Measles vaccination in the presence or absence of maternal measles antibody: impact on child survival

Peter Aaby, Cesário L Martins, May-Lill Garly, Andreas Andersen, Ane B Fisker, Mogens H Claesson, Henrik Ravn, Amabelia Rodrigues, Hilton C Whittle, Christine S Benn, Peter Aaby, Cesário L Martins, May-Lill Garly, Andreas Andersen, Ane B Fisker, Mogens H Claesson, Henrik Ravn, Amabelia Rodrigues, Hilton C Whittle, Christine S Benn

Abstract

Background: Measles vaccine (MV) has a greater effect on child survival when administered in early infancy, when maternal antibody may still be present.

Methods: To test whether MV has a greater effect on overall survival if given in the presence of maternal measles antibody, we reanalyzed data from 2 previously published randomized trials of a 2-dose schedule with MV given at 4-6 months and at 9 months of age. In both trials antibody levels had been measured before early measles vaccination.

Results: In trial I (1993-1995), the mortality rate was 0.0 per 1000 person-years among children vaccinated with MV in the presence of maternal antibody and 32.3 per 1000 person-years without maternal antibody (mortality rate ratio [MRR], 0.0; 95% confidence interval [CI], 0-.52). In trial II (2003-2007), the mortality rate was 4.2 per 1000 person-years among children vaccinated in presence of maternal measles antibody and 14.5 per 1000 person-years without measles antibody (MRR, 0.29; 95% CI, .09-.91). Possible confounding factors did not explain the difference. In a combined analysis, children who had measles antibody detected when they received their first dose of MV at 4-6 months of age had lower mortality than children with no maternal antibody, the MRR being 0.22 (95% CI, .07-.64) between 4-6 months and 5 years.

Conclusions: Child mortality in low-income countries may be reduced by vaccinating against measles in the presence of maternal antibody, using a 2-dose schedule with the first dose at 4-6 months (earlier than currently recommended) and a booster dose at 9-12 months of age.

Clinical trials registration: NCT00168558.

Keywords: 2-dose measles vaccination; age of measles vaccination; maternal measles antibodies; nonspecific beneficial effects of measles vaccine.

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Cumulative mortality between 4.5 months and 5 years of age in relation to age of measles vaccination (MV) and presence of maternal antibody (trial II [5]). Children randomized to MV at 4.5 months received also MV at 9 months of age. Controls received only MV at 9 months of age. Abbreviations: Ab, antibody; MV, measles vaccination.

