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

Aaby,-P; Samb,-B; Simondon,-F; Knudsen,-K; Seck,-A-M; Bennett,-J; Markowitz,-L; Whittle,-H

Trans-R-Soc-Trop-Med-Hyg. 1996 May-Jun; 90(3): 326-30

Transactions-of-the-Royal-Society-of-Tropical-Medicine-and-Hygiene

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.

Aaby,-P; Samb,-B; Simondon,-F; Knudsen,-K; Seck,-A-M; Bennett,-J; Markowitz,-L; Whittle,-H

Vaccine. 1996 Feb; 14(3): 226-9

Vaccine-

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.

 

Assumptions and contradictions in measles and measles immunization research: is measles good for something?

Peter Aaby^[*]

Social Science & Medicine, Vol. 41 (1995) pp 673-686

Measles infection, the major cause of childhood mortality among infections preventable by immunization, has been considered to kill mainly young and malnourished children. Assuming that mainly `weak' children are saved by immunizations, it has been speculated that the impact on survival of immunization is likely to be limited because the malnourished children are more prone to die of other infections. However, recent studies from developing countries have suggested that host factors may not be the most important determinants of acute and long-term mortality after measles infection. Instead, it was found that infection contracted after exposure at home is associated with much higher mortality than infection contracted from someone outside the home. Furthermore, measles is particularly severe if contracted from someone of the opposite sex. Hence, transmission factors, in particularly intensity of exposure and cross-sex transmission, may be more important determinants of measles mortality than the host factors usually emphasized. Consistent with these observations and in contrast to assumptions about `weak' children dying, immunization is associated with a major reduction in mortality. Since measles immunization is associated with a 30% reduction in mortality or more, the impact is much larger than should be expected from the proportion of all deaths attributed to measles. It has therefore been suggested that measles immunization may prevent the persistent immunosuppression and delayed mortality assumed to be associated with measles. However, several observations contradict the common understanding that the function of measles immunization is only to prevent the acute and long-term mortality associated with measles infection. Recently, the high-titre measles immunization recommended by WHO was found to be associated with reduced survival for female recipients compared with girls who had received the standard low-dose measles vaccine, and this difference in survival was not due to suboptimal protection against measles infection. Contrary to usual assumptions, standard low-dose measles vaccine reduces mortality even more when given before 9 months of age, the age currently recommended by WHO. The beneficial impact of standard vaccine is apparently temporary, lasting 1 to 2 years, whereas it should increase with the age of the child. The beneficial effect seems to be particularly strong for girls. The most likely interpretation of these observations, is that standard low-dose measles vaccine has a non-specific beneficial effect. Contrary to current assumptions, children who survive the acute phase of measles infection may have a survival advantage compared with unimmunized, uninfected children.  Hence, both disease and immunization may be associated with non-specific beneficial effects, presumably due to some form of immunostimulation. In this perspective, the problem of high-titre immunization was apparently not that the vaccine was immunosuppressive, but that it may have lacked the non-specific beneficial impact of standard vaccine. Should these observations be reproducable, they question the culture of `eradication' and have major implications for future immunization policies. Published by Elsevier Science Ltd

 

 

Am J Phys Anthropol 1994 Jul;94(3):421-5

Related Articles, Books

Brief communication: immunologic aspects of human colostrum and milk--a misinterpretation.

Hoshower LM.

Interpretations of the demographic impact of Western diseases are frequently clouded by a failure to appreciate the complex nature of immune responses. It is commonly assumed that epidemic diseases are generally characterized by both transplacental and lacteal transmission of maternal antibodies. This is not, however, the case for viral diseases, such as measles, smallpox, and influenza--all of which reached epidemic proportions during the post-Columbian era. In this paper I review the nature of the immune response for viral diseases, with emphasis upon measles, a disease that contributed heavily to the demise of native peoples.

Publication Types:

• Review
• Review, Tutorial

PMID: 7943195 [PubMed - indexed for MEDLINE]