Recommended Childhood Immunization Schedule Research Articles

Using Monte Carlo simulation to determine combination vaccine price distributions for childhood diseases.

The Recommended Childhood Immunization Schedule provides guidelines that allow pediatricians to administer childhood vaccines in an efficient and effective manner. Research by vaccine manufacturers has resulted in the development of new vaccines that protect against a growing number of diseases. This has created a dilemma for how to insert such new vaccines into an already crowded immunization schedule, and prompted vaccine manufacturers to develop vaccine products that combine several individual vaccines into a single injection. Such combination vaccines permit new vaccines to be inserted into the immunization schedule without requiring children to be exposed to an unacceptable number of injections during a single clinic visit. Given this advantage, combination vaccines merit an economic premium. The purpose of this paper is to describe how Monte Carlo simulation can be used to assess and quantify this premium by studying four combination vaccines that may become available for distribution within the United States. Each combination vaccine is added to twelve licensed vaccine products for six childhood diseases (diphtheria, tetanus, pertussis, haemophilus influenzae type B, hepatitis B, and polio). Monte Carlo simulation with an integer programming model is used to determine the (maximal) inclusion price distribution of four combination vaccines, by randomizing the cost of an injection. The results of this study suggest that combination vaccines warrant price premiums based on the cost assigned to administering an injection, and that further developments and innovations in this area by vaccine manufacturers may provide significant economic and societal benefits.

Strategies for development of combination vaccines.

The increasing complexity of the recommended childhood immunization schedule has resulted in the need for combination vaccines. Through an extensive review of the current literature, various strategies and issues related to the development of combination vaccines are discussed. Issues that should be considered when combining vaccine components include the current childhood immunization schedule, compatibility of components, availability of antigens for targeted diseases, safety, efficacy, immunogenicity and route of delivery. When choosing an appropriate combination of antigen(s)/serotype(s) for a global or national formulation, careful consideration must be made when selecting serotypes to combine depending on the market or area of use. It is important to know that potential interactions can involve other components of the vaccines, including buffers, adjuvants and preservatives. The Food and Drug Administration requires that the combination not only have immunogenicity comparable with those of the component vaccines, but that its safety profile be comparable with the most reactogenic component. The Food and Drug Administration also recommends that a test of noninferiority be performed, such that the combination performs similarly to the separate components with regard to antibody titers. Combination vaccines are critical to the success of vaccination programs, and each new combination must be carefully studied to ensure comparable safety and immunogenicity of the individual components.

Recommended Childhood Immunization Schedule—United States, 2001

Recommended Childhood Immunization Schedule—United States, 2001

POLIOVIRUS VACCINES: Progress Toward Global Poliomyelitis Eradication and Changing Routine Immunization Recommendations in the United States

