An Injection of Trust

Home , Neal Halsey, Paul Offit, Seth Berkley

in the United States alone1. Since the 1980s, every US state has required a standard bat- tery of vaccines for school enrolment. There is strong participation too in much of West- ern Europe, where these vaccines are merely ‘recommended’. “The vast majority of children are immunized, with coverage of over 90% MARMADUKE ST. JOHN/ALAMY MARMADUKE ST. across Europe,” says Pier Luigi Lopalco, head of the vaccine-preventable diseases programme at the European Centre for Disease Prevention and Control (ECDC) in Stockholm. When Australia faced falling vaccination rates in the 1990s it introduced incentives that rewarded both clinics and parents. “Our immunization rates rose by at least 10%, which was a major increase,” says Julie Leask, a social scientist Health-care workers in New York protest against compulsory swine flu vaccination. specializing in immunization policy at the University of Sydney. PUBLIC HEALTH But some vaccination programmes allow people to refuse for personal reasons. In much of Europe, no medical consultation is required. In the United States, parents must actively An injection register their refusal; 48 states recognize religious exemptions and 18 allow ‘personal belief exemptions’. The refusal numbers are low — just 2% for 2010–2011, according to the CDC of trust — but epidemiologist Saad Omer of Emory University in Atlanta, Georgia, has observed a disconcerting rise. “The rate of refusal has Faced with outbreaks of preventable diseases, public-health gone up, and even the rate of change compared experts need to win over parents who refuse vaccinations. to previous years has accelerated,” he says. Indeed, CDC data indicate that the percent- age of non-medical exemptions essentially BY MICHAEL EISENSTEIN 5,442 in just the first 4 months of 2013. And doubled between 2006 and 2011. Different in France, the World Health Organization states require different levels of effort: some n July 2013, public-health officials in Wales (WHO) reported 14,000 cases of measles in require medical consultation, others simply finally began to breathe a sigh of relief. The 2011. “There are lots of examples in wealthy, a signature. Omer found that non-medical measles epidemic that had raged through developed countries,” says Seth Berkley, chief exemption rates were 2.3 times higher in states Ithe country for eight months and infected executive of the Global Alliance for Vaccination with easy requirements than in those with more than 1,200 patients — hospitalizing 88 and Immunization (GAVI) in Geneva, Switzer- steeper administrative barriers2. “If you make and killing one — was finally coming under land. Given the narrow margins of ensuring it easier for a parent who is hesitant and on the control. The respite was brief, however, as protection against such outbreaks, even a few fence to claim an exemption, it looks like they just months later a second outbreak emerged parents who refuse paediatric vaccination will,” he says. in the same region, with 36 new cases by can jeopardize the control and elimination of Unvaccinated families also tend to cluster. mid-November (see “Exposed and unvacci- diseases that are prominent killers of infants Leask notes that in Australia “the refusal rate nated” page S18). and children elsewhere in the world. is 1.7% nationally, but in some regions that can The outbreaks primarily afflicted children Vaccine refusal dates back to the nineteenth climb to around 20%.” Some clustering also whose parents had opted not to let them have century, when the UK Government permitted occurs in self-contained religious groups. The the measles–mumps–rubella (MMR) vaccine. ‘conscientious exemption’ for those opposed ‘Bible Belt’ region of the Netherlands, which Their refusal was broadly attributed to lin- to smallpox vaccination. But today’s reasons is home to several communities of Orthodox gering fears related to a now discredited link for refusal are very different. “We ask citizens Protestants that have rejected vaccination, has between the MMR vaccine and autism. Parents to get vaccines to prevent 14 different diseases, been the site of a large ongoing measles out- remained hesitant even after the first outbreak, which can mean as many as 26 inoculations in break, and in October 2013 an unvaccinated and a strong vaccination push reached fewer the first few years of life, to prevent diseases 17-year-old girl died from measles. More than half of the eligible children. that people mostly don’t see, using biological recently, international travellers have enabled The re-emergence of vaccine-preventable fluids that most people don’t understand,” says this epidemic to make the leap to Canada. diseases has become increasingly common Paul Offit, head of the infectious-diseases divi- worldwide. For example, in 2012 the US Cent- sion at the Children’s Hospital of Philadelphia