The results of multiyear observations on the duration of the maintenance of immunity in those vaccinated and revaccinated against and recovered from measles

The results of 5-year observations on the duration of immunity to measles virus in persons vaccinated and revaccinated against measles, as well as in persons having had this infection, are presented. The intensity of immunity was determined in the same persons with the use of the passive hemagglutination test. The study revealed differences in the formation, intensity and duration of postvaccinal immunity. A significant decrease in the concentration of antibodies over the period of 5 years was established in 50.0-52.3% of vaccines. Revaccination with live measles vaccine is an effective measure for enhancing immunity to measles virus in persons with initial antibody titers less than 1:10-1:20, but revaccination made in a single injection is not sufficient for the stable maintenance of measles morbidity at the sporadic level. Postinfectious immunity is characterized by stability and has no tendency towards decrease. Persons having had measles have no need in additional measures irrespective of the time elapsed after the disease.     

Epidemiological and immunological study of the foci of measles infection

Anamnestic data in respect to measles failed to correspond to the results of serological examination of contacts at the foci of the given infection. The collective immunity level in children's institutions is inadequate for the prevention of measles outbreaks. The incidence of the disease depended both on the level of immunity among the children and on the duration of presence of the source of infection in the focus. Live measles vaccine protected 90 percent of the vaccinated children from contracting the disease in the foci. At the very beginning of the postvaccinal period immunization defects were revealed in 26.5 percent of the vaccinated children who fell ill with measles. Morbidity index among the vaccinated individuals constituted 3.8 percent. One of the causes of measles contraction by the vaccinated individuals was the loss of postvaccinal immunity. Systematic control over the antimeasles immunity level with the aid of serological investigations is necessary for the purpose of detection of persons sensitive to measles in children's collective bodies.     

Basic patterns in the epidemic process of measles under conditions of massive immunization]

Observations over the measles epidemic process in Leningrad showed that the sporadic morbidity level reached in 1974--4.1 per 100 000 residents; however periodic elevation and decline of morbidity and tis seasonal variations persisted. A rise of morbidity in 1972--1973, and by preliminary data--in 1975, occurred on account of the older age groups. There was revealed no dependence of the disease incidence among the persons vaccinated on the time lapse after their vaccination. Individual batches of live measles vaccine issued in 1963--1969 were not up to the standard, this serving as one of the cases of the occurence of group incidence of the infection in some foci.     

Immunoepidemiological observations on the duration of post-vaccinal immunity in children vaccinated against measles

In the course of 4 years the authors carried out an immunological and epidemiological observation over 4719 children which attended creches, kindergartens and schools, and were vaccinated with live measles vaccines L-16 and ASC in 1967--1972. A stable persistence of immunity was revealed in the majority of children vaccinated against measles which responded to the vaccination by the formation of humoral antibodies. Among these groups an insignificant number of persons with the appearance of measles sensitivity was noted during the observation period. The quality of the preparation, conditions of its storage, use, and different errors during the vaccination influenced the efficacy of the vaccination. Children immunized with the low-immunogenic series of the vaccine whose blood sera failed to display any specific antibodies in the reaction with 1 AU of the antigen, as a rule, were the ones that contracted the disease.     

Materials on the serologic study of children inoculated with live measles vaccine

The results of serological examination of children, residents of Leningrad, vaccinated with live measles vaccine, are presented. A total of 2012 children were examined. Antibodies were absent in children of different age in 4.2--15.8% of cases. The greatest percentage of secronegative children (15) was noted among those vaccinated at the age of under one year. The mean geometrical antibody titres were the greatest in children aged from 7 to 14 years. The values of these mean titres were less in children vaccinated at the age of under one year than in those vaccinated later--6.5--8.6 and 10.6--11.3, respectively.     

Analysis of a measles epidemic; possible role of vaccine failures.

A measles epidemic occurred in the Greensville (Ont.) Unit schools during January and February 1975. There were 47 cases of measles in 403 students: 26 (55%) of the children had a history of being vaccinated and 18 (38%) had not been vaccinated. Among children known to have been vaccinated at less than 1 year of age 7 of 13 contracted measles, while among the 48 children who had not been vaccinated 18 contracted measles. The attack rate among vaccinees increased with increasing time since vaccination. The observations of this study as well as those of similar studies suggest that vaccine failures contributed to the genesis of the epidemic. It is recommended that all children initially vaccinated at less than 1 year of age should be revaccinated with live attenuated measles virus vaccine.     

