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Combination Vaccines for Childhood Immunization

Recommendations of the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP)

Advisory Committee on Immunization Practices

Membership List, June 1998

CHAIRMAN

John F. Modlin, M.D.
Professor of Medicine and Maternal and Child Health
Dartmouth Medical School
Lebanon, New Hampshire

EXECUTIVE SECRETARY

Dixie E. Snider, M.D., M.P.H.
Associate Director for Science
Centers for Disease Control and Prevention
Atlanta, Georgia

MEMBERS

Richard D. Clover, M.D.
University of Louisville School of Medicine
Louisville, Kentucky

Barbara Ann DeBuono, M.D.
New York State Department of Health
Albany, New York

David W. Fleming, M.D.
Oregon Health Division
Portland, Oregon

Mary P. Glode, M.D.
The Children's Hospital
Denver, Colorado

Marie R. Griffin, M.D.
Vanderbilt University Medical Center
Nashville, Tennessee

Fernando A. Guerra, M.D.
San Antonio Metro Health District
San Antonio, Texas

Charles M. Helms, M.D., Ph.D.
University of Iowa
Iowa City, Iowa

Chinh T. Le, M.D.
Kaiser Permanente Medical Center
Santa Rosa, California

Jessie L. Sherrod, M.D.
Charles R. Drew University School of Medicine and Science
Los Angeles, California

EX OFFICIO MEMBERS

Robert F. Breiman, M.D.
Director, National Vaccine Program Office
Centers for Disease Control and Prevention
Atlanta, Georgia

Geoffrey S. Evans, M.D.
Health Resources and Services Administration
Rockville, Maryland

Randolph T. Graydon
Health Care Financing Administration
Baltimore, Maryland

M. Carolyn Hardegree, M.D.
Food and Drug Administration
Rockville, Maryland

John La Montagne, Ph.D.
National Institutes of Health
Bethesda, Maryland

Kristin Lee Nichol, M.D., M.P.H.
Veterans Administration Medical Center
Minneapolis, Minnesota

David H. Trump, M.D., M.P.H.
Department of Defense
Washington, DC

LIAISON REPRESENTATIVES

American Academy of Family Physicians

Richard K. Zimmerman, M.D.
Pittsburgh, Pennsylvania

American Academy of Pediatrics

Georges Peter, M.D.
Providence, Rhode Island

Larry K. Pickering, M.D.
Norfolk, Virginia

Neal A. Halsey, M.D.
Baltimore, Maryland

American Association of Health Plans

Gregory P. Gilmet, M.D.
Southfield, Michigan

American College of Obstetricians and Gynecologists

Stanley A. Gall, M.D.
Louisville, Kentucky

American College of Physicians

Pierce Gardner, M.D.
Stony Brook, New York

American Hospital Association

William Schaffner, M.D.
Nashville, Tennessee

American Medical Association

VACANT

Association of Teachers of Preventive Medicine

VACANT

Canadian National Advisory Committee on Immunization

Victor Marchessault, M.D.
Cumberland, Ontario, Canada

Hospital Infection Control Practices Advisory Committee

Jane D. Siegel, M.D.
Dallas, Texas

Infectious Diseases Society of America

William P. Glezen, M.D.
Houston, Texas

National Medical Association

Walter Faggett, M.D.
Atlanta, Georgia

Pharmaceutical Research and Manufacturers of America

Gordon R. Douglas, Jr., M.D.
Whitehouse Station, New Jersey

Subsecretaría de Prevención y Control de Enfermedades, República de México

José Ignacio Santos
Mexico City, DF, Mexico

 

Abbreviations Used in This Report*

DT Diphtheria and tetanus toxoids vaccine (for children)
DTaP Diphtheria and tetanus toxoids and acellular pertussis vaccine
DTaP-Hib Diphtheria and tetanus toxoids and acellular pertussis and Haemophilus influenzae type b vaccine
DTP Diphtheria and tetanus toxoids and pertussis vaccine (unspecified pertussis antigens)
DTP-Hib Diphtheria and tetanus toxoids and pertussis and Haemophilus influenzae type b vaccine (unspecified pertussis antigens)
DTwP Diphtheria and tetanus toxoids and whole-cell pertussis vaccine
DTwP-Hib Diphtheria and tetanus toxoids and whole-cell pertussis and Haemophilus influenzae type b vaccine
HepA Hepatitis A vaccine
HepB Hepatitis B vaccine
Hib Haemophilus influenzae type b conjugate vaccine
  PRP-OMP Hib polyribosylribitol phosphate polysaccharide conjugated to a meningococcal outer membrane protein
  PRP-T Hib polyribosylribitol phosphate polysaccharide conjugated to tetanus toxoid
  HbOC Hib oligosaccharides conjugated to diphtheria CRM197 toxin protein
  PRP-D Hib polyribosylribitol phosphate polysaccharide conjugated to diphtheria toxoid
Hib-HepB Haemophilus influenzae type b and hepatitis B vaccine
Hib-HepB-IPV Haemophilus influenzae type b, hepatitis B, and trivalent inactivated polio vaccine
INF Influenza vaccine
IPV Trivalent inactivated polio vaccine (killed Salk type)
Me Measles vaccine
Me-Rub Measles and rubella vaccine
MenCon Meningococcal (Neisseria meningitidis) conjugate vaccine
MenPS Meningococcal (Neisseria meningitidis) polysaccharride vaccine
MMR Measles-mumps-rubella vaccine
MMR-Var Measles-mumps-rubella and varicella vaccine
Mu Mumps vaccine
Mu-Rub Mumps and rubella vaccine
OPV Trivalent oral polio vaccine (live Sabin type)
PnuCon Pneumococcal (Streptococcus pneumoniae) conjugate vaccine
PnuPS Pneumococcal (Streptococcus pneumoniae) polysaccharide vaccine
Rub Rubella vaccine
Rv Rotavirus vaccine
Td Tetanus and diphtheria toxoids vaccine (for adolescents and adults)
TT Tetanus toxoid vaccine
Var Varicella (chickenpox) vaccine

* Excludes some pentavalent and larger combinations listed in Appendix A. As of publication date, some vaccine combinations listed are not licensed or approved for persons of all ages in the United States.