SCARE STORIES ers for Disease Control and Prevention (CDC) in Pennsylvania. “It’s not surprising that people Instead of religious dogma, many clusters of in Atlanta, Georgia, reported the largest num- are hesitant.” vaccine refusals result from shared concerns ber of US cases of about whether children may be harmed by the pertussis (whooping NATURE.COM PERSONAL REASONS inoculations. “Refusal is multifaceted, but per- cough) for nearly For some of the Most public-health experts view vaccination ceptions of vaccine safety contribute more than 60 years. In Japan, latest research on programmes as unalloyed successes. One other factors,” says Omer. These worries can rubella cases leapt immunization: analysis estimates that immunization has result in delayed vaccination, outright refusal from 87 in 2010 to nature.com/nm prevented 75–106 million cases of disease or selective inoculation of children, where the

schedules that leave children underprotected. EXPOSED AND UNVACCINATED Based on a large study of undervaccination A drop in coverage of MMR vaccine in in eight managed care organizations, Glanz Welsh children led to a rise in vulnerability concluded that at least 12–13% of parents “are to a measles outbreak. deliberately not giving vaccines on time.” PUBLIC HEALTH WALES PUBLIC HEALTH WEXHAM Many parents also visit anti-vaccination Number of cases websites that use anecdotal evidence to pro- per 100,000 people mote an agenda of parental choice that builds November 2012 to December 2013 on an underlying mistrust of the government In Wrexham, 3 where coverage is and the pharmaceutical industry . “They use high, there were narratives and tell stories,” says Neal Halsey, only a small director of the Institute for Vaccine Safety at number of cases. the Johns Hopkins Bloomberg School of Public ABEYSTWYTH Health in Baltimore, Maryland. “We present numbers and risk levels, and those things don’t resonate with hesitant parents.” For such parents, emotional descriptions of children who have allegedly been injured WALES by vaccines may prove more persuasive than tales of half-forgotten diseases. “My wife ran the intensive care unit at a major teaching hospital in America, and she’s never seen a case of NEATH Vaccine uptake among measles or tetanus,” says Berkley. “I think that’s 2-year olds April 2003 SWANSEA to March 2005 a big factor.” He points out that vaccines are generally embraced in the developing world, >85% CADIFF where these diseases remain all too real — the 81–85% Swansea, one of the WHO estimates that 158,000 people died from 76–80% lowest coverage was measles in 2011. “In general, people there des- <75% hit by the most cases. perately want vaccines and will walk for a day to get them,” he says. But in nations with long- standing vaccination programmes, such as the decision is a product of both risk calculation from the VSD helped disprove the connection United States or United Kingdom, it’s easy to and emotional response. between MMR and autism, but have also iden- dismiss these diseases as harmless unless you’ve A single scare can cast a long shadow. The tified real adverse events, such as when 197 experienced the potential complications, which story of Andrew Wakefield, a gastroenter- children in a cohort of 1.8 million who had include pneumonia and encephalitis. “When ologist at the Royal Free Hospital in London received the MMR vaccination developed I’ve talked with parents of unvaccinated chil- whose work led to a widespread belief in a link immune thrombocytopaenic purpura4. “It’s a dren who have been admitted to hospital with between the MMR vaccination and autism, is relatively benign blood disorder where there’s complications from pertussis or measles, they well known. As parents panicked, MMR vac- easy bruising and bleeding, but it can be scary,” inevitably say, ‘I never knew it could be this cination rates in England and Wales fell from says Jason Glanz, an epidemiologist affiliated serious’,” says Halsey. over 90% in 1997 to less than 80% in 2004, with the VSD at the Kaiser Permanente Institute If large numbers of parents continue to opt with similar drops in the United States and for Health Research in Denver, Colorado. out of vaccination programmes, these may well across Western Europe. Although thoroughly The CDC continues to fight the myth of become more familiar experiences. In a well- discredited, Wakefield’s ideas are kept in a vaccine–autism link and recently dem- vaccinated community, even unvaccinated circulation by vocal networks of anti-vaccine onstrated that there was no link between individuals benefit from herd immunity. The activists. “In southern Europe, especially Italy, exposure to numerous vaccine antigens and threshold for this benefit depends on both this alleged link between autism and MMR is autism5. “A substantial proportion of parents the disease and the vaccine; for measles, the re-emerging in the newspapers