The parasite that causes malaria is stealthy. When Plasmodium first infects a person via a mosquito bite, it hides in the liver before invading the bloodstream. It changes its outer coat and manipulates the immune system to avoid arousing the host's defenses.

Many countries around the world are scaling up interventions against malaria, with the goal of eliminating it. That calls for treating everyone who is infected, even people who don't feel sick yet. But here is the challenge: some forms of Plasmodium can persist in the liver and emerge to infect the blood weeks or even years later. The conventional diagnostic test—examining a person's blood sample under a microscope—can miss infections at the stage when parasites are hiding in the liver.

In addition, most drugs against malaria target the later blood-borne stage, not the liver. Parasite resistance to the most effective drugs against malaria, such as artemisinin, is a growing problem, and malaria experts see a need for new drugs that target the liver stage.

A new project based at the Emory Vaccine Center and Yerkes National Primate Research Center is seeking to address these challenges. The Malaria Host-Pathogen Interaction Center (MaHPIC), funded by up to $19 million from the National Institute for Allergy and Infectious Diseases, brings together Emory scientists with partners at the University of Georgia, Georgia Tech and the CDC. Led by Emory malaria expert, Mary Galinski, the project takes a systems biology approach to malaria. Researchers will build an encyclopedia of the disease, studying and cataloguing in molecular detail how malaria parasites interact with human and animal hosts. Computational researchers then will design mathematical models to simulate and analyze what's happening during an infection and to find patterns that predict the course of the disease and its severity.

For example, the MaHPIC team will examine how infection produces changes in host and parasite genes, proteins, and metabolites in both non-human primates and infected humans. In addition to tests for dormant parasites, these studies could help doctors identify biomarkers to predict which cases will become the most severe. Knowledge about the early, stealthy stages of Plasmodium infection could direct drug discovery and inform design of a malaria vaccine, Galinski says.