Scots researchers uncover malaria ‘master switch’

Researchers have discovered how malaria initiates the process of passing from human to human. Picture: Complimentary

The scientists have identified the factor that the parasite must produce to begin the process of passing from human to mosquito and then onwards through the insect’s bite.

They have discovered the “master switch” that triggers the development of specialised sexual cells that are responsible for the infection of the mosquito and initiation of transmission, the process of the parasite passing through the mosquito.

It is hoped the discovery will open up the way to the development of new drug treatments to prevent transmission of the potentially fatal disease.

The research was carried out by scientists from the University of Glasgow and the Wellcome Trust Sanger Institute, near Cambridge.

Andy Waters, professor and director of the Wellcome Trust Centre for Molecular Parasitology at the University of Glasgow, said: “Malaria is the biggest parasitic disease killer that there is in the world, so clearly we need to combat that. There are drugs, but they are losing their efficacy because the parasite is becoming resistant. There is currently no vaccine.”

Malaria is transmitted to people through the bites of mosquitoes which have themselves been infected by the Plasmodium parasites that cause the disease through a previous blood meal taken from an infected person.

When a mosquito bites an infected person, a small amount of blood is taken in which contains microscopic malaria parasites.

About two weeks later, when the mosquito takes its next blood meal, the progeny of these parasites mix with the mosquito’s saliva and are injected into the person being bitten.

The University of Glasgow/Wellcome Trust Sanger Institute team have now identified the way the parasite flicks the switch that allows transmission to take place.

Male and female sexual forms (termed gametocytes) of the malaria parasite are responsible for the infection of the mosquito and initiation of transmission.

The researchers have identified a single regulatory protein which acts as the “master switch” that triggers the development of the gametocytes.

If the malaria parasite is unable to develop gametocytes, then transmission of the disease from one host to another can no longer take place.

The researchers spent more than three years using highly-sophisticated genome sequencing techniques to identify mutants of the protein which prevent the development of gametocytes; then, they effectively reversed the process by genetic engineering of the mutant gene in the parasites to repair the protein switch which restored the parasite’s ability to make gametocytes.

The discovery of how the key regulatory protein works means this “transmission switch” could be disabled in future through the development of new drugs.

However, any drug treatment developed as a result of this research is likely to be what scientists describe as an “altruistic intervention”, where the drug would be taken by adults who were already infected by malaria but had developed resistance to the disease.

The drug would block the “transmission switch”, thus preventing re-infection or infection to, for instance, their children. It is anticipated that many parents would agree to take such a drug if it meant offering greater protection to their children.

Dr Oliver Billker, of the Wellcome Trust Sanger Institute, said: “This work has significant implications for basic research as well. The identification of this switch opens the way to study in great detail the process of gametocyte production by the parasite which in turn could eventually lead to new therapies such as drugs.”

The research is published in the February 23 edition of the journal Nature.

The World Health Organisation estimates that in 2012, 483,000 children under five died from malaria.

Some 90 per cent of all malaria deaths occur in sub-Saharan Africa and 77 per cent occur in children under five.

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