Poliomyelitis prevention in the United States has relied virtually exclusively on OPV during the past 30 years. Starting in 1997, a major change in the poliomyelitis vaccination policy occurred, facilitated by substantial progress toward worldwide poliomyelitis eradication. A sequential schedule of IPV followed by OPV became the preferred means to prevent poliomyelitis, although an all-OPV and an all-IPV schedule were considered acceptable alternatives. In 1999, two doses of IPV were recommended to start the primary series, followed by two doses of either poliovirus vaccine. As of January 2000, an all-IPV schedule is currently being implemented in the United States for routine childhood vaccination. Several unusual features are associated with the major public health policy change from an all-OPV to a sequential schedule, including (1) the process of involving a neutral party (i.e., the IOM); (2) the perceived concerns expressed before the change in policy with regard to provider and parent compliance, which could affect the hard-earned gains in raising immunization coverage rates; (3) the ethical issues surrounding the change (e.g., societal versus individual protection) and the influence that a single case of VAPP may have on national policy; (4) the relative lack of importance of cost-effectiveness data; and (5) the weight of progress in the global polio eradication initiative spurring the change in the United States and, increasingly, in other industrialized countries. The IOM assisted in the evaluation of the national poliomyelitis vaccination policy in 1977 and again in 1988. The 1988 review recommended that a sequential IPV-OPV schedule be considered at such time that a combination vaccine becomes available. Also, the IOM raised several important questions. Extensive research to address the questions raised by the IOM had been conducted so that, in 1996, more data were available for the decision-making process. The primary reasons for the change in vaccination policy were (1) the continued occurrence of VAPP in the absence of indigenously acquired wildtype poliovirus-associated paralytic disease, (2) the reduced risk for importation and spread of wild-type poliovirus caused by the progress of the global polio eradication initiative, (3) evidence from vaccine trials that combined IPV-OPV schedules are safe and immunogenic, and (4) maintenance of high levels of population immunity to poliovirus. The global effect of a national change in poliomyelitis vaccination policy was also considered in this policy-making process. Some members of the public health and medical communities raised objections that an increased reliance on IPV in the United States could lead other countries, especially developing countries, to inappropriately abandon OPV and increase reliance on IPV for routine vaccination. Experience from the global smallpox eradication campaign indicated that this scenario was unlikely. The United States ceased vaccinating against smallpox in 1971, 6 years before smallpox was eliminated from the world, without jeopardizing the global smallpox campaign. Subsequently, the effect on the global eradication initiative has been negligible. This article illustrates the potential discrepancy between expressed theoretic concerns about the number of injections and the actual practice once vaccination policy recommendations become the standard of care and that appropriate training and education can overcome these initial concerns. The authors found that compliance with the recommended use of IPV for the first and second doses as part of the sequential schedule was high, independent of socioeconomic status and ethnicity. The need for additional injections did not present a barrier to completion of the recommended childhood immunization schedule. (ABSTRACT TRUNCATED)

Immunization Coverage among Predominantly Hispanic Children, Aged 2–3 years, in Central Los Angeles

PURPOSE: To assess the immunization status of young children in a predominantly Hispanic region in and around downtown Los Angeles, and factors associated with complete immunization by age 24 months. METHODS: The information was gathered in a two-stage cluster survey with probability proportionate to estimated size (PPS) sampling of 30 clusters at the first stage, and simple random sampling of a constant number of children at the second stage. Vaccination coverage was determined by a review of the home immunization (HI) card, or of clinic records. RESULTS: Of the 270 sampled children, 91.5% were Hispanic and 6.7% were Black. Home telephone numbers were not available in 24.8% of the homes, and 34.1% reported having no health insurance. Vaccination coverage was over 90% for the first three doses of Diphtheria, tetanus toxoids and pertussis/diphtheria, tetanus toxoids and acellular pertussis vaccine (DTP/DTaP)/Diphtheria and tetanus toxoids vaccine (DT), first two doses of poliovirus (Polio) vaccine, first dose of measles, mumps and rubella (MMR) vaccine, and first two doses of hepatitis B (Hep B) vaccine. Yet, by age 24 months, only 72.2% of the children had received the combined series of 4:3:1 (i.e., four DTP/DTaP/DT, three Polio, one MMR). This was further reduced to 64.4% for the combined series of 4:3:1:3:3 (i.e., four DTP/DTaP/DT, three Polio, one MMR, three Haemophilus influenzae type b (Hib), three Hep B). Factors associated with completed on-time vaccination were having an HI card available during the interview and being enrolled in Supplemental Nutrition Program for Women, Infants and Children (WIC). CONCLUSIONS: While vaccination levels for individual antigens were found to be high, more emphasis needs to be placed on getting preschool children vaccinated on-time according to the Recommended Childhood Immunization Schedule.

Correction: Recommended Childhood Immunization Schedule—United States, 2000

Correction: Recommended Childhood Immunization Schedule—United States, 2000

Recommended Childhood Immunization Schedule—United States, 2000

Recommended Childhood Immunization Schedule—United States, 2000

Transgenic plants as edible vaccines.

Vaccinations are among the more cost-effective health care procedures (Hausdorff 1996). In the United States and Europe, a majority of newborn children are vaccinated against ten diseases (Recommended childhood immunization schedule from Center for Disease Control, USA). Recently in the United States hepatitis B was added to the recommended vaccinations for infants. Of these different immunizations, only one is an oral vaccine with the others requiring injections. In addition, approximately thirty new vaccines are currently under development in the United States (Division of Microbiology and Infections Diseases 1995; 1996).

