VACCINATION AGAINST SMALLPOX

1262 MAY 5, 1962

VACCINATION AGAINST SMALLPOX BY

W. DIXON, M.D., D.P.H1 Professor of Preventive and Social Medicine, University of C

Otago, Dunedin, New Zealand

No immunization procedure is of advantage in itself. Vaccination can have value only when there is a finite risk of smallpox and it is weighed against the risk of complications of the procedure. Used the right way and having regard to its limitations, vaccination is one of the soundest operations in preventive medicine. Jenner believed that vaccination always gave lifelong immunity, which is quite untrue, and many who followed him believed that every vaccinated person always had an advantage over the unvaccinated-but this also is not true. A vaccinated person, particularly one vaccinated in infancy, may well die of smallpox or have a severe unmodified attack. Although previous vaccination may not give an individual any advantage, a group of vaccinated persons will suffer a lower mortality rate than an unvaccinated As partial immunes, the former are still group. susceptible to smallpox and may have trivial- attacks, but, as has been pointed out many times, this may increase the chance of spread in the community through missed cases. The value to the individual and the value to the community are therefore quite different, depending on the degree of immunity which still persists after vaccination. Universal infant vaccination would produce immune infants, partially immune older children, and generally susceptible adults. About 10% of the population would be immune at any one time, but this would not appreciably affect the spread of the disease, which to-day is most likely to occur and be spread among adolescents and adults. A completely immune population would require a procedure akin to that used in the armed Forces with revaccination at least six times during life. In Britain this would involve about six million vaccinations and revaccinations a year, which, apart from the work involved, would produce a considerable number of major and minor complications. Available figures for generalized vaccinia and postvaccinial encephalitis suggest that about 29 people a year would die and probably double that number (of whom nearly half would have permanent neurological or psychiatric sequelae) would suffer non-fatal encephalitis. As one sees it at the moment, the production of herd immunity in a population as in Great Britain is impracticable and undesirable, not only because of the risk of complications but because it is perfectly feasible to control smallpox by limited vaccination on the ring vaccination" plan. In a country like Britain, with good medical services and a very co-operative public, smallpox is one of the easiest diseases to control, but it requires the medical officer of health to use skill in this and to use minimum, not maximum, measures consistent with reasonable safety. One cannot practise any branch of medicine or surgery, including public health, without some calculated risk. The medical officer of health must be allowed to deal with the situation in the way that he thinks best. The general practitioner, who one hopes does not try to tell the surgeon how to perform an operation, should realize that a great deal of specialized knowledge and skill is also required of the medical officer of health. "

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One source of confusion at the present time is that many older doctors have experience of variola minor or alastrim, which produces mild attacks and against which the protection from vaccination lasts much longer. Many of the claims put forward in favour of infant vaccination and school revaccination are pertinent if variola minor were the infecting agent, but they are not true of variola major. In the Sheffield outbreak of 1887, 7,001 cases and 653 deaths occurred in a population of whom 97.9% had been "vaccinated." In the London outbreak of 1901-02 in over 8,000 cases, with a case mortality of 16.2%, more than 6,000 cases occurred in persons who had been vaccinated, whereas among the 13,686 cases of variola minor described by J. Pickford Marsden (1956) only 1,756 were persons who had been vaccinated at some time. On the other hand, the incidence in different parts of the country was not related to the level of infant vaccination. Variola major in Britain is not a disease of infants and young children, and with its present mode of entrance is particularly likely to be a disease of the adolescent and adult, who will not be protected by infant vaccination even if supplemented by vaccination during school, as has been more than once demonstrated in France. In the Pennine outbreak of 1951 among 40 cases of smallpox, apart from two children infected in hospital, only one case was in a child under 10 years of age, but the infant vaccination rate for the area was less than 10%. In vaccination there are three categories of person to consider: smallpox contacts, overseas travellers, and routine vaccination and revaccination of other persons. Smallpox Contacts Contacts are divided for purposes of public health control into three classes, but class 1 contacts-in the family, close friends, workmates, etc.-will normally be vaccinated or revaccinated immediately the case is provisionally diagnosed clinically and then usually by the medical officer of health or his staff. Three vaccination insertions about 2 in. (5 cm.) apart should be done, using either the scratch technique with i-in. (6-mm.) scratches or the multiple-pressure method using 20 to 30 pressures on each site. This " horrific" vaccination may give considerable local and general reaction, but in the circumstances these risks must be taken. Investigations have been made into the use of gamma-globulin, but in my opinion no concrete evidence has been produced to date to suggest altering the policy that immediate and vigorous vaccination is the method of choice in endeavouring to prevent smallpox in contacts. Gamma-globulin, if available, should be used to supplement, not replace, vaccination. Overseaw Travellers Contrary to what is sometimes stated, vaccination certificates are obligatory for some countries where there is no risk of smallpox to the visitor, and are not obligatory for countries, such as India and Pakistan, where there may be a very great risk from time to time. The doctor has two services to perform: (1) to inoculate the traveller and provide him with the relevant certificates to facilitate his travel through epidemiological control posts at seaports and airports, and (2) to ensure that the traveller is immunized sufficiently

