̽��ֱ�� of Cambridge - infection

Virus attracts bumblebees to infected plants by changing scent

fpjl2 — Thu, 11 Aug 2016 18:05:25 +0000

Plant scientists at the ̽��ֱ�� of Cambridge have found that the cucumber mosaic virus (CMV) alters gene expression in the tomato plants it infects, causing changes to air-borne chemicals – the scent – emitted by the plants. Bees can smell these subtle changes, and glasshouse experiments have shown that bumblebees prefer infected plants over healthy ones.

Scientists say that by indirectly manipulating bee behaviour to improve pollination of infected plants by changing their scent, the virus is effectively paying its host back. This may also benefit the virus: helping to spread the pollen of plants susceptible to infection and, in doing so, inhibiting the chance of virus-resistant plant strains emerging.

̽��ֱ��authors of the new study, published today in the journal PLOS Pathogens, say that understanding the smells that attract bees, and reproducing these artificially by using similar chemical blends, may enable growers to protect or even enhance yields of bee-pollinated crops.

“Bees provide a vital pollination service in the production of three-quarters of the world’s food crops. With their numbers in rapid decline, scientists have been searching for ways to harness pollinator power to boost agricultural yields,” said study principal investigator Dr John Carr, Head of Cambridge’s Virology and Molecular Plant Pathology group.

“Better understanding the natural chemicals that attract bees could provide ways of enhancing pollination, and attracting bees to good sources of pollen and nectar – which they need for survival,” Carr said.

He conducted the study with Professor Beverley Glover, Director of Cambridge ̽��ֱ�� Botanic Garden, where many of the experiments took place, and collaborators at Rothamsted Research.

CMV is transmitted by aphids – bees don’t carry the virus. It’s one of the most prevalent pathogens affecting tomato plants, resulting in small plants with poor-tasting fruits that can cause serious losses to cultivated crops.

Not only is CMV one of the most damaging viruses for horticultural crops, but it also persists in wild plant populations, and Carr says the new findings may explain why:

“We were surprised that bees liked the smell of the plants infected with the virus – it made no sense. You’d think the pollinators would prefer a healthy plant. However, modelling suggested that if pollinators were biased towards diseased plants in the wild, this could short-circuit natural selection for disease resistance,” he said.

“ ̽��ֱ��virus is rewarding disease-susceptible plants, and at the same time producing new hosts it can infect to prevent itself from going extinct. An example, perhaps, of what’s known as symbiotic mutualism.”

̽��ֱ��increased pollination from bees may also compensate for a decreased yield of seeds in the smaller fruits of virus-infected plants, say the scientists.

̽��ֱ��findings also reveal a new level of complexity in the evolutionary ‘arms race’ between plants and viruses, in which it is classically believed that plants continually evolve new forms of disease-resistance while viruses evolve new ways to evade it.

“We would expect the plants susceptible to disease to suffer, but in making them more attractive to pollinators the virus gives these plants an advantage. Our results suggest that the picture of a plant-pathogen arms race is more complex than previously thought, and in some cases we should think of viruses in a more positive way,” said Carr.

Plants emit ‘volatiles’, air-borne organic chemical compounds involved in scent, to attract pollinators and repulse plant-eating animals and microbes. Humans have used them for thousands of years as perfumes and spices.

̽��ֱ��researchers grew plants in individual containers, and collected air with emissions from CMV-infected plants, as well as ‘mock-infected’ control plants.

Through mass spectrometry, researchers could see the change in emissions induced by the virus. They also found that bumblebees could smell the changes. Released one by one in a small ‘flight arena’ in the Botanic Gardens, and timed with a stopwatch by researchers, the bees consistently headed to the infected plants first, and spent longer at those plants.

“Bees are far more sensitive to the blends of volatiles emitted by plants and can detect very subtle differences in the mix of chemicals. In fact, they can even be trained to detect traces of chemicals emitted by synthetic substances, including explosives and drugs,” said Carr.

Analysis revealed that the virus produces a factor called 2b, which reprograms genetic expression in the tomato plants and causes the change in scent.

Mathematical modelling by plant disease epidemiologist Dr Nik Cunniffe, also in the Department of Plant Sciences at Cambridge, explored how the experimental findings apply outside the glasshouse. ̽��ֱ��model showed how pollinator bias for infected plants can cause genes for disease-susceptibility to persist in plant populations over extremely large numbers of generations.

