Publié dans : Nature, XXXVI, 7 juillet 1887, p
MALADIES VIRULENTES
investigate a considérable number of the cases of persons inoculated by bim : and, further, that a careful sériés of experiments should be made by Mr Horsley on the effeets of sucb inoculation on the lower animais. The detailed facts of these observations and experiments are placed in the Appendix to this Report: a summarv of them, and the conclusions which we believe may be drawn from them, are given in the next following pages.
The experiments by Mr Horsley entirely confirm M. Pasteur s discovery of a method by which animais mav be proteeted from the infection of rabies. The general facts proved bv them mav be thus stated :
If a dog, or rabbit, or other animal be bitten bv a rabid dog and dies of rabies, a substance can be obtained from its spinal eord which, being inoculated into a healthy dog or other animal, will produce rabies similar to that which would hâve followed directly from the bite of a rabid animal, or differing only in that the period of incubation between the inoculation and the appearance of the characteristic symptoms of rabies may be altered.
The rabies thus transmitted bv inoculation mav, by similar inoculations, be transmitted through a sucession of rabbits with marked increase of intensity.
But the virus in the spinal cords of rabbits that bave thus died of inoculated rabies may be graduallv so weakenedor attenuated, bvdrying the cords, in the rnanner devised bv M. Pasteur and related in the Appendix that, after a certain number of days’ drying, it may be injected into healthy rabbits or other animais without anv danger of producing rabies.
And by using, on each successive day, the virus from a spinal cord dried during a period shorter than that used on the previousday, an animal may be made almost certainly secure against rabies, whether from the bite of a rabid doff or other animal, or from anv method of subeutaneous inoculation.
The protection from rabies thus secured is proved bv the fact that. if some animais thus proteeted and others not thus proteeted he bitten by tlie saine rabid dog, none of the first set will die of rabies, and, with rare exceptions, ail of the second set will so die.
It may, hence, be deemed certain that M. Pasteur bas discovereda method of protection from rabies comparable with that which vaccination affords against infection from small-pox. It would be diffieult to over-estimate the importance of the discovery, whether for its practical utility or for its application in general pathology. It shows a new method of inoculation, or, as M. Pasteur sometimes calls it, of vaccination, the like of which it may become possible to emplov for protection of both men and domestic animais against others of the most intense kinds of virus.
The duration of the immunitv from rabies which is conferred by inoculation is not yet determined; but during the two vears that haA e passed since it was first proved there hâve heen no indications of its being limited.
The evidence that an animal may thus, by progressive inoculations, be proteeted from rabies suggested to M. Pasteur that if anv animal or any person, though unprotected, were bitten bv a rabid dog, the fatal influence of the virus might be prevented (* bv a timely sériés of similar progressive inoeula-
1. The terms referring to « préventive » treatment will be used for that designed to prevent
tions. J le lias accordingly, in the institution established by him in Paris, thus inoculated a very large number of persons believed to bave been bitten by rabid animais; and we hâve endeavoured to ascertain with what amounl of success lie lias done so.
The question might be answered with numerical accuracy if it wero possible to ascertain the relative numbers of cases of hydrophobia occurring among persons of whom, after being similarly bitten by really rabid animais, some were and somewere not inoculated. But an accurate numerical estimate of this kind is not possible. For
(1) h is often diffîcult, and sometimes impossible, to ascertain whether the animais by which people were bitten, and which were believed to be rabid, were really so. lliey may hâve escaped, or may hâve been killed al, once, or may hâve been observed by noue but persons quite incompétent to judge of their condition.
(2) The probability of hydrophobia occurring in persons bitten by dogs that were certainly rabid dépends very much on the number and character of the bites ; whether they are on the face or hands or other naked parts : or, if they hâve been inflicted on parts covered with clothes, their effects may dépend on the texture ol the clothes, and the extent to which they are torn ; and, in ail cases, t lie amount of bleeding from the wounds may affect the probability of absorption of virus.
(3) In ail cases, the probability of infection from bites may be alfected bv speedy cauterizing or excision of the wounded parts, or by various washino-s or other methods of treatment.