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to protect him against the risks to which he may be exposed in the course of his travels. For the reasons given above these two conditions are not necessarily the same. Most travel agencies give accurate and up-to-date information on vaccination requirements, but at times some advise passengers to be vaccinated when it is not essential for travel to the countries concerned. Final opinion on whether a traveller should be vaccinated or not is a professional matter and only a doctor should advise. The World Health Organization publishes up-to-date information on vaccination requirements for different countries and on the occurrence of smallpox, and medical officers of health are available to advise practitioners on these epidemiological matters. International certificates of vaccination are individual documents: they should not be issued collectively. Separate certificates should be issued for each child and not incorporated in a mother's certificate. A smallpox vaccination certificate is valid for a period of three years commencing eight days after the date on which a successful primary vaccination is performed. In the case of a revaccination the three-year period of validity starts on the day of revaccination. A certificate issued to a child who is unable to write should be signed by a parent or guardian, and the signature of an illiterate should be indicated by his mark certified by another person. In Great Britain the doctor's signature is authenticated by the certificate being stamped by the medical officer of health. If the vaccinator is of the opinion that vaccination is contraindicated on medical grounds he should provide the person with a letter giving the reasons underlying -that opinion, which the health authority at the port of entry may take into account.

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If the first vaccination fails, as shown by no response at the eighth day, primary vaccination should be repeated, increasing the amount of trauma, assuming that fresh or satisfactorily stored lymph has been used. With a " minimal trauma " technique the vesicle is often very small when it is inspected on the eighth day and may not -have been noticed by the patient 12 hours before examination. If a repeat primary fails more than once, using fresh vaccine, it suggests that the person is naturally (at least partially) refractory to vaccinia virus. Assuming the technique and virus are satisfactory, the opposite arm or the anterior aspect of the forearm should be tried. The traumatic factor can be increased by cross-hatching two or three scratches + in. (6.5 mm.) long at right-angles to each other. This technique is used only in those who have shown repeated failure to the " minimal trauma" technique. Occasionally people are genuinely, temporarily or permanently, insusceptible to vaccinia, but they should be warned that this does not mean that they are necessarily insusceptible to smallpox. If time permits, further attempts should be made at the end of a month, recommencing with a minimal insertion technique. Not infrequently a straightforward take results at the first attempt. If the person appears insusceptible to vaccinia the dates of the attempts should appear on the certificate, with a note stating that they were all negative. Unless the person has come from an infected area most countries will accept this in lieu of a vaccination certificate. On no account should a positive result be recorded when a typical primary vesicle has not resulted or the traveller is likely to pay dearly by relying on this when travelling in a country with endemic smallpox. Revacdnation

Primary Vaccination

When revaccination is requested only a definite visible scar should be accepted as evidence of successful primary vaccination. If a scar cannot be found, is too indefinite for certainty, or cannot be distinguished from a B.C.G. scar, then it should be discounted and the procedure for primary vaccination followed. If a person is travellingto or through a low-risk area a single insertion is given as for primary vaccination. If the interval since primary vaccination or the last revaccination is short an allergic reaction may follow with erythema, a small papule, and slight itching within 24 to 48 hours, fading rapidly so that on the eighth day little or nothing can be seen. If the residual immunity is less, a definite vesicle may develop by the fourth or fifth day, smaller and more superficial than with a primary vaccination and drving up by the eighth day. If the residual immunity is slight or absent a primary-type vesicle little different from a primary vaccination xvill occur with maximum effect about the ninth or tenth day and sometimes severe local or general reaction. A scar will result, but it is usually more superficial than that of a primary vaccination. Although common in persons vaccinated 20 years or more before, this type of reaction sometimes occurs a short time after a successful primary vaccination, and it is not uncommon in persons who have had a number of revaccination attempts at three-yearly intervals, presumably without immunity response. The lack of means of differentiating between the early allergic response, which can also be obtained with killed