Product Brand Names and Manufacturers/Distributors
for Principal Childhood Vaccine Types


DTaP
diphtheria and tetanus toxoids and
acellular pertussis vaccine

ACEL-IMUNE® (WLV)
Certiva(TM) (NAV, distributed by ALI)
Infanrix® (SBB, distributed by SB)
Tripedia® (CON, distributed by PMC)

DTaP-Hib
diphtheria and tetanus toxoids and
acellular pertussis and Haemophilus
influenzae
type b vaccine

TriHIBit®* (ActHIB® Hib reconstituted with
  Tripedia® DTaP; distributed by PMC)

DTwP
diphtheria and tetanus toxoids and
whole-cell pertussis vaccine

Tri-Immunol® (WLV)
(Generic products from other
manufacturers)

DTwP-Hib
diphtheria and tetanus toxoids and whole-
cell pertussis and Haemophilus influenzae
type b vaccine

ActHIB® Hib reconstituted with DTwP
  (CON; distributed by PMC)
TETRAMUNE® (WLV)

HepA
hepatitis A vaccine

HAVRIX® (SBB, distributed by SB)
VAQTA® (MRK)

HepB
hepatitis B vaccine

ENGERIX-B® (SBB, distributed by SB)
RECOMBIVAX HB® (MRK)

Hib
Haemophilus influenzae
type b conjugate
vaccine
 

  HbOC -- oligosaccharides conjugated to
    diphtheria CRM197 toxin protein

HibTITER® (WLV)

  PRP-OMP -- polyribosylribitol phosphate
    polysaccharide conjugated to a
    meningococcal outer membrane protein

PedvaxHIB® (MRK)

  PRP-T -- polyribosylribitol phosphate poly-
    saccharide conjugated to tetanus toxoid

ActHIB® (PMSV, distributed by CON, PMC)
OmniHIB(TM) (PMSV, distributed by SB)

  PRP-D -- polyribosylribitol phosphate poly-
    saccharide conjugated to diphtheria toxoid

ProHIBiT® (CON, distributed by PMC)

Hib-HepB
Haemophilus influenzae
type b and hepatitis
B vaccine

COMVAX® (Hib component = PRP-OMP)
  (MRK)

IPV
trivalent inactivated polio vaccine
(killed Salk type)

IPOL® (PMSV, distributed by CON, PMC)

MMR
measles-mumps-rubella vaccine

M-M-R® II (MRK)

OPV
trivalent oral polio vaccine (live Sabin type)

Orimune® (WLV)

Rv
rotavirus vaccine (live, oral, tetravalent)

RotaShield® (WLV)

Var
Varicella (chickenpox) vaccine

VARIVAX® (MRK)

* As of April 10, 1999, TriHIBit® was licensed only for the fourth dose recommended at age 15-18 months in the vaccination series.

† Manufacture discontinued.

Abbreviations: ALI=Ross Products Division, Abbott Laboratories Inc.; CON=Connaught Laboratories, Inc.; MRK=Merck & Co., Inc.; NAV=North American Vaccine, Inc.; PMC=Pasteur Mérieux Connaught; PMSV=Pasteur Mérieux Sérums & Vaccins, S.A.; SBB=SmithKline Beecham Biologicals; SB=SmithKline Beecham Pharmaceuticals; WLV=Lederle Laboratories Division of American Cyanamid Company (marketed by Wyeth-Lederle Vaccines, Wyeth-Ayerst Laboratories).

Summary

An increasing number of new and improved vaccines to prevent childhood diseases are being introduced. Combination vaccines represent one solution to the problem of increased numbers of injections during single clinic visits. This statement provides general guidance on the use of combination vaccines and related issues and questions.

To minimize the number of injections children receive, parenteral combination vaccines should be used, if licensed and indicated for the patient's age, instead of their equivalent component vaccines. Hepatitis A, hepatitis B, and Haemophilus influenzae type b vaccines, in either monovalent or combination formulations from the same or different manufacturers, are interchangeable for sequential doses in the vaccination series. However, using acellular pertussis vaccine product(s) from the same manufacturer is preferable for at least the first three doses, until studies demonstrate the interchangeability of these vaccines. Immunization providers should stock sufficient types of combination and monovalent vaccines needed to vaccinate children against all diseases for which vaccines are recommended, but they need not stock all available types or brand-name products. When patients have already received the recommended vaccinations for some of the components in a combination vaccine, administering the extra antigen(s) in the combination is often permissible if doing so will reduce the number of injections required.

To overcome recording errors and ambiguities in the names of vaccine combinations, improved systems are needed to enhance the convenience and accuracy of transferring vaccine-identifying information into medical records and immunization registries. Further scientific and programmatic research is needed on specific questions related to the use of combination vaccines.

INTRODUCTION

The introduction of vaccines for newly preventable diseases poses a challenge for their incorporation into an already complex immunization schedule. To complete the 1999 Recommended Childhood Immunization Schedule in the United States (1,2), a minimum of 13 separate injections are needed to immunize a child from birth to age 6 years, using vaccines licensed in the United States as of April 10, 1999. During some office or clinic visits, the administration of three or four separate injections can be indicated.

Combination vaccines merge into a single product antigens that prevent different diseases or that protect against multiple strains of infectious agents causing the same disease. Thus, they reduce the number of injections required to prevent some diseases. Combination vaccines available for many years include diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTwP); measles-mumps-rubella vaccine (MMR); and trivalent inactivated polio vaccine (IPV). Combinations licensed in recent years in the United States include diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) (3-6), DTwP-Haemophilus influenzae type b (Hib) vaccine (DTwP-Hib) (7,8), DTaP-Hib* (9), and Hib-hepatitis B (HepB) vaccine (Hib-HepB) (10). In the future, combination vaccines might include increasing numbers of components in different arrays to protect against these and other diseases, including hepatitis A, Neisseria meningitidis, Streptococcus pneumoniae, and varicella (Appendix A) (11).