(4) The bites of different species of animais, and even of different dogs, are, probably, for various reasons, unequally dangerous. Last year, at Deptford, five children were bitten by onc dog and ail died; in other cases, a dog is said to hâve bitten twenty persons, of whom only one died. And it is certain that the bites of rabid wolves, and probable that those of rabid cats, are far more dangerous than those of rabid dogs.
The amount of uncertainty dueto tliese and other causes may be expressed by the fact that the percentage ol deaths among persons who hâve been bitten by dogs believed to hâve been rabid, and who hâve not been inoculated or ortherwise treated, has been, in some groups of cases, estimated at the rate of only 5 per cent., in others at 60 per cent., and in others at various intermediate rates. lhe mortahty from the bites of rabid wolves, also, has been, in different instances, estimated at from 30 to 95 per cent.
To ascertain, as far as possible, the influence of these sources of fallacy in cases inoculated by M. Pasteur, the members of the Committee whowent to I ans requested him to enable tliem to investigate, by personal inquiry, the cases of some of those who had been treated by him. lie at once, and veiy courteously assented, and the names of 90 persons were taken from bis notebooks. No sélection was made, except that the names were taken from
thë oceurreiieê 0f the clisease in one already infected ; those referringto« protective » treatment i°r designed to protect a man or an animal from the risk of becoming infected. And it may be well to State that, though the usual custom is followed of employing tlie name of « hydrophobia » for the disease in men, and of « rabies » for that in animais, thev are really the same disease.
MALADIES VIRULENTES
liis earliest cases, in which lhe pcriods since inoculation were longest, and l'rom those of persons living within reach in Paris, Lyons, and St. Etienne.
The notes made on the spot concerning ail these cases are given in the Appendix, and they inclu.de, as far as was possible, the évidence whetlier the dogs deemed rabid were really so, the situation and kind ol hites, the immédiate treatment ol tliem, the statements ol medical practitioners and veterinary surgeons to whom any useful facts were known (*)•
Among the 90 cases there were 24 in which the patients were bitten on naked parts by undoubtedly rabid dogs, and the wounds were not cauterized or treated in any way likely to hâve prevented the action ol the vh us; there were 31 in which there was no clear évidence that the dog was rabid; others in which the bite, though inllicted by undoubtedly rabid animais, having been through clothes, may thus hâve been rendered harmlcss. Among these, therefore, it is probable that, even if they had not been inoeulated, tew would bave died. Still, the results observed in the total ol the 90 cases mav justly be compared with those observed in large numbers of cases similar to these as regards the uncertainties of infection, but not inoeulated. I be
estimâtes published as to the mortalities in such unassorted cases are, as we bave said, widely various. We believe that among the 90 persons, including the 24 bitten on naked parts, not less than eight would bave died il they had not been inoeulated. At the time of the inquiry, in April and May 1880, which was at least eighteen weeks since the treatment of the biles, not one had shown any signs of hydrophobia, nor bas any one of tliem since died ol that disease.
Thus, the personal investigation of M. Pasteur’ s cases by members of the Committee was, so far as it went, entirely satisfactory, and convinced them of the perfect accuracy of h is records.
After the first few months in which M. Pasteur practised his treatment, lie was occasionally obliged, in order to quiet l'ears, to inoculate persons who believed that they had been bitten by rabid animais, but could give no satisfactory évidence of it. It might, therefore, be deemed unjustto estimate the total value of his treatment in the whole ol his cases as being more than is represented by the différence between the rate ol mortality observed in them and the lowest rate observed in any large number of cases not inoculated. This lowest rate may be taken at 5 percent. Between October 1885 and the end of December 1886 M. Pasteur inoeulated 2.682 persons, including 127 who went l’rom this country. üf the whole number, at the rate of 5 per cent., at least 130 should hâve died. At the end of 1886, the number ol deaths stated by M. Vulpian speaking for M. Pasteur, was 31, including 7 bitten by wolves, in three of whom the symptoms of hydrophobia appeared while they were under treatment, and belore the sériés ol inoculations were complété. Since 1886 two more of those inoeulated in that year hâve died ol hydrophobia.
