Overview Introduction How Could Vaccines Cause Damage? Early Studies on Vaccine Complications The DPT Vaccine DPT and Brain Damage DPT and Autism DPT and Vaccine-Induced Neuropathies Diagnosis of Post-Vaccinal CNS Pathology Vaccine-Induced Demyelination Auto-Immunity, Vaccines and Autism Database of Vaccine Injury Vaccines and Mercury Origins of the Mercury Controversy Mercury Neurotoxicity Thimerosal and Neurotoxicity Is There a Link betwen Mercury Exposure and Autism? Ethylmercury and the DPT Vaccine Testing for Mercury Toxicity The MMR Vaccine MMR Vaccine and Autism MMR Vaccine and Other Complications Other Vaccination Concerns Concern About Vaccine Adjuvants Immunological Consequence of Vaccines Vaccination During Pregancy and Risks for Autism The Rubeola (Measles) Vaccine The Rubeola Vaccine, Measles and Autism The Risks of Not Vaccinating for Measles Conflict of Interest and Vaccine Development The Hepatitis B Vaccine Hepatitis B Vaccine: The Risks Hepatitis B: The Disease Available Data on the Safety of Hepatitis B Vaccines Information on Other Vaccines Polio Vaccine Pneumococcal Pneumonia Vaccine Hemophilus Meningitis Vaccine Appendix 1: Schedule for Routine Immunizations Appendix 2: Standards for Pediatric Immunization Practices Appendix 3: Decline of Number of Vaccine-Preventable Cases over Time Appendix 4: Childhood Immunizations  ' The Burden of Suffering Description of Preventive Measures Evidence of Effectiveness Public Policy Considerations Recommendations of Other Groups Rationale Statement Recommendations of the American College of Preventive Medicine

Childhood Immunizations
American College of Preventive Medicine
Practice Policy Statement

Rita Patel, MD and Linda Kinsinger, MD, MPH

Vaccine-preventable diseases were a major cause of morbidity and mortality in children prior to the institution of routine immunizations. The annual incidence of measles and pertussis in the United States, for instance, was greater than 800,000 and 70,000, respectively, in the 1940s, with high associated rates of pneumonia, encephalitis, and death.¹

Paralytic poliomyelitis occurred in epidemic waves, crippling thousands of children in its wake while Haemophilus influenzae b affected 1 in 200 U.S. children with severe systemic disease.² Rubella was responsible for causing devastating congenital defects in hundreds of children born to infected mothers.³ Tetanus, mumps, and diphtheria were likewise significant causes of childhood morbidity in prevaccination years.

Hepatitis B, infecting approximately 200,000 individuals annually in the United States, may cause complications such as cirrhosis and hepatocellularcarcinoma.⁴ Finally, the highly prevalent varicella infection is generally mild in healthy children, but results in lost school and work days as well as leading occasionally to serious medical complications.⁵

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Childhood immunizations consist of a series of intramuscular or subcutaneous injections or oral dosing of inactivated bacteria, toxoids, live attenuated viruses, or inactive viral antigens against 10 diseases: diphtheria, tetanus, pertussis, measles, mumps, rubella, polio, Haemophilus influenza b, hepatitis B, and varicella.

Most of the immunizations are given as combined vaccines during routine well-child checks in the first two years of life. A new unified Schedule for Routine Vaccinations recommended by the American Academy of Pediatrics (AAP), the American Academy of Family Practitioners (AAFP), and the Centers for Disease Control and Prevention's (CDC) Advisory Committee on Immunization Practices (ACIP) was released in January 1997, which simplifies the dosing intervals and includes the newly licensed varicella vaccine, as well as new recommendations for polio and pertussis vaccines.

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Clinical studies of vaccines have shown them to be 85%-100% effective after appropriate dosing, with the exception of pertussis, which is only 75%-90% effective.⁶ The clinical effectiveness of immunizations, however, is best substantiated by observing the dramatic decline in incidence of disease since their institution. During the first six years after licensure of an effective vaccine, the incidence of invasive Haemophilus influenzae disease, for example, declined by 95% among children younger than five years old. ⁷

This rapid decline has occurred in spite of a vaccination rate of only 36% in 12-23-month-old children in 1992 (CDC, 1994). Similar dramatic rates of decline of reported cases are seen with many of the other vaccine-preventable diseases.^9,10 Since hepatitis B affects chiefly adolescents and adults, the benefits of the hepatitis B vaccine will likely not be appreciated for another 10-20 years. Similarly, no data are yet available for the effect of the recently licensed varicella vaccine on incidence of disease.

