Claudia A. Chiriboga, MD, MPH
SUMMARYImmunization programs are most perhaps the most important public health initiative in which a country can invest as they are designed to protect children, the most vulnerable members of our population. As parents it is important to have a full understanding of the possible complications of vaccines, less we allow fear to guide us. Herein, I provide a framework that will provide information to guide parents in this endeavor.
INTRODUCTIONImmunization programs have been effective in protecting children against infectious disease thus, playing a crucial role in eradicating previously deadly diseases. The main example is smallpox, a formerly deadly childhood disease that was removed worldwide in 1980 as a result of a World Health Organization (WHO) program. However, in order for such programs to be effective they have to be able to reach over 80% of the community at risk (i.e., unvaccinated children). High vaccination rates in turn protect even unvaccinated people by lowering the level of infectious disease in the community. This phenomenon is known as herd immunity. Table 1 depicts the vaccination schedule recommended for healthy children in the United States (U.S.). Table 1. Approximate Schedule of Routine Immunization of Healthy Infants and Children.
|2 months||DTaP, HBV, Hib, eIPV, RV, PC|
|4 months||DTaP, Hib, eIPV, RV, PC|
|6 months||DTaP, Hib, eIPV, RV, PC|
|12-15 months||DTaP, Hib, MMR, eIPV, Var, PC,HBV (6-18 months) HepA (2 dose series 12-24 months)|
|4-6 years||DTaP, MMR, eIPV, RV, Var|
|11-12 years||TDap, MV (with or without Hib), HPV (3 dose series)|
|Yearly 6-23 Months > 2 Years||Influenza IIVLAIV or IIV|
Antivaccine movementsThe first objections to vaccination were religious in nature. In 1722, Rev Edward Massey, an English theologian, said small pox inoculation was “dangerous and sinful” and equated it with “a diabolical operation”. Mandatory vaccination policy in Great Britain in 1853 for all infants and later to children up to age 14 years resulted in public outcry, as the policy was viewed as an violation of individual liberties. Eventually the law was changed in 1898 to allow conscientious exemptions to mandatory vaccinations. In the U.S. anti-vaccine movements surfaced in the late 19th century [Porter & Porter 1988]. Anti-vaccine groups founded at the time doubted the science behind vaccination, such as the existence of the concept of immunity. They feared the introduction of “impurities” into their bodies. This concept is similar to the fears espoused by some of today’s vaccine opponents. Anti-vaccine sentiments unfortunately are global. In Africa, vaccine mistrust brought to a near halt in 2003, a WHO polio eradication program because of rumors that vaccination spread AIDS or sterilized Muslim girls. In developed countries, the inroads made by anti-vaccine movements are reflected in the growing number of vaccine exemptions. These exemptions fuel the return of previously eliminated diseases. In countries that have strong anti-vaccine movements (e.g. U.S.) the rates of pertussis are 10 to 100 times higher than rates in countries without such anti-vaccine movements, where levels of vaccination are very high (e.g. Hungary) (Gangarosa et al. 1998). Nowhere is the impact of vaccine exemptions more apparent than with measles. With multiple measles outbreaks crisscrossing the nation recently, U.S. faces the worst measles epidemic in over 2 decades (see Fig. 1). The CDC reports a 10-fold increase for the first half of 2014 alone [Gastañaduy et al., 2014]. Outbreaks typically originate from an unvaccinated U.S. citizen who contracts measles while traveling abroad and brings it home where it spreads primarily to children under the age of 5 years. Most individuals contracting imported measles (80%) are susceptible due to vaccine exemptions. The remainders are either too young or too ill to be vaccinated. In 2013, religious exemptions accounted for a measles outbreak of 58 in Brooklyn, New York imported from Britain. Most of those infected were young children, about half under the age 12 months (too young to be vaccinated) [CDC, 2013]. The reasons behind the growth of anti-vaccine sentiments in the United States and other industrialized nations are not clear. A combination of factors are likely contributing to the sentiment including fear, ignorance, celebrity endorsement of such practices (e.g. Jenny McCarthy, Kristen Cavallari), and media sensationalism. The internet, with its lack of scientific scrutiny, has expanded the reach of anti-vaccine movements via seemingly authoritative Web sites that disseminate misinformation about vaccine injuries. For example, such sites can make claims of vaccine injury without needing to show any proof. Further fueling this anti-vaccine sentiment is the fear generated by the lack of defined etiologies to explain neurological or developmental disorders (e.g. autism) that may temporally coincide with vaccination. This fear, termed risk perception, refers to the manner in which people perceive the severity of a specific risk. Paul Slovic (1987) discussed risk perception is not rational. Therefore, it is not lessened by rational arguments or compelling scientific information. Instead, the judgment of risk severity is curbed by psychological factors, such as whether risks are perceived as being uncontrollable, having catastrophic potential, or having fatal consequences. These key factors apply to autism (an uncontrollable risk with catastrophic potential). A disease that for unknown reasons has reached epidemic proportions, and that is temporally associated with measles vaccination. The spark lighting the fuse of the measles/autism hype was Wakefield’s report of an association between autism and measles vaccination (see Combination Vaccines and Additives) . Wakefield was forced to retract the report as flawed [Anonymous 2010], unfortunately, not before the report influenced measles vaccination practices first in Europe and then in the U.S. The report was later discovered to be fraudulent [Godlee 2011].
