ADULT IMMUNE SERUM IN THE PROPHYLAXIS AND
ATTENUATION OP MEASLES.
W.S.BURNET, M.B., D.P.H.(Glas.)
A Thesis for the Degree of M.D« ProQuest Number: 13905186
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The value of adult immune serum both in the
prophylaxis and attenuation of measles has not hitherto been definitely established. By 1 adult serumT is meant the blood serum of adults who have passed through an attack of measles in childhood. The volume of research which has
already been done in this field is small, and the conclusions
derived by different observers are, to say the least, con
flicting. In most of the previous enquiries uninoculated
control cases have not been included and the value of the
results is thus extremely difficult to estimate.
Convalescent serum is of proven value in measles but its application is distinctly limited by the difficulty
of securing adequate quantities, particularly at the begin ning of an epidemic. The supply of adult serum is, on the
other hand, almost unlimited and its employment eminently
practicable; but its value must be placed beyond doubt before
subjects will readily offer their blood in the cause, or
public health authorities approve its use in the attempt to
curtail measles morbidity and mortality.
The present work is a contribution to the assess ment of the true value of adult immune serum in measles,
both as a prophylactic and as an attenuative, and it has
been endeavoured also to present certain aspects of the
subject which have not, up to the present, received attention.
I am indebted to Dr.A.S.M.Macgregor. Medical
Officer of Health of the City of Glasgow who permitted me to
utilize the measles contacts which presented themselves in
various institutions under his control, and I am especially
beholden to Dr.William Dow, Physician-Superintendent,
Knightswood Infectious Diseases Hospital, Glasgow, who 2
afforded me every facility both clinical and laboratory and whose enthusiasm provided a stimulus to my efforts.
Nor must I leave unstated the willing co-operation of the nursing staffs in the several institutions to which I had access, a co-operation without which my work could scarcely have been accomplished.
April, 1935. ARRANGEMENT OF THESIS.
INTRODUCTION.
SCHEME OF THE INVESTIGATION.
TECHNICAL METHODS.
THE INVESTIGATION.
ANALYSIS OF DATA.
SUMMARY.
CONCLUSIONS.
REFERENCES. 4
INTRODUCTION.
The need for some form of treatment which will ameliorate the course of measles in young children, and thereby prevent the disastrous complications which are so apt to follow, is apparent to all workers in the field of infectious diseases. During the last century various methods of prophylactic inoculation against measles were advocated, but the first really successful immunisations were reported in 1918 by Nicolle and Conseil, who used serum from convalescent measles patients as a means of producing passive immunity in susceptible contacts. Since then a large number of workers have attested the value of convalescent measles serum as a prophylactic. Owing to the difficulty of obtaining convalescent serum, attempts have been made to produce measles immune serum from animals, and the necessity for a suitable antigen stimulated research on the aetiology of measles. Several workers notably Tunnicliff, isolated diplococci from the blood and naso-pharyngeal
secretions of patients, but these organisms have not gener ally been accepted as the aetiological agent, and the serum from animals immunised with strains of these organisms has been proved valueless in the prevention or attenuation of measles, as indeed have all animal sera however produced.
Degkwitz, in consideration of the fact that an attack of measles almost invariably confers lifelong immun ity, suggested that the blood or serum of adults who had passed through an attack of measles, when given in adequate doses, would contain sufficient antibodies to produce passive immunity. At Pfaundlerfs clinic in Munich in 1920, Degkwitz
inoculated such adult serum into seven children *fao had been in contact with measles, six receiving 30 c.c. and one 20 c.c. 5
Pour of the children subsequently developed very mild measles
Disappointed in these results he abandoned the idea, on the
grounds that the antibody content of adult blood was too low
to be of any value. During the next five years research on
the subject was confined to Germany. Reitschel (1921),
Salomon (1923), von Torday (1923), Kutter (1923), Gerlach
(1924), Goebel (1924), Hilsinger (1925), and Kovacs (1925),
reported varying results on the inoculation of adult whole blood or serum into small numbers of measles contacts.
Little work seems to have been done on the subject
in Prance, but in 1925, Debre, an authority on convalescent measles serum, suggested that good results could be obtained
by the use of adult serum, and W.S.C .Copeman who was then
"Assistant Etranger” in the Faculty of Medicine of the
University of Paris, successfully used adult serum in four
children exposed to measles infection by familial contact.
In America, a certain amount of research has been
carried out, but again the numbers immunised are small, as most of the workers considered that convalescent serum was much more effective. Zingher in 1924 noted that adult serum was of value in the attenuation of measles, but did not re
port any cases where it had been used. In 1927 Karelitz and
Levin, and Bivings and Dickson in America, Pasani-Casa in
Italy, and Zoepffel in Germany, reported favourably on series
of measles contacts who had been immunised with adult serum.
Two years later, Bader in America, and Morales and Mandry in
Porto-Rico, reported results showing that adult serum was more successful in the attenuation than in the prevention
of measles, and in 1930 Barenberg, Lewis, and Messer in
America reported similar results.
In Britain, the use of adult serum was first re
ported in 1930 by B.H.R.Harries then Medical Superintendent 6
of the Birmingham Infectious Diseases Hospital, and later
(1932), by M.Burn of the Birmingham Public Health Department.
The latter claims excellent results both in prophylaxis and attenuation, but unfortunately these are not substantiated by details of the investigation.
The amount of research which has been carried out on adult serum is relatively small, and only some twenty- five reports of its use are to be found in literature. A careful study of the literature of the subject reveals the fact that the vast majority of the investigators neglected entirely to provide uninoculated controls, thereby rendering their results valueless. It is evident that the interpreta tion of results must depend on a comparison of the behaviour of inoculated contacts with that of uninoculated controls who have been exposed to the same source of infection. The results of previous investigations are conflicting, some indicating that adult serum is an effective agent in the prevention of measles, others that it is almost useless as a prophylactic but is successful in modifying or attenuating the attack. Moreover there are certain important aspects of the subject which have not previously been explored. City- bred adults who have never had an attack of measles rarely contract the infection; their immunity has probably been built up gradually by the reception of sub-infective doses from intermittent contact with the disease. Is the blood- serum of such persons of value in the prophylaxis and attenuation of measles? When the serum is stored does its potency rapidly become impaired? Does the interval between the measles attack and the donation of blood have any influence on the potency of the serum? These are questions which previous investigators have left unanswered, and it is to these aspects of the subject that particular attention has been directed in the present work. 7
SCHEME OP THE INVESTIGATION.
Measles is perhaps the only infectious disease prevalent in temperate climates which shows marked epidemic periodicity. In most of the urban populations of Great
Britain biennial epidemics recur with unfailing regularity, and preparations for these can be made well in advance.
In order to have a store of adult serum on hand at the beginning of the 1934 measles epidemic, and also to enable the keeping properties to be proved, the collection of serum was begun at Knightswood Hospital, Glasgow, during the winter of 1932-1933, and carried on, as donors became available, right up to & during the epidemic. Owing to the unusually late appearance of the epidemic in the spring of
1934, batches of serum of different ages up to eighteen months old were available.
The donors were recruited from patients who were convalescing from a mild attack of an infectious disease such as pneumonia, scarlet fever, or diphtheria. Well- nourished adults whose histories for tuberculosis, malaria and syphilis were negative, alone were selected. The pneumonia wards furnished by far the largest number of donors, as many of the cases admitted to these wards were very mild or abortive in character, and many subsequently proved to be suffering not from pneumonia, but only from a transient febrile illness. The serum was collected under aseptic conditions and stored in an ice-chest.
Sixteen thousand cubic centimetres of blood were collected from one hundred and thirty-seven donors, and yielded eight thousand and three cubic centimetres of serum.
The average amount of blood from each donor was 116.8 c.c. and the average amount of serum 58.4 c.c. A sample of the 8
serum from each donor was subjected to the Wassermann and
Kahn tests by the staff of the Glasgow Public Health
Laboratory. In 15 (11.0 per cent.) of the donors, the blood serum was positive to either the Wassermann or Kahn reactions or to both, and the serum from these donors amounting in all to 955 c.c., was rejected. This waste of serum could readily have been avoided by drawing a small quantity of blood from each prospective donor, and subjecting the serum to the
Wassermann and Kahn reactions before taking the blood.
Twenty-two (16 per cent.) of the donors who were all city-bred, denied any history of measles, and from them
1368 c.c. of serum were collected.
The measles contacts made use of in the investiga tion were those who presented themselves in the wards of
Municipal general and fever hospitals and In children’s homes. In all there were thirty-one separate groups of children exposed to measles infection. The history of each child with regard to a previous attack of measles was very carefully enquired into, and those children who had not had measles were presumed to be susceptible.
The serum was given intramuscularly, the usual dose being 20 c.c. In a large number of the groups, a proportion of the susceptible contacts did not receive serum and these acted as controls. The contacts were kept under close observation until the twenty-first day after exposure to infection, and during that time their temperatures were taken four-hourly.
The type of measles attack which occurred in the contacts immunised with adult serum varied very considerably.
There were a very few abortive cases in which after the usual incubation period, slight or moderate pyrexia, headache, and slight eye suffusion occurred, without the appearance of a 9
rash or of Koplik’s spots, and without injection of the buccal mucosa. Recovery was very rapid in these cases, the whole illness lasting not much longer than twenty-four hours.
A large number of the cases were attenuated. In these, catarrhal symptoms and Koplik’s spots were entirely absent; the rash was faint, sparse, usually discrete, but sometimes confluent in isolated patches. Pyrexia was either absent or slight, and there were no constitutional symptoms and no complications. An attack of this kind did not appear to differ in any way from an extremely mild attack of measles such as occasionally occurs in children who have not been given measles serum. In a considerable number of cases the attack was distinctly modified but hardly warranted the term attenuated, which is here applied only to attacks of the very mildest possible nature. In these ’modified1 cases, the catarrhal symptoms were either very slight or absent,
Koplik*s spots were absent, and the first indication of the infection was the appearance of the rash which was fairly bright and generalised, morbilliform in character and some times confluent. Pyrexia was slight or moderate in degree, and persisted for two to four days. The objective signs were those of a mild or moderate attack of measles, but the constitutional symptoms usually associated with such an attack were entirely lacking, and the catarrhal symptoms were slight or absent. Prom the onset, the children were bright and alert; they playfully sat up or stood up in their cots and they ate well and slept well. The whole illness was not unlike rubella. There were no complications. The doctors and nurses in attendance were impressed by the difference between these ’modified* cases and the classical cases. The character of the rash might be the same in both but the difference in the well-being of the children was 10
marked. Barenberg, Lewis and Messer, in America noted this
type of modification in a small group of measles contacts
immunised with adult whole blood. A number of immunised
contacts developed classical measles with catarrhal symptoms,
Koplik's spots, typical rash, moderate or high and sometimes
prolonged pyrexia, and characteristic toxaemia. When measles
occurred in an immunised contact the type of attack was
classified in one of the above categories, i.e. either (a)
abortive, (b) attenuated, (c) modified or (d) classical.
Cases of measles which occurred in the uninoculated
or control series, were classified as very mild, mild or
classical. In general, cases admitted to these categories
corresponded respectively to the attenuated, modified, and
classical types occurring amongst the immunised children,
thus allowing a comparison of the severity of the attack in
immunised and non-immunised contacts.
Immunised contacts and controls who developed
measles after a second exposure to Infection by an attenuated
or classical case, were classified as above and in addition
labelled Secondary1.
The unusually late onset and consequent short
duration of the epidemic added much to the difficulties of
the investigation. In former years, measles in Glasgow has
reached epidemic proportions in October or November, and the
case incidence has remained high till the following April or
May. Through the courtesy of Dr.A.S.M.Macgregor, Medical
Officer of Health of the City of Glasgow, the Superintendents
of all municipal hospitals, and the matrons of all municipal
children's homes, were notified in September 1933, that
supplies of adult immune serum were available at Knightswood
Hospital, and that in the event of measles occurring in the
institution, the susceptible contacts should be immunised at 11 i the earliest possible moment. Prom the very beginning of the epidemic, every available opportunity of using the serum was utilized. Several hospitals without the city boundaries also knew of and asked for the serum. The first demand for the serum in Glasgow was made on the 16th.of March, 1934, and the last on the 17th. of June, 1934. , Had the epidemic been of the usual duration, the investigation would have been much more extensive, as the supply of serum was more than adequate. The type of infection however was severe and the incidence of complicating broncho-pneumonia was high.
The work of administering the serum and of observ ing and recording those contacts who developed measles, was carried out personally, and necessitated repeated visits to each institution. Children who were exposed to measles infection and who were dismissed within the incubation period, were visited in their own homes. The amount of travelling Involved was considerable and proved quite an arduous task especially during the height of the epidemic. 12
TECHNICAL METHODS.
The difficulty of collecting blood and of separating and storing the serum is commonly underestimated, but actually neither the bleeding and separation of the serum, nor the maintenance of strict asepsis from the moment of collection of the blood to the moment of injection of the serum, is in any way an easy task. Prom personal experience, the writer is of the opinion that the technique involved in the aseptic collection of blood, and separation and storage of the serum, is quite as difficult and demands just as much skill as that required in blood transfusion. Many pitfalls strew the path of the unwary. It is an easy matter to obtain the 5 c.c. or 10 c.c. of blood required for many of the serological, biochemical or bacteriological tests, such as the Wassermann, Widal, blood sugar estimations, blood culture etc. even although the only available vein is very small; it is also a comparatively easy matter to inject intravenously, fluids in small quantities as in the case of drugs, or in large quantities as in the case of isotonic solutions re quired to increase the volume of circulating blood. Of such operations the writer has had a comparatively large exper ience. It is however an entirely different matter to remove upwards of 100 c.c. of blood without resorting to the opera tion of venesection. The reason for this is obvious. The viscosity and coagulability of the blood demand that a needle of large bore be used. An ordinary serum needle, which can hardly be called small, cannot be relied upon to withdraw much more than 20 c.c. of blood without blocking due to coagulation of the blood. A needle of sufficient bore, when thrust into a small vein, instead of entering the lumen, simply causes a local rupture of the entire wall, and results 13
in a subcutaneous haematoma without letting of blood. The same size of needle thrust into a larger vein, causes a con siderable rent in the wall, and if the needle and vein be not in perfect alignment, the vein is pierced not entered and again a haematoma results and the blood flow from the needle is small or absent. In blood letting by venepuncture
without venesection, the choice of the needle is the most vital consideration. Experience gained in the investigation reported, has shown that a stout needle, number 17 in diameter and two and a quarter inches long gives the best results.
The cutting edge of the needle must be keen, and it Is well tro sharpen the needle on an Arkansas stone at each time of use.
In many persons the coagulation time of the blood is shorter than average and when such is the case in a donor, bloodletting is rendered more difficult.
For the purposes of this investigation an attempt was made to withdraw 160 c.c. of blood from each donor. In
74 of the 137 donors, the blood flow stopped before this quantity had been obtained. From 46 per cent, only of the donors could 160 c.c. of blood or more be collected by vene puncture. Such an experience shows that it is not easy, even for one practised in the art of venepuncture, to obtain by this method large quantities or even moderate quantities of blood from every donor.
The maintenance of strict asepsis from start to finish is a major problem of serum collection. It must be borne in mind that the preparation of serum is a responsible task, for great risk attends the injection, if the serum be contaminated; intramuscular abscesses and worse have been reported.
Technique of Blood Collection. The method of blood 14
collection employed a needle conforming to the above de
scription, a two-way tap, and a 20 c.c. syringe of
1 Record* pattern. The syringe chosen was a well used one,
the piston of which was a perfect sliding-fit in the
barrel. It was found that in a suitable syringe, if the barrel were held vertically, the piston placed at the upper end, would slowly travel by the force of its own weight to the lower end of the barrel. A ward sister
instructed in the technique, placed these Instruments - needle, two-way tap, and syringe (dismantled) together with two pairs of dissecting forceps, in a fish-kettle
sterilizer, and boiled them for half an hour or longer
in the side-room of the ward. After sterilizing her
hands by scrubbing with a nail brush and soap in warm
running water, she placed two sterile towels, the one
superimposed upon the other, on a tray. By means of a
pair of large forceps, the lower ends of which were in
the water and therefore sterilized, and the upper or
•handle* ends out, she lifted the instruments out of the
boiling water and placed them on the sterile towels.
