Written by Nóra Lehotai, MIMS
During the World Health Assembly in 2007, the World Health Organization (WHO) Member States established 25th April as World Malaria Day. Fourteen years have passed, and malaria is still a global threat, claiming over 400, 000 lives every year, mostly killing children under 5 according to the WHO.
Malaria, an infectious disease, is caused by the unicellular protozoan Plasmodium parasites. These parasites infect the Anopheles mosquitos which become carriers of the parasites and transmit them to humans when the infected female Anopheles mosquito bites us. The parasites are injected from the mosquito’s salivary glands to the blood in the form of sporozoites, which travel to the liver (liver stage) where they multiply and transform into merozoites. The merozoite form invades our red blood cells (RBCs; blood stage), grows, and transforms into trophozoite, schizont and finally, into gametocyte form, which induces the malaria symptoms. The typical incubation period, from the bite until the first symptoms, is 11 days.
Illustration: The Plasmodium life cycle from the scientific article AH Lee, LS Symington, DA Fidock (2014) DNA repair mechanisms and their biological roles in the malaria parasite Plasmodium falciparum. MMBR, 78(3) 469-486.
In the mosquito, the transformation continues to give birth to a new cycle. Gametocytes undergo sexual reproduction in the midgut and turn into zygotes, then ookinetes. The ookinete form is mobile and by breaking out from the midgut, it invades other organs of the mosquito to turn into oocysts, which, after undergoing several cell divisions, form the sporozoites. The newly formed, yet immature sporozoites travel to the salivary glands where they finish their development and become infectious to humans.
Two research groups at The Laboratory for Molecular Medicine Sweden (MIMS) at Umeå University, are working on breaking the chain of malaria transmission, which is the key to eliminating malaria. One research group, led by Dr Ellen Bushell, investigates the role of malaria parasite exported proteins in host-parasite interactions, while the other group, led by MIMS director Prof Oliver Billker, develops new genetic technologies to decipher how malaria parasites reproduce in mosquitoes and get transmitted.
Photo: Ellen Bushell and Oliver Billker, malaria researchers at MIMS, Umeå University. Credit: Mattias Petterson
I asked Ellen and Oliver to tell us what does World Malaria Day mean to them, and what do they think; where do we stand in reaching zero malaria?
"This year, World Malaria Day feels extra important to mark”-says Ellen. “During the ongoing COVID-19 pandemic, malaria continues to cause suffering and claim lives while many planned and ongoing malaria control campaigns have been paused. This poses a significant risk to achieving the global eradication goal. Nevertheless, I remain hopeful for the future, and we must celebrate the many small victories and progress we make.
One example is Algeria, that is now only the second ever country on the African continent (mainland) to be certified as malaria-free following its eradication in 2019. There is also a new promising blood-stage vaccine, RH5.1/AS01B. In phase I and II clinical trials, this vaccine has been shown to be safe and able to illicit robust antibody responses that are associated with inhibition of parasite growth. This is incredibly encouraging as an effective vaccine will be critical to achieving the goal of a malaria free world”.
For Oliver, World Malaria Day means a day for celebrating the enormous progress that has been made in fighting a devastating infection.
“We use the occasion in our research team to remind ourselves of the role we want to play in this global effort. The biggest challenge when fighting malaria is the fight against poverty because that disables giving poor people access to healthcare. Then comes research, which enables overcoming the problems of rising drug and insecticide resistance. We urgently need an effective vaccine, and we need drugs that will not only cure children but also help eradicate the disease. With my team, we have high hopes that the insights and methods we are developing here in Umeå, will help control malaria, and that with strong international collaboration and knowledge sharing, zero malaria is achievable.”
Last year, the first mosquito immune cell atlas was published to understandhow mosquitoes fight malaria and other infections. The research was done in the frame of a big international collaboration between the Wellcome Sanger Institute (UK), MIMS (Umeå University, Sweden) and National Institutes of Health (NIH, USA), where Oliver Billker was among the senior leaders of the project.
“We discovered a rare but important new cell type we called a Megacyte, which could be involved in immune priming, and which appears to switch on further immune responses to the Plasmodium parasite. This is the first time a specific mosquito cell type has been implicated in regulating the control of malaria infection.”-says Oliver.
“The research generated by the MIMS malaria teams, helps to break down the boundary of knowledge needed for malaria elimination. “- commented Dr Thanat Chookajorn, a malaria drug resistance expert (Mahidol University, Thailand, Head of the Genomics and Evolutionary Medicine Unit), visiting the Billker lab. “Ten years ago, no one expected that the malaria research community could have access to a comprehensive list of genes necessary for parasite survival and mating. These and other research findings have the power to transform how malaria control and elimination are implemented in Africa and Asia. For example, they may allow us to understand how drug-resistant parasites could effectively propagate in the field and how to develop novel drugs and vaccines in the lab.
Photo: Oliver holds a container with mosquitos. Credit: Mattias Petterson
Read more in the topic:
- News release from ExpreS2ion Biotechnologies about the RH 5.1/AS01B vaccine: : https://mb.cision.com/Main/14402/3329663/1404604.pdf
- Scientific article in Med Clinical Advances (CellPress) : https://www.cell.com/med/pdfExtended/S2666-6340(21)00116-1
- Publication on the first mosquito immune cell atlas: Gianmarco Raddi and Ana Beatriz F. Barletta et al. (2020) Mosquito cellular immunity at single-cell resolution. Science. DOI 10.1126/science.abc0322
- To read the full article, please go to: https://science.sciencemag.org/content/369/6507/1128.full
- To read the press release by MIMS, please go to: http://www.mims.umu.se/news-events/248-latest-news/1979-the-first-mosquito-cell-atlas-is-published-now-in-science-where-mims-director-oliver-billker-is-a-joint-senior-author.html
Read more about Ellen’s and Oliver’s work in Swedish:
- (Oliver Billker) https://kaw.wallenberg.org/forskning/soker-nyckelgener-att-hindra-malariasmitta
- (Ellen Bushell) https://kaw.wallenberg.org/forskning/streckkod-att-kartlagga-proteiner-och-skapa-vaccin-mot-malaria
- (Video about infectious diseases, including malaria research by Oliver Billker) https://kaw.wallenberg.org/tema-forskning-om-infektionssjukdomar-ska-radda-miljontals-liv/popup
MIMS group leader and malaria researcher interested in parasite-host interactions.
Research fellow at Department of Molecular Biology
Units: Group Ellen Bushell
6K och 6L, Sjukhusområdet
Umeå universitet, 901 87 Umeå
Professor at Department of Molecular Biology
Units: Group Oliver Billker
6K och 6L, Sjukhusområdet
Umeå universitet, 901 87 Umeå
Affiliated as research fellow at Molecular Infection Medicine Sweden (MIMS)