practice in the United States and Great Britain

Postgrad. med. J. (February 1969) 45, 147-160.

Immunization practice in the United States and Great Britain:a comparative study

DAVID T. KARZON*M.D.

Professor of Pediatrics, Professor of MicrobiologyState University ofNew York at Buffalo, Buffalo, New York, U.S.A.

'Epidemics that used to be excused as acts of God arenow not excused as the results of the inactivity of man.In short, the incidence of many diseases has been movedfrom the area of chance to the area of choice. That isa vast change intellectually. Not only intellectually butalso morally, for such a series of accomplishmentsleaves us with a new system of ethics to devise, somewhatas the perfection of the automobile has called for newtraffic laws. As physicians we cannot evade a moralresponsibility that goes with our newly acquired power.Having learned how disease comes about, we find our-selves answerable for why it should occur at all' (Gregg,1949).

THE EFFECTIVE control or eradication of manyinfectious diseases through prophylactic immuniza-tion stands as one of the more dramatic successstories of moder medicine. The number of diseasesamenable to prevention is increasing in recent years,and new developments on the horizon may beexpected to further compound the already com-plicated immunization schedule. We have arrived atthe point where, from infancy through youngadulthood, the individual will receive a formidablearray of biological products for the prevention ofdisease on a routine basis. Decisions concerning theoptimal use of immunizing agents have attained ahigh degree of sophistication, stemming from anumber of very real factors. Expert opinion has beendivided on many issues. Matters of finejudgment andpublic policy are involved. Thus, the individualpractitioner or public health officer finds that he mustbecome learned in such areas as: the relative meritsof inactivated versus live attenuated virus vaccines;the effect of adjuvants; the optimal sequence andinterval of administration; the efficiency andsafety of available products; the identification ofhighrisk groups to be singled out for special immuniza-tion schedules; the contraindications to administra-tion of individual products; the attributes of newly-introduced biologicals and weighing of risk of diseaseagainst the risk of the immunizing procedure; thelegitimacy of universal immunization against a

* Present address: Professor and Chairman, Departmentof Pediatrics, School of Medicine, Vanderbilt University,Nashville, Tennessee, 37203, U.S.A.

disease which is absent or uncommon in the popula-tion; and the problems of simultaneous administra-tion of immunizing agents, especially one or morelive products.

Final judgment on the safest and most effectiveprocedures to use for the immunization of theindividual, community or nation rests on a complexbalance of factors. More and more, the individualpractitioner and the public health authorities havelooked for guidance from expert national bodies.This guidance in recent years has been basedincreasingly on pre-designed studies such as vaccinefield trials, surveillance of disease morbidity andmortality, sero-epidemiology, and surveillance of theuntoward effects of vaccines. These data are thenweighed against the practicalities of scheduling suchimmunizations within the existing patterns ofdelivery of health care.The present article is an attempt to explore some

of the problems and solutions undertaken in the fieldof immunization practice in the United States andGreat Britain. A very limited review in the twocountries has shown that, despite the disparatesystems of delivery of health care, similar trends inimmunization practice have developed. Furthermore,the rate of use of various products and their effec-tiveness in reduction of disease again shows moreresemblances than differences. One conspicuousparallel development in the United States and GreatBritain has been the increasing emergence of unifiednational policy concerning the use of biologicalreagents for immunoprophylaxis. The recommenda-tions of national bodies, representing the consensusof informed opinion, have been powerful forces inthe use of immunizing agents. These developmentscan be briefly traced in each country.

In the United States, one of the early influenceshas been the Committee on the Control of InfectiousDiseases, a standing committee of the AmericanAcademy of Pediatrics. The first edition of theirreport, covering eight pages, was published in 1938.The current fifteenth edition, published in 1966, is a185-page desk reference which reviews recommenda-

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David T. Karzon

tions concerning prevention of most of the infectiousdiseases encountered in North and South America(American Academy of Pediatrics, 1966). Thereport has been translated into Spanish. Through theyears, the red-covered report, referred to as 'TheRed Book', has become the veritable bible for thepractitioner caring for children, as well as a referencepoint for public health authorities and well-babyclinicsDuring the early years of the introduction of

poliovirus and measles vaccines, the United StatesPublic Health Service issued recommendationsthrough expert committees assembled on an ad hocbasis. To meet the need for evaluation ofnew and oldvaccines on a continuing basis, the AdvisoryCommittee on Immunization Practices was createdin 1964. This committee was charged with apprisingthe Surgeon-General of the status of diseases forwhich effective vaccines are available, and to adviseregularly on immunization practices relevant tothese diseases in public health and preventive medicalpractice in the United States. The committee wasfurther charged with encouraging investigation ofvaccine usage and disease surveillance. Since itsinception, the committee has issued formal state-ments on most of the major vaccines, updating thesestatements as new information emerged. TheAdvisory Committee relies heavily on the staff of theNational Communicable Disease Center (NCDC)for program assistance. The NCDC has recentlypublished a volume, Immunization Against Diseases,1966-67 (United States Public Health Service, 1967),which includes current epidemiological reviews ofselected infectious diseases, a summary of immuniza-tion status and use of biologicals in the UnitedStates, and the complete reports of the AdvisoryCommittee recommendations.Another potent factor in increasing the utilization

of vaccines in the United States has been the trendat the state level to require certain immunizationsprior to school entry. Since February 1968, half ofthe states required immunization against one or morediseases, including twelve which require measles,sixteen poliovirus, thirteen diphtheria-tetanus-pertussis and twenty-one smallpox vaccines (UnitedStates Public Health Service, 1968a). These com-pulsory immunization laws are prosecuted withvarious degrees of conviction in different parts of thecountry, although exemptions are usually grantedwhen immunizations are contrary to religious beliefsor medically contraindicated. It would appear thatthe trend to increasing compulsory immunizationwill continue, insuring that children are adequatelyimmunized in this captive manner when enteringthis critical time of increased risk.