Using the same forceps, she carefully folded the upper
towel over the instruments, and then folded the lower or
outer towel over the inner towel. The tray was placed
near the bed or couch on which the donor was lying, and
in a few minutes the instruments were cool, dry, and
ready for use. The sister covered part of the side of
the bed or couch with sterile towels, and the donor was
instructed to rest the arm on these, and to place the
hand with the palm upwards. By means of gauze sponges
held in sterile forceps, the sister sterilized the skin
over the antecubital fossa, by swabbing with ether
followed by methylated spirit; she then applied a light 15
tourniquet of the Poulis pattern to the upper arm, and the donor was instructed to clench and unclench the hand several times, and finally to hold the hand tightly clenched. Meanwhile the writer had sterilized his hands hy scrubbing with a nail brush and soap in warm running water. The sister unfolded the towels, and the writer, using the sterile forceps, assembled the syringe, two- way tap and needle and performed the venepuncture. The skin over the antecubital fossa was drawn taut by traction exerted by the thumb of the left hand placed lower down on the donor*s forearm. The direction of any convenient vein was noted, and the syringe was held so that its axis was in line with the vein, the needle resting on the skin directly above it. Keeping the needle as horizontal and as close to the skin as possible, the point was gently but firmly insinuated for about a quarter of an inch into the subcutaneous tissue between the skin and the upper surface of the vein. The needle was then directed downwards by slightly raising the barrel of the syringe, and by a short sharp forward movement, the wall of the vein was pierced, giving a sudden characteristic * yield ing* sensation; the barrel of the syringe was immediately lowered, rendering the needle as nearly parallel with the vein as possible, while the point of the needle, now in the vein, was advanced about quarter of an inch into the lumen, by means of a forward movement. This technique of venepuncture proved very reliable; much more so than the usual method of thrusting the needle directly into the vein which resulted too often in transfixion of the vessel.
The first few cubic centimetres of blood were ejected into a small sterile test tube which was 16
subsequently transmitted to the Public Health Laboratory, where the blood-serum was subjected to the Wassermann and
Kahn tests. Thereafter each syringeful of blood (20 c.c.) was received into a separate test tube containing 1 c.c. of 7.5 per cent, sodium citrate solution. These citrate tubes prior to sterilization had been fitted with cotton wool plugs and wrapped in Kraft paper. While the syringe was being charged with blood, the sister unwrapped a citrate tube, removed the plug which she held in the left hand, and placed the mouth of the tube under the outlet nozzle of the two-way tap. When the syringe was full, the tap was turned, and the blood ejected into the citrate tube; the cotton wool plug was immediately replaced by the sister who proceeded to -unwrap another citrate tube while the syringe was being refilled.
The time taken to collect 160 c.c. of blood by this method was less than three minutes, and the mental upset sustained by the donor was little more than that occasioned ordinarily by the taking of blood for a
Wassermann test.
In the above technique, the syringe and needle for withdrawing the blood were dry when used - an impor tant factor in the maintenance of absolute sterility.
In a large series of blood cultures recently carried out at Knightswood Hospital by this method, not one was con taminated. In a previous series in which the syringe and needle were lifted out of the water in which they had been boiled, and were consequently used fwetT, a number of the blood cultures were contaminated, even although every possible care was taken to ensure sterility.
Laboratory Technique. After the venepuncture had been performed, the tubes of citrated blood were taken to the hospital laboratory, where the work of separating 17
and storing the serum was carried out immediately, or within a few hours after the withdrawal of the blood.
Occasionally in a very few of the tubes partial clotting occurred within a few minutes. When this happened the tubes were placed in the ice chest for two hours or longer, after which time the clot had contracted sufficiently to allow the plasma to be decanted.
Prom each citrate tube in turn, the cotton wool plug was removed, and after the mouth of the tube had been carefully sterilized in a bunsen flame, the blood was poured over the lip into sterile centrifuge tubes, each of which held 10 c.c. and had a graduation mark at this level. Prior to sterilization, each centri fuge tube had been fitted with a cotton-wool plug, and the latter had been transfixed by a piece of wire slightly longer than the diameter of the tube, the purpose of which was to prevent the plug from being driven into the tube during centrifugalisation. The cotton-wool plugs were immediately replaced after the introduction of the blood. The tubes were placed in an electric centrifuge and rotated at 4000 revolutions per minute for about ten minutes. After centrifugalisation the upper half of the contents of the tubes was clear straw-coloured plasma, and the lower half, red blood corpuscles, while at the line of separation there was a thin white film of leucocytes. The plasma was separated by means of a sterile 20 c.c. syringe and wide bore canula. This syringe and canula, together with a one cubic centimetre syringe and a long needle required for the addition of the antiseptic tricresol, had been sterilized in the same fashion as were the blood collecting syringe and instru ments, i.e. they had been boiled for half an hour or 18
longer and wrapped in two sterile towels. The outer towel was carefully opened out without touching the inner towel, and then the writer, after sterilizing the hands hy scrubbing with a nail brush and soap in warm running water, uncovered and assembled the 20 c.c. syringe, and proceeded to aspirate the plasma from the centrifuge tubes. The task of drawing up the plasma into the syringe proved to be rather a delicate one, because if a few drops of plasma were allowed to flow back from the syringe into the tube, the blood corpuscles were disturbed and were dispersed throughout the plasma.
By means of the graduated 20 c.c. syringe the plasma was measured into sterile bottles holding 10 c.c. or 20 c.c.
After the whole of the plasma of the batch had been apportioned to the various containers, the 1 c.c. syringe was removed from the sterile towels, assembled by means of the sterile forceps, and used to measure and add the antiseptic tricresol. One cubic centimetre of a 2.5 per j cent, solution of tricresol in water was added to each
5 c.c. of plasma, so that the ultimate concentration was
0.4 per cent. Immediately after the introduction of the plasma or tricresol, the cotton wool plugs were replaced in the mouths of the bottles.
Before commencing the separation of the serum, a sufficient quantity of rubber stoppers together with a pair of dissecting forceps, had been placed in a beaker of water over a bunsen flame. By the time the stoppers were required, they had been boiled for more than half an hour. The cotton wool plug was removed from each bottle of serum in turn, the neck flamed, and a rubber stopper held in s terile forceps was lifted out of the boiling water, passed through a bunsen flame to remove moisture, 19
and then fitted firmly into the mouth of the bottle. The bottles containing each batch of serum were appropriately
labelled, and stored in an ice-chest. A cultural sterility test was carried out on each batch by inoculating a tube of Hartley’s broth and a blood-agar slope with plasma, and incubating them at 37°C. for twenty four hours. In no case was a bacterial growth obtained.
The average time required in the laboratory to deal with the blood from each donor was about two hours.
The plasma when separated was clear and straw- coloured, but after standing for twenty-four hours it be came somewhat cloudy, owing to the precipitation of fibrin in a very finely divided state. When the plasma had been kept for weeks or months in the ice-chest, the precipitate usually collected on the surface of the serum which was clear and straw coloured: more rarely the pre cipitate settled to the bottom of the container, and in a few of the batches it remained uniformly distributed throughout the serum. In all cases the precipitate was extremely finely divided, and by shaking was easily dis persed throughout the serum which it rendered slightly cloudy.
Preparation and sterilization of Materials. The tubes used for collecting blood were | of an inch in diameter and 5£ inches long: when containing 20 c.c. they were about three-quarters full. A lip was drawn out at one point in the circumference of the mouth of each tube, to facilitate the pouring of the blood into
the centrifuge tubes. The tubes were carefully washed and dried, fitted with cotton wool plugs, and sterilized in the hot air oven for one hour at 160°P. By means of a sterile pipette one cubic centimetre of a sterile 7.5 20
per cent, solution of sodium citrate was added to each tube. The tubes were wrapped in Kraft paper and steamed for one hour in the Koch to ensure absolute sterility; thereafter they were stored in an upright position in a covered glass Jar.
The centrifuge tubes were f of an inch in diam eter and 3-J inches long. A graduation mark was filed on the tubes at the 10 c.c. level, so that an equal quantity of blood could be placed in each thereby ensuring balance in the centrifuge. Each tube was carefully washed and dried, and fitted with a cotton wool plug, and the latter was transfixed with a piece of wire slightly longer than the diameter of the tube. The function of the wire was to prevent the plug from being driven into the tube by centrifugal force, during centrifugalisation. The tubes complete with plugs and pins were wrapped in Kraft paper and sterilized in the hot air oven for one hour at 160°P.: thereafter they were stored ready for use in a covered glass Jar.
The bottles used were empty serum bottles of 10-
20 c.c. capacity. They were carefully washed and dried, and each was fitted with a cotton wool plug and wrapped in Kraft paper. Sterilization was effected in the hot air oven by maintaining a temperature of 160°P. for one hour. They were stored ready for use in a covered glass jar. The covering papers were not removed from the tubes and bottles until immediately before they were used.
The entire work of collecting the blood and separating and storing the serum, was carried out in the wards and laboratory at Khightswood Hospital. 21
THE INVESTIGATION.
In this section a brief report is given of each group of susceptible children exposed to measles infec tion. Each report is prefaced by a table containing the relevant data, and most are preceded by a series of temperature charts for the attenuated and modified, and many of the classical and control cases which occurred in the group. On each temperature chart the salient clinical features of the illness are recorded. The re ports terminate with summaries of the results obtained.
In estimating the interval of time between the beginning of the exposure to infection and the injection of the serum, or the number of days after the beginning of the exposure to infection on which the serum was given, it has been assumed - following the method of Zingher - that the infecting measles case had been actively dis seminating the causal agent for four days prior to the appearance of the rash. 22
to to
>rH *d > © rl *\ & 10 © © to ft 8 ft © a *H A to a © *d to £ tO £ © £ to A & © to *d > \ CM © 0 ■d rH £ 5 \ £ © (O P 01 o * © W rH n © £ £ © H © © a O © © © Put CO o t=> • 5 6 O CM © o o PS t rH 0 o *d «“ £ f. •d •d 1 a! &0 © © r© £ s •d »43 o Q •d M < © *H m o © u P« © • rHO2tO'*lO 1 «H rH rH O © © © © I I 1 * < S 2 5 © S 3 © S 3 © o & o & o rH Cb o 00 oi n n o O EH « 525 O « 1 02 O *"3 PQ rH o O o o EH « 525 o 1 1 % EH O pci o u K Contacts who proved to have been in pre-eruptive stage Measles when inoculated* 23 24 Commentary Group I . The first group of children exposed to measles infection were patients in a scarlet fever ward in Kilmarnock Infectious Diseases Hospital. Ten cases of measles occurred in the ward on 12/11/33, and one case two days later; they were transferred to the side-room of the same ward when the rash appeared. Twenty-one children had not had measles and were exposed to infection. Dr.Nisbet, Medical Officer of Health of Kilmarnock, was most anxious that as many as possible of these presumably susceptible children should be immunised, and for that reason, three only did not receive serum and served as controls. The serum was given on 14/11/33, the sixth day after exposure. Twelve of the immunised contacts did not contract in fection. Three developed a measles rash within four days after the injection of the serum; they had therefore been in the pre-eruptive stage of measles when the serum was given, and the source of their infection had not been the cases which occurred in the ward on 12/11/33 and 14/11/33. These cases are not comparable with the other contacts and are, for this reason, not included in the results. One immunised susceptible contact developed attenuated measles, one showed modified measles, and one classical measles. None of the uninoculated controls contracted the infection. An interesting example of the effect of human serum in the treatment of psoriasis, was observed in one of the susceptible children in this group. Prom a very early age the child, (W.M.No.ll) now three years old, had suffered from a severe and intractable form of psoriasis which had resisted all the usual therapeutic measures. 25 He had recently been under treatment in hospital for a period of six months, with but very little improvement. When the injection of human serum was given, the whole of the child*s skin was so severely affected that it was hardly possible to find a suitable area of healthy skin through which to administer the serum. After the in jection of the serum, rapid improvement in the condition of the skin was observed; the lesions healed and within a week the child was discharged from hospital, not alto gether cured but very markedly improved. The intractable nature of psoriasis is well re cognised, and reference to the literature shows that many fields of investigation have been explored in search of effective treatment, including protein shock and serum therapy. Autogenous serum and normal horse serum have been used from time to time with varying success. Conclusions and generalisations based on a single case are always dangerous; but in view of the rapidity and dramatic nature of the improvement following upon the in jection of the human serum, it is probable that in this child the improvement was really due to the serum. 