THE EFFECTS OF MATERNAL IMMUNITY AND AGE STRUCTURE ON POPULATION IMMUNITY TO MEASLES

Friday, 24th of July 2015

THE EFFECTS OF MATERNAL IMMUNITY AND AGE STRUCTURE ON POPULATION IMMUNITY TO MEASLES

A. McKee, M. J. Ferrari, and K. Shea

Department of Biology, Pennsylvania State University, 208 Mueller Laboratory, University Park, PA 16802 USA

Department of Biology, Pennsylvania State University, W243 Millennium Science Complex, University Park, PA 16802 USA

A. McKee, Phone: +1-609-4397628, Email: ude.usp@002mza.

Corresponding author.

Excerpt below; full text, with graphs and equations, is at

www.ncbi.nlm.nih.gov/pmc/articles/PMC4485449/

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.

Electronic supplementary material

The online version of this article (doi:10.1007/s12080-014-0250-8) contains supplementary material, which is available to authorized users.

Keywords: Context-dependent management, Disease elimination, Maternal immunity, Measles, Vaccination

Great progress has been made towards worldwide measles eradication, yet it still remains an elusive objective, as endemic disease persists in some places, and is reintroduced to others where it was long absent. One aspect of the measles problem is maintenance of elimination; the disease has begun to reemerge in places where it was thought to be eliminated. Measles was officially eliminated from the USA in 2000 and the Pan-American Health region (PAHO region) in 2002 (Castillo-Solórzano et al. 2011a, b), and, despite recent outbreaks, endemic transmission has not reemerged. However, other countries have not been as successful at maintaining elimination. Europe has seen recent increases in transmission, despite promising improvements in the early 2000s (Morbidy and Mortality Weekly Report 2011), including places like Germany (Roggendorf et al. 2010; van Treeck 2006) and France (Parent du Châtelet et al. 2010). Recent outbreaks have occurred in parts of southern Africa where measles was previously reduced near the point of elimination (Shibeshi et al.2014). Additionally, despite the disease officially remaining eliminated in the USA, there have been recent outbreaks that cast doubt on the actual population immunity to measles in the USA (Parker and Staggs 2006; Sugerman et al. 2010).

With measles, as with any other directly transmissible, immunizing infection, there is some threshold level of immunity in the population, called the herd immunity threshold, beyond which the disease cannot invade (Anderson and May 1991). The goal of measles vaccination programs is to achieve and maintain a sufficiently large immunized population that this threshold will be met, and measles will be locally eradicated and unable to reinvade. The conventional wisdom for measles is that this threshold level of immunity is 90–95 % (Hall and Jolley 2011; Moss and Griffin 2006).

Measles vaccination programs since the 2002 PAHO elimination are typically composed of multiple strategies for vaccine distribution (Danet and Fermon 2013; Koehlmoos et al. 2011). Here, we consider routine immunizations (RIs), in which children of specific ages are vaccinated during clinic visits (Bauch et al. 2009). RIs, in combination with other types of vaccination campaigns, were used to effectively eradicate measles in the Americas by 2002 (Castillo-Solorzano et al. 2011a, b). RIs are targeted at a specific age; the World Health Organization recommends measles vaccination between 9 and 12 months of age (WHO 2012).

Trans-placentally acquired maternal immunity temporarily protects infants born to immune mothers, but interferes with vaccine efficacy (Cutts et al. 1995; Gans et al. 2001). Vaccines administered before this maternal immunity wanes will be ineffective, but otherwise, there is minimal disadvantage to vaccinating children as early as possible. Therefore, there is a window of susceptibility between the waning of maternal immunity and the average age of infection during which vaccination is likely to be effective and prophylactic in most children (McLean and Anderson 1988a, b). The optimal age of vaccination will fall within this age window, where the lower end is determined by acquired maternal immunity (Moss and Griffin 2006; McLean and Anderson 1988a, b), and the upper end is classically considered to be determined by local disease incidence (McLean and Anderson 1988a, b).

There is uncertainty in the literature about when, on average, maternal immunity wanes in any specific population. Some evidence suggests that vaccine-derived maternal immunity wanes earlier than naturally derived maternal immunity (that is, maternal immunity from women who have been infected with measles) (Leuridan et al. 2010), but the magnitude of this difference and the effect it may have on the optimal age at which to vaccinate is unclear. Additionally, the mothers health (Scott et al. 2005) as well as local nutrition and breast feeding practices have been shown to affect the rate of waning of maternal immunity and are difficult to know precisely (Cáceres et al. 2000). What limited evidence we have available suggests that the rate at which maternal immunity wanes varies from country to country (McLean and Anderson 1988a, b).

In places where measles is endemic, children may become infected and therefore become naturally resistant before the age at first vaccination. Thus, vaccines administered too late fail to prevent disease and may be considered as “wasted” doses—doses administered to a person already immune. It is classically understood that, as disease incidence declines, average age of infection increases (Roggendorf et al. 2010), thus increasing the upper age limit on the window of infant susceptibility. In these settings, a common policy is to increase the target age of routine immunizations so that a greater proportion of infants will have lost maternal immunity, and each dose is more likely to be more effective (Christie and Gay 2011).

However, we have seen unexpected outbreaks in countries with what was thought to be good measles control, such as the 2009 epidemic in Burkina Faso (Kidd et al. 2012) and the 2010 epidemic in Malawi (Minetti et al. 2013a, b). These countries had otherwise low disease incidence and high routine coverage. However, these unexpected epidemics indicate that, despite the low measles incidence, there was a substantial susceptible pool. The interaction between vaccine effectiveness, maternal immunity, and the chosen age target for routine immunization may have contributed to the rapid build-up of this susceptible pool and the underestimation of outbreak risk.

Differences in age structure could also contribute to observed differences in population immunity resulting from similarly targeted RIs. Notably, the proportion of the population in the Americas that is <1 year old is much smaller than the proportion of the African population that is <1 year old. As such, the number of children in the susceptible window in Africa will make up a relatively large proportion of the population and may suggest the need for a different target age for routine immunization. Consequently, the upper end of the infant susceptibility window may also be determined by the age structure of the region, rather than solely by disease incidence. Importantly, if the target age of vaccination is not tailored to average local immunity and age structure, the proportion of infants no longer maternally immune but not yet vaccinated might be too large for herd immunity to be achievable (Fig. 1a). In essence, if more than 5 % of the population is in the susceptible window between waning of maternal immunity and vaccination, a 95 % population immunity level will be unachievable. . . .