Genomes of Trypanosoma brucei and Trypanosoma cruzi sequenced

Aug 15 2005

Oxford scientists have contributed to the genome sequencing of two parasites which cause major health problems in the developing world.

Researchers in the Sir William Dunn School of Pathology were involved in the sequencing of the DNA of Trypanosoma brucei and Trypanosoma cruzi, which cause sleeping sickness and Chagas’ disease respectively, diseases which in combination put 160 million people in developing countries at risk.

Their work was reported last month in a special section of the journal Science on the sequencing of the trypanosomatid parasites.

Sleeping sickness threatens over 60 million people in sub-Saharan Africa. The parasite causing it, Trypanosoma brucei, is transmitted through tsetse fly bites. Early symptoms include fever, headaches and joint pain, but after a period of several months or years, the parasites invade the minute blood vessels supplying the central nervous system, causing drowsiness and lethargy – after which the disease is named – and ultimately, if untreated, death. In certain villages of many provinces of Angola, the Democratic Republic of Congo and southern Sudan, it has become the first or second greatest cause of mortality, ahead of HIV/AIDS, with 20–50 per cent of the population infected.

Chagas’ disease threatens 100 million people in Central and South America, and is especially prevalent in children and young adults. The parasite causing it, Trypanosoma cruzi, is present in the faeces of the bloodsucking ‘assassin’ bugs, which live in cracks in walls and come out at night to feed on humans, transmitting the parasite when their faeces comes into contact with wounds and scratches on the skin or the delicate tissues of the nose and mouth. The presence of the parasite in the heart muscles and central nervous system results in serious inflammation and lesions, which can be fatal.

The sequencing of the genomes of the parasites is hoped to be the first step on a long road towards novel drugs for the diseases.This would be particularly welcome for sleeping sickness, as the current major drug for combating its later stages contains arsenic and kills five per cent of recipients.

The Trypanosoma brucei and Trypanosoma cruzi genomes were sequenced alongside a third, related parasite, Leishmania major – also a serious cause of human disease. All three parasites evolved from a common ancestor around 250 million years ago and still share many characteristics. By comparison of the three parasite genomes with the human genome, the researchers want to find genes that are vital to the parasites, but have no equivalent in humans. It is hoped this will allow the development of therapies that specifically target and kill the parasite without harming human cells.