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      Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger — United States, 2019

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          Abstract

          At its October 2018 meeting, the Advisory Committee on Immunization Practices (ACIP)* voted to recommend approval of the Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger, United States, 2019. The 2019 child and adolescent immunization schedule summarizes ACIP recommendations, including several changes from the 2018 immunization schedule, † on the cover page, three tables, and notes found on the CDC immunization schedule website (https://www.cdc.gov/vaccines/schedules/index.html). This immunization schedule is recommended by ACIP and approved by the CDC Director, the American Academy of Pediatrics, the American Academy of Family Physicians, and the American College of Obstetricians and Gynecologists. Health care providers are advised to use the tables and the notes together. ACIP’s recommendations on use of each vaccine are developed after in-depth reviews of vaccine-related data, including disease epidemiology and burden, vaccine efficacy and effectiveness, vaccine safety, quality of evidence, feasibility of program implementation, and economic analyses of immunization policy ( 1 ). The child and adolescent immunization schedule is published annually to consolidate and summarize updates to ACIP recommendations on vaccination of children and adolescents and to assist health care providers in implementing current ACIP recommendations. The use of trade names of vaccines in this report and in the child and adolescent immunization schedule is for identification purposes only and does not imply endorsement by ACIP or CDC. For further guidance on the use of each vaccine, including contraindications and precautions, health care providers are referred to the respective ACIP vaccine recommendations at https://www.cdc.gov/vaccines/hcp/acip-recs/index.html. Changes in recommended use of vaccines can occur between annual updates to the child and adolescent immunization schedule. These changes, if made, are available at https://www.cdc.gov/vaccines/acip/recommendations.html). § Printable versions of the 2019 child and adolescent immunization schedule and ordering instructions are available on the immunization schedule website. Vaccine Changes in the 2019 Immunization Schedule for Children and Adolescents Vaccine changes in the 2019 immunization schedule for children and adolescents aged ≤18 years include new or revised ACIP recommendations for hepatitis A vaccine (HepA) ( 2 ), hepatitis B vaccine (Hep B) ( 3 ), influenza vaccine ( 4 ), and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) ( 5 ), as well as clarification of the recommendations for inactivated poliovirus vaccines (IPV). Changes Affecting Multiple Portions of the Schedule The overall appearance of the 2019 child and adolescent schedule has been updated because of recommendations resulting from a recent evaluation of the child and adolescent immunization schedule. An internet survey of 249 pediatricians and family medicine physicians was conducted to assess their familiarity with the schedule, the environment in which the schedule is used, the frequency and circumstances of use, and their impressions and preferences on redesigned drafts of the child and adolescent immunization schedule. These changes have been applied to all portions of the immunization schedule, including the cover page, routine immunization schedule (Table 1), catch-up schedule (Table 2), medical indications for each vaccine (Table 3), and notes with details for each vaccine. Cover Page. Changes to the cover page are as follows: Guidance on how to use the schedule was added to the top of the document. Live attenuated influenza vaccine (LAIV) was added to the vaccine table. A Helpful Information section, which includes links to the ACIP recommendations, the General Best Practice Guidelines for Immunization, and the Manual for the Surveillance of Vaccine-Preventable Diseases, has been added. Table 1. Changes to Table 1 (previously known as Figure 1) are as follows: A separate row has been added for LAIV. A purple bar has been added to the Hepatitis A (HepA) row at age 6–11 months to represent use in infant travelers. Within the Tetanus, diphtheria, & acellular pertussis (Tdap: ≥7 yrs) row, the bar for persons aged 13–18 years has been split into a half green and half purple bar to represent catch-up vaccination and use in pregnant adolescents, respectively. Table 2. Changes to Table 2 (previously known as Figure 2) are as follows: Minor changes to the order in which guidance is presented in the Haemophilius influenzae type b and Pneumococcal conjugate rows were made. The criteria under which no further doses are needed are now presented first, followed by recommendation for those for whom additional doses are indicated. Table 3. Changes to Table 3 (previously known as Figure 3) are as follows: A new pink color has been added to the legend, which represents “Delay vaccination until after pregnancy if vaccine indicated.” This color is used in the pregnancy column for human papillomavirus vaccine. The Contraindicated and Precaution for vaccination boxes in the legend have been defined with narrative text. A row for LAIV has been added. The Pregnancy cell in the meningococcal B