I was called to casualty to assess one of my patients with MS who was on natalizumab. She had been admitted with a temperature, confusion, seizures and a generalised skin rash. Within thirty minutes of seeing her, she went into status epilepticus and had to be sedated, intubated and admitted to ITU. Within 72 hours she was dead. At post-mortem, she had a measles pan-encephalitis. Four days before presentation she had unknowingly come into contact with a friend’s child who had measles. The friend was a staunch anti-vaxxer who believed that the measles vaccine caused autism and would corrupt her child’s immune system.
The above scenario is fictitious, but could happen, or more likely will happen sometime in the near future. This is a ‘known unknown’.
Things have a tendency to happen in threes; I experienced two today let’s hope the third remains science fiction.
(1) As I left home this morning on my daily commute to Whitechapel I finished listening to an Audm podcast “FEAR, MISINFORMATION, AND MEASLES SPREAD IN BROOKLYN” by Amanda Schaffer (Wired, 24-06-2019); scary stuff about the real impact of the anti-VAXX campaign on residents in Brooklyn, New York.
(2) I followed this by reading a review about measles in the latest NEJM (Strebel & Orenstein. Measles. N Engl J Med. 2019 Jul 25;381(4):349-357), which reminded me of medical school and my time on the medical wards in South Africa.
I then had flashbacks to my days as a neurology registrar in South Africa seeing and managing many patients with SSPE (subacute sclerosing panencephalitis) a relatively rare, but fatal, complication of measles infection.
More recently there was a fatal case of measles inclusion body encephalitis presented at our Association of British Neurologists meeting; tragically this young woman had not been vaccinated against measles.
Why is this important? We are living through a measles epidemic. The anti-VAXX campaigners have convinced enough parents over the last two decades to not vaccinate their children against measles, mumps and rubella (MMR). Once a certain proportion of the population is not immune to measles, so-called herd immunity becomes ineffective; i.e. the shield offered by a population of people immune to measles is too porous to isolate susceptible people from wild-type infection in the community. In fact, vaccination works because of herd immunity.
Another factor to consider is that unvaccinated people also get MS. If you are unvaccinated and have not been exposed to the wild virus you are now at relatively high-risk of acquiring measles as an adult. If you then decide to go onto longterm immunosuppression to treat your MS you are putting yourself at risk of serious complications from these infections, in particular measles. In addition, once you are on a longterm immunosuppressive therapy you can’t be vaccinated with the MMR vaccine as it is a live attenuated vaccine.
Measles is also a neurotropic virus and hence seeds to the brain. If you are on natalizumab and contract measles you will be in serious trouble. Natalizumab works by blocking trafficking of lymphocytes to the CNS and hence will stop your lymphocytes detecting, attacking and clearing the virus from the brain. The consequences of an unimpeded measles virus infection of the brain will be in all likelihood be lethal. This is a similar scenario to what happens with PML. Although natalizumab is being fingered here there is a risk will all of our immunosuppressive DMTs.
Because of this known unknown, I am proposing that all MSers are screened at baseline, i.e. before initiating a maintenance immunosuppressive therapy, to make sure they have immunity to MMR. If they are antibody negative they should be offered the option of receiving the MMR vaccine, or at least the individual components of the vaccine if they are still available in your country, to make sure they are immune to these viruses before they start treatment with the DMT concerned.
I sincerely hope my case scenario remains fiction and things don’t have to happen in threes.