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The effects of maternal immunity and age structure on population immunity to measles.

ABSTRACT: Measles was successfully eradicated in the Pan-American Health Region in 2002. However, maintenance of elimination in parts of Africa, Europe, the USA, and other regions is proving difficult, despite apparently high vaccine coverage. This may be due to the different age structure in developed and developing populations, as well as to differences in the duration of maternal immunity. We explore the interaction between maternal immunity and age structure and quantify the resulting immunity gap between vaccine coverage and population immunity; we use this immunity gap as a novel metric of vaccine program success as it highlights the difference between actual and estimated immunity. We find that, for some combinations of maternal immunity and age structure, the accepted herd immunity threshold is not maintainable with a single-dose vaccine strategy for any combination of target age and coverage. In all cases, the herd immunity threshold is more difficult to maintain in a population with developing age structure. True population immunity is always improved if the target age at vaccination is chosen for the specific combination of maternal immunity and age structure.

SUBMITTER: McKee A

PROVIDER: S-EPMC4485449 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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The effects of maternal immunity and age structure on population immunity to measles.

McKee A A Ferrari M J MJ Shea K K

Theoretical ecology 20150501 2

Measles was successfully eradicated in the Pan-American Health Region in 2002. However, maintenance of elimination in parts of Africa, Europe, the USA, and other regions is proving difficult, despite apparently high vaccine coverage. This may be due to the different age structure in developed and developing populations, as well as to differences in the duration of maternal immunity. We explore the interaction between maternal immunity and age structure and quantify the resulting immunity gap bet ...[more]

PMID: 26140058

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Project description:BackgroundAssessing the risk of measles outbreaks and identifying the susceptible parts of the population is essential to timely intervention. Infants between 6-12 months are increasingly susceptible to measles but evaluating the performance of high throughput enzyme immunoassays (ELISAs) in infants < 9 months of age is lacking.MethodsA commercially available ELISA kit (Creative Diagnostics, DEIA359) for estimating measles seroprotection was evaluated in infants 5-7 months of age. In an immunogenicity substudy in the Danish MMR trial conducted between 2019-2021, infants (and mothers at baseline) were sampled before and one month after measles-mumps-rubella vaccination (MMR) or placebo as well as one month after routine MMR at 15 months. Measles IgG ELISA was compared to the gold standard but labor-intensive measles plaque reduction neutralization test (PRNT) by Pearson and Spearman correlations and by estimating sensitivity, specificity, and positive and negative predictive values (PPV and NPV).FindingsMeasles IgG levels compared to PRNT antibodies had a Pearson's correlation coefficient between 0.10-0.24. Seroprotection rates measured by ELISA in young infants were 10-14% lower than measured by PRNT. The sensitivity of the ELISA to detect serological protection compared to PRNT in the infant population differed markedly across sampling time points and was 14%, 40%, and 92% at baseline, post-intervention, and post-routine MMR, whereas the specificity was 99%, 93%, and 43%, respectively. The PPV and NPV were 68% and 87% in infants at baseline.InterpretationThe correlation between measles IgG and PRNT antibodies was low. Seroprotection was underestimated using ELISA. High-accuracy tests are needed to avoid misclassifications and practices that lead to primary or secondary vaccine failure or retention of vaccination in outbreak settings. Baseline PPV and NPV suggested some applicability of ELISA in predicting serological protection in this age group. However, PRNT may be the only accurate estimator of serological protection in young infants.

Project description:BackgroundOne of the United Nations' Millennium Development Goals of 2000 was to reduce maternal mortality by 75% in 15 y; however, this challenge was not met by many industrialized countries. As average maternal age continues to rise in these countries, associated potentially life-threatening severe maternal morbidity has been understudied. Our primary objective was to examine the associations between maternal age and severe maternal morbidities. The secondary objective was to compare these associations with those for adverse fetal/infant outcomes.Methods and findingsThis was a population-based retrospective cohort study, including all singleton births to women residing in Washington State, US, 1 January 2003-31 December 2013 (n = 828,269). We compared age-specific rates of maternal mortality/severe morbidity (e.g., obstetric shock) and adverse fetal/infant outcomes (e.g., perinatal death). Logistic regression was used to adjust for parity, body mass index, assisted conception, and other potential confounders. We compared crude odds ratios (ORs) and adjusted ORs (AORs) and risk differences and their 95% CIs. Severe maternal morbidity was significantly higher among teenage mothers than among those 25-29 y (crude OR = 1.5, 95% CI 1.5-1.6) and increased exponentially with maternal age over 39 y, from OR = 1.2 (95% CI 1.2-1.3) among women aged 35-39 y to OR = 5.4 (95% CI 2.4-12.5) among women aged ≥50 y. The elevated risk of severe morbidity among teen mothers disappeared after adjustment for confounders, except for maternal sepsis (AOR = 1.2, 95% CI 1.1-1.4). Adjusted rates of severe morbidity remained increased among mothers ≥35 y, namely, the rates of amniotic fluid embolism (AOR = 8.0, 95% CI 2.7-23.7) and obstetric shock (AOR = 2.9, 95% CI 1.3-6.6) among mothers ≥40 y, and renal failure (AOR = 15.9, 95% CI 4.8-52.0), complications of obstetric interventions (AOR = 4.7, 95% CI 2.3-9.5), and intensive care unit (ICU) admission (AOR = 4.8, 95% CI 2.0-11.9) among those 45-49 y. The adjusted risk difference in severe maternal morbidity compared to mothers 25-29 y was 0.9% (95% CI 0.7%-1.2%) for mothers 40-44 y, 1.6% (95% CI 0.7%-2.8%) for mothers 45-49 y, and 6.4% for mothers ≥50 y (95% CI 1.7%-18.2%). Similar associations were observed for fetal and infant outcomes; neonatal mortality was elevated in teen mothers (AOR = 1.5, 95% CI 1.2-1.7), while mothers over 29 y had higher risk of stillbirth. The rate of severe maternal morbidity among women over 49 y was higher than the rate of mortality/serious morbidity of their offspring. Despite the large sample size, statistical power was insufficient to examine the association between maternal age and maternal death or very rare severe morbidities.ConclusionsMaternal age-specific incidence of severe morbidity varied by outcome. Older women (≥40 y) had significantly elevated rates of some of the most severe, potentially life-threatening morbidities, including renal failure, shock, acute cardiac morbidity, serious complications of obstetric interventions, and ICU admission. These results should improve counselling to women who contemplate delaying childbirth until their forties and provide useful information to their health care providers. This information is also useful for preventive strategies to lower maternal mortality and severe maternal morbidity in developed countries.

Dataset Information

The effects of maternal immunity and age structure on population immunity to measles.

Publications

The effects of maternal immunity and age structure on population immunity to measles.

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