The immune system is a remarkable thing. It has mainly evolved to protect us from infections and has multiple intricate systems to detect and respond to novel infections. I used to warn my patients on the anti-trafficking DMTs, fingolimod and natalizumab, they should be hypervigilant of acquiring exotic new infections, particularly, neurotropic viruses. The theory was that if the virus got to the central nervous system (CNS), whilst you were being treated with one of these therapies, you would be at risk of developing a slowly progressive, untreatable, encephalitis.
Interestingly, I often used dengue fever as an example. Why? Dengue is an arborvirus (transmitted by mosquito bite) with no effective vaccine. Although it causes a self-limiting infection in most people it is neurotropic and hence can cause encephalitis. It is a very interesting virus in that it is a good example of what can go wrong when the immune system commits ‘original antigenic sin’. There are different subtypes of dengue virus. If you are infected with one subtype and develop antibodies to first subtype these antibodies (original antigenic sin) prevent an adequate immune response to subsequent infection with a different subtype of the virus. This results in subsequent dengue virus infection being more severe with high mortality (2-5%). In short, you don’t want to get dengue fever because of this issue.
In my lectures on derisking DMTs, I used to tell people that I advised my patients on fingolimod and natalizumab against travelling to countries where dengue fever was endemic. If they wanted to visit these countries it was preferable to go at a time of the year when infection risk was low and they should make sure they didn’t get bitten by mosquitoes (clothing, insect repellants, mosquito nets, indoor eating, etc.). Was this wise advice? At the time my advice it was based on a scientific principle and my desire to keep my patients safe. However, when data came along and I had to change my position on this; I now don’t use dengue fever as an example.
The small case series of 15 people with MS, on either fingolimod or natalizumab, clearly show that their immune systems were fine at dealing with dengue fever. All the patients recovered and none of them developed encephalitis. The moral of this story is that data trumps opinions and we should always be prepared to change our position on things. I now use this as an example of that fingolimod and natalizumab are not that immunosuppressive and that it should be fine if you get exposed to a novel infection.
For those people with MS on fingolimod and natalizumab, the dengue fever case study should help reassure you that your immune systems are not that compromised when it comes to responding and clearing a novel viral infection. This is one of the reasons why we are not recommending that our patients on natalizumab and fingolimod stop their therapy in response to the COVID-19 epidemic.
Fragoso et al. Dengue Fever in Patients With Multiple Sclerosis Taking Fingolimod or Natalizumab. Mult Scler Relat Disord, 6, 64-5 Mar 2016.
Dengue fever is the most prevalent mosquito-borne viral illness in humans. There may be different clinical manifestations of the disease, from mild symptoms to hemorrhagic forms of dengue fever and even neurological complications of this viral infection. Blood cells are usually affected, and thrombocytopenia is the hallmark of the disease. This paper presents 15 cases of dengue fever in patients with multiple sclerosis (MS) taking fingolimod or natalizumab. There were no complications of dengue fever or worse outcomes of MS in these patients, and only four of them needed short-term treatment withdrawal due to lymphopenia.