̽��ֱ��latest study is the culmination of work spanning almost eight years (and multiple bee stings). ̽��ֱ��findings will form the basis of a new collaboration with the Royal Horticultural Society, in which they aim to increase pollinator services for cultivated crops.

With the global population estimated to reach nine billion people by 2050, producing enough food will be one of this century’s greatest challenges. Carr, Glover and Cunniffe are all members of the Cambridge Global Food Security Initiative at Cambridge, which is involved in addressing the issues surrounding food security at local, national and international scales.

̽��ֱ��use of state-of-the-art experimental glasshouses at Cambridge Botanic Garden, and equipment at Cambridge and Rothamsted, was funded by the Leverhulme Trust.

Study of bee-manipulating plant virus reveals a “short-circuiting” of natural selection. Researchers suggest that replicating the scent caused by infection could encourage declining bee populations to pollinate crops – helping both bee and human food supplies.

Modelling suggested that if pollinators were biased towards diseased plants in the wild, this could short-circuit natural selection for disease resistance

John Carr

John Carr/Alex Murphy

Researcher Sanjie Jiang inside the 'flight arena' in the glasshouse of the Cambridge ̽��ֱ�� Botanic Garden.

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

Yes

Scientists discover genetic disease which causes recurrent respiratory infections

sj387 — Fri, 18 Oct 2013 08:36:28 +0000

Cambridge scientists have discovered a rare genetic disease which predisposes patients to severe respiratory infections and lung damage. Because the scientists also identified how the genetic mutation affects the immune system, they are hopeful that new drugs that are currently undergoing clinical trials to treat leukaemia may also be effective in helping individuals with this debilitating disease.

For the study, led by the ̽��ֱ�� of Cambridge in collaboration with the Babraham Institute and the MRC Laboratory for Molecular Biology, the researchers first examined genetic information from individuals who suffer from immunodeficiency and are predisposed to infections. From this group, the scientists identified a unique genetic mutation in 17 patients that suffer from severe respiratory infections and rapidly develop lung damage.

̽��ֱ��researchers, who were primarily funded by the Wellcome Trust, MRC, BBSRC and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, found that the mutation increases activity of an enzyme called Phosphoinositide 3-Kinase δ (PI3Kδ). ̽��ֱ��enzyme is present in immune cells and regulates their function. However, constantly activated PI3Kδ impairs work of these immune cells, preventing them from responding efficiently to infection and providing long-lasting protection. Consequently, patients with this mutation have severe and recurrent infections.

“Patients with this mutation have a defect in the immune cells, so their protection from infections is weak and inefficient,” said Sergey Nejentsev, Wellcome Trust Senior Research Fellow from the ̽��ֱ�� of Cambridge who led the research. “We called this newly identified disease Activated PI3K- δ Syndrome (APDS) after the enzyme in the immune system that is affected by the genetic mutation.”

̽��ֱ��researchers believe that it may be possible to treat APDS in future. There are currently drugs in clinical trials for leukaemia that were designed specifically to inhibit the PI3Kδ enzyme. ̽��ֱ��researchers have already shown that these drugs reduce activity of the mutant protein.

Alison Condliffe, joint senior author on the paper from the ̽��ֱ�� of Cambridge, said: “We are very excited by the prospect of using these drugs to help patients with APDS. We believe that they may be able to restore functions of immune cells, thereby reducing infections and preventing lung damage.”

Although the prevalence of the disease is not yet known, the scientists believe that it is relatively frequent compared to other immunodeficiencies and may underpin immunodeficiencies and chronic lung disorders in a substantial fraction of patients.

“It is very important that doctors consider a possibility of APDS in their patients,” said Dr Nejentsev. “A simple genetic test can tell if the patient has the mutation or not. We believe that now many more APDS patients will be identified all over the world.”

̽��ֱ��research was published by Science Express (the electronic publication of selected Science papers).

Discovery could lead to new treatments for this genetic disorder.

We believe that now many more APDS patients will be identified all over the world

Sergey Nejentsev

Chikumaya

X-ray photo of a chest

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Salmonella infection, but not as we know it

gm349 — Mon, 30 Apr 2012 11:52:29 +0000

Using real-time video microscopy, coupled with mathematical modelling, scientists have changed our assumptions about Salmonella and how it infects human cells. ̽��ֱ��research was published in Interface.