Combination vaccines have some drawbacks. Chemical incompatibility or immunologic interference when different antigens are combined into one vaccine could be difficult to overcome (12-16). Vaccine combinations that require different schedules might cause confusion and uncertainty when children are treated by multiple vaccine providers who use different products. The trend to develop combination products could encourage vaccine companies to merge to acquire the needed intellectual property (17). Competition and innovation might be reduced if companies with only a few vaccine antigens are discouraged from developing new products.

This report, published simultaneously by the Advisory Committee on Immunization Practices (ACIP) (18), the American Academy of Pediatrics (AAP) (19) and the American Academy of Family Physicians (AAFP) (20), provides general recommendations for the optimal use of existing and anticipated parenteral combination vaccines, along with relevant background, rationale, and discussion of questions raised by the use of these products. Principal recommendations are classified by the strength and quality of evidence supporting them (Appendix B) (21-24).

PREFERENCE FOR COMBINATION VACCINES

The use of licensed combination vaccines is preferred over separate injection of their equivalent component vaccines. Only combinations approved by the U.S. Food and Drug Administration (FDA) should be used.

Rationale

The use of combination vaccines is a practical way to overcome the constraints of multiple injections, especially for starting the immunization series for children behind schedule. The use of combination vaccines might improve timely vaccination coverage. Some immunization providers and parents object to administering more than two or three injectable vaccines during a single visit because of a child's fear of needles and pain (25-30) and because of unsubstantiated concerns regarding safety (31,32).

Other potential advantages of combination vaccines include a) reducing the cost of stocking and administering separate vaccines, b) reducing the cost for extra health-care visits, and c) facilitating the addition of new vaccines into immunization programs. The price of a new combination vaccine can sometimes exceed the total price of separate vaccines for the same diseases. However, the combination vaccine might represent a better economic value if one considers the direct and indirect costs of extra injections, delayed or missed vaccinations, and additional handling and storage (11).

Combining Separate Vaccines Without FDA Approval

Immunization providers should not combine separate vaccines into the same syringe to administer together unless such mixing is indicated for the patient's age on the respective product label inserts approved by the FDA. The safety, immunogenicity, and efficacy of such unlicensed combinations are unknown (33).

INTERCHANGEABILITY OF VACCINE PRODUCTS

In general, vaccines from different manufacturers that protect against the same disease may be administered interchangeably in sequential doses in the immunization series for an individual patient (e.g., hepatitis A [HepA], HepB, and Hib). However, until data supporting interchangeability of acellular pertussis vaccines (e.g., DTaP) are available, vaccines from the same manufacturer should be used, whenever feasible, for at least the first three doses in the pertussis series. Immunization providers who cannot determine which DTaP vaccine was previously administered, or who do not have the same vaccine, should use any of the licensed acellular pertussis products to continue the immunization series.

Interchangeability of Formulations

The FDA generally licenses a combination vaccine based on studies indicating that the product's immunogenicity (or efficacy) and safety are comparable with or equivalent to monovalent or combination products licensed previously (16,34). FDA approval also generally indicates that a combination vaccine may be used interchangeably with monovalent formulations and other combination products with similar component antigens produced by the same manufacturer to continue the vaccination series. For example, DTaP, DTaP-Hib, and future DTaP-combination vaccines (Appendix A) that contain similar acellular pertussis antigens from the same manufacturer may be used interchangeably, if approved for the patient's age.

Interchangeability of Vaccines From Different Manufacturers

The licensure of a vaccine does not necessarily indicate that interchangeability with products of other manufacturers has been demonstrated. Such data are ascertained and interpreted more easily for diseases with known correlates of protective immunity (e.g., specific antibodies). For diseases without such surrogate laboratory markers, field efficacy (phase III) trials or postlicensure surveillance generally are required to determine protection (35,36).

Diseases With Serologic Correlates of Immunity

Studies of serologic responses that have been correlated with protection against specific diseases support the interchangeability of vaccines from different manufacturers for HepA, HepB, and Hib.

Preliminary data indicate that the two hepatitis A vaccine products currently licensed in the United States (37) may be used interchangeably (38) (Merck & Co., Inc., unpublished data, 1998). Hepatitis B vaccine products (i.e., HepB and Hib-HepB if age-appropriate) also may be interchanged for any doses in the hepatitis B series (39).

Based on subsequent data (40-42), the guidelines for Haemophilus influenzae type b disease (7,43) were updated in the 1998 Recommended Childhood Immunization Schedule (44-47) to indicate that different Hib vaccine products from several manufacturers may be used interchangeably for sequential doses of the vaccination series. A PRP-OMP Hib (Hib vaccine with a polyribosylribitol phosphate polysaccharide conjugated to a meningococcal outer membrane protein) or a PRP-OMP Hib-HepB vaccine might be administered in a series with HbOC Hib (Hib vaccine with oligosaccharides conjugated to diphtheria CRM197 toxin protein) or with PRP-T Hib (polyribosylribitol phosphate polysaccharide conjugated to tetanus toxoid). In such cases, the recommended number of doses to complete the series is determined by the HbOC or PRP-T product, not by the PRP-OMP vaccine (1,2). For example, if PRP-OMP Hib is administered for the first dose at age 2 months and another product is administered at age 4 months, a third dose of any of the licensed Hib vaccines is recommended at age 6 months to complete the primary series.

Diseases Without Serologic Correlates of Immunity

Despite extensive research, no serologic correlates of immunity have been identified for pertussis. Limited data exist concerning the safety, immunogenicity, or efficacy of administering acellular pertussis vaccines (e.g., DTaP or DTaP-Hib) from different manufacturers between the fourth (at age 15-18 months) and fifth (at age 4-6 years) doses in the vaccination series (48). No data are available regarding the interchangeability of acellular pertussis products from different manufacturers for the first three pertussis doses scheduled at ages 2, 4, and 6 months. Thus, use of the same manufacturer's acellular pertussis vaccine product(s) is preferred for at least the first three doses in the series (5,49).