26 GROUP I. SUMMARY OF RESULTS. Immunised Presumably Susceptible Contacts, 18 Inoculated in Pre-eruptive stage of Measles, 3 No Measles 12 Attenuated Measles 1 Available Immunised Modified Contacts, 15 Measles 1 Classical Measles 1 Controls - 3 Uninoculated presumably susceptible contacts did not contract Measles. 27 PARTICULARS OP SUSCEPTIBLE CONTACTS O i f Q i U p < *H Pi © H rH * t E to KS h F © © o d © © h h H fOl CM CM CM CM CM CM CM £*■C~CM CM rHOS O fc*rH O C*" £*• t- £*■ rH iH rH»H iH rHrH rH MC CMto toCO < C- CO tO tO CO tO tO CM03 tO03 CM 03 tO OS << CO CO tOrH < << rH H CM rH l> tO CO rH tO K) tOlO (O tO lO H H» H» rH »H rHrH»H tH IHPO<< K K tO rH H H H O O O «H•H to to to ©a to to to to ra© m© O O © © © © •••••• H|OH\\\ \ \ H O | H 3 « 13 CM CM CMCM to tO tO ^ P- O •PH-P P© -P Vi +> *d © 49 •d »d < O JS25©S3®S3©S3©S3©S5© CM OFOPiOFOFOfi e \ \ N \ 3 O 0 0 0 10 10 10 10 tO 03 S H M tO CM rH O OS < a co ? S Q? S W o o o o O O CO CO CO to coco o S3 E w p iH HrH rH o rH •H O << O c- to MC HCM rH CM CM 0to 10 ♦ • o © © © O © O © h • • • • • t o O 3S3 S3 « OS o p rH rH •H *d *H O CO O to (0 © © © • © O d © d Fj © rH © © O © ^»rH O © O K K K K K N \ \ H H H rH rH rH rH o HEH EH « O p p p o CM to 1 • -tfJCMC-ICM tOlCM \ CJ H H rH rH rH O o S3 w o o o o O rH O rH iH to c- <** 10 O © © © © © © » \ Contacts marked died from Broncho-*Pneumonia 28 MARCH 3 8413 Z8A DATE DAY OF ILLNESS NAME ivARD OURNAL AGE Bowels A tt e n u a te d M e a s l e s . >ATE. AY OF ILLNESS IURNAL A.M. A M P.M.P.M. A.M.P.M. A M P.M. A.M. P.M. A.M. P.M. A.M. P.M. TIME 107 106‘ 105 ' 103* 101 100' )ATE. •AY OF ILLNESS. AME. 160 GE. ARD. 150 )URNAL 140 130 120 110 100 Bowels Urine : M a r c h DATE, )AY OF ILLNESS, ’AME. GE. ’ARD.. HJRNAL IGE Bowels Urine C l a s s ic a l M e a s l e s . 5 mu 2 &E M a r c h 3 o jfvmjksn A.TE., AY OF ILLNESS SB, ARD URNAL. GE. Bowels Urine At t e n u a t e d M easles 6 TIME 107“ 108° 105 ° 104° 103° 102s 101° 100° 99* )ATE 83° AY OF ILLNESS 97* AME 160 150 URNAL 140 130 120 110 100 90 80 70 60 60 !■ ! * n rxt if p. r r ' r i ^ i f l . T ? ai 40 30 20 10 Bowels Urine M e a s l e s . 3 EOBuK 2E waffmnr aasjosaSu ATE. AY OF ILLNESS. URNAL. Bowels Urine ATTENUATE!) MEASLES. A.M. P.M. A M P.M. A.M. P.M. AM P.M. A.M. P.M. A.M. P.M. A.M. P.M. TIME 107’ 103' 101 100“ >ATE. AY OF ILLNESS. AME. 160 ARD. 150 URNAL. 140 GE, 130 120 110 100 Bowels Urine M o o i f i e o M e a s l e s . 29 Commentary Group 2 . The second group included the children in Scotstoun House, a home for debilitated children of pre-school age. On 15/3/34, a child who had been admitted twelve days previously, showed Koplik's spots and the catarrhal symptoms of measles. He was removed to hospital on the following day and developed a typical rash on 17/3/34. Fifteen children were exposed to infection. Of these, thirteen had not had measles and were presumably susceptible. On 16/3/34, the third day after exposure to infection, seven of the presum ably susceptible children were each given 15 c.c. of adult Immune serum, and six did not receive serum so acting as controls. All the susceptible children con tracted measles. Three of the seven immunised contacts developed attenuated attacks, one showed modified measles, and three the classical disease. Two of the classical cases died as a result of complicating broncho-pneumonia and enteritis. All of the six non-immunised controls showed classical attacks, and four of them died from broncho-pneumonia. One of the non-immunised controls, (A.M.No.31) developed measles twenty-six days after the first expos ure to infection - a length of time beyond the recognised limits of the incubation period. In all probability the source of this infection was not the original or first case of measles, but was the cases arising as a result of contact with the original infection; if so, the in cubation period would be between nine and seventeen days. It is likely that this child possessed partial natural immunity to measles which was only overcome after a second long continued exposure to infection. In this group two children *sho had had adult immune serum died. It is apparent then, that in some cases there is a fatal termination in spite of the ex hibition of adult imaune serum. 31 SROUP 2. SUMMARY OF RESULTS. (Attenuated (Measles 3 Immunised. Presumably ( (Modified Susceptible Contacts, (Measles 1 ( (Classical (Measles 3 (2 died.) Controls - 6 Uninoculated Contacts contracted Classical Measles and 4 of them died* 32 to to to at a «H S § © ft >> Pi © © © •d • £ .0 0 • • • • © P Hi* Hi* H0* © CO Pi to 10 to to (0 00 N \\ N S to to to to © •H \ \\ \ 0 to IP (0 CO $ PL. 02 02 02 02 ©« •» to C- « I © •d rH s> •d © o 3 taO •d *d 0 © « 0 0 © © « © •H © 0 _ ^ a a © *d -t © © © 0 *d %H o Pi 0 o © P Pi 0 0 p P i 2 © © *H o co 00 00 •d ft © EH o © A ft •d 0 W © p 0 © © p p 0 > 0 EH rH © «H © jCj O o £3 00 * © p n g o O 0 •d © © © O No. Name. Number* Years. in Days. Attack* Appeared* C" to t0>- to ^ CM s s s s s s s s s s s lo^ooocoooicioioiotro H r-C\0 l r CMH tO CMtO CMW rH CM tO 02 \ H lOtDt-COOOHCMtO^lO GOHWCOCMf^EHW^OCQ WS«^McopQ|x}}ziSfs © 0 ( © © 0 t 0 ( © 0 © © © tototototototototototo W W W W N W l O W ^ O t W tOtOtOtOtO^^^^^x^ tOtOCOlOtOlOtOtOtOtOO 1 1 1 1 1 GO1 1 1 1 I i t i i i i i i i\ t • * o * * * * . * « o * ..*«..*.»*. o P •«**•••••« . . 01 rH \ H > CM rH to • Attenuated * OfcOfcOfcOfcOfc q ^ ^ H H H H 01 rH »H CM pH CMrH CM CM t S 4 b 4 SSAt O O O O GO CO CO CO CO 1 W ^ M1 C- to C S S W o PC ©* 1 > 1 1 G> 1 I « • • • # « * • • • • • • • - o o o * - • CONTROL z * * * PQ o 1 .*35 * © « CONTROL sz ;©: 00 Very mild > o o> CONTROL Measles. 14/4/34. z © & © ; CONTROL CONTROL 33 34 Commentary Group 3. In a ward in the Southern General Hospital containing children suffering from primary pneumonia, one showed a measles rash on 26/3/34. A nurse on duty developed a measles rash on 5/4/34: she was twenty-two years of age and was bora in Skye: it is likely that she contracted the infection from the child. Sixteen children who had not had measles were exposed to infection: eleven of these were each given 10 c.c. of adult immune serum on 28/3/34, the sixth day after exposure, while five, the controls, did not receive serum. Two only of the presumably susceptible children contracted measles; one an immunised child and one an un inoculated control. In both the attack was exceedingly mild. Koplik*s spots, catarrhal symptoms and pyrexia were entirely absent. The rash was faint, sparse and discrete, but morbilliform in character, and appeared on face, abdomen, and limbs. In the immunised contact the attack which is regarded as being attenuated by the serum, did not appear to differ in any way from the exceedingly mild attack in the non-immunised control. Throughout the catarrhal stage of her illness, the nurse was engaged in attending to the children: she went off duty only when the rash appeared: yet only one of the five presumably susceptible children who were not immunised contracted measles. It is highly probably that these children possessed a considerable degree of natural immunity. 35 GROUP 3. SUMMARY OF RESULTS. Immunised Presumably (No Measles 10 ( Susceptible Contacts, 11 (Attenuated (Measles 1 Uninoculated Presumably (No Measles ( SusceptibleContacts, 5 (Very Mild (Measles (Controls) ' f XS 36 • *d • • • 4 © Hi* Htf Hi* Hi © £ A £ to to to to 49 © © © 1 N © A © © H|* Hi* hi Q * fa ft \ w ft o> a> o o < rH rH %H • rH rH rH rH fit OM © © © © o O O o O © d «rl «H «H •rH ft 49 © © « 1 © ►*49 © © © © ►* EH < © © © © (4 of rH rH rH rH © •d O O O O > © • fa 3 • xn to CO i *d ►* 49 • • •• EH A £ O © © H|» Hi* Hi* Hi* O £ O - H p 10 tO H|* 1 Ht* rH to to to to < O H £ HHH rH fa £ \ \ \ \ 1 EH £ 4 9 © c © to to to to fa H © fa *H 8 o \\ \ *. - wo fa • CO 00 c- t- c- • o iH to rH OJ 02 02 h|* •d o £ a to © O £ £ to o o •d 1 \ to © £ *rl © 02 02 02 to •H 02 to o © a •d \ H < P H P P & to *d •d GO C_l CO £ £ © a 02 1 E* *H _ o o Eh rH t H © £ fa 8 fa ° f l • © £ fa a *d •H o £ £ © h|* o O fa fa 49 © © © i CO © £ «H ►» tO IP to Eh t H *■« o Pi £ 5 1 © £9 to © © to to to EH tH fa P i 49 P i © u £ CO «JC0 P O a £ © © u « » fa o o © •d Pi * fa • w © A P i •d *d o _ _ £ O o CO © 49 u © © © © §.£ © £ £ 49 h > « 49 CO 3 O X J lO C- O O 3 © © •rl a A o •H O fa £ 49 g to to to CO ► * 49 « 8 £ © <2 © © p The fourth group of measles contacts was composed of children in a scarlet fever ward in Blawarthill Hospital, Clydebank. A child in the Ward showed a typical rash on 27/3/34. Five pre sumably susceptible children were exposed to in fection: three of them were each given 10 c.c. of adult immune serum on 28/3/34, the fifth day after exposure; two controls did not receive serum. One of the uninoculated controls escaped Infection, but all the other susceptible children developed classical measles. G R O U P 4. SUMMARY OF RESULTS. 3 Immunised Presumably Susceptible Contacts Contracted Classical Measles. Uninoculated Presumably Susceptible (No Measles Contacts, 2 (Classical ( (Controls) (Measles 39 1 1 1 when Rash Date : .-n** Appeared* ^H * o x o 0 0 1 1 1 ftp p i p EH < 0 •d to eh • • • • • • ft CO n P i «d >» to © SO to to to to EH ft P O 0 «rt \ S N \ S3 P OrlQ 1 1 1 ft ft to to to to o O iH (h P at \ \\ \ 1 u P ft © P o o co 0 1 GO 03 M 0 ft •H to rH 02 02 02 • c£>PS •d a *-t • to 0 O P 0 i N 0 a o p p 02 02 • to «H EH 0 P Commentary Group 5 . Several children were receiving Indoor treatment for scabies in Moffat Street Reception House, when one of them contracted measles, the rash appearing on 28/3/34. Three presumably susceptible children were exposed to infection; two of these were given 10 c.c. of adult immune serum on 30/3/34, the sixth day after exposure, and one did not receive serum and acted as a control. None of the contacts developed measles. G R 0 U P 5. SUMMARY OF RESULTS. 2 Immunised Presumably Susceptible Contacts did not contract measles. One Uninoculated Control escaped Infection. -- ? * |r V. : : 1 e? . » -A - \ - , ' - 4: - i -Q £: s-v* -■£ •' f 42 . *d W:"ill a ISIS T: © © P 43 ft P © © © i i 1 1 © 43 00 © Q ft *?%Zu a < • 00 p o • i i 1 1 •H ©» P © O *d © © Type of Attack. 43 ft p M • .• • <0 § O to to to to < to *H \ \ \ Eh • P to 10 10 to 1 S3 i i 1 1 cu Pi \\\ \ O £> © © o l> 00 oo o ation in Days. Period o o 03 02 02 02 02 • Incub P3 •H n* •d © ■P to © 3 Vi * Pi (\ n o p » © to •H 9 2 a h 02 02 03 •d \ ft EH © P W B CO 02 •H © ft O o o Eh H ft ©E 3 •d 03 o © © © © P 03 P3 < •d Vi O Pi © 1 © 03 EH p P P i 3 p P in Eh Eh 345 » © P © © Vi © 345 1 Serum Age Age of o £ © ■d Pi * O Days. & & o © A P i *d *d © p P © © © © 03 o o 03 P ft p h > © P P3 3 © •H 3 43 o iH O o o o o 3 i * a p ra a © © fr-1- 03 ft ■d © © © p P 0 < •H © o a P 0 Serum Batch dumber • Vi ■p s o w P o •H o Eh © • M © © p O o o p No ■ © p O «rl • rH rH No • 5 Serum © p P 5 01 P o Serum •H o p © 43 ft o o © © O «H • 02 P 43 © P © © © a © rH o o A O P t0*H ftto\ to to •H «H p © O 3 c 3 to > © © © © © ■»* * «P « 43 ft P o SH a o rH p H P P< © o a © o X w ft o n © *d o o © o « « « ft P © © p *-» a v< © a n p P • • • . © rH o © © © Name. < < tP Q P © P Vi Pi p A P O « O O K o © rH 00 « •H © © *3© © • © © • . ■P p P © p © ri O 0> O H 02 fl iH P © o p p P ©5 LO to to to O H © © o © © © o M 04 O ► o PP 43 Commentary group 6 , While under treatment in the Septic Ward of the Victoria Infirmary, a child contracted measles and exposed to infection four children in the ward who had not had measles. Two of the presumably susceptible contacts were each given 10 c.c. of adult immune serum on the sixth day after exposure, and two who were chosen as controls did not receive serum. None of the contacts developed measles. SUMMARY OF RESULTS 2 Immunised Presumably Susceptible Contacts did not contract Measles. Controls - 2 Uninoculated Presumably Susceptible Contacts did not contract Measles. 45 *d _ © ® d A b p © © S I I I © A © © £?• Q ► « CM A < Vt • O ^ O I I I § © © © © •d EH < # £ • • • • A Hj* p to to to to to CO ro b \ \ \\ EH i «d H © to to to to 1,0 d O © 6 V S\ J3 O «H Q 1 I I P 02 to CO CO EH OhH b 04 b P 02 02 02 55 d P © d & 04 O jp © 04 P o •d O © g to © O f4 © P 2 d b CO CO CO •d > CQ © C P ® rH i-l rH W •d •d u p bO O © ti © © > Eh < P >H ►3 h3 P Si Be to A GO •d b IK Si *d W Vl- o O Eh b © © © O O g • O © Vi o A © CO ? d w to Commentary Group 7. Patients in a children1 s ward for primary pneumonia in Knightswood Hospital, formed the seventh group. One of the children contracted measles and ex posed five presumably susceptible contacts to infection: three of these were each immunised with 10 c.c. of adult immune serum on the sixth day after exposure, and two did not receive serum and acted as controls. Hone of the contacts developed measles. 47 GROUP 7. SUMMARY OF RESULTS. 3 Immunised Presumably Susceptible Contacts did not contract Measles. Controls - 2 Uninoculated Presumably Susceptible Contacts did not contract Measles. 48 ir •d - • H« © A i d Pi to P © © a I I © A © © |q ► ft; p. •V Pi ^0 «< Vi rH •,7** h * H« H* o M © Oltto to to to O ©m g© I I I •rl © to jo > f t p © Pi a © © © o 03 > © © l> o f w to *d H a> _o fe •d Pi cO © p to E-» i «d © • H* H« H< <5* o £ a o © rH HltO to to to C ^ O r lQ I I I Hi GO Pi Eh O H t, H © © to to « A p © A o 01 > O M © Ph «H t=> CO ©too > efr > o o fc3 rH to *d ft; h * © HO Pi w o to © O A Pi tO IO <0 O rt © A Commentary Group 8 . Two patients in a scarlet fever ward in Shieldhall Hospital contracted measles. Five pre sumably susceptible contacts were exposed to infec tion: four of these each received 15 c.c. of adult immune serum on the third day after exposure, and one who was not given serum acted as a control. One of the immunised contacts developed a classieal attack and three did not contract measles. The uninoculated control remained free from infection. 50 GROUP 8. SUMMARY OF RESULTS. (No Measles Immunised Presumably Susceptible ( (Classical Contacts, 4 (Measles One Uninoculated Control escaped Infection 51 • • • •d 5X _ © to to JL%? . Vs pS © *3© 5© 1 \5X ©ri © © \ „v ■ w-”V ' ’"Sr* p © fa a (0 o * §&..i* MAX- p H rH «© '■Si-. fU -1': • H Vh • »d © O M © O o p P ft © © 1 Vi © © ftp p © > h P •d © © Eh < o rH S fa • O 43 • 4> • • • © • Commentary Group 9 . This group was formed by patients in another scarlet fever ward in Shieldhall Hospital; they were exposed to measles infection from a case which showed a typical rash on 30/3/34. Two presumably susceptible contacts were each given 15 c.c. of adult immune serum on 1/4/34, the sixth day after exposure, and one did not receive serum and acted as a control. One of the immunised contacts who was suffer ing from post-scarlatinal cervical adenitis accompanied by remittent pyrexia, contracted measles in a modified form. The pyrexia remained rather high for a few days, owing, probably, to the adenitis; Kopllk's spots were absent, catarrhal symptoms were slight, and the rash was faint, generalised and morbilliform in character. Fortunately the measles attack did not increase the severity of the illness. The uninoculated control developed a classical attack. 