New Test can detect Among a Vast Range of Infections

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"2 people I know have already had this done last week still awaiting results"

ARTICLE
A genome sequencing test developed at UC San Francisco that can rapidly pinpoint the cause of a bacterial, viral, fungal or parasitic infection from among a huge range of possibilities is now available to help physicians nationwide diagnose mysterious cases of neurological infection in acutely ill patients.

Scientists at UCSF have already used the test on a trial basis to diagnose a number of patients, including the well-known case of a 14-year-old boy who was near death with swelling in his brain. The boy had undergone months of unsuccessful attempts to identify the cause of his illness with conventional lab tests, expensive imaging technologies and invasive procedures, including a brain biopsy. By sequencing his cerebrospinal fluid (CSF), UCSF scientists found that he had a bacterial infection called leptospirosis, and he rapidly recovered after receiving targeted treatment with penicillin.

The test has now been validated in UCSF’s Clinical Laboratory Improvement Amendments (CLIA)-licensed clinical microbiology laboratory and is approved for clinical use.

Pinpointing Genomic Signatures of Pathogens
Over the last year, UCSF physicians and researchers have examined the utility of the test using CSF collected from more than 200 patients enrolled in a nationwide study of eight hospitals, including three University of California medical centers. All of these patients suffered from acute neurological illnesses, including meningitis (inflammation of the coverings around the brain and spinal cord), encephalitis (inflammation of the brain), and myelitis (inflammation of the spinal cord).

Doctors often have trouble figuring out why these tissues become inflamed, as these conditions can have many causes, including infection, cancer and autoimmune disease. This can lead to inappropriate treatment. For example, steroids and immunosuppressive agents that are commonly used to treat autoimmune diseases make it harder for the body to fight infection.

The new sequencing test can help overcome this uncertainty by pinpointing the genomic signatures of a wide range of pathogens – including fungi, bacteria, viruses and parasites – all at once. If no pathogen is detected using this comprehensive test, doctors can also be more confident in pursuing other non-infectious causes of the illness. While the test does not always establish the cause of inflammation, it has the potential to speed up the diagnostic process significantly, and to spare patients from having to undergo a large number of diagnostic tests and invasive procedures.

Starting with Neurological Illnesses
The technique, known as metagenomic next-generation sequencing, or mNGS, is a “shotgun” approach in which all of the DNA and RNA in a clinical sample are sequenced at very high depth, with the generation of 10 to 20 million reads per sample. Currently, only testing of CSF for patients with neurological illnesses is available in the clinical lab. UCSF is actively working on making clinical mNGS testing available for other sample types including blood for patients with sepsis and lung fluid for patients with pneumonia. The testing process in the diagnostic laboratory takes about 72 hours, and results are generally available within one or two weeks.

More information on the test and how to order it is available at the Center for Next-Gen Precision Diagnostics. The center serves as a reference lab to help doctors make diagnoses, but it does not provide consulting services directly to patients. The mNGS test must be ordered by a licensed provider authorized to order clinical laboratory tests and results are reported to the provider’s referring laboratory.

FULL LINK
https://www.ucsf.edu/news/2017/07/407736/next-gen-precision-diagnostics-now-available-ucsf
 
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Markus83

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I think one should distinguish between acute and chronic conditions. In chronic conditions there is typically a much lower pathogen load and therefore you need much more sensitive methods (for example borrelia are normally not found in CSF, even in acute cases). I'm skeptic if this tests are of benefit for chronically ill people. But let's see what it will bring up in the future.
 
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I think one should distinguish between acute and chronic conditions. In chronic conditions there is typically a much lower pathogen load and therefore you need much more sensitive methods (for example borrelia are normally not found in CSF, even in acute cases). I'm skeptic if this tests are of benefit for chronically ill people. But let's see what it will bring up in the future.
2 people with CFS/ME?

Does Ron Davis know of this test?
one has a CFS diagnosis , other had undiagnosed neuro symptoms
 

Hip

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It's great that this single test is able to cover all classes of pathogen — viral, bacteria, fungal and protozoan; I wonder what the cost is. Doctors can order the test for their patients here.

However, I suspect this test will still not be able to detect the enteroviruses found in ME/CFS patients, unless an actual stomach or muscle tissue sample is provided (or brain tissue, but that's only usually possible in deceased patients).

You do not find much enterovirus in the blood of ME/CFS patients, as in chronic form, this infection exists as an intracellular infection, mostly in the tissues.

And Dr John Chia points out that in enterovirus infections, the cerebrospinal fluid is often negative for enterovirus. In this video presentation (at timecode 9:33), Dr Chia says that:
the common wisdom is that if you have a brain infection, you should find it in the cerebrospinal fluid; that's clearly not true: even in acute infection of enterovirus 71 infections, only 5% of the CSF samples are positive.
So it's not in 95%, in the acute setting; and this [ME/CFS] is chronic.
 

Sidny

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If enterovirus is so difficult to detect in an acute setting and even less so in a chronic presentation I wonder how many other pathogens are equally difficult to detect in CSF.

@SK2018 thanks for sharing this. Would you happen to have an idea on what the test costs?
 

Sidny

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In the case multiple pathogens are detected in either acute or chronic infections does the test determine the levels of those microbes in the CSF as well or just identifies there presence?
 

Hip

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If enterovirus is so difficult to detect in an acute setting and even less so in a chronic presentation
Enterovirus is actually quite easy to detect in acute infections, because the bloodstream at the acute stage is full of virus (although you have to be quick, because the acute phase may be over in a week or so). It's only the chronic infections which are hard to detect, and the reason is because in chronic infections, enterovirus goes off and hides inside cells, in the body tissues.

