Parasite genome sequences offer hope of new drugs

The genomes of two parasites that cause the debilitating tropical disease schistosomiasis (also known as bilharzia or snail fever) have been sequenced. The findings are published in two articles in the journal Nature. As well as uncovering possible targets for new drugs, the r...

The genomes of two parasites that cause the debilitating tropical disease schistosomiasis (also known as bilharzia or snail fever) have been sequenced. The findings are published in two articles in the journal Nature. As well as uncovering possible targets for new drugs, the researchers identify a number of existing drugs that could be effective against the disease.

Schistosomiasis is caused by tiny parasitic worms that spend part of their life cycle in humans and part of their life cycle in freshwater snails. The larvae of the parasite are released into the water by the snails. When people wade through or bathe in the water, the worm larvae burrow into their skin and make their way to the blood vessels.

Once mature, the female parasites lay eggs in the walls of the intestine. They leave the body via faeces. If they manage to get into water infested with their snail hosts, the life cycle starts again.

Symptoms of infection include anaemia, diarrhoea, internal bleeding and organ damage. Over 200 million people in 76 countries are affected by this neglected tropical disease, which causes around 200,000 deaths every year in sub-Saharan Africa alone.

Patients are currently treated with the drug praziquantel, which is both cheap and effective, although it does not prevent subsequent re-infection. However, there are concerns that the parasites could one day become resistant to it, and so researchers are keen to find alternatives.

These studies focused on Schistosoma mansoni, which is found in Africa, parts of the Middle East, Brazil, Venezuela and some islands of the West Indies, and Schistosoma japonicum, which is prevalent in southern China, the Philippines and parts of Indonesia. An analysis of its genome reveals how well adapted the worm is to its lifestyle. It has a lot of genes for enzymes that break down proteins; these help the worm to burrow through the host's skin and other tissues. It also has a sophisticated sensory system that allows it to analyse chemical, light and temperature in the water and in its hosts.

'This genome sequence catapults schistosomiasis research into a new era,' commented Dr Matthew Berriman of the Wellcome Trust Sanger Institute in the UK, the lead author of the study on S. mansoni. 'It provides a foundation for understanding aspects of the parasite's complex biology as well as a vehicle to immediately identify new targets for drug treatment.'

The researchers hope that comparing the genomes of these closely related parasites will result in more information on their biology, and lead to the development of new drugs.

The team working on S. mansoni also identified 120 parasite enzymes that, if blocked by drugs, would interfere with the creature's metabolism. Furthermore, they identified a number of existing drugs that could be effective against schistosomiasis.

'This list represents a good starting point, but, of course, more research is needed to determine whether any of the compounds could also be used to treat schistosomiasis,' noted Dr Martin John Rogers of the National Institute of Allergy and Infectious Diseases (NIAID) in the US.

The findings also improve our understanding of the evolution of simple animals. 'Blood flukes, such as S. mansoni, are flatworms that represent a poorly explored area of biology,' explained Dr Berriman. 'Their genome sequence allows us to shed more light on the evolution of simple animals. Their body designs share a common plan with all animals, from fish to humans.'

However, the primary goal of the new research was to identify new drug targets. 'Chronic infection with Schistosoma parasites makes life miserable for millions of people in tropical countries around the globe, and can lead to death,' said NIAID Director Anthony Fauci. 'New drugs and other interventions are badly needed to reduce the impact of a disease that lowers quality of life and slows economic development.'