In 1962, Congress passed the Vaccination Assist-ance Act, which provided financial assistance to

state and local health departments for improvementof immunization programs. Funds were madeavailable for purchase of vaccines for immunizationof pre-school children, support of the organizationand administration of immunization programs, im-provement of laboratory and epidemiologicalsurveillance, and promotional and educationalactivities. Although the bulk of the support hasemphasized public health and community-basedprograms, it has been observed in most areas thatthe balance between immunizations given privatelyand publicly does not change when a communityaccelerates its immunization activities (Freckleton,1967). Appropriations for the program have rangedfrom 8 to 10 million dollars a year. At present thereare forty-eight state and twenty-four local grant-assisted programs, covering approximately 90% ofthe population of the United States, Puerto Ricoand the Virgin Islands. By design, the program haspermitted a high degree of flexibility of administra-tion to adapt to local needs.Another dimension that bears on the final

efficiency of immunization programs has becomeevident in the United States. There are wide differ-ences in the rates of immunization in various demo-graphic groups in the population. For example,vaccine acceptance has been particularly poor inthe poverty areas of the large cities in the UnitedStates, especially among the Negro population.This has also been true in certain rural regionswhere poverty and other special cultural factors mayprevail. Such under-immunized groups often have ahigher incidence of preventable diseases and in turnhave been the target for intensive immunizationcampaigns. Specific examples of this phenomenonwill be pointed out under individual diseases.

In Great Britain, over the past 20 years, there hasbeen increasing guidance concerning immunizationpolicy from the Ministry of Health. In 1948, whenthe National Health Service Act was established,smallpox vaccination and diphtheria immunizationwere the only officially recommended procedures inEngland and Wales (Ministry of Health, 1964).Pertussis immunization was undertaken by somelocal health authorities. BCG vaccination was laterintroduced to school children on a discretionarybasis. Various alternative schemes for immunizationwith diphtheria, pertussis and tetanus were recom-mended in 1954 (Ministry of Health, 1955). Officialschedules of combined vaccines were prepared in1961 and adopted by local health authorities. Specialcommittees dealing with matters such as diphtheriatoxoid and poliomyelitis vaccine were superceded in1962 by a Joint Committee on Vaccination andImmunization appointed by the Central HealthServices Council and the Ministry of Health, to'advise the Health Ministers on all the medical

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Immunization in United States and Great Britain

TABLE 1. Recommended schedules for routine immunization

United States* England and Walest

Age DTP OPV M SP Age DTP OPV M SP BCG2-3 months X X 3-6 months X X3-4 months X4-5 months X X 5-8 months X X12-18 months X X X 9-14 months X X12-24 months X 12-24 months X XSchool entry X X X School entry Td X X

(3-6 years) (3-6 years)10-13 years X

Every 10 years Td Xt School leaving Td X X

DTP, Diphtheria-tetanus-pertussis vaccine; OPV, oral poliovaccine; M, measles vaccine; SP, smallpox vaccine; Td, tetanus-diphtheria toxoid, adult type.

* Adopted from United States Public Health Service (1967): Immunization Against Disease 1966-67 (National CommunicableDisease Center publication).t Adopted from Ministry of Health (1968a,b).t For high risk groups, i.e. health personnel and overseas travel-every 3 years.

aspects of vaccination and immunization'. Suggestedschedules were published in 1963 in a bookletentitled Active Immunization Against InfectiousDisease (Ministry of Health, 1963). This Joint Com-mittee has the same general mission as the UnitedStates Public Health Service Advisory Committee onImmunization Practices.

Schedules for those immunization proceduresrecommended for all children are shown in Table 1.The table has been constructed using the mostrecent statements available from the United StatesPublic Health Service and the Ministry of Health(United States Public Health Service, 1967; Ministryof Health, 1963, 1968a). It is notable that theschedules are remarkably similar, despite the factthat, historically, there have been differences in theapproach to the use of individual vaccines. There areseveral points of difference. DTP combined antigenis recommended at an earlier age in the UnitedStates, and three doses are administered in theprimary series to make up for the handicaps of im-maturity and maternal antibody. In the schedulerecently recommended for Great Britain, initiationof immunization at approximately 6 months isfavoured. This is an effort to avoid the immunologicalhandicap and also to lessen the risk of reactions topertussis vaccine thought to be more common inchildren under 6 months. A booster dose of pertussisvaccine is included in the United States schedulebecause of the continued threat of disease beyondinfancy and the apparently more benign experiencewith reactions. BCG is not used routinely in school-aged children in the United States, but is reservedfor selected individuals considered to be at highrisk. An additional dose of oral poliovaccinerecommended at school-leaving in Great Britain isthought to be unnecessary in the United States.

Status of individual diseasesCertain diseases for which immunoprophylaxis is

available will be discussed in further detail. Informa-tion concerning immunization rates, morbidity andmortality, and other problems related to vaccine use,have been gathered from a variety of sources.Except when noted, all British data refer to Englandand Wales. In looking at the statistical data, it isuseful to remember that the population of theUnited States, 196 million, is approximately fourtimes that of England and Wales, 48 million (1966).In attempting to assemble comparable data for theUnited States and Great Britain, it was immediatelyevident that a strict comparison of the use ofvaccine or disease incidence was not possiblebecause of inherent differences in notification ofdisease, surveillance methods, and book-keepingprocedures. Despite this, many instructive com-parisons can be drawn between practices in the twocountries.

Diphtheria, tetanus and pertussisThe three diseases may be discussed profitably

under one heading, because of the current generalpractice of immunization with combined antigens.Table 2 shows the percentage of children in theUnited States who had completed a primary coursein DTP in 1966. Approximately 83 % of school-agedchildren have received at least three, and 65% havereceived four or more, doses of vaccine. The differ-ence in rates between white and non-white popula-tions is striking at all ages, but is most marked in theyounger age groups. Immunization rates for a prim-ary series of diphtheria and pertussis in England andWales were similar to those in the United States forthe first 2 years of life. The somewhat lower per-centages of children under 5 or under 16 who were

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TABLE 2. Immunization rate (%Y), combined diphtheria andtetanus toxoids and pertussis vaccine (1966)

UNITED STATES

Diphtheria-tetanus-pertussis*Age

(years) Total White Non-white

1 69 74 442 74 78 523 76 79 564 79 82 601-4 74 79 535-9 83 86 70

ENGLAND AND WALES

Age(years) Diphtheria Pertussis

It 73 722t 76 74

Under 5t 68Under 16t 52

* Three or more doses of vaccine (United States PublicHealth Service, 1967).

