General Recommendations on Immunization may interfere with live parenteral vaccines for as long as (v. ory syncyt does not esponse to live virus vaccines. General Rule There is no contraindication to the simultaneous administration of any vaccines. Simultaneous and Nonsimultaneous Administration Simultaneous administration of the most widely used live and inactivated vaccines does not result in decreased antibody responses or increased rates of adverse reactions. Simultan nes for which a child is eligible can be very important in childbood vaccination programs because it increases the probability that a child during a me in the 11 prevented if MMR had been administered at the same visit when another vaccine was given. Administration.Only the sanofi-p asteur Hib/DTaP(TriHIBit) vaccine is licensed for mixing in the same syringe. ministration child is iders)Iive ted)va ine (MMR,varicella,and yellow fever)and live attenuated Combination aroy t ously epara 4 we eks is inten to rec minate All other None two live parenteral vaccines or LAl are not adminisrered eeks or 11
2 human immune globulin product. RSV-IG contains other human antibodies in addition to antibody to RSV, and may interfere with live parenteral vaccines for as long as 9 months. Palivizumab (Synagis) contains only monoclonal antibody to respiratory syncytial virus (RSV). It does not interfere with the response to live virus vaccines. Simultaneous and Nonsimultaneous Administration Simultaneous administration of the most widely used live and inactivated vaccines does not result in decreased antibody responses or increased rates of adverse reactions. Simultaneous administration of all vaccines for which a child is eligible can be very important in childhood vaccination programs because it increases the probability that a child will be fully immunized at the appropriate age. A study during a measles outbreak in the early 1990s showed that about one-third of measles cases in unvaccinated but vaccine-eligible preschool children could have been prevented if MMR had been administered at the same visit when another vaccine was given. Individual vaccines should not be mixed in the same syringe unless they are licensed for mixing by the Food and Drug Administration. Only the sanofi-pasteur Hib/DTaP (TriHIBit) vaccine is licensed for mixing in the same syringe. Nonsimultaneous Administration of Different Vaccines In some situations, vaccines that could be given simultaneously are not (e.g., if the child is receiving vaccines from two different providers). Live parenteral (injected) vaccines (MMR, varicella, and yellow fever) and live attenuated influenza vaccine (LAIV) that are not administered simultaneously should be separated by at least 4 weeks. This precaution is intended to reduce or eliminate interference from the vaccine given first on the vaccine given later. If two live parenteral vaccines or LAIV are not administered simultaneously but are separated by less than 4 weeks, the vaccine given second should be repeated in 4 weeks or confirmed to be effective by serologic testing of the recipient (serologic testing is not recommended for LAIV). An exception to this recommendation is yellow fever vaccine 11 General Recommendations on Immunization There is no contraindication to the simultaneous administration of any vaccines. General Rule
General Recommendations on Immunization Not vo simultancousy administered less than 4 weeks after single-antigen measles vaccine.A 1999 study demonstrated that yellow fever vaccine days earlier. mumps, Live vaccines administered by the oral route (oral polio ]oral typhoid)are not believed to interfere not given simult than 6 of 器2doa2mn地h r available in the United Stares. Par given by the oral roure (OPy oral ryphoid).Live oral vaccines may be given at any time before or after live parenteral vaccines or LAIV. at a or after each other. General Rule Increasing the interval between doses of a multidose vaccine does not diminish the effectiveness of the vaccine. Decreasing the interval between doses of a multidose vaccine may interfere with antibody response and protection nizations are nded for members of the youngest age group at risk for a disease for whom efficacy, immunization e require two or more an minin recommended childhood immunization schedule. 12
2 administered less than 4 weeks after single-antigen measles vaccine. A 1999 study demonstrated that yellow fever vaccine is not affected by measles vaccine given 1–27 days earlier. The effect of nonsimultaneously administered rubella, mumps, varicella, and yellow fever vaccines is not known. Live vaccines administered by the oral route (oral polio vaccine [OPV], oral typhoid) are not believed to interfere with each other if not given simultaneously. These vaccines may be given at any time before or after each other. Oral typhoid is not licensed for children younger than 6 years of age, and OPV is no longer available in the United States, so these vaccines are not likely to be given to the same child. Parenteral live vaccines (MMR, varicella, and yellow fever) and LAIV are not believed to have an effect on live vaccines given by the oral route (OPV, oral typhoid). Live oral vaccines may be given at any time before or after live parenteral vaccines or LAIV. All other combinations of two inactivated vaccines, or live and inactivated vaccines, may be given at any time before or after each other. Interval Between Doses of the Same Vaccine Immunizations are recommended for members of the youngest age group at risk for a disease for whom efficacy, immunogenicity, and safety of a vaccine have been demonstrated. Most vaccines in the childhood immunization schedule require two or more doses for stimulation of an adequate and persisting antibody response. Studies have demonstrated that recommended ages and intervals between doses of the same antigen(s) provide optimal protection or have the best evidence of efficacy. Table 1 of the General Recommendations on Immunization (included in Appendix A) shows the recommended minimal ages and minimal intervals between immunizations for vaccines in the recommended childhood immunization schedule. 12 General Recommendations on Immunization Increasing the interval between doses of a multidose vaccine does not diminish the effectiveness of the vaccine. Decreasing the interval between doses of a multidose vaccine may interfere with antibody response and protection. General Rule