0 R 0 U P 9 SUMMARY OF RESULTS. Immunised Presumably Susceptible (No Measles 1 ( Contacts, 2 (Modified (Measles 1 One Unlnooulated Control contracted Classical Measles. 54 • •d © © d .d* P © «a © A ©© « ► tfft ft 14/4/34. 12/4/34. v< • • ox OJItO o to to ©© ©Co* m > > t>» es as © Eh P % 3 • II rH tO <«* 13 ■s to to Period ation •H Incub © to Days. [in put a © s > © id O O H > *d © in to to ra <© tH S A Age Age of Years. to *d Donor d •d •d •H © S •d © * o a * ft CO O -P © © ft «d ■d o •H d p ■g © © © ra o ft 4> p ra p 02 02 co 02 5C Si .d o •H o to to O p © e © Serum a M 09 1 © © © § p Batch • Number 03 P o « ft o P in rH rH ft © C.C. J5 d © d Dose CO 02 o U « +5 0 d © £ 09 o S* 3 w A © © *rl A** a A rH P © in H«eo to *H p © O P Age H £ © © o • Years 3 Vi © © © ra O .d p o • 8 p H d ft © • • U 1 a Vt o H « • EH U ft o »d O o © i • • & © P ft M • 02 rH a © ft P 02 0 © o © g © rH O 02 o © ft P P 84 « • . © © •H © K O •rl O to fc- p a P o © © * ft ft t- r- 78. d h P © © o © o d p 03 o M ft A o © 5 * o a 9413 P.M. DATE., JAY OF ILLNESS, TAME, GE rARD JURNAL 1GE. Bowels Urine ATTENUATED M e ASL&S. April n A.M. P.M. A.M. P.M. M P.M.A A.M. P.M. AM. P.M. A.M. P.M. A.M. P.M. TIME TTTTTo ^ 107 1Q6‘ 105' 104s 103' 102' 101 100' DATE. OAY OF ILLNESS. TAME. 160 GE. ’ARD. 150 JURNAL. 140 IGE. 130 120 110 100 !»£ n j M T f n n i v i »ci L=IAJ U2AS tamiL* M a l i q h a n T M e a s l e s Commentary Group 10. Patlent8 in a diphtheria ward in Knightswood Hospital formed the group. On 1/4/34, one of the children showed a measles rash, and on the following day another child was found to have a typical rash also. Three presumably susceptible children were exposed to infection. Two of these were immunised with 1 0 c.c. of adult immune serum on 1/4/34, the fourth day after ex posure, and one did not receive serum and acted as a control. One of the Immunised contacts developed an attenuated attack which was so mild that the child was not in the least upset. The uninoculated contact or control developed measles. The rash appeared on 12/4/34, and catarrhal symptoms were in evidence. Grave toxaemia was soon apparent. On 14/4/34 the rash was almost confluent, and was haemorrhagic in character; profuse rhinorrhoea and gastro-enteritis were present, and the child died on the following day. Signs of broncho-pneumonia or bronchitis were not present during the short illness. Although the possibility of diph theritic cardiac paralysis cannot altogether be ruled out, death was regarded as due to malignant measles. 56 GROUP 1 0 . SUMMARY OP RESULTS. Immunised Presumably Susceptible (No Measles 1 (Attenuated Contacts, 2 (Measles 1 One Uninoculated Control contracted Classical Measles. PARTICULARS OF SUSCEPTIBLE CONTACTS u H p < J • I n c u b ■■T>ate U o d d o 3 d » ^ © A ge D o se S e ru m P a t i o n w h e n S e r i a l i n i n B a tc h P e r io d Type o f R a s h S5 u 1 • N o . Y e a r s • C.C. Number • in D a y s . A t t a c k • A p p e a r e d . H \tOCM^VfO rH \ \ \ O G 0 0 COCO COCO 00 GOCO CO00 Oi Oi 0(( t QJrH rHrH iH tO (0(0 (0 rl H rH»H rH rH rH rH H l r H M C M M rHCM CMrH CMCM rHrH rH rH «H CM rH rHiH rH o O’P^ ^ ’tP tO ^ to S e c o n d a ry 2 4 / 4 / 3 4 . Attenuated S e c o n d a r y 2 4 / 4 / 3 4 . A t t e n u a t e d Oi otot- - t o t io ^ o t iH to 03 to iH A M CM CM M o d if ie d 1 0 / 4 / 3 4 . p H z © lz; k o c f o i f o c f o O H M CM CM rH tO O o o co go go cO M r r rH rH CMrH GOCO CO - l"3 P as •-3^ f t i h ^ 'I* ^ 1 • © © • • • . . . • « © • • CONTROL > > > M H H CM M M CM CMCM o o to to to Oi £5 • . • • © rH O CONTROL S e c o n d a r y 10 \ tO ^ C l a s s i c a l i Oi Oi GO £5 . >& CONTROL 15 C l a s s i c a l 58 24 25 27 28 P.M. A.M. P.M. P.M. A M P.M. A.M. P.M. A. M. P.M. A.M. TIME 107' 106‘ 105' 104' 103' 102° 101 100' AY OF ILLNESS. 160 150 URNAL. 140 GE, 130 120 110 100 e s ; Bowels Urine At t e n u a t e d M e a s l e s 25 2 b 28 P.M. A M P.M. A.M. P.M. A M P.M. A.M. P.M. A.M, P.M. A.M. P.M. 107* 105' 104' 103’ 100' WE. LY OF ILLNESS. 160 RD. 150 IRNAL. 140 3E, 130 is 120 110 Bowels Urine At t e n u a t e d M e a s l e s AfrftlL 3 A.M. P.M. A M P.M. A.M. P.M. M P.M. A.M.P.M. A.M.A P.M. A.M. P.M. time 107 106' 105' 104' 103' 102' 101 100' VY OF ILLNESS. i^rv'«-inr 160 150 JRNAL 140 GE, 130 120 110 100 llWSir*JMlriMI lUMkflblUi'UI M o d ifie d M e a s l e s 26 27 3 0 A.M. P.M. A M P.M. A.M. P.M.AM P.M. A.M. P.M. A.M. P.M. A.M. P.M. TIME 705' 104° 103° 100' r OF ILLNESS. 160 150 .NAL. 140 130 120 110 100 Bowels Urine C l a s s ic a l M ea sles - P.M. V OF ILLNESS.. RNAL. Bowels Urine C l a s s ic a l M e a s l e s . ftPRL 16 A.M. RNAL., C l a s s ic a l M e a s l e s * 59 Commentary Group 11. The children who formed the eleventh group were patients in Stobhill Hospital suffering from primary pneumonia, A child who had been admitted to the ward on the previous day showed a measles rash on 2/4/34, and on 4/4/34, the third day after exposure to infection, nine of the presumably susceptible children each received 15 c.c. of adult immune serum, and four were not given serum and acted as controls. One of the immunised contacts (J.L.No.85) developed a modified attack of measles (rash 10/4/34), and two of the uninoculated controls (D.McG. and J.G. Nos,90 and 91) showed classical attacks (rashes 13/4/34 and 17/4/34), These cases were the source of infection of two inoculated contacts (J.K. and J.B. Nos.81 and 82) who contracted attenuated attacks (rashes 24/4/34), and also of one uninoculated control (J.Q. No.89) who showed a classical attack (rash 28/4/34). Since the latter cases developed only after a second exposure to infection, they are designated 11 secondary” attacks. It is note worthy that the secondary attacks in the immunised con tacts were attenuated, whereas in the uninoculated con trol the secondary attack was classical. GROUP 11. SUMMARY OP RESULTS. Immunised Presumably Susceptible (No Measles 6 ' Contacts, : 9 (Secondary (Attenuated (Measles 2 ( (Modified (Measles 1 Uninoculated Presumably ( No Measles 1 ( Susceptible Contacts (Classical (Measles 3 (Controls) . . 3 4 3 4 / / 4 4 / / 1 4 2 5 Rash when Date appeared• • • © X *rl o d © • o 43 a 43 Type Type of P \N ft d to 1 b >* O u \ N d © at CD 02 *d *d d rH 11 • o ft © ation in in Days. Period 02 ft b rH Incub rH 43 ft O (A OS ft ft • ft rH -9 O b ^ © t> O 1 « d o d b 17 O CO rH o © d ft at 17 pci M O tt) O © c*> >— ' bO ft •d d • •d <*S P >H d P © ft © CQ ft d b to © ft _ 96 1 02 u o © •d •d \ •h O g • 96 © © © © d d d © ft o ft b d \ d ® b ft co •d 43 ft © •rH to ©} © © d < © © 1 < CO P o © © *d ft 8 •h © 43 b <1 b 1 © % rH b 43 b 43 o © © ft © P © O u 43 * 6 43 © © © 111 ft •o © © © •d 43 111 Number • Number 05 Serum ft CO c O ^ P S o © d Batch p3 CO 43 w >w» © O M O O ft o CO m © d in 20 < 43 d 20 rH • C.C. H d © Dose rH o d 1 ft o o ft ■6 P ft 02 02 P p © ■P © © rH rH O o p O 43 in 43 ft 43 © O § Age CO P © © 'H © © Xears. JC ft © P d 43 o • 6 O rH 43 H d ft P o g © o K O • b o a © •d O o © a a ft b b © © 43 « « ft © a © d b • Name PS H 09 rH o © © © 43 a d ft & 4> P 43 . . O a O o K O > at © ft © © 02 tO 43 d 43 © 43 © No. 03 03 rH b m o d 43 ►> © rH © © p o © © Serial o H ft o * o p P 62 Commentary Group 12. Three infants occupied a small cubicle which was part of a pneumonia ward in Stobhlll Hospital. One of them contracted measles (rash 2/4/34) but was not re moved from the cubicle owing to lack of isolation accom modation. Each of the two contacts, neither of whom had had measles, was given 20 c.c. of adult immune serum on 3/4/34, the fifth day after exposure. One infant who was suffering from primary broncho-pneumonia and pyelitis, was so gravely ill that it was feared he would die if he contracted measles. He did not escape infection, but the attack was so much attenuated that his condition did not become any worse, and finally he made a good recovery. The other infant although continuously in con tact with the first case of measles, resisted infection from that source, but later developed a classical attack, having derived the infection from the second case. G R O U P 12. SUMMARY OF RESULTS. Immunised Presumably (Attenuated (Measles 1 ( Susceptible Contacts, 2 (Classical (Measles 1 * >* tO to to p \ P • «H to 0 H \ © © •H to o rH -p *d P rH rH P • © © *d o d © to to H u d © o •rl d 4-t © © i d P P © O 1 o d © © • o © P s »d to O o to © iH 0 d © W \ © o •H © *rl ft \ d to © *d o p O a © rH « •H § *0 8 & P. w •d © © © © a 4-1 0 ft •H p ft © d * © © s © 03 ■tf ft © * CO © P ft d •d EH § © -p d © © a m d P © © P © •H & P © «H o EH © * ■p a a © » © 1 © © © § p o 03 <$ o ft o C o 8 P o w O o CO © d p © d 3 d © d © CO o o a d © <*! p o © o * a rH ■H * p P © © P a o o P © O P o •H P © © o w P s © ■b © E ft p o P o a O ft p H d ft o 6 o o hi d o a •d O o © 4h d d n © P © © © d © rH © o © § © P © d © ft P p O © O O K o © © •H © © * P d P d p © d P d 3 o d p o rH © o p o © s? o H ft ft * o P o PARTICULARS OF SUSCEPTIBLE CONTACTS u < O o © bO o © © h O • Age of &H p Incub Bate <4 2 * h * 2 (3 © S3 h OH © bO*H Dose ^erum Serum *«h© ation when Serial in Batch in Period Type of Rash I h i © w • Appeared. No. C.C. Number • Days. in Days. Attack. K HH K K Hoi rH rH HOIS' HOIS' h(oiHoi rH rH lOlOfc-fr-l>C- 02 tOtOtOCOtOtQrHrH aooococoaocoaoco t h h h h h O t O h t H H H H O O 0 0 5 0 5 0 5 0 5 0 0 5 0 1 »« . . . . « • • « ...... 05 to Classical 15/4/34. 02 rH H i O<0I>G005OH 1 I W W • • 02 1 » 2 0 toe* Mild 14/4/34. 01 CQtOtO rH I I Attenuated 23/4/34. 2 0 to N W C\i to *z i o l o i o i o 5 rH ►3 M \ N N (M h h h Eh Eh « Eh Eh « « O O O GO GO COCO S a O O O O < I I O o o o o o o o o o : £ Q g: £ H ©£i©s ...... 102. P Classical 21/4/34. j Hn rH HenHjw a & ft 3 103. P » 3 Q vA • o ®fc . 104. 5 00 00 CQ 02 03 03 ® 5 105. -P •H *o o * S3P •P -P © P P •H *d *d •H 2 © u i> o £3 ft h a © rH O > © © U © O © © a o S3 © o tsO a ti• © © © O ©© © fl -p 5 5 © rH I * © © O ! A pril z ? 26 27 A.M. P.M. A.M. P.M. A M P.M. A.M. P.M. AM P.M. A.M. P.M. A.M. P.M. TIME 107* 106‘ 105' 104' 103' 102' 101 100' DATE. DAY OF ILLNESS. m m 160 LGE. YARD. 150 OTJRNAL. 140 130 120 110 100 A t t e n u a t e d M e a s l e s . M M — — — — — I ■ i i n ■ 24 2 S A.M. P.M. A M P.M. A.M.P.M. A M P.M. A.M. P.M. A.M. P.M. A.M. P.M. TIME 07* 02" or 00" 99* >ATE. r AY OF ILLNESS. AME. 160 GE. 150 JURNAL. 140 130 120 110 100 Hd-& m Bowels Urine C l a s s ic a l M e a s l e s . m 66 Commentary Group 15. Scotstoun House Convalescent Home suffered a second outbreak of measles and provided the thirteenth group. On 10/4/34, four of the children had catarrhal symptoms and Koplik!s spots, and each showed a typical rash next day. There were twelve presumably susceptible con tacts: eight of these each received 20 c.c. of adult immune serum on 10/4/34, the third day after exposure, and four did not receive serum and acted as controls. Three children, believed to have had a pre vious attack of measles, contracted the infection (rashes appeared on 11/4/34, 12/4/34, and 13/4/34). Owing to lack of hospital accommodation the measles cases were not removed, and for the time being, the home was transformed into a miniature measles hospital. Two of the immunised contacts (W.S. and J.McL. Nos.94 and 98) showed typical measles rashes within four days after the administration of the serum; they had been therefore in the pre-eruptive stage of measles when the serum was given, and had probably con tracted the infection from the same source as the pre vious cases - not from them: they are not comparable with the other contacts and have not been included in the results. One immunised contact developed an attenuated attack, and five did not contract measles. Three of the four uninoculated controls escaped infection, de spite the fact that they occupied the same dormitory as the cases for over a week: apparently they possessed natural immunity. The one uninoculated contact or control who contracted the infection, had a severe attack compli cated by catarrhal laryngitis. GROUP 13. SUMMARY OP RESULTS. Immunised Presumably Susceptible Contacts, . • • ••• 8 Inoculated in Pre-eruptive Stage of Measles, ...... 2 (No Measles Available Inoculated Contacts, 6 (attenuated ( Measles, (No Measles Uninoculated Presumably Susceptible ( Contacts (CONTROLS), ... 4 (Classical ( Measles, MEASLES CONTACTS GROUP 14. Sg H -P «H rH w d •H p .d p -p w o p 0 O 0 Pi at £ o o CO bD p g p o P o CO o at • •H ,p t p •rl ,p «H « P to I ^. w v^s. N*s<* ' —' ' 1 ^ ^ 1 W 3 i—1 rH 03 O CO 60 tO 00 P *0*0 O ^ CO p p 1 p 0 p P Q 0 1 © 0 *Q 0 _> 1 > _ • p p Pi d H p 1P 1 0 P 1 O,p •H 0 <3{ CP I ppo P< 0 1 P 1 1 1 • « 1 1 1 1 \ ^ ^ CO P H d rH H 1 •H O d H P P A W o o P P © 1 © P 1 PP 1 P 0 0 0 0 £ £ 1 0.P © 0 1 0 0 p o p G s 0 0 0 O 0 0 £ d & M I O p P 0 0 0 1 0 § g 1 P g P P p 1 O 0 * t>S * 1 1 i I 1 1 oa to EH o EH o to O CQ id Age of Age of Incub Date Age Dose Serum Serum Donor ation When Serial in in Batch in in Period Type of Rash Number Name Years c .c. 'Number Days Years in Days Attack Appeared H i— 1rH rH to g5 o o o s s s w s ini in m lO 03 03 03 lO — C 1 CO 1 • « • • 106 i 1 124 Secondary 3/5/34 Attenuated CO P — h •o ! 107 S 124 Attenuated 20/4/34 i H|G2 to 5S rH * * 108 124 Very Mild 15/4/34 H|M w P tO i i i 109 • No CONTROL Serum 68 * * Contact who proved to have been in Pre-eruptive Stage of Measles when Inoculated. P.M. A.M. P.M. A M P.M. P.M. A MA.M. P.M. A.M. P.M. A.M. PM. A.M. TIME 107' 103’ 102° 101 KY OF ILLNESS. 160 150 URNAL. 140 GE, 130 120 110 100 IP Bowels Urine A t t e n u a t e d M easles 22 24 zs P.M. A M P.M. P.M. A M.A.M. P.M. A.M. P.M. A.M. P.M. A.M. P.M. 106‘ 105' 104' 103' 102' 101 100' iY OF ILLNESS. 160 LRD. 150 ■JRNAL. 140 GE, 130 120 110 100 nr. m m * 4 n n«uirn.t.-ii-i^i U JbU A IullJS2 1 Bowels Urine At t e n u a t e d M e a s l e s 69 COMMENTARY GROUP 14. A diphtheria ward in Knightswood Hospital provided group fourteen. A child showed a measles rash on 14/4/34, and was removed from the ward on that day. Pour presumably susceptible children were exposed to infection: each of three received 15 c.c. of adult immune serum on 14/4/34, the fourth day after exposure, and one who did not receive serum was the control. An immunised child (E.McM.No.108) showed a measles rash on the day after the serum was given. This case must have been in the pre-eruptive stage of measles when the serum was administered, and is not included in the results, since the source of infection differed from that to which the other contacts were exposed. One of the immunised contacts (M.P.No.107) developed an exceedingly attenuated attack. There was no catarrh, no Koplik!s spots, and no pyrexia. The rash appeared on 20/4/34, on the face, trunk and lower limbs, and consisted of slightly raised macules, faint dull red in colour, and widely separated except on the thighs, where they were confluent in small patches. This exceed ingly mild case appeared, however, to be infectious and was probably the source from which the other immunised contact (M.W.No.106) received the Infection. The latter developed a secondary attenuated attack, the rash appearing on 3/5/34. The uninoculated control was the only contact who did not contract measles, and apparently possessed natural immunity. GROUP 14. SUMMARY OP RESULTS. Immunised Presumably Susceptible Contacts, ... ••• 3 Inoculated in Pre-eruptive Stage of Measles, ...... 