Wednesday, 20 August 2014

A Potential New Way to Attack Aspergillosis?

There has been notable success in the clinical application of a recent advance in cancer research whereby patients with Chronic Lymphoid Leukemia (CLL) have been treated with T cells that have been modified so as to target them directly at the cancer cells. T cells are an important part of our response to infection and help our bodies attack and destroy invading microbes or other foreign material.

The targeting is carried out by inserting a specific gene (Chimeric Antigen Receptors) into the T cells so as to enable the to recognise tumour specific cell surface proteins. Presumably the T cells can then recognise the cancer cells, attach to them and aid their destruction with high efficiency. Thus far we have tried this in two patients who have cancer and have achieved total remission of the cancer after 11 months. Remarkable!

Green fungal spore attacked by modified T cells

This new research group are now attempting the same thing but this time the targeted illness is not cancer but aspergillosis. They are using the same techniques but this time are guiding the T cells to the fungal cell wall and have had good success so far. They are not yet at the stage where they can start to treat 'real patients' but have released several videos (see link to paper above) that show cells attaching to the germinating fungus and killing it. The image above is a still from one of those videos - the green object in the middle is a germinating fungal spore which is surrounded by activated T cells that ultimately destroy it. Experiments in mice have also given positive results.

This may well result in a useful addition to our weaponry as we attack fungal infection - time will tell how effective it will be but we can speculate that combined with antifungal drugs that utilise different targets of attack we will have more chance of nullifying fungal infection in future.

Wednesday, 30 July 2014

Longitude Prize 2014: Antibiotic Action call for contributors!

 The 2014 Longitude Prize asked for a public vote on which of six challenges for the 21st century should receive a prize of £10 million to fund research work.


The winner was the proposal to help prevent the rise in antibiotic resistance within 5 years by finding a way to create a cheap, accurate, rapid and easy-to-use point of care test kit for bacterial infections.

To aid deliberations in advance of the call, The Longitude Prize Committee has announced an open call through to invite inventors, innovators and academics to help shape the criteria of the Longitude Prize for antibiotics.

Antibiotic Action encourages all to respond - we want to help the committee formulate a truly effective Prize.  You can contribute to the open review, which closes on 10 August 2014 by clicking here.

Tuesday, 29 July 2014

New Rapid Aspergillus-Specific Diagnostic Lateral Flow Device

Rapid diagnosis of invasive aspergillosis is important as the earlier treatment begins the better the eventual outcome. However early diagnosis is very problematic as amongst other things we breathe in Aspergillus and other fungal spores every day so an accurate test must be able to distinguish between those inactive spores (which are usually rapidly removed by our immune system) and actual invasive infection.

Existing techniques work well but this new test has several potential advantages:

  1. Very rapid - a drop of blood takes 15 mins to analyse 
  2. Very convenient - the test can be carried out 'at point of care' 
  3. Very cheap @ £10 per test 
  4. Highly specific to Aspergillus (so other fungi will not confuse the result)
  5. Does not rely on the response of the (often immunocompromised) patient's immune system

A new lateral flow device has been invented by Prof Chris Thornton of Exeter University , UK, to accurately diagnose invasive pulmonary aspergillosis. The affordable device uses a highly specific monoclonal antibody which detects a diagnostic marker of Aspergillus infection and uses a small blood sample.
Aspergillosis is a notoriously difficult disease to diagnose - affecting many immunosuppressed individuals such as cancer patients, transplant or HIV patients. Invasive aspergillosis is a principle cause of death in acute leukaemia and bone marrow transplant patients.
The new device costs just £10 is rapid and the compatibility of the device with hospital procedures, means that detection of aspergillosis can be accurately monitored at the point of care using either a blood sample or fluids collected during lung biopsy.There is also an ongoing trial with leukaemia patients at the Royal Devon and Exeter Hospital under the care of Consultant Haematologist Dr Paul Kerr.
A further benefit is that this new device specifically detects growing (and thus invasive) Aspergillus so results will not be confused with inhaled or otherwise non-growing fungal material.

Clinical trials are ongoing and there is no large quantity of data to demonstrate the efficacy of this test in the clinic but the early signs are very promising.

This lateral flow device will be available for use in hospitals around the world from August 2014.

Monday, 28 July 2014

The Gravity of Our Immune Response to Fungi

We know that spaceflight has a connection with our ability to respond to infection (includig fungal infection)  as there is a long history of astronauts on long space flight missions being more susceptible to infection on return to earth. It might be the result of all the stressors of spaceflight; highly unusual living conditions, long periods away from family or something else - including the result of experiencing short periods of high gravity (during launch) or long periods of very low gravity is something that must now be taken into consideration.

A recent report on research undertaken with fruit flies that have been taken up to a zero gravity laboratory in the International Space Station have show that gravity has a profound and very specific effect on aspercts of the fly immune system that beara  great resemblence to that in people. High gravity tends to increase immune activity whereas low (or no) gravity tends to switch off important parts of our immune system controlled by the Tol-like receptor. These same parts of our immune system are important for our resistance to fungal infection so it is correct to say that lack of gravity reduces our ability to fight off fungal infection.

Why should a genetic mechanism have evolved to respond to gravity? After all we are unlikely to have experienced zero gravity in all of human history - and nor is anything else on earth (unless we are descended from space travellors who had no need of an immune system in space!). Understanding how this happens will give us some answers and the work mentioned above aims to dissect out the signal & control systems involved. Future space travellors are likely to need this information in order to survive long journeys. At the same time it might reveal to us new information about our antifungal immune system that will be useful on earth.

Friday, 11 July 2014

Amphibians 'Learn' to Avoid Pathogenic Fungi

There is some data that supports the impression that fungi are causing increasing numbers of fatal infections in the wild over a large part of the world. Worryingly many completely different groups of organisms seem to be in decline e.g. bats, corals (Aspergillus sydowii), bees, snakes and amphibians but also plants. Some of this has been suggested to be a result of global warming - environments are changing as temperatures shift and those organisms trapped in a warmer environment are stressed to such an extent that they are more vulnerable to infection or predation. Some is being suggested to be a result of human activity spreading pathogens to parts of the world that they had not reached before now.

Aside from the importance of each species with respect to itself and the global diversity of living organisms, many of these species are of fundamental economic importance to us all so we need to understand why these populations are declining so as to be able to stop and reverse the decline.

Osteopilus septentrionalis
This new paper in the highly important journal Nature offers us one clue on how amphibians may be helped to start to resist pathogenic fungi. This particular group of frogs are living in an environment that has become infested with a pathogenic fungus (Batrachochytrium dendrobatidis). Conservationalists have taken frogs away from the infested areas and bred them successfully in captivity, however when they re-introduce them to the infected areas they fail to thrive - after all the fungus is still there so we might predict this outcome.

How can we help?

It turns out that if you expose the frogs to the fungus two things happen to enable resistance: they quickly learn to avoid it, and gradually become immune. This happens whether or not the fungus is alive. If then we carefully expose the frogs to dead fungus prior to re-release into the wild they should be able to avoid the fungus and thus thrive more readily. Perhaps other organisms have similar survival strategies we can use to help protect them?

The authors put it like this:
these results offer hope that other wild animal taxa threatened by invasive fungi might be rescued by management approaches based on herd immunity.

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