By David Tuller, DrPH

When I visited Melbourne in March of last year, I heard a lot about Dr Don Lewis, a local physician beloved by those with ME—or “chronic fatigue,” as Australian patients, scientists and clinicians routinely called the illness, to my dismay. At the time, Dr Lewis was transitioning out of his medical practice because of serious illness. Unfortunately, I did not have the time to visit him. Last month, he passed away.

Emerge Australia, a group based in Melbourne, issued the following statement on July 29th:

It is with deep sadness that we announce the passing of Melbourne ME/CFS doctor, Dr Don Lewis, who died this morning following a long illness.

Dr Lewis cared for ME/CFS patients for more than 30 years. He has touched the lives of many, through his clinical and research work, but also through his dedication and compassion.

We know that he will be deeply missed, and we offer our condolences to his loved ones and to his patients.

His family has released a short statement to the ME/CFS community:

“This morning our amazing Dad passed away into the presence of God after living with a rare form of cancer for years.

Many know of Dad’s quiet strength and determination and his journey with illness was no different. He carried himself with grace and peace to the end.

He was much loved by his family, an amazing friend to many and an incredible support to his patients – he will always be remembered.”

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In the course of this project, I have often done interviews and not written them up or posted them—almost always because I simply haven’t had the time to do so. I find myself feeling constantly behind and constantly needing to address new concerns, so balancing those imperatives can be a struggle. Although I didn’t meet Dr Lewis in person, I interviewed him from my hotel room in Perth a few weeks after I had been in Melbourne. I am very sorry I didn’t get around to editing and posting it while he was alive. But I wanted to share some of what he told me now.

How did you first become interested in this illness or start working with this patient population?

My wife became suddenly very unwell and collapsed, and I had her admitted to hospital. She was in hospital for about a week and there was nothing that was found, despite all the tests that were done. Despite being a doctor and presumably knowing something, I knew nothing–this was in 1985. I had experienced the disbelief from medical professionals, and being recommended various avenues of psychotherapy that were just really quite out of place and inappropriate. We didn’t pursue those because we knew that wasn’t the case, but that’s what started my quest.

How did patients start coming?

They started to appear—through word of mouth they just started to turn up.
I knew what they were going through, because I had personally experienced it. I had experienced the illness by close observation. I didn’t prescribe exercise because I knew what it would do. And patients would tell me—they just knew they couldn’t do it. They knew if they tried to do more than they should, they would become unwell.

The patients could have symptoms of depression, but everyone wanted to get better. They weren’t happy because of the way they were, but they were not primarily depressed. I started to observe that I was getting responses when I used medications that improved neurotransmitter function. By enhancing levels of serotonin, nortriptyline, dopamine you could lessen the severity of quite a number of symptoms. This led me to consider that we’re dealing with a neurological problem. That was my baseline understanding. Then I just sort of worked my way along using those things but keeping my ear open to what might impact it.

What did you hear from them about previous interactions with the health care system?

It’s embarrassing as far as medicine is concerned. Doctors are just about their worst enemies. They’ve been told that it doesn’t exist, they’ve been told, ‘You’ve got a mental illness, a psychiatric illness, you must go and have that attended to.’ And they really can actually get abused by the doctors.

How did your understanding of the illness develop?

By the time they present, they’ve often been unwell for years, or the whole illness may be developing before they actually become unwell. There’s a certain absorptive capacity that people have to sort of adjust and keep going, until eventually something more major or just one too many things happen, and they just fold up and become unwell. You’ve got changes that have been happening for a long time, and the body’s systems are like interlinked wheels. So if one starts to turn one way the other wheels do as well.

So we’ve actually got evidence that these people have some background medical issues before becoming completely unwell. They have increased immune activity or some neurological dysfunction or gastrointestinal dysfunction, for example. They might have a number of medical problems and organ systems that are not working properly. If something else comes along that is more significant, like an infection, like major stress, like doing too much–all these things together seem to be part of the onset that these people have. It led me to consider, for example, that the infections might be just be the trigger on top of what was already happening in that person.