The number of deaths assigned by those who hâve sought to prove the inutility of M. Pasteur’s treatment is, as nearly as we ean ascertain, 40 ont
1. The Commiltee are much indebted to M. Arloing, Director of lhe Veterinary School at Lyons; M. Savary, Veterinary Surgeon at Brie-Comte-Robert; and M. Charlois, Veterinary Surgeon at St. Etienne, for assistance in tlieir inquiries.
ol' the 2.682 ; and in thirf number are included the seven deaths from bites bv wolves, and probably not less than four in which it is doubtful whether the deaths were due to hydrophobia or to some other disease. Making fair a llou ance for uncertainties and for questions which cannot now be settled, we believe it sure that, excluding the deaths after bites byrabid wolves, thé proportion of deaths in the 2.634 persons bitten by other animais was lietu een 1 and 1/2 per cent., a proportion far lower than the lowest estimated among those not submitted to M. Pasteur’s treatment, and showing, even on tins lowest estimate, the saving of not less than 100 lives.
1 lie evidence ol the utility of M. Pasteur’s method, indicated by these H”’1 18 Confirmed by the results obtained in certain groups of bis cases.
Ut 233 persons bitten by animais in which rabies was proved, either by inoculation from their spinal cords, or by the occurrence of rabies in other animais or ni persons bitten by them, only 4 died. Without inoculation it would hâve been expected that at least 40 would hâve died.
Among 186 bitten on the head or face by animais in which rabies was proved by experimental inoculations, or was observed by veterinary surgeons only 9 died, instead of at least 40.
And of 48 bitten by rabid wolves only 9 died ; while, without the préventive treatment, the mortality, according to the most probable estimâtes yet made, would bave been nearly 30.
i Beî'Innn the end °.f Iast December and the end of March, M. Pasteur inoculated 509 persons bitten by animais proved to hâve been rabid, either by inoculation with their spinal cords, or by the deaths of some of those bitten by them, or as certifïed by veterinary surgeons. Only 2 bave died, and one ol these was bitten by a wolf a montli before inoculation, and died after only three days treatment. If we omit half of the cases as being too recent, the
other 250 hâve had a mortality of less than 1 per cent., instead of 20 or 90 per cent.
It bas been objected that the number treated by M. Pasteur, which, from October i88o to the end of 1886, included 1.929 French and Algerians, was mucli greater than could reasonably be supposed to hâve been bitten bv rabid animais. But there had hitherto been no careful registration of such cases, and the numbers that hâve occurred in the présent year are not less than in the saine part ol lastyear, when the alarm about hydrophobia was greatest.
From the evidence of ail these facts, we think it certain that tfie inoculations practised by M. Pasteur on persons bitten by rabid animais bave prev'ented the occurrence of hydrophobia in a large proportion of those who il they ^ had not been so inoculated, would bave died of that disease. And ue believe that the value of lus discovery will be found much greater than oan lie estimated by its présent utility, for it shows that it may become possible toavertby inoculation, even after infection, other diseases besides hydrophobia. Some hâve, indeed, thought it possible to avert small-pox by vaccmating those very recently exposed to its infection; but the evidence ol this is, atthe best, inconclusive ; and M. Pasteur’s may justly be deemed the first proved method of overtaldng and suppressing by inoculation a piocess ol spécifie infection. IIis researches bave also added very largely to the knowledge of the pathology of hydrophobia, and hâve supplied what
MALADIES VIRULENTES
is of the highest practical value, namely, a sure means of determining whether an animal, which lias died under suspicion of rabies, was really affected with that disease or not.
The question has been raised whether M. Pasteur’s treatment can be submitted to without danger to health or life ; and, in answering it, it is necessary to refer to two different methods of inoculation which lie has practised, and wich are fully described in the Appendix.
In the first, which may be called the ordinary method, and which has been employed in the very large majority of cases, the préventive material obtained from the spinal cords of rabbits that hâve died of rabies derived, originally, from rabid dogs isinjected under the skin, once a day for tendays, in gradually increasing strengths.
In the second or intensive method ( méthode intensive) which M. Pasteur adopted for treatment of cases deemed especially urgent, on account either of the number and position of the bites or of the long time since their infliction, the injections, gradually increasing in strength, wer eusually made three times on each of the first three days, then once daily for a week, and then in different degrees of frequency for some days more. The highest strength ol the injections used in this method was greater than the highest used in the ordinary method, and was such as, il used at first and without the previous injections of less strength, would certainly produce rabies.
