33

4. Scott, M. J. Amer. med. Ass. 1960, 172, 889.5. Sibley, W. A., Morledge, J. H., Lapham, L. W. Amer. J. med. Sci.

1957, 234, 663.6. Marshall, J. J. Neurol. Neurosurg. Psychiat. 1959, 22, 347.7. Brown, G. C., Napier, J. A. J. Immunol. 1960, 84, 463.8. Logan, J. S., Field, A. M., Macrae, A. D., Miller, A., Tobin, J. O’H.

Brit. med. J. 1960, i, 1692.9. Kendall, E. J. C., Beswick, T. S. L., Miller, A., Tobin, J. O’H. ibid.

p. 1689.

than, agreements. A tendency of two observers to callfilms normal was reflected in the statistics: they diagnosedcorrectly more " normals " than " abnormals ".At the end of the diagnostic road lies still the unsettled

question of treatment. Here the overriding difficulty isthat of finding a control group to match a similar grouptreated actively. Scott 4 considers that the late follow-upof spontaneous cerebral haemorrhage into the internalcapsule treated by immediate surgical operation justifiessuch treatment: " Probably all of these patients wouldhave died without operation." But where are the statisticsto justify such a statement ? At necropsy old hxmorrhagiccysts are found in the brain years later. In this common

condition, what is the mortality-rate ? Scott points outthat the operative mortality for hasmatoma of the temporallobe is low, and 3 of his 7 cases were alive seven to elevenyears later; but, as regards the brain generally, small seriesof less than 10 cases account for seventeen out of nineteen

reported series in which operation was undertaken, theoperative mortality varying from 0 to 100%. Statistics of

conservatively treated cases are confined to reports ofcases vertified by necropsy: it is hardly surprising that themortality-rate of cases treated conservatively is thendiscovered to be 100%. We simply must not ask thewrong questions in mathematical language because wecannot find an answer to the right ones in English. Eventhe selection of cases in which the non-dominant hemi-

sphere is affected would be generally considered to weighin favour of survival, as the hemiplegic, aphasic patientwho survives an initial stroke commonly dies subsequentlyin a state of inanition. Where thrombosis occurs in asmall vessel, as opposed to a main stem, active treatmentby anticoagulants is at present thought to be contra-indicated owing to the danger of hmmorrhage .5 6 As Bulland his colleagues remark:

" Until the value of the various forms of treatment is known,the place of angiography as a step towards definitive treatmentcannot be finally assessed. Meanwhile angiography is clearlynot justified for all patients with an acute stroke, but centreswith the facilities should continue their endeavours to assessthe place of angiography in the management of acute strokes inrelation to the methods of treatment available."

DURATION OF IMMUNITY AFTER

POLIOMYELITIS VACCINATION

WE do not yet know how long immunity to poliomyelitiswill persist in those given a full course of killed vaccinecomprising two or three primary doses and a booster dosewhile antibodies to the primary course persist. Thestudies demonstrating the effectiveness of vaccination inthe field have all been made within a few months of

completion of vaccine courses.A little more is known about the persistence of anti-

bodies. Follow-up studies have lately been reported onchildren originally vaccinated in the field trials in theU.S.A.7 and in this country,8 and also on young adultsin this country.9 9 The difficulties of this sort of assess-ment are clearly brought out in the American study byBrown and Napier,1 which showed a high incidence ofnatural poliomyelitis infection in the children in the four

10. Lennette, E. H., Schmidt, N. J. Amer. J. Hyg. 1957, 65, 210.11. Dane, D. S., Dick, G. W. A., Briggs, M., Nelson, R. Brit. med. J. 1958,

ii, 1187.12. Salk, J. E. J. Amer. med. Ass. 1958, 167, 1.13. Plotkin, S. A., Jervis, G., Norton, T., Stokes, J., Jr., Koprowski, H. ibid.

1959, 170, 8.14. See Brit. med. J. June 4, 1960, p. 1729.15. Medical Research Council report. ibid. ii , 1207.

years after they were first vaccinated. Thus it wascalculated that 57% became infected with type 1 virus,73% with type 2, and 42% with type 3. (These figures,incidentally, are additional evidence that killed vaccinedoes not materially limit alimentary infection with polio-viruses.) Despite this high incidence of infection, itwas found that of 135 children first vaccinated in 1954and given a booster dose in 1955 25%, 7%, and 30%lacked antibodies to poliovirus types 1, 2, and 3

respectively by 1958. In the British investigations 8 it wasfound that all of 27 individuals (except 1 child for type 1whose serum was tested only at 1/16) still had antibodiestwo years after a booster dose. The majority of thechildren responded well to a fourth dose of vaccine,producing titres of over 1/1000 to all three types by thecolour-test method of titration (although the titre wasabout ten times lower by a cytopathic inhibition test).In the two years that followed the booster dose there was

nearly a fivefold decrease in titre. A similar follow-upstudy of 54 public-school boys and medical personnelgave very similar results. In this group there was noevidence of reinfection, and again it was calculated thatthe average fall in titre was about fivefold in two years,although the differences between individuals was notable,some showing much greater rates of fall than others.Lennette and Schmidt 10 in a study of poliovirus-neutralising antibodies after clinically manifest infectionobserved a similar fall in type-1 antibody titre in two years,so it seems to make little difference whether the antibodiesare induced by active infection or by killed vaccine. Dane etal.11 have shown that a similar rate of decline of antibodiesfollows the administration of an attenuated vaccine.

Salk 12 with killed vaccine and Koprowski 13 with at-tenuated vaccine have found that in a few children anti-bodies persisted for much longer than these average ratesof decline would suggest, but in view of the wide variationbetween individuals this is not too surprising. As Kendallet awl. say, it is those with a greater than average rate ofdecline of antibody who need protection. They concludethat titres of at least 1/100 are required after a third dose toensure adequate protection for five years and a satisfactoryresponse to a booster dose. At present killed vaccine, whilesubstantially achieving this for types 2 and 3, producesthis level for type 1 in only 70-75% of subjects. Vaccinewith a more potent type-1 component is therefore required,and with vaccines at present available a fourth dose isrecommended two years after the third, at least for

specially exposed groups (for example, young adults

going overseas). The reported findings with living vaccineare not yet extensive enough to establish whether this willgive better results. , At the recent Moscow conference onliving vaccines a group of Estonian children were reportedto have geometric mean titres of 1/52, 1/162, and 1/128 fortypes 1, 2, and 3 respectively after attenuated vaccine.!!The results for killed vaccine in the first Medical ResearchCouncil tria115 after two doses were 1/78, 1/283, and 1/118,and after a booster dose greater than 1/1000 for all threetypes. Too much should not be made of such comparisonsof antibody titres obtained in different laboratories, asminor technical differences can make great differences inar’tnal titre- nhtnini-cl