More frustration - infectious mononucleosis (IM) care will become more fragmented because local community-based pharmacists will now manage many patients with sore throats.
As you know, I have been a proponent of Epstein Barr Virus (EBV) being the cause of MS for over 20 years. I have stuck to my guns despite a sceptical MS community. It is not for lack of trying, but there has been very little research funding in this area, which I hope will change with the recent epidemiological evidence strengthening the causal link between EBV and MS.
Many of the hypotheses we want to test around the prevention of MS involve upstream events during acute EBV infection or infectious mononucleosis (IM).
How EBV causes MS is unknown, but IM is a stronger MS risk factor than asymptomatic EBV infection. People with a history of IM have approximately 2.2x greater risk of developing MS. One hypothesis is that the exuberant immune response that occurs during IM provides the immunological substrate for the development of autoimmunity via molecular mimicries or other mechanisms, such as enhanced autoimmune B-cell survival and dysfunctional immune responses.
Sadly we had grants rejected in 2015, 2017 and 2022 to set up a diagnostic and management pathway to study and treat IM. Why would anyone fund a principal investigator (PI) who is a neurologist to study infectious mononucleosis? I guess nobody.
Sorting out IM is a challenging task that requires multidisciplinary input from general practitioners (GPs), microbiologists, virologists, immunologists and now community-based pharmacists. To sort out the shortage of GPs, the government is allowing pharmacists to diagnose and treat sore throats. Will this help or exacerbate the poor management of IM? Only time will tell.
As part of our case for funding our IM work, we performed a clinical audit of acute IM diagnosed in the Barts Health Department of Virology from January 2008 - August 2014. We showed that 60% of 63 subjects were inappropriately prescribed antibiotics in their acute care at the Royal London Hospital. Doctors, usually in A&E, did this to cover the possibility that the purulent pharyngitis was due to group A streptococcal (S. pyogenes) or another bacterial infection. The high misdiagnosis rate is because the diagnostic EBV serology takes 48-72 hours to be processed. Therefore, we want to establish rapid diagnostic testing (EBV lateral flow test or PCR) with fewer than 24 hours turnaround times to diagnose and treat purulent pharyngitis properly.
I am convinced that diagnosing and treating IM with effective antivirals will alter the immunological fingerprint associated with symptomatic EBV infection and ultimately reduce the incidence of MS. The only way to test this theory is for me to get involved in primary care and start diagnosing and managing people with IM.
A rapid IM diagnostic pathway and clinical service will not only allow this to happen but has the potential to revolutionise the management of acute pharyngitis in general practice, which is how the majority of people who have IM present. Other benefits of this service will include a reduction in the inappropriate use of antibiotics, the recruitment of patients with IM into clinical trials and hence the development of effective treatments for acute IM. Creating a rapid diagnostic pathway for acute pharyngitis is a win-win-win situation. (1) The GPs win as the pathway will free up their time, i.e. less work. (2) Patients win as they get diagnosed and treated properly, with the promise of less postviral and chronic fatigue and potentially a lower risk of getting MS or other autoimmune diseases and a potentially lower risk of getting EBV-associated cancers. (3) The NHS wins because fewer antibiotics will be used, and patients will have better outcomes.
From a personal perspective, our MS research group will also win. Having the necessary clinical infrastructure will enable us to apply for additional grants to test novel EBV antiviral agents and track IM incidence. The latter will be an important indicator of whether or not EBV vaccines work in real life when licensed in the future.
What frustrates me is that the medical literature still considers IM a self-limiting benign disease. It is not. IM may be a self-limiting infection in most people. Still, there is a significant minority who have severe IM, with prolonged post-viral fatigue, which may develop into chronic fatigue syndrome. Other people develop severe and often other life-threatening complications from IM, which include hepatitis, ruptured spleen, upper airway obstruction, haemolytic anaemia, thrombocytopaenia, aplastic anaemia, thrombotic thrombocytopaenic purpura or the haemolytic–uraemic syndrome, disseminated intravascular coagulation, haemophagocytic lymphohistiocytosis, Guillain–Barré syndrome, facial nerve palsy, meningoencephalitis, aseptic meningitis, transverse myelitis, peripheral neuritis, cerebellitis and post-infectious optic neuritis. There is even a small number of people who die from IM. Then there are the delayed complications of EBV, including MS and other autoimmune diseases and EBV-associated malignancies. Isn’t this proposal a no-brainer? Clearly not; if it were a no-brainer, we would have had one of our grants funded.
Compelling reasons exist to prevent IM with an EBV vaccine and develop effective antiviral therapies. So if anyone is involved with primary care and/or has political influence, please help. Similarly, if anyone out there wants to help, we need funding and grants to help shift the direction of our research towards IM. This plea also goes out to the pharmaceutical companies. Please consider funding this project if you want to develop therapies for EBV, IM, and EBV-related conditions. It will also help raise your social responsibility profile.
Please note some of the issues I covered in this Newsletter were also covered in ‘Help, my daughter has infectious mononucleosis’ (17-March-2023).
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General Disclaimer: Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust. The advice is intended as general and should not be interpreted as personal clinical advice. If you have problems, please tell your own healthcare professional, who will be able to help you.