This is the first in a POLITICO special report on vaccines: the accomplishments, history, controversy and business challenges.

The march of modern medicine promises each generation better health than their parents, but fatal diseases from bygone eras are beginning to creep back as public trust in vaccines takes a hit.

After eradicating diseases such as smallpox, vaccines may be the victims of their own success: Worldwide coverage is 86 percent, below the World Health Organization’s global target of 90 percent. And although steady at a global level, the average masks very low vaccination rates in some areas, for example 30 percent in Southeast Asia.

Some countries are experiencing a “historic breakdown in public trust in vaccines,” said Heidi Larsen, director of the Vaccine Confidence Project at the London School of Hygiene & Tropical Medicine. “I would say that hesitancy is increasing in pockets around the world.”

Because vaccines work via herd immunity — coverage needs to hit a certain rate to stop transmission of infection and begin to eradicate infectious diseases in populations — big pockets of resistance can threaten disease protection within a community.

Reports of adverse events, marginalized populations suspicious of governments and corporations, pushback from elites seeking more “natural” remedies and opposition from those with an agenda beyond public health are among the culprits of resistance, she said.

Larsen’s group has surveyed nearly 6,000 parents from the U.K., India, Pakistan, Nigeria and Georgia about whether confidence, convenience or complacency were the main reasons for their hesitation to vaccinate. Confidence — not trusting the vaccine or provider — was the biggest reason in all the countries surveyed.

These three factors define vaccine hesitancy as a behavior, according to the European Centre for Disease Control and Prevention.

Apples-to-apples comparisons are not yet available across countries. Philippe Duclos, senior health adviser for the WHO’s immunization, vaccine and biological department, said officials are in the early days of quantifying skepticism on a global level.

Hesitant Europe

Fear of vaccines is probably as old as vaccination itself, one famous example being Brazil’s 1904 riots over compulsory smallpox vaccination.

Throughout the 20th century, however, vaccines were credited with protecting populations from a host of diseases that used to kill and cripple. Still today, vaccines save between 3 and 6 million of lives each year, according to estimates from the WHO and health economist Jenifer Ehreth.

Hesitancy is putting Europe behind global targets on reducing diseases.

Take measles. A highly contagious disease caused by a virus that affects membranes lining various cavities in the body and then spreads throughout the body, global health experts expected it to be eliminated in Europe by 2015. Some 15 EU countries have managed to do so, according to the WHO. Among them: Bulgaria, Cyprus, the Czech Republic, Estonia, Finland, Hungary and Latvia. A few others are in the process of eliminating it.

But measles remains endemic in eight EU countries, a WHO report released in early April showed. They are Austria, Belgium, France, Germany, Ireland, Italy, Poland and Romania.

Almost 4,000 cases of measles in Europe were reported to the ECDC, with more than half from Germany. About 85 percent of those who contracted measles were not vaccinated.

In early April, the Romanian health ministry called on all local health authorities to mobilize urgently for the measles-mumps-rubella vaccination campaign, following a measles outbreak involving 79 cases in two western Romanian counties.

It is not just children suffering from diseases they are not vaccinated against, according to Lucia Pastore Celentano, head of the ECDC’s vaccine preventable disease program. A third of the measles cases detected in Europe in 2015 involved adolescents and young adults, she said.

“Measles is not a childhood disease anymore,” she said.

The death of an unvaccinated three-year-old girl from diphtheria in March in Belgium showed that universal immunization was the only effective way to prevent the disease, according to the ECDC. There has also been an increase in diphtheria cases in Europe since 2011, it said.

The skepticism cuts across class lines.

“We see an increase in the number of well-educated parents who believe that vaccines are not so important because they don’t see the disease around anymore,” the ECDC’s Pastore Celentano said. “They don’t see diphtheria, polio anymore or they believe that varicella and rubella are childhood diseases and are not dangerous anymore.”

Each government has to tailor communication and social marketing campaigns to specific groups to respond to this behavior, she said.

Andrea Rappagliosi, the president of the industry organization Vaccines Europe, said drugmakers need to be part of the discussion as well, providing evidence of safety, for example.

“This is not something that we have to fight; we have to facilitate this conversation,” said Rappagliosi, who also sits on the executive committee of the joint venture of Sanofi Pasteur and MSD. “We need to fill the gap between the deep technical knowledge and expertise and how we can take this information to real people to make it valuable for them.”

Anti-vaxxers

While there are some who believe vaccines are no longer necessary, there is a small but vocal group who see them as dangerous and in some cases see those that promote them as having sinister motives.

For example, a lack of communication led some in Romania to claim a vaccine to protect against cervical cancer was being nefariously tested on Romanian children, said Alexandru Rafila, president of the country’s Society of Microbiology and adviser to the current health minister. Studies done in the country afterwards show that vaccine distrust started then, he said.

Many who claim vaccines don’t work or are harmful cite the now-retracted and disputed work of former British gastroenterologist Andrew Wakefield, who in 1998 published findings from a tiny study of 12 people purporting to show a link between the measles, mumps and rubella vaccine and autism.

In addition to being retracted by the British medical journal the Lancet, an investigation found Wakefield falsified facts and failed to disclose he got funding from lawyers working for parents suing vaccine producers. But that didn’t come until 2010. The impact of that article still lingers.

A recent documentary accusing the U.S. Centers for Disease Control and Prevention of covering up the link between the vaccine and autism was pulled from the Tribeca film festival in the U.S., after it initially garnered support from the event’s co-founder Robert De Niro, the parent of an autistic child. The controversy may have only made the documentary more appealing, with crowds turning up to watch it.

Wakefield is not the only doctor who questioned vaccines. According to an ECDC report, more studies are now showing that health care workers themselves can be vaccine hesitant, whether considering vaccination for themselves, their children, or their patients.

Despite their ability to grab headlines, anti-vaccination campaigners are not rising in numbers. “The anti-vaccination groups are stable over time: They represent usually 2 percent of the people who refuse to vaccinate,” said ECDC’s Pastore Celentano. Working to convince them otherwise is hard, she said, noting that the efforts should focus on people who are hesitant about vaccination rather than completely against it.

Supply issues

Given the rising numbers of people who do not end up getting vaccinated, for whatever reason, one would expect that there are enough vaccine supplies on hand to cover needs.

But over the past year, nine countries in the EU and the European Economic Area have had to adjust their immunization programs due to a shortage of vaccines containing whooping cough (pertussis) immunization, according to the ECDC.

“There are two manufacturers today in the world that are able to produce this vaccine and for different reasons they had manufacturing problems, which were completely different,” said Vaccines Europe’s boss Rappagliosi. Some vaccine lots did not pass the final tests for the pertussis part, he said. This, combined with rigid public tenders through which vaccines are usually purchased, led to the shortage, which has now been solved, he said.

At the Commission, a recent concept paper will be discussed with the Health Security Committee, a gathering of national representatives from EU countries addressing cross-border health threats. The aim is to “further identify and specify policy challenges to deal with the shortages,” one Commission official said.

Natalie Huet and Kim Dixon contributed reporting.