Recommended Childhood Immunization Schedule—United States, January–December 2000

Recommended Childhood Immunization Schedule—United States, January–December 2000

Tetanus and diphtheria immunization

Tetanus and diphtheria are easily preventable diseases that cause significant morbidity and mortality in unvaccinated or inadequately immunized persons. Tetanus is caused by a sporulating bacillus, found in soil and human and animal feces, that may contaminate acute or chronic wounds and release an exotoxin that causes muscle spasms and interferes with release of transmitters in autonomic nerves. Diphtheria is caused by a nonsporulating bacillus, found only in humans, that ordinarily resides in the superficial layers of the respiratory mucosa and in skin lesions and is spread by direct contact with these areas. Active immunization with diphtheria and tetanus toxoids and pertussis vaccine (DTP, whole cell or acellular) is part of the current recommended childhood immunization schedule. Booster doses of tetanus and reduced-dose diphtheria toxoids (Td) are recommended every 10 years following completion of a childhood primary series. For persons beginning a primary series at 7 years of age or older, including adults with uncertain vaccination histories, an initial dose of Td should be followed 4–8 weeks later by a second dose of Td. The second dose should be followed 6–12 months later by a third dose of Td, with booster doses every 10 years thereafter. Vaccine also is indicated for patients recovering from clinical tetanus or diphtheria and for postexposure prevention of tetanus under certain circumstances. The major contraindication to vaccine use is a history of a neurologic or severe hypersensitivity reaction following a prior dose of tetanus and diphtheria toxoids. Among the adverse effects associated with administration of tetanus and diphtheria toxoids are local reactions; mild systemic reactions such as fever, headache, and malaise; and, rarely, more severe systemic reactions, including generalized urticaria, anaphylaxis, and neurologic complications such as Guillain-Barré syndrome (GBS) and brachial neuritis.

Recommended Childhood Immunization Schedule—United States, 1999Outbreak of Infection Associated With Eating Raw Oysters and Clams Harvested From Long Island Sound—Connecticut, New Jersey, and New York, 1998Conference on Vaccine ResearchRecommended Childhood Immunization Schedule—United States, 1999Outbreak of Conference on Vaccine Research

Recommended Childhood Immunization Schedule—United States, 1999Outbreak of Infection Associated With Eating Raw Oysters and Clams Harvested From Long Island Sound—Connecticut, New Jersey, and New York, 1998Conference on Vaccine ResearchRecommended Childhood Immunization Schedule—United States, 1999Outbreak of Conference on Vaccine Research