t Primary series (Ministry of Health, 1967a).t Percentage of children under 5 years or 16 years that

'may be regarded as remaining protected against diphtheria)(Ministry of Health, 1967a).

regarded as protected against diphtheria wouldrepresent children who had not received appro-priately timed booster doses. Data were not availableto the author regarding rates of tetanus immuniza-tion in England and Wales, but the magnitude canbe assumed to be of the same order as that for diph-theria and pertussis. Immunization rates are farfrom uniformly distributed within each country.For example, while 74% of the children between 1and 4 years of age received DTP in the United States,sections of the country varied considerably in theirrates. In the New England region, 81 %, and in thewest south-central region, 66% had received three

or more doses of DTP. Rates of 91 and 92% for bothdiphtheria and pertussis immunization in the 1stand 2nd years of life, respectively, attained in WestSussex, were well above the general rates forEngland. West Sussex has instituted an automaticdata-processing procedure to permit an intensivefollow-up of all infants (Ministry of Health, 1967a).

There are several factors which historically havedelayed the enthusiastic endorsement of combinedtriple antigen early in infancy, especially in GreatBritain. The use of DTP received a temporary set-back as a result of reports such as that prepared bythe Medical Research Council in 1956, which drewattention to the increased risk of provoking polio-myelitis with such injections (Ministry of Health,1964). The virtual disappearance of poliovirusfrom the community largely discounted this objec-tion. However, until recently, it was recommendedthat triple antigen be separated from oral polio-vaccine by 3 weeks (Ministry of Health, 1963). Thisin itself has complicated the orderly scheduling ofimmunization and required an increased numberof visits. Concern has been expressed regarding thenumber of important reactions (e.g. shock, neuro-logical damage) accompanying the pertussis com-ponent of the combined antigen, and this type ofevent is said to occur more frequently under the ageof6 months. Similar alarming suggestions concerningthe high rate ofneurological complications in Swedenhave been reported (Strom, 1960). In the UnitedStates, reactions to triple antigen administered inthe first 6 months of life as a routine measure haveresulted in very few documented instances of neuro-logical damage since 1952, when a ceiling was placedupon the antigenic content of pertussis vaccine bythe United States Public Health Service (Edsall,1961). The suggestion has been made that theprevalent antigenic strains of Bordetella pertussishave changed in the past few years, and that recentvaccine breakthroughs in England are largelyassociated with serotypes not represented in the

TABLE 3. Reported cases and deaths from diphtheria, tetanus and pertussis (5 years, 1962-66)Annual rates/million

CaseCases/year Deaths/year fatality* Cases Deaths

United StatestDiphtheria 285 36 13 1-5 0.19Tetanus 294 196 67 1-5 1.0Pertussis 12,481 86 0-69 64 0-44

England and Wales§Diphtheria 23 1-8 13 -47 0-04Tetanus 28$Pertussis 21,409 30 0-14 443 0-61* Deaths per 100 reported cases.t From United States Public Health Service (1967).t Tetanus is not reportable in England and Wales, therefore this figure probably underestimated the true incidence.

(Ministry of Health, 1967a).§ From Ministry of Health (1967a).

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Immunization in United States and Great Britain 151

vaccine (Preston, 1965). To date, there are no similarreports of antigenic shift in the United States.The average number of reported cases and deaths

from diphtheria, tetanus and pertussis for the5-year period 1962 to 1966 is recorded in Table 3.It can be seen that the number of diphtheria casesand deaths annually per million population issomewhat higher in the United States than inEngland and Wales. For pertussis, the death-rate isapproximately the same, although the number ofreported cases appears to be relatively lower inthe United States. Because the number of deaths isprobably a more reliable estimate of the true inci-dence of disease, and there is no obvious reason toexpect a different death-to-case ratio, one couldpostulate that there is a greater under-reporting ofpertussis cases in the United States. Under-reportingof a common, frequently mild and often undiagnoseddisease is not surprising for the United States, andthis phenomenon appears again in the discussion ofmeasles (see below). Fig. 1 illustrates the decline inmorbidity and mortality for diphtheria in the

Toxin-400- antitoxin

200Introduction

Case rate of toxoids800 A\ General use60 of toxoid40

20 Death rate10

6

4 -

0

2 - -20

n : 10o os ..'.... ..... ' _.: 80 0.6 Death-to-case ratio 60,

008 aA _006 \004 _ 00

\ °o

00.02

~~O.O·~~~~~ll001 )

0.0080 006

0-002 ~-00004

01001 19 1950 1960

1920 1930 1940 1950 1960 1970FIG. 1. Morbidity and mortality due to diphtheria in theUnited States, 1920-66 (United States Public HealthService, 1967).

United States from 1920 onward (United StatesPublic Health Service, 1967). The case fatality,however, has not similarly yielded to modern therapy.The historical data on diphtheria for England andWales available to the author would indicate asimilar pattern. Fig. 2 illustrates the geographicdistribution of diphtheria cases in the United Statesin 1966 (United States Public Health Service, 1967).Although general in distribution, the majority of the209 cases occurred in the south-eastern states andaffected primarily unimmunized segments of thepopulation. In urban as well as rural areas, diphtheriawas reported generally in lower socio-economicgroups. The epidemic in Rosebud County occurredin an Indian population.

PoliovaccineThe rates of immunization with poliovaccine are

shown in Table 4. Although the criteria for a primaryTABLE 4. Immunization with poliovaccine (1966)

3-OPV or 2-OPV andAge (years) 3-IPV 0 to 2 IPV

United States*1-4 White 73 82

Non-white 57 65Total 70 79

England and Walest1 682 723 76

OPV, Oral poliovaccine; IPV, inactivated poliovaccine.* From United States Public Health Service (1967).t From Ministry of Health (1967a,b).

course of vaccine are somewhat different, the overallrates are quite comparable. In the United States, inthe age group 1-4 years, approximately 70% havehad either three doses of oral or inactivated vaccineand 79% two doses of oral poliovaccine. It is notablethat the immunization rates are different in thewhite and non-white populations, reflecting thesocio-economic differential in the distribution and/oracceptance of vaccine. The overall rates in Englandand Wales for the early years of life are very close tothe United States data. The shift away from the useof inactivated poliovaccine is of interest. In 1966,less than 1% of the vaccine distributed in Englandand Wales was the inactivated type; in the UnitedStates, the figure was 17 %, compared to 20% in 1965.