VACCINE SUPPLY

Immunization clinics and providers should maintain a supply of vaccines that will protect children from all diseases specified in the current Recommended Childhood Immunization Schedule (1,2). This responsibility can be fulfilled by stocking several combination and monovalent vaccine products. However, not stocking all available combination and monovalent vaccines or multiple products of each is acceptable.

New and potential combination vaccines can contain different but overlapping groups of antigens (Appendix A). Thus, not all such vaccines would need to be available for the age-appropriate vaccination of children. Those responsible for childhood vaccination can stock several vaccine types and products, or they may continue to stock a limited number, as long as they prevent all diseases recommended in the immunization schedule (1,2). Potential advantages of stocking a limited number of vaccines include reducing a) confusion and potential errors when staff must handle redundant products and formulations, b) wastage when less commonly used products expire, c) cold storage capacity requirements, and d) administrative overhead in accounting, purchasing, and handling.

EXTRA DOSES OF VACCINE ANTIGENS

Using combination vaccines containing some antigens not indicated at the time of administration to a patient might be justified when a) products that contain only the needed antigens are not readily available or would result in extra injections and b) potential benefits to the child outweigh the risk of adverse events associated with the extra antigen(s). An extra dose of many live-virus vaccines and Hib or HepB vaccines has not been found to be harmful. However, the risk of adverse reactions might increase when extra doses are administered earlier than the recommended interval for certain vaccines (e.g., tetanus toxoid vaccines and pneumococcal polysaccharide vaccine) (23,50).

General Immunization Practice

Patients commonly receive extra doses of vaccines or vaccine antigens for diseases to which they are immune. For example, some children receiving recommended second or third doses of many vaccines in the routine immunization series will already have immunologic protection from previous dose(s). Because serologic testing for markers of immunity is usually impractical and costly, multiple doses for all children are justified for both clinical and public health reasons to decrease the number of susceptible persons, which ensures high overall rates of protection in the population.

Extra vaccine doses also are sometimes administered when an immunization provider is unaware that the child is already up-to-date for some or all of the antigens in a vaccine (see Improving Immunization Records). During National Immunization Days and similar mass campaigns, millions of children in countries around the world are administered polio vaccine (51,52) and/or measles vaccine (53,54), regardless of prior vaccination status.

Extra Doses of Combination Vaccine Antigens

ACIP, AAP, and AAFP recommend that combination vaccines may be used whenever any components of the combination are indicated and its other components are not contraindicated (1,2). An immunization provider might not have vaccines available that contain only those antigens indicated by a child's immunization history. Alternatively, the indicated vaccines might be available, but the provider nevertheless might prefer to use a combination vaccine to reduce the required number of injections. In such cases, the benefits and risks of administering the combination vaccine with an unneeded antigen should be compared.

Live-Virus Vaccines

Administering an extra dose of live, attenuated virus vaccines to immunocompetent persons who already have vaccine-induced or natural immunity has not been demonstrated to increase the risk of adverse events. Examples of these include MMR, varicella, rotavirus, and oral polio vaccines.

Inactivated Vaccines

When inactivated (killed) or subunit vaccines (which are often adsorbed to aluminum-salt adjuvants) are administered, the reactogenicity of the vaccine must be considered in balancing the benefits and risks of extra doses. Because clinical experience suggests low reactogenicity, an extra dose of Hib or HepB vaccine may be administered as part of a combination vaccine to complete a vaccination series for another component of the combination. Administration of extra doses of tetanus toxoid-containing vaccines earlier than the recommended intervals can increase the risk of hypersensitivity reactions (55-61). Examples of such vaccines include DTaP, DTaP-Hib, diphtheria and tetanus toxoids for children (DT), tetanus and diphtheria toxoids for adolescents and adults (Td), and tetanus toxoid (TT). Extra doses of tetanus toxoid-containing vaccines might be appropriate in certain circumstances, including for children who received prior DT vaccine and need protection from pertussis (in DTaP) or for immigrants with uncertain immunization histories.

Impact of Reimbursement Policies

Administering extra antigens contained in a combination vaccine, when justified as previously described, is acceptable practice and should be reimbursed on the patient's behalf by indemnity health insurance and managed-care systems. Otherwise, high levels of timely vaccination coverage might be discouraged.

Conjugate Vaccine Carrier Proteins

Some carrier proteins in existing conjugated Hib vaccines (62) also are used as conjugates in new vaccines in development (e.g., for pneumococcal and meningococcal disease) (63). Protein conjugates used in Hib conjugate vaccines include a mutant diphtheria toxin (in HbOC), an outer membrane protein from Neisseria meningitidis (in PRP-OMP), and tetanus and diphtheria toxoids (in PRP-T and PRP-D [polyribosylribitol phosphate polysaccharide conjugated to a diphtheria toxoid], respectively). Administering large amounts of tetanus toxoid carrier protein simultaneously with PRP-T conjugate vaccine has been associated with a reduction in the response to PRP (64) (see Future Research and Priorities).

IMPROVING IMMUNIZATION RECORDS

Improving the convenience and accuracy of transferring vaccine-identifying information into medical records and immunization registries should be a priority for immunization programs. Priority also should be given to ensuring that providers have timely access to the immunization histories of their patients.

As new combination vaccines with longer generic names and novel trade names are licensed (Appendix A), problems with accurate recordkeeping in medical charts and immunization registries will likely be exacerbated.

Monitoring Vaccine Safety, Coverage, and Efficacy

All health-care providers are mandated by law to document in each patient's medical record the identity, manufacturer, date of administration, and lot number of certain specified vaccines, including most vaccines recommended for children (65,66). Although such data are essential for surveillance and studies of vaccine safety, efficacy, and coverage, these records are often incomplete and inaccurate. Two major active (67) and passive (68,69) surveillance systems monitoring vaccine safety in the United States have detected substantial rates of missing and erroneous data (greater than or equal to 10%) in the recording of vaccine type, brand, or lot number in the medical records of vaccine recipients (CDC, unpublished data, 1997). Similar rates of incomplete and incorrect vaccination medical records were encountered by the National Immunization Survey and the National Health Interview Survey (CDC, unpublished data, 1997).