and on a lot of still have concerns along these lines,” says CDC estimates that herd immunity requires websites,” says Lopalco. Activist organizations DeStefano. Leask notes that the MMR story 92–94% vaccine coverage. But herd immu- also promote unfounded fears that vaccines draws strength from the lack of a robust bio- nity breaks down when coverage drops even trigger medical conditions such as multiple logical explanation for autism. “This causal in small pockets of otherwise well-vaccinated sclerosis or contain toxic levels of chemicals hunger drives people to look around for a culprit,” regions. Omer and colleagues found that this such as aluminium, or that infants’ immune she says, adding that vaccines were once linked to effect may have contributed to a 2010 pertussis systems are overwhelmed by the number sudden infant death syndrome (SIDS) until the outbreak in California that infected more than of vaccinations3. medical community got a better understanding 9,000 individuals6. “The clustering of refusals In fact, vaccines undergo extensive and of the risk factors. was associated with the clustering of pertussis,” continuous surveillance to identify adverse says Omer. Pertussis is particularly problem- events overlooked during clinical trials. For FORGOTTEN FOES atic because the vaccine is less protective than example, the CDC operates the Vaccine Safety Studies suggest that parents who delay or refuse others and its effectiveness wanes over time. Datalink (VSD) with nine large US ‘managed vaccines tend to be well educated and seek out Loss of herd immunity could also help more care organizations’, tracking data from more information that gives them active control of serious diseases to return: the detection of than 9 million individuals. “We can update their child’s health. Some consult practitioners poliovirus in Israel and outbreaks in war-torn these databases weekly, and thus virtually con- of complementary and alternative medicine, Syria led the ECDC to announce7 that such duct real-time monitoring when a new vaccine who may eschew vaccines in favour of non- countries “should urgently consider imple- is introduced,” says Frank DeStefano, director pharmaceutical approaches to preventing menting targeted action and improving vac- of the CDC’s Immunization Safety Office. Data diseases, or promote alternative vaccine cine coverage”.

Wary parents are only part of the problem. “It’s also people who haven’t gotten up to date, CASE STUDY either unwittingly or because they have fallen through the cracks,” says Leask. But those who Adverse reactions sit on the fence represent a potentially serious gap in a nation’s immunity, and the MMR panic Vaccination initiatives are generally initially focus on the vaccine safety issue, but has shown how quickly this gap can widen. welcomed in the developing world, where when they weren’t being listened to, they disease mortality and morbidity remain searched for adverse events because that OFF THE FENCE clearly visible threats, but even there they gets more of a reaction.” The trick is to address worries while preserving are vulnerable to misinformation and Larson believes that more attentive public confidence — often a difficult balancing miscommunication. In the mid-1990s, monitoring of online expressions of public act. Controversy lingers over a 1999 recom- a Catholic organization disseminated concern — through her Vaccine Confidence mendation from the CDC and the American misinformation that the tetanus vaccine Project (VCP), for example — could bring Academy of Pediatrics to remove the ethyl had contraceptive effects. Vaccination rates attention to these issues sooner. Local mercury-containing preservative thiomersal plummeted in Catholic communities until protests are often fuelled by online activists from single-dose vaccines. This precaution public-health professionals reached out to in the United States and Europe. By keeping was based on concerns over cumulative envi- the Vatican to help resolve the crisis. tabs on rumours and reports of possible ronmental mercury exposure in children, The handling of such conflicts can make adverse events, governments and public- although subsequent research showed that or break a vaccination programme. In 2003, health officials can adapt engagement ethyl mercury is eliminated from the body northern Nigeria boycotted the polio vaccine, strategies accordingly. This won’t solve every much faster than predicted. Offit believes this fuelled by political issues and mistrust of problem — Larson notes that recent attacks decision fuelled misconceptions that thiom- the Western pharmaceutical industry and against vaccination workers in Pakistan and ersal contributes to autism. “We branded it by rumours that the vaccine was a plot Nigeria are the acts of militants, rather than with a scarlet letter, and today people are still to sterilize Muslims. The public-health