Fig. 3 (United States Public Health Service, 1967)and Fig. 4 (Miller & Galbraith, 1965) show thedramatic decline in the incidence of poliomyelitis.In 1966, there were only nineteen cases of paralyticdisease in England and Wales, a record low. Thecases were sporadic, and no epidemic foci werereported. In the same year, 108 cases of paralyticdisease occurred in the United States, two-thirds of

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El Rosebud county

'

'-^ '' -I ID -Ir-^-. 9 "" ' . 22

Hawaii " ---""'7-Hawav .-^^OrRleons parishd county

fLafayette parish P R

Ha- Puerto Rice

FIG. 2. Geographic distribution of reported cases (*) of diphtheria in the United States, 1966 (United StatesPublic Health Service, 1967).

40 Inactivated 240Paralytic cases

.2 30o ;° t\Total 0 o

--41 00.5 1 1961 1962 1963 1964 1965 1966o 20 1-0

80 A \ .;\ Oral"I0O vaccine

0, 1I1941 1945 1949 1953 1957 1961 1965 1969

1943 1947 1951 1955 1959 1963 1967

FIG. 3. Total poliomyelitis and paralytic cases reportedin the United States, 1941-66 (United States PublicHealth Service, 1967).

which occurred in the state of Texas, where a type 1poliovirus epidemic occurred (Fig. 5). The caseswere concentrated primarily along the Mexicanborder. Seventy-five per cent of the paralytic caseshad received no poliovaccine, and only seven caseshad histories of adequate immunization. Surveillancein the United States since licensing of poliovaccineshas shown that no more than one case of 'vaccine-related' paralytic disease has occurred for every 3million does of oral poliovaccine administered, andthese have occurred largely in adult males (UnitedStates Public Health Service, 1967). In 1966, there

8000 r Salk vaccine Sobin vaccine

7000

6000

_ 5000

§ 4000

3000

2000 \

1000 \

1950. 1952 1954 1956 1958 1960 1962 1964FIG. 4. Total poliomyelitis and paralytic cases reported inEngland and Wales, 1950-64 (Miller & Galbraith, 1965)-, Total notifications; ..., non-paralytic cases.

were ten possible 'vaccine-related' cases of polio-myelitis reported in the United States. One wasrelated to the administration of inactivated polio-vaccine, the other nine to oral vaccine, on thebasis of the epidemiological criteria used. A similarstudy in England and Wales for the 3 years 1962 to1964 revealed four cases with residual paralysisoccurring between 5 and 28 days after vaccination,an incidence of one case in 4-5 million doses of livevaccine (Miller & Galbraith, 1965). Weighing thebenefits of poliovaccine against the minute risksinvolved, its routine use appears to be well justified.

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n-

FIG. 5. Geographic distribution of reported paralytic poliomyelitis cases (0) in the United States, 1966(United States Public Health Service, 1967).

TABLE 5. Immunization with smallpox vaccine

U.S.* England and Walest

1964 1964 1965 1966

Total immunizations (thousands) Primary 5420 340 390 480Revaccination 7370 70Unknown history 560

Per cent infants immunized 0-2 years 57 32 33 38

* United States Public Health Service (1967).t Ministry of Health (1967a).

Smallpox vaccineInfants were immunized with smallpox vaccine

at the rate of 32-38% in England and Wales in theyears 1964-66. In comparison, the rate in theUnited States in 1964 was 57% (Table 5). Fig. 6shows the smallpox immunization status of thepopulation in the United States. A rate of 80%was attained by school entry, and over 95% of thepopulation eventually received a primary vaccina-tion (United States Public Health Service, 1967).In England and Wales, the 480,000 individuals whoreceived primary smallpox immunization in 1966were equivalent in number to slightly more than

one-half the births for the year. In the UnitedStates in 1964, 5-4 million primary vaccinations weregiven, which is more than one and one-half times thenumber of births. In England and Wales, there wereapproximately 70,000 persons (1966) revaccinated,compared to 7-4 million revaccinations in the UnitedStates (1964). In the 10-year period 1951-60 inEngland and Wales, there was an average of 124,000revaccinations per year. In recent years in theUnited States, there have been approximately 3million individuals who have travelled overseas andreceived vaccinations on this account. Most of theseare revaccinations. Thus, while all the data which

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100

80

60

40

20 1

20 I i-- r--i--l--I-5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80

Aae (yeors)FIG. 6. Smallpox immunization status in the UnitedStates, surveyed in 1964 (United States Public HealthService, 1967). -, % vaccinated during lifetime;..., %vaccinated within past 12 months.

would be desirable are not at hand, indications arethat the population of the United States is morehighly vaccinated and revaccinated than that inEngland and Wales. However, in neither case arethe rates sufficiently high to have a dependable herdimmunity in face of an introduction of a case ofsmallpox.

In 1962, the Joint Committee on Vaccination andImmunization recommended that vaccination beperformed optimally during the 2nd year of life,rather than at 4-5 months, as previously practiced(Ministry of Health, 1964). Further, it was urgedthat smallpox immunization be universally adopted,because it was clear that the vaccination rate forsmallpox was well below that of other regular immu-nization procedures in infancy.

In the 10-year period 1957-66, in England andWales, there were 142 cases of smallpox, withtwenty-nine deaths, a mortality rate of 20-4%(Table 6) (Ministry of Health, 1967b). Theseresulted from eleven documented importations. In

TABLE 6. Smallpox in England and Wales, 1957-66*

KnownYear importations Cases Deaths

1957 1 4 21958 1 6 11959 11960 1 11961 2 21962 6 66 26

1963-651966 62

Totals 11 142 29

* Ministry of Health (1967b)

1966, there were four outbreaks of Variola minor.The origins of these apparently multi-centeredoccurrences were not determined. Between 1961 and1964, there were eleven instances of importation ofsmallpox into Great Britain, Germany, Swedenand Poland, resulting subsequently in a total of 222cases and thirty-nine deaths before effective controlwas achieved (Karzon & Henderson, 1966). Inmany of the introductions, half or more of thesubsequent cases were in hospital personnel.