By the first or ordinary method, there is no evidence or probability that anyone has been in danger of dying, or has in any degree suffered in health even for any short time. But after the intensive method deaths hâve occurred under conditions which hâve suggested that they were dueto the inoculations rather than to the infection from the rabid animal.
There is ample reason tobelieve that in many of the most urgent cases the intensive method was more efficacious than the ordinary method would hâve been. Thus, M. Pasteur mentions that, of 19 Russians bitten by rabid wolves, 3 treated by the ordinary method died, and the remaininglô, treated by the intensive method, survived; and he contrasts the cases of 6 children, severely bitten on the face, who died after the ordinary treatment, with those of 10 similarly bitten children who were treated by the intensive method, and of whom none died; and M. Vulpian reports that, ôf 186 persons badly bitten by animais that were most probably rabid, 50 treated by the intensive method survived, and of the remaining 136 treated by the ordinary method 9 died.
The i 'ate of mortality after the intensive method was not greater than that after the ordinary method; for among 624 patients thus treated only 6 died, or, countingone doubtful case, 7. But that which excited suspicion was the manner of death in some of them; and this manner was observed in a man namecl Goffi, sent from England. On September 4 last, he was severely bitten at the Brown Institution by a rabid cat, to which, in spite of repeated warnings, he exposed his naked hand. Twelve wounds were inflieted. They were at once treated with pure carbolic acid, and, six hours later, he was put under the influence of chloroform at St. Thomas’s Hospital, the wounded portions of skin were freely excised, and the wounds thus made were treated with carbolic acid. On the same evening he was sent to Paris,
and on the followin£ morning M. Pasteur eommenced the intensive treatment, and ît. was continued during twenty-four days. During ail this tune the man was repeatedly intoxicated (*). ‘fie once fell into tlïe Seineand wlnle Crossing the Channel on his return home he was severelv chilled’ n cto er 10 he returned to his work, and appeared to he in his usual Health; but he became unwell, with pain in the abdomen, like colic, and with pain in the baek. On the 18th he had partial motor paralysis in the lower limbs, and on the 19th complété motor paralysis of these limhs and ot the trunk, and partial motor paralysis of the upper limbs and face. 1 le was taken to St. Thomas’s Hospital, where he died on the 20th.
do the last he was free from ail the usual symptoms of hydrophobia, and the progress of lus disease and the manner of his deathwere so similar to hose of what is descnbed as acute ascending paralysis, or Landry’s paralysis, a a verdict to this effect was given at a coroners inquest. But the cerainty that his death was due to the virus of rabies was proved by experirnents by Mr Ilorsley. A portion of his spinal cord was taken to provide matenal for inoculations, and rabbits and a dog inoeulated with it died with charactenstic signs of paralytic rabies, sucli as usually occurs in
In most of the other cases of death after treatment by the intensive method, the symptoms hâve been nearly the sanie as those just related; but in none of them has the same test of death from hydrophobia been applied.
îe likeness of the symptoms to those of the form of rabies called dumb or para ytic, usually observed in rabbits, has suggested, as we hâve said, that
6 defhs wer° due not ^ the virus of the rabiddog or cat, butto thatiniected Irom the spinal cord of the rabbit. But this is far from certain. In the case o Golfi, especially , the incubation period was such as would hâve followed t le bite of the cat, not the inoculation of highest intensity; and the incubation period in the rabbits and dog inoeulated from his spinal cord were such as bave been observed after similar inoculations with virus derived, not onlv Irom rabbits inoeulated in sériés by M. Pasteur, but from a dog, a cat, and a wo that died of ordinary rabies. It may well hâve been, therefore, that the intensive inoculations in him and in the other persons who die*d after them were not themselves destructive, but that they failed to prévent the rabies wh.ch was due to the bites. They may also hâve modified the form in w ic î the rabies manifested itself ; giving it the characters of the paralytic i a nés usual in rabbits, instead of the convulsive or violent form usually, but not always, (») observed in man after bites of cats or dogs.