Salmonella is an important bacterium to study as it causes a range of diseases in humans and animals. It is capable of growing and reproducing inside macrophages - a type of white blood cell that ingests foreign material - ultimately destroying them. These macrophage cells are key players in the immune response to invaders and so the control of Salmonella within these cells is critical to surviving an infection. However, fundamentally important factors in infection events - such as the rate at which Salmonella infects cells, how frequently this occurs and the probability of infection - had not previously been calculated because it was thought impossible to do so.

Dr Clare Bryant, from the ̽��ֱ�� of Cambridge's Department of Veterinary Medicine, said: “Understanding how these bacteria invade, survive, proliferate and kill vital macrophage cells provides a wealth of knowledge to help improve our health. For the first time, we have been able to calculate the rate at which Salmonella can infect macrophages and we have also seen evidence of dual infection and reinfection of a single cell.”

Instead of relying on figures from large populations of infected cells, such as changes in total bacterial number over time, finer measurements of the individual steps of infection were considered. ̽��ֱ��researchers used two independent approaches for their calculations: mathematical modelling of Salmonella infection experiments, and analysis of real-time video microscopy of individual infection events.

Their research found that many incorrect assumptions had been made about Salmonella infection, particularly that macrophages are highly susceptible to infection. Their data showed that infection occurrences after initial contact between a bacterium and macrophage were low. ̽��ֱ��probability of that bacterium infecting the cell is less than 5 per cent. However, they also showed that an infected macrophage can be reinfected by a second bacterium. ̽��ֱ��concept of reinfection by Salmonella had not been considered before and this previously overlooked mechanism may make an important contribution to total bacterial numbers in infection studies.

̽��ֱ��study also highlighted the fact that some cells are far more susceptible to infection than others. Rather than grouping all macrophages together in terms of their susceptibility to infection, the research shows that there is a spectrum of susceptibility.

“Our research revealed novel biological processes that occur when Salmonella interacts with macrophages. It will lead to a reconsideration of the mechanisms behind infection which will be important for the future development of intervention strategies,” added Dr Bryant.

Cambridge ̽��ֱ�� researchers, funded by the BBSRC, have shed new light on a common food poisoning bug.

Understanding how these bacteria invade, survive, proliferate and kill vital macrophage cells provides a wealth of knowledge to help improve our health.

Dr Clare Bryant

Clare Bryant

Salmonella

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Researcher gets green light for new Hep B test

bjb42 — Fri, 21 May 2010 00:00:00 +0000

Developed by Cambridge researcher Dr Helen Lee, the inexpensive test delivers accurate while-you-wait results and allows doctors to take immediate action - circumventing the need to send samples away for laboratory analysis.

With around 400 million people worldwide estimated to carry the disease, the Hepatitis B Rapid Test could revolutionise detection of the condition in poorer countries.

Dr Helen Lee from Diagnostics for the Real World (DRW), who led the development of the test said: "Our test is simple, quick, inexpensive and can survive very hot conditions for many months - all vital factors when you are working in poorer parts of the world".

Dr Lee, who works at the ̽��ֱ��'s Diagnostics Development Unit, set up DRW in 2002. ̽��ֱ��group has already launched a rapid test for Chlamydia that is currently sold within the EU and many other countries around the world. Other tests in the pipeline include rapid tests for the detection of HIV and influenza.

Hepatitis B virus (HBV) is highly infectious and is endemic in many parts of the world. In the UK alone, one in 1,000 people are infected and in China and Africa as many as one in six people carry the virus.

Spread through contact with infected blood or other body fluids, including sexual contact, infection rarely kills but can cause serious health problems and places enormous strain on healthcare resources.

Compared with existing diagnostics, which involve sending patient samples away to laboratories for analysis by skilled technicians using expensive machinery, the new Hepatitis B Rapid Test, developed with funding from the Wellcome Trust, uses a dipstick technology to deliver an accurate diagnosis on-site within half an hour and can be used with minimal training.

According to Professor Baruch S. Blumberg, who was awarded the Nobel Prize for Medicine in 1976 for the discovery of the Hepatitis B virus and the invention of the HBV vaccine said: "Approval of the new Hepatitis B Rapid Test is positive news for the estimated 400 million HBV carriers worldwide."

