In regions of high transmission, falciparum malaria and other important infectious diseases exhibit vast diversity from the perspective of the immune system, which underlies only partial protection to re-infection and a large fraction of infections lacking symptoms. This vast and dynamic parasite diversity represents a major challenge to control efforts, and to the application of the basic reproductive number (known as R0) because strains cannot be clearly defined. To develop a complementary reproductive number, we investigate here whether and how the diversity of new genes (encoding antigens) is able to accumulate. We derive an analytical expectation for the existence of a threshold concerning diversity accumulation, and test it with a stochastic and agent-based model of malaria transmission that incorporates the major antigen-encoding multigene family known as var.
COS 80 Abstract - An antigenic diversification threshold for falciparum malaria and its control at high endemicity
Background/Question/Methods
Results/Conclusions
We present a novel reproductive number we call Rdiv comparing the generation speed and death rates of new genes. We demonstrate a positive association between this reproductive number and the intensity of transmission, and the existence of a sharp transition at Rdiv equal one. When Rdiv is pushed below this threshold, transmission still occurs while new genes generated by either mutation or recombination fail to accumulate, resulting in a lower number of persistent strains, which should facilitate successful further intervention. The derivation of a reproductive number for antigenic diversification can be applied to other infectious diseases with a fast turnover of antigens, where large standing diversity similarly opposes intervention.