EBV, Glandular fever (infectious mononucleosis)

As it seems a lot of people go on to develop ME following a virus (children in partic seem particularly susceptible after mono,EBV), I thought I'd take a look at the NICE guidelines for EBV.

"
Management
How should I manage a person with suspected or confirmed glandular fever?
Give information and advice:

• Advise on the use of paracetamol or ibuprofen to relieve pain and fever symptoms. See the CKS topics on Analgesia - mild-to-moderate pain and NSAIDs - prescribing issues for more information.
• Explain the expected course of the illness and reassure the person that symptoms usually last for 2–3 weeks. Tiredness is common and is often the last symptom to resolve.
• Advise the person:
  • That exclusion from work or school is not necessary.
  • To return to normal activities as soon as possible. If they are tired, they should tailor their activities to what they can manage comfortably. Bed rest is not normally needed.
  • To limit spread of the disease, by avoiding kissing and sharing eating or drinking utensils, and to thoroughly clean all items that may have been contaminated by saliva.
  • To avoid contact or collision sports or heavy lifting for the first month of the illness (to reduce the risk of splenic rupture).
• Advise the person to seek urgent medical advice if they:
  • Develop stridor or respiratory difficulty.
  • Have difficulty swallowing fluids or have signs of dehydration, such as reduced urine output.
  • Become systemically very unwell.
  • Develop abdominal pain (may indicate splenic rupture).
• If a person has ongoing fatigue, see the section on Assessment in the CKS topic on Tiredness/fatigue in adults for more information on ongoing management."

full text here: https://cks.nice.org.uk/glandular-fever-infectious-mononucleosis#!scenario

I was rather surprised to find that the evidence this is based on is very sparse and that rest is not really deemed necessary, in fact they say that normal activity should be resumed as soon as possible.
I have not had mono/EBV myself so cannot comment from personal experience, but from an ME perspective (and having had some kind of virus followed by pneumonia before onset) this seems very counter intuitive.
(NB: I haven't read the research)

eta:
webmd has different advice:
"

• Get plenty of rest.
• Drink a lot of water and other liquids to stay hydrated.
• Suck on lozenges or ice pops, or gargle with warm salt water, to make your sore throat feel better.
• Take painkillers like acetaminophen or ibuprofen to bring down fever and relieve body aches. (Don't give aspirin to children under 19 years of age because of the risk of a rare but serious condition called Reye’s syndrome.)

Ease back into work or school, taking things slowly until you feel better. For a month or so, avoid sports, heavy lifting, or other vigorous activities in which you could injure your spleen."

https://www.webmd.com/a-to-z-guides/epstein-barr-virus#2

And the NHS..........
"
You should:

• rest and sleep
• drink plenty of fluids (to avoid dehydration)
• take painkillers like paracetamol or ibuprofen (don't give aspirin to children under 16)
• don't drink alcohol - your liver might be weak while you have glandular fever"

"You should feel better within 2 to 3 weeks. Some people might feel extremely tired for months."

"
Glandular fever complications
Most people get better with no problems. Sometimes glandular fever may lead to other illnesses, such as:

• lower level of blood cells, such as anaemia
• an infection, such as pneumonia
• a neurological illness, such as Guillain-Barre syndrome or Bell's palsy

Page last reviewed: 17/11/2017"

 

The advice seems bizarre. Anyone contemplating contact or collision sports within a month of the illness becoming apparent, and having to be advised against it, cannot have had much of an illness.

And what do they mean by "exclusion from work or school"? Do they mean there is no need to exclude, once the patient feels well enough to go, to avoid infection of others? Or do they mean that the patient should be encouraged to go, even though still feeling unwell?

 

The advice seems to me to be a reasonable policy on the basis of limited information. Information is always going to be limited since nobody is going to do trials of people playing rugby earlier and earlier after the illness until the rate of splenic rupture rises by a statistically significant amount.

Infectious mononucleosis is very often pretty transient and minor. A large proportion of people who have it late (as teenagers rather than infants) are unaware that they had more than a standard sore throat. Infants rarely get diagnosed because the illness just looks like a usual virus. Splenic rupture is probably only an issue for the less than 10% of teenage cases who have major lymphoid enlargement.

The bit about exclusion is based on the relatively low infectivity rate in older groups.

I don't see anything in this suggesting that people should go back to school or work if they feel too ill to do so. My impression is that it is more that if you have been feeling OK for a month than there seems no good reason not to do sport.

In my experience most doctors are aware that people can find it impossible to do much for many weeks after EBV infection and would advise people to pace themselves and go back to activities when they are ready. I don't think we have any good reason to do otherwise. The small study of graded exercise seems likely to be meaningless but it is not really affecting the tone of the advice.

