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Measles antibody titres were determined by haemagglutination inhibition and by neutralization in 221 sets of serum collected from delivering mothers, umbilical cords, and infants when about six months of age. Radio-immunoassay was also used to measure antibody in 120 sera. Total IgG concentration was determined in the infant sera. All mothers had measles antibody and the mean titre was high. At the time of birth, measles antibody had been further concentrated in the infant. Nevertheless, many children lost protective titres before six months of age. The rate of loss was correlated with the infant's total serum IgG so that high IgG levels at six months correlated with rapid loss of measles-specific antibody. It is suggested that in homes where sanitation is poor, antibody is made to many agents at an early age. To maintain physiological balance, homeostatic mechanisms then increase the rate of catabolism of all IgG, including that passively acquired. In keeping with its stage of sanitary development, vaccination in Jamaica can profitably be given earlier than in the United States, but it must be later than in many African countries.

A version of the Western blot was developed to detect serum antibodies against measles virus polypeptides. With this technique, a seroepidemiological survey of antibodies to the several measles virus proteins in diverse measles-related conditions was conducted. The sera were obtained from individuals with a recent or long-past history of natural measles, from persons with a history of immunization with live attenuated measles vaccine, and from patients with multiple sclerosis, subacute sclerosing panencephalitis, or atypical measles. The findings indicated that live attenuated measles vaccine elicits an antibody response qualitatively resembling that of a natural infection. In addition, multiple sclerosis patients made less antibody to the measles virus M protein than did individuals with a long-past history of natural measles. Thus, the immunological reaction of multiple sclerosis patients to measles virus is qualitatively, as well as quantitatively, different from that of normal persons. Finally, persons with subacute sclerosing panencephalitis and atypical measles mounted abnormally high antibody responses to measles virus polypeptides, in particular the P protein.

Children vaccinated when aged between six and thirteen months against measles in Taipei showed a high frequency of response, similar to that reported from Nairobi, Kenya and contrasting with analogous data for the USA. The age for optimal protection against measles mortality by a single dose of vaccine in this group of children is nine months. Maternal antibody exerted a negative effect on measles antibody titre in vaccinees beyond the age at which it blocked the response so that the infants of mothers with the higher titres themselves had lower titres. A separate effect of immunological immaturity on titre of the response could not be demonstrated in children over six months of age.

'The simplest of all virus disease is measles' said Kenneth Maxy 40 years ago in a chapter on epidemiology. I hope that the data set out here provide the reader with a sufficiently complete and clear picture of the factors that determine measles epidemiology, that he or she will agree with Maxy's prescient words. Measles is an antigenically complex virus, but few components of the immune response to this virus are epidemiologically relevant. The relevant components are durable for a lifetime. They can be conveniently measured by serological tests, and the results of these tests correlate well with measles immunity. The tests show that measles is an extremely infectious disease, and that very high antibody prevalence rates are needed for herd protection. The currently available measles vaccine is capable of yielding adequate antibody prevalence rates for herd immunity, but to achieve this, immunization procedural flaws and faulty records must be kept to very low levels. The greatest obstacle to worldwide control of measles is a failure of vaccination programs to produce adequate herd immunity levels in less-developed countries. There, vaccine must be given promptly after passive immunity wanes, because the level of endemicity is so high. It is difficult to determine just what age is optimal, because it varies from one country to another. Premature vaccination not only fails to immunize, but also interferes with subsequent re-immunization. Because we now know this, further direct tests of vaccine effectiveness in very young children are ethically undesirable, and methods that use determination of passively acquired antibody are to be preferred. The levels of antibody that mothers have to pass to their children vary considerably. These differences are important in comparisons of South Asian countries with others, but not elsewhere. Differences in efficiency of transport of antibody across the placenta also play a role, but usually a minor one. Most important seems to be variation in antibody durability in the infant. Where families are poor, the children acquire many infections at an early age, and passively acquired antibody is swept out. These children who are least able to withstand the effects of measles infection, are hit at the earliest age. To provide protection for them, the vaccine must be given at a carefully determined age, specific for each community. Only when this is done can we hope to reduce measles worldwide to a sufficiently low level that it will be removed as a threat to persons in the United States, or anywhere else.