"HBV infection and the diseases related to it are solvable problems. ̽��ֱ��Hepatitis B Rapid Test developed by Diagnostics for the Real World can make a significant contribution to the solution."

̽��ֱ�� ̽��ֱ�� of Cambridge's Diagnostics Development Unit (DDU) was established a decade ago by a group of industry scientists who worked at a multinational diagnostic company. Its aim is to develop innovative tests that are rapid, simple, cost-effective and more sensitive than currently available rapid tests.

This new generation of point-of-care tests is intended to detect infectious agents that cause serious health problems in resource-limited settings, particularly in developing countries.

A ‘dipstick’ test that detects Hepatitis B within 30 minutes – and could be used in some of the world’s poorest countries – has been given the green light for use in the European Union.

Our test is simple, quick, inexpensive and can survive very hot conditions for many months - all vital factors when you are working in poorer parts of the world.

Dr Helen Lee

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U.S. Army medical researchers take part in World Malaria Day 2010, Kisumu, Kenya, April 25, 2010

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Scientists make new discoveries in battle with superbug

bjb42 — Fri, 22 Jan 2010 00:00:00 +0000

They have for the first time shown how transmission of the bacterial infection can be tracked between people in different continents and from patient to patient in a single hospital

They used new DNA sequencing technologies on samples taken from people with MRSA across the world.

̽��ֱ��superbug killed a total of 2,823 people in 2007 and 2008 in the UK according to the Office for National Statistics. Annual deaths related to MRSA infection in the USA increased from 11,000 in 1999 to 17,000 in 2005.

One of the authors on the study, Dr Sharon Peacock, professor of clinical microbiology, said: "Until now it has not been possible to examine transmission of MRSA between countries and within and between healthcare institutions.

" ̽��ֱ��fine scale discrimination that is now possible between two or more highly related MRSA strains means that it becomes possible to identify where strains have spread and implement control measures to prevent this from happening."

̽��ֱ��sequencing and data analysis were performed at the Wellcome Trust Sanger Institute and Dr Peacock was involved in clinical interpretation of the data, as well as considering the future application of the technology.

She added: "Our research should inform global surveillance strategies to track the spread of MRSA."

" ̽��ֱ��implications for public health are clear. This technology represents the potential to trace transmission pathways of MRSA more definitively so that interventions or treatments can be targeted with precision and according to need."

Two very different sets of samples were used. ̽��ֱ��first contained 42 samples from people throughout the globe who became infected with MRSA between 1982 and 2003.

̽��ֱ��second set was from a single hospital in north-east Thailand and comprised 20 samples from patients who developed the infection within seven months of each other and which were possibly transmitted from person to person.

Dr Simon Harris, from the Wellcome Trust Sanger Institute, the co-lead author on the study, said: "We wanted to test whether our method could successfully zoom in and out to allow us to track infection on a global scale - from continent to continent, and also on the smallest scale - from person to person."

̽��ֱ��team also developed an evolutionary tree of MRSA by looking at samples from hospitals in North and South America, Europe, Australia and Asia over more than 20 years. ̽��ֱ��research suggests that the infection emerged in the 1960s in Europe.

̽��ֱ��new approach could also help future studies into the transmission and evolution of other bacteria.

̽��ֱ��challenge now is to control infections by antibiotic-resistant bugs such as MRSA.

̽��ֱ��research is published in this week's Science.

New research from Cambridge should help hospitals control the spread of MRSA and other emerging superbugs.

̽��ֱ��fine scale discrimination that is now possible between two or more highly related MRSA strains means that it becomes possible to identify where strains have spread.

Dr Sharon Peacock

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Bacteria

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Robot scientist becomes first machine to discover new scientific knowledge

bjb42 — Thu, 02 Apr 2009 00:00:00 +0000

̽��ֱ��robot, called Adam, is a computer system that fully automates the scientific process. ̽��ֱ��work, which was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) was published today, 03 April 2009, in the journal Science.

̽��ֱ��scientists designed Adam to carry out each stage of the scientific process automatically without the need for further human intervention. ̽��ֱ��robot has discovered simple but new scientific knowledge about the genomics of the baker's yeast Saccharomyces cerevisiae, an organism that scientists use to model more complex life systems. ̽��ֱ��researchers have used separate manual experiments to confirm that Adam's hypotheses were both novel and correct.