If a person has never been successfully vaccinated before, a primary vaccination is necessary and the date it is performed and the result are recorded separately on the certificate. In all primary vaccinations a " minimal trauma " technique should be used, either a single scratch not more than * in. (3 mm.) long or 6 to 10 pressures over an area not more than I in. (3 mm.) in diameter. This should give a small vesicle about 3/16 in. (5 mm.) in diameter by the seventh or eighth day, enlarging to about I to I in. (6.5 to 9.5 mm.) in diameter by the ninth or tenth day, then drying up and leaving a scar about 3/16 in. (5 mm.) in diameter. This method will minimize the chance of local and general reaction, which can be quite severe, particularly if larger insertions are used and in the elderly and obese. This method gives a lower take rate, perhaps a failure of 1 in 20 compared with more horrific methods, but it is worth it in minimizing discomfort to the patient. In the case of young babies who are relatively resistant to vaccinia, or where a failure would be inconvenient if the traveller must leave soon after the eighth day, the area of the insertion can be increased in size-a scratch about 3/16 in. (5 mm.) long, multiple pressure 15 to 20 pressures. It should be noted that the certificate is not valid until the eighth day after the vaccination is performed. In the case of sea travel a ship's doctor can complete the certificate, but for air travel a completed certificate is essential before vaccine, from a similar reaction where virus growth has occurred and immunity been stimulated, has led the departure.

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W.H.O. to allow revaccination to be certified without reading the result. The travelier's safety, however, depends on the conscientious and effective performance of revaccination by his doctor. The revaccination certificate can be given straight away, which is of great value to the traveller in a hurry. A person who is going to stay in India, Pakistan, Burma, or East and West African countries, where smallpox is a considerable risk, requires (in my opinion) something more than a valid certificate. If the person has to leave immediately revaccination should be done with three minimal insertions about 2 in. (5 cm.) apart. This will reduce the chance of failure. If there is time, and the person has been vaccinated or revaccinated within three to five years, revaccination should be done with three insertions as before and the result should be read at the eighth day, when one or more may be seen to have taken. If the interval since the last vaccination or revaccination is longer and time is available then a single revaccination can be done and read on the eighth day, and if it is negative a further threeinsertion revaccination is done. This may be considered unnecessary, but it does save the middle-aged or elderly obese person from having three primary-type takes from It cannot be overemphasized that if a revaccination. a person is going to live or work in a high-risk area then one should not be afraid to do too many revaccinations rather than too few. If they are done in this order the person can be spared unnecessary discomfort. The procedure is not followed with all revaccinations simply because compromise is necessary in the case of persons requiring a certificate but travelling in areas of negligible risk. It is always advisable, however, to warn the traveller that close contact in a high-risk area warrants further revaccination even if the certificate is still valid. Routine Vaccination and Revaccination of Other Persons The most important persons in the British community to maintain at a high level of immunity against smallpox are doctors, nurses, and other hospital personnel, health visitors, public-health inspectors, ambulance drivers, etc., and their immediate families-persons who are most likely to come in contact with an undiagnosed case of smallpox. The difficulty of maintaining a high immunity level in nursing staff in hospital is often due to their being primarily vaccinated on entering hospital by doctors using " horrific " techniques and not giving sufficient explanation of the effects of vaccination. In a young, frightened, homesick nurse-trainee this produces a determination never to be vaccinated again, although the revaccination would be a trivial matter. For all personnel in this category the minimum-trauma technique should be used which admittedly will produce immunity slowly, but this does not matter. If every effort has been made to minimize the chances of local and general reaction, the good will of these persons will be assured and revaccination at three-yearly intervals can be maintained without difficulty. Great Britain, France, Germany, and other countries over the last 20 years have a sorry record of smallpox in medical and nursing personnel who should never have been infected. Vaccination procedure to be followed is the same as that for travellers. no