Consequences of vaccine exemptionsThe loss of herd immunity is the most detrimental consequence of vaccine exemptions. Over the last decade an increasing number of educated parents are choosing vaccine exemptions in the U.S. (6% of children in Seattle and 4% in Colorado are unvaccinated). These high rates of vaccine exemptions are mirrored by an increase in base rates of pertussis (3-fold increase) and measles (10-fold increase). These increased rates have tragic implications, as susceptible children succumb to preventable diseases. In the case of pertussis, half of infected infants under a year of age are hospitalized and most deaths happen in infants < 3 months of age. Another example is the devastating consequence of meningitis in an Oklahoma boy that tragically resulted in the loss of 4 limbs and facial deformities [Alcindor 2014]. This outcome underscores how personal actions, such as vaccine exemptions, have important public health consequences on children too young to be vaccinated. Hence, children contract diseases they never would have been in contact with had there been proper levels of vaccination in their community. It is these public health considerations that have prompted some States to require parental education prior to granting vaccine exemptions. This requirement is intended to create greater knowledge of the implications of vaccine exemptions for parents’ own children, and the children in their community prior to making such decisions.
ASSESSING CAUSALITYTemporal association is a requirement when assessing causality. However, events that are temporally associated are not necessarily causally linked. Determining causal relationships between vaccinations and speciﬁc disorders with certainty is difﬁcult. It requires additional factors to increase the level of certainty. A temporal association may be taken as causally related when it may be linked by simple chance, especially when the biological phenomenon (e.g. onset for a specific neurological outcome) overlaps with the timing of infant vaccinations. The role of chance becomes an even more likely occurrence when the factors being linked occur frequently in the population. Associations by chance between these two common events (developmental disorder and vaccines) are to be expected and do not denote causality. The role of the coincidence between timing of vaccine and disease onset was the focus of the Melchior study. In the 1970s the DPT (diphtheria, pertussis and tetanus) vaccine was going through media hype. Similar to current scrutiny of the relationship between autism and MMR, early DPT vaccination was linked with claims of vaccine-induced neurological injury, because of the onset of infantile spasms (IS), an epileptic syndrome of childhood.. To dispel this temporal link, Melchior and colleagues sought to examine the effect on the onset of infantile spasms in Denmark by changing the timing of initiating DPT vaccine from 5 months to 5 weeks. The study found that the mean age of onset of IS did not change together with the change in DPT administration. This proved IS was independent of vaccine administration [Melchor 1977]. With greater medical understanding, a greater proportion of IS cases were found to have specific causes (genetic or metabolic). This helped further break the perception of a link with vaccination. As the mystery of autism and a better understanding of its biology is revealed, it is intended that the perception of its risk linked to measles vaccines will also end. Determining causal relationships between vaccinations and speciﬁc disorders with certainty is difﬁcult. There are several methods by which to assess the strength of an association between vaccine and an adverse outcome. The least helpful manner to determine the role of vaccines in causing harm is the anecdotal report. Anecdotal reports are commonly employed by anti-vaccine movements to support claims. A good example of the lack of scrutiny of this type of report is the case in 2013 of a teenage girl in Britain who died shortly after receiving a human papilloma vaccine (HPV) vaccine. The media, as well as anti-vaccine websites, were quick to blame the