Mandatory vaccination in Italy: Time for engagement of immunologists

Vaccines are the most effective health intervention and it has been estimated that they will save approximately 25 million deaths over 10 years from 2010 to 2020, which is equivalent to five lives saved /minute 1. Vaccination has played a major role in the unprecedented increase in life expectancy, from 40 to over 80 years, which has occurred in developed countries in ≃100 years. To have a sense of the drama of polio or other infectious diseases in the western wealthy world, one has to resort to literature, for instance the novel Nemesis by Philip Roth. In spite of the dramatic impact of vaccines on human health and of progress made in understanding the immunology of vaccination and potential vaccination strategies as evidenced by recent reviews in the European Journal of Immunology 2-5 including one in this issue of the Journal 6, possibly involving trained innate immunity 7, and the successful development of new vaccines addressing unmet health needs 7-10, skepticism and sometimes overt hostility (the no-vax movement) have grown in western opulent countries. In sharp contrast, at a global level only one out of 6 children born on the planet has access to the full vaccine repertoire 11, 12. The recent reintroduction of mandatory vaccination in Italy as a requirement to be able to attend school, preceeded by similar decisions in California 13 and other states in the USA, and followed by France, offers a chance for reflection on this apparent paradox. Mandatory vaccination and the offer in the context of the National Health Service of a broad range of vaccines has changed the landscape of infectious diseases in Italy, with for instance the virtual disappearance of hepatitis B. However, in spite of this dramatic health benefit, no-vax attitudes have gained momentum at all levels, from Parliament to public and private television programmes, and this has resulted in a steady slow downhill slide in vaccine coverage, which for instance has reached a low of 85.3% in 2015 and 87.3 in 2016 for measles, well below the herd immunity threshold. This dismal state of affairs was a matter of concern in the medical community with some of its members engaging in communication to the public via books 14, conferences to the lay public and media. As was predicted, the fall in vaccine coverage was followed by a return of infection. Italy in 2017 faced an outbreak of measles with serious consequences for public health. As of December 10, there were 4,885 cases with 4 deaths, 44% needing hospital admission, 22% admitted to hospital as an emergency, and 35% with at least one complication (data from Istituto Superiore di Sanità (http://www.epicentro.iss.it/). Unfortunately complications also matched the textbook figures, with for instance the loss of three children. In the general context of a new action scheme covering all ages of life licensed by the consulting body of the Ministry of Health, Consiglio Superiore di Sanità, the Parliament approved a law proposed by the Minister of Health Mrs. Beatrice Lorenzin, which introduced mandatory vaccination (Poliomyelitis; Diphteria; Tetanus; Hepatitis B; Hemophilus influenzae type B; Measles; Rubella; Chickenpox) in order to be eligible for school. Vaccination against Meningococcus B and C, pneumococcus and rotavirus are recommended, offered and promoted. The enforcement of mandatory vaccination for school eligibility has encountered fierce opposition. The scientific and immunological community has taken strong stands on this issue as testified by the document of Accademia Nazionale dei Lincei 15. The obvious open question is what are the reasons for the spread of anti-vaccine feelings at all levels. We think that there are five main reasons underlying increasing skepticism regarding vaccines (Fig. 1). First, the memory of infection is short-lived and new generations have no sense for instance of what polio used to be. Second, scientific illiteracy is widespread and includes a lack of perception that a timing association does not mean a cause-effect relationship as is the case for the association between the age when autism becomes manifest and vaccination. Moreover people fail to perceive that any medical intervention should be based on a risk-to-benefit assessment. Third, fake news in the social media are hard to dispell, as exemplified by the Wakefield affair. Fourth, there is a widespread perception that a disease like measles is a good training of our immune system as opposed to vaccination, while data show the opposite. This misconception occurs in the context of a widespread perception that “natural” is good. Five, there is no appreciation of the social value of vaccines whereby vaccinated people protect the most needy members of our community (immunodeficiency, cancer, transplantation, neonates and elderly) 16. Interestingly, polls suggest that the introduction of mandatory vaccination and the associated debate has resulted in an improved perception in the general public of the benefits of vaccination. We think that the standing and engagement of the Italian immunological community contributed to the decision taken by the Administration and to an improved public perception. While vaccines have met increased skepticism and opposition in developed countries, the situation in the developing world remains dismal in spite of progress 11, 12. Indeed, one of the biggest challenges for vaccines in global health is to provide existing vaccines to the people who need them. Unfortunately, as we have already mentioned, today only 5% of