Measles outbreak in 31 schools: risk factors for vaccine failure and evaluation of a selective revaccination strategy.

OBJECTIVE: To examine the risk factors for measles vaccine failure and to evaluate the effectiveness of a selective revaccination strategy during a measles outbreak. DESIGN: Matched case-control study. SETTING: Thirty-one schools in Mississauga, Ont. SUBJECTS: Eighty-seven previously vaccinated school-aged children with measles that met the Advisory Committee on Epidemiology''s clinical case definition for measles. Two previously vaccinated control subjects were randomly selected for each case subject from the same homeroom class. INTERVENTIONS: All susceptible contacts were vaccinated, and contacts who had been vaccinated before Jan. 1, 1980, were revaccinated. When two or more cases occurred in a school all children vaccinated before 1980 were revaccinated. MAIN OUTCOME MEASURES: Risk of measles associated with age at vaccination, time since vaccination, vaccination before 1980 and revaccination. RESULTS: Subjects vaccinated before 12 months of age were at greater risk of measles than those vaccinated later (adjusted odds ratio [OR] 7.7, 95% confidence interval [CI] 1.6 to 38.3; p = 0.01). Those vaccinated between 12 and 14 months of age were at no greater risk than those vaccinated at 15 months or over. Subjects vaccinated before 1980 were at greater risk than those vaccinated after 1980 (adjusted OR 14.5, 95% CI 1.5 to 135.6). Time since vaccination was not a risk factor. Revaccination was effective in reducing the risk of measles in both subjects vaccinated before 1980 and those vaccinated after 1980 (adjusted OR reduced to 0.6 [95% CI 0.1 to 5.3] and 0.3 [95% CI 0.13 to 2.6] respectively). However, only 18 cases were estimated to have been prevented by this strategy. CONCLUSIONS: Adherence to routine measles vaccination for all eligible children is important in ensuring appropriate coverage with a single dose. The selective revaccination strategy''s high labour intensiveness and low measles prevention rate during the outbreak bring into question the effectiveness of such a strategy.     

Case Based Measles Surveillance in Pune: Evidence to Guide Current and Future Measles Control and Elimination Efforts in India

Background

According to WHO estimates, 35% of global measles deaths in 2011 occurred in India. In 2013, India committed to a goal of measles elimination by 2020. Laboratory supported case based measles surveillance is an essential component of measles elimination strategies. Results from a case-based measles surveillance system in Pune district (November 2009 through December 2011) are reported here with wider implications for measles elimination efforts in India.

Methods

Standard protocols were followed for case identification, investigation and classification. Suspected measles cases were confirmed through serology (IgM) or epidemiological linkage or clinical presentation. Data regarding age, sex, vaccination status were collected and annualized incidence rates for measles and rubella cases calculated.

Results

Of the 1011 suspected measles cases reported to the surveillance system, 76% were confirmed measles, 6% were confirmed rubella, and 17% were non-measles, non-rubella cases. Of the confirmed measles cases, 95% were less than 15 years of age. Annual measles incidence rate was more than 250 per million persons and nearly half were associated with outbreaks. Thirty-nine per cent of the confirmed measles cases were vaccinated with one dose of measles vaccine (MCV1).

Conclusion

Surveillance demonstrated high measles incidence and frequent outbreaks in Pune where MCV1 coverage in infants was above 90%. Results indicate that even high coverage with a single dose of measles vaccine was insufficient to provide population protection and prevent measles outbreaks. An effective measles and rubella surveillance system provides essential information to plan, implement and evaluate measles immunization strategies and monitor progress towards measles elimination.     

Reduced childhood mortality after standard measles vaccination at 4-8 months compared with 9-11 months of age.