HPV vaccine [Kotz, 2009]. It was only after the autopsy was performed that the true cause of death was revealed and the girl was found to have an undiagnosed metastatic cancer surrounding her heart. This example illustrates the limitations of the anecdotal report and highlights the need to employ more rigorous methods in linking causality. The case report is not much better than the anecdotal report, with one exception: the peer-review process. This is an important safeguard found in medical journals and missing from Web sites. Any publication in medical journals is reviewed by experts in the field who hold the author accountable for the content. This ensures the report does not overstate the findings or associations. These reports play an important role in alerting of a possible association that may prompt further study. The other two study types:
- clinical trials
- population studies
- no evidence bearing on a causal relationship
- evidence is inadequate to accept or reject a causal relationship
- evidence favors rejection of a causal relationship
- evidence favors acceptance of a causal relationship
- evidence establishes a causal relationship [IOM, 1993, 2012]
- vaccines composed of whole-killed organisms
- vaccines composed of live-attenuated viruses
- vaccines composed of components of organisms
- recombinant vaccines
VACCINE INJURY COMPENSATION PROGRAMThe U.S. Vaccine Injury Compensation Program (VICP) came into being in 1988. This was a time in which vaccines became scarce because pharmaceutical companies, fearing the cost of litigation, were ceasing the manufacture of vaccines. By providing a no-fault alternative to the traditional tort system for resolving vaccine injury claims, the VICP was instrumental in fostering the production of a full, steady supply of vaccines. Vaccines covered under the VICP are:
- Diphtheria,tetanus, , and pertussis (DTP, DTaP, DT, TT, or Td)
- measles, mumps, and rubella (MMR or any components)
- polio (OPV or IPV)
- hepatitis B
- hepatitis A
- Haemophilus inﬂuenzae type b
- varicella (chickenpox)
- human papillomavirus
- trivalent influenza
- meningococcal and pneumococcal conjugate ( whether administered individually or in combination)
TYPES OF VACCINESVaccines Composed of Whole-Killed Organisms Vaccines composed of whole-killed organisms were the ﬁrst laboratory-produced vaccines. They provoke an antibody response that provides temporary immunity. Some vaccines made from whole-killed organisms may cause immune-mediated disorders. Inactivated Polio Vaccine Licensed in 1955, the Salk inactivated polio vaccine (IPV) immediately led to a drop in the cases of paralytic poliomyelitis. The Salk vaccine has been highly effective, with a 70% to 90% protection rate. It was replaced in 1963 by Sabin’s oral poliovirus vaccine (OPV), which by 1979 had eradicated polio (wild type) in the U.S. Because OPV is prepared with a live-attenuated virus, it is associated with a low risk of eliciting polio in healthy individuals and a larger risk among immune-suppressed individuals (see “Vaccines Composed of Live-Attenuated Viruses”). OPV was replaced by an easier to administer, enhanced-potency trivalent polio vaccine (eIPV) in 1997. No cases of vaccine-associated poliomyelitis have been identified in the U.S. since 1999 [Alexander et al., 2004]. Inﬂuenza Virus Vaccine Epidemic human inﬂuenza illness is caused by inﬂuenza A and B. Inﬂuenza A viruses are categorized into subtypes based on two surface antigens:
- hemagglutinin (H)
- neuraminidase (N).
- inactivated ﬂu vaccine
- the nasal-spray ﬂu vaccine (i.e., live-attenuated inﬂuenza vaccine [LAIV])
- the trivalent flu vaccine that contains three inﬂuenza viruses (one A (H3N2) virus, one A (H1N1) virus, and one B virus)
- the new quadrivalent flu vaccine that includes 4 different flu viruses (two influenza A viruses and two influenza B viruses)
- demyelination of brain and spinal cord (encephalomyelitis);
- nerve roots (polyradiculitis);, and
- peripheral nerves (polyneuritis) [Hemachudha et al., 1987].
- sore arm (15 to 25 of 100 recipients);
- headache (5 to 8 of 100 recipients; or
- nausea and vomiting (2 to 5 of 100 recipients)