Excess haemoglobin digestion by malaria parasites: A strategy to prevent premature host cell lysis

To understand the osmotic stability of a Plasmodium falciparum-infected red blood cell, whose membrane permeability becomes highly increased during parasite growth, we developed an integrated mathematical model of the homeostasis of an infected red cell. The model encoded the known time courses of red cell membrane permeabilisation and of haemoglobin digestion, as well as alternative options for parasite volume growth. Model simulations revealed that excess haemoglobin digestion, by reducing the colloid-osmotic pressure within the host red cell, is essential to preserve the osmotic stability of the infected cell for the duration of the parasite asexual cycle. We present here experimental tests of the model predictions and discuss the available evidence in the context of the interpretations provided by the model.