Tuesday, June 9, 2015

New blood test for viral infections shows promise

NHS: "New test uses a single drop of blood to reveal entire history of viral infections," The Guardian reports. Every time you are infected by a virus, your immune system produces specific types of antibodies in response. These antibodies remain in your body long after the infection has gone. The new test, called VirScan, is able to assess all these antibodies, building up a detailed immune "history" of viral infections.
Researchers looked at how well the test performed on blood samples from more than 500 people from North and South America, Africa and Asia.

The test correctly identified most of the people with known infections – though there were cases of both false negatives (saying an infection was not present even though it was) and false positives (wrongly diagnosing infection when there was none).
The test could theoretically be expanded to cover other types of organisms that cause human disease, such as bacteria, but this has not been tested yet. The test will also need to be updated as new viruses are discovered or as they change.
This test should be thought of as being at an early stage, likely to undergo further development and testing before it is ready for wider use. 

Where did the story come from?

The study was carried out by researchers from Harvard University and other research centres in the US, Europe, Peru, Thailand and South Africa.
It was funded by the US National Institutes of Health, the International AIDS Vaccine Initiative, the South African Research Chairs Initiative, the Victor Daitz Foundation, the Howard Hughes Medical Institute, the HIVACAT program and CUTHIVAC, the Thailand Research Fund, and the Chulalongkorn University Research Professor Program, NSF.
Some of the authors of the study are listed as inventors on a patent application related to the techniques used in the study (the use of bacteriophage phage display libraries to detect antiviral antibodies).
The study was published in the peer-reviewed journal, Science.
BBC News covered this story well and did not overstate the potential uses of the technique. Experts quoted in the story caution that while this technology may prove very useful in research, it may not be appropriate for diagnosing individual patients with diseases such as HIV.
The Mail Online suggested the test could be used to "help doctors diagnose patients with 'mystery illnesses'." But we do not yet know how this test performs compared with existing diagnostic methods for viral diseases.
Doctors and diagnostic laboratories would need to know that the new test performs as well as existing methods before they consider using it for diagnostic purposes or how well it identifies "mystery illnesses".

What kind of research was this?

This laboratory study aimed to develop a new blood test that could detect all of a person's previous viral infections at once.
Existing tests for viruses tend to look for a specific single virus and do not detect other viral infections. These tests tend to be based on detecting a virus' genetic material in our blood or how our immune system responds.
Once a viral infection has been successfully fought off by the body, its genetic material may not be detected, but an immune "memory" of the virus can last for decades. This research looked at developing a test for any virus based on looking at our immune memory of previous viral infections.
The researchers hoped this would help them better study the interaction between our immune system and these viruses. It is thought this interaction may influence the development of diseases involving the immune system, such as type 1 diabetes, and potentially even help the immune system fight other infections. 

What did the research involve?

Our immune system makes special proteins called antibodies to fight viruses and other infections. These antibodies work by "recognising" and binding to specific proteins and other molecules on the cell that are produced by the virus.
The immune system remembers the viruses it has been exposed to and continues to produce antibodies against them at a low level, even after the virus has been removed from the body. The researchers took advantage of this in developing their new test.
The researchers started by generating almost 100,000 bits of protein from more than 1,000 strains of all 206 different viral species identified as infecting humans. They were able to do this using genetic information from these viruses, as these sequences carry instructions for making all of the viruses' proteins.
The proteins were made in viruses that typically infect bacteria, called bacteriophages or just phages. These bacteriophages were genetically engineered to each produce one small bit of protein from a human virus, and thousands were then placed on a tiny microchip.
The researchers then took blood samples from 569 participants from four countries (the US, Peru, Thailand and South Africa) on four different continents. They extracted the part of the blood that contains antibodies (the serum) and washed a small amount (less than a microlitre) of this over the microchip.
When antibodies recognise a viral protein they have been exposed to before, they bind to it. This response allowed the researchers to identify which of the bacteriophages had antibodies bound to them, and how much.
They then assessed what viral protein each of those bacteriophages were producing and which viruses they came from. These were the viruses the person would have been exposed to in the past.
The researchers particularly looked for cases where the person's antibodies recognised more than one piece of protein from a given virus, as this would give greater confidence that the person really had been exposed to this virus. They also developed ways to help tell antibody reactions apart from related viruses that produce similar proteins.
They then compared which viruses people in different countries had been exposed to. Some of the participants had known viral infections, such as HIV or hepatitis, so the researchers checked how well this test picked these up. 

What were the basic results?

The researchers found the VirScan test was able to detect 95% or more of known infections with HIV or hepatitis C that had already been diagnosed with existing single virus tests.
VirScan was also able to correctly differentiate between different forms of the hepatitis C virus in 69% of people with known infections. Similar results were found for its ability to detect and differentiate between similar herpes simplex viruses (HSV1 and HSV2).
The researchers found the participants had antibodies against an average of 10 viral species. Younger participants tended to have had fewer viral exposures than older participants from the same country.
This is what would be expected, as they have had less time to be exposed. The pattern of different infections seen in participants from different countries was also similar to what was expected.
The researchers found there were some bits of viral protein that people who had been exposed to that virus almost always produced antibodies against. This suggests that these bits of protein are particularly good at causing a similar immune response in different people and therefore might be useful in making vaccines.
The researchers also found some "false positives" where their test appeared to be detecting pieces of viral protein because of their similarity to proteins from bacteria.

How did the researchers interpret the results?

The researchers concluded that the VirScan test provides a way to study all current and past viral infections in people using a small sample of blood. The method can be performed in samples from large numbers of people at the same time and is able to distinguish between related viruses.
They said: "VirScan may prove to be an important tool for uncovering the effect of host-virome interactions on human health and disease, and could easily be expanded to include new viruses as they are discovered, as well as other human pathogens, such as bacteria, fungi, and protozoa [single celled micro-organisms that cause diseases such as malaria]."


This research has developed a test that is able to identify past viral infections using a small sample of blood, giving an insight into a person's history of viral infections. The test could theoretically be expanded to cover other types of organisms that cause human disease, such as bacteria.
No test is perfect, however, and there were some cases where a known infection was not identified (false negative) and where an infection was picked up that was not thought to have really occurred (false positive). The test detects antibodies generated in response to viruses as the result of vaccination.
Antibody response also reduces over time, so the test may not be able to identify all previous infections. The researchers thought this was why they detected less exposure to some common viral infections, such as flu, than they expected.
The use of shorter bits of protein may also mean that some antibodies that recognise larger sections of the protein, or only recognise the protein after it has other molecules added to it, may not be identified.
While the test showed promise for telling different related viral strains apart, the researchers note it won't be as good at this as some genetic tests.
The test is reported to potentially cost only $25 per sample, but it is unclear whether this included the cost of all the machines needed to carry out the testing. Not all diagnostic labs may have access to these machines.
This test should be thought of as being at an early stage. While it might be able to cover other organisms, this has not been tested yet. The researchers suggest it could eventually be used as a first-stage rapid screen for viral infections, which could be followed up by more specific diagnostic tests. Again, more research will be needed to test this.
VirScan will also need to be updated as new viruses are discovered or as viruses change. For now, it is likely to have further development and largely be used as a research tool, rather than for diagnosing disease.