1 Attenuated Measles, 1 Available Inoculated Contacts, Secondary Attenuated Measles, 1 One Uninoculated Control Escaped Infection. 71 01 «H to ^ 00 ^ to O \ rH \ (ft 1 03 \ ... •- 3 ■■ ( 5/5/34 Appeared 03 03 Rash Date O When u 0) • ■9 © d O P £ • © • ♦ • ^ P ^ ,d • rH to -P tO P d © to o o \ «H *H 1 \ bD \ Classical Secondary Classical Secondary Type Type of Attenuated rH bO \ to d lO •» Attack •H d 03 rH *rl H *d > d d CD o aS CO d GO <$ ft p Eh io 1 •t •s S i i 00 | 1 O o bO i d © d 1 g o in Daysin ation Period (Xi •H d i © d * © 1 a Incub P +5 *H 1 © *d 3: i H o © d I © © 1 a « rH © I o Pi d d I © PQ & O f t 1 p Pi © -H 1 d H c-1> 00 ft ■ <*5 © 1 © Eh rH 03 CO H d » tJ ft»d « •V & P h in Age Age of Donor E h CO 1 © p ft © 1 •d P Years o rH 1 p d < d I © © O < © © 1 p d «H 1 © p CO Eh P d I •H © Xl © 1 •rH o p S «H © I a P © g i d © CO o Pi fc 1 »o © © © i 3 p 98 o 00 I ©•H P CO © Cm © © 5 o o d d © a .d © ,d d p O ft 03 03 o © O © CO in c .c. c £ d rH d © £ ° © © Name P H P w O rH © o & o p p O H PH 112 113 111 114 110 Serial Number 72 COMMENTARY GROUP 15. All children entering Mearnskirk Tuberculosis Hospital are admitted to the isolation block and remain there for three weeks, after which time, if free from infection, they are transferred to the pavilions. In the isolation block six cases of measles had occurred as follows (1) Rash appeared 15/3/34. (2) ” w 28/3/34. (3) " 11 5/4/34. (4) " 11 9/4/34. (5) 11 w 14/4/34. (6) 11 tt 15/4/34. The measles cases had to remain with the contacts in the isolation block, as there was no other suitable accommodation. On 15/4/34 there were five children in the block who had not had measles. Two of these (D.J. and I.Gr.Nos. 110 and 111) had been admitted on 12/4/34, and each received 20 c.c. of adult immune serum on 15/4/34, when they had been exposed to infection for four days. One child (J.L. No.113) had been admitted on 5/4/34, one (D.S. No.112) on 4/4/34, and one (E.S. No.114) on 22/2/34. None of the latter received serum. The uninoculated child (D.S. No.112) who had been admitted on 4/4/34 developed a classical attack, the rash appearing on 22/4/34. The uninoculated child (J.L. No.113) admitted on 5/4/34, had been exposed to infection from four cases of measles showing rashes on 5/4/34, 9/4/34, 14/4/34, and 15/4/34, without contracting the disease. She contracted infection from the case (D.S. No.112) who showed a measles rash 22/4/34, the fifth case 73 with which she had heen in contact, and developed a classical attack, the rash appearing on 2/5/34. This child apparently possessed a considerable degree of natural immunity which was only overcome after repeated exposures to infection. Complete natural immunity to measles appeared to be possessed by an uninoculated child (E.S. No.114) who was admitted on 22/2/34, and was continuously exposed to infection from 15/3/34 to 2/5/34, by nine consecutive cases, and remained free from infection. Her parents were sure that she had never had a previous attack of measles. One of the immunised contacts (admitted on 12/4/34) developed an attenuated attack after a second exposure to infection; the other remained free from measles. 74 T' •' * .• GROUP 15. SUMMARY OP RESULTS. Immunised Presumably Susceptible (No Measles, 1 Contacts, ...... 2 ( (Secondary ( Attenuated ( Measles, 1 Uninoculated Presumably Susceptible (No Measles, 1 Contacts (CONTROLS), ... 3 ( (Classical ( Measles, 2 75 1 1 1 1 A p p e a r e d R a s h D a t e W h e n u o x o © © 1 1 1 1 f t p h P • >i EH < ^ ^ o5 10 tO tO tO to p CO 03 \ • EH i d j© ft O ft £ o © \P < d o d p 1 1 1 1 t> lO lO to lO EH O d £ tD 02 rH rH rH ft £ P © £ O H © P-t d d O P h • © ft 1 d 01 O £ 03 O 1 d d £ ft O £ CO o o ft 1 £ © © PQ © £ © 02 tO 10 ft 1 © £ S* M bO O £ © ft 1 * © d Eh «© P d CO 1 © © a P i O Eh • 1 o ft £ o H ft d O 02 1 p ft © £ O o S P£ <5 CO 1 © COMMENTARY GROUP 16. In a surgical ward in Oakbank Hospital, four children who had not had measles were exposed to infection by a child who showed a measles rash on 15/4/54. Three of the children were each given 20 c.c. of adult Immune serum on 16/4/34, the fifth day after exposure, and one did not receive serum and acted as a control. Neither the immunised contacts nor the uninoculated control contracted the infection, but a child believed to have had a previous attack of measles showed a typical rash on 22/4/34. GROUP 16. SUMMARY OP RESULTS. 3 Immunised Presumably Susceptible Contacts did not contract Measles. One Uninoculated Control Remained free from Infection. ' c 'A i * *A i * *3 t ~A ■ ' -*■ * "• " ' . 78 Rash Date When 29/4/34 29/4/34 28/4/34 29/4/34 26/4/34 27/4/34 Appeared i ^ ^ to to tO to ^ tD Type Type of Attack ■*#» h# iO 0> Modified Attenuated Modified Classical Attenuated • HHHH rH fo Classical 01 0 CO »d oi 'd *d Ph 14 14 14 11 13 o PH 0 0 12 n 3 PH & • «H £ 0 *d Period in in Days Incub Ph CQP i 0 0 6 ation i P to o ft Ph o o c ! •p ft 0 Ph « >rt <5 oi u ■ & 43 0 g 00 o Eh -p 1 'd 0 0 0 K O £5 •H <10(4(4 91 91 91 O ft W) 1 99 o 00 C 1 _ ._ , _ in Serum O *H 1 H O Age of Days to « Ph I 0 1 a rH * <+H H 43 M 43 o 15 15 15 No o 0 d ft No § serum serum c .c. c 0 in 0 •d O o X Dose d 43 0 0 0 43 o w u o d a 0 CM OJ CM 0 0 o 0 d Ph rH rH rH 09 -P I—1 Age i—1 rH rH O o o W 0 Years oJ o •H 0 43 M 43 43 0 o d 0 • • • • • • d 0 Ph 0 fH o 43 W (U c5 p P to o & 0 O 5 o 0 0 • « • « • • O EH Ph PP Name a p a < a w 123 120 122 124 121 119 Number Serial A p r il , 2fc 2.9 3o A.M. P.M. A M P.M. A.M.P.M. A M P.M. A.M. P.M. A.M. P.M. A.M. P.M. TIME TTT IT ^t 107* 105' 104' 103' 101 100' vY OF ILLNESS. 160 150 JRNAL. 140 130 120 110 100 Bowels Urine At t e n u a t e d Me a s l e s A pril 2 9 30 A.M.P.M. P.M. A.M. P.M. A M P.M. A.M. P.M.A.M. P.M. A.M. P.M. TIME 105' 104’ 103' 101 100' OF ILLNESS. 160 150 INAL. 140 130 120 no 100 m Bowefs Urine Mo d if ie d Me a sles A Z b i *E„ ...... r OF ILLNESS...... IE...... 3X RNAL. E...... MoPlFlED M£<\SLE.S. 29 A.M. P.M. A M P.M. A.M. P.M. A M P.M. A.M. A.M. P.M.P.M. A.M. P.M. TIME 107 106' 105' 103' 102' 101 100' OF ILLNESS. 160 150 INAL. 140 130 120 110 100 Bowels Urine At t e h l I ated Me a s l e s April. 2 'i OF ILLNESS. C l a s s ic a l M e a s l e s OF ILLNESS, -NAL. a.. *1 £ rT!TSH! r*:*3rrrtf?fw: Bowels Urine C lassical - M e a s l e s . 79 COMMENTARY GROUP 17, A child showing catarrhal symptoms was admitted to a dermatological ward in Stohhill Hospital on 14/4/34, and on the following day developed a typical measles rash. Owing to the insufficiency of fever hospital accommodation the child was not removed from the ward till 19/4/34. Six children who had not had measles were exposed to infection; four were each given 20 c.c. of Sr ^ adult immune serum on 19/4/34, the sixth day after exposure, and two did not receive serum and acted as controls. All the susceptible contacts contracted measles. The uninoculated controls showed classical attacks. Two of the inoculated contacts had attenuated measles and two had modified attacks. The accompanying temperature charts show that the degree and duration of the pyrexia in the modified cases was not very different from that in the classical cases; the rash was typically morbilliform, but Koplik!s spots were absent and the catarrhal symptoms were slight. The remarkable feature about these modified cases was the entire absence of constitutional symptoms during the illness which somewhat resembled rubella. The clinical differences between the children suffering from modified attacks and those suffering from classical attacks were apparent to all who observed them. 80 GROUP 17. SUMMARY OF RESULTS. (Attenuated Immunised Presumably Susceptible ( Measles, 2 Contacts, ...... 4 ( (Modified ( Measles, 2 CONTROLS * 2 Uninoculated Presumably Susceptible Contacts Contracted Classical Measles. 81 0 p aS 4 / 5 / 3 4 Appeared Rash Q When •d • © © • • • • o M p •H ^ ^ ^ o © Pi to to to to © © 1 1 P 1 1 1 1 0 \\\\ ftp P ,c| ^ ^ ^ ^ h p © P EH d EH l •d r>s 1 •d *d p O fit P o as • Pi 0 © C P O *H P 1 1 CM 1 1 1 1 00 bO © P & EH O *H Pi H rH P gc aJ •d . 12? P P © P *H © © s O M © CM *H Ph 1 • p i o Pi p o O P> 1 GO 0 1 P ft as P P O 1 CM COMMENTARY GROUP 18. The children in this Croup were patients in a diphtheria ward in Ruchill Hospital. A child showed catarrhal symptoms and Koplikfs spots on 20/4/34 and was removed from the ward on that day: the rash appeared on 22/4/34. Seven presumably susceptible children were exposed to the infection and each was given 20 c.c. of adult immune serum on 22/4/34, the fifth day after exposure. One child only contracted measles - an attenuated attack, the rash appearing on 4/5/34. It was not possible to secure permission to leave any of the presumably susceptible contacts uninoculated, to act as controls. 83 GROUP 18. SUMMARY OF RESULTS. (No Measles, 6 Immunised Presumably Susceptible ( Contacts, ...... 7 (Attenuated ( Measles, 1 MEASLES CONTACTS GROUP 19. to ft ft ft P rH •d 5 t f 45 rH p •H P Sfc rH *D rH •H •H p 4a ft o p© p d d © o g o o o o ro O t f rH © © o o © A • P rH P t B ft d © © © © d © h © d O © d © © l>s © H • to lO to <0 O \ M C to CM o rH tO o O rH 03 o ^ | to ^ \ W co to \ J a \ © o © \ © to © © © 00 • • • • • ^ to ft to to to •>— ^ Td'd •d p ■H © rH t H p ft ft € •H s p v rH t f o P ft •H _ d d © ft d ft 1 © © ft © ft © © P © © © m © d d © © © © © > O ft © ^ \ \ © \ \ O ^ • to to CMP H to CM to CM O P O to -- — nd *H nd *d a? t f xj O © rH © ft s ft w t f © © © © © p t f o rH © o • • ■ *d ft •H & < _ «H P o p p < d to © d d © o © d O o d © o © o d _ •rH t O H ft ft ft O P « a « p ft © d © © IP © © p P W d d d o £ d s g © © J p Hi p © u o £ © © d © o © £ o © d d d © ft © o CO 3 B B ft CO CO ft CO o ft ft B H ft o O ft ft 5 B o ft o ft < <4 H a Age of Age of Incub Date Age Dose Serum Serum Donor ation When Serial in in Batch in in Period Type of Rash ft Number © Years c .c. Number Days Years in Days Attack Appeared H H H l r H H H H r l r l r H H H H H H H H r l r H H H H H H l r tOtOtO'^^^^^CMCMCM’!}*^ ^^^O030303CJit0t0t0CMCM CMCMCMCMCMCMCMCMCMCMCMCMCM tOtOtOCMtOtOtOtO^^^OO cococoa>£>c>i>C'-^'^'^oo 03£>LO^tOrHrHtOtOOOOtO CMtO’^lOtOC'COOOrHCMtO^h O O O O O O O O O O O O O O O O O O O O O O O O O O CDtOtOcOlOtOlOlOtOtOCOCOCO o o o S ^ ^ ^ o O o C t f O o * g g « g s P Q g B ^ f t $ : B < 4• H H l r H H r H r H H r H l r H r H H t O t Q t O t O t O t O C O t O ^ ^ , ^ ^ , ^^i, , c ^ , llllCMlrHrHIIIII * * Classical 24/4/34 1-3 • rH h Attenuated 2/5/34 | w 1 —1 rH Modified 1/5/34 Modified 1/5/34 Classical 24/4/34 rH rH ft • # Contacts who Proved to have been in the Pre-eruptive Stage 84 of Measles when Inoculated. 85 COMMENTARY GROUP 19. In Stobhill Hospital there are several blocks for healthy children who for various reasons have become chargeable to the Corporation of Glasgow. A child in one of these blocks had contracted measles, the rash appearing on 11/4/34. Pour children had received infection from this case and showed rashes on 20/4/34, 21/4/34 (two cases), and 23/4/34. On 23/4/34 there were thirteen children in the block who had not had measles. Because of the insufficiency of fever hospital accommodation, the measles cases could not be removed, and had to remain in the block. Owing to this circumstance, all of the thirteen presumably susceptible contacts were each given 20 c.c. of adult immune serum on 23/4/34, the seventh day after the second exposure to infection. Two of the immunised contacts showed a rash on the following days they also had received their infection from the first case (rash 11/4/34) and are not included in the results. Eight of the remaining eleven immunised contacts escaped infection, one showed an attenuated attack and two modified attacks. It is notable that of seventeen uninoculated and presumably susceptible children, exposed to infection from the case showing a rash on 11/4/34, only six contracted the infection from that case, the rashes appearing on 20/4/34, 21/4/34 (two cases), 23/4/34, and 24/4/34 (two cases). The eleven contacts who escaped infection apparently possessed at least partial immunity; each was given 20 c.c. of adult immune serum on 23/4/34, the seventh day after the second exposure, and three received infection from the second generation of cases. 86 GROUP 19. SUMMARY OF RESULTS. Immunised Presumably Susceptible Contacts, ...... 13 Inoculated in Pre-eruptive Stage of Measles, ...... 2 (No Measles, 8 ( (Attenuated Available Immunised Contacts, 11 ( Measles, 1 ( (Modified ( Measles, 2 MEASLES CONTACTS GROUP 20 CM P © © P © P © bO £ © P 6 & p © o o © o P © © O P © 1 | • CM H \ CM h rH w v to ' -P C - C M C M C M (U -P •H ,P *d -d Tj 43 43 -P C C o fP fP % ssP © O p © © o o ro © o © • < o o to to to <4H ft rH 43 H tp ftTJ Kf* d O »d P W A A © © ft • R 2 43 1 •H *d 43 i i © \ CO ^ h «sfT CM *H O to Q O •H 43 43 .P 43 O H £ GO4-> © © © O O £ © © P © I 43 p cd P P P © © 6 o • +3 < fd ,P Q M P o © © 1>a K ft P i>a * © P © © • • Age of Age of Incub Late Age Dose Serum Serum Donor ation When Serial in in Batch in in period Type of Rash Number Name Years c.c. | Number Days Years in Days Attack Appeared ' ^ ^ ^ rH H H rH rH rH rH rH rH rH H H rH OC -C 3OrH O 03 CO CD LO c- M rH rH rH rH rH rH |— | h o c C M C M C M C M C M C M C M jgj O O O O O O O i— 1 i— rH rH 1 rH rH i— 1 O £> CM CM OO O C M rH rH C M r t < ^ ^ C M C M rH rH rH rH rH rH rH rH rH rH rH rH rH o o t o t oo t o t o L O t o ^ ^ ^ ^ t l O o ^ l^ t O o t o t o L O t o l O t o t o t o O S S ft o £ « £ o ft S S O ♦ , Attenuated c CM ! | h n 3 <• »-3 1-3• pci t-3 • •••••• Attenuated C ^ C O C O C O I T - 03 03 03 03 03 03 03 03 03 CO CO CO CO CO « M Attenuated H H r o l • • < '^ o Modified H CM o H|0WjW '' l CM CM Classical rH rH rH O O CM CM rH rH rH O k j o • • LO Attenuated ' I> o l Attenuated 87 88 COMMENTARY GROUP 20. In a scarlet fever ward in Ruchill Hospital, a child was observed to have catarrhal symptoms and Koplik!s spots on 21/4/34, and was immediately removed; a typical rash appeared next day. Seven children who had not had measles were exposed to the infection, and each was given 20 c.c. of adult immune serum on 24/4/34, the sixth day after exposure. All of the susceptible contacts contracted measles; five of the cases were attenuated, one was modified, and one only was classical. Permission was not obtained to leave any of the presumably susceptible contacts uninoculated, to act as controls. 89 GROUP 20. SUMMARY OF RESULTS. Attenuated Measles, 5 Immunised Presumably Susceptible Modified Contacts, ...... 