The average length of illness before they came to see me was 5 years. Some have 20 years of illness, but on average people have been trying to find an answer for five years.
Only one out of five were able to fully care for themselves. That is the degree of limitation we find at initial presentation. Some of those limitations may well have appeared prior to presenting themselves for treatment. There may have been some manifestation of this illness to a lesser degree—there may have been times when these sorts of symptoms appeared until ultimately there was an event or events at a period of time that undid everything, and then you ended up with a multi-system illness.

How would you actually diagnose people with the illness?

When people started to come to see me, I began to just see a similarity in their histories. Though the details of what actually accompanied them becoming unwell were different, the nature of the history was similar. Then I came across the so called case definition, the CDC criteria. I could see whether they fulfilled the criteria and of course they would, and then after that the Canadian criteria [Canadian Consensus Criteria, or CCC] came out. Before, when I would follow the CDC criteria, I would say, ‘We’ve done that, and what else is the matter?’ They would go off on their other symptoms as well, and my list of symptoms grew and grew and grew—there would be quite a list of complaints that they had. Then to my delight, the actual Canadian criteria said a lot of what CDC criteria didn’t say and basically took account of the different things I had begun to notice when talking to the patients. So that’s what got me into using CCC rather than the CDC criteria.

How would you develop treatment plans?

They’re not going to get better unless you start to deal with these baseline things. First you need to spend some time uncovering these foundational issues. I’ve created the concept of a tree with trunk and roots and many branches. So often the attention is what’s going on in the branches but not what’s in the trunk and even the roots. This analogy helped my patients understand why we do what we do.

When we went over their medical history, people would remember that when they had an infection, maybe it took them two months to get over it. You could often find these experiences, which were the whole deal to a lesser degree, and they’d get over it. This really became the basis of what I do—I’ve developed a protocol that takes into account all the things that I would have to know to justify what I’m doing. Before patients come, they’re sent a history, and it’s about maybe 10 or so pages—questions about the sorts of things we need to know about their history and family background.

So is it managing or treating the illness?

It’s managing, it is explaining the whole thing, supporting them and suggesting this or that and the other thing. I’m not saying that I’m treating their CFS, which implies that you know what is wrong with them and are going to get them better. But there are some things we might find that are wrong with them, and managing their illness means treating that and addressing the mechanisms if we can.

The Autonomous CollecTWiVe reveal two effective treatments for Ebolavirus infection, how a virus in a fungus confers heat tolerance to a plant, and dampened inflammation as a mechanism for bat tolerance to viral infection.

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The Centers for Disease Control and Prevention thinks that viruses play a role in the childhood paralysis called acute flaccid myelitis (AFM). The finding of antibodies to enterovirus D68 (EV-D68) in the cerebrospinal fluid of patients with AFM strengthens the link between infection with this virus and AFM.

Acute flaccid myelitis (AFM), which mainly occurs in children, involves weakness of the arms and legs and may include other symptoms such as inability to breathe or swallow. There have been outbreaks of AFM in the US in 2014, 2016, and 2018, mainly in the late summer and early fall. The outbreaks of AFM are associated with infection with enteroviruses.

AFM was first defined in 2014 after reports of limb weakness in children across the US during an outbreak of respiratory disease caused by EV-D68 (pictured). AFM may also be associated with infections caused by other viruses, such as enterovirus A71, Coxsackievirus A16, West Nile virus and adenovirus.

Of the 233 patients with confirmed AFM in 2018, EV-D68 was the most frequently detected virus, mainly in respiratory samples. Confirming a viral etiological agent of AFM would be greatly strengthened by finding virus in the cerebrospinal fluid (CSF). However in 2018 only two samples of cerebrospinal fluid from AFM patients were found to be positive for viral RNA: one for EV-D68 and one for EV-A71. There may be multiple reasons for the failure to detect viral RNA in CSF, including clearance of virus by the time AFM is diagnosed, or very low levels of viral genomes.