expressions of public refusal. More generally, scared of getting flu vaccines in the multidose community overcame this boycott (and a however, the VCP could help to engage preparations that contain thiomersal,” he similar movement in India) by working with disenfranchised communities early, before says. However, Halsey defends the decision as local Islamic clergy and community leaders. boycotts or protests become necessary. “We’re necessary to protect public trust. “None of us In contrast, two demonstration projects for trying,” says Larson, “to be anticipatory, rather had any concerns about autism,” he says. “But the human papillomavirus vaccine in India than in crisis management.” M. E. if we had not done it, I think that more people were derailed in 2010 by campaigners from would be rejecting those vaccines.” In other women’s groups. After early attempts to cases, the negative impact is clearer. For exam- engage the national government over the ple, France still has poor uptake of the hepati- programme were rebuffed, the activists tis B vaccine following the government’s 1998 mounted an aggressive campaign calling for suspension of vaccination, a decision based on an investigation of the deaths of four vaccine REUTERS/GEORGE ESIRI REUTERS/GEORGE false reports of a link with multiple sclerosis. recipients. The deaths proved unrelated to When the press spotlights potential adverse the vaccine, but the projects were halted events, especially with backing from celebrities amid public opposition. “[The protesters] such as actress Jenny McCarthy or high-profile started talking about things related to it being scientists such as Wakefield, it can even shake too expensive, not giving cervical screening, the faith of medical professionals. “If you have and the need to have a public forum,” a provider who is less confident in a vaccine’s says Heidi Larson of the London School of safety and less motivated, that will have a lot of Hygiene and Tropical Medicine. “They didn’t Polio vaccination in Nigeria. carry-over effects,” says Leask. Heidi Larson of the London School of Hygiene and Tropical Medicine helps public- rate.The final decision on whether to vac- the baby is, reaching mothers ahead of any health experts respond rapidly to avoid cre- cinate, however, happens in the clinic. “Even decisions about vaccination. ating a lingering atmosphere of doubt by among vaccine refusers, we found that primary Offit notes that in his experience, the trump identifying pockets of concern early (see health-care providers were the most frequently card of medical authority also helps. “Both par- “Adverse reactions”). “Publics have long mem- used and trusted source of vaccine information,” ents and doctors want to do what’s best for the ories,” says Larson. “We need to be vigilant and says Omer. Honesty is the best policy. Like any child,” he says. “But they’re coming for your never for a minute take for granted any indi- medicine, vaccines carry real risks, ranging expertise — it’s okay to be an expert.” ■ vidual’s acceptance of any health technology.” from minor swelling to rare but serious events Larson directs the Vaccine Confidence Project such as seizures or anaphylaxis, and doctors Michael Eisenstein is a freelance journalist (VCP), which scans news and social media can build trust by candidly framing these facts based in Philadelphia, Pennsylvania for signs of concern8. “We’re trying to use a alongside the dangers of disease. systematic approach to characterize what “If you put boundaries around the risk and 1. van Panhuis, W. G. et al. N. Engl. J. Med. 369, breeds confidence and lack of confidence, and you say what it is, it becomes much less mys- 2152–2158 (2013). 2. Omer, S. B. et al. N. Engl. J. Med. 367, 1170–1171 identify things that tip it one way or another,” terious,” says Leask. Her team has devised a (2012). she says. Networks of pro-immunization par- decision-support framework that helps clini- 3. Kata, A. Vaccine 30, 3778–3789 (2012). ents are also helping to counter anti-vaccine cians to deliver targeted information for parents 4. O’Leary, S. T. et al. Pediatrics 129, 248–255 (2012). 5. DeStefano, F. et al. J. Pediatr. 163, 561–567 (2013). propaganda. For example, epidemiologist who are cautious supporters, hesitant or ardent 6. Atwell, J. E. et al. Pediatrics 132, 624–630 (2013). Edgar Marcuse of the University of Wash- refusers. The emphasis is on winning over the 7. Risk Assessment: Wild-type Poliovirus 1 Transmission ington in Seattle is recruiting such parents as parents through listening and empathy, rather in Israel — What is the Risk to the EU/EEA? (European Centre for Disease Prevention and Control, 2013). peer-educators through the Vax Northwest than challenging contrary beliefs. Ideally, she 8. Larson, H. J. et al. Lancet Infect. Dis. 13, 606–613 programme to lower his state’s exemption says, this intervention will be delivered before (2013).