Chapter 116. Immunization Principles and Vaccine Use (Part 5) For common and highly communicable childhood diseases such as measles, the target population is the universe of susceptible individuals, and the time to immunize is as early in life as is feasible and effective. In the industrialized world, immunization with live-virus vaccine at 12–15 months of age has become the norm because the vaccine protects >95% of children immunized at this age and there is little measles morbidity or mortality among infants <1 year of age. In contrast, under crowded conditions in the developing world, measles remains a significant cause of death among young infants. For optimal benefit in this situation, it is necessary to immunize early enough to narrow the window of vulnerability between the rapid decline of maternal antibody 4–6 months after birth and the development of vaccine-induced active immunity; this choice must be made despite the less efficient immune response in children <1 year old. Invasive infections due to Hib (meningitis, pneumonia, and epiglottitis) occur primarily in young children, with rates rising sharply after the disappearance of maternally derived antibody. First-generation Hib polysaccharide vaccines often failed when administered during infancy because very young children cannot respond to pure polysaccharides. This problem has been overcome by conjugating the capsular polysaccharide with a protein to create a T cell–dependent antigen, to which infants effectively respond. In contrast, rubella is primarily a threat to the fetus rather than to infants and young children. The ideal strategy would be to immunize all women of reproductive age before they became pregnant. Because it is difficult to ensure this type of coverage, rubella is included in a combination vaccine with measles and mumps (MMR) that is administered during infancy and boosted at the age of 4–6 years. It is recommended that pregnant women be screened for rubella antibodies and that seronegative women be given rubella vaccine after delivery. Similar considerations apply to the use of the vaccine against HPV that was recently approved in the United States and is intended primarily to prevent cervical cancer in women. Accordingly, it is recommended that the vaccine be given at the age of 11–12 years (or as early as 9 years), so that all are immunized before becoming sexually active. Some vaccines, such as the influenza and polyvalent pneumococcal polysaccharide products, were originally formulated to prevent pneumonia hospitalizations and deaths among the elderly. These products have been consistently underused, in large part because physicians and otherwise-healthy older individuals ignore the recommendations but also because vaccines continue to be thought of as interventions for infants and children. There is considerable debate about alternative strategies to reduce the burden of these diseases in the elderly by indirectly protecting them through childhood vaccination, which would reduce transmission. The development of new vaccines and the exploitation of new routes of administration may facilitate this approach; examples include the development of pneumococcal conjugate vaccines and the administration of influenza vaccine by the intranasal route, respectively. The pneumococcal conjugate vaccine has made it possible to immunize young infants at risk of pneumococcal pneumonia, meningitis, and otitis media, but whether immunity will persist or will need boosting in adulthood remains to be determined. What is clear is that the number of recommended vaccines and the strategies for their deployment are undergoing constant revision. Adjuvants The immune response to some antigens is enhanced by the addition of adjuvants—nonspecific boosters of immune responses. Adjuvants include aluminum salts or, in the case of polysaccharides such as the polyribose phosphate oligosaccharide of Hib, a carrier protein to which the polysaccharide is conjugated. Adjuvants are essential to the efficacy of a number of inactivated vaccines, including diphtheria and tetanus toxoids, acellular pertussis vaccine, and hepatitis B vaccine; they also appear to be required for enhancement of the response to killed H5N1 avian influenza vaccines. The mechanism by which adjuvants enhance immunogenicity is not well defined but appears to relate to the ability of the adjuvant to activate antigen-presenting cells, frequently through stimulation of Toll-like receptors. Other reported mechanisms for adjuvant effects include rendering of soluble antigens into a particulate form, the mobilization of phagocytes to the site of antigen deposition, and the slowing down of antigen release in order to prolong stimulation of the immune response. Identification of new adjuvants that are safe, more effective, and inexpensive is a high priority for vaccine researchers and manufacturers. Use of Vaccines Recommendations for Use Two or more vaccines should not be mixed in the same syringe in an effort to diminish the number of needle sticks unless such a practice is specifically endorsed by licensure. Disposable needles and syringes must be safely discarded to prevent inadvertent needle stick injury. While the importance of using a new syringe and needle for each vaccine recipient is obvious, reuse of contaminated equipment is a common reality in resource-poor settings. One-time-use, "auto- destruct" needles and syringes have been designed to prevent this practice, but their use adds to the cost of vaccine delivery. Wherever effective primary health care systems ensure access to medical services for the majority and the population is educated about the need for and efficacy of vaccines, coverage rates for basic immunizations are usually high, regardless of the route of vaccine administration or the number of doses necessary. However, without systematic attention to the completion of multiple-dose vaccine schedules, coverage rates for second, third, and booster doses may drop off, and the efficacy of immunization may be significantly diminished. . Chapter 116. Immunization Principles and Vaccine Use (Part 5) For common and highly communicable childhood diseases such as measles,. effective, and inexpensive is a high priority for vaccine researchers and manufacturers. Use of Vaccines Recommendations for Use Two or more vaccines should not be mixed in the same syringe. essential to the efficacy of a number of inactivated vaccines, including diphtheria and tetanus toxoids, acellular pertussis vaccine, and hepatitis B vaccine; they also appear to be required for enhancement