Malaria, is a blood borne disease caused by single cell parasites from the Plasmodium genus. It is a major global public health issue with millions of cases, and nearly half a million deaths every year. Our scientists, along with their collaborators, have discovered that malaria parasites can occupy sites outside the bloodstream, specifically in the bone marrow and spleen where red blood cells are formed.

The studies show, both in animal models and in human infection, that this is the major niche for the development of malaria transmission stages and a significant reservoir for the parasite’s replicative stages. These results demonstrate, for the first time, the movement of blood stage parasite forms and their migration across the vascular barrier to other parts of the body. This work also demonstrates that localisation in the bone marrow and spleen allows the parasite not only to build a ‘reservoir of infection’, but also to gain additional protection from certain antimalarial drugs including the current frontline drug artemisinin. These new findings suggest that this invasion of the bone marrow and spleen could be crucial to targeting the disease.

Professor Andy Waters, Director of the Wellcome Centre for Molecular Parasitology, said: “These papers together represent a step forward in our understanding of the behaviour of the malaria parasite. It is possible that bone marrow serves as the reservoir of infection avoiding the immune system and preferentially producing and releasing gametocytes so that when mosquitoes appear the disease can be retransmitted.”

Malaria is a blood borne disease caused by single cell parasites that invade, grow and then replicate in red blood cells, which then burst releasing new parasites that initiate a new blood stage cycle of invasion – a process which makes malaria such a deadly disease. Malaria is transmitted by female mosquitoes which themselves become infected when they take up parasites from an infected person as they take their blood meal.  However, this human to mosquito transmission is only achieved if a small subset of blood borne parasites have escaped the cycle described above and instead have developed into a specialised form (a gametocyte) for transmission.

‘A cryptic cycle in haematopoietic niches promotes initiation of malaria transmission and evasion of chemotherapy’is published in Nature Communications;

'Bone marrow is a major parasite reservoir in Plasmodium vivax infection’ is published in mBio;

and ‘Plasmodium gametocytes display homing and vascular transmigration in the host bone marrow’ is published in Science.

Two of the three studies were performed in an international collaborative effort including groups led by Prof. Volker Heussler (University of Berne, Switzerland), Prof. Terrie Taylor (College of Medicine, Blantyre, Malawi), Profs. Dyann Wirth, Manoj Duraisingh and Curtis Huttenhower (Harvard University, Boston, USA), Prof. Tom Wellems (National Institute of Health, Bethesda, USA) and Dr. Nicanor Obaldia (Gorgas Institute, Panama).

The Glasgow work was funded by the Wellcome Trust, the MRC and ERC BoneMalar.

 

First published: 3 May 2018

<< Centre News