Patient Migration Among Immunization Providers

Changing immunization providers during the course of a child's vaccination series is common in the United States. The 1994 National Health Interview Survey documented that approximately 25% of children were vaccinated by more than one provider during the first 2 years of life (CDC, unpublished data, 1997). Eligibility for Medicaid and resulting enrollment in Medicaid managed-care health plans tend to be sporadic, with an average duration of 9 months and a median of less than 12 months in 1993 (Health Care Financing Administration, unpublished data, 1998).

The vaccination records of children who have changed immunization providers are often unavailable and incomplete. Missing or inaccurate information regarding the vaccines received previously might preclude accurate determination of which vaccines are indicated at the time of a visit, resulting in the administration of extra doses.

Strategies for Accurate Vaccine Identification

Potential strategies to improve the accuracy and timely availability of vaccination information include the following:

  • Designing and adopting a recommended, nationally standardized, uniform vaccination medical record form. A copy provided to parents could serve as a record of vaccination history for subsequent immunization providers and satisfy school entry requirements. Immunization registries could generate printouts to document vaccinations received from multiple providers and to replace misplaced forms.
  • Expanding and coordinating immunization registries, which track vaccinations received by children and make the information available in a convenient and timely manner to parents and authorized immunization providers with a need to know, while protecting confidentiality and privacy.
  • Developing technologies, standards, and guidelines to improve the accuracy and convenience of recording and transferring information from the vaccine package or vial into a patient's medical record, compatible with both manual and computerized medical record systems. These methods could include standardized, peel-off identification stickers on vaccine packaging and standardized coding of vaccine identity, expiration date, and lot number. Machine-readable bar codes following Uniform Code Council standards (70) on vaccine packaging and/or stickers could facilitate accurate electronic transfer of this information into computerized medical record systems and immunization registries.

FUTURE RESEARCH AND PRIORITIES

Further efforts are needed to study and obtain more data on the following key subjects related to combination vaccines:

  • The interchangeability of vaccines produced by different manufacturers to prevent the same disease, particularly those that differ in the nature or quantity of one or more component antigens.
  • The safety and efficacy of administering combination vaccines to patients who might already be fully immunized for one or more of the components.
  • Economic and operations research on a) the frequency of delayed or missed vaccinations because of objections to multiple injections; b) the costs of any increased disease burden caused by such missed vaccinations; c) the costs of extra visits needed to comply with the routine immunization schedule; and d) the administrative overhead and cost of errors and confusion that might result when handling a greater number of products.
  • The effects on immunogenicity and safety of simultaneous or repeated exposures to the same proteins used as antigens (e.g., tetanus and diphtheria toxoids) and/or as carrier components in existing and future conjugated vaccines.
  • Research to develop and evaluate alternative means of antigen delivery by the mucosal (71,72), parenteral (73), and cutaneous routes (74-77), which would allow new and existing vaccines to be administered less painfully and more safely than with needles and syringes (78-80).