Stephen Oliver, one of the co-authors on the paper and Professor of Systems Biology and Biochemistry at the ̽��ֱ�� of Cambridge, said: " ̽��ֱ��novel thing is that Adam is able to formulate hypotheses on its own and test them. In this project, a machine has discovered new scientific knowledge.

"As we start to consider living systems in a holistic manner, the complexity of such systems means that it will become increasingly difficult for scientists to formulate hypotheses unaided. Thus it will be necessary for human and robot scientists to work together to achieve the goals of biological research.

"It is not the management and analysis of complex data that is the big deal about Adam, it is the ability of the machine to reason with those data and make proposals about how a living thing works."

Prof Ross King, who led the research at Aberystwyth ̽��ֱ��, said: "Ultimately we hope to have teams of human and robot scientists working together in laboratories. Because biological organisms are so complex it is important that the details of biological experiments are recorded in great detail. This is difficult and irksome for human scientists, but easy for Robot Scientists."

Using artificial intelligence, Adam hypothesised that certain genes in baker's yeast code for specific enzymes which catalyse biochemical reactions in yeast. ̽��ֱ��robot then devised experiments to test these predictions, ran the experiments using laboratory robotics, interpreted the results and repeated the cycle.

Adam is a still a prototype, but Prof King's team believe that their next robot, Eve, holds great promise for scientists searching for new drugs to combat diseases such as malaria and schistosomiasis, an infection caused by a type of parasitic worm in the tropics.

Prof King continued: "If science was more efficient it would be better placed to help solve society's problems. One way to make science more efficient is through automation. Automation was the driving force behind much of the 19th and 20th century progress, and this is likely to continue."

Professor Oliver of Wolfson College and his post-doc Pnar Pir participated in the construction of the logical model of yeast metabolism that formed Adam's background knowledge. They also designed the basic experimental format in terms of media, growth conditions, etc., and analysed Adam's hypotheses to figure out why human scientists failed to connect those genes to the orphan enzymes.

̽��ֱ��image and video were kindly provided by Aberystwyth ̽��ֱ��.

Scientists from the ̽��ֱ�� of Cambridge and Aberystwyth ̽��ֱ�� have created a "robot scientist" which the researchers believe is the first machine to have independently discovered new scientific knowledge.

It is not the management and analysis of complex data that is the big deal about Adam, it is the ability of the machine to reason with those data and make proposals about how a living thing works.

Stephen Oliver

Roger Schultz from Flickr

Rusty C3PO

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New research provides insight into cause of type 1 diabetes

bjb42 — Thu, 05 Mar 2009 00:00:00 +0000

Everyone carries the IFIH1 gene, which plays a role in the body's antiviral responses. Importantly, it is also located in the region of the human genome associated with T1D, an autoimmune disorder which results in the body attacking its own insulin-producing pancreatic cells. ̽��ֱ��IFIH1 gene codes for a protein that recognizes the presence of viruses in the cell and controls immune activation. It is within this gene that scientists have identified four gene variants that protect against T1D.

Enteroviruses are well known to be associated with T1D: enterovirus infections are more common among newly diagnosed T1D patients and pre-diabetic subjects than in the general population and often precede the appearance of biological markers for pre-diabetes. However, no one knows if these infections are a cause of type 1 diabetes.

̽��ֱ��study by Nejentsev et al., which was conducted at the Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, establishes that the IFIH1 protein is involved in T1D, highlighting a molecular pathway by which enterovirus infections may contribute to the development of the disease. ̽��ֱ��four rare variants they identified, which are predicted to reduce function of the IFIH1 protein, consistently decrease the risk of T1D, rather than predispose to it. This suggests a model where normal immune activation caused by enterovirus infection and mediated by IFIH1 protein stimulates autoimmunity that eventually leads to T1D.

Professor John Todd, senior author on the study, said: "We have been able to pin-point one particular gene among a long list of candidates. Now we and others can begin to study the biology of IFIH1 in the context of type 1 diabetes knowing that it is part of the cause of the disease."

In the past three years genome-wide association studies have been a major success, revealing dozens of regions in the human genome that harbour genes which predispose individuals to various diseases, such as diabetes or cancers. Nevertheless, as disease-associated regions may contain several genes with different functions, scientists rarely know which gene or gene variant (mutations of the gene) in these regions cause the disease.