7 Measles, 1 Classical Measles, 1 90 1 p Rash 0 Bate When 12/5/34 o 13/5/34 6/5/34 12/5/34 Appeared d Eh * 0 • u d >> o o 0 •H P 1 0 ft • • • • Type of 0 O • P A t t a c k O © • ^ ^ ft Classical 525 ft CO to to CO P Attenuated Attenuated Attenuated ft to ' v W CO '*v«5jr d 0 t O \ \ \ \ d O ft \ C O CO CO 0 < CD 05 1 LO lO 1 1 02 02 02 02 02 0 Eh iH rH rH iH 1 •H 52? 02 O in Daysin ation Period tiO d O Incub ft d d d d i § 0 • *H d 0 0 1 B O <$ d 0 d fe 1 H a O ^ ^ O ft t> 0 £ 0 d i CQ 02 CO 02 CO CO 02 O ft © 0 B « 0 H in d ft o ft d O I d Eh Years Age Age of ft Donor CO h ^ p ft 0 d 1 0 Eh 0 co <5 © ft I £ W O St d ft I d o < 0 © P f t d i 0 0 CO CO LO CO LO LO CO Eh rH d p £j O •H 0 P O i 0 0 Days Serum o S* g P 0 B » P P ft Age of ft 0 rH 0 0 0 1 g d o CO 0 -p <35 O ft ft I jE; o o o 1 H o CO ^ to O CO CO O CONTROL s ft 0 v— H rl r) rl rl rl co ft 1 0 d s rl rl rl rl rl rl <3 i—l d d i d © 5 Serum Number rH o o 0 P p Batch •H o •H £ £ o p P H p p 0 O 0 0 Eh o o o o o o o o P 0 P d in 02 02 02 02 02 02 No serum c.c. ft •H P m 0 ft O p § Dose to 0 P d 0 0 ft § ft rH P H P o 02 02 ryj a O 0 d ft H|02 02 HjCH rH rH o> o s 0 d o o w rH rH 02ssvsvs>«. in d o 0 © © P o w Age ft d d s 0 Years ft 0 O 0 d d • 0 rH ft f t P © 0 -P 0 0 o K o P P • • • • • § Contacts in this Group were Immunised with Serum from O 0 O 0 0 £ ft PQ O P P f t O Adults who had not had Measles. 0 0 •H 0 p 0 * • • • • 0 F.R. Name S pq ft B • P ft d P 0 o d 0 *”0 C rH d 0 P ° p Eh O rH 0 o o 0 0 O M ft p P 02 co ^ to to c- lO LO LO LO LO LO r~\ i—i t—i r-i r-{ r-A 158 Number Serial LTE, IY OF ILLNESS, lME. iE .... IRD URNAL GE Bowels Urlnt At t e n u a t e d M e a s l e s l a ^ S O B A.M. 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 i i i AY OF ILLNESS m JURNAL tie s n IP 3K0? n i n n m-wmi 5i!nr?ir*Ti - 9 tt x s i S i c l a s s i c a l . Measles. !lY OF ILLNESS., \ME„,...... ATTENUATE!? MEASLES ' OF ILLNESS. At t e n u a t e d M easles 91 COMMENTARY GROUP 21. The Ear, Nose and Throat Department in Stobhill Hospital furnished this group of seven presumably susceptible contacts, who were exposed to infection by a case of measles showing a typical rash on 27/4/34. On 28/4/34, the fifth day after exposure, six of the contacts each received 20 c.c. of serum from adults who had not had measles, and one did not receive serum and acted as a control. Two of the immunised contacts escaped infection, three showed attenuated attacks and one had a classical attack: the uninoculated control did not contract measles. GROUP 21. SUMMARY OP RESULTS. Presumably Susceptible Contacts (No Measles, Immunised with Serum from Adults (Attenuated Who had not had Measles, 6 ( Measles, (Classical ( Measles, One Uninoculated Control Escaped Infection. 93 *d © © P .P P to P © 01 © \ © xj © © to P ^ « ft \ ft to < © •d •H ft i— ! © © o ^sj © .P © •« o O • ^ ^ <^}4 • © © ft p to to to to g f t p 03 o • m \ft h p 03 P «H p p p fc- Eh 5 o 02 od f *d p S3 d P O © 02 Q TJ *d O P O ft f t O £ — bQ P © § O O ft p rH p © p ft P cd p p P> o P rH © © O H © O p o 53 © O H ft « P rH P £ © © 0> ft £ lO ^ 1 H © P t O M 94 COMMENTARY GROUP 22. The day-room of the Ear, Nose and Throat Department in Stobhill Hospital was occupied hy several children one of whom showed a typical measles rash on 25/4/34, One child only, had not had measles and was given 20 c.c. of serum from an adult who had not had measles, on 28/4/34, the seventh day after exposure. She nevertheless developed a classical attack, the rash appearing on 5/5/34. 95 GROUP 22. SUMMARY OP RESULTS. One contact Immunised with Serum from an Adult who had not had Measles developed a Classical Attack. -S • -SI -fc S C:- 4 X X 4 S'; M: £ ■V»y j "S S -W .V 3 ■■ g> 4 S >'.'7 4 ? ' ' &> ■&> .'3 . 3.4 S" 4 ' w ,: X...- S S- X i. 3 S S X ip'-; & 4> S *3 43 vS 4 'S' .1 1 - t . * ,4 - 4 ** S 3 :. jS O S X S ;t 3-? ,4 -J V --‘ *■ - £'■ ?“4 . - fis 96 to 60 ID 1 F 1 Rash Date When \ 0^ d Appeared S H © > © © ft P 43 • • • • -a © 60 ^ ^ ^ ^ d Type Type of rH \tO 60 to to to Attack d ^ \NN. \ Modified © \ © U M O to Attenuated o 00 W H N H rH © c0 • © Eh 43 I O 00 •d *© 16 60 P © © © S O 'd ft 0 ft d 0 © ft d ft 43 ft © d d a 00 00 00 CM o © 3 < © <4-4 © ft in CM CM CM ^ fgr m 'd ft £ H Years Donor CO © A ft'd ft Eh Age of © & h H © 43 d < © © ft 43 > TO 43 O © d d pa 03 03 tO •H 0 •H O o Oi < 43 g Days O 00 00 «© 0 ft ft d £ Serum g Age of o O 43 0 H 0 W o __ ft 00 ai _„ o © 00 CO CO 03 i> rd © O © © ft 43 d o iH O £ © OOOO © *H 43 00 0 3 H in CM CM CM CM CQ ,d © SS © ro EH c .c. c £ ft H 43 H 43 0 ft Dose S o © d ft o 6 © »d o 0 « ft tOH|0W|W£> 43 0 ft d o n © © CM CM d d S © ft in ft © o © d d Age H <4-1 f t 43 © © Years © 43 43 © 3 O X o •£3 • • o © o w © £ •H © 43 O P © © © O - O Eh -p d 43 © o d S O • • d H © •d o -p l>9 . . p H O H a O gB O © © Name O H ft p P CO CO O 1—1 CM tO to to to to rH rH rH rH Number Serial COMMENTARY GROUP 23. On 1/5/34, a child in a scarlet fever ward in Belvidere Hospital, showed catarrhal symptoms and Koplik!s spots, and was at once removed; a typical rash appeared on the following day. Pour children in the ward had not had measles and each was given 20 c.c. of adult immune serum on 1/5/34, the third day after exposure. Two of the immunised contacts escaped infection, one had an attenuated attack, and one, who had returned home on 5/5/34, had a modified attack and was not ill, although the rash was bright. Ten days later two brothers of this child who had been in close contact with him, contracted very sharp attacks of measles. The contact who developed measles at home, had not the temperature taken regularly, and therefore, a chart is not available. GROUP 23. SUMMARY OF RESULTS. (No Measles, 2 ( Immunised Presumably Susceptible (Attenuated Contacts, ... ••• ^ ( Measles, 1 (Modified ( Measles, 1 ; 5": ,A Aj A A -i % £'/■ V ‘--Z- Ai •A & ' ■& A A? ■ A,, ;A< © -A A ’.AS VA A A " '&■ 'h '''i ,S.7 ■r.v ’ V AS 7> - - ' ! ,<* A- O ££ *.■> MEASLES CONTACTS GROUP 24 rH « •d 1 to CO •H ,C{ 1 43 l te © •H © 1 •H© 1 rH © rl rl1 ft O CO © ft ft» 43P ft ft P 3pP KK O P 43 43p E O •» P fto © rHI O t>s« 1 O 03 © P i P © 43P O 43© O © o o s O © O p o p © p 1 • t rd h 431 03 £ © H1 h 1 1 1 1 1 X X rH to H 1 rH to ■ ' i -■— rH d *d•d H •H © fto 3 4 3 4 © ^ d © © © © «d 3 p >1•HO 1 > 43p ft •d ;o<;ft o ft » ft rH 43 H rH ft ft 43 43 Si n 3 J | t © ft H © 43 •H© ft 43 © ©i © © p © f o1 fto O P gs i P © O © a a p GO43© © O © © O P © P O P © P n o © © • ft p<*jp » © ft to to W o> o *d ftT} ftT} as 01 0 • p © i p © p to 'd ft *H 1 43 i P 1 O P t 0 • i O M i i 1 » « i _ \ © \ jS t ft P H © P 1 © £ 0 3 01 P © 0 K pr> • J m o ft 8 p; ft CO o w < s o ft ft ft ft 3 o ft ft E M o ft ft CO H o h t f ft <4 <4 CO < © P ft O©*H P hO © © 6 tn P © g o £ © bO O P o P H P •H +3 © coca's p ft Eh 'd ft 43 00 © © O Pa 43 © M < •H P go P N O o P © W O t O t H r H r W W W 0>050lI>I>r-lrH01 H H H H H H H r H O O C O O H H i O O l O O t W W O O H H H C- tO CO cf (J) ^ 05 rl rl ^ rl COCOCOCOCOCDC'-O■^lOCOOCOOlOrH - WCMCMWCMCMCMCM H r ^ ^ W W tototo^^tototo O l O l O O O O O O O O O g g jz; O s • • •o • s ' • *H 1 II lO \ lO I LO lO I I . b ^ b b S • . OC ^H ^ CO CO \ rH rH f i H 01 H iH rHTf* O o X \ X N to toto \ \ to toto ^ m O © 01 © 01 I C-O I LO w * • * «H *H 1 •H *H 1 ...... ______rH rH 0 rHO I —I rH rH rH W I—I rH HHrH H rH 01 © O »d O © O 01 'd © a ft rH W *H i5 * ^ ^ ^ * -i5* r H|G2W W H|G2W lO 1 O sgrgr —1 01 101 01 © © © 1—I O 01 © * Contact who Proved to have been in the Pre~eruptive Stage of Measles when Inoculated. 99 100 COMMENTARY GROUP 24. In Stobhill Hospital, another block containing healthy children, suffered an outbreak of measles. A child showed a typical rash on 29/4/34, and was removed from the block on the following day. Eight children who had not had measles were exposed to infection, and each received 20 c.c. of adult immune serum on 2/5/34, the seventh day after exposure. Permission to leave any of the presumably susceptible contacts uninoculated, to act as controls, was not granted. One child showed a rash two days after receiving the serum; he had been therefore in the pre- eruptive stage of measles when inoculated, and it is likely that he had received infection from a source other than the case who showed a rash on 29/4/34. This contact is not comparable with the others, and has therefore been excluded from the results. Three of the immunised contacts remained free from infection, one had a modified attack and three had classical attacks. GROUP 24. SUMMARY OP RESULTS. Immunised Presumably Susceptible Contacts , . • • ... 8 Inoculated in Pre-eruptive Stage of Measles, ...... (No Measles, (Modified Available Inoculated Contacts, 7( Measles, ( (Classical ( Measles, MEASLES CONTACTS GROUP 25 •rl iH ps rH *d rH rH w XJ o JS 0> a p X PM ffl W P P O EH P o i P P”>i-H OS o 0 OS i P B o d d -p 0 o GO aS 3 P 03 B O aS o XJ d aS O • * co rH •H o *CJ P rH o O 0 0 GO 2 P< b0 0 0 d 0 O 0 GO d 0 0 d > 0 0 d 0 o £ 0 O o d 0 0 • to o t W \\LO\n" • • ^ tO ^ 60 i—! l r W l r D Oi\\ \ i Xl TS ° H P s s o P w aS pd o p 0 d Pi 0 © 0 0 03 P O P.-P 03 O K O o d d o •H U >0 +3 d 0 0 d > o 0 0) O O B o B d o p § CO CO P co CO PM PS E H p o W O E 172 B.C. 4 20 87 299 38 12 Classical 13/5/34 173 M.S. 2 20 88 296 39 174 D.M. 6 20 87 299 38 175 J.McM. 8 20 84 312 36 102 103 COMMENTARY GROUP 25. East Park Home admits children convalescing after serious illness or operation. One of the children in this home showed a measles rash on 1/5/34. Four children who had not had measles were exposed to infection and each was given 20 c.c. of adult immune serum on 3/5/34, the sixth day after exposure. One child only contracted the infection, and showed a classical attack, the rash appearing on 13/5/34. GROUP 25. SUMMARY OF RESULTS. (No Measles, Immunised Presumably Susceptible ( Contacts, ...... 4 (Classical (Measles, MEASLES CONTACTS GROUP 26 to to rH*d 'd P 43 P rH © © P rH iH ,d w P 3 W .3 -P to 'tJ1to rH tO tO ^ d P< *d d © ft p _ P © ,dP O *d© © © © <3p d p <4 d © < d o o ®£° ® d £ o © LO tO to to to to p t f i P Cit'd W *d P •rH s o d lO •d • O M O p O W O ,d ^ p P P p d h © © © p © o S i £ © d © Cl d © © © © * w Pi d © © Ci d O © © © © © o rri to H si p Ci ► © © X to O EH o E tO W fd « a o sz; O E H <3 o « to W g t=> o EH H a (X, PC <»3 h h P © w © © w P Q o * o d IQ H © i WWWtOtOtOOODCOO tOtOtOlOlOlOtOtOtO^ WCMWtOtOtOHi^^tO ^H^}i^JHtOtOtDrHOOOOCs" D t 0 t D t 0 t 3 0 > 0 > rH 0 H rH r H rH r H ^ } i ^ i ^ ‘ 0 3 C M < M , t t 4 0 3 0HrHHCMCMCVltOtOtO^ > C M W W W W W W N H r W W O O O O O O O O l O O • ^ i C v l t O C v l c O t O ^ c ^ t O t O C - C - I > J > O O C O C O O O C O O O tOC-GOOiOrHCtftO^lO C .^H^HOPfti t f P O H ^ H ^ . PCs COW I fc- 03 I O I03 t> • • • •S • * * • • rij 'v. l - \ rH rH rH •H to lO O to © O © © © 1-3 1 \ W \ \ \ rH rH rH rH H H P O O O P rH to i—1to to to LO LO to to to to rH o o o o o © © © © © © © © © ______••••••• t ^ ^ ^ H P to © © 1 © 1 V. \ P rH rH rH O LO O © © © — I I I I C OC O0 0C O to t- 00 03 t- to £scogr ^ C O C O C O C O O O O O H P ^ ffl ^ P H O O O O P P P P E p d p d P d p d to to o>toto W|Z! W 25 O O O O SB125 w Szs © © © © © Cl Ci Ci Cl O O O O I I I I I I I I lilt • • • • h E h E h E 00 105 h Jf P a X o +3 p *d p P CO iH P p •d p rd 'd d o d © > d © O S O b © © £ © © H d d © © © £ © Cl d d o o o a d © »d si © © © © © © • 106 COMMENTARY GROUP 26. An outbreak of measles occurred In still another of the blocks in Stobhill Hospital, occupied by healthy children. A child was observed to have catarrhal symptoms on 3/5/34, and was removed on the following day; the ra3h appeared on 6/5/34. Fourteen children who had not had measles were exposed to infection. On 8/5/34, the sixth day after exposure, four of the presumably susceptible contacts were each given 20 c.c. of adult immune serum, six were given 20 c.c. of serum from adults who had not had measles, and four did not receive serum and acted as controls. Three of the four contacts who were given adult immune serum, escaped infection, and one had a classical attack. Two only, of the six contacts who were given serum from adults who had not had measles, escaped infection, and four had classical attacks. All the uninoculated controls escaped infection. 107 GROUP 26. SUMMARY OP RESULTS. P r e s u m a b l y Susceptible Contacts (No Measles, 3 Immunised with Adult Serum, 4 ( (Classical ( Measles, 1 Presumably Susceptible Contacts (No Measles, 2 Immunised with Serum from Adults 6 ( who had not had Measles, (Classical ( Measles, 4 CONTROLS - 4 Uninoculated Presumably Susceptible Contacts did not Contract Measles. 108 sj* -st* to t o \ \ t O 1 1 1 Rash Date When 26/5/34 3/6/34 10 CM Appeared > to 21 © p H tO © EH CM H f t P © rH •H O Pi f t O <} in Daysin Period ation £- 0 tt) Pi •H p EH Incub CM H P © P f t o ft O •H P o h LO ft o C- C- LO f t P< © EH f t H ft tO rH H tO tO u © O ft © P in O © © © p © ft ft p © Pi a Years PJ © H H © © ft Age of Donor H CO ft © H ft «= H g P f t Eh ft CO © ft m O rH i—1 O O -P p CONTROL CONTROL o < h o ft CONTROL ft O o £> to ft j> j> CO o © o p © Pi Pi Pi © to Number 3 Serum Batch ► £ O © ft ft 1 to ra o < <5 p o •rl ► * ft ft . P © © ft § 1 1 tiOft © O o U Pi U •H O £ © P Pi © © © £ -H O P H © © Eh o o o o o to CO CO in CM CM CM CM CM t n H P H P o ft who had not had Measles. c.c. o o o < Dose g O © PS ft ft ft ft © f t o o K f t 8 S 31 /oT Pi o © © © p o ft Pi S © 6 <4H Pi Hi© H|OJ 9 ft © o ra P Pi si* ^ ft rH © in P © 2 o K o ft «P Age o © O ft © ► *3 Years © © *H © p © • P m o pi © . p Pi p N • • • o * PSH © f t o © © gs o O o ft O H 9 o o I • • « S • Contacts in this Group were Immunised with Serum from Adults E.B. O H ft ft ft ft CQ H H • ft E.G. ft W.McI. © O rH CM CO lO to t- o>o>roo3® One of the nurses in a scarlet fever ward in Knightswood Hospital, although suffering from catarrhal symptoms, remained on duty in the ward till she developed a typical measles rash. Eight children who had not had measles were exposed to infection. Five of these presumably susceptible contacts were each given 20 c.c. of serum from city-bred adults who had not had measles, and three did not receive serum and acted as controls. Three of the contacts who had been given serum escaped infection, and two had classical attacks. One of the three uninoculated controls did not contract measles, one had a mild attack, and one, a classical attack. 110 GROUP 27. SUMMARY OF RESULTS. Pre3umably Susceptible Contacts (No Measles, 3 Immunised with Serum from Adults 5 ( Who had not had measles, (Classical ( Measles, 2 (No Measles, 1 ( Uninoculated Presumably Susceptible (Mild Contacts (CONTROLS), ... 3 ( Measles, 1 (Classical ( Measles, 1 GROUP 27. SUMMARY OP RESULTS. Presumably Susceptible Contacts (No Measles Immunised with Serum from Adults 5 ( Who had not had measles, (Classical ( Measles, (No Measles ( Uninoculated Presumably Susceptible (Mild Contacts (CONTROLS), ... 