The state of the antivaccine movement in the United States: A focused examination of nonmedical exemptions in states and counties

In a Policy Forum, Peter Hotez and colleagues discuss vaccination exemptions in US states and possible consequences for infectious disease outbreaks.

• Several US "hotspot" metropolitan areas stand out for their very large numbers of NMEs. They include Seattle, WA, Spokane, WA, and Portland, OR in the Northwest; Phoenix, AZ, Salt Lake City, UT, Provo, UT, Houston, TX, Fort Worth, TX, Plano, TX, and Austin, TX in the Southwest; Troy, MI, Warren, MI, Detroit, MI, and Kansas City, MO in the Midwest; and Pittsburgh, PA in the Northeast. Additional smaller countiesespecially in ID, WI, and UT-also stand out for their high exemption rates.
• We analyzed the relationship between NME rates and actual vaccine coverage, and found an inverse association between NME rate and measles, mumps, and rubella (MMR) vaccine coverage of kindergarteners in these states (P = 0.03 by Spearman correlation), indicating that states with higher overall NME rates do in fact have lower MMR vaccine coverage (P = 0.007 by beta regression).
• Our findings indicate that new foci of antivaccine activities are being established in major metropolitan areas, rendering select cities vulnerable for vaccination-preventable diseases. As noted by the recent experience in Anaheim, California, low vaccination rates resulted in a measles outbreak. In contrast, state closure of NMEs has resulted in an increase of MMR coverage.

Going granular: Vulnerable communities identified by high NME rates at the county level
Beyond the statewide data, many county-level NME rates were publicly available from state health departments for the school year 2016 to 2017. State-and county-level data included in our analysis have also been made publicly accessible (doi 10.6084/m9.figshare.6288968). County NME rate is defined as the number of enrolling kindergarteners with an NME out of the total kindergarten enrollments (public and private) in the county. Some data inconsistencies were present, including some missing county data for 3 states (AR, ND, OR), absent county data for 4 states (CO, LA, OH, and OK), and lacking data from the year 2016 to 2017 for 3 states (AR, PA, and TX). For AR, PA, and TX, we used data from the 2015 to 2016 school year. Missing data from NME-permitting states were either not collected by the state or publicly inaccessible.
Furthermore, we examined total numbers of kindergarteners with NMEs per county to identify focal areas with large numbers of potentially vulnerable pediatric populations. County NME totals were also provided by state health departments. The exception is MO, whose private kindergarten (2015-2016) and public kindergarten (2014-2015) enrollment numbers were taken together from the National Center for Education Statistics (nces.ed.gov) to derive  Table 2 are the counties-associated with large metropolitan areas-where more than 400 kindergarteners have received NMEs. They include Phoenix, AZ (Maricopa County); Salt Lake City, UT and Provo, UT (Salt Lake and Utah Counties, respectively); Seattle, WA and Spokane, WA (King and Spokane Counties, respectively); Portland, OR (Multnomah County); Troy, MI, Warren, MI, and Detroit, MI (Oakland, Macomb, and Wayne Counties, respectively); Houston, TX, Fort Worth, TX, Plano, TX, and Austin, TX (Harris, Tarrant, Collin, and Travis Counties, respectively); Pittsburgh, PA (Allegheny County); and Kansas City, MO (Jackson County). The high numbers of NMEs in these densely populated urban centers suggest that outbreaks of vaccine-preventable diseases could either originate from or spread rapidly throughout these populations of unimmunized, unprotected children. The fact that the largest count of vaccine-exempt pediatric populations originate in large cities with busy international airports may further contribute to this risk.  Are high NME rates associated with preventable and costly disease outbreaks?
