Title: First-in-man evaluation of magnetic blood filtration device for the treatment of severe and drug-resistant malaria
Funder: Department of Health and Social Care

Abstract: The MediSieve Filter is a magnetic blood filter that can remove malaria infected red blood cells (RBC) directly from a patient s bloodstream by exploiting their naturally occurring magnetic properties. The magnetic properties of malaria infected cells are well-established &ndash; parasites that have invaded a RBC produce a paramagnetic waste product haemozoin (&ldquo;the malaria pigment&rdquo;), stored within infected cells. Haemozoin production is essential to the parasite s lifecycle, and has been used as a target for malaria drugs in the past. Magnetic blood filtration is similar to dialysis: a patient s blood is continuously circulated through an external blood loop, passing through a magnetic filter which captures infected cells; the rest of the blood returns to the patient unharmed. The device is targeted at hospitalised severe malaria patients who receive IV treatment, mainly children; there are 6M such patients around the world, and over 1,500 per year in the UK. Used in conjunction with existing chemotherapies, a one-off treatment provides a rapid, effective and selective removal of malaria infected RBCs from the bloodstream in just 2-3h, during which over 2-3x a patient s total blood volume is processed. Disease severity, recovery times and mortality are all strongly linked to the parasite clearance rate and the patient s initial parasitaemia. Our pre-clinical results indicate that the MediSieve Filter could reduce a child s parasitaemia by 90% in 2h, compared to 24-30h today. Used in combination with IV drugs, potential patient benefits include not only reduced mortality, but also faster recovery times and reduced side effects, leading to improved quality of life. Lower time in hospital and reduced doses of IV drugs would provide a net economic benefit to the hospital also lead directly to economic benefits for patients and their families, as they are able to return to work or school sooner. The device can also be used to treat drug-resistant malaria strains, which are a growing problem particularly in SE Asia. The device has undergone extensive in vitro and in vivo pre-clinical testing, culminating in animal safety trials, performing the procedure with sheep under full clinical conditions. A total of 3x the animals total blood volume was processed without any adverse effects. In vitro separation of malaria infected cells from both cultured P. falciparum and donated P. vivax have demonstrated that the device can capture infected cells at the late ring, trophozoite and schizont stages, with a single pass efficiency of 70%. This project will support pivotal first-in-man clinical safety studies of the MediSieve Malaria Filter, performing the procedure with 10 healthy volunteers to investigate safety. This is a vital milestone in the development of the device, and will subsequently enable clinical efficacy trials to be performed on malaria patients and support applications for regulatory approvals.

Lay abstract: The MediSieve Filter is a magnetic blood filter that can remove malaria infected red blood cells (RBC) directly from a patient s bloodstream by exploiting their naturally occurring magnetic properties. The magnetic properties of malaria infected cells are well-established &ndash; parasites that have invaded a RBC produce a paramagnetic waste product haemozoin (&ldquo;the malaria pigment&rdquo;), stored within infected cells. Haemozoin production is essential to the parasite s lifecycle, and has been used as a target for malaria drugs in the past. Magnetic blood filtration is similar to dialysis: a patient s blood is continuously circulated through an external blood loop, passing through a magnetic filter which captures infected cells; the rest of the blood returns to the patient unharmed. The device is targeted at hospitalised severe malaria patients who receive IV treatment, mainly children; there are 6M such patients around the world, and over 1,500 per year in the UK. Used in conjunction with existing chemotherapies, a one-off treatment provides a rapid, effective and selective removal of malaria infected RBCs from the bloodstream in just 2-3h, during which over 2-3x a patient s total blood volume is processed. Disease severity, recovery times and mortality are all strongly linked to the parasite clearance rate and the patient s initial parasitaemia. Our pre-clinical results indicate that the MediSieve Filter could reduce a child s parasitaemia by 90% in 2h, compared to 24-30h today. Used in combination with IV drugs, potential patient benefits include not only reduced mortality, but also faster recovery times and reduced side effects, leading to improved quality of life. Lower time in hospital and reduced doses of IV drugs would provide a net economic benefit to the hospital also lead directly to economic benefits for patients and their families, as they are able to return to work or school sooner. The device can also be used to treat drug-resistant malaria strains, which are a growing problem particularly in SE Asia. The device has undergone extensive in vitro and in vivo pre-clinical testing, culminating in animal safety trials, performing the procedure with sheep under full clinical conditions. A total of 3x the animals total blood volume was processed without any adverse effects. In vitro separation of malaria infected cells from both cultured P. falciparum and donated P. vivax have demonstrated that the device can capture infected cells at the late ring, trophozoite and schizont stages, with a single pass efficiency of 70%. This project will support pivotal first-in-man clinical safety studies of the MediSieve Malaria Filter, performing the procedure with 10 healthy volunteers to investigate safety. This is a vital milestone in the development of the device, and will subsequently enable clinical efficacy trials to be performed on malaria patients and support applications for regulatory approvals.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: INFECTION