by Linda Whitney

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Professor Matthias Marti, Wellcome Centre for Integrative Parasitology (WCIP), The University of Glasgow Institute of Infection, Immunity and Inflammation

Bringing together scientists from various disciplines is helping to develop novel ways to tackle the parasites that cause malaria with new tools, drugs and vaccines.

Scientists in Glasgow are aiming to halt the spread of malaria by tackling malaria-causing parasites in their human hiding places.

“The parasite that causes malaria lodges in various tissue niches where it causes disease” says Professor Marti, a parasitologist at the Wellcome Centre for Integrative Parasitology (WCIP) at The University of Glasgow Institute of Infection, Immunity and Inflammation.

Marti is working mainly with Plasmodium falciparum, the human parasite that caused over 435,000 malaria-related deaths a year in 2017.

Bone marrow is the headquarters for malaria infection and transmission

“The parasite travels via the blood and binds to the walls of blood vessels (vasculature). Discovering that the extravascular niche of the human bone marrow was also a hiding place for Plasmodium parasites was a surprise,” says Marti, lead author on the 2014 study that resulted in the discovery.

“Even more intriguing, we found that the bone marrow is also the major place where transmission stages mature until they are ready to be picked up by a mosquito.

“Knowing that the bone marrow is the headquarters for parasite growth and transmission opens up a whole new field for research,” says Marti. “Why does the parasite go to the bone marrow and how does it survive in this place without being attacked by the immune system?”

Great success in malaria elimination amid warning signs

Ongoing efforts for malaria elimination and eradication had brought down infections from 260 million to just over 200 million and fatal cases from 1 million to about 400,000 between 2000 and 2015. However, since then, progress has stalled and there is concern of a rebound.

“This is a critical time to maintain the momentum. When the previous campaign was abandoned in the 1960s, it resulted in a huge resurgence of cases.”

“Our research focuses on closing a knowledge gap in the malaria transmission cycle, as a basis for efforts to reduce or completely block transmission from humans to mosquitos” says Marti.

Multidisciplinary teams to understand parasites’ lifestyle

Three years ago, Marti came to WCIP to continue his research. “With the combination of in vitro studies and field work, in particular in Malawi, we have started to understand the hidden stages of parasites’ lives,” he says.

The WCIP has been essential to this. “It brings together a critical mass of people from multiple disciplines, and attracts the best researchers, students, collaborators and attention from funders,” says Marti.

“Here we have experts in clinical research, immunology and computational biology, epidemiology and vector biology. Access to bioengineering skills means we can develop a model of bone marrow on a chip to study the parasite interactions in the marrow under controlled in vitro conditions.”

“Bringing together people with state-of-the art skills, excellent technology, resources and collaboration opportunities means moving further, faster.”

Targeting parasites in the bone marrow, or before it reaches it

Marti identifies at least three ways that WCIP research could lead to new ways to tackle malaria – with drugs, vaccines, and earlier diagnosis.

“If we can prevent the parasites going into the marrow, or trap them there, we can block the transmission cycle. Alternatively, if we can help the body flush the parasite-infected red blood cells out via the spleen, we will also have a way forward,” he says.

Old or otherwise altered blood cells are normally cleared from the body by the spleen, but this does not usually happen with those infected by malaria parasites.

“If we can create a vaccine that acts against the proteins on the infected red blood cells then they could be cleared by the immune system, or they may be prevented from binding within the bone marrow,” he says.

“Also, we could possibly develop diagnostic markers that indicate the presence of the parasites in the marrow before they get detected in the blood and get to the next stage of the cycle,” he says.

Bone marrow studies may also identify ways to make anti-malarial drugs more effective.

“Cancer studies show that bone marrow is less accessible to drugs because of the low blood flow. If we can find a method of reaching the parasites in the bone marrow more efficiently, we could make the drugs more effective,” says Marti.

The future needs a funding pipeline

“Malaria is far from eradication and maintaining a research and drug discovery pipeline is essential in our fight to get rid of this deadly disease.

“Here we are among the world’s leading places to do malaria research, and we are on our way towards creating new tools to tackle malaria.”

For more information visit glac.ac.uk/researchinstitutes/iii

By Linda Whitney