In order to overcome this limitation, the scientists searched for variants that had obvious biological effects, e.g. those affecting gene expression or protein function. They hypothesized that if a gene harbors several such variants, then it is likely to be causative. Most of such variants are rare in the population and are not tested in genome-wide association studies. Nevertheless, they could be discovered by sequencing (examining the sequence of the pairs of nucleotides which make up a gene).

̽��ֱ��researchers studied 10 candidate genes associated with T1D. Using a novel technique (high throughput sequencing of DNA pools) in collaboration with 454 Life Sciences, a Roche company, they examined the DNA of 480 T1D patients and 480 healthy controls. This approach allowed them to not only discover several rare variants associated with T1D, but also to accurately measure their frequency in the pools of patients and controls.

̽��ֱ��researchers then genotyped approximately 30,000 individuals who were either T1D patients, controls or family members and proved that four rare variants or versions that reside in the gene IFIH1 reduce the risk of developing T1D.

̽��ֱ��study demonstrates that re-sequencing genes associated with diseases can help pinpoint the specific gene or genes that lead to the disease.

"Finding several new rare disease variants with clear biological functions was crucial. Not only has this proved that IFIH1 is involved in type 1 diabetes, it also gave us clues to understand the mechanism" said Dr. Sergey Nejentsev, Royal Society Research Fellow at the Department of Medicine, the first author of the study. He added: "This experiment shows the way to identify causative genes contributing to various common diseases."

Scientists from Cambridge ̽��ֱ�� have discovered four rare mutations of a gene associated with type 1 diabetes (T1D) that reduce the risk of developing the disease. Their findings, published today in the journal Science, suggest a link between T1D and the enterovirus (a common virus that enters via the gastrointestinal tract but is often non-symptomatic).

Finding several new rare disease variants with clear biological functions was crucial.

Dr. Sergey Nejentsev

Jill A. Brown from Flickr

Diabetes

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Parasites: the master manipulators

tdk25 — Sat, 01 Sep 2007 00:00:00 +0000

̽��ֱ��human race used to have a consensus attitude towards the organisms that we call parasites. They were simply pests, causative agents of disease that warranted nothing else other than extermination. As soon as new life-cycles were described in the literature, the race began to find a way of interrupting transmission and end the misery. ̽��ֱ��literature is therefore full of examples of control programmes for just about every parasite that has ever been identified. Some, such as the programme against the guinea worm, Dracunculus medinensis, have been so successful that complete eradication is now on the World Health Organization’s agenda.

As we wave goodbye to the guinea worm, it will be time to re-visit the hit-list, and to see how far we’ve progressed. In doing so, we are likely to observe that not much has changed. In fact, the guinea worm is the only parasitic infection that has ever been described and then systematically eradicated. There are even signs that the parasitic fauna of the planet is flourishing – recent estimates put the toll of malaria at between 300 and 660 million cases a year, and there are still hundreds of millions of people infected by each of several parasitic worm species. This group includes the trematode parasite Schistosoma mansoni – a blood fluke that infects approximately 200 million people in the tropics and sub-tropics, and which has been the focus of research efforts at the ̽��ֱ�� of Cambridge Department of Pathology for the past 30 years.

Fighting the fluke

Theodor Bilharz formally described schistosome parasites in 1851, at which point the centimetre-long, red-blood-cell-eating worm joined the most-wanted list. Like every other parasitic infection, S. mansoni was viewed with fear and loathing – and with good reason. Infection occurs through contact with free-living larvae in freshwater, with rapid penetration of intact human skin. ̽��ֱ��adults live in the mesenteric veins between the liver and gut. Females produce eggs that become trapped in the liver, promoting an inflammatory response that eventually leads to a form of hepatic fibrosis and portal hypertension. About half the eggs pass through the gut wall, each puncture causing a small amount of blood to be lost. As the worm burden increases with repeated exposure, so the number of eggs in both the liver and gut increases, leading to ever more severe disease.

Early attempts at large-scale control of schistosome infections relied on crude drugs and environmental modification, with success in some areas, but in most places the parasite persisted. Although treatment (praziquantel) is available, re-infection occurs rapidly, especially in children. ̽��ֱ��lack of effective, non-toxic medicine, and the success of vaccination programmes against bacterial diseases, led to the emergence of renewed research efforts aimed at understanding the biology of the worm and its relationship with the human host.