Whereas measles was thought to have been eliminated from the US in 2000, we have seen local outbreaks of this vaccine-preventable disease and others, like measles and pertussis (whooping cough), in recent years due to inadequate immunization coverage in schools. For instance, a child with an NME from the measles, mumps, and rubella (MMR) vaccine is 35 times more likely to contract measles than is a vaccinated child [4]. Moreover, a child without the  diphtheria, tetanus, and acellular pertussis (DTaP) vaccine is 3 times more likely to contract pertussis than is a vaccinated child [5]. NMEs weaken herd immunity that protects the population at large, particularly children who are unable to get vaccinated for medical reasons. The target vaccination coverage rate to achieve the ideal herd immunity is 90% to 95%, depending on the infectious agent [6]. To evaluate the influence of NMEs on vaccine uptake, Spearman correlation was calculated between state NME rate (%) and MMR vaccination rate (%) for 20 states either allowing NMEs (OK was excluded due to lack of MMR vaccine data) or 3 control states prohibiting NMEs in the 2016 to 2017 school year (CA, MS, WV) (CDC MMWR annual report) using R programming language (version 3.4.2) with the "cor.test" function. As shown in Fig 4 and Table 3, there was a significant inverse association between state NME rate and MMR vaccination rate by Spearman correlation (P = 0.03; Fig 4) and beta regression (P = 0.007). Similarly, we calculated Spearman correlation between state NME rate and MMR rate for all 50 US states and the District of Columbia. States with no information for either NME rate or MMR vaccination rate were excluded (CO, IL, MN, MO, OK, and WY). From this analysis, we found a significant inverse association between state NME rate and MMR vaccination rate (P = 0.04) as compared to states allowing NMEs. Overall, states with more NME students exhibited lower MMR vaccination rates. In contrast, states that have banned NMEs-MS, CA, and WV-exhibit the highest MMR vaccine uptake and lowest incidence of vaccinepreventable diseases.

Discussion
Our analysis reveals that, since 2009, NMEs have risen in 12 of the 18 states that currently allow philosophical-belief exemptions. A recent analysis found that the average annual change in state vaccine exemption rates in recent school years has begun to level off nationally, whereas it had been increasing in earlier years [7]. In at least one-half of the 18 states allowing NMEs, the rates have begun to plateau over the last few years. However, it is important to note that NMEs continue to rise in at least one-third of the 18 states, with no signs of slowing in those rates. In addition, in those states with plateauing levels, the potential for outbreaks still exists.
To better understand the problem of NMEs in the US, it is also helpful to examine the rates at the county level, given that NMEs are not distributed homogeneously within each state. Indeed, there are several counties representing hotspots of high NME rates, including some counties associated with large metropolitan areas where more than 400 kindergarten-aged children are not receiving their vaccines. For instance, TX has seen a particularly dramatic increase in NMEs of students in kindergarten through the 12th grade, multiplying nearly 20-fold since the policy's inception in 2003 [6,8]. Our analysis identified the following hotspot metropolitan areas: Seattle, WA, Spokane, WA, and Portland, OR in the Northwest; Phoenix, AZ, Salt Lake City, UT, Provo, UT, Houston, TX, Fort Worth, TX, Plano, TX, and Austin, TX in the Southwest; Troy, MI, Warren, MI, Detroit, MI, and Kansas City, MO in the Midwest; and Pittsburgh, PA in the Northeast. It is important to note that our study is limited in its ability to correlate outbreaks with high NME communities, so the subsequent years will be critical in seeing how these potentials play out in a real-world setting.