vaccine row has been changed to the orange Precaution for vaccination color. Notes. The notes (previously known as footnotes) are presented in alphabetical order rather than linked by numerical superscripts as in previous years. Edits have been made throughout the Notes section to harmonize language between the child and adolescent schedule and the adult immunization schedule, where possible. In addition, the following content changes were made: The HepA note was revised to include information regarding the use of combined HepA-HepB vaccine in persons aged ≥18 years. A section for international travel has been added with recommendations for vaccination of travelers aged 6–11 months and unvaccinated travelers aged ≥12 months. Homelessness also has been added as an indication for HepA vaccination. The HepB note was revised to include information regarding the use of CpG-adjuvanted HepB vaccine and combination HepA-HepB vaccine in persons aged ≥18 years. Within the IPV note, a bullet has been added regarding the use of combination vaccines that contain IPV. The Influenza vaccines note has been updated to indicate that LAIV can be used during the 2018–19 influenza season. A Special Situations section has been added with information regarding vaccination of persons with a history of egg allergy and circumstances under which LAIV use is not recommended. During mumps and meningococcal disease outbreaks, the Additional Information section at the beginning of the notes directs providers to their state or local health department for information regarding vaccination during an outbreak. Therefore, language regarding the use of measles, mumps, and rubella (MMR) vaccine in the setting of a mumps outbreak or the use of meningococcal (groups A, C, W-135, and Y) conjugate (MenACWY) and meningococcal group B (MenB) vaccines in the setting of meningococcal disease outbreaks has been removed from the MMR and meningococcal vaccine notes. The Tdap note has been updated to indicate that those persons who received a dose of Tdap or diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) at age 7–10 years inadvertently or as part of the catch-up series should still receive the routine dose of Tdap at age 11–12 years. A link to information regarding use of Tdap/tetanus and diphtheria toxoids (Td) for wound prophylaxis also has been added.

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          Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices—United States, 2018–19 Influenza Season

          Summary This report updates the 2017–18 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2017;66[No. RR-2]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. A licensed, recommended, and age-appropriate vaccine should be used. Inactivated influenza vaccines (IIVs), recombinant influenza vaccine (RIV), and live attenuated influenza vaccine (LAIV) are expected to be available for the 2018–19 season. Standard-dose, unadjuvanted, inactivated influenza vaccines will be available in quadrivalent (IIV4) and trivalent (IIV3) formulations. Recombinant influenza vaccine (RIV4) and live attenuated influenza vaccine (LAIV4) will be available in quadrivalent formulations. High-dose inactivated influenza vaccine (HD-IIV3) and adjuvanted inactivated influenza vaccine (aIIV3) will be available in trivalent formulations. Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 25, 2017; February 21, 2018; and June 20, 2018. New and updated information in this report includes the following four items. First, vaccine viruses included in the 2018–19 U.S. trivalent influenza vaccines will be an A/Michigan/45/2015 (H1N1)pdm09–like virus, an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus, and a B/Colorado/06/2017–like virus (Victoria lineage). Quadrivalent influenza vaccines will contain these three viruses and an additional influenza B vaccine virus, a B/Phuket/3073/2013–like virus (Yamagata lineage). Second, recommendations for the use of LAIV4 (FluMist Quadrivalent) have been updated. Following two seasons (2016–17 and 2017–18) during which ACIP recommended that LAIV4 not be used, for the 2018–19 season, vaccination providers may choose to administer any licensed, age-appropriate influenza vaccine (IIV, RIV4, or LAIV4). LAIV4 is an option for those for whom it is appropriate. Third, persons with a history of egg allergy of any severity may receive any licensed, recommended, and age-appropriate influenza vaccine (IIV, RIV4, or LAIV4). Additional recommendations concerning vaccination of egg-allergic persons are discussed. Finally, information on recent licensures and labeling changes is discussed, including expansion of the age indication for Afluria Quadrivalent (IIV4) from ≥18 years to ≥5 years and expansion of the age indication for Fluarix Quadrivalent (IIV4), previously licensed for ≥3 years, to ≥6 months. This report focuses on the recommendations for use of vaccines for the prevention and control of influenza during the 2018–19 season in the United States. A Background Document containing further information and a brief summary of these recommendations are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used within Food and Drug Administration–licensed indications. Updates and other information are available at CDC’s influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check CDC’s influenza website periodically for additional information.