So unless you chop a bit of the patient's tissues out and check that tissues for infection (ie, perform a tissue biopsy), it's hard to get direct evidence of the infection in ME/CFS.

In the past, enterovirus researchers used to take muscle tissue samples from ME/CFS patients, and these were found to contain enterovirus RNA, indicating a chronic enterovirus infection in the muscles.

But such muscle biopsies are painful and leave a scar, and so are not ideal for routine clinical use. Dr John Chia's great innovation is that he realized that in ME/CFS, enterovirus also infects stomach tissues, and that it is much easier to take a stomach tissue biopsy than a muscle biopsy. So this stomach tissue biopsy is what Dr Chia uses in routine clinical use for enterovirus testing.


Dr Chia is at pains to point out that unless researchers start testing the tissues for infection in ME/CFS, we are never going to make much progress in ME/CFS viral research.
 
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I’m a CFS/ME patient with significant brain inflammation and an altered state of consciousness (delta (slowest) brain waves even while awake, which makes me very sleepy and confused all the time) and Dr Peterson sent my spinal fluid to UCSF to have this done.

It came back positive for HHV-7 DNA in my spinal fluid.

I don’t know if I’m allowed to upload the test results here since I think it’s pretty new. It was done by the DeRisi Lab.

I’d originally asked for VirCapSeq-VERT, which is a very similar test but only for viruses, developed by Dr. Lipkin. My CSF is being sent there too and we’ll see if the HHV7 is confirmed.

I’m not sure what to think. I don’t want to place too much hope on having a virus to chase and treat. The spinal fluid was also drawn a year ago and I’ve just been in limbo treatment wise (I see Dr Peterson and Dr Kaufman). I have small fiber neuropathy, sjogrens early antibodies, antibodies against my liver and against multiple receptors in my brain. So there’s autoimmune issues but I have many infections and there has always been concern about an active brain virus. So no one wants to suppress my immune system if there’s a brain virus. I understand this but I’m also frustrated because I’ve been sick 7 years (POTS for 12 years) and haven’t been on antivirals or IVIG yet.

It’s going to be tricky if the UCSF test is positive and the Lipkin test is negative. And my blood has always been negative for HHV7. I’d love for this to be the answer to my brain inflammation, I just don’t know what to think right now.
 

Gingergrrl

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So there’s autoimmune issues but I have many infections and there has always been concern about an active brain virus. So no one wants to suppress my immune system if there’s a brain virus. I understand this but I’m also frustrated because I’ve been sick 7 years (POTS for 12 years) and haven’t been on antivirals or IVIG yet.
I am always so happy when I see a post from you @GlassHouse and I know that you are fighting for your life. I agree completely with what you said above that you should not suppress your immune system, in spite of all the autoimmunity, because of the active infections and potential brain virus. I was confused though why something like low-dose IVIG (for immune deficiency) to strengthen your immune system to fight the viruses is not an option?
 
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@Gingergrrl @Sidny @crypt0cu1t

I apologize for such a delayed response!

I was hospitalized with C diff again. The gastritis and colitis after the acute infection actually lead to a very helpful emergency colonoscopy and endoscopy. I got my GI doctor in touch with Dr Kaufman and they had my biopsies sent for viral culture.

Every single sample from the stomach, small intestine, and colon tested positive for HHV7. This has confirmed the UCSF test and confirms that I’ve had active encephalitis for 7 years since the initial high fever, and that the virus is in all of my organs (which likely explains the idiopathic hepatitis and gallbladder failure in previous years).

Yes, the HHV7 was the only virus I was positive for in my CSF. I was actually shocked the test gave me an answer. I’d been warned that it had been negative for everything in some other ME/CFS patients.

I think I must have been confused about the IVIG and immune suppression (I must have been mixing it up with Rituxin). I’m not sure why they waited so long to start the insurance fight for IVIG. I think they were waiting to try and get a better case built up. My autoantibodies aren’t crazy high, except on the Cunningham panel for PANDAS, but I don’t think that’s accepted by insurance as proof of anything.

My specialists have run the IGG subclass test a lot, but I’ve never gotten a low enough result to have a deficiency, which is an easier way to get coverage.

The autoimmune route is the hardest, or so they’ve said.

I’m trying to get a lip biopsy to confirm Sjögren’s and that might give me a better chance. I think the fight with my insurance has already begun, but I haven’t heard any updates yet.

I’ve been on Valcyte for over a month now for the HHV7 but sadly I don’t feel any different. I know it could take many months to notice a difference so I’m trying not to get discouraged. There’s also IV Vistide to try if Valcyte doesn’t work for me.

It’s possible that the damage to my brain is permanent from having a viral infection in there for so long. I’m still extremely grateful for the UCSF test. It’s brought a huge sense of validation. But I also experience a lot of anger that I was sent to psych for years for “malingering” when I could have been treated earlier and prevented additional brain damage.

I hope they can make this test cost effective so other people won’t end up like me. I understand that doctors are usually only able to find the cause in 50% of encephalitis cases. Hopefully this test can change that.

Sorry this is a bit rambly.

My specialists have gotten in touch with each other and agree that the ideal treatment would be antivirals and IVIG at the same time.

Hopefully I’ll be able to get insurance approval for the IVIG. Fingers crossed!
 

Hip

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I’ve been on Valcyte for over a month now for the HHV7 but sadly I don’t feel any different.
When taking Valcyte for herpesviruses, it's only after around 1 or 2 years that you get the full effects in terms of improvements to ME/CFS. Though Dr Lerner says benefits may begin to manifest after 3 or 4 months See this post.

Though if you are taking an antiviral for the encephalitis, then it should work much more quickly.


But as far as I can work out, Valcyte does not have much antiviral effect against HHV-7 anyway. See this post.
 
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