children born on the planet receive all 11 vaccines recommended by the WHO (BCG, Tetanus, Pertussis, diphtheria, polio, measles, rubella, pneumococcal, rotavirus, Hib, and hepatitis B) for infants everywhere, and 19.5 million children still miss out on a full course of basic vaccines. Inequity occurs primarily in developing countries and among poorer and marginalized populations in developed countries. In order to overcome this obstacle that individual institutions could never achieve on their own, the Expanded Programme on Immunization (EPI), a program of the WHO with the goal to make all relevant vaccines universally available to all at risk, was initially established in 1974, and in 2000 the Global Alliance for Vaccines and Immunisations (GAVI) - today called GAVI, the Vaccine Alliance, - was created whose role is to scale up the use of new and underused vaccines in the poorest countries, through the cooperation between public and private sector. GAVI represents all the key partners in global immunization, namely the governments of donor and implementing nations, WHO, UNICEF, the World Bank, the Bill & Melinda Gates Foundation, civil society organizations, the vaccine industry of both industrialized and emerging countries such as Brazil, India, China, Republic of Korea, and Indonesia. GAVI's mission is to save children's lives and to protect people's health by increasing equitable use of vaccines in lower-income countries. GAVI's mission relies on four strategic goals: the vaccine goal that contributes to accelerating access to vaccines and strengthening vaccine delivery platforms; the health system goal that contributes to strengthening country capacity of integrated health systems to deliver more efficient and effective immunization; the sustainability goal that contributes to improve sustainable national immunization programmes; and the market shaping goal that contributes to create healthy markets and ensure a sufficient supply of proper and affordable vaccines and cold chain equipments. GAVI provides support for 73 low income countries and lower-middle income countries with a gross national income (GNI) per capita ≤US$1570. All countries co-finance a share of the cost of their GAVI-supported vaccines. As countries become more wealthy, they transition out of GAVI support, being eventually able to fully support their immunization programs and continuing to have access suitable products at affordable prices. The GAVI vaccine portfolio includes Pentavalent, Pneumococcal, Rotavirus, Human papilloma, Inactivated polio, Japanese encephalitis, Measles and measles-rubella, Meningitis A, Multivalent Meningitis (A,C, W and Y), Oral cholera, and Yellow fever vaccines. Recently, at the last GAVI board held on December 2017, support for a typhoid conjugate vaccine was also approved. As a result of GAVI action, since 2000 immunization coverage with three doses of Diphtheria-Tetanus-Pertussis (DTP)-containing vaccines in targeted countries raised dramatically from less than 10% in 1980 to more than 60% in 1990, rising to 83% by 2012 17, 18. In 2016, a record number of children with three doses of DTP-containing vaccine was reached and more vaccines than ever were introduced through GAVI support. Nonetheless, between 2015 and 2016 DTP3 coverage remained flat due to population growth, according the WHO-UNICEF Estimates of Immunisation Coverage (WUENIC) released in July 2017. Overall, although this represents a great result, multiple and diversified efforts will be needed to achieve 100% coverage, including the introduction of innovative digital technologies 19. In addition, even with improved coverage for existing vaccines, the development of vaccines for diseases with a high burden for which no good vaccine exists such as for HIV, malaria, and dengue and the improvement of vaccines for tuberculosis control and influenza, are urgently needed. These five diseases cause more than 300 million severe cases of illness and around 3.9 million deaths annually. Regarding malaria, in 2016 GAVI supported a pilot implementation of the RTS,S malaria vaccine, conditional on matching funding then provided by Global Fund and Unitaid Boards. The progress in innovative vaccine technologies will be important not only for the generation of new vaccines but also will allow a more efficient and safer vaccine delivery and overcome the logistical difficulties present in a number of developing countries 20. The above reflections on the “vaccine paradox” (unprecedented success and outstanding medical needs versus increasing opposition) convey a general message to immunologists. In relation to vaccines and health at a national and, no less important, global level, it is part of our social responsibility to take a strong stand, engage in public debate and promote education. The recent experience in Italy, the activities undertaken by other Immunological Societies such as those of the British Society for Immunology as highlighted in the accompanying article covering a brief history of vaccination through to current European vaccination policies 21 and the engagement of immunologists in GAVI 6, 7, including the two of us, conveys the important message that indeed we can have an impact. *The Authors have served (AM) or serve (AS) in the Board of the Global Alliance for Vaccines and Immunization (GAVI). AS is the current President of the Italian Society of Immunology and Clinical Immunology (SIICA). AM serves as President of the International Union of Immunological Societies (IUIS), whose Vaccine Committee is chaired by Ursula Wiedermann (http://iuisonline.org/).