OBJECTIVE--To evaluate the impact on mortality of standard Schwarz measles immunisation before 9 months of age. DESIGN--Children vaccinated in 1980-3 at 4-5, 6-8, and 9-11 months of age were followed to migration, death, or the age of 5 years. SETTING--One urban district and nine villages in two rural areas of Guinea-Bissau. SUBJECT--307 children vaccinated at 4-8 months and 256 at 9-11 months. MAIN OUTCOME MEASURES--Mortality from 9 months to 5 years of age for children immunised at 4-5, 6-8, and 9-11 months. RESULTS--Mortality was significantly lower in children vaccinated at 6-8 months than at 9-11 months (mortality ratio = 0.63, (95% confidence interval 0.41 to 0.97), p = 0.047). As vaccination was provided in semiannual or annual campaigns it is unlikely that age at vaccination reflected a selection bias. The trend was the same in all three study areas. Improved survival after early immunisation was not related to better protection against measles infection. With a Cox multivariate regression model to adjust for age, sex, season at risk, season at birth, measles infection, and region, children vaccinated at 4-8 months had a mortality ratio of 0.61 (0.40 to 0.92, p = 0.020) compared with children vaccinated at 9-11 months. Reimmunised children tended to have lower mortality than children who received only one vaccine (0.59 (0.28 to 1.27, p = 0.176)). CONCLUSION--Standard measles vaccination before 9 months is not associated with higher childhood mortality than is the currently recommended strategy of immunising from 9 months, and it may reduce mortality. This has implications for measles immunisation strategy in developing countries.     

Altered Reactivity to Measles Virus in Previously Vaccinated Children

In children vaccinated with killed measles vaccine, exposure to natural rubeola within two to four years can result in a clinical syndrome of altered measles reactivity.During a small epidemic of measles in Edmonton, Alberta, 51 children who had received their last killed measles vaccination 27 to 45 months before, were admitted to hospital with this syndrome.The syndrome consists of a prodromal cough and high fever followed by a maculopapular rash appearing on the extremities and progressing centrally. Pulmonary consolidations with or without pleural effusions were evident, but these cleared rapidly in four or five days. Initial WBC and ESR values suggested a bacterial etiology, but no pathogens could be isolated.Complement fixation titres for rubeola are present in acute and convalescent sera and indicate a definite measles infection.Previous killed measles vaccination excites a delayed hypersensitivity which is activated by the natural measles infection to account for this syndrome.It is recommended that killed measles vaccine be no longer used in routine vaccinations.     

Live measles vaccine: a 21 year follow up.

21 years after receiving Schwartz strain live measles vaccine 4500 trial participants showed a continuing high level of protection compared with those who were unvaccinated. Over the last seven years of the follow up no cases of measles were reported in vaccinated participants who had had close contact with the disease. Immunity induced by the vaccine seems to survive the challenge of close contact with measles in young children, even after 21 years.     

沪191麻疹疫苗免疫持久性和影响因素的评价

１９９１～１９９８年,我们对荆州区川店镇５０３名６～１５月龄儿童进行了现行沪１９１麻疹疫苗血清流行病学效果观察,结果表明,初次免疫后１个月麻疹ＩｇＧ抗体阳转率为９１６５％,ＧＭＴ为１∶２６６７４,达保护滴度者比例为４６５％。随着时间的推移,第４年上述指标迅速下降到４６８６％、１∶１２７４和１８５％,第６年时低至２９４３％、１∶４８９和１３６％。０２ｍｌ、０３ｍｌ和０５ｍｌ麻疹疫苗组的近期和远期效果是类似的,初免后１个月时ＩｇＧ滴度越高,其免疫持久性越好;初免月龄是影响麻苗免疫效果的主要原因,６月龄初免组的免疫效果明显低于≥８月龄组。结果提示麻苗８月龄初免是可行的。     

Revaccination of children during school-based measles outbreaks: potential impact of a new policy recommendation.

OBJECTIVE: To evaluate the potential impact of revaccination on measles outbreak control during school-based epidemics. DESIGN: Retrospective cohort study. SETTING: Thirty-two public elementary and high schools in 14 communities on the west island of Montreal. PARTICIPANTS: All 19,439 children attending these schools during the 1989 measles epidemic in Quebec. INTERVENTION: After notification of a case children with provider-verified records of vaccination on or after their first birthday were identified; the remaining children were vaccinated or excluded from school. OUTCOME MEASURE: Clinical or confirmed measles cases not prevented by this intervention that could have been prevented had revaccination been included during the outbreak. RESULTS: Of the 88 measles cases (74 confirmed) proof of one adequate vaccination was present in 48 (55%). Intervention generally occurred within 5 school days after case notification. The nonpreventable cases involved 75 children who had measles onset before the intervention and 11 (7 vaccinated) who had onset within 8 days after the intervention. The two remaining cases occurred 20 and 25 days after the intervention among nonvaccinated students who refused to be vaccinated. Except for these two cases measles was eliminated at every school. Application of the new Canadian guidelines for measles outbreak control would have required the administration of at least 10,000 additional doses during the outbreak to students vaccinated before 1980; implementation of the new US guidelines would have required the administration of 16,629 additional doses to children previously vaccinated only once. Well-enforced provincial regulations ensuring vaccination of every student upon school entry might have prevented 38 (43%) of the cases. The US recommendation of two routine doses of vaccine before school entry might have prevented 86 (98%) of the cases. However, revaccination during the outbreak would not have prevented a single additional case. CONCLUSION: Revaccination of previously vaccinated students during a measles outbreak would have been costly and of little benefit.     

