UNIVERSITY PARK, PA. – Malaria parasites survive the mosquito-free dry season by quietly waiting for the rainy season to return, which mosquitoes bring with it. New research by an international team including Penn State scientists helps explain how the Plasmodium falciparum parasite survives the life cycle disruption that requires development within the mosquito host for transmission between humans. An article describing the research appears in Nature Medicine on October 26th.
“One of the great puzzles in studying malaria,” said Manuel Llinás, professor of biochemistry, molecular biology and chemistry at Penn State and author of the paper, “is understanding how malaria parasites survive during the dry season, when mosquitoes are not around Transmission there. ” between people. “
Malaria parasites, affecting hundreds of millions of people around the world and killing nearly 300,000 children in Africa every year, spread among people through the bites of infected mosquitos. In many regions of the world where malaria is endemic, an extreme dry season clears all breeding grounds for mosquitoes, causing the mosquitoes to disappear and the transmission of malaria to be interrupted for several months each year. There are asymptomatic people infected with the parasite in these areas all year round. Symptomatic malaria cases, however, are very high when mosquitoes are present before disappearing again during the dry season. The falls resume in the following rainy season when mosquitoes return and the cycle begins again.
The research team was headed by Silvia Portugal at Heidelberg University Hospital. Members of her laboratory visited Mali and worked with Boubacar Traoré’s group at the University of Science, Techniques and Technologies of Bamako in Mali to educate nearly 600 Malians between the ages of three months and 45 years over several cycles of the annual dry and rainy season follow . By comparing blood samples from people with malaria parasites to uninfected people, they found that parasites did not induce host immunity during the dry season.
According to the researchers, malaria parasites persist in humans in small quantities during the dry months, which do not endanger the health of the host, and guarantee their survival until the next rainy season, when parasite transmission can resume. A distinctive feature of the malaria parasite is that it can appear to disappear from the bloodstream by clinging to the wall of blood vessels as the parasite grows in the red blood cells. This adhesion to the blood vessel helps the parasite avoid clearance when red blood cells are routinely passed through the spleen, thereby removing old, damaged, or infected red blood cells.
Malaria in the rainy and dry season. Above: Histogram of the incidence of malaria cases over a year, showing the decrease in the number of cases in humans during the dry season. Middle: View of Bamako in the rainy and dry season, during the dry season mosquito breeding grounds disappear and the transmission of the malaria parasite is interrupted for several months. Bottom: Plasmodium falciparum, the malaria parasite, stained with Giemsa on thick blood smears from a case of malaria in the rainy season (left) and an asymptomatic infection at the end of the dry season (right), which shows a reduced parasite load in the asymptomatic sample.
BILD: Portugal Laboratory
Although the malaria parasites reproduce within the red blood cells throughout the year, the infected cells are less adhesive during the dry season and circulate longer in the body during the parasite’s replication cycle. The longer circulation time makes them more susceptible to removal by the human spleen, which minimizes the parasite load on infected individuals.
Using parasites collected throughout the year, the researchers tried to answer a number of questions: were parasites that persisted during the dry season were genetically different? How was the parasite genome transcribed? How quickly and efficiently did replication occur in the human host? How have circulating host metabolites been affected? How well did the parasites escape a spleen-like filter? And which adhesive molecules could promote the differences?
‘With the help of a large team of experts in many of these areas,’ said Portugal, ‘we were able to show that the parasites collected during the dry season look very different, but most of these differences were promoted by less efficient adhesion of infected cells.’ on the vasculature, leading to more developed parasites that are present in the circulatory system during the dry season and also to more efficient removal of infected cells by the spleen. “
The Penn State team used mass spectrometric metabolomics to identify differences in human blood serum from infected individuals in both the dry and rainy seasons.
“Our team wanted to investigate whether there are metabolic differences in people infected with the malaria parasite at different times of the year when mosquitoes are common or absent,” said Llinás. “What metabolic changes can affect the parasites so that they can fly under the radar in the human host until the next rainy season when the mosquitoes return and transmission resumes?”
Although the analysis clearly showed a separation between human metabolites collected in the dry season and the rainy season, the sample size was too small to determine specific metabolites that can increase the circulation time required to minimize parasite load.
“Our collective results are very exciting as they suggest that there are both human adaptations and parasite adaptations during the dry season when people are not exposed to mosquitos,” said Llinás. “It is tempting to speculate that mosquito bites alter the development of the parasite in the human host during the rainy season to promote improved development and transmission to mosquitoes. How this could be done remains a mystery and has yet to be determined. “
In addition to Llinás, Portugal and Traoré, the research team includes Erik Allman, a former postdoctoral fellow in the Llinás Laboratory at Penn State, now at AstraZeneca, and members of the US National Institute for Allergies and Infectious Diseases. the Indiana University School of Medicine; Karolinska Institutet in Stockholm, Sweden; University Hospital Copenhagen in Denmark; the University of Minho in Portugal; the Institut Cochin in Paris, France; the University of Glasgow in Great Britain; and the University of Exeter in the UK