General Recommendations on Immunization Administering doses of a multidose vaccine at shorter than the recommended intervals might be necessary when an infant or child is behin In these te quc or is pen an ac schedules should not be used routinely. red at intervals less than the inter Minimum Intervals and Ages mimal e下ycc the vaccine may be administered at an age younger than als or earlier mum ages repeated at of age or the than substantially negative effect on the immune res to that dbeAlthouehacnatioasshouidnotbeChduid9th mmended minimums,a n b ought to the echeck)In the situations,the clinician can consider administering the own to the anan it is ild 6 r vac appointments),it may be preferable to administer the hamyo than to reschedul later ppointment kept Vaccine doses administered up to4 days before the minimum interval or age can be counted as valid.This 4-dav ACI that va ccine of the unique schedule s ag minimum interval shown in Table 1 of the General Recommendations In c ate th Extended Interval Between Doses 4-day recommendations. of all schedule i心enalemioioecafahitorLeo intervals between doses longer than those routinely recom- 13
2 Administering doses of a multidose vaccine at shorter than the recommended intervals might be necessary when an infant or child is behind schedule and needs to be brought up-to-date quickly or when international travel is pending. In these cases, an accelerated schedule using the minimum age or minimum interval criteria can be used. Accelerated schedules should not be used routinely. Vaccine doses should not be administered at intervals less than the recommended minimal intervals or earlier than the minimal ages. Two exceptions to this may occur. The first is for measles vaccine during a measles outbreak, when the vaccine may be administered at an age younger than 12 months (this dose would not be counted, and would be repeated at 12 months of age or older). The second consideration involves administering a dose a few days earlier than the minimum interval or age, which is unlikely to have a substantially negative effect on the immune response to that dose. Although vaccinations should not be scheduled at an interval or age less than the recommended minimums, a child may have erroneously been brought to the office early, or may have come for an appointment not specifically for vaccination (for example, for an ear recheck). In these situations, the clinician can consider administering the vaccine earlier than the minimum interval or age. If the parent/child is known to the clinician and is reliable, it is preferable to reschedule the child for vaccination closer to the recommended interval. If the parent/child is not known to the clinician or is not reliable (e.g., habitually misses appointments), it may be preferable to administer the vaccine at that visit than to reschedule a later appointment that may not be kept. Vaccine doses administered up to 4 days before the minimum interval or age can be counted as valid. This 4-day recommendation does not apply to rabies vaccine because of the unique schedule for this vaccine. Doses administered 5 days or earlier than the minimum interval or age should not be counted as valid doses and should be repeated as age appropriate. The repeat dose should be spaced after the invalid dose by a time greater than the recommended minimum interval shown in Table 1 of the General Recommendations. In certain situations, local or state requirements might mandate that doses of selected vaccines be administered on or after specific ages, superseding these 4-day recommendations. In some cases, a scheduled dose of vaccine may not be given on time. If this occurs, the dose should be given at the next visit. Not all permutations of all schedules for all vaccines have been studied. However, available data indicate that intervals between doses longer than those routinely recom- 13 General Recommendations on Immunization
General Recommendations on Immunization mended do not affect seroconversion rate or titer when the schedule was completed.C sequently,it is not necessary to restart th rva the case of oral tunboid some exner mmend repeating the series if the four-dose series is extended to more than 3 weeks. General Rule Live attenuated vaccines generally produce ong-lasting immunity with a single dose. Inactivated vaccines require multiple doses and may require periodic boosting to maintain immunity Number of Doses For live injected vaccines,the first dose administered at the recommended age usually provides protection.An additional dose is given to ensure seroconversion.For instance,95% emm e second For inactivated vaccines,the first dose administered at the recommended age usually does not provide protection (hepatitis A vaccine is an exception).A protective immune response may not develop until the second or third dose. For w protective decr ls after a fev Thi p”n ntibody back to protective levels. Not all inactivated vaccines require boosting throughout life. For example,Haemophilus influenzae type b(Hib)vaccine does 10 14
