Researchers identifying biomarkers to predict that if someone infecting with malaria will get sick; Immunological signatures can predict whether malaria-infected children will develop fever or other symptoms; Surprisingly, activation of the well-known tumor-suppressor protein p53 is associated with enhanced protection against malaria fever and increasing p53 in human immune cells and in mice results in a decrease in malaria-induced inflammation.
But the findings could lead to new strategies for dampening the harmful inflammatory; responses associating with some infections and identifying individuals who might be at risk for such responses. Malaria is caused by the Plasmodium falciparum parasite and remains a major killer of children in Africa. Our limited understanding of how the human immune system controls malaria-induced inflammation and parasite growth impedes the development of vaccines and adjunctive therapies for this devastating disease.
Malaria is caused by parasites that are transmitted to people through the bites of infected mosquitoes. In 2017, there were approximately 219 million malaria cases worldwide and 435,000 malaria deaths. P. falciparum is the most prevalent malaria parasite in Africa and is responsible for most malaria deaths globally. In areas of intense transmission, children who survive the first five years of life have typically acquired immunity to severe malaria.
Biomarkers predicting Malaria
But in non-immune individuals, P. falciparum malaria can cause fever and rapidly progress to severe illness and death if not treated early. The development of a safe and effective vaccine could play a critical role in malaria elimination efforts. Although progress is being makinge, a malaria vaccine; that reliably inducing long-term protection remaining as elusive. The complexity of the Plasmodium parasite and the incomplete understanding of critical processes, such as host immune protection and disease pathogenesis, have hampered efforts to develop a vaccine.
Antimalarial drugs, in combination with mosquito control programs; have played a key role in controlling malaria in endemic areas, resulting in significant reduction of the geographic range of malarial disease worldwide. But the emergence and spread of drug-resistant parasites and insecticide-resistant mosquitos have contributed to a re-emergence of malaria; turning back the clock on control efforts. The need for new strategies to prevent malaria infection and disease has become a critical priority on the global malaria research agenda.
To gain insights into host factors that might protect against malaria disease; Crompton and first author Tuan Tran of Indiana University School of Medicine applied a systems biology approach; to study children who differed in their ability to control parasite growth and fever following P. falciparum infection. They collected and analyzed blood samples from healthy; uninfected Malian children at enrollment before the malaria season, during bi-weekly scheduled visits; and at their first malaria episode of the ensuing season.
Specifically, the researchers integrated whole blood transcriptomics with flow-cytometric analysis of blood cells; and cytokine and antibody profiles. They focusing on children aged 6-11 years, the age during which malaria immunity begins to be acquiring in this region. During the first malaria season, the researchers identified three distinct outcomes of P. falciparum infection.