In the United States, the last major outbreakoccurred in 1947 in New York City, from a caseimported from Mexico. The last potential introduc-tion occurred as recently as 1962, when a 12-year-oldboy from Brazil was admitted into the country atKennedy Airport in New York. He departedimmediately by train for Canada, where he becameill with typical smallpox shortly after arrival. Earlydiagnosis of the case, effective control measures, andan element of luck prevented the development ofsecondary cases (Karzon & Henderson, 1966).

Deaths, as well as central nervous and dermalcomplications of smallpox vaccination, in variousage groups are shown in Table 7. The data from

TABLE 7. Complications associated with primary smallpox vaccination

Illness/million primary vaccinations

Age (years) United States* England and Walest

Encephalitis Dermal Encephalitis Dermal

1 1-5 145 15 471-4 0-7 41 6-2 275-14 3-7 34 30 34

15t 2-3 48 15 64Overall rates 1.9 50 15 46

TotalsIllnesst 12 318 56 174Death 5 0 19 11

Rate/million vaccinationsIllness 51 60Death 0-8 7-9

*6,240,000 primary vaccinations (1963) (Neff et al., 1967b).t 3,820,000 primary vaccinations (1951-60) (Conybeare, 1964).t Illness includes deaths.

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TABLE 8. Comparative rates of complications associated with primary smallpoxvaccination or revaccination (per 1,000,000 vaccinated)

United States England and Wales$

U.S.* Four Statest

Primary vaccinationIllness 51 134 61Death 0-8 0 7-9

RevaccinationIllness 2-2 11 16Death 0 0 2-4* 6,240,000 primary and 7,780,000 revaccinations (1963) (Neff et al., 1967a).t 298,000 primary and 370,000 revaccinations (1963). An intensive survey which

reflects increased frequency of minor dermal complications (Neff et al., 1967b).: 3,820,000 primary and 1,240,000 revaccinations (1951-60) (Conybeare, 1964).

England and Wales was reported routinely to thehealth authorities (Conybeare, 1964); the UnitedStates data stemmed largely from the list of patientsfor whom vaccinia immune-globulin had beenrequested, death certificates, routine reports to statehealth departments, and a national physicianquestionnaire (Neff et al., 1967a, b). Based on thiscrude information, the incidence of encephalitis andthe overall death rate were higher in England andWales than in the United States. However, the rateof various types of dermal complications wasapproximately equal. Theoretically, half to two-thirds of the complications such as Eczema vaccina-tum and Vaccinia necrosum may be prevented bymore careful screening for known contraindications,and by delaying vaccination until after the 1st yearof life. Contraindications include patients withdepressed immune-response, either spontaneous ordrug-induced; pregnancy; simultaneously admini-stered live vaccines; and skin diseases, such aseczema, in the recipient or household contact. Ingeneral, there were approximately one death permillion primary vaccinations in the United States,and fifty-three total complications per million.There were no deaths and 2-2 complications permillion among 7-8 million revaccinees. In England,the death rate was somewhat less than eight permillion, and the complications rate about sixty-oneper million. There were 2-4 deaths and sixteencomplications per million after revaccination. Thus,in both countries, revaccination was accompaniedby a very small risk compared to primary vaccination(Table 8).

In another study, physicians in four states weresurveyed by questionnaire concerning major andminor complications associated with smallpoxvaccination. A significantly higher rate of Eczemavaccinatum and generalized vaccinia of a mild naturewas uncovered. A total of 134 complications wasreported per one million primary vaccinations andeleven per million revaccinations. Of the reported

279 patients with available data, only twenty-twowere hospitalized (Neff et al., 1967b) (Table 8).The incidence and mortality from central nervous

complications in both England and the United Statesis clearly less than that reported from certain othercountries. In several studies reported from thecontinent, rates as high as one case in 1000 primaryyoung adult vaccinees have been documented. Thereis no satisfactory explanation for this significantvariation in incidence, although it should be notedthat different strains of vaccinia virus are employedin various countries. The recommendation to deferimmunization to the second year was based uponstudies of Conybeare (1964), in which it was shownthat encephalitis as well as dermal complications arefar more frequent under 1 year of age than in thesecond year of life. Similar studies in the UnitedStates have also shown an excessive risk in childrenunder 1 year of age (Table 7) (Neff et al., 1967b).

In the United States, official policy has alwaysbeen rather firm in advocating universal smallpoximmunization, although this policy has beenincreasingly questioned (Dixon, 1962; Dick, 1962;Kempe & Benenson, 1965). Despite the requirementfor a valid vaccination certificate, the possibility ofintroduction of a case into the United States is areal one. This risk is constantly changing, withincreasing travel, but with a decreasing reservoir ofendemic smallpox. Immunization to the fullestpossible extent of infants and pre-school children isa principal means for community protection againstintroduced smallpox. Successfully vaccinated chil-dren should be essentially wholly immune for perhaps3-5 years, with decreasing protection for a longerperiod. With primary sensitization accomplished,revaccination of older children and adults is attendedby a much lower frequency of complications. Shoulda case of smallpox be introduced and recognized,subsequent control is accomplished by quarantineand selective vaccination; mass vaccination is con-sidered inadvisable. Partial immunity of the popula-

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tion as a result of previous vaccination offers certainadvantages, in that the likelihood of spread in thecommunity is diminished, and the antibody responseto revaccination is more rapid and attains a highertiter (Ministry of Health, 1963). The value of chemo-prophylaxis (methisazone) as an aid in epidemiccontrol is not established, and the use of the drug isaccompanied by a significant incidence of toxicity.

Measles vaccineLive attenuated measles virus vaccine became

available in the United States in 1963, and morethan 30 million doses were distributed by thebeginning of 1968. In late 1966, an intensive pro-gram was initiated, supported largely by the VaccineAssistance Act, to eradicate measles in the UnitedStates. This was conducted through regular publicand private immunization channels as well asthrough special community campaigns, the latterespecially in areas with low immunization rates.Also, epidemics have been effectively aborted by theprompt administration of measles vaccine to selectedgroups of children, especially susceptibles in nurseryschool, kindergarden, and the first two or threegrades of elementary school. The effectiveness of thetotal national effort is demonstrated in Fig. 7

III III III III III*II Il

120 I III III IIIMeasles vaccine 11

100 -licensed MarchI 1963V 80

60

u 400

1962 1963 19641965 1966 1967 19681962 1963 1964 1965 1966 1967 1968

FIG. 7. Reported cases of measles in the United States,1962-67, and distribution of live measles vaccine (UnitedStates Public Health Service, 1968a). Blocks, 1 milliondoses. *Estimated total for 1967.