Occasionally individuals

produce

successful vaccination after repeated attempts, and

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in the case of doctors or nurses this is of some importance. Every effort should be made to produce a successful vaccination by increasing the trauma, crosshatching, and vaccinating on the forearm. It is well worth trying a " minimal trauma " vaccination after an interval of a few months, when it may quite unexpectedly take. (I have recently performed a perfectly normal primary vaccination on two doctorsone who had been vaccinated six times over some 20 years, and another who had been vaccinated 10 times without success.) Such a person, who has never had a successful primary vaccination as shown by a scar and has not had smallpox, must be regarded as susceptible to smallpox and told so. General Remarks on Vaccination Technique Handling and Storage of Smallpox Vaccine (sometimes called " calf lymph," although it may be prepared on the sheep).-Smallpox vaccine is a live virus culture and must be stored at low temperatures. It should be stored in a refrigerator, and, although likely to remain potent under temperate climatic conditions for 24 hours at room temperature, should not be returned to the refrigerator if unused but should be destroyed. Dried vaccine remains potent for many months, but when reconstituted it has a short life similar to liquid vaccine. Lymph which has been kept at room temperature for many days may give some successful primary vaccinations, but it is likely to fail in revaccination where there is residual immunity, and it is just in this case that the operator will not know of his failure. Site of Vaccination.-The deltoid area of the arm is the site least likely to give rise to complications. Many other sites have been used. The site should be easy of access both for doing the vaccination and for sho'wing the scar on future occasions, and should not be liable to be knocked. The inner aspect of the arm is sometimes used and the forearm when vaccination on the upper arm fails to take. The thick skin on the outer aspect of the thigh is not suitable, but if the arm is refused the anterior abdominal wall, just above Poupart's ligament, can be used in older children or adults. Many other sites have been used from time to time. Operation of Vaccination.-The skin should not be cleaned with disinfectant of any kind, including ether or alcohol, and normally requires no preparation. If it is really dirty it should be washed first with soap and water, preferably by the patient. Techniique.-Tlhere is no virtue in any particular technique, bearing in mind the size of the inoculated area. A small scratch about 1/16 in. (1.5 mm.) long produces exactly the same type of vaccination as a multiple pressure of 6 to 10 pressures. Large scratches 2 in. (1.3 cm.) or more in length, common in the past, produce much more severe vaccinations, and crosshatching should not be done except where the person is shown to be unusually resistant to vaccinial infection. It is often stated that blood should not be drawn, but every satisfactory vaccination shows minute haemorrhages if a careful examination is made, and more vaccinations fail from being too superficial rather than being too deep. A dressing is not required on a vaccination at the time it is done; it should be left open to the air. If it is knocked after the vesicle has developed talcum powder can be applied or a piece of sterile gauze pinned to the inside of the sleeve or fixed to the skin at the shoulder and elbow a long way from the vaccination site. Special occlusive vaccination

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dressings are most unsatisfactory and greatly increase the likelihood of sepsis. If a person is engaged in very dirty work a pad of gauze can be affixed with two bands of adhesive, but it should be removed immediately on ceasing dirty work. Reading Reactions.-Primary vaccinations should be read on the eighth day, but they can be read later, as the scab will be present up to the twentieth day. Contraindicatlons

Owing to the risk of generalized vaccinia no infant with infantile eczema should be vaccinated purely for travel purposes. If vaccination is withheld for medical reasons a letter should be given stating the reasons. If the infant is going to an area of high smallpox risk it will require vaccination, but this should be done in

