on their infection hereditarily.

(4) When infected lice feed on healthy men, a certain number ofinfections will be produced; though the time that such louse feedingrequires to be continued before infection results is often as much asthirty days or longer. Young men react mnore readily to louse bites

16


than do old men, and old men, though equally susceptible to infectionwhen their skin is artificially broken, rarely contract trench fever wheninfected lice are fed on them.

In this connexion it is well to note that lice are constantlycontaminated with their own exereta, masses of which may be seen,by means of a hand lens, adhering to their surface, and that, no matterwhat position lice are fed in, their excreta will generally reach the skinon which they are feeding, and often in a semi-fluid condition as theresult of solution in the sweat.

(5) The excreta passed by lice, which have been fed on trench feverpatients several days previously, are capable of producing trench fever inhealthy men. The minimum interval varies in different instances fromfive to eight days.

(6) Such infective exereta may enter the body through abrasions ofthe skin, particularly those resulting from scratching induced by theirritation of lice, through gunshot and other wounds, and throughthe healthy conjunctival sac.

(7) A very high percentage of lice eventually become infectedwhile continuing to feed on a trench fever patient. In this connexionan experiment we carried out is of interest. Lice, from a non-infective stock, were obtained from Mr. Bacot at the Lister Instituteand fed for five days on an active case of trench fever, being placed onthe patient for half an hour every morning and evening. Twelve licewere then selected at random, and isolated in twelve glass tubes, whichwere numbered 1 to 12. Thereafter the lice were fed separately,twice daily, on healthy men, and transferred to fresh sterile tubes eachmorning. The excreta passed each day were collected separately andexamined for Rickettsia bodies. No Rickettsia bodies were seen in theexcreta of any of the lice passed during the first twenty-four hours aftersegregation. By the twenty-sixth day from the first infecting bloodfeed, lice Nos. 7 and 9 were dead, and No. 12 had escaped. Theexcreta from all these lice, however, had been demonstrated to containRickettsia bodies before this. Of the remaining nine lice, No. 6 hadnever shown Rickettsita bodies in its exereta, while the other eight licehad done so-Rickettsia being intermittently present from the seventhday of the experiment, and consistently, and in increasing numbers,from the seventeenth day onwards. On the twenty-seventh day ofthe experiment, louse No. 6 (Rickettsia-negative) was crushed andemulsified in two drops of normal saline solution. One minute later, thisemulsion was rubbed into a scarified skin area of a healthy volunteer.

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2Byam and Lloyd: Trench Fever

Immediately afterwards, louse No. 8 (Rickettsita-positive from theeighth day) was treated in the same way, and inoculated similarlyinto another healthy man. The man who received the louse whichnever showed Rickettsita bodies, remained healthy during two months'observation, while the volunteer inoculated with the Rickettsia-positivelouse, developed a typical attack of trench fever after seven days'incubation.

This result strongly supports Arkwright's findings with regard toRickettsia, and suggests that eleven out of twelve lice became infectedwith trench fever as the result of ten feeds on a trench fever patient.Other experiments similar to the above, though modified in variousways, have provided much confirmatory evidence.

(8) The exereta from a single louse or its gut contents, are capableof producing trench fever.

(9) 01 mgm. of infective louse excreta has produced typical trenchfever by inoculation subcutaneously.

(10) Lice can be infected by being fed when on an afebrile trenchfever patient while the disease is still active, as indicated by pains inthe limbs, and similar symptoms. Sometimes patients who haveinfected lice in this way have suffered subsequently from febrilerelapses, while others have not.

(11) Even as late as the four hundred and forty-third day of diseasea patient's blood may remain infective and be capable of infecting licefed on such a patient while slightly febrile. A patient showing suchpersistent symptoms is by no means rare, though we have not beenuniformly successful in transmitting the disease from such cases.

(12) Infection probably does not take place by the mouth or byinhalation, attempts to transmit the disease by means of infective louseexereta, in such ways, having failed.

(13) The evidence against transmission by mechanical transferenceof blood by lice is extremely strong; and from what has been said it isobvious that a healthy person may contract trench fever without everhaving had a louse upon him, being infected by louse exereta dislodgedfrom garments or blankets, or by louse exereta conveyed as dustthrough the air.

We see, therefore, that trench fever is conveyed by the exeretaor crushed bodies of infected lice; that the v'irus may enter throughthe broken skin or unbroken conjunctiva; that rubbing and scratchingpromote infection, but that the bites of lice may cause a sufficient lesionto enable infective material to enter the body.