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            Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant

            Hepatitis B (HepB) vaccination is the primary means of preventing infections and complications caused by hepatitis B virus (HBV). On February 21, 2018, the Advisory Committee on Immunization Practices (ACIP) recommended Heplisav-B (HepB-CpG), a yeast-derived vaccine prepared with a novel adjuvant, administered as a 2-dose series (0, 1 month) for use in persons aged ≥18 years. The ACIP Hepatitis Vaccines Work Group conducted a systematic review of the evidence, including data from four randomized controlled trials assessing prevention of HBV infection and six randomized controlled trials assessing adverse events in adults. Seroprotective antibody to hepatitis B surface antigen (anti-HBs) levels were achieved in 90.0%–100.0% of subjects receiving HepB-CpG (Dynavax Technologies Corporation), compared with 70.5%–90.2% of subjects receiving Engerix-B (GlaxoSmithKline Biologicals). The benefits of protection with 2 doses administered over 1 month make HepB-CpG an important option for prevention of HBV. Introduction Vaccination is the primary means for preventing hepatitis B virus (HBV) infection and its complications. Existing hepatitis B (HepB) vaccines use an aluminum adjuvant. On November 9, 2017, Heplisav-B (HepB-CpG), a single-antigen HepB vaccine with a novel immunostimulatory sequence adjuvant, was approved by the Food and Drug Administration for the prevention of HBV in persons aged ≥18 years. The vaccine is administered as 2 doses, 1 month apart ( 1 ). On February 21, 2018, the Advisory Committee on Immunization Practices (ACIP)* recommended HepB-CpG for use in persons aged ≥18 years. HepB-CpG contains yeast-derived recombinant HepB surface antigen (HBsAg) and is prepared by combining purified HBsAg with small synthetic immunostimulatory cytidine-phosphate-guanosine oligodeoxynucleotide (CpG-ODN) motifs (1018 adjuvant). The 1018 adjuvant binds to Toll-like receptor 9 to stimulate a directed immune response to HBsAg ( 1 ). HepB-CpG is available in single-dose 0.5 mL vials. Each dose contains 20 μg of HBsAg and 3,000 μg of 1018 adjuvant. HepB-CpG is formulated without preservatives and is administered as an intramuscular injection in the deltoid region of the upper arm ( 1 ). HepB-CpG is the fifth inactivated HepB vaccine currently recommended for use in the United States. This report contains ACIP guidance specific to HepB-CpG and augments the 2018 ACIP recommendations for the prevention of HBV infection ( 2 ). This report does not include new guidance for populations recommended to receive HepB vaccination or immunization management issues other than those that pertain specifically to HepB-CpG. The intended audience for this report includes clinical and public health personnel who provide HepB vaccination services to adults. These recommendations are meant to serve as a source of guidance for health care providers; health care providers should always consider the individual clinical circumstances of each patient. Methods From February 2016 to January 2018, the ACIP Hepatitis Vaccines Work Group † participated in three teleconference meetings to review the quality of evidence for immunogenicity and safety of HepB-CpG and implementation issues. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach for evaluating evidence was adopted by ACIP in 2010 (https://www.cdc.gov/vaccines/acip/recs/grade/). The Work Group identified critical and important outcomes for inclusion in the GRADE tables, conducted a systematic review of the evidence, and subsequently reviewed and discussed findings and evidence quality ( 3 ). Key outcomes were designated as critical (hepatitis B infection, severe adverse events, and cardiovascular safety) or important (mild adverse events). Factors considered in determining the recommendation included benefits and harms and evidence type. Values and preferences and economic factors were not systematically considered. The scientific literature