consultation with a dermatologist or paediatrician treating the case. Although generalized vaccinia may occur in adults who have a history of eczema in childhood, this rare complication may also occur in those with no such history. Many adults do not know about diseases during infancy, and it therefore seems of little value to question all adults on this point and withhold vaccination from those with such a history. If this is done the patient must be warned that he has no protection against smallpox and be told of the real dangers of this disease, particularly in India and Pakistan. If travel is to those countries vaccination should be done even if chronic eczema is present. Although there is a viraemia during vaccination the foetus does not appear to be affected as in rubella. Some observations have suggested that vaccination done in the first three months of pregnancy may slightly raise the stillbirth rate, but this is by no means certain. In view of our increasing concern in avoiding any possible virus infection of the foetus it would appear prudent to avoid vaccination in the first three months of pregnancy if this is practicable. In the face of any smallpox risk vaccination must be done at any stage of pregnancy. In general it is better to avoid giving multiple antigens, particularly live viruses, such as vaccine and yellow fever, too close to one another. Yellow-fever inoculation may be given four days before a primary vaccination, but if the primary vaccination is done first the yellow-fever inoculation should not be given for three weeks. Although short-interval revaccinations will have a trivial effect and yellow-fever vaccine may be given concurrently, if the interval since primary vaccination is a long one a revaccination should be regarded as similar to a primary vaccination in regard to yellowfever inoculation. In the case of infants under 1 year it is advisable not to give smallpox vaccine until at least three weeks after yellow-fever vaccine. Although cholera vaccine may be given at the same time as the short-interval revaccination, and this is of value to the businessman in a hurry, it seems better to avoid giving cholera inoculations until the reactions from primary vaccination have subsided. In an emergency one can give primary vaccination and yellow fever and cholera inoculation at the same time, but the certificates will not be valid until the normal procedure for each is completed. Complications of Vaccnation

A "minimal trauma" vaccination produces a very small vesicle by the seventh day which enlarges to the tenth day accompanied by increasing erythema, and the patient may suffer no local or general inconvenience.

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On the other hand,

particularly in the older adult, there erythema surrounding the vaccination ; this has been misinterpreted by some practitioners as indicating secondary infection, and the patient has been treated with the prevailing antibiotic although it has no effect. The vesicle disappears as the vaccination matures. A proportion of patients develop a pyrexia on about the tenth day with " minimal trauma" and about the seventh or eighth day with more " horrific " techniques. This is due apparently to an acute viraemia and is clinically similar to influenza. Some patients say their arm is perfectly all right, but that they have had an attack of influenza and do not associate the one with the other, whereas other patients credit every minor malady to the vaccination from the moment it is may be considerable

performed when there is

no connexion. It is normal for there to be some enlargement of the axillary lymph nodes. Some patients notice this because of stiffness of the arm, others do not appear to notice it at all.

Although the vaccinial lesion becomes " pustular" a descriptive term, and the unbroken vesicle, although filled with milky fluid consisting of virus and cellular debris, may contain no secondary organisms. If the vesicle is broken it may become infected, and if large insertions are given there is an increased tendency for infection to occur because of the larger area of tissue necrosis. this is

These appearances can best be described as variations of the normal. Real complications are relatively rare and may include secondary vesicles either around the primary one or sometimes on more distant parts of the body, and when numerous are given the term " generalized vaccinia." Their distribution is irregular and they are of importance particularly in smallpox contacts because it requires some skill to differentiate this condition from mild smallpox. Generalized vaccinia of this type is self-curing; the lesions heal without a scar. In the case of infants with infantile eczema who have been intentionally or accidentally infected a severe generalized eruption may occur very similar to malignant smallpox, and it is often fatal. Post-vaccinial encephalitis is a rather complication both because a high proportionimportant of the patients will die and also because at least 50% of patients will develop psychiatric or neurological sequelae. Its incidence varies greatly from time to time and in different countries. Sometimes it is extremely rare (less than I in 1,000,000 in Gloucester; in Worcester in 1923 the incidence was 1 in 800), whereas in small towns in Holland it has been as high as I in 63. It is impossible to predict what will be the incidence at any time or place. It occurs at all ages and after revaccination as well as after primary vaccination, but it is impossible to discuss this complex problem fully in the present brief account. Dutch investigators (Nanning, 1961) showed that in primary vaccination in military recruits 2 ml. of antivaccinial gamma-globulin reduced the 1 in 4,500 incidence of encephalitis in adults by about 70%. Although it did not appear to influence the development of normal vaccination the acid test of degree and duration of immunity against smallpox has yet to be made. How practicable would be the supply of gamma-globulin to a civil population is at present

undetermined. Primary vaccination of those between 1 and 4 years of age (with a death rate of 1.9 per million) would

