Cambridge researchers help develop new diagnostic test for African sleeping sickness

cjb250 — Mon, 11 Sep 2017 08:27:04 +0000

Sleeping sickness, or Human African Trypanosomiasis, is caused by parasites transmitted by tsetse flies in sub-Saharan Africa and has a devastating impact, causing thousands of deaths each year. After sustained control efforts to reduce the number of new cases, the number of reported cases dropped below 10,000 for the first time in 50 years in 2009, and in 2015 there were 2,804 cases recorded, though the estimated number of actual cases is thought to be closer to 20,000.

̽��ֱ��international not-for-profit organisation FIND and the diagnostics company Alere have today launched their second-generation rapid diagnostic test for sleeping sickness. This second-generation test is easier and safer to produce, using recombinant protein technology to produce the two diagnostic antigens, one of which is completely new.

̽��ֱ��new test, SD BIOLINE HAT 2.0, costs US $0.50 each and requires no specialist equipment to diagnose sleeping sickness from a pin-prick of blood, providing the same level of accuracy but in a more robust production format.

̽��ֱ��test has been developed from research performed in the laboratories of Professor Mark Carrington at Cambridge and Professor Mike Ferguson at Dundee, who collaborated to identify, produce and initially validate the trypanosome proteins that form the basis of the tests. Device prototyping done at BBI Solutions in the Dundee Technology Park.

“This is a terrible disease that causes character disintegration, psychological deterioration followed by coma and death, and current treatments are far from ideal,” said Professor Carrington from the Department of Biochemistry.

“ ̽��ֱ��World Health Organisation’s goal is to eliminate Human African Trypanosomiasis, and rapid and accurate diagnosis is essential to achieving this objective. It is extremely encouraging for us as researchers to see our work now being deployed in the field where it can make a real difference to people.”

̽��ֱ��work at Cambridge and Dundee was supported through separate funding streams from the Wellcome Trust and the Medical Research Council (MRC).

Both the Dundee and Cambridge labs were supported by the Wellcome Trust at the time the research was done, and much of the work was performed by Dr Mandy Crow, an MRC PhD student at Cambridge between 2000 and 2004, and Dr Lauren Sullivan, and MRC PhD student and then MRC Centenary fellow at Dundee between 2008 and 2013.

Professor Ferguson said: “Sometimes impactful work comes from side-projects where one synthesises funding streams, in this case from the MRC and the Wellcome Trust, and works across institutions and with industrial partners to do something more speculative or applied. ̽��ֱ��science underpinning this new diagnostic device is a good case in point.”

Adapted from a press release from the ̽��ֱ�� of Dundee

A new diagnostic test developed from research at the Universities of Cambridge and Dundee has been launched with the aim of helping eliminate the disease known as African sleeping sickness.

̽��ֱ��World Health Organisation’s goal is to eliminate Human African Trypanosomiasis, and rapid and accurate diagnosis is essential to achieving this objective

Mark Carrington

Gull Lab courtesy of Sue Vaughan, Wellcome Images

Life cycle of sleeping sickness causing parasite

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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New tool in the fight against tropical diseases

gm349 — Wed, 27 Feb 2013 01:01:00 +0000

A novel tool exploits baker’s yeast to expedite the development of new drugs to fight multiple tropical diseases, including malaria, schistosomiasis, and African sleeping sickness. ̽��ֱ��unique screening method uses yeasts which have been genetically engineered to express parasite and human proteins to identify chemical compounds that target disease-causing parasites but do not affect their human hosts.

Parasitic diseases affect millions of people annually, often in the most deprived parts of the world. Every year, malaria alone infects over 200 million people, killing an estimated 655,000 individuals, mostly under the age of five. Unfortunately, our ability to treat malaria, which is caused by Plasmodium parasites, has been compromised by the emergence of parasites that are resistant to the most commonly used drugs. There is also a pressing need for new treatments targeting other parasitic diseases, which have historically been neglected.

Currently, drug-screening methods for these diseases use live, whole parasites. However, this method has several limitations. First, it may be extremely difficult or impossible to grow the parasite, or at least one of its life cycle stages, outside of an animal host. (For example, the parasite Plasmodium vivax, responsible for the majority of cases of malaria in South America and South-East Asia, cannot be continuously cultivated in laboratory conditions.) Second, the current methods give no insight into how the compound interacts with the parasite or the toxicity of the compound to humans.

In an effort to develop new drugs to fight parasitic diseases, scientists from the ̽��ֱ�� of Cambridge have collaborated with computer scientists at Manchester ̽��ֱ�� to create a cheaper and more efficient anti-parasitic drug-screening method. ̽��ֱ��clever screening method identifies chemical compounds which target the enzymes from parasites but not those from their human hosts, thus enabling the early elimination of compounds with potential side effects.

Professor Steve Oliver, from the Cambridge Systems Biology Centre and Department of Biochemistry at the ̽��ֱ�� of Cambridge, said: “Our screening method provides a faster and cheaper approach that complements the use of whole parasites for screening. This means that fewer experiments involving the parasites themselves, often in infected animals, need to be carried out.”

̽��ֱ��new method uses genetically engineered baker’s yeast, which either expresses important parasite proteins or their human counterparts. ̽��ֱ��different yeast cells are labelled with fluorescent proteins to monitor the growth of the individual yeast strains while they grow in competition with one another. High-throughput is provided by growing three to four different yeast strains together in the presence of each candidate compound. This approach also provides high sensitivity (since drug-sensitive yeasts will lose out to drug-resistant strains in the competition for nutrients), reduces costs, and is highly reproducible.

̽��ֱ��scientists can then identify the chemical compounds that inhibit the growth of the yeast strains carrying parasite-drug targets, but fail to inhibit the corresponding human protein (thus excluding compounds that would cause side-effects for humans taking the drugs). ̽��ֱ��compounds can then be explored for further development into anti-parasitic drugs.

In order to demonstrate the effectiveness of their screening tool, the scientists tested it on Trypanosoma brucei, the parasite that causes African sleeping sickness. By using the engineered yeasts to screen for chemicals that would be effective against this parasite, they identified potential compounds and tested them on live parasites cultivated in the lab. Of the 36 compounds tested, 60 per cent were able to kill or severely inhibit the growth of the parasites (under standard lab conditions).

Dr Elizabeth Bilsland, the lead author of the paper from the ̽��ֱ�� of Cambridge, said: “This study is only a beginning. It demonstrates that we can engineer a model organism, yeast, to mimic a disease organism and exploit this technology to perform low-cost, fully-automated drug screens to select and optimise drug candidates as well as identify and validate novel drug targets.”

“In the future, we hope to engineer entire pathways from pathogens into yeast and also to construct yeast strains that mimic diseased states of human cells.”

̽��ֱ��research, which was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), was published today, 27 February, in the journal Open Biology.

Screening method created to expedite the development of new drugs in the fight against tropical diseases such as malaria and African sleeping sickness.

Our screening method provides a faster and cheaper approach that complements the use of whole parasites for screening.

Steve Oliver

Harry J. Moss

Different yeast cells are labelled with fluorescent proteins to monitor the growth of the individual yeast strains

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̽��ֱ�� of Cambridge - African sleeping sickness

Cambridge researchers help develop new diagnostic test for African sleeping sickness

New tool in the fight against tropical diseases