An alternative to searching for viral genomes in CSF is to identify anti-viral antibodies, which may be produced during infection of the brain and spinal cord. Peptide microarrays were used to detect antibodies against enteroviruses in CSF of AFM patients. In this method, 160,000 unique peptides from the capsid proteins of all known human enteroviruses were spotted on slides. CSF samples were incubated with the slides and binding of antibodies to peptides was quantified. The results revealed antibodies to an 18 amino acid peptide of capsid protein VP1 in serum and CSF of 11/14 AFM patients and 3/26 controls. This amino acid sequence is known to be conserved among diverse human enteroviruses.

More importantly, antibodies to a 22 amino acid sequence in VP1 of EV-D68 were identified in CSF of 6/14 AFM, and in 8/11 serum samples. No immunoreactivity to this peptide was detected in samples from 26 controls.

Detection of antibodies in the CSF is not diagnostic of CNS infection because antibodies are known to pass from blood to CSF. The normal ratio of antibodies in blood to CSF is 250:1. Consequently, for diagnostic purposes, both serum and CSF should be analyzed for the presence of antibodies.

The authors of the study acknowledge this issue, noting that they do not have sufficient simultaneously collected serum and CSF samples to exclude that antibodies they detected in the CSF simply came from the blood. They note that of the 16 control patients with serum antibodies to enteroviruses, only 3 also had such antibodies in CSF. Furthermore, in a study of unexplained encephalitis in India, of 77 children with serum antibodies to enteroviruses, only 3 also had EV antibodies in CSF. For these reasons the authors do not believe that the anti-EV-D68 antibodies they have detected in CSF have come from the blood.

How can it be definitively proven that EV-D68 causes AFM? With an outbreak of AFM expected in the late summer of 2020, there should be ample opportunity to obtain numerous clinical samples – nasopharyngeal wash, serum and CSF – to examine for the presence of EV-D68 antibodies and viral genomes.

By David Tuller, DrPH

People who know little or nothing about the illness or cluster of illnesses variously called myalgic encephalomyelitis, chronic fatigue syndrome, CFS/ME, and ME/CFS can’t seem to stop writing stupid and ill-informed stories about it. And Professor Michael Sharpe seems to blame “Americans”–rather than his own disastrous research–for his current problems and the reputational damage he has suffered. That’s mainly what I got from articles in The Guardian and Psychology Today that followed one another in quick and dispiriting succession last month.

[continue reading…]

From the meeting of the Centers of Excellence for Influenza Research and Surveillance, Vincent speaks with Alan, Florian and Jennifer about their careers, the purpose of CEIRS, universal influenza vaccines, and cellular responses to infection in pediatric populations.

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RNA viruses exist close to their error threshold, the point beyond which additional mutations cause loss of infectivity. It has been suggested that RNA recombination prevents viruses from exceeding the error threshold – a situation called error catastrophe – but there has been little experimental support for this hypothesis. An analysis of poliovirus RNA synthesis suggests that this hypothesis is correct.

[continue reading…]

The complete TWiV team give a report on the Ebola virus outbreak in DRC, and reveal that cell surface nectin proteins cause the transfer of cytoplasmic cargo, including measles virus, between cells.

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by Gertrud U. Rey

Type 1 diabetes is an organ-specific autoimmune disease that is characterized by the loss of insulin-producing beta cells in the pancreas. The loss of these cells leads to decreased insulin production (hypoinsulinemia) and increased levels of glucose in the blood (hyperglycemia). While it is still unclear what exactly causes the loss of beta cells, experts agree that it is likely a combination of genetic and environmental factors. An increasing body of evidence suggests that Coxsackievirus strain B4 is an environmental trigger, because it specifically targets beta cells, causing them to die.

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By David Tuller, DrPH

Some Australian members of the GET/CBT ideological brigades have published yet more nonsense and drivel about “graded exercise therapy” as a treatment for ME/CFS, or what they are still calling “chronic fatigue syndrome.” The article, simply called “Chronic fatigue syndrome: graded exercise therapy,” is in a peer-reviewed journal from a reputable publisher yet is full of unsupported and questionable claims. It references the PACE trial without discussing the developments that have undermined the trial’s credibility, including published re-analyses that refute the core findings. In fact, it reads as if the authors are unaware that the entire debate has been transformed in recent years–which isn’t surprising, because it is basically a reprise of material created in 2015 by the Royal Australian College of General Practitioners.

[continue reading…]