2 mended do not affect seroconversion rate or titer when the schedule was completed. Consequently, it is not necessary to restart the series or add doses of any vaccine because of an extended interval between doses. The only exception to this rule is oral typhoid vaccine in some circumstances. In the case of oral typhoid, some experts recommend repeating the series if the four-dose series is extended to more than 3 weeks. Number of Doses For live injected vaccines, the first dose administered at the recommended age usually provides protection. An additional dose is given to ensure seroconversion. For instance, 95% to 98% of recipients will respond to a single dose of measles vaccine. The second dose is given to ensure that nearly 100% of persons are immune (i.e., the second dose is “insurance”). Immunity following live vaccines is long-lasting, and booster doses are not necessary. For inactivated vaccines, the first dose administered at the recommended age usually does not provide protection (hepatitis A vaccine is an exception). A protective immune response may not develop until the second or third dose. For inactivated vaccines, antibody titers may decrease (“wane”) below protective levels after a few years. This phenomenon is most notable for tetanus and diphtheria. For these vaccines, periodic “boosting” is required. An additional dose is given to raise antibody back to protective levels. Not all inactivated vaccines require boosting throughout life. For example, Haemophilus influenzae type b (Hib) vaccine does not require boosting because Hib disease is very rare in children older than 5 years of age. Hepatitis B vaccine does not require boosting because of immunologic memory to the vaccine and the long incubation period of hepatitis B (which can produce an “autoboost”). 14 General Recommendations on Immunization Live attenuated vaccines generally produce long-lasting immunity with a single dose. Inactivated vaccines require multiple doses and may require periodic boosting to maintain immunity. General Rule
General Recommendations on Immunization Adverse Reactions Following Vaccination Vaccine Adverse Reactions that is to the vaccine's priman Adverse reaction purpose of production of immunity.Adverse reactions are d句 also called ersto ay adverse event that occurs following vaccination. lowing vaccination rse event distinguish between them. The most commo type of Vaccine Adverse Reactions t of .Local vaccine doses.depending on the type of vaccine.Local reactions are most common with inactivated vaccines, at those,suchas DTa with inactivated s gen sually mild and self-limited rare occasions.local reactions may be very exaggerated or 气菱芒 reactions are believed to be due to very high titers of antibody,usually because of too many doses of toxoid. 11 Vaccine Adverse Reactions loss of appetite,and others.These symptoms are common ific;they may occur in a vaccinated persons .headache caconcomtatslnietion may be unrelated to vaccine use,including acellular pertussis vaccine. Live Attenuated Vaccines may occ ti following receipt of Micateto produce ·Symptoms usually mild reactions that follow live attenuated v accines such as fever ced from that replication sease 6
2 Adverse Reactions Following Vaccination Vaccines are intended to produce active immunity to specific antigens. An adverse reaction is an untoward effect caused by a vaccine that is extraneous to the vaccine’s primary purpose of production of immunity. Adverse reactions are also called vaccine “side effect”. A vaccine adverse event refers to any adverse event that occurs following vaccination. An adverse event could be a true vaccine reaction or just a coincidental event, with further research needed to distinguish between them. Vaccine adverse reactions fall into three general categories: local, systemic, and allergic. Local reactions are generally the least severe and most frequent. Allergic reactions are the most severe and least frequent. The most common type of adverse reactions are local reactions, such as pain, swelling, and redness at the site of injection. Local reactions may occur with up to 50% of vaccine doses, depending on the type of vaccine. Local reactions are most common with inactivated vaccines, particularly those, such as DTaP, that contain adjuvants. Local adverse reactions generally occur within a few hours of the injection and are usually mild and self-limited. On rare occasions, local reactions may be very exaggerated or severe. These are often referred to as hypersensitivity reactions, although they are not allergic, as the term implies. These reactions are also known as Arthus reactions, and are most commonly seen with tetanus and diphtheria toxoids. Arthus reactions are believed to be due to very high titers of antibody, usually because of too many doses of toxoid. Systemic adverse reactions are more generalized events and include fever, malaise, myalgias (muscle pain), headache, loss of appetite, and others. These symptoms are common and nonspecific; they may occur in a vaccinated persons because of the vaccine or may be caused by something unrelated to the vaccine, like a concomitant viral infection. Systemic adverse reactions were relatively frequent with DTP vaccine, which contained a whole-cell pertussis component. However, comparison of the frequency of systemic adverse events among vaccine and placebo recipients shows they are not common with inactivated vaccines currently in use, including acellular pertussis vaccine. Systemic adverse reactions may occur following receipt of live attenuated vaccines. Live attenuated vaccines must replicate in order to produce immunity. The adverse reactions that follow live attenuated vaccines, such as fever or rash, represent symptoms produced from that replication and are similar to a mild form of the natural disease. 15 General Recommendations on Immunization