Major malaria discovery offers hope on how to confuse parasite

Scientists have discovered a sensor used by malaria parasite to understand its host environment, opening up promising avenues for tampering with the signal in a way that could help combat the disease that plagues millions of people worldwide.

Disorienting the deadly microbes can stop them from replicating, scientists at the University of Geneva found in a ground-breaking development. The work was published in the journal Science Advances.

– Key numbers to note

Malaria remains a significant public health concern globally, particularly in sub-Saharan Africa, with almost 250 million cases reported each year, resulting in 621,000 deaths., most of them children.

Ninety-six percent of all cases occur in Africa, according to the World Health Organization, and over  half of those occur in Nigeria, the Democratic Republic of Congo, Uganda, Mozambique, Angola, and Burkina Faso.

In April, Nigeria approved the use of a ground-breaking malaria vaccine, R21 to help save lives.

– What’s new

The parasitic disease, transmitted through mosquito bites, is caused by a microbe called plasmodium. During its journey from mosquito to human, plasmodium must adapt to various organs and cells it parasitizes.

But microbes generally do not have sensory organs, instead, they have sensors made of proteins to detect molecules specific to the environments they colonize. While most living organisms share the same types of sensors, plasmodium doesn’t.

Biologists at the University of Geneva (UNIGE) identified a new type of sensor that enables plasmodium to know precisely where it is and what to do.

The discovery opens up the possibility of scrambling the signals perceived by this sensor to disorientate the parasite and thus prevent its replication and transmission.

“Understanding this very specific biological mechanism is an important step towards countering the parasite,” explains Mathieu Brochet, associate professor in the Department of Microbiology and Molecular Medicine at the UNIGE Faculty of Medicine, who led the project.

“At each stage of its life cycle, the parasite must logically pick up signals that enable it to react correctly, but which ones and how?”

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– This is how the University of Geneva explains what happens

When a person is bitten by a Plasmodium-infected mosquito, the parasite enters the bloodstream and travels to the liver, where it thrives for around 10 days without causing any symptoms. After this period, Plasmodium re-enters the bloodstream, where it attacks red blood cells.

Once inside the red blood cells, the parasites multiply in a 48-hour cycle. At the end of each multiplication cycle, the newly-formed parasites leave their host red blood cells, destroying them and infecting new ones.

It is this destruction of red blood cells that causes the waves of fever associated with malaria. Severe forms of malaria are linked to the obstruction of blood vessels by infected red blood cells.

When a mosquito bites a human whose blood is infected with Plasmodium, the parasite changes its development program to colonize the intestine of its new host. After a further period of multiplication, plasmodium returns to the mosquito’s salivary glands, ready to infect a new human.

Unknown communication channels

There are small molecules absent in the blood but present in the mosquito that the parasite is able to detect.

“Starting from this single known element, we have identified a sensor that enables the parasite to detect the presence of these molecules when it is ingested by a mosquito”, explain Ronja Kühnel and Emma Ganga, PhD students in Mathieu Brochet’s laboratory and first authors of this study.

“This sensor is made up of five proteins. In its absence, the parasite does not realize that it has left the bloodstream for the mosquito, and is therefore unable to continue its development”.

Surprisingly, this sensor is also present at other stages of the parasite lifecycle, notably when the parasite has to leave the red blood cell. “We then observe exactly the same mechanism: without this sensor, Plasmodium is trapped in the red blood cells, unable to continue its infection cycle.”

However, scientists have not identified the human molecules detected by the parasite; identifying them could provide a better understanding of how waves of fever are caused by Plasmodium.