20


DISCUSSION.

Dr. BuCHANAN: I admire the greatness of the results which have beenachieved by Major Byam and his colleagues by the experimental methodswhich have been so amply set out in the paper. I think it important clearlyto distinguish between three conditions: (1) Those which favour the trans-mission of lice from man to man; (2) those which, given the presence of lice,favour the spread of typhus and relapsing fever from man to man; and (3)those which, also given the presence of lice, favour the transmission of trenchfever from man to man. Notwithstanding all the brilliant investigations, ourunderstanding of the epidemiology of trench fever is incomplete until satisfac-tory explanation is forthcoming of the different behaviour of trench feverepidemics on the one hand and those of typhus and relapsing fever on theother. I may refer to the evidence of the habitual association of typhus andrelapsing fever in epidemics, laying special stress on this occurrence in theepidemics which are now prevalent in the Balkans and in Poland and Galicia.The general epidemic of trench fever on so many fronts in Europe in 1916affected Poland, Austria and the Balkans, and a priori, there was as muchreason to anticipate the continuance of chronic carriers of trench fever andlocal centres of trench fever infection in these regions as there was in the caseof typhus and relapsing fever. It does not seem a sufficient explanation of thenon-appearance of trench fever during the last year or two in these typhusand relapsing fever-ridden countries to suggest that the infection of trenchfever has not been introduced or that trench fever might have been presentbut was overlooked. I have made inquiries in Poland and elsewhere ofmany doctors who were fully acquainted with trench fever as seen in 1916,and they had no suspicion that any trench fever was associated with theother louse-borne diseases with which they were constantly dealing. I mayrefer also to the practical absence of trench fever in Egypt and Mesopotamiawhere typhus and relapsing fever occurred, and where apparently all theconditions existed for the propagation of trench fever also, including thepresence of men liable to relapses, who, on the experimental evidencegiven by Major Byam, might be supposed to remain active carriers of theinfection for long periods. Since the regulations, made early in 1919, by theLocal Government Board, trench fever has been notifiable in this country, but,with one exception, the notifications appear to have related to ex-soldiers whohave contracted the disease in France. It is, of course, possible that cases oftrench fever occur which are contracted in this country but are not diagnosed.One frequently hears of specialists in trench fever who discover the diseasewhere it has been previously unsuspected. I hope that whenever this is donein a case which has apparently contracted the infection in England, thespecialist concerned will keep in mind the requirements of notification imposedby the Ministry of Health regulations so that the facts of transmission can befully investigated.


Mr. A. BACOT: As a member of the War Office Trench Fever CommitteeI am in too close agreement with my colleague, Major Byam, to be able use-fully to discuss the lecture as a whole, but I will refer to a few points thathave been mentioned this evening. With regard to the very valuable andinteresting experiments conducted by Major Byam and Captain Lloyd con-cerning the migration of lice from patients when in a febrile condition: Iwould point out that in normal circumstances the lice are less likely to hurryaway to a new host before infecting themselves than under the conditions ofthe experiment. During war both the patient and his sleeping companionwould probably rest in more or less complete uniform in place of wearingpyjamas, while the lice instead of being suddenly released on a fevered skinwould be distributed among the patient's garments, having had time graduallyto dispose of themselves to their own comfort in accordance with the increase*of his body temperature. Lice migrate to the outer garments when they findthe heat or moisture between skin and underclothing uncomfortable or availthemselves of the better ventilated situations afforded at wrist, knee, fork orneck. Under these circumstances the insects would probably indulge theirnormal appetites for blood to satiety before they wandered on to a new host.The importance of the factors of humidity or drought in regard to the distri-bution of body lice, and as a consequence of the diseases they convey, was notsufficiently emphasized by Major Byam. Body lice appear to have a greatdislike to sweat or sweat-moistened garments. Cold climates, even if humid,are not unfavourable, because of the dryness of the atmosphere between cloth-ing and skin consequent upon the wide difference between the temperature ofthe host's body and that of the surrounding air. Dry hot climates, especially-if the range between night and day temperature is great may also provefavourable to the insects, but hot humid countries are unsuitable. The dangerof the spread of the disease by the excreta of infected lice in discarded clothingseems to me to be a relatively unimportant risk provided that the active licethemselves are destroyed, so that irritation due to their bites is avoided. Dr.Buchanan has referred to the scarcity of evidence of any spread of the diseasehaving been caused in this country owing to the return of trench fever patientswho might reasonably be suspected of acting as carriers. I would suggestthat the reason is that, in the great majority of cases, upon the man's returnhome, even if his clothes do harbour a few lice, they are very speedily disposedof by the normal routine of the washing of underclothing and the use ofseparate night garments by both the man and his wife. The man's familymay harbour head lice but these are unlikely to infest him owing to the short-ness of his hair, and it follows that a link is wanting in the sequence of thecycle.