(United States Public Health Service, 1968a). Thenumber of reported cases of measles in 1967-68 islower than any year since the onset of measlesreporting in 1912, and is less than 10% of theexpected incidence. The long-term trends are shownin Fig. 8.A high percentage of pre-school children have

now been immunized. In areas where specialcampaigns have been conducted, the rates are veryhigh; for example, 94% in Los Angeles County and91 % in the state of Rhode Island. Other statesreported between 50 and 80% of the pre-schoolpopulation immunized at the end of 1967 (United

coo600400

I DtIAl-A

20

Cases

006

0-040A

0020-01

I2 195 I0 192 1930 1935 1940 1945 1950 1955 1019o 1970

FIG. 8. Reported measles cases and deaths in the UnitedStates, 1912-67. Live measles vaccine was licensed in1963 (United States Public Health Service, 1968c).

States Public Health Service, 1968a). Approxi-mately thirty states report rates of 90% or more inschool-aged children, a direct result of school-wideprograms (United States Public Health Service,1968a).Some of the factors concerning the problems of

introducing a new immunizing product into thepopulation are illustrated in a study of measlesvaccine in Erie County, New York, population1 million (Lennon et al., 1967). A survey wasconducted in 1966, 3 years after the licensing of livemeasles virus vaccine, but prior to the launching ofthe intensive national effort to eradicate measles.The immunization rates reflected distributionthrough normal channels of health care. The surveyshowed that 82% of the vaccinations were receivedfrom private physicians, 15% through health de-partment clinics and 3% from other medical facili-ties, such as hospitals. There was a sharp division ofthe rate of immunization of susceptible children bysocio-economic group. In the urban area, 73% ofthe upper, 57% of the middle and 19% of the lower,socio-economic group were immunized. As a conse-quence of these findings, an intensive campaign toimmunize the lower socio-economic group in ErieCounty, concentrated in the core area of the City ofBuffalo, was successfully instituted.

Prior to the introduction of vaccine, approximately400,000 cases had been reported annually in theUnited States. Because 90-95% of all young adultshave a history of clinical measles, it may be assumedthat, if all cases were reported, almost 4 million

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cases should be reported per year. It may thus becalculated that somewhat over 10% of clinical casesare in fact reported. Since the introduction ofmeasles vaccine and the initiation of more carefulsurveillance, the percentage of cases reported hasundoubtedly improved beyond this figure. InEngland and Wales, a similar number, over 400,000cases a year, are reported. On the basis of the sametype of calculations, one can estimate that almosthalf of the cases of clinical measles are thereforereported. In recent years (prior to vaccine introduc-tion) there have been 300-400 measles deathsannually in the United States, and approximately50-150 deaths annually in England and Wales.Thus, in both countries, the mortality from measleshas been approximately two per million populationannually.

Measles vaccine became available in Great Britainearly in 1966. Clinical trials of live vaccine precededby inactivated vaccine have indicated that a betterdegree of long-term protection can be expected fromlive vaccine alone. The untoward effects observed inthe United States in children who had receivedmultiple doses of inactivated vaccine and then,after several years, were given live measles vaccineor were exposed to natural measles have so far notbeen observed in Great Britain. There is a strongcase for the use of live measles virus vaccine alone.The desirability of adopting a vigorous nationalpolicy for the elimination of measles was proposedby the Ministry of Health recently (1968a). All sus-ceptible children through the age of 15 years arerecommended to receive a dose of live attenuatedvirus. This should be given during the 2nd yearof life and not earlier than 9 months of age.Other vaccinesComments concerning the use of certain vaccines

which are used only under special circumstances maybe of interest. The status of the vaccines in theUnited States will be compared to that in GreatBritain whenever possible.

While exposure to rabies in the United Kingdomwould be exceptional, rabies is a problem of signi-ficant proportions in the United States. Fig. 9 showsthe trends in animal rabies in the United States from1953 to 1966. Rabies in domestic animals, largelydogs, livestock and cats, has fallen sharply, whilethere has been an increase in rabies in wildlife,especially skunks, foxes, and bats (United StatesPublic Health Service, 1967). However, the numberof human deaths from rabies declined from thirty-four in 1946 to one or two annually in recent years.This decline has resulted in great part from a reduc-tion in rabies in dogs through immunization (UnitedStates Public Health Service, 1967). As prophylaxisfollowing proven or assumed exposure, an estimated

FIG. 9. Reported rabies in domestic and wild animals inthe United States, 1953-66 (United States Public HealthService, 1967). -, Total; ..., wild; -- -, domestic.

30,000 persons received rabies vaccine and approxi-mately 8000 also received anti-rabies serum in 1966.BCG is recommended for tuberculin-negative

children between the ages of 10 and 13 years, at thediscretion of the Medical Officer of Health in Englandand Wales. In certain areas, BCG is given as aroutine in infancy. On the other hand, BCG vaccinein the United States is advised only for infants orchildren who are at special risk of known heavyexposure to tuberculosis in their immediate environ-ment, and, as a consequence, is used far less fre-quently. In England and Wales in 1966, 640,000school children and tuberculosis contacts were skin-tested. Five hundred and fourteen thousand werefound to be tuberculin-negative, and of these,479,000 were vaccinated with BCG. Twenty-nineper cent of contacts and 14% of school childrenwere tuberculin-positive. In 1966, there were approxi-mately 15,000 tuberculosis notifications in Englandand Wales, or a rate of twenty-one per 100,000population (Ministry of Health, 1967a). In theUnited States, there were approximately 48,000 newactive cases, or a rate of twenty-four per 100,000(United States Public Health Service, 1968b), witha low of 6-5 in North Dakota and a high of 55-5 inAlaska. At the end of 1966, there were 316,000 casesunder supervision because of a tuberculous lesion inEngland and Wales, and at the same time there were320,000 persons in the United States on state andlocal health department tuberculosis registers.There are undoubtedly significant differences inrecording and classification contributing to thesedata, and they may not be directly comparable.The general recommendations for the use of

influenza vaccine are quite similar in the twocountries-namely, for the protection of thoseindividuals suffering from certain chronic diseases forwhom influenza might prove to be an unusual medi-cal risk. In addition, in the United States, all in-dividuals over the age of 65, a group in which there