Maternal and cord measles and rubella antibodies were compared in 15 populations from Brazil, Ecuador, Chile, India, Jordan, Nigeria, South Africa, Taiwan, and the United States. Review of the literature concerning these countries showed that a higher proportion of children 6-12 months of age responded immunologically to measles vaccine in areas with low per capita product than in wealthier populations. The authors show that this difference reflects differences in maternal antibody titer and differences in efficiency of transport of measles immunity across the placenta. No variation in the half-life of passive measles immunity in the infant was found in comparing three geographic areas. When these biologic factors are fully evaluated, it should be possible to predict the response to be expected from vaccination at any particular age without directly testing the vaccine in children below and above generally recommended ages for vaccination. With regard to rubella, high antibody prevalence rates were found in most of the developing countries, as well as in the United States, and these countries are therefore unlikely to encounter widespread problems with congenital rubella. However, Taiwan, and all of four areas of Brazil have prevalence rates which are no higher than those which pertained in the United States prior to establishment of the rubella immunization program. The authors believe that protection of the infants in these countries is a matter of high priority, but that, if approached hastily, it could exacerbate the problem.

Measles vaccine cannot give high sero-conversion rates in developing countries. The high birth rates characteristic of these countries lead to infection at a very early age, thus making it difficult to vaccinate before exposure to the disease. Nevertheless, if given early in life, the vaccine can reduce the rate of virus circulation and thus raise the age at which children are infected. Once that is done, higher sero-conversion rates can be obtained by raising the age at vaccination. During the period when vaccine is given at an early age, the titers in responding children will be low, and this will leave children of the next generation with little protection. It is important, therefore, that if vaccine is used early the program be intensively and consistently applied to control virus circulation before the next generation is born.

This report describes a follow-up serological study of 79 Brazilian children who, because of their young age, had failed to develop protective levels of immunity after vaccination against measles. There was serological evidence that infection with wild virus had occurred at a rate of about 17% per annum. Approximately 1(1/2) years after the initial vaccination, 46% of the uninfected children maintained very low levels of neutralizing antibody, but did not have a measurable haemagglutination-inhibition titre. Revaccination did not elicit an IgM response in most children, but stimulated anti-measles IgG production in all of them. In 36% of the children, the IgG titres fell again within three months to levels that may permit reinfection. If it is assumed that some of the persistent titres can be attributed to wild virus infection, the actual effect of revaccination would have been to immunize no more than 60% of the susceptible group. The results suggest that early administration of measles vaccine may produce a cohort of children with inadequate immunity who cannot be fully immunized by revaccination. The implications of these findings for measles immunization programmes are discussed.

Vaccine induced measles antibody titers in the Upper Xingu Indians remained at satisfactory levels without evidence of decline over a period of six years without re-exposure. However, in another area, a vaccination program which used a reduced dose of vaccine was only 63% effective. When measles virus was introduced to the latter area a protracted epidemic ensued with 23% of the population becoming ill and six deaths. The deaths occurred exclusively under 13 months or over 40 years of age.

Measles hemagglutinin-inhibiting and neutralizing antibody titers are lower in women young enough to have been immunized by vaccination than in older women. In the children of both young and older mothers the antibody is concentrated 1.7-fold across the placenta, and the child's initial titer remains proportional to that of its mother. The transferred antibody is diluted by the baby's growth and degraded with a mean half-life of 48 days. By 8 1/2 months of age, 95% of the children of the mothers born since 1963 would have become susceptible to measles and responsive to immunization; the same level of susceptibility is not reached by children of mothers born before 1958 until 11 1/2 months of age. Among the offspring of younger mothers, a small group remains, about 2% of the total, with titers high enough to provide protection for 12 months, and these children would be poorly served if the age for vaccination were reduced for all. However, selective early vaccination of children of young mothers who have low antibody titers would eliminate an important focus of measles susceptibility.

Measles in an unvaccinated virgin population exacted a death toll of 4.2% which fell particularly hard on the age groups which would ordinarily be protected by maternal antibody. The organ system most affected was quite variable. When the virus spread to a largely vaccinated village it caused only one death. Herd immunity seemed to protect many who were not vaccinated. Vaccine failed to protect 7.7% of the recipients. Some of these failures may have been due to erroneous record, vaccination in the presence of maternal antibody or inactivated vaccine, but most occurred in a few family groups related by genetics and similar past immunological experience.

Measles has had particularly serious effects when epidemics have occurred in isolated susceptible adult populations and hence the newly developed measles vaccines may be of special importance to these groups. This paper reports on one of the first sizeable trials of live-virus vaccine (Enders Edmonston B strain) in a group of measles-susceptible adults. Over 700 persons, mostly adults, were vaccinated in Iceland in 1962. Detailed records of the reactions in the vaccinated and control groups were obtained and serological tests were made on paired serum specimens. The reactions in all age-groups were basically similar and showed only minor differences in severity. The incubation period was found to increase progressively with age. As well as confirming the general safety of the Enders live measles virus vaccine in adults, this study provides new information on the nature of the reactions induced by measles vaccine and on the comparative immunological response of various age-groups.