Credit: U.S. Centers for Disease Control
Malaria parasites survive the mosquito-free dry season by quietly waiting for the return of the rainy season that mosquitoes bring with them. 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 there is none Mosquitos for transmission. ” 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. These areas have asymptomatic people infected with the parasite year-round. Symptomatic cases of malaria, 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, ages three months to 45 years, over multiple cycles of annual dry and rainy seasons 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 amounts 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.
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.
Malaria in the rainy and dry season. Above: Histogram of the frequency 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 seasons, during the dry season mosquito breeding grounds disappear and the transmission of the malaria parasite is interrupted for several months. Below: 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. Photo credit: Portugal Laboratory
With the help of parasites collected throughout the year, the researchers tried to answer several questions: whether 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 a less efficient adhesion of infected cells to the vasculature, which leads to more developed parasites present in the circulatory system during the dry season and also to more efficient clearance 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 keep parasite load down.
“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 evolution of the parasite in the human host during the rainy season to favor improved development and transmission to mosquitoes. How this could happen remains a mystery and has yet to be determined.”
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Carolina M. Andrade et al. A prolonged circulation time of Plasmodium falciparum underlies a persistent asymptomatic infection in the dry season, Nature Medicine (2020). DOI: 10.1038 / s41591-020-1084-0 Provided by Pennsylvania State University
Quote: Malaria parasites hide in humans when it is not mosquito season (2020, October 27th). Retrieved November 4, 2020 from https://medicalxpress.com/news/2020-10-malaria-parasites-humans-mosquito-season.html
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