References

  1. CDC. Recommended childhood immunization schedule--United States, 1999. MMWR 1999; 48:12-6.
  2. American Academy of Pediatrics, Committee on Infectious Diseases. Recommended childhood immunization schedule--United States, January-December 1999. Pediatrics 1999; 103:182-5.
  3. CDC. Food and Drug Administration approval of use of diphtheria and tetanus toxoids and acellular pertussis vaccine. MMWR 1991;40:881-2.
  4. CDC. Food and Drug Administration approval of a second diphtheria and tetanus toxoids and acellular pertussis vaccine. MMWR 1992;41:630-1.
  5. CDC. Pertussis vaccination: use of acellular pertussis vaccines among infants and young children. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1997;46(No. RR-7):1-25.
  6. CDC. Notice to Readers. Food and Drug Administration approval of a fourth acellular pertussis vaccine for use among infants and young children. MMWR 1998;47:934-6.
  7. CDC. Recommendations for use of Haemophilus b conjugate vaccines and a combined diphtheria, tetanus, pertussis, and Haemophilus b vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1993;42(No. RR-13):1-15.
  8. CDC. Notice to readers. Food and Drug Administration approval of use of Haemophilus influenzae type b conjugate vaccine reconstituted with diphtheria-tetanus-pertussis vaccine for infants and children. MMWR 1993;42:964-5.
  9. CDC. FDA approval of a Haemophilus b conjugate vaccine combined by reconstitution with an acellular pertussis vaccine. MMWR 1996;45:993-5.
  10. CDC. Notice to readers. FDA approval for infants of a Haemophilus influenzae type b conjugate and hepatitis B (recombinant) combined vaccine. MMWR 1997;46:107-9.
  11. Weniger BG, Chen RT, Jacobson SH, et al. Addressing the challenges to immunization practice with an economic algorithm for vaccine selection. Vaccine 1998;16:1885-97.
  12. Corbel MJ. Control testing of combined vaccines: A consideration of potential problems and approaches. Biologicals 1994;22:353-60.
  13. Anthony BF. FDA perspective on regulatory issues in vaccine development. In: Williams JC, Goldenthal KL, Burns DL, Lewis BP Jr, eds., Combined vaccines and simultaneous administration: current issues and perspectives. New York: Annals of the New York Academy of Sciences, 1995;754:10-6.
  14. Insel RA. Potential alterations in immunogenicity by combining or simultaneously administering vaccine components. In: Williams JC, Goldenthal KL, Burns DL, Lewis BP Jr, eds., Combined vaccines and simultaneous administration: current issues and perspectives. New York: Annals of the New York Academy of Sciences, 1995;754:35-47.
  15. Eskola J, Olander RM, Hovi T, Litmanen L, Peltola S, Kayhty E. Randomized trial of the effect of co-administration with acellular pertussis DTP vaccine on immunogenicity of Haemophilus influenzae type b conjugate vaccine. Lancet 1996;348:1688-92.
  16. Food and Drug Administration. Guidance for industry for the evaluation of combination vaccines for preventable diseases: production, testing and clinical studies. Washington, DC: US Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research, April 1997; Docket no. 97N-0029.
  17. Pauly MV, Robinson CA, Sepe SJ, Sing M, Willian MK, eds. Supplying vaccines: an economic analysis of critical issues. Washington, DC: IOS Press, 1996:1-225.
  18. CDC. Combination vaccines for childhood immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP). MMWR 1999;48(No.RR-5):1-15.
  19. American Academy of Pediatrics, Committee on Infectious Diseases. Combination vaccines for childhood immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics (AAP), and the American Academy of Family Physicians (AAFP). Pediatrics 1999:103:1064-77.
  20. American Academy of Family Physicians. Combination vaccines for childhood immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP), American Academy of Pediatrics (AAP) and American Academy of Family Physicians (AAFP). Am Fam Physician 1999;59:2565-74.
  21. Gross PA, Barrett TL, Dellinger EP, et al. Purpose of quality standards for infectious diseases. Infectious Diseases Society of America. Clin Infect Dis 1994;18:421.
  22. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn't [Editorial]. BMJ 1996;312:71-2.
  23. CDC. Prevention of pneumococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1997;46(No. RR-8):1-24.
  24. CDC. 1997 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. MMWR 1997;46(No. RR-12):1-46.
  25. Madlon-Kay DJ, Harper PG. Too many shots? Parent, nurse, and physician attitudes toward multiple simultaneous childhood vaccinations. Arch Fam Med 1994;3:610-3.
  26. Melman ST, Chawla T, Kaplan JM, Anbar RD. Multiple immunizations: ouch! Arch Fam Med 1994;3:615-8.
  27. Szilagyi PG, Rodewald LE, Humiston SG, et al. Immunization practices of pediatricians and family physicians in the United States. Pediatrics 1994;94:517-23.
  28. Askew GL, Finelli L, Lutz J, DeGraaf J, Siegel B, Spitalny K. Beliefs and practices regarding childhood vaccination among urban pediatric providers in New Jersey. Pediatrics 1995;96 :889-92.
  29. Woodin KA, Rodewald LE, Humiston SG, Carges MS, Schaffer SJ, Szilagyi PG. Physician and parent opinions: are children becoming pincushions from immunizations? Arch Pediatr Adolesc Med 1995;149:845-9.
  30. Zimmerman RK, Bradford BJ, Janosky JE, Mieczkowski TA, DeSensi E, Grufferman S. Barriers to measles and pertussis immunization: the knowledge and attitudes of Pennsylvania primary care physicians. Am J Prev Med 1997;13:89-97.
  31. Zimmerman RK, Schlesselman JJ, Mieczkowski TA, Medsger AR, Raymund M. Physician concerns about vaccine side effects and potential litigation. Arch Pediatr Adolesc Med 1998; 152:12-9.
  32. Freed GL, Kauf T, Freeman VA, Pathman DE, Konrad TR. Vaccine-associated liability risk and provider immunization practices. Arch Pediatr Adolesc Med 1998;152:285-9.
  33. CDC. Notice to readers. Unlicensed use of combination of Haemophilus influenzae type b conjugate vaccine and diphtheria and tetanus toxoid and acellular pertussis for infants. MMWR 1998;47:787.
  34. Midthun K, Horne AD, Goldenthal KL. Clinical safety evaluation of combination vaccines. Dev Biol Stand 1998;95:245-9.
  35. Granoff DM, Rappuoli R. Are serological responses to acellular pertussis antigens sufficient criteria to ensure that new combination vaccines are effective for prevention of disease? Dev Biol Stand 1997;89:379-89.
  36. Clements-Mann ML. Lessons for AIDS vaccine development from non-AIDS vaccines. AIDS Res Hum Retroviruses 1998;14(suppl 3):S197-S203.
  37. CDC. Prevention of hepatitis A through active or passive immunization. Recommendations of the Advisory Committee on Immunization Practice (ACIP). MMWR 1996;45(No. RR-15):1-30.
  38. Connor BA, Phair J, Sack D, McEniry D, Hornick RB. Preliminary hepatitis A antibody responses in a cohort of healthy adults who received HAVRIX(TM) followed by VAQTA(TM) or HAVRIX(TM) 6-12 months later [Abstract]. In: Program and abstracts of the Second Asia Pacific Travel Health Congress, Taipei. Hong Kong: Asia Pacific Travel Health Association, 1998:23.
