Malaria is one of the world's biggest killers, responsible for over a million deaths every year, mainly in children and pregnant women in Africa and South-east Asia. It is caused by the malaria parasite, which is injected into the bloodstream from the salivary glands of infected mosquitoes. There are a number of different species of parasite, but the deadliest is the Plasmodium falciparum parasite, which accounts for 90 per cent of deaths from malaria.
The malaria parasite infects healthy red blood cells, where it reproduces. The P. falciparum parasite generates a family of molecules, known as PfEMP1, that are inserted into the surface of the infected red blood cells. The cells become sticky and adhere to the walls of blood vessels in tissues such as the brain. This prevents the cells being flushed through the spleen, where the parasites would be destroyed by the body's immune system, but also restricts blood supply to vital organs.
Symptoms can differ greatly between young and older children depending on previous exposure to the parasite. In young children, the disease can be extremely serious and potentially fatal if untreated; older children and adults who have grown up in endemic areas are resistant to severe malaria but rarely develop the ability to rid their bodies of the parasite.
Each parasite has 'recipes' for around sixty different types of PfEMP1 molecule written into its genes. However, the exact recipes differ from parasite to parasite, so every new infection may carry a set of molecules that the immune system has not previously encountered. This has meant that in the past, researchers have ruled out the molecules as vaccine candidates. However there appear to be at least two main classes of PfEMP1 types within every parasite, suggesting different broad tactical approaches to infecting the host. The most efficient tactic or combination of tactics to use may depend on the host's immunity.
Now, Dr George Warimwe and colleagues from the Kenya Medical Research Institute (KEMRI)-Wellcome Trust Programme and the Wellcome Trust Sanger Institute, have shown that the parasites adapt their molecules depending on which antibodies it encounters in the host's immune response. They have also found evidence to suggest that there may be a limit to the number of molecular types that are actually associated with severe disease.
"The malaria parasite is very complex, so our immune system mounts many different responses, some more effective than others and many not effective at all," explains Dr Peter Bull from the KEMRI-Wellcome Trust Programme and the University of Oxford, who led the research. "We know that our bodies have great difficulty in completely clearing infections, which begs the question: how does the parasite manage to outwit our immune response? We have shown that, as children begin to develop antibodies to parasites, the malaria parasite changes its tactics to adapt to our defences."
The researchers at the KEMRI-Wellcome Trust Programme studied malaria parasites in blood samples from 217 Kenyan children with malaria. They found that a group of genes coding for a particular class of PfEMP1 molecule called Cys-2 tended to be switched on when the children had a low immunity to the parasite; as immunity develops, the parasite switches on a different set of genes, effectively disguising it so that immune system cannot clear the infection
Dr Warimwe and colleagues also found an independent association between activity in Cys-2 genes and severe malaria in the children, suggesting that specific forms of the molecule may be more likely to trigger specific disease symptoms. This supports a previous study in Mali which suggested that the same class of PfEMP1 molecule was associated with cerebral malaria.
The findings could suggest a new approach to tackling malaria, in terms of both vaccine development and drug interventions, argues Dr Bull.
"If there exists a limited class of severe disease-causing variants that naturally-exposed children learn to recognise readily, this opens up the possibility of designing a vaccine against severe malaria that mimics an adult's immune response, making the infections less dangerous. But this would still be an enormous task.
"Similarly, if we can establish what the particular class of molecules are doing, then we may be able to develop a drug to modify this function and relieve symptoms of severe disease."
Craig Brierley | EurekAlert!
GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University
Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy