Researchers from The University of Manchester suggest that during the Early Pleistocene, the arrival and presence of these early hominins drove the mosquitoes to adapt to feeding on humans.

The study, published in , uncovers how and why certain mosquitoes developed this preference, and the environmental triggers which brought about its development.

The findings could provide critical insight into mitigating the impacts of novel diseases caused by mosquito-borne pathogens, which place a significant burden on global human health, and shed light on the colonisation of Southeast Asia by early humans.

, Senior Lecturer in Earth and Environmental Sciences at The University of Manchester, said “Our findings suggest that early humans must not only have been present in Sundaland at this time, but there in substantial numbers, which is an important piece of evidence, beyond fossil records, to the broader puzzle of the colonization of hominins in insular Southeast Asia.

The team focused on the Anopheles leucosphyrus group, made up of 20 different species of mosquitoes native to Southeast Asia. Some species are extremely anthropophilic (human targeting) and very efficient spreaders of human malaria parasites. Others feed mainly on monkeys, gibbons, and orangutans in forest canopies, spreading a form of malaria that would be harmless to humans, but can be deadly for these other primates.

In the study, the researchers sequenced 38 mosquitoes - supplemented with publicly available genome data of two others - from 11 species within the leucosphyrus group.  The specimens were collected between 1992-2020 and involved sampling larvae from animal wallows hidden deep in the forest or in remote areas of Southeast Asia.

The study included species of all three subgroups (Leucosphyrus, Riparis and Hackeri), and represent all three blood-feeding behaviours - human, non-human primate, and mixed - providing a solid evolutionary framework mapping host preference within the Leucosphyrus group.

They found that the ancestors of the Leucosphyrus Group likely originated in the permanently humid conditions of Sundaland (Borneo, peninsular Malaysia, Sunda Shelf), during the early Pliocene, between 5.3 and 3.6 million years ago. These conditions favoured feeding in the canopy, so the mosquitoes most likely fed primarily on non-human primates.

However, the late Pliocene and into the Pleistocene, saw extensive environmental change, where the global climate became cooler and drier. The shift from permanent humidity to seasonal, open forest and expanding savannah, saw the arrival of a host of new mammals. This led to an adapted species of mosquitoes that could feed readily both in the canopy and on the ground.

The researchers suggest that this shift toward more flexible feeding behaviour may have been the bridge to human-feeding behaviour.

This paper was published in the journal Scientific Reports

Full title: Early hominin arrival in Southeast Asia triggered the evolution of major human malaria vectors

DOI:

A potential new way of treating cerebral malaria has been discovered by scientists at the Universities of Manchester and Glasgow, in a study using mice.

The authors found that inhibiting a complex called the inflammasome, at the same time as delivering anti-malarial drugs, reduced mortality from experimental cerebral malaria in mice.

The research, published in PNAS and funded by the Medical Research Council, also shows that animals treated with inflammasome inhibitors and anti-malarial drugs had significantly reduced levels of cerebral pathology and signs of neurological impairment, compared with mice treated only with anti-malarial drugs.

Though the team are yet to trial the drug on humans, the research constitutes a significant breakthrough in the fight against malaria, which according to the World Health Organisation kills 438, 000 people every year.

“Cerebral malaria is so deadly because there are no early symptoms; it’s often hard to spot until it’s too late, “said Dr Kevin Couper from The University of Manchester, who supervised the project.

“We were particularly interested in looking at why anti-malarial drugs, the only current treatment for the condition, do not promote optimal recovery from cerebral malaria, as well as developing new therapies. So, we were delighted when we discovered some of the biological processes involved.”

After sequencing the RNA in brain cells of mice, the team including Dr Patrick Strangward, Dr Michael Haley, Dr Manuel Garcia-Albornoz and Mr Jack Barrington who performed most of the experiments, realised that recovery associated with experimental cerebral malaria was regulated by a family of genes involved in controlling the immune response within the brain.

When the product of one of the genes called IL33 was given with anti-malarial drugs, mortality in mice went from 20% to 0% and pathological features in the brain such as haemorrhage, blocked vessels, leakage and impaired neuronal signalling were also significantly reduced.

The results suggested that IL33 was important for inhibiting the inflammasome, and when the team used an inflammasome inhibitor alongside anti-malarial drugs to treat experimental cerebral malaria they got the same result as treatment with IL33.

Dr Couper said: “This is an extremely promising area of research and we are excited that there is now a targetable process for researchers to work on.

“But it’s clear that mice are not humans and our next stage will be to check if this dysregulation in the IL-33-inflammasome pathway occurs in people who have cerebral malaria and influences their recovery, and we are starting to do that with partners in Africa.

Prof David Brough, from The University of Manchester, co-supervised the project. He said: “The identification of the inflammasome in experimental cerebral malaria highlights it as an important therapeutic target and complements our ongoing research to develop more effective inhibitors for use in treating inflammatory disease.”

T is published in PNAS