Joint press release of the DZIF and the Heidelberg University Hospital
Malaria parasites of the species Plasmodium need the Anopheles mosquito to enter the human body. In turn, mosquito larvae need water in order to develop. But in many areas where malaria is endemic, a strict dry season dries all mosquito breading sites and interrupts malaria transmission for several months. Dr Silvia Portugal from the Heidelberg University Hospital (UKHD) and the German Center for Infection Research (DZIF) has now shown with studies in Mali how malaria parasites remain silently inside humans during the dry months, at low levels that do not risk the host’s health, guaranteeing survival until the next wet season when parasite transmission can resume. The study describes that malaria parasites are less able to avoid removal of infected cells by the human spleen, an organ of major importance to clear the blood.
The malaria parasite replicates inside red blood cells of the human body. Old or damaged red blood cells and also red blood cells containing large parasites that circulate are regularly cleared by the human spleen. In order to avoid clearance when passing through the spleen, the cell with the growing parasite is to seemingly disappear from blood circulation by adhering to the wall of the blood vessels. “We found low levels of more developed parasites circulating in the dry season, although malaria parasites replicate alike inside red blood cells throughout the year.” Dr Silvia Portugal describes the surprising result of the study she led. “A part of the parasites are seemingly less able to avoid removal of infected cells by the human spleen and their reduced levels can guarantee survival of the host and the parasites until the next wet mosquito season,” the study resumes.
The Heidelberg team collaborated with the Mali International Center of Excellence in Research in Bamako, Mali, the National Institute of Allergy and Infectious Diseases, National Institutes of Health in the US, and other research groups worldwide. Understanding the malaria pathogen and its survival strategies is one of the major challenges of infection research: the malaria parasite affecting millions worldwide and killing almost 400.000 people in 2018.
Carolina M Andrade together with other members of Silvia Portugal’s laboratory visited Mali several times in the past years and collaborating with Prof Boubacar Traoré’s group followed for several dry and transmission seasons ~600 Malian individuals with 3 months to 45 years of age. With blood samples from parasite carriers and non-infected individuals the team determined that dry season parasites were not triggering host immunity during the dry season. And with parasites collected at different times of the year the researchers could question if persisting the dry season parasites were genetically different, how parasite genome was transcribed, how fast and efficiently it could replicate when cultured in vitro, how it affected host circulating metabolites, and how well it could escape a spleen-like filter.
With the help of a vast team of experts in many of these areas, they could show that parasites collected during the dry season appear very different, but most of those differences were promoted by a less efficient adhesion to the vasculature of infected cells, leading to more developed parasites present in circulation during the dry season, but also leading to more efficient clearance of infected cells by the spleen. The reduced parasite can survive in the host till the next wet season. If the parasite adapts its adhesion phenotype to the season in response to environmental factors or lower adhesion is achieved through accumulating replication cycles remains to investigated. Dr Silvia Portugal recently moved from the University Hospital in Heidelberg to the Max Planck Institute for Infection Biology in Berlin, where she will also continue her malaria projects.
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