 

That does not seem so very different when NICE says: If they are tired, they should tailor their activities to what they can manage comfortably.

 

Serological profiling of the EBV immune response in Chronic Fatigue Syndrome using a peptide microarray

• Madlen Loebel,
• Maren Eckey,
• Franziska Sotzny,
• Elisabeth Hahn,
• Sandra Bauer,
• Patricia Grabowski,
• Johannes Zerweck,
• Pavlo Holenya,
• Leif G. Hanitsch,
• Kirsten Wittke,
• Peter Borchmann,
• Jens-Ulrich Rüffer,
• Falk Hiepe,
• Klemens Ruprecht,
• Uta Behrends,
• Carola Meindl,
• Hans-Dieter Volk,
• Ulf Reimer,
• Carmen Scheibenbogen

• Published: June 12, 2017
• https://doi.org/10.1371/journal.pone.0179124

Background
Epstein-Barr-Virus (EBV) plays an important role as trigger or cofactor for various autoimmune diseases. In a subset of patients with Chronic Fatigue Syndrome (CFS) disease starts with infectious mononucleosis as late primary EBV-infection, whereby altered levels of EBV-specific antibodies can be observed in another subset of patients.

Methods
We performed a comprehensive mapping of the IgG response against EBV comparing 50 healthy controls with 92 CFS patients using a microarray platform. Patients with multiple sclerosis (MS), systemic lupus erythematosus (SLE) and cancer-related fatigue served as controls. 3054 overlapping peptides were synthesised as 15-mers from 14 different EBV proteins. Array data was validated by ELISA for selected peptides. Prevalence of EBV serotypes was determined by qPCR from throat washing samples.

Results
EBV type 1 infections were found in patients and controls. EBV seroarray profiles between healthy controls and CFS were less divergent than that observed for MS or SLE. We found significantly enhanced IgG responses to several EBNA-6 peptides containing a repeat sequence in CFS patients compared to controls. EBNA-6 peptide IgG responses correlated well with EBNA-6 protein responses. The EBNA-6 repeat region showed sequence homologies to various human proteins.

Conclusion
Patients with CFS had a quite similar EBV IgG antibody response pattern as healthy controls. Enhanced IgG reactivity against an EBNA-6 repeat sequence and against EBNA-6 protein is found in CFS patients. Homologous sequences of various human proteins with this EBNA-6 repeat sequence might be potential targets for antigenic mimicry."

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179124

see also:
"Significance
Epstein–Barr Virus infects human B cells and drives them into proliferation and transformation. Although more than 90% of the human population is EBV-infected, EBV-driven pathologies including B-cell lymphomas are limited by a potent T-cell immune response. Here, we present a mouse model for acute EBV infection through conditional expression of two key EBV proteins, LMP1 and LMP2A. This model reproduces EBV-driven B-cell expansion, T-cell–mediated immune surveillance of EBV-infected B cells, and fatal lymphoproliferative disease when the T-cell response is compromised as in immunosuppressed or genetically impaired patients. It thus allows one to study EBV–host interaction functionally and from an angle that should help to develop new therapies for EBV-driven hematological diseases."

http://www.pnas.org/content/113/48/13821.abstract

eta: just adding stuff as I find it............
"Many infectious agents, including EBV infectious mononucleosis, are known to initiate a state of chronic fatigue. Appreciate that EBV may trigger chronic fatigue, but it does not cause chronic fatigue. The fatigue of EBV infection usually resolves within 3 months and uncommonly lasts for longer than 6 months. Patients with CFS have otherwise unexplained fatigue for a duration equal to or greater than 1 year (for a full discussion on CFS, see Chronic Fatigue Syndrome). In summary, acute, but not chronic, fatigue is a feature of EBV infectious mononucleosis."
https://emedicine.medscape.com/article/222040-differential

a nice honest bit on CFS:
"
Background
Chronic fatigue syndrome (CFS) is a disorder characterized by a state of chronic fatigue that persists for more than 6 months, has no clear cause, and is accompanied by cognitive difficulties.

CFS was initially termed encephalomyalgia (or myalgic encephalomyelitis) because British clinicians noted that the essential clinical features of CFS included both an encephalitic component (manifesting as cognitive difficulties) and a skeletal muscle component (manifesting as chronic fatigue).

