Despite the rigorous vaccine safety systems in place in the US, some parents remain concerned about the safety of the childhood vaccines and immunization schedule. These concerns have led some parents to not allow their children to receive some or all of the recommended vaccines. In the US, rates of vaccine exemptions increased from 1% in 2006 to 2% in 2016 to 2017 (1); some states reported that 6% of children received exemptions. The rate of vaccine-preventable diseases is higher in children whose parents have refused ≥ 1 vaccines for nonmedical reasons. Specifically, they are 23 times more likely to contract pertussis (2), 8.6 times more likely to contract varicella (3), and 6.5 times more likely to contract pneumococcal disease (4). Children in the US still die from vaccine-preventable diseases. In 2008, there were 5 cases (one fatal) of invasive Haemophilus influenzae type b infection in Minnesota, the most since 1992 (5). Three of the infected children, including the child who died, had received no vaccines because their parents had deferred or refused the vaccine.
The decision to defer or refuse vaccines also affects public health. When the proportion of the overall population that is immune to a disease (herd immunity) decreases, disease prevalence increases, increasing the possibility of disease in people at risk. People may be at risk because
- They were previously vaccinated, but the vaccine did not induce immunity (eg, 2 to 5% of recipients do not respond to the first dose of measles vaccine).
- Immunity may wane over time (eg, in the elderly).
- They (ie, some immunocompromised patients) cannot receive live-virus vaccines (eg, measles-mumps-rubella, varicella) and rely on herd immunity for protection against such diseases.
Parents hesitate to vaccinate their children for many reasons. Two of the more prominent parental concerns over the past decade have been that
- Vaccines may cause autism.
- Children receive too many vaccines.
Conversations with reluctant parents typically require more than presenting evidence. Finding common ground with parents' goals and hopes for their children and sharing compelling individual accounts can help (6).
- 1. Seither R, Calhoun K, Street EJ, et al: Vaccination coverage for selected vaccines, exemption rates, and provisional enrollment among children in kindergarten–United States, 2016-17 school year. MMWR Morb Mortal Wkly Rep 66(40):1073–1080, 2017. doi: 10.15585/mmwr.mm6640a3.
- 2. Glanz JM, McClure DL, Magid DJ, et al: Parental refusal of pertussis vaccination is associated with an increased risk of pertussis infection in children. Pediatrics 123(6):1446–1451, 2009. doi: 10.1542/peds.2008-2150.
- 3. Glanz JM, McClure DL, Magid DJ, et al: Parental refusal of varicella vaccination and the associated risk of varicella infection in children. Arch Pediatr Adolesc Med 164(1):66–70, 2010. doi: 10.1001/archpediatrics.2009.244.
- 4. Glanz JM, McClure DL, O'Leary ST, et al: Parental decline of pneumococcal vaccination and risk of pneumococcal related disease in children. Vaccine 29(5):994–999, 2011. doi: 10.1016/j.vaccine.2010.11.085.
- 5. Centers for Disease Control and Prevention (CDC): Invasive Haemophilus influenzae type B disease in five young children—Minnesota, 2008. MMWR Morb Mortal Wkly Rep 58(3):58–60, 2009.
- 6. Politi MC, Jones KM, Philpott SE: The role of patient engagement in addressing parents’ perceptions about immunizations. JAMA. 318(3):237–238, 2017. doi:10.1001/jama.2017.7168.
Measles-mumps-rubella (MMR) vaccine and autism
In 1998, Andrew Wakefield and colleagues published a brief report in The Lancet. This report concerned 12 children with developmental disorders and gastrointestinal (GI) problems; 9 of them also had autism. According to the report, parents claimed that 8 of the 12 children had received the combined MMR vaccine within 1 month before the development of symptoms. Wakefield postulated that the measles virus in the MMR vaccine traveled to the intestine where it caused inflammation, enabling proteins from the GI tract to enter the bloodstream, travel to the brain, and cause autism. This study received significant media attention worldwide, and many parents began to doubt the safety of the MMR vaccine. In another study, Wakefield claimed to find the measles virus in intestinal biopsy specimens of 75 of 90 children with autism and in only 5 of 70 control patients, leading to speculation that the live measles virus in the MMR vaccine was somehow implicated in autism.