Most of the adverse effects of immunizations such as fever, local tenderness at the site of administration, and irritability are mild and self-limited. Of the more serious side effects, the pertussis vaccine is most likely to cause adverse events with incidence of seizures or hyporesponsive episodes in 1 per 1,750 doses; whether this may result in any long-term sequelae is controversial.⁸

MMR vaccine rarely is associated with encephalopa- thy (one in 1 million doses) and one in 2.4 million doses of oral polio vaccine results in paralytic poliomyelitis.⁸ However, the significant public health benefits of these vaccines far outweigh their minimal harm. Other risks such as transmission of disease with live-virus vaccines to immunocompromised individuals (oral polio vaccine) or the risk of anaphylaxis in egg-allergic individuals (MMR) can be minimized by eliciting a brief history prior to administration.

The full list of adverse effects from immunizations is listed in the AAP's Red Book Report of the Committee on Infectious Diseases and in the Standards for Immunization Practices.^8,11

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The cost-effectiveness of routine childhood immunizations has been well documented, with one estimate suggesting that for each dollar spent now on immunization, $10-$14 will be saved by preventing diseases in the future.¹² However, despite the incontrovertible evidence that vaccines are an efficient and cost effective means of reducing morbidity and mortality, immunization coverage remains suboptimal in preschool children. In 1995, only 72% of 19-35-month-old children were fully immunized.¹³

Part of the problem lies with health care providers who misinterpret contraindications or miss opportunities such as sick visits, emergency room visits, or visits during which a sibling or parent is being seen to administer needed vaccines. During the 1989-1991 measles outbreak, 53% of preschool children in a study in Dallas and New York in whom measles developed had been eligible to receive the vaccine at the time of a health care visit.¹⁴

In addition, parents frequently face many obstacles in seeking immunizations for their children, both logistic and financial. Inconvenient office hours, long waiting times, and the often unnecessary prerequisite for a full well-child check impede the efficient delivery of vaccines.

In order to address these issues, the Ad Hoc Working Group for the Development of Standards for Pediatric Immunization Practices developed 18 standards that constitute essential vaccine policies.¹¹ In addition, compliance, especially for preschool children, can be enhanced by vaccination registries, follow-up and reminder systems, incentives, and performance measures such as HEDIS.^15,16

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Two major groups, the AAP's Committee on Infectious Diseases and the ACIP, have traditionally developed vaccine guidelines since the 1960s. Because of confusion over their differing immunization schedules, however, these two groups recently joined with the American Academy of Family Physicians in producing a unified schedule for childhood immunizations.

These recommendations appear regularly in the CDC's Morbidity and Mortality Weekly Report and the AAP Red Book. The joint group also included representatives from the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) and received input from state immunization programs, the Maternal and Child Health Bureau, and vaccine manufacturers.

The U.S. Preventive Services Task Force recommendations for childhood immunizations in its Guide to Clinical Preventive Services echo those of the joint group. The current schedule is designed to facilitate early administration of vaccines while providing flexibility for individual circumstances.

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All the vaccines licensed for routine use in children and recommended by the joint committee have been efficacious in studies. Most of them, including measles, mumps, rubella, polio, diphtheria, pertussis, tetanus, and Hib, have also been proven effective and safe during their many years of use. It is unclear whether the newer vaccines, hepatitis B and varicella, will result in similar public health benefits although studies do suggest that they are safe and cost-effective.^17,18

There have recently been several controversies in the area of childhood immunizations. One such controversy was the concern that all cases of endemic paralytic poliomyelitis in the United States are now caused by vaccine-strain poliovirus infections. This concern prompted a change in the immunization schedule that now offers the option of replacing oral poliovirus vaccine (OPV) with inactivatedpoliovirus vaccine (IPV).

Also, in response to recent studies showing acellular pertussis vaccine to be equally efficacious to the wholecell vaccine with fewer side effects, it is now offered as an option at 2, 4, and 6 months of age.¹⁹ These changes will likely become more acceptable once combination vaccines including IPV and DTaP are developed, thus obviating the need for separate injections.

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All children without established contraindications should receive DTP, DTaP, MMR, Hib, hepatitis B, varicella, and OPV or IPV vaccinations as outlined in the Unified Schedule of Childhood Immunizations and as detailed in the ACIP's General Recommendations on Immunization.

Children with special risk factors, such as compromised immune systems or residence in high-risk areas, may require additional immunizations.⁸ Furthermore, all health care providers should adopt the 18 standards of immunization practice to work toward the Childhood Immunization Initiative goal of 90% vaccination rate of 2 year olds.

