Implications of spatially heterogeneous vaccination coverage for the risk of congenital rubella syndrome in South Africa.

Rubella is generally a mild childhood disease, but infection during early pregnancy may cause spontaneous abortion or congenital rubella syndrome (CRS), which may entail a variety of birth defects. Since vaccination at levels short of those necessary to achieve eradication may increase the average age of infection, and thus potentially the CRS burden, introduction of the vaccine has been limited to contexts where coverage is high. Recent work suggests that spatial heterogeneity in coverage should also be a focus of concern. Here, we use a detailed dataset from South Africa to explore the implications of heterogeneous vaccination for the burden of CRS, introducing realistic vaccination scenarios based on reported levels of measles vaccine coverage. Our results highlight the potential impact of country-wide reductions of incidence of rubella on the local CRS burdens in districts with small population sizes. However, simulations indicate that if rubella vaccination is introduced with coverage reflecting current estimates for measles coverage in South Africa, the burden of CRS is likely to be reduced overall over a 30 year time horizon by a factor of 3, despite the fact that this coverage is lower than the traditional 80 per cent rule of thumb for vaccine introduction, probably owing to a combination of relatively low birth and transmission rates. We conclude by discussing the likely impact of private-sector vaccination.

Impact of birth rate, seasonality and transmission rate on minimum levels of coverage needed for rubella vaccination.

Childhood rubella infection in early pregnancy can lead to fetal death or congenital rubella syndrome (CRS) with multiple disabilities. Reduction of transmission via universal vaccination can prevent CRS, but inadequate coverage may increase CRS numbers by increasing the average age at infection. Consequently, many countries do not vaccinate against rubella. The World Health Organization recommends that for safe rubella vaccination, at least 80% coverage of each birth cohort should be sustained. The nonlinear relationship between CRS burden and infection dynamics has been much studied; however, how the complex interaction between epidemic and demographic dynamics affects minimum safe levels of coverage has not been quantitatively evaluated across scales necessary for a global assessment. We modelled 30-year CRS burdens across epidemiological and demographic settings, including the effect of local interruption of transmission via stochastic fadeout. Necessary minimum vaccination coverage increases markedly with birth and transmission rates, independent of amplitude of seasonal fluctuations in transmission. Susceptible build-up in older age groups following local stochastic extinction of rubella increased CRS burden, indicating that spatial context is important. In low birth-rate settings, 80% routine coverage is a conservative guideline, particularly if supplemented with campaigns and vaccination of women of childbearing age. Where birth and transmission rates are high, immunization coverage must be well above 80% and campaigns may be needed. Policy-makers should be aware of the potential negative effect of local extinction of rubella, since heterogeneity in vaccination coverage will shape extinction patterns, potentially increasing CRS burdens.

Structured models of infectious disease: inference with discrete data.

The usage of structured population models can make substantial contributions to public health, particularly for infections where clinical outcomes vary over age. There are three theoretical challenges in implementing such analyses: (i) developing an appropriate framework that models both demographic and epidemiological transitions; (ii) parameterizing the framework, where parameters may be based on data ranging from the biological course of infection, basic patterns of human demography, specific characteristics of population growth, and details of vaccination regimes implemented; (iii) evaluating public health strategies in the face of changing human demography. We illustrate the general approach by developing a model of rubella in Costa Rica. The demographic profile of this infection is a crucial aspect of its public health impact, and we use a transient perturbation analysis to explore the impact of changing human demography on immunization strategies implemented.

Modelling the first dose of measles vaccination: the role of maternal immunity, demographic factors, and delivery systems.

Measles vaccine efficacy is higher at 12 months than 9 months because of maternal immunity, but delaying vaccination exposes the children most vulnerable to measles mortality to infection. We explored how this trade-off changes as a function of regionally varying epidemiological drivers, e.g. demography, transmission seasonality, and vaccination coverage. High birth rates and low coverage both favour early vaccination, and initiating vaccination at 9-11 months, then switching to 12-14 months can reduce case numbers. Overall however, increasing the age-window of vaccination decreases case numbers relative to vaccinating within a narrow age-window (e.g. 9-11 months). The width of the age-window that minimizes mortality varies as a function of birth rate, vaccination coverage and patterns of access to care. Our results suggest that locally age-targeted strategies, at both national and sub-national scales, tuned to local variation in birth rate, seasonality, and access to care may substantially decrease case numbers and fatalities for routine vaccination.

The epidemiology of rubella in Mexico: seasonality, stochasticity and regional variation.

The factors underlying the temporal dynamics of rubella outside of Europe and North America are not well known. Here we used 20 years of incidence reports from Mexico to identify variation in seasonal forcing and magnitude of transmission across the country and to explore determinants of inter-annual variability in epidemic magnitude in rubella. We found considerable regional variation in both magnitude of transmission and amplitude of seasonal variation in transmission. Several lines of evidence pointed to stochastic dynamics as an important driver of multi-annual cycles. Since average age of infection increased with the relative importance of stochastic dynamics, this conclusion has implications for the burden of congenital rubella syndrome. We discuss factors underlying regional variation, and implications of the importance of stochasticity for vaccination implementation.