References

    1. Expanded Programme on Immunization. The optimal age for measles immunization. Weekly Epidemiol Rec. 1982;57:89–91.
    1. Gans H, Yasukawa L, Rinki M, et al. Immune responses to measles and mumps vaccination of infants at 6, 9, and 12 months. J Infect Dis. 2001;184:817–26.
    1. De Quadros CA, Izurieta H, Venczel L, Carrasco P. Measles eradication in the Americas : Progress to date. J Infect Dis. 2004;189(suppl 1):S227.
    1. Strategic Advisory Group of Experts. Meeting of the immunization Strategic Advisory Group of experts, November 2006—conclusions and recommendations. Weekly Epidemiol Rec. 2007;82:1–16.
    1. Aaby P, Martins CL, Garly ML, et al. Non-specific effects of standard measles vaccine at 4.5 and 9 months of age on childhood mortality: Randomised controlled trial. BMJ. 2010;341:c6495.
    1. Aaby P, Samb B, Simondon F, Coll Seck AM, Knudsen K, et al. Non-specific beneficial effect of measles immunisation: analysis of mortality studies from developing countries. Br Med J. 1995;311:481–5.
    1. Aaby P, Andersen M, Sodemann M, Jakobsen M, Gomes J, et al. Reduced childhood mortality after standard measles vaccination at 4–8 months compared with 9–11 months of age. Br Med J. 1993;307:1308–11.
    1. Aaby P, Garly ML, Balé C, et al. Survival of previously measles-vaccinated and measles-unvaccinated children in an emergency situation: an unplanned study. Pediatr Infect Dis J. 2003;22:798–803.
    1. Aaby P, Pedersen IR, Knudsen K, et al. Child mortality related to seroconversion or lack of seroconversion after measles vaccination. Pediatr Infect Dis J. 1989;8:197–200.
    1. Velema JP, Alihonou EJ, Gandaho T, Hounye FH. Childhood mortality among users and non-users of primary health care in a rural West African community. Int J Epidemiol. 1991;20:474–9.
    1. Martins CL, Benn CS, Andersen A, et al. A randomized trial of a standard dose of EZ measles vaccine given at 4.5 months of age: effect on total hospital admissions. J Infect Dis. 2014;209:1731–8.
    1. Sørup S, Benn CS, Poulsen A, Krause T, Aaby P, Ravn H. Live vaccine against measles, mumps, and rubella and the risk of hospital admissions for nontargeted infections. JAMA. 2014;311:826–35.
    1. Kasongo Project Team. Influence of measles vaccination on survival pattern of 7–35-month-old children in Kasongo, Zaire. Lancet. 1981;1:764–7.
    1. Benn CS, Aaby P, Balé C, et al. Randomised trial of effect of vitamin A supplementation on antibody response to measles vaccine in Guinea-Bissau, West Africa. Lancet. 1997;350:101–5.
    1. Benn CS, Balde A, George E, et al. Effect of vitamin A supplementation on measles-specific antibody levels in Guinea-Bissau. Lancet. 2002;359:1313–14.
    1. Martins C, Carlitos Bale C, Garly ML, et al. Girls may have lower levels of maternal measles antibodies and higher risk of subclinical measles infection before the age of measles vaccination. Vaccine. 2009;27:5220–5.
    1. Whittle H, Rowland MG, Mann GF, Lamb WH, Lewis RA. Immunisation of 4–6 month old Gambian infants with Edmonston-Zagreb measles vaccine. Lancet. 1984;2:834–7.
    1. Samb B, Aaby P, Whittle H, et al. Serological status and measles attack rates among vaccinated and unvaccinated children in rural Senegal. Pediatr Infect Dis J. 1995;14:203–9.
    1. Aaby P, Bukh J, Kronborg D, Lisse IM, da Silva MC. Delayed excess mortality after exposure to measles during the first six months of life. Am J Epidemiol. 1990;132:211–19.
    1. Aaby P, Andersen M, Knudsen K. Excess mortality after early exposure to measles. Int J Epidemiol. 1993;22:156–62.
    1. Poulsen AG, Kvinesdal B, Aaby P, et al. Prevalence of and mortality from human immunodeficiency virus type 2 in Bissau, West Africa. Lancet. 1989;1:827–31.
    1. da Silva ZJ, Oliveira I, Andersen A, et al. Changes in prevalence and incidence of HIV-1, HIV-2 and dual infections in urban areas of Bissau, Guinea-Bissau. Is HIV-2 disappearing? AIDS. 2008;22:1195–202.
    1. Aaby P, Lisse IM, Whittle H, et al. Long-term survival in trial of medium-titre Edmonston-Zagreb measles vaccine in Guinea-Bissau: five year follow-up. Epidemiol Infect. 1994;112:413–20.
    1. Aaby P, Jensen H, Samb B, et al. Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus: a re-analysis of the West African studies. Lancet. 2003;361:2183–88.
    1. Aaby P. Measles immunization and child survival: uncontrolled experiments. In: Rashad H, Gray R, Boerma T, editors. Evaluation of the impact of health interventions, IUSSP. Liege: Derouaux Ordina Editions; 1995. pp. 11–45.
    1. Aaby P, Biai S, Veirum JE, et al. DTP with or after measles vaccination is associated with increased in-hospital mortality in Guinea-Bissau. Vaccine. 2007;25:1265–9.
    1. Bertley FM, Ibrahim SA, Libman M, Ward BJ. Measles vaccination in the presence of maternal antibodies primes for a balanced humoral and cellular response to revaccination. Vaccine. 2004;23:444–9.
    1. Lemke H, Coutinho A, Lange H. Lamarckian inheritance by somatically acquired maternal IgG phenotypes. Trends Immunol. 2004;25:180–96.
    1. Navarini AA, Krzyzowsko M, Lang KS, et al. Long-lasting immunity by early infection of maternal antibody-protected infants. Eur J Immunol. 2010;40:113–6.
    1. Shann F. Heterologous immunity and the non-specific effects of vaccines. A major medical advance? Pediatr Infect Dis J. 2004;23:555–8.
    1. Siegrist CA. Mechanisms by which maternal antibodies influence infant vaccine responses: review of hypotheses and definition of main determinants. Vaccine. 2003;21:3406–12.
    1. Welsh RM, Selin LH. No one is naïve: the significance of heterologous T-cell immunity. Nat Rev Immunol. 2002;2:417–26.
    1. Kleinnijenhuis J, Quintin J, Preijers F, et al. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A. 2012;109:17537–42.
    1. Benn CS, Netea MG, Selin LK, Aaby P. A small jab—a big effect: non-specific immunomodulation by vaccines. Trends Immunol. 2013;34:431–9.
    1. Koenig MA, Khan MA, Wojtyniak B, et al. Impact of measles vaccination on childhood mortality in rural Bangladesh. Bull WHO. 1990;68:441–7.
    1. Aaby P, Bhuyia A, Nahar L, Knudsen K, de Francisco A, Strong M. The survival benefit of measles immunization may not be explained entirely by the prevention of measles disease: a community study from rural Bangladesh. Int J Epidemiol. 2003;32:106–15.
    1. Martins C, Garly ML, Bale C, et al. Measles antibodies responses after an early two dose schedule with Edmonston-Zagreb standard-titre measles vaccine at 4 1/2 and 9 months of age [Epub ahead of print] J Infect Dis. 2014
    1. Martins CL, Garly ML, Balé C, et al. Protective efficacy of standard Edmonston-Zagreb measles vaccination in infants aged 4.5 months: interim analysis of a randomised clinical trial. BMJ. 2008;337:a661.
    1. Jacobson RM, Ovsyannikova IG, Vierkant RA, Pankratz VS, Poland GA. Independence of measles-specific humoral and cellular immune responses to vaccination. Hum Immunol. 2012;73:474–9.
    1. Moxon R, Nossal G, Heymann D, Plotkin S, Levine O. Authors’ reply. Lancet. 2012;379:27.
    1. Aaby P, Martins CL, Garly ML, Rodrigues A, Benn CS, Whittle HC. The optimal age of measles immunization in low-income countries: a secondary analysis of the assumptions underlying the current policy. BMJ Open. 2012;2:e000761.
    1. Shann F. The non-specific effects of vaccines. Arch Dis Child. 2010;95:662–7.

Source: PubMed

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