3 ( Measles, (Classical ( Measles, Ill • • • ^ s» ^ to to to to © 0 Ph P to to to \ p © ra © LO 1 L O LO LO • CO lO C0 I \ z> to to I > P O 00 CM H CM 03 CM u •d © »d ft rH rH © > o >} © © p © & o O O © © © •H *H ft £ ftp © © a • -P © I» p © © © {>» © i Eh < © © p COMMENTARY GROUP 28. A scarlet fever ward in Bridge Street Hospital, Paisley, was cross-infected by a case of measles showing the rash on 25/5/34. On that day, the case was removed to a cubicle which had been constructed by partitioning-off a corner of the ward by boarding not reaching to the roof. The so-called (!) cubicle had no door, and the doorway communicated with the ward, so that, in effect, the case was barrier-nursed in the ward. Five children who had not had measles were exposed to infection; four were given each 20 c.c. of adult immune serum on 27/5/34, the sixth day after exposure, and one did not receive serum and acted as a control. One of the contacts showed a rash on the day after inoculation, and had been therefore in the pre emptive stage of measles when the serum was given. This case is not comparable with the other contacts, and has been excluded from the results. One of the immunised contacts escaped infection, one had an attenuated attack and one showed classical measles. The uninoculated control developed mild measles. 113 GROUP 28. ^ SUMMARY OP RESULTS. Immunised Presumably Susceptible Contacts, ...... 4 Inoculated in Pre-eruptive Stage of Measles, ...... 1 (No Measles, 1 (Attenuated Available Immunised Contacts, 3 ( Measles, 1 ( (Classical ( Measles, 1 One Uninoculated Control Developed Mild Measles. 114 • d © d 'O i i i i 1 1 rH Rash Date «ri When .d o Appeared © 4*3 © A o P •H o to •Jl iiii 1 1 £ • ^ ^ ^ p Ph to to to to lO Attack Type Type of ro O \ P ft to LO to lO rH LO\W \* d rH \ < o o o H © d © • LO 03 to to to ro •d P ro •H i i i i 1 1 Incub I 03 ro © *d •d Ph o o © a ft Ph « © M \=> i—I O i—i © © © 0 © CO CO o o in lO 03 03 © o o ft d o Ph to OS © Ph O *H -p ft © Ph © Ye ars Ye Donor £ Age of o »d Years a ro P rH (p ftp © © P P p d d o K o ro o o o W © . P © o • r l © "P ** o p ro o d © © p P ©.do J.I. R.H. H.M. p A.C d © © © Name a o £ o C.McL. o £ W.McA. d o EH Ph P P o o to ^ m co OOOO 207 03 03 03 03 208 -* * Number Serial 115 COMMENTARY GROUP 29. The Country Branch of the Royal Hospital for Sick Children at Drumchapel accommodates patients from the hospital whose convalescence is protracted. A child here showed a measles rash on 30/5/34, and was removed on that day. Six children who had not had measles were exposed to infection. On 31/5/34, the fifth day after exposure, two of the presumably susceptible contacts were immunised each with 20 c.c. of adult immune serum, two were each given 20 c.c. of serum from city-bred adults who had not had measles, and two did not receive serum and acted as controls. None of these presumably susceptible contacts contracted measles. GROUP 29. SUMMARY OP RESULTS. 2 Presumably Susceptible Contacts Immunised with Adult Serum did not Contract Measles. 2 Presumably Susceptible Contacts immunised with Serum from Adults who had not had Measles escaped Infection. CONTROLS - 2 Uninoculated Presumably Susceptible Contacts did not Contract Measles. MEASLES CONTACTS GROUP 30 to ^ to to W to I (U to © © +3 © © to cd £O O o ft; o to to to o to to H O © m 1 1 Age of Age of Incu b Date Age Dose! Serum Serum Donor ation W h e n Serial in in Batch | in in Period Type of R a s h Number Name Years c.c. Number; Days Years in Days| Attack Appeared 02 03 W020JOlCV2CVlCMWCvJWW CV o o o o o o o o o o o o o WW0JCVJ03WCV3WCVJCViOJO2(M l O i O l O l O l O l O l O l O l O l O l O i O l O CV]CVJCv2W (Continued) 118 •a © P P p Tt» © d P d « to tO t o m t o P © to © i i i l I i © © 1 \ 1 \ 1 » i © • \ i i i i i © p © © K « CD CD (d CD Q ^ id f t \ \ \ f t o o 02 02 o t o <5 S3 S3 H P S3 p d © u P P O M © © © © © p o > > O O > © © © i i i i i I P P I 1 P 1 P 1 1 1 P i d I I I I I I I I f t p P P 03 © P d d d © © d © e h <4 O O © © O p P P P P P p cd P4 R R R P-4 hO © 0 P 0 0 <4 tO o O 0 0 to 0 &H d o O P © ,—ltObOCGtOtO',cf,,tf,''::f © d 00 O O P o © © CDOiOOOO^l>Pl>t>CD^^t>c0cDCO£>0iI>0iGOtD bO d © <4 P >h o W • • © o - 5d ^ ^ O • • • «o S s p CD C"C0 03 H d © © 03 0302 02 P P d © P 119 COMMENTARY GROUP 30. Nazareth House Is a residential institution for homeless girls under thirteen years of age. One of the girls had catarrhal symptoms on 30/5/34, but was not removed from the home till 1/6/34, when a typical measles rash was observed. Forty-one contacts who slept in the same dormitory had not had measles and were exposed to infection. Thirty-six of these were each given 20 c.c. of adult immune serum on 3/6/34, the sixth day after exposure, and five only, did not receive serum and acted as controls. On 13/6/34, twelve days after the appearance of the rash in the first case, four of the Immunised contacts were observed to have watery eyes; they com plained of headache and their temperatures were found to be elevated, ranging from 99.4° to 101°. None showed a rash, or Koplik!s spots, or injection of the buccal mucosa, and except for eye suffusion, there were no catarrhal symptoms; the illness was over within twenty-four hours. Since these immunised susceptible contacts developed, after a normal incubation period, mild illnesses of which eye suffusion was a symptom, it is likely that they suffered from abortive forms of measles, and as such their illnesses have been regarded. Twenty-nine of the immunised contacts remained free from infection, one had an attenuated attack, and two showed classical attacks. None of the five'uninoculated controls contracted measles. 120 GROUP 30. SUMMARY OP RESULTS. No Measles, 29 Abortive Measles, 4 Immunised Presumably Susceptible Contacts, ...... 36 Attenuated Measles, 1 Classical Measles, 2 CONTROLS - 5 Uninoculated Presumably Susceptible Contacts did not Contract Measles. 121 i i i i R a s h W h e n TSafe " ‘ TSafe " > > A p p e a r e d © P to • • ^ & •d H 1 to P i i i i ft to © I CO to to > Type of A t t a c k 'o-'d PJ > rH © © 0 1 ft P d i i i i i—4 d d •H ft © a t i o n P e r i o d © I n c u b to in D a y1 s O ^ © d H ft. © © g P M O f t t ) o © CD 00 CO 00 o P f t 0} ^ ft o in LO rH rl H « •H d © ft © ,d o N ame © o £ o © © ^ S S S M- O° EH£ ft. p P o rH CM CO L0 lO lO LO CM CM CM CM Number Serial 122 COMMENTARY GROUP 31. A medical ward in the Royal Hospital for Sick Ghlldren, provided the last group of measles contacts. A patient in the ward showed a measles rash on 17/6/34, and was removed on that day. Pour children who had not had measles were exposed to infection, and on 17/6/34, the fourth day after exposure, each was given 20 c.c. of adult immune serum. Permission to leave any of these presumably susceptible contacts uninoculated, to act as controls, was not granted. None of the contacts developed measles. GROUP 31. SUMMARY OP RESULTS. Immunised Presumably Susceptible Contacts did not Contract Measles. AGGREGATE OF THE RESULTS OBTAINED IN THE DIFFERENT GROUPS OF MEASLES CONTACTS. 125 SUM OP RESULTS IN THE SERIES OF MEASLES CONTACTS INOCULATED WITH ADULT IMMUNE SERUM. *0 Type of u 0 Measles Attack © © co p Croup Institution where P 0 i 0 •d No. Contacts Presented O rH «H •H o 0$ 00 cd pj P #0 •d o Ft 0 0 •H co p* ft O PP •d cd X O P a! o A Q W O H 525 1 Kilmarnock Fever Hospital 6th. 15 12 2 Scotstoun House Home 3rd. 7 3 Southern General Hospital 6th. 11 10 4 Blawarthill Fever Hospital 5th. 3 5 Moffat St.Reception House 6 th. 2 2 6 Victoria Infirmary Ward 12 6th. 2 2 7 Knightswood Hospital Ward 7 6th. 3 3 8 Shieldhall Hospital Ward 5 3rd. 4 3 9 Shieldhall Hospital Ward 4 6th. 2 1 10 Knightswood Hospital Wd.I.(M„ 4 th. 2 1 1 11 Stohhill Hospital Ward 42B 3rd. 9 6 2 1 12 Stobhill H o s p . Wd.42B(Isolation; 5th. 2 13 Scotstoun House Home 3rd. 6 1 2 14 Knightswood Hospital Wd.I.(E$ 4 th. 2 1 15 Mearnskirk Hospital (Isol.) 4 th. 2 1 3 16 Oakbank Hospital Ward 2 5 th. 3 4 2 17 Stobhill Hospital Ward 3B 6th. 7 6 1 18 Ruchill Hospital Ward 28 5 th. Stobhill Hospital Ward 37 7 th. 11 8 1 19 5 20 Ruchill Hospital Ward 21 6th. 7 3rd. 4 2 1 23 Belvidere Hospital Wd.3.W. 7th. 7 3 24 Stobhill Hospital Ward 36 6 th. 4 3 25 East Park Home Stobhill Hospital Ward 35 6 th. 4 3 26 6th. 3 1 28 Paisley Fever Hospital R.H.S.C.- Country Branch 5 th. 2 2 29 36 29 Nazareth House 6 th. 30 4 th. 4 4 31 Royal Hosp.foi* Sick Children 110 25 11 18 Total 168 126 SUM OP RESULTS IN THE SERIES OF MEASLES CONTACTS INOCULATED WITH SERUM FROM ADULTS WHO HAD NOT HAD MEASLES. Type of 00 Measles Attack H Group Institution where 00 © No. Contacts Presented > a> •ri S -P P o O ated Inoculated Attenu Contacts Exposure Day Day after a Classical •fll Modified 21 Stobhill Hospital Ward 7A 5 th. 6 2 3 - 1 22 Stobhill Hospital Wd.7A 7 th. 1 - - -- 1 (Day-Room) 26 Stobhill Hospital Ward 35 6th. 6 2 - - - 4 27 Knightswood Hospital Wd.10 5th. 5 3 - - - 2 29 R.H.S.C.Country Branch 5 th. 2 2 -- - - Total 20 9 m 3 - 8 127 SUM OP RESULTS IN THE SERIES OF MEASLES CONTACTS WHO DID NOT RECEIVE SERUM (Controls). Type of Measles,. Croup Institution where No. Contacts Presented cal Mild Mild Very Classi No No Measles | No. No. of | Controls i 1 Kilmarnock Fever Hospital 3 3 .. 2 Scotstoun House Home 6 - -- 6 3 Southern General Hospital 5 4 1 - - 4 Blawarthill Fever Hospital 2 1 - • 1 5 Moffat St.Reception House 1 1 -- - 6 Victoria Infirmary Ward 12 2 2 --- 7 Knightswood Hospital Ward 7 2 2 -- - 8 Shieldhall Hospital Ward 5 1 1 --- 9 Shieldhall Hospital Ward 4 1 - -- 1 10 Knightswood Hospital Wd.I.(Mj 1 - - - 1 11 Stobhill Hospital Ward 42B 4 1 - - 3 13 Scotstoun House Home 4 3 - — Mi 1 14 Knightswood Hospital Wd.I.(F.) 1 1 - - - 15 Mearnskirk Hospital (Isol.) 3 1 - - 2 16 Oakbank Hospital Ward 2 1 1 -- 17 Stobhill Hospital Ward 3B 2 - - • 2 21 Stobhill Hospital Ward 7A 1 1 - -- 26 Stobhill Hospital Ward 35 4 4 - - - 27 Knightswood Hospital Ward 10 3 1 mm 1 1 28 Paisley Fever Hospital 1 1 ** 29 R.H.S.C.Country Branch 2 2 " — 30 Nazareth House 5 5 ** Total 55 34 1 2 L8 128 TOTAL NUMBER OP CONTACTS OBSERVED. Contacts Immunised with Adult Immune Serum, 168 Contacts Immunised with Serum from Adults who had not had Measles, ... 20 Controls (No Serum), ...... 55 243 Contacts Subsequently Pound to Have been in Pre-eruptive Stage of Measles when Inoculated and Excluded from Results, 10 Total Contacts, 253 129 ANALYSIS OP DATA. One hundred and sixty-eight presumably susceptible contacts received an injection of adult immune serum. Of these 110 ($5.5 per cent.) did not contract measles, 4 had abortive attacks, 25 showed very mild or attenuated attacks, 11 had mild or modified attacks and 18, classical attacks. Twenty presumably susceptible contacts received an injection of serum from city-bred adults who had not had measles. Of these 9 (45 per cent.) escaped infection, 3 showed very mild or attenuated attacks, and 8 had classical measles. As controls, 55 presumably susceptible contacts did not receive serum. Thirty-four (61.8 per cent.) did not take measles. One showed very mild measles; two had mild measles and 18, classical measles. 130 TABLE I. - GENERAL RESULTS. of 01 Type o +1 Attac £ 0 No > Total Type of Serum Measles •H Mild ■P U Cases cal Gontac Mild o Very Number p Classi ! ! Mild Adult Immune Serum 168 110 (65.5$) 4 25 11 18 40 (23.8$) Serum from Adults 1 who had not had Measles 20 9 (45.0$) mm 3 8 3 (15.0$) Controls (No Serum) 55 34 (61.8$) - 1 2 18 3 (5.4$) The proportion of naturally immune children may seem high, but the controls in each group were subject to the same conditions of infection as the immunised children - a most important condition, since it was clearly evident through out the investigation, that infectivity depended largely on propinquity, being greater where the children were in close contact, as in the convalescent homes, and less where contact was not so intimate, as in the hospital wards. It is not sufficient to compare groups of contacts where all have been immunised, with different groups where all have been left uninoculated, because infectivity varies, and is dependent mainly on propinquity, but also on the severity of the attack in the infecting case, and on the duration ofcontact. From the above figures (Table I.) it is apparent that adult immune serum is practically useless in the prevention of measles. TABLE II. - PROPORTION OP MILD ATTACKS IN IMMUNISED AND NON-IMMUNISED CASES. Type of Measles Attack Total S9ISB9W £ o m S9SBQ Mild Type of Serum Very Cases Abortive Mild Mild Classical Per Per [Per Per Per SB5 J5 jz; o o o • 9 No. Cent. No. Cent. • Cent. Cent. Cent. Oi to Adult Immune Serum 58 25 43.1 11 19.0 18 31.0 40 69.0 Serum from Adults 1 1 who had not had 11 i i 3 27.3 8 72.7 3 27.3 Measles Controls (No Serum) 21 1 4.8 2 9.5 18 85.7 3 14.3 132 The attack was mild in 69 per cent, of the measles cases who had been immunised with adult immune serum, in 27.3 per cent, of the measles cases who had been given serum from city-bred adults who had not had measles, and in 14.3 per cent, only of the measles cases who had not received serum. The attenuative value of adult immune serum is therefore considerable, whilst that of serum from adults who have not passed through an attack of measles is small. Effect of Interval Between Exposure to Infection and Immunisation. The results of injection of adult immune serum on various days after exposure to infection are set forth in Table III. TABLE III. - EFFECT OF INTERVAL BETWEEN EXPOSURE AND IMMUNISATION. r Pype of JIttack dumber of Days Percentage after Exposure of Measles when Serum No Measles Cases which was Given. Cases were Mild. ated Total Total Mild Attenu Contacts Number Number of Total Total Measles Classical Modified Abortive 3 30 16 (53.0$) 7 4 3 14 11 79.0 4 10 6 (60.0$) - 4 -- 4 4 100.0 5 17 11 (64.7$) - 2 - 4 6 2 33.3 6 93 66 (71.0$) 4 11 5 7 27 20 74.0 7 18 11 (61.1$) - 1 2 4 7 3 43.0 Total 168 110 (65.5$) 4 25 11 18 58 40 69.0 The proportion of attenuated cases was relatively high when the serum was given on or prior to the fourth day after exposure, but thereafter fell considerably. 133 TABLE IV. - GROUPED FINDINGS OF TABLE III. Number of Days Percentage After Exposure of Measles When Serum No Measles Cases which Total Total Contacts Mild Cases Was Given. Cases were Mild. Measles Number Number of Classical 3-4 40 22 (55.0$) 15 3 18 83.3 5-7 128 88 (68.7$) 25 15 40 62.5 Controls 55 34 (61.8$) 3 18 21 14.3 The table shows that when the serum was given on the third and fourth days after exposure, the attack was mild in 83.3 per cent, of those contacts who developed measles, whereas when given on the fifth to seventh days after exposure, 62.5 per cent, only, of the measles cases were mild. Effect of Time on Serum Potency. An analysis of the results with serum stored for varying periods is given in Table V., which shows that the attenuating power of the serum remained unimpaired for some 200 days, but thereafter fell to a lower level at which the potency was maintained for over 500 days. i 134 TABLE V. - EFFECT OF TIME ON SERUM POTENCY. (type of Attack Age of Percentage Serum of Measles in Cases which Days. No Measles were Mild. Contacts Modified Classical Abortive Number Number of Total Measles Attenuated Total Total Mild Cases i 0- 50 12 8 (66.7$) - 3 - 1 4 3 75.0 50-100 23 12 (52.2%) - 7 3 1 11 10 87.0 100-150 15 10 (66.7$) - 2 2 1 5 4 80.0 150-200 33 20 (60.0$) - 7 4 2 13 11 84.0 200-250 3 2 (66.7$) - - - 1 1 - - 250-300 4 2 (50.0$) - 1 - 1 2 1 50.0 300-350 15 7 (46.7$) - 3 1 4 8 4 50.0 350-400 22 16 (72.6$) - 1 1 4 6 2 33.3 400-450 11 8 (72.7$) 1 1 - 1 3 2 66. 