But, despite promises of an anti-schistosome vaccine ‘within five years’ for the past 20 years or so, there is still no vaccine available, because we don’t yet understand the biology of the schistosome worm. Like a fractal puzzle, as we peer more closely we see even greater complexity.

Keeping things quiet

Such is the intimate relationship between host and parasite that we can use the study of schistosome parasites to understand how humans work. One of the key questions that has kept scientists busy is how schistosomes manage to evade the immune response for extended periods. It has been estimated that adult worms live for up to 10 years in their human host. To make this possible, the worms have evolved several mechanisms for diverting, blocking and repressing the immune response. ̽��ֱ��adult worms coat themselves in host proteins to appear invisible to the immune system. They induce the host to produce ineffective immune responses and they manipulate host cells to produce molecules that signal a general downregulation of the host’s response. This essentially produces a drowsy immune response with impaired vision against a camouflaged target – perfect conditions for the parasite to thrive and reproduce

Recent studies in Cambridge in the laboratory of Professor David Dunne have demonstrated the magnitude of this repressive effect by treating people who are already infected with the parasite and measuring their immune responses before and after taking praziquantel. Responses that are thought to be effective against the parasite often increase several fold after drug treatment, and this ‘boosting’ of the host’s ability to respond appears to help prevent re-infection in the future. Recently, the scientists also reported that the ability to respond after treatment is genetically restricted – an observation that has important implications for the development of any therapy or vaccine that relies on increasing the magnitude of the immune response for its protective effect.

Medical benefits

Although a vaccine is not yet in sight, recent discoveries have raised an interesting conundrum: rather than simply being agents of disease, it appears that parasitic infections, including schistosome worms, may bring medical benefits. Scientists in Cambridge are leading the field in efforts to find out just what is going on.

As more knowledge of the host–parasite relationship is gained, it is becoming increasingly clear that parasitic infections are not necessarily pests that need to be eradicated. Nobody used to have any sympathy for leeches or maggots, but both creatures are now used in medical settings: leeches to clear blood from congested tissues after surgery, and maggots to liquefy dead tissue and kill harmful bacteria in infected wounds. ̽��ֱ��same thing is now happening to parasites, as it emerges that their influence on the immune system can benefit both host and parasite.

In the Department of Pathology, a clear example of this win–win scenario was demonstrated when researchers in Professor Anne Cooke’s group prevented type 1 diabetes from developing in mice by injecting them with antigens of schistosome parasites. This is likely to be due to the same skewing and downregulation of the host immune response described above.

It seems that by diverting and subverting the immune response, schistosome parasites may prevent the immune system from over-reacting to other proteins. One hypothesis gaining popularity is that, when parasites are removed, the immune response finds new targets, either in harmless allergens (leading to allergy), or in the host itself (leading to autoimmune diseases such as type 1 diabetes).

With such tantalising evidence, it may be time to look at the parasite hit-list with fresh eyes, and ask: can we exploit the intimate relationship parasites have with humans at the same time as reducing their tremendous burden on affected populations?

̽��ֱ��Matangini Project

̽��ֱ��Matangini Project was created by Dr Mark Booth, in the Schistosomiasis Research Group at the Department of Pathology, to raise funds for community projects in Kenya and Uganda. ̽��ֱ��aim in 2007 is to raise £5000 to bring safe water to thousands of school children in areas of Kenya affected alternately by drought and water-borne infections such as schistosomiasis.

Cambridge Infectious Disease Initiative

̽��ֱ�� ̽��ֱ�� of Cambridge is currently developing a major Infectious Disease Initiative, with the aim of increasing the ̽��ֱ��’s contribution to reducing the global impact of infectious diseases. By building new partnerships based on core strengths, the vision is to establish the ̽��ֱ�� as a leading international centre for infectious disease teaching and research.

For further information, please contact the Co-ordinator Dr Gill Rands (gfr21@cam.ac.uk).

For more information, please contact the author Dr Mark Booth (mb350@cam.ac.uk) at the Department of Pathology (www.path.cam.ac.uk/~schisto).

̽��ֱ��common view has been that parasitic infections cause disease and must be eliminated. But can we live without them?

As more knowledge of the host–parasite relationship is gained, it is becoming increasingly clear that parasitic infections are not necessarily pests that need to be eradicated.

Max0rz from Flickr

Flatworm

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