I he question is likely to remain undecided ; for to avoid the possible îowever improbable, risk of his intensive treatment, M. Pasteur has greatlv
modified it, and even in this modified form employs it in none but the most urgent cases.
hvirnSv Cases’ ? wel1 as 1!lis- have led M- Pasteur to believe that the risk of death from hydrophobia is much mereased by habits of drunkenness.
rabid hy+di;ofhobia bave been observed, though rarely, in men hitten bv
of the cTZ Z T treated by inoculation. It may, indeed, be suspected that at least sonie
aUlionab fn t ‘ ^ re"dmg pa/alyS1S * may have been cases of this form of hydrophobia.
Sf 2.u “s SKStaS**" ”s"al ïiol"“ S5’"p‘oms’ ”spicion of the »'
MALADIES VIRULENTES
The considération of the whole subject lias naturally raiscd the question whether rallies and hydrophobia can be prevented in this country.
If the protection by inoculation sbould prove permanent, the disease migbt be suppressed by tbus inoculating ail dogs ; but it is not probable that sucb inoculation would be voluntarily adopted by ail owners of dogs, or could be enforced on them.
Police régulations would sufficc if tbey could be rigidly enforced. But to make tbem effective it would be necessary : 1. — that they sbould order the destruction, under certain conditions, of ail dogs having no owners and wandering in eitber town or country; 2. — that the keeping of useless dogs sbould be discouraged by taxation or other means; 3. — that the bringing of dogs from countries in wbicb rallies is prévalent sbould be forbidden or subject to quarantine; 4. — - that, in districts or countries in which rabies is prévalent, the use of muzzlcs sbould be compulsory, and dogs ont of doors, if not muzzled or led, sbould be taken by the police as “ suspected An exception might be made for sheep-dogs and others while actually engaged in tbe purposes for which tbey are kept.
There are examples sufficient to prove that, by these or similar régulations, rallies, and consequently hydrophobia, would be in this country “ stamped ont, ” or reduced to an amount very far less than bas bitherto been known.
If it be not thus reduced it may be deemed certain that a large number of persons will every year require treatment by the method of M. Pasteur. The average annual number of deaths from hydrophobia, during tbe ten years ending 1885, was, in ail England, 43; in London alone, 8‘5. If, as in the estimâtes used for judging tbe utility of that method of treatment, these numbers are taken as representing only 5 per cent of tbe persons bitten, the préventive treatment will lie required for 860 persons in ail England; for 170 in London alone. For it will not lie possible to say which among tbe whole number bitten are not in danger of hydrophobia, and tbe methods of prévention bv eautery, excision, or other treatment, cannot be depended on.
We bave tbe honour to be,
Sir,
Your obedient Servants,
(Signed) James Paget, Chairman,
T. Lauder Bruxtox,
George Flemixg,
Joseph Lister,
Richard Quaix,
Henry E. Roscoe,
J. Burdon Saxdersox.
Victor Horsley, Secretary,
June 1887.
Abstract Report of Mr Horsley' s Experiments
The first object of the experiments was to test M. Pasteur’s method of transmittmg rabies by inoculation, and to compare its effeets with those of rabies due to the bites of dogs found rabid in the streets (2).
Through the kindness of M. Pasteur, two rabbits inoculated by him were placed at the disposai of the Committee on May 5, 1886, and were conveved witlnn 24 hours safely to the Brown Institution, where the experiments were earned out by Mr Horsley.
In these two rabbits the first symptoms of rabies appeared on May I L aiu 12 and the disease followed exactly the course described by M. Pasteur.
At first the animais appeared dull, but contmued totake food readily until symptoms of paralysis appeared. The first of these symptoms was commencing paralysis of motion of the hind-legs, not accompanied by any loss of l'eus! 1 ltJ- *ie paralysis soon extended to the muscles of the fore-leo-s and later to those of the head, and the animal died comatose.
Alter post-mortem examination, portions of the spinal cord of each of rnse rabbits were crushed, according to M. Pasteur’s method, in sterilized f h, and the liquid so obtained was injected beneath the dura mater into
finir rabbits and the same number of dogs, ail being first rendered insensible with chlorolorm or ether (3).
