This month's issue of Pediatrie Annaís, with its Guest Editor Samuel L. Katz, MD, Professor and former Chairman of Pediatrics at Duke University School of Medicine, provides an immunization update. It addresses the potential for new vaccines to prevent infections due to Streptococcus pyogenes (group B), respiratory syncytial virus, Salmonella rypHi, Shigella species, Vibrio choleroe, enterotoxigenic Escheric/iia coii, herpes simplex virus, varicella-zoster virus, hepatitis A virus, rotavirus, Streptococcus pneumonias, Neisseria meningitidis, influenza and parainfluenza viruses, Borrelia burgdorferi Lyme disease), Plosmodmm species (malaria), and Mycobocterium tuberculosis.
While not all of these vaccines, when developed, will be appropriate for most infants and children living in the United States and other industrialized countries (eg, Soimoneiia typhi, Vibrio choleras, and Piasmodium species), the rest will, and all will be important in developing countries. One can add to the above list of potential vaccine -preventable diseases those caused by dengue virus, M^coÍOCterium Ieproe, Streptococcus pyogenes (group A), Neisseria gonorrhoeae , cytomegalovirus, and human immunodeficiency virus (HIV).
The Institute of Medicine of the National Academy of Sciences estimates that worldwide millions of lives will be saved annually by these new vaccines, including 2 million from respiratory infections, 2 million from diarrhea, 1 million from malaria, and 1 million from meningitis.1 Add to this the 3.2 million deaths from measles, neonatal tetanus, and pertussis that are prevented each year through vaccination,2 and one can begin to appreciate how important vaccinations are in our world.
But, wait a minute. It's not that simple. We must consider that currently we have great difficulty immunizing children in the United States (no less than in the rest of the world), with well-established vaccines to prevent diphtheria, tetanus, pertussis, poliomyelitis, rubeola, mumps, rubella, and Hemophiiws in/Iuenzae, type b and hepatitis B infections. Although 98% of all American children are fully immunized at age 5 to 6 years (because state laws require it for school entry), only 46.6% of children under 2 years of age, who are at greatest risk from these diseases, were up to date for their DTP, polio, MMRf and HIB immunizations in 1991, according to the latest available figures from the Centers for Disease Control (1991. Unpublished data). Hepatitis B virus was not given routinely to infants in the United States that year. The 1991 up-to-date percentage was a bit higher for white children (49.1%) and quite a bit lower for nonwhite children (34.1%). There are lots of reasons for this poor record - one that likely will not improve to the level of 90% of 2-year-old children being fully immunized by the year 2000, a restated national goal initially set for attainment by 1990.3 The reasons include:
* nonaccessibility to any element of our health-care system by many underprivileged rural and urban families,
* the cost of currently recommended vaccines to the uninsured or underinsured who use private physician care, which, according to current catalog prices, amounts to $250.58 (plus the administration fees physicians charge) for all immunizations needed up to age 2 years,
* belief by parents that their children should not receive vaccines during visits for acute illnesses,4 a belief held by 68.4% of practicing pediatricians, according to a 1992 survey conducted by the American Academy of Pediatrics,5
* parental fear, because of horror stories appearing in the media, that vaccines may cause serious adverse reactions in their children, even if they are healthy,
* parental concern that too many injections are given during one visit (as many as four at age 15 months).4
* parental difficulties in being able to schedule and keep appointments for immunizations because of full-time employment, lack of transportation, or just being "plain too busy," and
* failure of physicians to take advantage of immunizing children who are not "up to date" when they come to the office or emergency room or are hospitalized having illnesses that do not preclude administering those vaccines that are needed.6'7
Portions of President Clinton's Comprehensive Child Immunization Act were passed as part of the Budget Reconciliation Act (Public Law 103-66) in August of this year. These portions address full vaccination for all American children by requiring all health insurers, including Medicaid, that currently cover the costs of immunizations to continue to do so; by providing physicians with free vaccine for their uninsured patients and prohibiting them from charging an administration fee if the family cannot afford it; and by providing totally free vaccines at public health clinics for children whose current health insurance does not cover immunizations. All of this is great because it removes the cost barrier to full immunization and will save $10 to $14 for every dollar invested.8 But it doesn't remove any of the other barriers. Certainly, the Institute of Medicine's recently released report linking all currently used vaccines to severe adverse reactions, even though rarely so, will not help.9 Should those parts of the Comprehensive Child Immunization Act that were excluded from Public Law 103-66 and that now comprise Senate bill 732 (ie, funding of state immunization action plans, implementing a national immunization campaign, and establishing a national immunization registry and surveillance system for all children) become law, we would see marked improvements in the immunization status of all of our children.