Because Wakefield's methodology could show only a temporal association rather than a cause-and-effect relationship, numerous other researchers studied the possible connection between the MMR vaccine and autism. Gerber and Offit reviewed at least 13 large epidemiologic studies, all of which failed to support an association between MMR vaccine and autism (1). Many of these studies showed that national trends of MMR vaccination were not directly associated with national trends in the diagnosis of autism. For example, in the UK between 1988 and 1999, the rate of MMR vaccination did not change, but the rate of autism increased.
Other studies compared the risk of autism in individual children who did or did not receive the MMR vaccine. In the largest and most compelling of these studies, Madsen et al assessed 537,303 Danish children born between 1991 and 1998, 82% of whom had received MMR vaccine (2). After controlling for possible confounders, they found no difference in relative risk of autism or other autism-spectrum disorders in vaccinated and unvaccinated children. Overall incidence of autism or an autistic-spectrum disorder was 608 of 440,655 (0.138%) in the vaccinated group and 130 of 96,648 (0.135%) in the unvaccinated group. A follow-up study of all children born in Denmark between 1999 and 2010, for a total of 657,461 children concluded that MMR does not cause autism (hazard ratio 0.93 [95% CI, 0.85 to 1.02]) overall, nor does it increase the risk in children who are at high risk of autism because of their family history (3). Other population-based studies from across the world have reached similar conclusions.
In response to Wakefield's increased detection of measles virus in intestinal biopsy specimens from autistic children, Hornig et al searched for the measles virus in biopsy samples taken from 38 children who had GI symptoms and were having a colonoscopy; 25 children had autism, and 13 did not (4). The measles virus was not detected more often in the children with autism than in those without.
In 2010, The Lancet fully retracted the 1998 publication based on the findings of the British General Medical Council (5). Three months after The Lancet's retraction, Wakefield was removed from the UK medical register, with a statement regarding his intentional falsification of his research; as a result, he was barred from practicing medicine in the UK.
Despite the overwhelming evidence to support the safety of the MMR vaccines, many parents remain unconvinced. As a result, the US is experiencing the largest measles outbreak since 1994. According to the Centers for Disease Control and Prevention (CDC), most infected people are not vaccinated (6).
- 1. Gerber JS, Offit PA: Vaccines and autism: A tale of shifting hypotheses. Clin Infect Dis 48(4):456-461, 2009. doi: 10.1086/596476.
- 2. Madsen KM, Hviid A, Vestergaard M, et al: A population-based study of measles, mumps, and rubella vaccination and autism. N Engl J Med 347(19):1477-1482, 2002. doi: 10.1056/NEJMoa021134.
- 3. Hviid A, Hansen JV, Frisch M, Melbye M: Measles, mumps, rubella vaccination and autism: A nationwide cohort study. Ann Intern Med 170(8):513-520, 2019. doi: 10.7326/M18-2101.
- 4. Hornig M, Briese T, Buie T, et al: Lack of association between measles virus vaccine and autism with enteropathy: A case-control study. PLoS ONE 3(9):e3140, 2008. doi: 10.1371/journal.pone.0003140.
- 5. Eggertson L: Lancet retracts 12-year-old article linking autism to MMR vaccines. CMAJ 182(4):E199-E200, 2010. doi: 10.1503/cmaj.109-3179.
- 6. Patel M, Lee AD, Redd SB, et al: Increase in measles cases—United States, January 1–April 26, 2019. MMWR 68(17);402–404. doi: 10.15585/mmwr.mm6817e1.
Thimerosal and autism
Thimerosal is a mercury compound previously used as a preservative in many multidose vaccine vials; preservatives are not needed in single-dose vials and cannot be used in live-virus vaccines. Thimerosal is metabolized to ethylmercury, which is eliminated quickly from the body. Because environmental methylmercury (which is a different compound that is not eliminated from the body quickly) is toxic to humans, there was concern that the very small amounts of thimerosal used in vaccines might cause neurologic problems, particularly autism, in children. Because of these theoretical concerns, even though no studies had shown evidence of harm, thimerosal was removed from routine childhood vaccines in the US, Europe, and several other countries by 2001. However, in these countries, thimerosal continues to be used in certain influenza vaccines and in several other vaccines intended for use in adults (see Thimerosal Content in Some US Licensed Vaccines). It is also used in many vaccines produced in developing countries; the World Health Organization (WHO) has not recommended its removal because there is no clinical evidence of toxicity due to routine use.