Of the four rabbits so inoculated, the first two showed the first symptoms s< ven c ays after the inoculation; the third and fourth on the sixth day. The symptoms as well as the incubation period exhibited by these rabbits were exactly the same as were observed in those brought from M. Pasteur’s Iabooiy Lare fui notes and photograplis were taken in the case of ail the animais, in order that the constant and spécifie nature of the disease might demonstrated by observations during life and after death. It was also o serve that during the incubation period the température of the body remai lied normal, that is, about 39°4 C. With the first definite svmptom the température rose to about 40°4 C., which is the température usuallv ob erved during the first day of the obvions illness. By the next day it begaii
averaaernd7o°Rnr ^ n t dfy after ,the «PPearance of the first symptom it
P ‘ n tîe ast day d was always below normal, and on one
nainTh T t0 24° C‘ The ani,nals did not appear to suffer any
wlhch n H?" " ?" C°UrSe °! the disease’ . They -ere free from the spasms of the d i G Gai 'f '• Stf^e,S ° the malady 111 raan) form so painful a feature • 1 1 fY6’ and mdeed the dlsease in them resembled throughout that 1 sPisd 7 ’ but Pamless’ disease of man known as acute ascending para-
n!u<i p0St;,m0rte™ aPPearances in the rabbits were remarkably uniform. b - an.le nothiug abnormal, save congestion, presented itself either in the bram’ Spinal COrd’ heart> blood-vessels, or serons membranes. The larynx
l; ^®mier appendice au « Report ». JSature , XXXVI, 7 juillet 1887 u 287
•j’ A„mepTeSS10n 18 ad°Pted from that usual in France, “ raqe des 'rues ” 3. Ail the experiments performed in tins inquiry were thus made painS. '
MALADIES VIRULENTES
pharynx, and, more especially, the epiglottis, and tlie root of the tongue, were frequently intensely congested. The lungs showed almost invariably capillary congestion; and sometimes small patelles resembling broncho-pneumonia were observed. The nmcous membrane of the stomach was very markedly congested, and there were at its cardiac extremity nnmerous bæmorrhages (i). The constancy of these appearances was most remarkable, and corresponded in every partieular with tbose subsequently observed in rabbits wbich had died of l'abies fromtbe bite of rabid dogs.
Of the four dogs inoculated, the first showed on the eighth day after inoculation an alteration in the voice and commencing excitement; on the following day the excitement became excessive, and the bark was quite characteristic; on the eleventh day the dog was aggressive, notwithstanding slight paralysis of the legs; on the twelfth day the paralysis had increased, and on the next day there was complété paralysis and coma, and death occurred on the fifth day after the onset of the symptoms.
The second dog showed the first symptom on the ninth day after inoculation, when it was very dull and partially paralyzed: its bark was characteristic. Next day the paralysis was almost complété, and on the twelfth day the animal died. This was therefore a case of the rapid paralytic form; whilst in the first dog the disease was of the ordinary furious form of rallies terminating in paralysis.
The third dog showed the first symptom on the ninth day after inoculation, and from that time became gradually paralyzed, and died on the sixteenth day.
The l'ourth dog showed the first symptom in from eight to nine days after inoculation, and during the first day was extremely aggressive; on the two following days the characteristic bark was observed; and on the twelfth day there was paralysis of the hind-legs ; it died on the thirteenth day. Thus the furious form and the paralytic or dumb form of rabies were represented in equal numbers, whereas, in the usual mode of infection bv biting, the former is more prévalent.
The post-mortem appearances were as follows : — The brain and central nervous System were in some of the dogs the seat of considérable congestion ; in others these organs appeared normal. The serous membranes were perfectly normal ; the larynx especially, and sometimes the pharynx, were congested; the lungs always congested, especially in the lower lobes; the heart normal; the blood usually fluid, occasionally with post-mortem clots ; the stomach was always found to contain foreign bodies, such as straw; and its mucous membrane was congested, frequently showing numerous hæmorrhages ; the small intestine was always empty, and the large glandular organs showed venous congestion.
For the purpose of exaet comparison of the disease just described with that produced when rabies is communicated to the rabbit in the ordinary way, some rabbits previously narcotized with ether were caused to be bitten by rabid dogs of the streets, or were inoculated by trephining with material obtained from the spinal cord of dogs or other animais which had died of