6 450-500 ------ 500-550 30 25 (83.3$) 3 . - 2 5 3 60.0 Total 168 110 (65.5$) 4 25 11 18 58 40 69.0 135 Interval Between Attack and Donation. An attempt was made to ascertain5 whether the interval between the attack of measles and the donation of blood by the subject, had any effect on the value of the serum. The donors had invariably forgotten the age at which they had measles, and so, the ages of the donors have been used as indices of the interval between the attack and the donation of blood. TABLE VI. - EFFECT OF AGE OF DONOR ON SERUM POTENCY. tj} CD Eack 1° ^ i \> - - TS Age of Contacts at Number Number of < Modified rH O Total Total Measles Attenuated Total Total Mild Cases _ i 15-20 31 19 (61.3$) 1 6 2 3 12 9 75.0 20-25 32 19 (59.4%) - 6 2 5 13 8 61.5 25-30 26 19 (73.0%) 1 3 1 2 7 5 71.4 30-35 24 18 (75.0%) - 3 1 2 6 4 66.6 35-40 27 19 (70.4%) 2 3 1 2 8 6 75.0 40-45 14 9 (64.3%) - 2 1 2 5 3 60.0 45-50 14 7 (50.0%) - 2 3 2 7 5 71.4 Total 168 110 (65.5%) 4 25 11 18 58 40 69.0 Table VI. exhibits the results with sera from donors of different ages, and shows that the attenuative value of the serum remains unimpaired in adults up to 50 years of age. Dose of Adult Immune Serum. The first few contacts received doses of 10 c.c. or 15 c.c. of adult immune serum, but as uniform results were not obtained, a standard dose of 20 c.c. was adopted and maintained throughout the investigation. The foregoing results suggest that where the injection is given later than the fourth day after exposure, or 136 where the serum has been kept for more than six months, the dose may with advantage be increased to, say, 30 c.c. in order to obtain optimum results. Incubation Period and Infectivity of Attenuated Measles. The incubation period was judged by observing the interval between the first appearance of the rash in the infecting case, and its first appearance in the contacts. The average incubation period was 12.6 days in attenuated cases, 13.0 days in modified cases, 13.0 days in classical cases, and 12.0 days in the non-immunised contacts or controls. The incubation period in the immunised cases, therefore, did not differ materially from that in the controls. Attenuated cases of measles are infectious, though less so than classical cases, owing to the absence or trifling nature of the catarrhal symptoms. In several groups exposed to infection by an attenuated case, classical attacks resulted both in immunised contacts and non-immunised controls. Natural Immunity. Several presumably susceptible uninoculated contacts or controls, although in very close contact with measles over a comparatively long period, failed to contract the infection. A nurse whose duties brought her into close contact with the children, remained in the ward throughout the catarrhal stage of her illness, and went off duty only when the rash appeared: four of five presumably susceptible uninoculated contacts did not contract measles. (Group Number 3.) In one of the convalescent homes, four presumably 137 susceptible uninoculated children occupied the same dormitory as several children in the catarrhal stage of measles, and were otherwise in very intimate contact with them, yet one only, contracted measles (Group Number 13). Complete natural immunity appeared to be possessed by a presumably susceptible uninoculated child, who was almost continuously exposed to infection for fifty days, by nine consecutive cases of measles, and did not contract the infection (Group Number 15). One control was continuously exposed to infection for seventeen days by five consecutive cases of measles, and only contracted infection from the fifth case (Group Number 15). Two presumably susceptible uninoculated contacts (controls) contracted classical attacks after a second exposure, gaining their infections from an immunised contact or control who had developed measles. Five immunised contacts contracted measles after a second exposure to infection, and in four the attack was attenuated. A child, then, may come into close contact with measles on several occasions, and resist the infection and yet contract the disease at a subsequent contact. It is probable that the degree of natural immunity varies in different children, and that in the individual child, the level of natural immunity varies from time to time, so that, infection resisted when immunity is high, may be contracted later, when immunity is low. In this series, 61.8 per cent, of the presumably susceptible uninoculated contacts (controls) did not contract the infection: as it is likely that many 138 of these children were in contact with measles for the first time, it is not surprising that the proportion who resisted the infection is relatively high. Throughout childhood and adolescence, members of urban populations repeatedly come into contact with cases of measles and the majority contract the infection before reaching adult life. Only SIXTEEN per cent, of the adult donors stated that they had not had measles. It appears that in the children of urban populations, partial natural immunity to measles is common, and complete natural Immunity is not rare. 139 SUMMARY. During the measles epidemic which occurred in Glasgow in the spring of 1934, opportunity was taken to test the value of adult immune serum in the prophylaxis and attenuation of measles. By ttadult immune serum11, is meant the blood-serum from adults who have had an attack of measles in childhood. In order to have a store of serum on hand at the beginning of the epidemic, and also to enable the keeping properties to be proved, the collection of serum was begun at Knightswood Hospital during the winter of 1932-1933, and carried on, as donors became available, right up to and during the epidemic. Owing to the unusually late appearance of the epidemic in the spring of 1934, batches of serum of different ages up to eighteen months old were available. In all 16,000 c.c. of blood were collected from 137 donors and yielded 8,003 c.c. of serum. Twenty-two (16 per cent.) of the donors who were all city-bred, denied any history of measles, and from them 1,368 c.c. of serum were collected in order to compare its value with that of adult immune serum. The serum from each donor was collected under aseptic conditions, Wassermann tested, and stored separately in an ice-chest. The investigation was carried out on susceptible measles contacts in children’s homes and wards of municipal hospitals, and comprises thirty-one groups, involving in all, 243 contacts. The subjects of the investigation were therefore under close observation. The serum was given intramuscularly, and the usual dose was 20 c.c. In a large number of the groups, a proportion of 140 the susceptible contacts did not receive serum and acted as controls. The contacts were kept under close observa tion until the twenty-first day after exposure to infection, and during that time their temperatures were taken four-hourly. When measles occurred in immunised contacts, the type of attack was classified as (a) abortive, (b) attenuated, (c) modified, or (d) classical. Cases admitted to these categories showed the following characters:- (a) Abortive. - No rash: slight or moderate pyrexia occurring after the usual incubation period, and accompanied by headache and slight eye suffusion: no Koplikfs spots: no injection of buccal mucosa: recovery within twenty-four hours. Only four such cases occurred in the whole series. (b) Attenuated. - No catarrhal symptoms: no Koplik’s spots: sparse ill-defined rash: little or no pyrexia: no constitutional symptoms: no complications. An attack of this kind did not appear to differ in any way from an exceedingly mild attack of measles, such as occasionally occurs in children who have not had measles serum. (c) Modified. - Little or no catarrhal symptoms: no Koplik's spots: fairly bright and more or less typical morbilliform rash: slight or moderate pyrexia: no constitutional symptoms: no complications. The objective signs were those of a mild or moderate attack of measles, but the constitutional symptoms usually associated with such an attack were entirely lacking. Prom the onset the children were bright and alert; they playfully sat up or stood up in their cots, and they ate and slept well. The whole illness was not unlike rubella. 141 (d) Classical. - Catarrhal symptoms: Koplik's spots: typical rash: moderate or high pyrexia: characteristic toxaemia. Cases of measles which occurred in the "control" series were classified as very mild, mild, and classical. In general, cases admitted to these categories corresponded respectively to the attenuated, modified, and classical types which occurred amongst the immunised children, thus allowing a comparison of the severity of the attack, in immunised and non-immunised contacts. One hundred and sixty-eight susceptible contacts received an injection of adult immune serum. Of these 110 (65.5 per cent.) did not contract measles, 4 had abortive attacks, 25 showed very mild or attenuated attacks, 11 had mild or modified attacks and 18, classical attacks. Twenty susceptible contacts received an injection of serum from city-bred adults who had not had measles. Of these 9 (45.0 per cent.) did not take measles, 3 showed very mild or attenuated measles and 8, classical measles. As controls, 55 susceptible contacts did not receive serum. Thirty-four (61.8 per cent.) did not take measles. One showed very mild measles; two had mild measles, and 18, classical measles. The proportion of naturally immune children may seem high, but the controls in each group were subject to the same conditions of infection as the immunised children. Prom the above figures it is apparent that adult immune serum is practically useless in the prevention of measles. The attack was mild in 69.0 per cent, of the measles cases who had been immunised with adult immune 142 serum, in 27,3 per cent, of the measles cases who had been given serum from city-bred adults who had not had measles, 14.3 per cent, only, of the measles cases who had not received serum. The attenuative value of adult serum is therefore considerable, whilst that of serum from adults who have not passed through an attack of measles is small. The proportion of attenuated cases was relatively high when the serum was given on or prior to the fourth day after exposure to infection, but thereafter fell considerably. When the serum was given on the third and fourth days after exposure, the attack was mild in 83.3 per cent, of those contacts who developed measles, whereas when given on the fifth to seventh days after exposure, 62.5 per cent, only of the measles cases were mild. An analysis of the results with serum stored for varying periods shows that the attenuating power of the serum remained unimpaired for some 200 days, but thereafter fell to about 60 per cent, of its former value, at which level the potency was maintained for over 500 days. An attempt was made to ascertain whether the interval between the attack of measles and the donation of blood by the subject, had any effect on the value of the serum. The donors had invariably forgotten the age at which they had measles, and so the ages of the donors were used as indices of the interval between the attack and the donation of blood. It was found that the attenuative value of the serum remained unimpaired in adults up to 50 years of age. first few contacts received doses of 10 c.c. or 15 c.c. of adult immune serum, but as uniform results were not obtained, a standard dose of 20 c.c. was adopted and maintained throughout the investigation. The 143 foregoing results suggest that where the injection is 81^®** later than the fourth day after exposure, or where the serum has been kept for more than six months, the dose may with advantage be increased to, 3ay, 30 c.c. in order to obtain optimum results. The average incubation period was 12.6 days in attenuated cases, 13.0 days in modified cases, 13.0 days in classical cases, and 12.0 days in the non-immunised controls. The incubation period in the immunised cases therefore, did not differ materially from that in the controls. Attenuated cases of measles are infectious, though less so than classical cases, owing to the absence, or trifling nature of the catarrhal symptoms. In several groups exposed to infection by an attenuated case, classical attacks resulted in both immunised contacts and non-immunised controls. Evidence has been adduced to show that in city bred children who have not had measles, susceptibility varies within very wide limits, and it is apparent that some possess complete natural immunity. 144 CONCLUSIONS. 1. Adult immune serum when administered in 20 c.c. doses to susceptible measles contacts does not prevent the onset of the disease, but has considerable power to attenuate or modify the attack. If given within the first four days after exposure to infection, the attack may be expected to be attenuated or modified in about 80 per cent, of those contacts who develop the disease; if given on the fifth to seventh day after exposure, 60 per cent, of the cases may be expected to be attenuated or modified. Normally, when serum is not given, only about 14 per cent, of the cases are mild. 2. When stored in the ice box the serum retains its full potency for six months; thereafter the potency drops to about 60 per cent, of its former value, and remains at this level for at least one and a half years. 3. The serum from adults up to 50 years of age is as potent as that of adolescents. 4. The serum from city-bred adults who have not had measles possesses but slight attenuating power. 5. Attenuated measles is infectious and the incubation period corresponds to that of ordinary measles. 6. In contacts who have been inoculated with adult immune serum, and who, notwithstanding, develop unmodified measles, complications may occur as in uninoculated cases, and the attack may even prove fatal. 7. Partial natural immunity to measles is common in city- bred children, and complete natural immunity is not rare. 145 REFERENCES. Bader, G.B.; Jour.Amer.Med.Assoc., 1929, xciii., 668. Barenherg, L.H., Lewis, J.M., and Messer, W.H. ; Jour. Amer.Med.Assoc., 1930, xcv., 4. Bivings, F.L., and Dickson, R.W.; Arch.Pediat., 1927, xliv., 629. Burn, M.; Jour.Royal Sanitary Institute, 1932, liii., 3, 126. Burnet, W.S.: The Lancet, 1935, i., 631. Copeman, W.S.C.; Jour.of Hyg., 1925, xxiv., 427. Harries, E.H.R.s The Lancet, 1930, i., 519. Karelitz, S., and Levin, S.: Amer.Jour.Dis.Child.1927, xxxiii., 408. Morales, E.G., and Mandry, O.C .; Amer .Jour .Dis .Child. I930j xxxix., 1214. Nash, H.T., and Gammie, A.E.: The Lancet, 1934, ii., 507. Report of M.O.H. of Lond.County Co. on Measles Epidemic 1931-1932.