The ability of malaria parasites to persist in the body for
years is linked to the expression of a set of genes from thepir gene family, scientists from the Francis Crick
Institute and the Wellcome Trust Sanger Institute have found. Their results are published today inNature Microbiology.
The researchers show in a mouse study that as few as 1 in 10 of
the parasites that initially appear in the blood express this set
of pir genes. But almost all the parasites found
persisting in the body at later times express the genes, and can be
a source of further spread of the disease.
Malaria is caused by parasites which are passed between people
by mosquitoes. The body's immune system will eventually destroy
most of the malaria parasites. But some will continue to reside
dormant in the body year after year without causing any
symptoms.
The team hopes that a better understanding of the pirgene family will make it possible to destroy this reservoir of
parasites that allows ongoing transmission of malaria despite
increased efforts to eradicate the infection.
The World Health Organisation reports that 303,000 children
under five years old died from malaria in 2015 and an estimated 212
million people suffered the infection worldwide.
The Crick team, led by Dr Jean Langhorne, collaborated with Dr
Adam Reid and Dr Matthew Berriman at the Sanger Institute to
identify which genes are most active in parasites that establish
long-lasting infection.
They used mice infected with the rodent malaria parasitePlasmodium chabaudi by mosquito bites and studied the
expression of parasite genes during the blood stage of the
infection. They confirmed their results with a second rodent
malaria parasite, Plasmodium berghei.
Dr Jean Langhorne, Group Leader at the Francis Crick Institute,
says: "We found that the first malaria parasites to appear in the
blood were a highly varied population. From this population only a
minority of parasites expressing a specific set of pirgenes survived to establish a long-lasting, persistent infection.
Surprisingly, parasites expressing these pir genes take
over as the dominant parasites very quickly, and independently of
the mouse's antibody or T-cell response."
All species of malaria parasites, including the five that infect
humans, have related pir genes. This suggests thepir gene family could be a clue to preventing chronic
infection more generally.
Dr Adam Reid, joint first author from the Sanger Institute,
explains: "The pir genes are likely to be common to all
species of malaria, and so it is possible that there is a shared
mechanism across malaria species that enables them to create
chronic infections. The parasite then has a way to establish a
reservoir to ensure it is eventually passed on to another human or
animal host."
This is the first time that scientists have identified a
potential role for these genes in establishing chronic infection.
The group hopes that if a way can be found to target the biological
mechanisms involved, it could prevent long-lasting persistent
malaria infection and empty the reservoir.
Dr Langhorne adds: "Understanding how certain parasites go on to
establish chronic infection and determining how a particular set ofpir genes are involved may provide us with a means to
prevent chronic infection which could be applicable to all types of
malaria in humans."
The paper 'Antibody-independent mechanisms regulate
the establishment of chronic Plasmodium infection' is published
in Nature Microbiology.
The research was funded by the Francis Crick Institute
(which receives its core funding from Cancer Research UK, the UK
Medical Research Council and the Wellcome Trust) and by the
Wellcome Trust.