was searched through a systematic review of Medline (Ovid), CAB Abstracts, Embase, Global Health (Ovid), Scopus, and Cochrane databases. Search terms included “Heplisav,” “HBV-ISS,” “HBsAg-1018,” “1018 immunostimulatory sequence,” and “hepatitis B surface antigen-1018 ISS.” To qualify as a candidate for inclusion in the review, a study had to present immunogenicity or disease endpoints or safety data on HepB-CpG. Studies were excluded if they were basic science, a secondary data analysis, immunogenicity outcomes for a nonlicensed formulation or use of HepB-CpG, a general review or opinion perspective, conducted on nonhuman primates, or if data could not be abstracted. Supporting evidence for the Work Group’s findings is available online (https://www.cdc.gov/vaccines/acip/recs/grade/hepb.html). A summary of Work Group discussions was presented to ACIP on October 25, 2017, and February 21, 2018. At the February 2018 meeting, a proposed recommendation was presented to the committee, and, after a public comment period, was approved by the voting ACIP members as follows: HepB-CpG is recommended as an option for HepB vaccination for persons aged ≥18 years (14 voted in favor, with none opposed, none abstained, and none recused). This report summarizes the data considered, the quality of evidence, and the rationale for the recommendation. Summary of Key Findings The body of evidence consisted of four randomized controlled trials assessing prevention of HBV infection and six randomized controlled trials assessing adverse events (mild adverse events, serious adverse events, and cardiovascular adverse events) in adult subjects. Outcomes compared HepB-CpG with Engerix-B. Data from these studies informed HepB-CpG licensure. Studies assessing prevention of HBV infection used antibody to hepatitis B surface antigen (anti-HBs) ≥10 mIU/mL as a serologic correlate of protection. Protection among 7,056 subjects receiving 2 doses of HepB-CpG was compared with protection among 3,214 subjects receiving 3 doses of Engerix-B. Seroprotective anti-HBs levels were achieved in 90.0%–100.0% of subjects receiving HepB-CpG, compared with 70.5%–90.2% of subjects receiving Engerix-B ( 4 – 7 ). The body of evidence for the benefits of protection against HBV infection was deemed to be GRADE evidence type 2 (i.e., evidence from randomized controlled trials with important limitations, or exceptionally strong evidence from observational studies). The evidence type was downgraded for indirectness because immunogenicity was used as a surrogate for protection. Safety profiles among 9,871 subjects receiving 2 or 3 doses of HepB-CpG were compared with those among 4,385 subjects receiving 3 or 4 doses of Engerix-B. Among subjects receiving HepB-CpG, 45.6%, 5.4%, and 0.27% experienced a mild adverse event, serious adverse event, or cardiovascular event, respectively. Among subjects receiving Engerix-B, 45.7%, 6.3%, and 0.14% experienced a mild adverse event, serious adverse event, or cardiovascular event, respectively ( 1 , 4 – 9 ). The body of evidence assessing adverse events was deemed to be GRADE evidence type 1 (evidence from randomized controlled trials, or overwhelming evidence from observational studies). Rationale Based on the available immunogenicity evidence, a 2-dose schedule (0, 1 month) of HepB-CpG will be efficacious for the prevention of HBV infection. The risk for adverse events, including cardiovascular adverse events, was reviewed and will be monitored. The benefits of protection with 2 doses administered over 1 month make this an important option for prevention of HBV. ACIP Recommendations HepB-CpG may be used as a HepB vaccine in persons aged ≥18 years recommended for vaccination against HBV (Box) ( 2 ). BOX Adults who are recommended to receive hepatitis B vaccine Persons at risk for infection through sexual exposure Sex partners of hepatitis B surface antigen (HBsAg)–positive persons Sexually active persons not in a long-term, mutually monogamous relationship Persons seeking evaluation or treatment for a sexually