Genetic characterization of measles vaccine strains.

The complete genomic sequences of 9 measles vaccine strains were compared with the sequence of the Edmonston wild-type virus. AIK-C, Moraten, Rubeovax, Schwarz, and Zagreb are vaccine strains of the Edmonston lineage, whereas CAM-70, Changchun-47, Leningrad-4 and Shanghai-191 were derived from 4 different wild-type isolates. Nucleotide substitutions were found in the noncoding regions of the genomes as well as in all coding regions, leading to deduced amino acid substitutions in all 8 viral proteins. Although the precise mechanisms involved in the attenuation of individual measles vaccines remain to be elucidated, in vitro assays of viral protein functions and recombinant viruses with defined genetic modifications have been used to characterize the differences between vaccine and wild-type strains. Although almost every protein contributes to an attenuated phenotype, substitutions affecting host cell tropism, virus assembly, and the ability to inhibit cellular antiviral defense mechanisms play an especially important role in attenuation.

Comparative efficacy of three measles vaccines in Indian children.

A Comparative study of three types of measles vaccines was undertaken among 1005 children. Of these 527 were vaccinated with the Serum Institute of India (SII) vaccine, 230 with Schwarz (SC) and 248 were vaccinated with Edmonston-Zegreb (EZ) vaccine (imported from Zegreb). Though the majority of children reacted favourably with all the three vaccines (SII: 98.43%; SC: 93.40%; EZ: 93.0%) with a rise in titre, but the percentage of seroconversion was significantly higher with the SII vaccine (p < 0.01). The Schwarz and Edmonston Zagreb vaccines showed significantly less GM titre as compared with the other age group i.e. 9-12 months (p < 0.05). With Serum Institute of India (SII) vaccine the GM titres were almost similar in the different age groups. The overall GM titre obtained with the SII vaccine was significantly higher than the SC vaccine (p > 0.001) as well as the EZ vaccine (p > 0.001). It is of interest to note that among the infants, 22.5% children had measles antibody in them before vaccination.

PIP: This study compares the efficacy of the three types of measles vaccines undertaken among 1005 children at the General Hospital pediatrics department in Pune, India. Of these children, 527 were vaccinated with the Serum Institute of India (SII) vaccine, 230 with Schwarz (SC), and 258 were vaccinated with Edmonston-Zagreb (EZ) vaccine. Results showed that the percentage of seroconversion was significantly higher with SII vaccine (98.43%) when compared with the SC (93.40%) or the EZ vaccines (93.0%). Majority of the children reacted favorably with the 3 vaccines after the rise in titer. The GM titer in the age group less than 9 months of the Schawarz vaccine was significantly less as compared with 9-12 months. The EZ vaccine also showed significantly less GM titer in the age group less than 9 months compared with the 13-18 month group. The SII vaccine and the GM titer were almost similar in different age groups. The overall GM titer obtained in the SII vaccine was significantly higher than the SC and the EZ vaccines. From this study, a direction to the strategy of measles vaccination was enlightened.

The effect of dose and strain of live attenuated measles vaccines on serological responses in young infants.

High morbidity and mortality from measles among infants under 9 months of age is an obstacle to measles control in many developing countries. In this paper, we review 30 studies conducted on the serological response to measles vaccine in infants aged less than 9 months. Among children aged under 9 months, Edmonston Zagreb and AIK-C vaccines produce higher seroresponse rates than Schwarz vaccine of equivalent titre. For Edmonston Zagreb and Schwarz vaccine, seroresponse rates increase with increasing vaccine titre. The absolute rate of seroresponse to Edmonston Zagreb vaccine in 6-month old infants varied greatly between studies because of differences in methods of vaccine titer measurement, serological assays, definitions of seroresponse, and maternal antibody profiles of the populations studied. Seroconversion rates to Edmonston Zagreb or AIK-C vaccines at 6 months of age were generally similar to those to Schwarz vaccine at 9 months of age, but antibody levels were lower after vaccination below 9 months of age. Although the increased mortality documented in other studies after use of high titer vaccines in 4-6 month old infants led to withdrawal of these vaccines, this review of vaccine trials highlights the need for standardization of study methods and for a better understanding of the biological action of measles vaccines.

Measles control in Kinshasa, Zaire improved with high coverage and use of medium titre Edmonston Zagreb vaccine at age 6 months.