The PRESIDENT (in calling upon Dr. Arkwright to continue the discussion):Will Dr,'-Arkwright be good enough to explain the nature of the Rickettsiabodies ? These bodies were first described in connexion with typhus fever, laterthey were found also in trench fever. Have they, therefore, any specialsignificance in respect of either of these two diseases, and are there any

'22


differences in the Rickettsia bodies of typhus and trench fever? I drawattention to a fact that has been established by certain of the observationsmade by Major Byam and others in trench fever-namely, that a very smallamount of infecting agent is sufficient to infect a person. The virus containedin one louse is apparently ample. The same fact has been observed in typhus.

Dr. J. A. ARKWRIGHT: In reply to the President's question as to whatRickettsia bodies are, I am unable to do more than state that they have a definiteappearance and are fairly easily recognized in films stained with Giemsa'sstain, when they are present in large numbers. They resemble round or oblongbacteria and are very small, about 03 by 03-0 5 micron in diameter. Theirrelationship to bacteria, spirochbtes or protozoa is undefined, and failure to obtaincultures on artificial media retards advance in our knowledge of them. Theyare found in enormous numbers in the stomach or mid-gut of lice which havefed on patients, when five to ten days have elapsed since the first infecting feed.It is not necessary that the lice should have fed on the patient during thewhole of this time, so long as they have had a good meal of blood twice dailyand have been kept at a temperature of about 300 C. between the feeds. Theexcreta of such lice also show very large numbers of Rickettsia bodies afterabout a week or ten days from the first infecting feed. This period correspondsvery well with the time after the first feed at which the lice become infectivefor man. The variety of Rickettsia associated with trench fever was firstdescribed by Toepfer. Rocha Lima has also published observations on thesubject in a paper written with Munk. We have done some work with typhusfever Rickettsia and virus obtained by feeding lice on human cases of typhus,and we have reproduced the disease in monkeys and guinea-pigs by inoculatingthem with the infected lice and passing on the disease by the blood to otheranimals. Our work on typhus has not been very extensive, but we have beenable to satisfy ourselves as to the occurrence of a form of Rickettsia in very largenumbers in infected lice, and we believe that we can distinguish the typhusorganism by its staining properties, its slightly larger size and its morebacillary shape. These differences on the whole agree with those described byother workers, especially the fact that the typhus Rickettsia stains redder andthe trench fever form a more purple colour. Since the papers on Rickettsia byArkwright, Bacot and Duncan were published,' we have continued ourobservations in connexion with the clinical work of the Trench Fever Committeewhich has been carried on by Major Byam and his colleagues at the New EndMilitary Hospital. We have had the advantage of the special knowledge andskilled help of Captain Lloyd, the entomologist to the hospital. We have nowexamined 108 boxes of lice which had been fed on sixty-four cases of trenchfever, and from all these boxes we have obtained films definitely showing largenumbers of Rickettsia bodies. Two boxes of lice fed on recent cases of trenchfever did not show Rickettsia, but the reason for these two failures wasprobably that these two boxes were insufficiently examined; films were made

I Journ. Hyg., 1919, xviii, p. 76, and Trans. Soc. Trop. Med. and Hyg., 1919, xii, p. 61.

