Dengue fever and exotic infections

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.

I am on holiday with my wife in Bali, a small island in the South of the Indonesian archipelago. It is my first trip to Indonesia; it is beautiful, and the people are so welcoming. The culture is fascinating and very rich with otherworldly traditions and rituals. This also explains why I have not addressed many of the questions in my inbox from subscribers.

Earlier this week, we met a young woman from the UK who is living and working in Bali as a digital nomad. She told us many of her friends have been seriously ill with dengue fever. One of them was in hospital for 5 weeks and almost died. As someone with a ‘normal’ immune system, traveling to subtropical and tropical countries comes with risks. These risks are very different if you are immunocompromised.

Aedes aegypti, the mosquitoes that transmit the dengue virus

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 new infections. I warn people with MS on the anti-trafficking DMTs, S1P modulators (fingolimod, siponimod, ozanimod, ponesimod) and natalizumab that they should be hypervigilant about exposing themselves to exotic new infections, particularly neurotropic viruses. The theory is that if the virus gets into the central nervous system (CNS) whilst being treated with one of these therapies, you would be at risk of developing a slowly progressive, untreatable encephalitis.

I often used dengue fever as an example. Why? Dengue is an arborvirus (transmitted by mosquito bite) with a relatively new vaccine with questionable efficacy. The vaccine is not universally recommended and not for travellers because of concerns about vaccine-induced immune enhancement leading to more severe disease.

Although dengue causes a self-limiting infection in most people, it is neurotropic and can cause encephalitis. It is a fascinating virus that is a good example of what can go wrong when the immune system commits ‘original antigenic sin. ’ There are different subtypes of the dengue virus. If you are infected with one subtype and develop antibodies to the 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 and a second infection because of this issue.

In my lectures on derisking DMTs, I used to tell people that I advised my patients on S1P modulators (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 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, I now don't use dengue fever as an example.

The small case series of 15 people with MS (see abstract below), on either fingolimod or natalizumab, shows that their immune systems could deal with dengue fever. All the patients recovered, and none of them developed encephalitis. The moral of this story is that data trumps opinions, and when new data comes along, we should always be prepared to change our position on things. I now use this as an example to demonstrate that S1P modulators and natalizumab are not that immunosuppressive and that most pwMS should be fine if exposed to a new exotic viral infection. However, as always, it remains a gamble and numbers game; pwMS are probably at the same risk of getting severe dengue as people from the general population.

I would be interested to know if any of you on a DMT have had dengue fever or other exotic infections and how quickly you recovered from them.

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.

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Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Queen Mary University of London or 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 healthcare professional, who will be able to help you.