A new study finding published in the journal Nature Microbiology has revealed that an increase in the levels of pro-oxidants caused by dietary shifts leads to a 90% reduction in Plasmodium parasite load during the hepatic phase of the infection and consequently lowers the severity of the malaria disease.

Malaria, an infectious disease caused by Plasmodium parasites while infecting red blood cells (RBCs). Prior to infecting RBCs, Plasmodium parasites must infect a hepatocyte and undergo a period of remarkable division and expansion, termed schizogony, to become an exoerythrocytic form (EEF). The extreme replication rate of Plasmodium parasites inside hepatocytes must impose a high demand for lipids.

Researchers have found that the host's susceptibility to developing malaria depends on his or her metabolic state, which can be easily manipulated through external stimuli such as dietary patterns. The progression and development of an infectious disease are directly dependent not only on the characteristics of the causing infectious agent but also on the genetic characteristics of the host, which also dictate the efficiency of the infection.

During the last years, scientific discoveries have suggested that external factors independent of the host-parasite dichotomy, such as eating habits, can impact in the establishment, progression and endpoint of infections. The team manipulated the diet fed to lab mice for very short periods of time and evaluated the level of infection caused by the malaria parasite. The study showed that administration of a high-fat diet to mice for a short period decreased Plasmodium liver infection.

Plasmodium sporozoites can successfully invade and initiate replication but die inside hepatocytes, thereby are unable to cause severe disease. Transcriptional analyses combined with genetic and chemical approaches reveal that this impairment of infection is mediated by oxidative stress. The reactive oxygen species, probably produced from fatty acid β-oxidation, directly impact Plasmodium survival inside hepatocytes, and parasite load can be rescued by exogenous administration of the antioxidant N-acetylcysteine or the β-oxidation inhibitor etomoxir.

The current study results revealed that the mechanism used by the host to eliminate the malaria parasite might contribute to explain how certain genetic alterations associated to high levels of oxidative stress, such as sickle-cell anaemia or beta thalassemia, have been selected in the population due to their protective effect against malaria. The data showed that acute and transient dietary alterations markedly impact the establishment of a Plasmodium infection and disease outcome