Despite the removal of thimerosal, rates of autism have continued to increase, strongly suggesting that thimerosal in vaccines does not cause autism. Also, 2 separate Vaccine Safety Datalink (VSD) studies have concluded that there is no association between thimerosal and autism. In a cohort study of 124,170 children in 3 managed care organizations (MCOs), Verstraeten et al found no association between thimerosal and autism or other developmental conditions, although inconsistent associations (ie, seen in one MCO but not another) were seen between thimerosal and certain language disorders (1). In a case-control study of 1000 children (256 with an autism-spectrum disorder and 752 matched controls without autism), Price et al, using regression analysis, found no association between exposure to thimerosal and autism (2).
Practitioners who work with parents who are still concerned about thimerosal in the influenza vaccine may use single-dose vials of injectable vaccine or the live-attenuated nasal spray vaccine, neither of which contains thimerosal.
- 1. Verstraeten T, Davis RL, DeStefano F, et al: Safety of thimerosal-containing vaccines: A two-phased study of computerized health maintenance organization databases. Pediatrics 112:1039-1048, 2003. Clarification and additional information. Pediatrics 113(1):184, 2004.
- 2. Price CS, Thompson WW, Goodson B, et al: Prenatal and infant exposure to thimerosal from vaccines and immunoglobulins and risk of autism. Pediatrics 126(4):656-664, 2010. doi: 10.1542/peds.2010-0309.
Use of multiple, simultaneous vaccines
A nationally representative survey done in the late 1990s revealed that nearly one fourth of all parents felt that their children receive more immunizations than they should. Since then, additional vaccines have been added to the immunization schedule so that by age 6, children are now recommended to receive multiple doses of vaccines for 15 different infections (see table Recommended Immunization Schedule for Ages 0–6 Years). To minimize the number of injections and visits, practitioners give many vaccines as combination products (eg, diphtheria-tetanus-pertussis, measles-mumps-rubella). However, some parents have become concerned that children's (particularly infants') immune system cannot handle multiple simultaneously presented antigens. This concern has caused some parents to request alternative immunization schedules that delay and sometimes completely exclude certain vaccines. A recent nationally representative survey found that 13% of parents use such a schedule.
The use of alternative schedules is risky and scientifically unfounded. The official schedule is designed to protect children against diseases when they are most susceptible. Delaying vaccination increases the amount of time children are at risk of acquiring these diseases. In addition, although parents may plan to only delay vaccination, the increased number of visits needed for alternative schedules increases the difficulty of adherence and thus the risk that children will not receive a full series of vaccines. Regarding the immunologic challenges, parents should be informed that the amount and number of antigens contained in vaccines is miniscule compared with that encountered in everyday life. Even at birth, an infant's immune system is prepared to respond to the hundreds of antigens the infant is exposed to while passing through the birth canal and being handled by the (unsterile) mother. Children typically encounter and respond immunologically to dozens and perhaps hundreds of antigens during an ordinary day without difficulty. A typical infection with a single organism stimulates an immune response to multiple antigens of that organism (perhaps 4 to 10 in a typical upper respiratory infection). Furthermore, because current vaccines contain fewer antigens overall (ie, because key antigens have been better identified and purified), children are exposed to fewer vaccine antigens today than they were for most of the 20th century.
In summary, alternative vaccine schedules are not evidence-based and put children at increased risk of infectious diseases. More importantly, they offer no advantage. Using data from the VSD, Smith and Woods compared neurodevelopmental outcomes in a group of children who received all vaccines on time with those who did not (1). The children in the delayed group did not do better on any of the 42 outcomes tested. These results should reassure parents who are concerned that children receive too many vaccines too soon.
- 1. Smith MJ, Woods CR: On-time vaccine receipt in the first year does not adversely affect neuropsychologic outcomes. Pediatrics 125(6)1134-1141, 2010. doi: 10.1542/peds.2009-2489.
- Thimerosal Content in Some US Licensed Vaccines