Protective immunity in macaques vaccinated with a modified vaccinia virus Ankara-based measles virus vaccine in the presence of passively acquired antibodies

Recombinant modified vaccinia virus Ankara (MVA), encoding the measles virus (MV) fusion (F) and hemagglutinin (H) (MVA-FH) glycoproteins, was evaluated in an MV vaccination-challenge model with macaques. Animals were vaccinated twice in the absence or presence of passively transferred MV-neutralizing macaque antibodies and challenged 1 year later intratracheally with wild-type MV. After the second vaccination with MVA-FH, all the animals developed MV-neutralizing antibodies and MV-specific T-cell responses. Although MVA-FH was slightly less effective in inducing MV-neutralizing antibodies in the absence of passively transferred antibodies than the currently used live attenuated vaccine, it proved to be more effective in the presence of such antibodies. All vaccinated animals were effectively protected from the challenge infection. These data suggest that MVA-FH should be further tested as an alternative to the current vaccine for infants with maternally acquired MV-neutralizing antibodies and for adults with waning vaccine-induced immunity.     

Swedish experience of two dose vaccination programme aiming at eliminating measles,mumps, and rubella.

In 1982 a two dose regimen was introduced in Sweden for the combined vaccination against measles, mumps, and rubella of children aged 18 months and 12 years. Since 1977 about half of the preschool children were vaccinated against measles annually, and since 1974 about 80% of 12 year old girls were vaccinated against rubella. During the period 1982 to 1985 90-93% of the eligible age cohorts of 18 month old children and 88-91% of the 12 year old children were immunised with the new combined vaccine. A study in 1982 of about 140 18 month old children who were nearly all seronegative before vaccination showed that 96%, 92%, and 99% seroconverted against measles, mumps, and rubella, respectively. A second study was carried out in 1983 of 247 12 year old children, of whom 11% lacked antibodies to measles, 27% to mumps, and 45% to rubella. This showed seroconversion in 82% and 80% against measles and mumps, respectively, and all children seroconverted against rubella. In the latest study in 1985 of 496 12 year olds 9% and 13% were seronegative against measles and mumps before vaccination, and 41% against rubella. Of these, 88% seroconverted to measles and 80% to mumps, and all converted to rubella when sera were tested by the haemolysis in gel method. After a neutralisation test against measles as well all children showed immunity to the disease. A low incidence of measles and declining figures for mumps and rubella were reported in 1984 to 1986. An outbreak of rubella during 1985 affected mainly boys in age cohorts in which only the girls had been vaccinated during the 1970s.     

Recombinant Measles Virus Vaccine Expressing the Nipah Virus Glycoprotein Protects against Lethal Nipah Virus Challenge

Nipah virus (NiV) is a member of the genus Henipavirus, which emerged in Malaysia in 1998. In pigs, infection resulted in a predominantly non-lethal respiratory disease; however, infection in humans resulted in over 100 deaths. Nipah virus has continued to re-emerge in Bangladesh and India, and person-to-person transmission appeared in the outbreak. Although a number of NiV vaccine studies have been reported, there are currently no vaccines or treatments licensed for human use. In this study, we have developed a recombinant measles virus (rMV) vaccine expressing NiV envelope glycoproteins (rMV-HL-G and rMV-Ed-G). Vaccinated hamsters were completely protected against NiV challenge, while the mortality of unvaccinated control hamsters was 90%. We trialed our vaccine in a non-human primate model, African green monkeys. Upon intraperitoneal infection with NiV, monkeys showed several clinical signs of disease including severe depression, reduced ability to move and decreased food ingestion and died at 7 days post infection (dpi). Intranasal and oral inoculation induced similar clinical illness in monkeys, evident around 9 dpi, and resulted in a moribund stage around 14 dpi. Two monkeys immunized subcutaneously with rMV-Ed-G showed no clinical illness prior to euthanasia after challenge with NiV. Viral RNA was not detected in any organ samples collected from vaccinated monkeys, and no pathological changes were found upon histopathological examination. From our findings, we propose that rMV-NiV-G is an appropriate NiV vaccine candidate for use in humans.     

