“Malaria parasites can hide inside the bone marrow and evade the body's defences, research confirms,” BBC News report.
It is hoped that this insight into the activities of the parasites could lead to new treatments.
While most people associate malaria with mosquitoes, the disease is actually caused by tiny parasites called Plasmodium, which infect mosquitoes and spread the infection to humans by injecting them with spores.
These spores grow and multiply in the liver and then infect blood cells, causing the symptoms of malaria.
To continue their lifecycle, some of the parasites sexually mature and are then transferred back into mosquitoes during another bite, where they can breed.
The researchers looked at tissue samples from autopsies of children who had died from malaria.
The study found evidence that sexual maturation of the parasite is likely to take place in the bone marrow, but outside of the blood vessels. This might be why the immune system rarely destroys them, as infection-fighting antibodies are unable to target bone marrow tissue.
It is hoped that these results can pave the way for the development of new drugs to target this key stage. This has the potential to reduce the number of infected mosquitoes, thus decreasing the number of malaria cases.
The ultimate hope is that malaria could be eradicated in the same way as smallpox.
Where did the story come from?
The study was carried out by researchers from around the globe, including the Harvard School of Public Health, the Liverpool School of Tropical Medicine, the University Of Malawi College Of Medicine, and Brigham and Women’s Hospital, Boston. It was funded by the US National Institutes of Health.
The study was published in the peer-reviewed medical journal Science Translational Medicine.
The study was briefly reported by BBC News, which provided an accurate summary of the research.
What kind of research was this?
This was an autopsy study designed to investigate where a key stage in the lifecycle of the parasite that causes malaria takes place.
The tropical disease is caused by Plasmodium parasites. The most severe form of malaria is caused by Plasmodium falciparum. The lifecycle of the parasite relies on blood-feeding mosquitoes and humans. When an infected mosquito bites a human, sporozoites are injected into the human, and they travel to the liver. They mature into schizonts in the liver and then rupture to release meroziotes into the blood. These merozoites divide and multiply asexually by sticking to the sides of small blood vessels. This process causes the symptoms of malaria, which include shivering and fever.
However, for the parasites to continue their lifecycle, some of the meroziotes mature into the sexual stage; these are called gametocytes. These male and female gametocytes are then ingested by mosquitoes the next time they have a blood meal; they can then fertilise and replicate within the mosquito.
The gametocytes are only present in the bloodstream when they are mature enough to be taken up by mosquitoes. They take six to eight days to mature, and it is believed this takes place in human tissue. This stage has not been studied in depth, as the Plasmodium falciparum will only live in humans, so rodent studies are not possible. This study looked for these immature gametocytes in multiple tissue sites in autopsies of children who had died from malaria, to find out where this stage takes place.
What did the research involve?
The researchers initially used antibodies to identify the parasite in general, as well as specific antibodies to the sexual gametocytes, to detect them in various tissues from six autopsies. They looked at tissue samples from eight organs and the subcutaneous fat.
They measured the total proportion of parasites in each organ compared to the level of gametocytes.
They then measured the level of gene activity of three stages in the gametocyte maturation process in the different organs, to see if the first of these stages takes place in one particular site.
The researchers then looked in detail at the bone marrow from 30 autopsies to gather more information about where the gametocytes mature.
Finally, they performed experiments with growing Plasmodium falciparum in the laboratory.
What were the basic results?
Results from the first six autopsies revealed that:
- The spleen, brain, heart and gut had the highest numbers of total parasites.
- Levels of gametocytes were high in the spleen, brain, gut and bone marrow.
- There was a significantly higher proportion of gametocytes compared to total parasites in the bone marrow (44.9%), in comparison to the gut (12.4%), the brain (4.8%) and all other organs.
- The first stage of gametocyte gene activity was highest in the bone marrow.
Results from the 30 autopsies of bone marrow found that:
- The youngest gametocytes did not stick to blood vessels as happens in the asexual reproduction of merozoites; instead, they were outside of the blood vessels in the bone marrow.
- Immature gametocytes appeared to grow inside young red blood cells.
The laboratory experiments confirmed that Plasmodium falciparum gametocytes can mature inside young red blood cells.
How did the researchers interpret the results?
The researchers said there is evidence that gametocytes develop within the bone marrow, probably in early red blood cells, and that this process uses a different mechanism to the asexual cell replication.
This means there is potential for drugs to be developed that could target this process.
This interesting study has found evidence of the likelihood that the sexual reproductive stage in the lifecycle of Plasmodium falciparum takes place outside of the blood vessels, in the bone marrow.
It has also shown that these immature gametocytes are rarely destroyed by the immune system.
It is hoped that these results can pave the way for the development of new drugs to target this key stage in the Plasmodium falciparum lifecycle.
While this would not treat the symptoms of malaria – which come from the asexual reproduction of merozoites – it could potentially stop the transmission of the sexual gametocytes back into mosquitoes.
This could reduce the number of infected mosquitoes, thus decreasing the number of malaria cases.
Eradicating malaria is a challenge, but many public health experts think it is plausible.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
BBC News, 9 July 2014
Links to the science
Science Translational Medicine. Published online July 9 2014