Awa Marie Coll Seck

Non-specific beneficial effect of measles immunisation: analysis of mortality studies from developing countries

Abstract Objective: To examine whether the reduction in mortality after standard titre measles immunisation in developing countries can be explained simply by the prevention of acute measles and its long term consequences. Design: An analysis of all studies comparing mortality of unimmunised children and children immunised with standard titre measles vaccine in developing countries. Studies: 10 cohort and two case-control studies from Bangladesh, Benin, Burundi, Guinea-Bissau, Haiti, Senegal, and Zaire. Main outcome measures: Protective efficacy of standard titre measles immunisation against all cause mortality. Extent to which difference in mortality between immunised and unimmunised children could be explained by prevention of measles disease. Results: Protective efficacy against death after measles immunisation ranged from 30% to 86%. Efficacy was highest in the studies with short follow up and when children were immunised in infancy (range 44-100%). Vaccine efficacy against death was much greater than the proportion of deaths attributed to acute measles disease. In four studies from Guinea-Bissau, Senegal, and Burundi vaccine efficacy against death remained almost unchanged when cases of measles were excluded from the analysis. Diphtheria-tetanus-pertussis and polio vaccinations were not associated with reduction in mortality. Conclusion: These observations suggest that standard titre measles vaccine may confer a beneficial effect which is unrelated to the specific protection against measles disease.

Serologic status and measles attack rates among vaccinated and unvaccinated children in rural Senegal

During a measles vaccine trial in a rural area of Senegal, antibody status was examined within 10 days of exposure for 228 previously vaccinated and 313 unvaccinated children more than 12 months old who were exposed to measles at home. Thirty-six percent of the children developed clinical measles, the clinical diagnosis being confirmed for 135 of the 137 children from whom 2 blood samples were collected. Vaccine efficacy was 90% (95% confidence interval, 83 to 94%). The hemagglutinin-inhibiting antibodies (HI) or plaque neutralizing antibodies (PN) assays were equally efficient in predicting susceptibility and protection against measles. Vaccinated children who had no detectable HI or PN antibodies at exposure had significant protection against measles compared with seronegative unvaccinated children (HI vaccine efficacy, 49% (95% confidence interval, 21 to 68%); PN vaccine efficacy, 43% (95% confidence interval, 12 to 62%)). The attack rate was high for children with a titer of 40 to 125 mIU) 67% (4 of 6) of those with a positive hemagglutinin-inhibiting antibody test and 36% (13 of 36) of those with a positive PN test developed measles. Attack rates among children with HI or PN titers above 125 mIU were 2% (6 of 295) and 3% (7 of 258), respectively. Because titers of ≥120 mIU have been found to offer little protection in another study, this antibody level may be the best screening value for assessing susceptibility and protection against measles. However, it should be noted that many seronegative vaccinated children are protected against measles infection.

Protective efficacy of high-titre measles vaccines administered from the age of five months: a community study in rural Senegal

Using data on incidence and secondary attack rates, we examined the protective efficacy of high-titre Edmonston-Zagreb (EZ) and Schwarz (SW-HT) measles vaccines administered at 5 months. Control children were assigned to placebo at age 5 months and standard Schwarz (SW-std) measles vaccine at 9-10 months of age. A large proportion of measles cases was verified serologically. Though high-titre vaccines seemed to be protective before 10 months of age, a significant reduction in disease could not be demonstrated due to low incidence of measles. After 10 months of age, SW-std given at 10 months gave a vaccine efficacy of 100% and induced better protection than SW-HT (P = 0.030) and EZ-HT (P = 0.128) administered at 5 months. In studies of secondary attack rates in the compound, vaccine efficacy was 91% (75%-97%) for EZ-HT, 85% (40%-96%) for SW-HT, and 100% for SW-std. Attack rates were correlated with intensity of exposure (P = 0.0006), being much higher for children exposed in the same hut than for those living in the same compound but in a different household (relative risk = 3.36 [1.32-8.57]). The attack rate was significantly lower among vaccinated than unvaccinated children with no detectable measles antibody (relative risk = 0.41 [0.18-0.93]). In rural areas with a high coverage in the surrounding community, a single dose at 9-10 months may provide sufficient protection. Since high-titre vaccines have been associated with higher mortality than SW-std, further improvements in measles control before 9 months may require two-dose strategies with standard vaccines.

A comparison of vaccine efficacy and mortality during routine use of high-titre Edmonston-Zagreb and Schwarz standard measles vaccines in rural Senegal

Vaccine efficacy and mortality in successive cohorts of children who routinely received either Edmonston-Zagreb high-titre (EZ-HT) or Schwarz standard (SW-STD) measles vaccines have been examined in a rural area of Senegal. The 2 vaccines were equally protective against measles infection (vaccination efficacy: EZ-HT 94%; SW-STD 93%). Children who did not attend a scheduled session to receive measles vaccine had a higher mortality rate between 9 months and 2 years of age than did children receiving either EZ-HT (mortality ratio [MR] = 1.81, 95% confidence interval [CI] 1.06-3.08) or SW-STD measles vaccine (MR = 1.74, 95% CI 0.95-3.21). Children of either sex vaccinated with EZ-HT had lower mortality than their equivalents who had not received any measles vaccine. There was no difference in overall mortality between recipients of EZ-HT and SW-STD (MR = 0.96, 95% CI 0.70-1.30). Using a Cox regression analysis to adjust for sex, age and significant background factors (season and death of mother), mortality rates tended to be lower for male recipients of EZ-HT than for boys receiving SW-STD (MR = 0.73, 95% CI 0.50-1.11) and higher for girls receiving EZ-HT than for girls receiving SW-STD (MR = 1.30, 95% CI 0.81-2.09) (test of interaction between sex and vaccine, P = 0.067). The tendency to reduced survival benefit for girls following receipt of high-titre measles vaccines substantiated observations from randomized trials in Guinea-Bissau, Senegal and Haiti. Existing data provide little support for the notion that high-titre vaccine is deleterious but it may not have the same beneficial effects as standard-titre measles vaccine.

Five year follow-up of morbidity and mortality among recipients of high-titre measles vaccines in Senegal

At 3-5 years of age, female recipients of Edmonston-Zagreb high-titre (EZ-HT) and Schwarz high-titre (SW-HT) measles vaccine had lower survival rates than female recipients of Schwarz standard measles vaccine (SW-STD) in Guinea-Bissau, Senegal and Haiti. In Senegal, the children who received high-titre vaccines have now been followed to the age of 5-7 years to determine whether the difference in mortality persisted, and whether differences in vaccine efficacy were apparent. At this age there was no difference in mortality between female recipients of high-titre and standard titre measles vaccines. There was no indication that high-titre EZ-HT vaccine at 5 months (EZ-HT,5m) provided suboptimal protection, as vaccine efficacy after exposure was 97% and 95%, respectively, for EZ-HT,5m and SW-STD,10m vaccines, whereas SW-HT,5m vaccine had an efficacy of 81%. The difference in mortality between recipients of high-titre vaccines and SW-STD observed in several studies during the first few years after vaccination may be explained by non-specific beneficial effects of the standard measles vaccine rather than a harmful effect of the high-titre vaccines.

High-titre measles vaccines for boys

From data in the thesis and using a different cut-off of -2. z-scores Garenne concludes that EZ-HT measles vaccine is de!ererious for boys, the difference being especially striking for wasting (weight-for-height). It should be noted that with a prevalence of 6.3% and 2.0% for EZ-HT and SW-STD boys, respectively (table), wasting was uncommon in bo& groups, being acrually lower than expeczed (2.5%) in the