VACCINATION AGAINST SMALLPOX

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appear to be safer than of those under 1 year (with a death rate of 15.4 per million) (Wynne Griffith, 1962). The rate of complication of vaccination in those aged 1 to 4 must be added to that at 15 + when required. The incidence of complications in those done twice appears to be lower, but the mortality is about the same. Unless a large proportion of adults require vaccination for travel purposes, a requirement likely to decrease in the future, or for a real smallpox risk in the United Kingdom, which really involves very few people, the routine vaccination of even the 1 to 4 age-group hardly seems justified. The diagnosis of the complications of vaccination may be difficult, but the collection of statistics is quite incomplete and I would plead for general practitioners to tell their medical officers of health of any vaccinial troubles they may come across, as only in this way can sound advice eventually be given.

Conclusion Finally, I would stress that vaccination is a medical operation. A doctor, whether in the National Health

Service or not, is under no obligation to do what a patient instructs himn to do if he considers there is no medical justification. A doctor must accept, however, that his medical coUeagues in other countries demand vaccination certificates from travellers in order to protect their own patients, expressing this administratively by certificate requirements. On the other hand, the occurrence of complications not in themselves usually due to errors in technique are still the moral and, I feel, the legal responsibility of the doctor if the operation was performed without any medical indication of its need. Much of this information is from Smallpox (Dixon, 1962), and the part dealing with vaccination for travel purposes isx that contributed by me to a booklet on immunization information for international travel issued by the New Zealand Department of Health. REFERENCS

Dixon, C. W. (1962). Smallpox. Churchill, London. Griffith, J. Wynne (1962). In C. W. Dixon's Smallpox. Churchill, London. Marsden, J. Pickford (1956. L.C.C. Report 3209. Nanning, W. (1961). WIJ.O. Committee on Int. Quarantine,

Decembler.

Nova et Vetera HOSPITAL FOR DISEASES OF THE THROAT A GOLDEN SQUARE CENTENARY The Hospital for Diseases of the Throat was founded Inn Road. and in 1887 another group founded the London as a dispensary by Morell Mackenzie in 1862 to enable Throat Hospital in Great Portland Street. The latter him to carry out the research and treatment made amalgamated with the Golden Square Hospital in 1913 and possible by the invention of the laryngoscope eight the Central London Hospital amalgamated with; this combined hospital in 1939 to form the present Royal National years befQre. Throat, Nose and Ear Hospital. The name of the hospital The clinic, the " Metropolitan Free Dispensary of the had been changed in 1927 from thay-of the Hospital for Throat and Loss of Voice," which he set up in King Street, Diseases of the Throat now Kingly Street, just north of Golden Square, was such- to the Golden Square a success that Mackenzie was faced with the need for pro- Throat, Nose and Ear viding in-patient accommodation, and in 1865 the clinic Hospital so that whatmoved to No. 32 Golden Square. The new hospital pros- ever happened to it a pered, and assistants who had worked there later set up record of its birthplace clinics in London, in other parts of Great Britain, and in would be preserved. Morell Mackenzie ,. North America. In 1882 a special clinic for the observation and treatment founded three other of diseases of the ear was established- Further houses in institutions in- addition Upper John Street were taken over, in 1883 and in 1897, to the hqspital: a firm and,in Beak Street and Golden Square in- 1908-11, by which of instrument makers time the whole of the present site of the hospital had been (now Ma y e r a n d V-. Phelps) in 1863, the In 1874 a group of Mackenzie's assistants founded the journal now known as Central London Throat, Nose and Ear Hospital in Gray's the Journal of Laryngology and Otology in 1887, and the British Laryngological a n d Rhinological Association in 1888. All have survived in some form Moreli Mackenzie. to the present day. Mackenzie's gifts of teaching and training established a tradition which has continued throughout the century that has elapsed since the hospital was founded. T'he .d same tradition was established by Lennox Brown, the founder of the Gray's Inn Road Hospital and maintained until the two teaching units became one in 1939, and in 1947 were formedinto the Institute of Laryngology and Otology affiliated to the Postgraduate Medical Federation r of the University of London. The influence of the institutions founded by Morell Mackenzie has spread wide and- lasted long, and even after the passage of 100-years it has not seriously been challenged. A sketch of the IHospital for Diseses of the Throat in Golden F. C. ORMEROD. Square as it was in 1893.

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