Research priorities include the development of new vaccines for disease as well as improvement of immunogenicity and minimizing of the adverse effects of existing vaccines. Moreover, investigating new combinations of vaccines will help to minimize the emotional and physical trauma and inefficiency of multiple injections in children while promoting compliance.

Research should also be conducted that helps define optimum systems-level interventions for childhood immunizations. Such health services research would include investigation of the role of managed care entities in immunization delivery; the impact of local, state, and national immunization registries; and exploration of other community-wide programs and projects aimed at enhanced immunization (e.g., the role of schools).

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1. Bloch AB, Orenstein WA, Stetler HC, et al. Health impact of measles vaccination in the United States. Pediatrics 1985;76:524-32; Centers for Disease Control and Prevention. Pertussis - United States, January 1992-June 1995. MMWR 1995;44(28):525-9.
   
   
2. American Academy of Pediatrics. 1994 Red Book, Report of the Committee on Infectious Diseases, 23rd ed, 1994; Cochi SL, Broome CV, Hightower AW. Immunization of children with Haemophilus influenzae type b vaccine: a cost-effectiveness model of strategy assessment. JAMA 1985;253:521-9.
   
   
3. American Academy of Pediatrics. 1994 Red Book, Report of the Committee on Infectious Diseases, 23rd ed, 1994.
   
   
4. Margolis HS, Alter MJ, Hadler SC. Hepatitis B: evolving epidemiology and implications for control. Sem Liver Dis 1991;11:84-92.
   
   
5. Preblud SR. Varicella: complications and costs. Pediatrics 1986;78(suppl):728-35.
   
   
6. Black SB, Shinefield HR, Fireman BH, et al. Efficacy in infancy of oligosaccharide conjugate Haemophilus Influenzae type b vaccine in a US population of 61,080 children. Pediatr Infect Dis J 1991;10:97-104; McBean AM, Thoms ML, Albrecht P, et al. Serologic response to oral polio vaccine and enhanced-potency inactivated vaccines. Am J Epidemiol 1988;128:615-28; Onorato IM, Wassilak SG, Meade B. Efficacy of whole-cell pertussis vaccine in preschool children in the United States. JAMA 1992;267:2745-9.
   
   
7. Centers for Disease Control and Prevention. Progress toward elimination of Haemophilus influenzae type b disease among infants and children - United States, 1987-1993. MMWR 1994;43:144-8.
   
   
8. American Academy of Pediatrics. 1994 Red Book, Report of the Committee on Infectious Diseases, 23rd ed, 1994.
   
   
9. Orenstein WA, Brugliera PD. Preface - Immunization in medical education. Am J Prev Med 1994;10(suppl):v-viii.
   
   
10. Templeton DM, Chaitu N. Effects of divalent metals on the isolated rat glomerulus. Toxicology. 61(2):119-33, 1990 Apr 17.
    
    
11. Ad Hoc Working Group for the Development of Standards for Pediatric Immunization Practices. Standards for pediatric immunizations practices. JAMA 1993;269:1817-22.
    
    
12. Centers for Disease Control and Prevention. Monthly immunization table--United States, 1994-1995.
    
    
13. Centers for Disease Control and Prevention. National, state, and urban area vaccination coverage among children aged 19-35 months - United States, April 1994-March 1995. MMWR 1996;45(7):145-50.
    
    
14. Hutchins SS, Escolan J, Markowitz LE, et al. Measles outbreak among unvaccinated preschool-aged children: opportunities missed by health care providers to administer measles vaccine. Pediatrics 1989;83:369-74.
    
    
15. Merkel PA, Caputo GC. Evaluation of a simple office-based strategy for increasing influenza vaccine administration and the effect of differing reimbursement plans on the patient acceptance rate. J Gen Intern Med 1994;9(12):679-83.
    
    
16. Bordley WC, Freed GL, Garrett JM, et al. Factors responsible for immunizations referrals to health departments in North Carolina. Pediatrics 1994;94(3):376-80.
    
    
17. Krahn M, Detsky AS. Should Canada and the United States universally vaccinate infants against hepatitis B? A cost-effectiveness analysis. Med Decis Making 1993;13:4-20.
    
    
18. Lieu TA, Cochi SL, Black SB, et al. Cost-effectiveness of a routine varicella vaccination program for US children. JAMA 1994;271:375-81.
    
    
19. Edwards KM, Meade BD, Decker MD, et al. Comparison of 13 acellular pertussis vaccines: overview and serologic responses. Pediatrics 1995;96:548-57.