Byamn and Lloyd: Trench Fever

on two days only from one box (thirteenth and fourteenth day from the firstfeed), and one day only (seventeenth) in the other case. A number of oldtrench fever cases on whom lice were fed gave negative results as regardsRickettsia, showing either that these lice did not acquire Rickettsia from thesecases or only in numbers too small for recognition. Six boxes of lice were fedon experimental cases of trench fever on the first day of the disease only andnone of these showed Rickettsia; these were the only instances in which itwas attempted to infect lice on the first day only of the disease. Two boxesof lice which were fed on two cases during the first and second day only, andon the third day only of the disease respectively, did not show Rickettsia,though lice fed later on the same cases yielded large numbers. It appears,therefore, that lice fed on one day only, and especially if that is the first day ofthe disease, may not show Rickettsia: this may be because they only becomeslightly infected, the septicaemia existing in tho patient at this stage of thedisease being of a low grade. Rickettsia can only be recognized when presentin large amounts. On the other hand septicaemia may usually be absent atthis early period of the disease. A very large number of examinations of boxesof lice fed on healthy men have been made, with negative results. Twenty-fiveboxes of normal lice fed on twelve healthy men have been examined repeatedly;some over long periods with negative results, and lice taken from six otherhealthy men, have also been found negative. Only on one occasion has a boxof lice fed on a man not under suspicion of trench fever given a film stronglysuggesting trench fever Rickettsia, but even this did not show definitely typicalappearances. The typhus fever lice have also yielded uniformly negativeresults as regards trench fever Rickettsia, and the trench fever lice have nevershown forms like the typhus fever organism. Lice fed on five other febrilemen (phthisis, cerebro-spinal meningitis, &c.), have also served as negativecontrols. The association in lice of trench fever virus and Rickettsia is thusextraordinarily close and the control observations on lice from healthy men inLondon have been quite satisfactory. It is difficult to disbelieve in a causalrelationship. betw.een the Rickettsia and trench fever. However, as no one hasyet obtained a culture, and as the attempt to recognize definitely so small andsimple an object as Rickettsia in small numbers in a blood film from a patientis too difficult a task, certainty has not yet been reached. It is interesting andimportant from the epidemiological point of view (1) that lice which havebecome infected with trench fever Rickettsia appear to remain infected tillthey die, and that their life is not apparently shortened by the infection;(2) that trench fever patients who are no longer febrile will often infect lice withRickettsia. Lice coming into both these categories have been shown not onlyto contain Rickettsia but also to be infective for man.

Surgeon-Captain P. W. BASSETT-SMITH, R.N.: Cases of trench fever havebeen very few in the Naval Service. I have been through all our hospitalreturns from 1914-1919 and find only one case recorded. In the Gallipolicampaign we had a large force of the Royal Naval Division employed when

24


diseases were rampant. In France there were many Naval and Marine unitsbut most of the sick were treated in military hospitals. Anyway the conditionson board naval ships do not favour the spread of the disease. The atiology ofthe disease is still unknown but probably it is allied to the typhus and relapsingfever group. The clinical and epidemiological characters of that type known as"febris quintana " strongly suggest a spirochsetal origin, and in view of thework of Leishman and Balfour on the granule-forming properties of spiro-chaetes, can the minute Rickettsia bodies found in lice be distinguished fromthe spirochEetal granules ? At any rate much further investigation is requiredbefore it can be definitely stated that trench fever is not a spirochaetosis.When we bear in mind the long period that was taken to demonstrate the veryprevalent Treponenma of syphilis, negative results count for little as proofagainst the theory.

Major-General Sir W. G. MACPHERSON: Major Byam's experiments referonly to the louse as the transmitting agent of trench fever. But, if I rememberrightly, the first experiments of the American Committee in France, of whosework I saw a good deal, showed that direct inoculation of the blood of a trenchfever patient produced the disease; so that there is a possibility of trenchfever being contracted without the agency of the louse or its excreta. MayI ask Major Byam to state how far this point was taken up in his experiments ?

Dr. CARMALT JONES: I will comment on two points in Major Byam's andCaptain Lloyd's paper. The first point is epidemiological, the second clinical.In describing the epidemiological distribution of trench fever Major Byamremarked on its occurrence in Egypt: this is quite contrary to my experience.I spent six months in Egypt at the end of the war, where I had access to allmedical units outside the Army areas, but I never saw any cases of this disease,for which I was on the look-out, as I had become interested in it in France.I think Dr. Butler will bear me out that it was never mentioned at this timein the returns of diseases occurring among the troops, and when I discussed itwith medical officers who had served only in Egypt they always told me thatthey were unfamiliar with it. Its absence was certainly not due to any lackof lice, which are ubiquitous in those parts. I recollect finding lice in myclothes after merely walking through the streets of Damascus, without evensitting down, an event which had considerable interest for me as there was agreat deal of typhus fever in the place. Will Major Byam tell us at what timetrench fever was prevalent in the Egyptian theatre of war? The second pointis this: Major Byam has remarked on the difficulty of making a laboratorydiagnosis of trench fever in the absence of any demonstrable parasite. Thereis, however, a clinical method of diagnosis which has a certain value; this isthe presence of areas of hyperalgesia of the skin, corresponding to thedistribution of the eighth cervical and first dorsal, the seventh dorsal andthe lumbar segments. These areas, or some of them, are to be found in nearlyall cases of trench fever, and in no other fever, I believe, with the exception ofmalaria, which is capable of accurate laboratory diagnosis. I came across

