A theoretical framework for the immunoepidemiology of blocking antibodies to helminth infection

Epidemiological evidence is widely cited in support of the hypothesis that certain antibody responses to human helminth, especially schistosome, infection exhibit blocking activity. This evidence includes positive correlations between antibody levels and the rate of re-establishment of infection following chemotherapy, antibody levels which peak in younger and more susceptible age classes, lower ratios of blocking antibodies to others in older and less susceptible age classes. In this paper simple mathematical models are used to explore expected age-specific relationships between antibody levels, parasite burdens and re-establishment rates for different combinations of protective, neutral and blocking immune responses. In general, all the above cited patterns may be generated without invoking blocking activity, especially if the abilities to produce different antibody responses have different immunological memories, i.e. persist for different lengths of time in the absence of continued exposure to antigen. None of these patterns, including a positive correlation between antibody levels and rates of re-establishment following chemotherapy, offers unambiguous evidence for blocking activity. Blocking activity is also predicted to affect the shape of the age-intensity curve and the relationship between susceptibility to infection and age in ways which are not necessarily consistent with the epidemiological evidence. The importance of the blocking activity, which has been convincingly demonstrated in vitro, to population level immunoepidemiological patterns in the field therefore remains uncertain.