  39. Bush LM, Moonsammy GI, Boscia JA. Evaluation of initiating a hepatitis B vaccination schedule with one vaccine and completing it with another. Vaccine 1991;9:807-9.
  40. Greenberg DP, Lieberman JM, Marcy SM, et al. Enhanced antibody response in infants given different sequences of heterogeneous Haemophilus influenzae type b conjugate vaccines. J Pediatr 1995;126:206-11.
  41. Anderson EL, Decker MD, Englund JA, et al. Interchangeability of conjugated Haemophilus influenzae type b vaccines in infants. JAMA 1995;273:849-53.
  42. Bewley KM, Schwab JG, Ballanco GA, Daum RS. Interchangeability of Haemophilus influenzae type b vaccines in the primary series: evaluation of a two-dose mixed regimen. Pediatrics 1996;98:898-904.
  43. American Academy of Pediatrics. Haemophilus influenzae infections. In: Peter G, ed. 1997 Red book: report of the Committee on Infectious Diseases. 24th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1997:220-31.
  44. CDC. Recommended childhood immunization schedule--United States, 1998. MMWR 1998; 47:8-12.
  45. CDC. Notice to readers. Erratum: Vol. 47, No. 1. MMWR 1998;47:220.
  46. American Academy of Pediatrics, Committee on Infectious Diseases. Recommended childhood immunization schedule--United States, January-December 1998. Pediatrics 1998; 101:154-7.
  47. American Academy of Pediatrics, Committee on Infectious Diseases. Immunization schedule errata. AAP News, May 1998;14(5):7.
  48. Pichichero ME, Edwards KM, Anderson EL, et al. A comparison of 6 DT acellular pertussis (DTaP) vaccines with one whole cell pertussis (DTwP) vaccine as a fifth dose in 4 to 6 year-old children [Abstract G-96]. In: Abstracts of the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society of Microbiology, 1997:210.
  49. American Academy of Pediatrics. Pertussis. In: Peter G, ed. 1997 Red book: report of the Committee on Infectious Diseases. 24th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1997:394-407.
  50. American Academy of Pediatrics. Pneumococcal infections. In: Peter G, ed. 1997 Red book: report of the Committee on Infectious Diseases. 24th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1997:410-9.
  51. CDC. Mass vaccination with oral poliovirus vaccine--Asia and Europe, 1995. MMWR 1995;44: 234-6.
  52. CDC. Progress toward poliomyelitis eradication--Africa, 1996. MMWR 1997;46:321-5.
  53. CDC. Measles eradication: recommendations from a meeting cosponsored by the World Health Organization, the Pan American Health Organization, and CDC. MMWR 1997;46(No. RR-11): 1-20.
  54. CDC. Progress toward elimination of measles from the Americas. MMWR 1998;47:189-93.
  55. Edsall G, Elliott MW, Peebles TC, Panaro RJ, Eldred MC. Excessive use of tetanus toxoid boosters. JAMA 1967;202:111-3.
  56. Peebles TC, Levine L, Eldred MC, Edsall G. Tetanus-toxoid emergency boosters: a reappraisal. N Engl J Med 1969;280:575-81.
  57. Jacobs RL, Lowe RS, Lanier BQ. Adverse reactions to tetanus toxoid. JAMA 1982;247:40-2.
  58. Baraff LJ, Cody CL, Cherry JD. DTP-associated reactions: an analysis by injection site, manufacturer, prior reactions, and dose. Pediatrics 1984;73:31-6.
  59. Jones AE, Melville-Smith M, Watkins J, Seagroatt V, Rice L, Sheffield F. Adverse reactions in adolescents to reinforcing doses of plain and adsorbed tetanus vaccines. Community Med 1985;7:99-106.
  60. CDC. Diphtheria, tetanus, and pertussis: recommendations for vaccine use and other preventive measures. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR 1991;40(No. RR-10):1-28.
  61. American Academy of Pediatrics. Tetanus (Lockjaw). In: Peter G, ed. 1997 Red book: report of the Committee on Infectious Diseases. 24th ed. Elk Grove Village, IL: American Academy of Pediatrics, 1997:518-23.
  62. Ward J, Lieberman JM, Cochi SL. Haemophilus influenzae vaccines. In: Plotkin SA, Mortimer EA, Jr, eds. Vaccines. 2nd ed. Philadelphia: W.B. Saunders Co., 1994:337-86.
  63. Paradiso PR, Lindberg AA. Glycoconjugate vaccines: future combinations [Review]. Dev Biol Stand 1996;87:269-75.
  64. Dagan R, Eskola J, Leclerc C, Leroy O. Reduced response to multiple vaccines sharing common protein epitopes that are administered simultaneously to infants. Infect Immun 1998;66: 2093-8.
  65. National Childhood Vaccine Injury Act of 1986. Recording and reporting of information. Public Health Service Act, Title XXI, ***2125. Codified at 42 U.S.C. ***300aa-25 (suppl 1987).
  66. CDC. Current trends. National Childhood Vaccine Injury Act: requirements for permanent vaccination records and for reporting of selected events after vaccination. MMWR 1988; 37:197-200.
  67. Chen RT, Glasser JW, Rhodes PH, et al. Vaccine safety datalink project: a new tool for improving vaccine safety monitoring in the United States. Pediatrics 1997;99:765-73.
  68. Chen RT, Rastogi SC, Mullen JR, et al. The Vaccine Adverse Event Reporting System (VAERS). Vaccine 1994;12:542-50.
  69. Ellenberg SS, Chen RT. The complicated task of monitoring vaccine safety [Review]. Pub Health Rep 1997;112:10-20.
  70. Miller M, Terwilliger J. Data requirements for bar coding small packages of healthcare products. Uniform Code Council, Inc. website, January 1996. Available at <http://www.uc-council.org/d01-t.htm>. Accessed December 7, 1998.
  71. Walker RI. New strategies for using mucosal vaccination to achieve more effective immunization. Vaccine 1994;12:387-400.
  72. Levine MM, Dougan G. Optimism over vaccines administered via mucosal surfaces. Lancet 1998;351:1375-6.
  73. Reis EC, Jacobson RM, Tarbell S, Weniger BG. Taking the sting out of shots: control of vaccination-associated pain and adverse reactions [Review]. Pediatr Ann 1998;27:375-86.
  74. Tang D-C, Shi Z, Curiel DT. Vaccination onto bare skin [Letter]. Nature 1997;388:729-30.
  75. Bellhouse BJ, Sarphie DF, Greenford JC, inventors; Oxford Biosciences Ltd., assignee. Method of delivering powder transdermally with needleless injector. US patent 5 630 796. May 20, 1997.
  76. Glenn GM, Rao M, Matyas GR, Alving CR. Skin immunization made possible by cholera toxin [Letter]. Nature 1998;391:851.
  77. Glenn GM, Scharton-Kersten T, Vassell R, Mallet CP, Hale TL, Alving CR. Transcutaneous immunization with cholera toxin protects mice against lethal mucosal toxin challenge. J Immunol 1998;161:3211-4.
  78. Aylward B, Lloyd J, Zaffran M, McNair-Scott R, Evans P. Reducing the risk of unsafe injections in immunization programmes: financial and operational implications of various injection technologies. Bull World Health Organ 1995;73:531-40.
  79. Aylward B, Kane M, McNair-Scott R, Hu DH [corrected to DJ]. Model-based estimates of the risk of human immunodeficiency virus and hepatitis B virus transmission through unsafe injections. Int J Epidemiol 1995;24:446-52.
  80. Global Programme on Vaccines and Immunization. Steering group on the development of jet injection for immunization [Report]. Geneva: World Health Organization, 1997:1-37.

