The return of measles to Europe highlights the need to regain confidence in immunisation.

Abstract

Measles is one of the most contagious infectious diseases and it has had a dreadful impact on mankind for thousands of years. Before the introduction of an efficient vaccine, it is estimated that there were 30 million cases and two million deaths each year, mostly among children in low-income countries 1. Children below the age of one, malnourished children, pregnant women and immunocompromised patients have the greatest risk of adverse outcomes. Infectious and post-infectious complications are common and still occur in approximately 30% of cases. Post-infectious diarrhoea, pneumonia, otitis media and other bacterial infections are common. A less common, but feared, complication is acute measles encephalomyelitis, which occurs in 1–4 per 1000–2000 cases and often has neurological sequelae 1. Measles-induced immunomodulation has been found to have an immunosuppressive effect and this may last for 2–3 years, not just for a transient period after infection 2. The high global coverage of the measles mumps rubella (MMR) vaccination provides protection from measles and may also have a beneficial effect on all-cause mortality in children due to potential post-measles infections 1. Immunisation with an attenuated virus since the 1960s has been one of the greatest achievements in medical history. During the 1980s, measles was almost eliminated in many European countries and there were even hopes that it could be eliminated as it cannot be transmitted by animals. Global measles deaths decreased by 84% from 2000 to 2016 according to the World Health Organization (WHO) 1. The resurgence of measles in Europe in the last few years is both paradoxical and painful. Although national immunisation programmes offer an affordable and efficient vaccine, the latest data show that more than 47 000 people in the WHO European Region were infected with measles from January to July 2018, which is the highest rate for many years 3. The worst affected countries were Ukraine, Serbia, France, Greece and Italy, but eight countries in the Region reported no cases during that period. Recent outbreaks, often with nosocomial transmission and infected health care workers, have been reported from several European countries, such as France, Ireland, Portugal, Sweden and Ireland, where the virus had been eliminated. Transmission from unvaccinated index cases from measles endemic countries is the most common cause of outbreaks. Lack of awareness of measles, and the late clinical presentation of the typical maculopapular measles rash, 3–4 days after the onset of fever, raises the risk of nosocomial and household transmission. Measles is still a killer and the 63 deaths in Europe from January to July 2018 – one to two cases per 1000 cases – are consistent with earlier reports 3. In the French outbreak, from October 2017 to July 2018, there were two deaths in 1101 cases. It is possible that these figures are underestimated due to possible underreporting of unverified cases, with no laboratory results, and a higher prevalence of susceptible patients with risk factors for severe measles. The breakdown of national immunisation programmes due to conflicts, war and social tensions is important causes of the ongoing European measles epidemic. In Ukraine, the percentage of children receiving their second MMR vaccine dose fell from 95% in 2008 to 31% in 2016 4. The migration of unvaccinated people from war zones in the Middle East with insufficient primary healthcare systems, such as Syria, has increased transmission risks. Other causes are inadequate vaccinations in hard-to-reach groups and minority populations in several European Countries. The general anti-vaccination debate accelerated in Europe after British doctor Andrew Wakefield published a widely discredited paper on links between the MMR vaccine and autism. The paper was subsequently withdrawn, and Wakefield was struck off the medical register, but it contributed to decreased immunisation rates in many countries. Misconceptions about measles vaccine have shifted the focus from the benefits to distrust and social media posts about possible side effects. There are even more serious accusations about fake online debates about vaccine safety. A survey of nearly two million Twitter messages from 2014 to 2017, published in the American Journal of Public Health, stated that Russian trolls, identified in lists compiled by the US Congress and NBC News, were more than 20 times as likely as average Twitter accounts to tweet about vaccines 5. The WHO and the European Centre for Prevention and Disease Control have published resources for assessing and addressing vaccine hesitancy and recommended evidence-informed responses to build and sustain vaccination uptakes 6, 7. They aim to regain confidence and promote increased MMR vaccinations in many countries. There are substantial reasons to focus on the risk of measles among children who are unprotected or not yet vaccinated, as even newborn infants may be at risk if they are exposed to the virus. Infants born to vaccinated women have significantly lower antibody concentrations than those born to naturally immune women and may not have any protection before their first MMR vaccination 8. Furthermore, children under the age of one are seven times more likely to die than older children due to post-infectious complications, such as pneumonia 9. A rare, but deadly, complication under the age of two years is subacute sclerosing panencephalitis, a delayed and progressive neurological measles virus infection that is localised in the brain and has recently been reported to be more common than earlier described. In a study from California covering 1998–2014, one in 609 children under one and one in 1367 under the age of five had measles 10. This devastating complication of childhood measles has a latency period of 2.5–34 years after the primary measles infection and is always lethal within a few years. The current European outbreaks are affecting both adults and children. In an outbreak in Gothenburg, Sweden, from December 2017 to January 2018, the median age of the 28 cases was 32 years and only six were children (unpublished data). A large proportion of the cases in several European measles outbreaks have been healthcare workers and most of them were vaccine failures. The efficacy of two doses of the MMR vaccine is considered to be approximately 95% 1. Immunity to measles acquired from the live-attenuated vaccine is much lower than the protection conferred by natural infection and a 2018 study reported that immunity wanes over time, regardless of how it was acquired 11. The concept of modified measles needs to be further explored. Breakthrough measles in previous vaccinated cases seems to be milder, with less respiratory symptoms, and it is rarely transmitted to others 11. The mode of transmission may be important, as healthcare workers who are in close contact with primary measles cases and are exposed to high doses of the measles virus seem to have a greater risk of vaccine breakthrough measles (unpublished data). Certain genotypes of the measles virus may also affect the risk of breakthrough infections. Vaccination is the only way to prevent measles and eliminate the disease and greater efforts are also needed to rebuild trust in vaccinations. Mandatory measles vaccinations are currently included in the national immunisation programmes of nine of the 28 European Union countries, but Italy has recently decided to abandon mandatory MMR vaccinations. It is doubtful whether mandatory vaccinations will contribute to enhanced trust in vaccines. The most important task must be to rebuild the confidence in the healthcare workers who can provide advice and influence vaccination decisions. The European Commission has proposed strengthened cooperation between countries against vaccine preventable diseases, such as measles, pertussis and seasonal influenza. Proposals from the European Union 12 emphasise the importance of joint action to increase vaccination coverage and provide reliable and comprehensible vaccine information to the general public. They also address the need for sufficient vaccine supplies and the support needed to advance vaccine research, development and vaccine education. None. None.