BACKGROUND: To improve measles control in Kinshasa, Zaire, a project to increase vaccine coverage was begun in 1988, and in 1989, the city vaccination programme changed measles vaccination policy from Schwartz vaccine at age 9 months to medium titre Edmonston Zagreb (EZ) vaccine at age 6 months. We report the impact of the programme on measles incidence and mortality. METHODS: Data on vaccine coverage were obtained from cluster sample surveys conducted every 1-2 years and from routine reports of vaccine doses administered. Data on measles incidence and mortality were obtained from sentinel surveillance sites. The serological response to EZ measles vaccine was evaluated at a health centre in 1989 and in a community survey in 1990. RESULTS: Measles vaccine coverage estimated in cluster surveys increased from 50% of the 1984 birth cohort to 89% of the 1989 birth cohort, accepting either a home-based record or a verbal history of vaccination. Reported measles incidence per 10,000 [corrected] population decreased by over 90%, from 37.5 in 1980 (early vaccination years) to 1.6 in 1991. There was a relative decrease in the proportion of cases aged < 9 months (32% of cases in 1986-1987 and 23% of cases in 1990-1991) and an increase in the proportion aged > 23 months (29% of cases in 1986-1987 and 43% in 1990-1991). According to ELISA assays, 74-76% of children seroresponded to EZ vaccine administered at age 6-7 months under routine programme conditions. CONCLUSIONS: Measles can be controlled in urban areas, although it is difficult to determine how great a contribution vaccination at age 6 months makes over and above the achievement of high coverage.

Measles vaccine: a 27-year follow-up.

In 1964, the Medical Research Council undertook a trial of measles vaccine in over 36,000 United Kingdom children; 9577 of whom received live vaccine, 10,625 received inactivated followed by live vaccines, and 16,328 acted as unvaccinated controls. Participants in this study have been followed to determine the long term protection from measles vaccine and follow-up data were available on 4194, 4638 and 274 respectively. During the 5-year period 1986-90, the protective efficacy of live measles vaccine has remained high at 87%, but the 95% confidence interval was wide (-43 to 99%) due to the small numbers of cases. Between 1976 and 1990, however, the overall efficacy of the live vaccine was 92% (95% confidence interval 86 to 95%) and there was no evidence of a decline in efficacy (P = 0.13) over the 15-year period. This study suggests that the protection from live measles vaccine persists for up to 27 years after vaccination, and that no change in the current United Kingdom measles immunization policy should be made on the grounds of waning immunity.

Long-term survival in trial of medium-titre Edmonston-Zagreb measles vaccine in Guinea-Bissau: five-year follow-up.

A trial of protective efficacy which compared medium-titre Edmonston-Zagreb (EZ) measles vaccine (10(4.6) p.f.u.) from the age of 4 months with the standard Schwarz (SW) measles vaccine given from the age of 9 months was started in an urban community in Guinea-Bissau in 1985. Because trials of high-titre measles vaccine have found increased mortality among female recipients, we examined whether EZ medium-titre vaccine was associated with any long-term impact on mortality, suppression of T-cells, or growth. The mortality rate ratio over 5 years of follow-up was 1.12 for EZ children compared with children in the standard group (P = 0.63). Seventy-five percent of the children still residing in the area at 5 years of age took part in an immunological and anthropometric examination. There was no difference in T-cell subsets between the two groups. There was no difference in mid-upper-arm circumference, but EZ children were significantly shorter than the children in the standard group. In conclusion, medium-titre EZ was not associated with reduced survival or persistent immunosuppression.

Vacunas anti-sarampión / Vaccines anti-measles

El sarampión es una enfermedad infecciosa causada por un virus con RNA de la familia de los paramixovirus. Aunque generalmente es benigna en la niñez, a veces se complica con infecciones secundarias y se le ha implicado como agente etiológico de la panencefalitis subaguda esclerosante, que es una expresión tardía de una infección sarampionosa latente. Debido a que este virus sólo infecta a seres humanos, su control o erradicación son situaciones que pueden hacerse posibles a través de la vacunación específica. Los subtítulos que componen este trabajo son: Cuadro clínico, Definición de caso, Complicaciones, El agente etiológico; Transmisión, epidemiología. El influjo de la vacunación; Sarampión y vacunación en México, El sarampión en los Estados Unidos, El problema continental, El sarampión en el ámbito universal, Vacunas antisarampionosas: A.Vacunas "vivas" atenuadas, B.Vacunas sobreatenuadas, C.Vacunas "muertas"; Especificaciones para las vacunas antisarampionosas de uso corriente, y Vacunas parenterales de alto título. Experiencias recientes

[Vaccination against measles at 6 months of age]. / Etude de la vaccination contre la rougeole a six mois.