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is excess mortality accompanying influenza epi-demics, are recommended to have annual doses ofinfluenza vaccine. Influenza vaccine is not recom-mended for general use in the population.The live attenuated mumps virus vaccine was

introduced in the United States early in 1968.Seroconversion and clinical protection have beendemonstrated in field trials to last for at least 3years, which is the longest period of follow-up. Theproduct appears to be free of toxicity. The long-termduration of protection is under continued study.The United States Public Health Service AdvisoryCommittee on Immunization Practices has suggestedthat live mumps vaccine be considered for use inchildren approaching puberty, in adolescents, andin adults, especially males, if they have not hadmumps (United States Public Health Service, 1967).The vaccine should also be considered in certaininstitutional settings. The vaccine is not recom-mended for routine use in younger children, althoughit is not specifically contraindicated. The rationalefor the use of mumps vaccine lies in the preventionof certain complications. Approximately 15% ofreported cases of mumps occur after the onset ofpuberty. Orchitis has been observed in 20% ormore of post-pubertal males, and other organsystems, including the central nervous system, areoccasionally involved. Sequelae are uncommon,although unilateral deafness is not a rare event(Karzon, 1968a). In terms of public health priorities,the Advisory Committee has stated that mumpsimmunization programs should not pre-empt otherpublic health programs of established importance.However, should observation confirm the long-termeffectiveness and freedom from toxicity, it may bepredicted that increasing use will be made of mumpsvaccine, both in privatepractice and publicprograms. *

A live attenuated rubella virus vaccine is at thepresent time undergoing field trials in the UnitedStates in closed and semi-closed populations. Ser-conversion and clinical protection are of a highorder. The attenuated virus replicates and can berecovered from the pharynx, although it does notappear to be transmissible. Studies are continuingto evaluate the safety of the rubella vaccine in theopen population and in adults, before a licensedproduct can be made available.

Simultaneous use of immunizing agentsThere are several factors which have tended to

support the recommendation that administration of* Recently, the Advisory Committee has liberalized its

recommendations for mumps vaccine and suggests considera-tion be given to immunizing all susceptible children over1 year of age. However, the position was reaffirmed thatmumps vaccine programs should not be allowed to takepriority over essential ongoing health activities. U.S. PublicHealth Service (1968d).

immunizing agents be separated whenever feasible,especially when one is a live vaccine. The bases forthis recommendation are two-fold: (1) possible inter-ference between two or more antigens, and (2)possible enhancement of toxicity. An example of thelatter is the provocation effect of DTP on polio-myelitis infection. It is recommended that admini-stration of two live vaccines be separated by 4weeks in the United States and 3-4 weeks in Englandand Wales. The need for separation of antigens iscausing an increasing hardship in scheduling visits ofsmall infants. In the United States there are four liveproducts-poliovirus, measles, smallpox and mumps-and a fifth live product, rubella, may soon beavailable. It is, therefore, of more than theoreticalinterest to determine the legitimacy of the objectionswhich have been raised to simultaneous use of livevaccines. Studies are in progress to explore theantibody responses to multiple vaccines and possibleenhancement of toxicity. If simultaneous administra-tion were feasible, a multivalent product would beof great public health significance. The earliestschedules of vaccination and immunization pro-cedures suggested by the Ministry of Health. In therecommended that DTP and live vaccine other thanlive poliovaccine be separated by 3-4 weeks. Such arestriction has not been placed in the United States,and at the present time no ill-effects have beendocumented from simultaneous DTP and livevaccine administration. Recent studies have shownthat measles or yellow fever vaccine virus maydepress, at least in part, the replication of a secondvirus, presumably on the basis of interferon produc-tion. The maximum inhibition is during the secondweek following administration of the first virus.Thus, the recommendation that yellow fevervaccine be given at least 4 days before primaryvaccination against smallpox (Ministry of Health,1967a) may be expected to decrease the effectivenessof the smallpox take and antibody response (Karzon,1968b).Discussion and conclusions

There has been a consistent downward trend inthe morbidity, mortality and residua due to mostinfectious diseases in the developed countries of theworld. Improvements in the social and economicsphere and the control of environmental humanwaste and arthropod vectors have played majorroles. However, the widespread use of immunizingagents has notably contributed to this decline.Society is becoming increasingly expectant thatpreventable disease will indeed be prevented.The present review is a modest beginning in the

effort to relate official policy on immunizationpractice in the United States and England andWales, and the actual use of various biological

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Immunization in United States and Great Britain 159

products, with trends in morbidity and mortality ofpreventable diseases. The settings for the study forman interesting backdrop. Child health practices arequite distinct in England and Wales under the tri-partite National Health Service Program, whencompared to the United States, where a combinationof the board-certified pediatrician and the generalpractitioner, as well as public agencies such as thewell-baby clinic and hospital outpatient department,all participate in aspects of preventive and curativemedicine. Through the two different pathways,similar mechanisms for evaluation of optimalimmunization schedules have evolved. Also, it isincreasingly evident that the specific recommenda-tions have drawn more closely together. There havebeen minor differences of emphasis. For example,the American philosophy has shown less concernwith immunodepression due to maternal antibodyand immunological immaturity and has regularlyimmunized beginning at 8-12 weeks, with combinedvaccine, adding a third dose to increase efficiencyof the program. In Great Britain, there has evidentlybeen a greater concern regarding the risks ofsmallpoximmunization, which has resulted in the lower levelsof immunization attained with smallpox vaccine.The very conspicuous disparities in immunization

