Available online 30 March 2022

The liver and blood stages of Plasmodium infection exert a marked influence on each other.

In high-transmission settings, concomitant liver and blood stage infections are the rule rather than the exception.

Blood-stage Plasmodium infection negatively influences the protective efficacy of pre-erythrocytic malaria vaccines.

The liver stage of Plasmodium infection impacts the outcome of erythrocytic infection and pathology.

While the liver and blood stages of the Plasmodium life cycle are commonly regarded as two separate fields of malaria research, several studies have pointed towards the existence of a bidirectional cross-talk, where one stage of mammalian infection may impact the establishment and progression of the other. Despite the constraints in experimentally addressing concurrent liver and blood stage Plasmodium infections, animal models and clinical studies have unveiled a plethora of molecular interactions between the two. Here, we review the current knowledge on the reciprocal influence of hepatic and erythrocytic infection by malaria parasites, and discuss its impacts on immunity, pathology and vaccination against this deadly disease.

Plasmodium

Liver infection

Blood stages

Malaria

© 2022 The Authors. Published by Elsevier Ltd on behalf of Australian Society for Parasitology.