Measles immunization with the Edmonston Zagreb stain was carried out in 71 six-month-old infants. Proportions of subjects with immunity were 91% among the 47 subjects retested before one year of age and 100% among the 28 subjects retested between two and three years of age. These results support the WHO recommendation that measles immunization should be given at the age of six months. The concerns expressed by some about possible adverse effects of early measles immunization (decreased immune defenses) are discussed, as well as the transfer of maternal antibodies and persistence of these antibodies in the child. The obstacles to such studies in developing countries, including the need for repeated phlebotomies with centrifugation of specimens and freezing of sera, could be circumvented by the use of filter paper dried blood spot samples which seem to provide reliable results although with values somewhat lower than those found in frozen sera.

Efecto de la vacunación en la morbilidad por sarampión, en población amparada por el Instituto Mexicano del Seguro Social / Effect of vaccination on the morbility of measles in a population covared by the Instituto Mexicano del Seguro Social

Desde el inicio de la vacunación masiva contra sarampión se ha observado un descenso en la morbilidad por esta enfermedad. En el Instituto Mexicano del Seguro Social se inició la inmunización en los últimos años de la década de 1960. Con el fín de correlacionar la vacunación con la ocurrencia de la enfermedad se analizó el comportamiento secular de estas dos variables en el último cuarto de siglo. Se utilizaron asimismo modelos de regresión lineal simple y múltiple para evaluar el efecto de la vacunación en la morbilidad. La tendencia del sarampión ha sido descendente en el período analizado (r=0.75;p<0.0001), y este descenso guarda relación con la vacunación. A su vez existe una correlación negativa que sigue una curva exponencial entre el número de casos de sarampión y las dosis de vacunas aplicadas uno y dos años antes. Se propone el modelo Iny=alfa+beta1Inx1+beta2Inx2 donde y es el número de casos de sarampión, X1 el número de dosis aplicadas un año antes, y x2 el número de dósis aplicadas dos años antes (r=0.82;r2+0.69;p<0.0001). De acuerdo al modelo de reducción en el número de casos sigue una curva exponencial en relación al incremento en el número de dósis, es decir a medida que se aumentan las dosis la proporción en la reducción del número de casos es cada vez menor. A su vez existen un período de latencia (lagtime) entre la vacunación y el impacto en la morbilidad por sarampión

Antibody persistence in Gambian children after high-dose Edmonston-Zagreb measles vaccine.

Measles antibody concentrations in Gambian children immunised at 4 months of age with a high-dose Edmonston-Zagreb (EZ) measles vaccine or at 9 months with conventional Schwarz vaccine were measured 5 months after vaccination, and at 18 and 36 months of age. Schwarz vaccinees produced, on average, a 2.4-fold higher concentration of measles haemagglutinin inhibiting (HAI) antibody than EZ vaccinees, but at 36 months of age 82 of 93 (88%) EZ vaccinees and 83 of 87 (95%) Schwarz vaccinees had measles plaque-neutralising antibody concentrations above the assumed protective level of 200 mIU/ml (p greater than 0.1). HAI antibody concentrations 5 months after vaccination were inversely related to the presence of maternal antibody at vaccination, but above protective levels; at 18 and 36 months of age there was no relation to antibody concentration at vaccination, and decay of HAI antibody between 18 and 36 months of age was similar for EZ and Schwarz vaccinees.

Comparison of Edmonston-Zagreb and Schwarz strains of measles vaccine given by aerosol or subcutaneous injection.

The serological response to measles vaccine was tested in Bangladesh in groups of infants aged 4-6 months who received equal doses of Edmonston-Zagreb or Schwarz vaccine by subcutaneous injection or by aerosol. Seroconversion (as measured by the haemagglutination test) occurred in 62% of infants receiving Edmonston-Zagreb strain by injection compared with only 37% of those receiving Schwarz strain. Seroconversion occurred in 35% of those given Edmonston-Zagreb and 34% of those given Schwarz vaccine by aerosol. Edmonston-Zagreb strain appears more effective than Schwarz vaccine in this population and further studies are indicated in other populations where early measles immunisation is desirable.