Epidemiological consequences of enduring strain-specific immunity requiring repeated episodes of infection

Abstract

GAS are under development, but their effective use will require better understanding of how immunity develops following infection. Evidence from an animal model of skin infection suggests that the generation of enduring strain-specific immunity requires two infections by the same strain within a short time frame. It is not clear if this mechanism of immune development operates in humans, nor how it would contribute to the persistence of GAS in populations and affect vaccine impact. We used a mathematical model of GAS transmission, calibrated to data collected in an Indigenous Australian community, to assess whether this mechanism of immune development is consistent with epidemiological observations, and to explore its implications for the impact of a vaccine.We found that it is plausible that repeat infections are required for the development of immunity in humans, and illustrate the difficulties associated with achieving sustained reductions in disease prevalence with a vaccine.

Modelling the effect of within-host dynamics on the diversity of a multi-strain pathogen

“…• The period diversity of ATs: It is a measure of the number and evenness of ATs in circulation in the population over a period of time. It demonstrates how many antigenic types circulating in the population as well as the evenness among the number of infections by each AT in a given time interval u (Smeesters et al, 2009;Chisholm et al, 2020). We use Simpson's reciprocal index to calculate period diversity, D(t):…”

“…Our conceptual framework for understanding the interaction between direct and indirect competition in multi-strain systems (Figure 8) can help us to interpret the observations of certain multi-strain pathogens. For example, it has been suggested that a Group A Streptococcus infection results in an antigen-specific host immune response, however, there is not yet consensus on the duration of immunity after an infection and the strength of within-host competition among strains (Pandey et al, 2016;Hysmith et al, 2017;Chisholm et al, 2020Chisholm et al, , 2021.…”

“…Gog and Grenfell (2002) showed that when the immune response to an infection by one strain provides some level of immunity against other strains (cross immunity), multiple strains with varying serotypes can only co-exist in the population when the duration of immunity is sufficiently long, otherwise at most only one group of strains with similar serotypes can co-exist. Chisholm et al (2020) showed that diversity may also depend non-monotonically on transmissibility and can be maximized by an intermediate level of transmissibility. These models tend to make varied assumptions about the direct competition that occurs within hosts.…”

“…While other models assume that co-infection is not possible and that one strain will always outcompete other strains (Abu-Raddad and Ferguson, 2004;Aquino et al, 2015;Alizon, 2013). Some models incorporate the effects of competition within hosts in a phenomenological way by, for example, assuming there is increasing resistance to co-infection as additional strains co-infect the host (Buckee et al, 2004;Chisholm et al, 2020;Bianco et al, 2009). Other models incorporate more biologically realistic representation of within-host competition.…”

“…For example, in the model proposed by Watkins et al (2015) strains were classified according to their antigenic and metabolic type, and it was assumed that infection could not occur if a host was currently infected by a strain with the same metabolic type. There is often little immunological (host level) and strain-specific metabolic (strain level) data to support these assumptions about direct competition (Watkins et al, 2015;Chisholm et al, 2020). Given this uncertainty, multi-strain models with different assumptions of direct competition may produce different epidemiological dynamics.…”