Strict policy changes have elicited significant decreases in NME rates, with philosophicalbelief NME prohibitions serving as an effective policy intervention. Several states have also attempted to decrease the NME rate through less stringent means (S1 Table). One common option is requiring parents to view an educational module prior to obtaining an NME (OR in 2014, MI in 2015), yet the effect of curbing the NME rate may not persist beyond the short term. This assertion is supported by an initial drop in OR's rate followed by a steady climb since 2014. Furthermore, AR-which mandated parental education and an annual application for an NME in 2003-has nonetheless seen a yearly increase in NMEs. In 2011, WA enacted a more rigorous requirement of a physician's signature prior to obtaining an NME. Although the rate declined in the following school year, the outcome was short-lived, and the rate plateaued in subsequent years. Another potentially influential policy was in the form of a federal grant issued by ME's state government in 2014 to train healthcare providers on effective communication surrounding vaccines. However, it is unclear whether this multiyear grant was primarily responsible for reversing the NME trend in a single year. In contrast to the states that sought to decrease NMEs, PA controversially began allowing the philosophical-beliefs exemption in 2014. The measles epidemic from 2014 to 2015 originating from the Disneyland theme park in Anaheim, CA was a consequence of low MMR vaccination coverage of children (50%-86% vaccination rate among the exposed population) [9]. In direct response to the measles epidemic, the CA State Legislature passed Senate Bill 277 (SB 277) [10], which placed a statewide ban on NMEs starting January 1, 2016 to mirror previous actions in MI and WV [11]. The policy's effect has been both immediate and significant. The number of kindergarteners with NMEs from 2016 to 2017 dropped to 3,133, the lowest that the state has seen in over a decade [11]. Each county reported significantly fewer children with NMEs. Accordingly, the new law also increased the state's kindergarten vaccination rates, which reached a record high during 2016 to 2017: 95.6% of kindergarteners received all required vaccines compared to 92.8% in 2015 to 2016 [11]. Given the effectiveness of closing the exemption policy, evidence suggests that other states should consider discontinuing the NME option and protect schoolchildren from vaccine-preventable diseases.
Stricter legislative action to close NMEs should become a higher priority because of the positive correlation between leniency of state vaccination policies and exemption rates. On average, states with policies that permit both types of NMEs have 2.5 times higher exemption rates [12]. Although many states demonstrate rising exemption totals irrespective of the exemption policy, states that make it harder to obtain exemptions have demonstrated slower-growing opt-out rates over time. Therefore, it is critical to identify states at highest risk for an outbreak due to a rise in NMEs.
As has been demonstrated by past policy changes, uptake in vaccination rates by communities requires multiple measures (S1 Table). It has been pointed out that a vertical policy change, such as the one highlighted above, should be accompanied by expanded horizontal efforts to increase access to vaccines and booster shots, educational programs, and awareness campaigns [12][13][14]. For instance, healthcare providers might play a greater role in promoting vaccination. The presumptive strategy of health communication, which promotes the safety and routineness of vaccination, between provider and parent has been shown to discourage parents from seeking to obtain NMEs [13]. Furthermore, greater community involvement through churches, neighborhood clinics, and provaccination celebrity allies would help to reach both undervaccinated communities-who are affected by vaccine access-related issues-and unvaccinated groups. Recently, Opel and colleagues identified key policies in the areas of enforcement and reimbursement for pediatricians or other providers who advise vaccine-hesitant parents [14]. As indicated by the increase in NME rates despite ND's policy passage to increase vaccine supply without physician education (S1 Table), it is critical to achieve community buy-in through targeted education campaigns. A multifaceted approach with a central emphasis on discontinuing NMEs will work to increase vaccination rates across a wider scope of the American population and reduce the risk of otherwise preventable and costly disease outbreaks.
The results reported here for the US have potential relevance internationally. While NMEs continue to rise in most of the 18 US states that allow them, several European countries, including France and Italy, as well as Australia, have taken measures to either make vaccines compulsory or even fine parents who refuse to vaccinate their children [15][16][17]. Romania has experienced serious and large measles outbreaks and may also tighten vaccine legislation [18]. Our concern is that the rising NMEs linked to the antivaccine movement in the US will stimulate other countries to follow a similar path. It would be especially worrisome if the very large low-and middle-income countries-such as Brazil, Russia, India, and China (the BRIC nations), or Bangladesh, Indonesia, Nigeria, and Pakistan-reduce their vaccine coverage. In such a case, we could experience massive epidemics of childhood infections that may threaten achievement of United Nations global goals [19].