 

Appendix A

COMBINATION VACCINES*

COMBINATION VACCINES

* Combination vaccines are defined as those containing multiple antigens to prevent different diseases or to protect against multiple strains of infectious agents causing the same disease. Existing combination vaccines are listed according to the year they were first licensed in the United States. Potential combination vaccines are listed in order of their number of components. Horizontal lines connect multiple antigens combined into one vaccine. Vertical alignment illustrates how antigens may be joined in different combinations.

† As of publication date, some vaccine combinations listed are not licensed or approved for all ages in the United States.

Adapted from: Weniger BG, Chen RT, Jacobson SH, et al. Addressing the challenges to immunization practice with an economic algorithm for vaccine selection. Vaccine 1998;16:1885-97.

Sources: Mitchell VS, Philipose NM, Sanford JP, eds. The Children's Vaccine Initiative: achieving the vision. Washington, DC. National Academy Press, 1993. Grabenstein JD, ImmunoFacts: vaccines and immunologic drugs. St. Louis: Facts and Comparisons, August 1998.

Abbreviations: DT=diphtheria and tetanus toxoids vaccine (for children); DTaP=diphtheria and tetanus toxoids and acellular pertussis vaccine; DTaP-Hib=diphtheria and tetanus toxoids and acellular pertussis and Haemophilus influenzae type b vaccine; DTwP=diphtheria and tetanus toxoids and whole-cell pertussis vaccine; DTwP-Hib=diphtheria and tetanus toxoids and whole-cell pertussis and Haemophilus influenzae type b vaccine; HepA=hepatitis A vaccine; HepB=hepatitis B vaccine; Hib= Haemophilus influenzae type b conjugate vaccine; Hib-HepB=Haemophilus influenzae type b and hepatitis B vaccine; Hib-HepB-IPV= Haemophilus influenzae type b, hepatitis B, and trivalent inactivated polio vaccine; INF=influenza vaccine; IPV=trivalent inactivated polio vaccine (killed Salk type); Me=measles vaccine; Me-Mu=measles and mumps vaccine; Me-Rub=measles and rubella vaccine; MenCon=meningococcal ( Neisseria meningitidis) conjugate vaccine; MenPS=meningococcal (Neisseria meningitidis) polysaccharride vaccine; MMR=measles-mumps-rubella vaccine; MMR-Var=measles-mumps-rubella and varicella (chickenpox) vaccine; Mu=mumps vaccine; Mu-Rub=mumps and rubella vaccine; OPV=trivalent oral polio vaccine (live Sabin type); PnuCon=pneumococcal (Streptococcus pneumoniae) conjugate vaccine; PnuPS=pneumococcal ( Streptococcus pneumoniae) polysaccharide vaccine; Rv=rotavirus vaccine; Rub=rubella vaccine; Td=tetanus and diphtheria toxoids vaccine (for adolescents and adults).

 

Appendix B

EVIDENCE FOR RECOMMENDATIONS*

Recommendation

Strength of evidence

Comment
Preference for Combination Vaccines

B

Parent and provider surveys
Manufacturer Interchangeability    
Permissible:    
  Diphtheria†, Tetanus, Hib, HepB

A

Good evidence
  HepA

B

Preliminary data
Discouraged:    
  Acellular pertussis (in DTaP, DTaP-Hib)

C

Little or no evidence
Vaccine Supply

C

 
Extra Doses of Vaccine Antigens    
Permissible:    
  HepB, Hib, MMR, OPV, Rv, Var

A

Little or no risk of adverse events for those already immune
Cautioned:    
  Tetanus

B

Frequent revaccination could cause hypersensitivity reactions

 

 

* Principal recommendations are classified by the strength and quality of evidence supporting them according to principles described elsewhere ( a,b ), using categories adapted from previous publications (c,d).

A=Strong epidemiologic evidence (i.e., at least one properly randomized, controlled trial) and/or substantial clinical or public health benefit.

B=Moderate epidemiologic evidence (i.e., at least one well-designed clinical trial without randomization, or cohort or case-controlled analytic studies, preferably from more than one center) and/or moderate clinical or public health benefit.

C=Epidemiologic evidence minimal or lacking; recommendation supported by the opinions of respected authorities based on clinical and field experience, descriptive studies, or reports of expert committees.

† Vaccines containing diphtheria toxoids and tetanus toxoids include DT, Td, DTaP, DTwP, DTaP-Hib, and DTwP-Hib. TT contains tetanus toxoid only.

Abbreviations: DT=diphtheria and tetanus toxoids vaccine (for children); DTaP=diphtheria and tetanus toxoids and acellular pertussis vaccine; DTaP-Hib=diphtheria and tetanus toxoids and acellular pertussis and Haemophilus influenzae type b vaccine; DTwP=diphtheria and tetanus toxoids and whole cell pertussis vaccine; DTwP-Hib=diphtheria and tetanus toxoids and whole cell pertussis and Haemophilus influenzae type b vaccine; HepA=hepatitis A vaccine; HepB=hepatitis B vaccine; Hib= Haemophilus influenzae type b conjugate vaccine; MMR=measles-mumps-rubella vaccine; OPV=trivalent oral polio vaccine (live Sabin type); Rv=Rotavirus vaccine. Td=tetanus and diphtheria toxoids vaccine (for adolescents and adults); Var=varicella (chickenpox) vaccine.

Sources:

  1. Gross PA, Barrett TL, Dellinger EP, et al. Purpose of quality standards for infectious diseases. Infectious Diseases Society of America. Clin Infect Dis 1994;18:421.
  2. Sackett DL, Rosenberg WM, Gray JA, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn't [Editorial]. BMJ 1996;312:71-2.
  3. CDC. Prevention of pneumococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1997;46(No. RR-8):1-24.
  4. CDC. 1997 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. MMWR 1997;46(No. RR-12):1-46.


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