More recently, the US Institute of Medicine (IOM) proposed that the condition be renamed “systemic exertion intolerance disease” (SEID) to better reflect the condition's hallmark defining symptom, postexertional malaise. [1]

Various unrelated infectious diseases (eg, pneumonia, Epstein-Barr virus [EBV] infection, diarrhea, upper respiratory tract infections) appear to lead to a state of prolonged fatigue in some persons. Generally, if this condition is accompanied by cognitive difficulties, it is referred to as CFS.

The cause of CFS is unknown, but the disorder is probably an infectious disease with immunologic manifestations. EBV has been excluded as a cause of CFS, even though EBV infection is one of the many causes that may lead to a state of chronic fatigue. CFS is not synonymous with chronic EBV infection or chronic infectious mononucleosis.

Because no direct tests aid in the diagnosis of CFS, the diagnosis is one of exclusion but that meets certain clinical criteria, which are further supported by certain nonspecific tests. The diagnosis of CFS also rests on historical criteria (ie, otherwise unexplained fatigue for more than 6 months accompanied by cognitive dysfunction). The absence of cognitive dysfunction should exclude CFS as a potential diagnosis.

Because no cause of CFS has been determined, no effective therapy exists for CFS."
https://emedicine.medscape.com/article/235980-overview

 

This post has been copied and following discussion moved from this thread

If that happens please make sure there is an option for 'never tested/dont know'..... rather than just 'ever had EBV'? yes or no. Otherwise you'll get a lot of 'No' responses confounding the results. I mention that because i was filling out a research survey recently and it asked a question that had a yes no answer to something similar, but if you never had a test then saying no as an answer is misleading.

ETA Many apologies if this seems absurdly patronising to the excellent researchers & management team. Its blatanty obvious for smart people like yourselves i know, it likely didnt even need mentioning!

 

Serology is not usually done here.
We simply have a positive for glandular fever.
Whether its EBV or CMV is not differentiated.

 

I would frankly assume that the vast majority cases of mono are missed. Unless it lasts for months, it would usually be assumed to be a flu or common cold and never even be tested for. Not sure how useful confirmed numbers would be given most wouldn't be. This is the kind of data that are inherently unreliable.

It would be great to have a reliable way to do this, however, but this is data that were simply never recorded for the most part. Same with most other pathogens, really. Only a small % ever even get tested, let alone do the right test at the right time and end up in a usable format.

Which really makes the standard practice of not bothering much about common infections look downright neglectful. Can't even have hindsight when there's no memory to provide it. What a shame.

 

i have to disagree with you. I couldn’t miss my own mono. i was very foggy at work, hard to concentrate, exhausted, felt the flu was coming so i went home early. It was a Monday. I spent the next few days in bed, still awaiting the onset of the respiratory symptoms. After all I had a horrible sore throat, continuing aches, flu-like illness, swollen and tender lymph nodes, crushing fatigue. The respiratory symptoms never came. I went to my doctor a week later, EBV igM was positive. i said flu-like illness, but it’s not the flu, no respiratory illness.

2 weeks later, I had enlarged spleen, very sore liver and elevated liver enzymes requiring pain meds for the liver.

i was 39.


Young adults and teen also usually miss school and unable to carry on sports activities following onset.

 

but you were still reliant on yr dr actually testing for it. Cases get 'missed' because at least in the uk, many Drs arent (or at least weren't) interested in which virus you have, even when symptoms are severe/indicative of EBV. They just brush it off as 'a virus'

 

I am sorry that UK is not doing that. i think NICE should be approached in that regard, if only providing objective evidence of illness which can be helpful in disability cases.

i remember i had to ask my doctor to test me.

 

I'm not concerned about people not noticing their illness, but the circumstances where someone with EBV would get tested for it are very narrow. By far most cases would simply never even see a doctor unless they are concerned that it could worsen enough for hospitalization, they'd just be sent home without testing, and that's for the small % who would bother going to see a doctor. Hell in the OCDE about 1/4 of the population don't even have a GP, that's a sizable chunk just to begin with.

But there's also no reason to think it only happens with severe cases of infectious mononucleosis. Most of the human population carries EBV, which means they got infected at some point in their life, and yet what % of people have a confirmed lab finding of mono? Is it even 5%? It probably happens regardless of severity of infection, or at least there's no reason to suspect it matters much, that old trope is based on an obsession that only injury counts and recovery is nothing but repairing that damage. And 100% of those would be missed other than by checking regularly, such as in the military cohort where they checked for the EBV-MS link.

 

In the UK, testing for CMV and EBV is different.

If there are questions about viruses it should not be limited to EBV. The outbreaks did not follow the infection pattern of herpesvirus. Enteroviruses are more prevalent in the Summer months so the time of infection is important as well.