Monkey malaria weak spot could prevent hop to humans

13 June 2016

Immuno-fluorescence microscopy image of P. knowlesi infected red blood cells. The outline of red blood cells shown in red, and the parasites are labelled with green and blue.

Immuno-fluorescence microscopy image of P. knowlesi infected red blood cells. The outline of red blood cells shown in red, and the parasites are labelled with green and blue. (Click to view larger image)
© Robert Moon

Scientists have identified a gene that lets monkey malaria infect humans. Plasmodium knowlesi, a malaria parasite carried by macaque monkeys in South East Asia relies on a single gene, called NBPXa to invade human red blood cells. The discovery, made by researchers at the Francis Crick Institute in London and funded by the MRC, opens a new research route to develop a vaccine to protect people from the disease.

Recent deforestation and changing land use brings macaque monkeys infected with P. knowlesi into closer contact with people. In 2014, Malaysia recorded 2,500 cases of monkey malaria in people. This is almost 8 in every 10 incidences of malaria and reports of the disease are increasing across South East Asia.

"The parasite's presence in wild monkeys means that controlling and eventually eradicating malaria caused by P. knowlesi will be extremely difficult," says research team leader Dr Tony Holder, "but our study has found a weak link that could be exploited to develop a human vaccine to prevent this emerging disease."P. knowlesi can hop between monkeys and people if a mosquito bites an infected macaque and then a person. It is the only malaria parasite that can infect both humans and animals and the disease is as severe as that caused by the most dangerous of the human malaria parasites.

Cynomologus macaque, the natural host which can be infected by P. knowlesi

Cynomologus macaque, the natural host which can be infected by P. knowlesi
© Robert Moon

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Dr Holder's team, based at the Francis Crick Mill Hill Laboratories, looked at the process of red blood cell invasion using samples of monkey malaria in the lab. They found that a gene called NBPXa is essential for the parasite to infect human blood cells. When they stopped the gene from working the parasite still infected monkey cells but could no longer get inside human cells - a process essential for the parasite to multiply and spread.

"This is the first time a role for the NBPXa gene has been demonstrated in malaria, and it is a crucial one, allowing this potentially killer disease to invade human cells," said lead author Dr Rob Moon, now at the London School of Hygiene & Tropical Medicine where he is continuing research into NBPXa.

"Whether our research can be taken forward to develop a vaccine depends on how well antibodies against the NBPXa protein block parasite invasion of blood cells. We also know there is lots of variation in this protein in parasites strains from the field, so a vaccine will need to work against all strains - not just the ones in the lab." says Dr Moon.

The team collaborated with researchers in Saudi Arabia and Malaysia to generate a complete picture of the parasite's genetic code. They say a vaccine to protect against malaria caused by P. knowlesi is still a long way off.

Scientists have been working on a vaccine to protect against malaria caused by the human parasite Plasmodium falciparum. It is proving difficult because P. falciparum can use many different proteins to invade red blood cells. P. knowlesi doesn't have this flexibility as it uses just one protein to infect human cells. The team hope this lack of back-up infection options could make P. knowlesi much more vulnerable to a vaccine targeted at the blood cell infection stage in people.

The paper, Normocyte binding protein required for human erythrocyte invasion by the zoonotic malaria parasite Plasmodium knowlesi, is published today in Proceedings of the National Academy of Sciences (PNAS).

 

Notes to editors:

For more information, please contact:

Elaine Snell, elaine.snell@crick.ac.uk

Laura Dibb, laura.dibb@crick.ac.uk

020 7611 2169

The Francis Crick Institute is a new and distinctive biomedical research institute. Its purpose built laboratory in the King's Cross area of London will open in 2016.  The institute's work - which is already underway at the Crick's Clare Hall, Lincoln's Inn Fields and Mill Hill laboratories - will help to understand why disease develops.

We will find new ways to diagnose, prevent and treat a range of illnesses − such as cancer, heart disease and stroke, infections and neurodegenerative diseases. We will bring together outstanding scientists from all disciplines, carrying out research that will help improve the health and quality of people's lives, and keeping the UK at the forefront of medical innovation. The Francis Crick Institute is a charity supported by the Medical Research Council, Cancer Research UK, the Wellcome Trust, UCL (University College London), Imperial College London and King's College London.