郑州市麻疹疫苗强化免疫前后麻疹流行病学特征分析

目的了解郑州市麻疹疫苗强化免疫对疾病流行特征的影响,为消除麻疹采取针对性措施提供科学依据。方法对郑州市麻疹强化免疫活动前后的2010年和2011年麻疹发病情况进行描述性流行病学分析。结果郑州市强化免疫后麻疹病例大幅减少,2011年较2010年病例数减少90%;全年病例散发,无明显季节性高峰出现;病例构成仍以1岁以下儿童和无免疫史者为主;城区发病高于农村。结论此次麻疹强化免疫活动效果明显,致使麻疹发病率显著下降。     

Early kinetics of antibody response to inactivated influenza vaccine

The aim was to examine the rapidity of haemagglutination inhibiting (HI) antibody response induced by immunization with a current inactivated trivalent influenza vaccine. Five to six sequential serum samples collected in autumn 1992 from each of 68 vaccinees in three age groups were studied for HI antibodies to ten influenza virus strains representing vaccine and epidemic viruses. Geometric mean titres, response rates and protection rates are presented. Response rates of > 70% were overall, but not until two weeks after the vaccination. Significant two- and four-day post-vaccination antibody responses were detected only occasionally. In previously vaccinated persons, average antibody titres to some of the viruses decreased during the first days after the vaccination. In the subsequent samples, the titres remained lower than in persons who were not vaccinated against influenza in preceding years. Protection against influenza infection may be frequently developed not until two weeks after vaccination. This has relevance to prophylactic administration of amantadine and rimantadine when an influenza A outbreak is imminent and the vaccination is late.     

Content of A-, G- and M-class immunoglobulins in adults perorally immunized with a liver Sonne dysentery vaccine]

The authors studied the immunological shifts in the blood and saliva of 357 adults immunized with live enteral dysentery Sonne vaccine from a spontaneous mutant according to different schemes (1, 2, 3, 4 injections at 2--3-day intervals. The general level of IgA, IgG, and IgM increased during the immunization; there was also an elevation of the specific antibodies level of these classes in the blood of the persons vaccinated. Accretion was the greatest of IgA both in the blood and in saliva of the immunized persons; this pointed to a marked, chiefly local, immunological activity of the vaccine. As shown, during the immunization the rise and the changes in the antibody level of various immunoglobulin classes differed from such in dysentery infection; in the latter case, along with the IgA-antibodies there was a marked elevation of the IgG- and IgM-antibodies level. It is supposed that there was a possibility of a changed of a 4-time immunization scheme to-3-time one, with increase of intervals between the vaccine administration.     

Neonatal immunization with a Sindbis virus-DNA measles vaccine induces adult-like neutralizing antibodies and cell-mediated immunity in the presence of maternal antibodies

Infants younger than age 9 mo do not respond reliably to the live attenuated measles vaccine due the immaturity of their immune system and the presence of maternal Abs that interfere with successful immunization. We evaluated the immune responses elicited by Sindbis virus replicon-based DNA vaccines encoding measles virus (MV) hemagglutinin (H, pMSIN-H) or both hemagglutinin and fusion (F, pMSINH-FdU) glycoproteins in neonatal mice born to naive and measles-immune mothers. Despite the presence of high levels of maternal Abs, neonatal immunization with pMSIN-H induced long-lasting, high-avidity MV plaque reduction neutralization (PRN) Abs, mainly IgG2a, that also inhibited syncytium formation in CD150(+) B95-8 cells. IgG secreting plasma cells were detected in spleen and bone marrow. Newborns vaccinated with pMSINH-FdU elicited PRN titers that surpassed the protective level (200 mIU/ml) but were short-lived, had low syncytium inhibition capacity, and lacked avidity maturation. This vaccine failed to induce significant PRN titers in the presence of placentally transferred Abs. Both pMSIN-H and pMSINH-FdU elicited strong Th1 type cell-mediated immunity, measured by T cell proliferation and IFN-gamma production, that was unaffected by maternal Abs. Newborns responded to measles DNA vaccines with similar or even higher PRN titers and cell-mediated immunity than adult mice. This study is the first demonstration that a Sindbis virus-based measles DNA vaccine can elicit robust MV immunity in neonates bypassing maternal Abs. Such a vaccine could be followed by the current live attenuated MV vaccine in a heterologous prime-boost to protect against measles early in life.