Recommended Childhood Immunization Schedule—United States, January–December 1999

The annual Recommended Childhood Immunization Schedule of the American Academy of Pediatrics (AAP), the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC), and the American Academy of Family Physicians (AAFP) is issued in January of each year. Several significant changes for the 1999 Schedule have been made since publication of the 1998 Schedule.1This report provides the 1999 Schedule and delineates the changes, including those in the footnotes, as follows:1. Rotavirus vaccine (Rv) at 2, 4, and 6 months of age is recommended. Details of the AAP recommendations for rotavirus vaccination were published in the December 1998 issue ofPediatrics.2 Rv is shaded in theSchedule to indicate that implementation of the recommendation for routine use will require reconciliation of related economic issues, as noted in the AAP statement.2. Inactivated poliovirus vaccine (IPV) is recommended at 2 and 4 months of age. For the third and fourth doses of poliovirus vaccine, either IPV or oral poliovirus vaccine (OPV) can be administered. Details of the AAP recommendations regarding this change are given in the statement in this issue of Pediatrics.33. The manufacturer of Recombivax HB (Merck and Co, Inc, West Point, PA) has standardized the dose of this hepatitis vaccine to 5 μg for children from birth through 19 years of age regardless of maternal hepatitis B surface antigen carrier status. The change was made to avoid the confusion that occasionally occurred due to the availability of multiple dose formulations of this vaccine product. Children who have received a 2.5-μg dose of Recombivax for any or all the recommended doses are considered adequately immunized and no additional doses need to be administered. The other available hepatitis B vaccine, Engerix B (SmithKline Beecham, Pittsburgh, PA), also has a standard dose (10 μg) for all children from birth through 19 years of age. The vaccines are interchangeable when given in the doses recommended by the manufacturers.4. Acellular pertussis vaccines combined with diphtheria and tetanus toxoids (DTaP) are listed on the Schedule as the recommended product for pertussis vaccination. Whole-cell pertussis-containing vaccines (DTP) remain acceptable, as noted in the footnote.A fourth acellular pertussis-containing vaccine (Certiva [North American Vaccines, Beltsville, MD]) has been approved by the Food and Drug Administration (FDA) for immunization of infants and children. Clinical data to support the superiority of one DTaP product in comparison to the others are not available, and therefore the four approved DTaP products are considered equally acceptable. Additional questions regarding acellular pertussis vaccines have been addressed in a recent article in AAP News.45. The footnote in the Schedule pertaining toHaemophilus influenzae type b (Hib) vaccine has been modified to indicate that currently available DTaP/Hib combination products should not be used for the primary immunization series of infants unless approved by the FDA for the specific ages. The use of one such product in infants has resulted in suboptimal antibody responses.56. Minor changes to clarify recommendations have been made in the measles–mumps–rubella vaccine (MMR) and varicella footnotes, and the numbers (1, 2, and 3) for the respective doses of hepatitis B vaccine in the Schedule have been omitted to make the information consistent with that for other vaccines.Detailed recommendations for the use of the vaccines routinely indicated during infancy, childhood, and adolescence are given in the1997 Red Book,6 AAP statements (www.aap.org), and ACIP statements (www.cdc.gov/nip) on specific vaccines, and the respective manufacturers' package inserts.

Recommended Childhood Immunization Schedule—United States, 1998

Recommended Childhood Immunization Schedule—United States, 1998

Recommended Childhood Immunization Schedule—United States, January–December 1998

Recommended Childhood Immunization Schedule—United States, January–December 1998

From the Centers for Disease Control and Prevention. Recommended childhood immunization schedule--United States, 1997

From the Centers for Disease Control and Prevention. Recommended childhood immunization schedule--United States, 1997

Recommended Childhood Immunization Schedule—United States, 1997

Recommended Childhood Immunization Schedule—United States, 1997

Recommended Childhood Immunization Schedule—United States, July-December 1996

Recommended Childhood Immunization Schedule—United States, July-December 1996

Recommended Childhood Immunization Schedule

The Recommended Childhood Immunization Schedule United States, July—December 1996 was developed by the Committee on Infectious Diseases of the American Academy of Pediatrics in collaboration with the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention, and the American Academy of Family Physicians. Since the Schedule was last published in January 1996, no new vaccines have been approved by the Food and Drug Administration and as of May 15, 1996, no changes had been made in Academy recommendations.1 If additional changes are made before the next publication in the January 1997 issue of Pediatrics, the membership will be informed through other channels. For detailed information on the use of vaccines, providers should refer to the l994 Red Book: Report of the Committee on Infectious Diseases,2 the ACIP General Recommendations on Immunization3 and the vaccine package inserts.

Clinical Notes

In January 1995, the Recommended Childhood Immunization Schedule, developed by the Advisory Committee on Immunization Practices (ACIP) the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP), was published. This unified schedule represented the first such schedule developed through a collaborative process among the recommending groups, the pharmaceutical manufacturing industry, and the Food and Drug Administration. This process is intended to maintain a common childhood immunization schedule and to work toward further simplification of the schedule. The Recommended Childhood Immunization Schedule--United States, January-June 1996 (Figure 1) has been updated by these groups to incorporate newly licensed and/or recommended vaccines and to clarify specific issues. Since publication of the schedule in 1995, Varicella Zoster Virus Vaccine (Var) has been licensed, and recommendations for adolescent hepatitis B vaccination have been developed. The following changes are incorporated into the Recommended Childhood Immunization Schedule.

From the Centers for Disease Control and Prevention. Recommended childhood immunization schedule--United States, January-June 1996

From the Centers for Disease Control and Prevention. Recommended childhood immunization schedule--United States, January-June 1996