Immunisation Status Against Major Communicable Diseases Preventable With Vaccines, and Safety of Vaccines, in a Cohort of MS Patients. An Italian Multicenter Study

The different available treatments for MS influence the immune system in distinct ways and, therefore, may lead to specific infectious risks. Whereas immunomodulating therapies have no impact on infection risks [Cahill 2010; Winkelmann 2016], the most recent drugs with immunosuppressant activity could increase persons with MS' vulnerability to infections [Löbermann 2012; Olsson 2014]. MS patients are routinely screened for latent or active infections before starting any disease modifying drugs (DMDs). Specific infectious agents should be evaluated for each second line [Williamson 2015, Yang 2014, Kohlmann 2015]. Another cause of increased susceptibility to infections in MS patients is disability: patients have a greater risk for serious and fatal infections due to MS-related functional limitations as pulmonary problems and bladder and bowel dysfunctions [Montgomery 2013; Nelson 2015]. In addition, there is consistent evidence that exacerbations could be a consequence of infectious diseases, such as bacterial infections of urinary tract, viral respiratory diseases or gastroenteritis, with a two-fold increase in risk of relapse after infection [Panitch 1994; Rutschmann 2002; Loebermann 2012; Williamson 2015]. In such case, the mechanisms underlying relapses are not fully understood [Steelman 2015], but probably molecular mimicry and bystander activation play a role in this process [Loebermann 2012]. Therefore, it is important to promote any prevention strategy that may reduce the risk of acquiring infections, such as vaccination.

Vaccination is the main proven tool for primary prevention of serious, and sometimes life-threatening diseases and one of the most cost-effective public health measures available.

There are 4 main types of vaccines: live-attenuated vaccines, inactivated vaccines, subunit/recombinant/polysaccharide/conjugate vaccines and toxoid vaccines. Live vaccines are made using an attenuated or weakened form of the pathogen. These vaccines have a high efficacy but, containing a live pathogen, they have a potential risk of infection, particularly in patients with a natural or acquired immunodeficiency. Further, concerns about live vaccines administration to close family members of patients have been raised, as there could be the risk that immunised individual release the live pathogens [Williamson 2016]. On the contrary, the other types of vaccines can be safely used by persons with an impaired immune system [www.vaccines.gov\].

In Italy, before 2017, 4 vaccinations were mandatory for children (against diphtheria from 1939, polio from 1966, tetanus from 1968 and hepatitis B from 1991), whereas several others were only recommended. Due to inadequate immunisation coverage, the obligation was recently extended to 10 vaccines, adding the ones against Haemophilus influenzae type B, pertussis, measles, mumps, rubella and varicella for newborns. In addition, there are other recommended vaccines at different ages, i.e. vaccination against rotavirus, meningitis B and C, pneumococcal disease in childhood, against human papilloma virus in adolescents, and against tetanus, diphtheria, pertussis, influenza, pneumococcal disease and herpes zoster for those aged 65 years and older [www.salute.gov.it\].

In MS population, there are some concerns about the utilization of vaccines. It is unclear (at least for some vaccines) whether vaccinations may trigger the disease or increase the risk of relapse due to the stimulation of the immune system, as the infections themselves [Loebermann 2012]. The vaccines against hepatitis B virus, tetanus, tick-borne encephalitis, H1N1 virus and seasonal influenza are considered safe, even if small groups of patients (with a very active form of MS) report an increased risk of relapse after influenza or H1N1 vaccine [Loebermann 2012]. An increased risk of relapses was reported also after yellow-fever immunisation in a single study conducted in a very small cohort of RR-MS patients [Farez 2011b]. On the other hand, a protective role is reported for some vaccines, for example for bacillus Calmette-Guérin vaccine, and for vaccines against tetanus and diphtheria [Loebermann 2012]. For all other vaccines, no data are available [Mailand 2017].