25


these areas in the following way: I was investigating segmental hyperalgesiain visceral lesions in general, and in heart disease in particular, for whichI used to visit a "heart centre." In the course of this work I found theseventh dorsal segment frequently hyperalgesic, and I was unable to understandthe connexion between this and any cardiac lesion. I referred the matter toMajor H. F. Marris, R.A.M.C., an expert cardiologist, who asked me if thesepatients had had trench fever, and showed me a case of trench fever in anacute stage, in which it was easy to demonstrate this hyperalgesic area.I asked him if the characteristic shin-pains were segmental in origin, and hereplied that he thought this was probable, and on examination the lumbarhyperalgesia was found. I made a large number of investigations on thesecases after this, and bearing in mind that the patients often complain of ulnarpains, I looked for and found the same condition in the eighth cervical andfirst dorsal areas.' The presence of these areas will, I think, be found a verygood rough guide as to whether any case of fever, other than malaria, istrench fever or not.

Major BYAM (in reply to Dr. Buchanan): Trench fever was well recog-nized by the Germans as occurring in the Eastern European war zones.When introduced into our Army on the Salonika front, by men from France,the disease spread till steps were taken to reduce the prevalence of lice. InFrance trench fever was rampant, a high percentage of our men were infectedby lice, and yet the other louse-borne diseases were absent. In Germany,during the war, all forms of louse-borne infection were common. In Egyptand Palestine relapsing fever was the only louse-borne disease that assumedepidemic proportions in the Army, and the troops chiefly affected were the menof the Egyptian labour corps and those coming in contact with them. Fromall of which, I think, we may conclude that the spread of louse-borne diseaseinto new areas is a slow process, requiring intimate contact between the sickand the healthy. That trench-fever-infected lice do not pass on their infectionhereditarily must also do much to limit the endemic area of the disease. It ismore than likely that trench fever will be passed unrecognized during an out-break of the more serious louse-borne infections.

With regard to Mr. Bacot's remarks, our experimental subjects were clothedin pyjamas to facilitate the removal of the lice, but we always failed to retrievea certain percentage of them. The fact that in both series of experiments theconditions were identical, with the exception that in one series the primaryhost was febrile and in the other he was not, would, we believe, justify us inattributing the marked difference in the wandering proclivities of the lice tothe one difference in the conditions-namely, the presence or absence of fever.That trench fever often spreads in the absence of lice is unlikely, but theinfectivity of the adherent louse exereta becomes of great importance whenhospital bedding or clothing is under consideration, as the sick and wounded

I See Lancet, 1918, ii, pp. 443, 444.

26 b


present many portals of entry for the virus that are absent in the healthy.At the same time, it is likely that infective garments were often issued tolouse-infested men whose lice were non-infected but whose skin was broken asthe result of scratching.

Sir William Macpherson has raised the question of transmission by other-means than the louse or its exereta. The blood of trench fever patients, as hesays, is infective both during fever and in the afebrile intervals. Direct bloodtransmission was carried out successfully by us with blood obtained frompatients on various days of the disease up to and including the fifty-seventhday. Three attempts to infect by applying the urinary sediment of trenchfever patients to the scarified skin of human volunteers gave negative results,the urine being collected from patients at all periods from the first to the-twenty-first days of illness. The fact that infection cannot be produced bythe ingestion of known infective material robs such experiments of much oftheir importance.

That trench fever was ever prevalent in Egypt, I think, is more thanunlikely. Having worked in that country for nearly twelve years, and havingonly left it at the end of 1916, I can say that I never saw a case there.During 1918, however, full records of cases in Egypt were sent to me bycompetent observers, and I am inclined to believe that sporadic infections didoccur among those coming in contact with men from France. One case wasthat of an English hospital nurse. The Egyptians did not suffer from thedisease either before or during the war, and yet they are particularly liable tocontract louse-borne infections. Their time is probably yet to come. Theareas of skin hyperalgesia alluded to by Dr. Carmalt Jones are well known to-us, and I can corroborate his statements as to their value for diagnosticpurposes.

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5ection. of Epibemtiologi anb state f1ebicIne