The physician's role in ensuring universal immunization is complex and time consuming, and goes well beyond administering vaccines. The Centers for Disease Control and Prevention in collaboration with the National Vaccine Advisory Committee recently developed 18 standards for pediatrie immunization practices10; 14 relate to physicians and other providers of vaccines requiring them to:
1. Use all clinical encounters to screen and, when indicated, immunize children.
2. Educate parents and guardians about immunization in general terms.
3. Question parents or guardians about contraindications and, before immunizing a child, inform them in specific terms about the risks and benefits of the immunizations their child is to receive.
4. Follow only true contraindications.
5. Administer simultaneously all vaccine doses for which a child is eligible at the time of each visit.
6. Use accurate and complete recording procedures.
7. Schedule immunization appointments in conjunction with appointments for other child health services.
8. Report adverse events following immunization promptly, accurately, and completely.
9. Operate a tracking system.
10. Adhere to appropriate procedures for vaccine management, eg, storage, refrigeration, expiration, and administration.
11. Conduct semiannual audits to assess immunization coverage levels and to review immunization records in the patient populations they serve.
12. Maintain at all locations where vaccines are administered up-to-date, easily retrievable medical protocols for management of adverse reactions.
13. Operate with patient-oriented and communitybased approaches.
14. Receive ongoing education and training on current immunization recommendations.
No one would argue with these standards, but they do place a tremendous burden of work on providers. Adding to the list of vaccines available for children will increase that burden and further diminish compliance on the part of parents unless some drastic changes are made. Combining diphtheria/tetanus/ pertussis and H influenzas , type b (Tetramune, LederlePraxis Biologicals, Wayne, New Jersey) is a step in the right direction. Dr Katz anticipates adding inactivated polio vaccine and hepatitis B virus vaccine to that quartet soon, as well as pneumococcal and meningococcal vaccines later on." Eradication of poliomyelitis and measles worldwide, which seems a reasonable expectation, would eliminate those components from a combined "supervaccine."
The Children's Vaccine Initiative (CVI) presented at the 1990 Summit of World Leaders on Children defines a goal of developing a single supervaccine that "could be given once at or near birth, provide immunity for life, require no boosters, permit storage without refrigeration, obviate the use of needles and syringes, and protect against as many as 20 diseases at once."12 The ultimate goal is to develop vaccines that are given orally, rather than by injection. All of this will require enormous investments in research and development (R&.D). Pharmaceutical companies spend a relatively small share (<5%) of their R&D budgets on vaccines because of the high risk for liability, poor profits (relative to other products), the lengthy Food and Drug Administration licensure process, and inadequate patent protection.13 Nevertheless, CVI with backing from UNICEF, the Wotld Health Organization, the United Nations Development Program, the World Bank, and the Rockefeller Foundation plans to effect collaboration in and integration of new vaccine R&D among private vaccine manufacturers and national vaccine institutes in developed countries, using their own scientists and those working in for-profit biotechnology laboratories and nonprofit academic medical centers.12 Funding from governmental sources, such as the National Institutes of Health in the United States, and from private foundations also will be required.
There is much to do in developing new vaccines, and it will take a long time to do it. How long is anyone's guess.
I. Institute of Medicine. New Vaccine Development Establishing Prioria. Vol 2. Washington, DC: National Academy Press; 1986.
2. UNICEF. State of th World's Children 1992. New York, NY: Oxford University Press; 1992.
3. US Public Health Service. Hcahhy People 2000. National Health Promotion and Disease Prevention Objectives. Washington, DC: US Government Printing Office; 1990.
4. Abbotts B, Osborn LM. Immuniation status and reasons for immunization delay among children using public health immunication clinics. Am J Dis Child. 1993;147:945-968.
5. Szilagyi PG, Rodewald LE, Humiston SG, et al. Immunization practices of primary care physicians in the United States. Pediatr Res . 1993;33:122a.
6. Salagyi PG, Rtidevild LE, Humiswn SG, et al. Missed opportunities for primary vaccinations in office practices and the effect on vaccination status. Pediatrics. 1993:91:1-7.
7. Rodewald LE, Szilagyi PG, Humiston SG, et al. U an emergency department visit a marker fur undervacc ination and missed vaccination opportunities arnonp children who have access to primary care? Pediatrics. 1993;91:605-611.
8. Shaiala DE. Giving pediatrie immunizations the priority they deserve. JAMA. 1993;269:1844-1845.
9. Institute of Medicine. Adverse Events Associated With Cnildnood Vaccines: Evidence Bearing on Causality, Washington. DC: National AcaJemy Ptess; 1993.
10. Ad Hoc Working Group for the Development of Standards for Pediatrie Immunalion Practices. Standiirds for pediatrie immunization practices. JAMA. 1993;269:1817-1822.
11. Katz SL. Prospects for childhood immunization in the nexi decade. Pediatr Ann. 1993;22:733-738.
12. Robbins A, Freeman P, Poweil KR. International childhood vaccine initiativePediatr Infect Dis J. 1993:12:523-527.
13. Vanderemiswn W. Availability of quality vaccines, the industria poin of view. Vaccine. 1992; 10:933-937.