rates, based upon social class and reflected in lowimmunization rates in such areas as urban Negroghettos and rural poverty areas, have posed one ofthe major residual public health problems in in-fectious disease control in the United States. It wouldbe of interest to study the acceptance of various im-munizing procedures by social class in Great Britain,to determine whether the freely available servicesmay be unevenly distributed in a similar fashion,based on cultural and behavioral characteristics ofpopulation groups. For example, poliomyelitis in theUnited States, once a disease with relative selectivityfor the upper classes with a high level of environ-mental and personal hygiene, is now a disease of thelower classes, in residual pockets with inadequateimmunization. It has been generally observed thatimmunization rates in a given population bear adirect relationship to the general extent of contactbetween the infant and those charged with early childhealth care. That is, children who attend a physicianonly for episodic illness and do not receive regularwell-baby care will have poorer immunizationrecords. A corollary of this would state that im-provement of the general level of immunizationwould be tied to an improvement in the general levelof infant care and regularity of contact betweenthe family and health facilities. However, the lattersituation is not always simple to achieve, and moredirect efforts aimed specifically at attaining higherimmunization rates can be successful, both as singlemass community campaigns or in some form of

ongoing program.It is hoped that the information presented and the

interpretations which have resulted will be a stimulusfor others to continue to study comparative im-munization practices.

AcknowledgmentsThis paper could not have been written without the help

and advice of Dr A. T. Roden of the Ministry of Health, whokindly provided much of the published and unpublishedinformation from England and Wales. For data from theUnited States, I have leaned heavily on the Reports of theNational Communicable Disease Center of the United StatesPublic Health Service. In particular, I would like to thankDr F. Robert Freckleton and Dr Alexander Langmuir andtheir staffs for their encouragement and for permission to usedata placed at my disposal. For errors in presentation orinterpretation, I lay personal claim. Morbidity and mortalityinformation has been obtained from publications of theMinistry of Health, for which I would like to make acknow-ledgement to the Controller of Her Majesty's StationeryOffice.Dr Karzon is recipient of a Research Career Award

(AI-1136) from the National Institutes of Allergy andInfectious Diseases, United States Public Health Service.

ReferencesAMERICAN ACADEMY OF PEDIATRICS (1966) Report of theCommittee on the Control of Infectious Diseases.

CONYBEARE, E.T. (1964) Illnesses attributed to smallpoxvaccination, 1951-1960. Monthly Bull. Minist. Hith Publ.Hith Lab. Serv. 23, 126 and 150.

DICK, G.W.A. (1962) Prevention of virus diseases in thecommunity. Brit. med. J. ii, 1275.

DIXON, C.W. (1962) Vaccination against smallpox. Brit. med.J. i, 1262.

EDSALL, G. (1962) Efficacy of immunization procedures usedin public health practice. Wld Hlth Org. Pbl. HlthPapers No. 8, p. 51.

FRECKLETON, F.R. (1967) Federal government programs inimmunization. Arch. environ. Hlth, 15, 512.

GREoG, A. (1949) The golden gate of medicine. Ann. intern.Med. 30, 811.

KARZON, D.T. (1968a) Rationale for mumps vaccine usage.Proc. Fifth Annual Immunization Conference, San Diego,California, United States Public Health Service. 12 March,1968.

KARZON, K.T. (1968b) Simultaneous administration of liveantigens. Proc. Fifth Annual Immunization Conference, SanDiego, California, United States Public Health Service. 12March, 1968.

KARZON, D.T. & HENDERSON, D.A. (1966) Current status oflive attenuated virus vaccines. Advanc. Pediat. 15, 121.

KEMPE, C.H. & BENENSON, A.S. (1965) Smallpox immuniza-tion in the United States. J. Amer. med. Ass. 194, 161.

LENNON, R.G., TURNBULL, C.D., ELSEA, W.R., KARZON,D.T. & WINKELSTEIN, W., JR. (1967) Measles immunizationin a northeastern metropolitan county. J. Amer. med. Ass.200, 815.

MILLER, D.L. & GALBRAITH, N.S. (1965) Surveillance of thesafety of oral poliomyelitis vaccine in England and Wales1962-4. Brit. med. J. i, 504.

MINISTRY OF HEALTH (1955) Annual report of the ChiefMedical Officer for the Year 1954., p. 66, H.M.S.O.,London.

MINISTRY OF HEALTH (1963) Active immunisation againstinfectious disease (prepared by Standing Medical AdvisoryCommittee).

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MINISTRY OF HEALTH (1964) Annual report of the ChiefMedical Officer for the Year 1963, p. 170, H.M.S.O.,London.

MINISTRY OF HEALTH (1967a). Annual Report of the ChiefMedical Officer for the Year 1966, pp. 30 and 243,H.M.S.O., London.

MINISTRY OF HEALTH (1967b) Memorandum on VaccinationAgainst Smallpox. Memo 312/MED, H.M.S.O.

MINISTRY OF HEALTH (1968a) Circular 29/68.MINISTRY OF HEALTH (1968b) Letter to General Practitionersand all Medical Officers of Health (England and Wales),G. E. Godber.

NEFF, J.M., LANE, J.M., PERT, J.H., MOORE, R., MILLAR,J. D. & HENDERSON, D. A. (1967a) Complications of small-pox vaccination. I. National survey in the United States,1963. New Engl. J. Med. 276.

NEFF, J.M., LEVINE, R.H., LANE, J.M., AGER, E.A., MOORE,H., ROSENSTEIN, B.J., MILLAR, J.D. & HENDERSON, D.A.

(1967b) Complications of smallpox vaccination, UnitedStates, 1963. II. Results obtained by four statewide surveys.Pediatrics, 39, 916.

PRESTON, N. W. (1965) Effectiveness of pertussis vaccines.Brit. med. J. ii, 11.

STROM, J. (1960) Is universal vaccination against pertussisalways justified? Brit. med. J. ii, 1184.

UNITED STATES PUBLIC HEALTH SERVICE (1967) Immuniza-tion Against Disease, 1966-67 (Prepared by NationalCommunicable Disease Center).

UNITED STATES PUBLIC HEALTH SERVICE (1968a) Personalcommunication.

UNITED STATES PUBLIC HEALTH SERVICE (1968b) Morbidityand Mortality Weekly Report, March 30.

UNITED STATES PUBLIC HEALTH SERVICE (1968c) Morbidityand Mortality Weekly Report, June 8.

UNITED STATES PUBLIC HEALTH SERVICE (1968d) Morbidityand Mortality Weekly Report, October.

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practice in the United States and Great Britain