transmitted infection Men who have sex with men Persons with a history of current or recent injection drug use Persons at risk for infection by percutaneous or mucosal exposure to blood Household contacts of HBsAg-positive persons Residents and staff of facilities for developmentally disabled persons Health care and public safety personnel with reasonably anticipated risk for exposure to blood or blood-contaminated body fluids Hemodialysis patients and predialysis, peritoneal dialysis, and home dialysis patients Persons with diabetes mellitus aged <60 years and persons with diabetes mellitus aged ≥60 years at the discretion of the treating clinician International travelers to countries with high or intermediate levels of endemic HBV infection (HBsAg prevalence ≥2%) Persons with hepatitis C virus infection, persons with chronic liver disease (including, but not limited to, those with cirrhosis, fatty liver disease, alcoholic liver disease, autoimmune hepatitis, and an alanine aminotransferase [ALT] or aspartate aminotransferase [AST] level greater than twice the upper limit of normal) Persons with human immunodeficiency virus infection Incarcerated persons Other persons seeking protection from hepatitis B virus infection (even without acknowledgment of a specific risk factor) CDC Guidance for Use Interchangeability and dosing schedule. Data are limited on the safety and immunogenicity effects when HepB-CpG is interchanged with HepB vaccines from other manufacturers. When feasible, the same manufacturer’s vaccines should be used to complete the series ( 10 ). However, vaccination should not be deferred when the manufacturer of the previously administered vaccine is unknown or when the vaccine from the same manufacturer is unavailable ( 10 ). The 2-dose HepB vaccine series only applies when both doses in the series consist of HepB-CpG. Series consisting of a combination of 1 dose of HepB-CpG and a vaccine from a different manufacturer should consist of 3 total vaccine doses and should adhere to the 3-dose schedule minimum intervals of 4 weeks between dose 1 and 2, 8 weeks between dose 2 and 3, and 16 weeks between dose 1 and 3. Doses administered at less than the minimum interval should be repeated. However, a series containing 2 doses of HepB-CpG administered at least 4 weeks apart is valid, even if the patient received a single earlier dose from another manufacturer. Special populations. There are no clinical studies of HepB-CpG in pregnant women. Available human data on HepB-CpG administered to pregnant women are insufficient to inform assessment of vaccine-associated risks in pregnancy. Until safety data are available for HepB-CpG, providers should continue to vaccinate pregnant women needing HepB vaccination with a vaccine from a different manufacturer. Postvaccination serologic testing. To assess response to vaccination and the need for revaccination, postvaccination serologic testing 1–2 months after the final dose of vaccine is recommended for certain persons following vaccination (e.g., hemodialysis patients, HIV-infected and other immunocompromised persons, health care personnel, and sex partners of HBsAg-positive persons) ( 2 ). Postvaccination serologic testing should be performed using a method that allows determination of the protective level of anti-HBs (≥10 mIU/mL) ( 2 ). Persons with anti-HBs <10 mIU/mL following receipt of 2 doses of HepB-CpG should be revaccinated. Revaccination may consist of administration of a second complete HepB vaccine series followed by anti-HBs testing 1–2 months after the final dose. Alternatively, revaccination may consist of administration of an additional single HepB vaccine dose followed by anti-HBs testing 1–2 months later (and, if anti-HBs remains <10 mIU/mL, completion of the second HepB vaccine series followed again by anti-HBs testing 1–2 months after the final dose) ( 2 ). Administration of more than two complete HepB vaccine series is generally not recommended, except for hemodialysis patients ( 2 ). HepB-CpG may be used for revaccination following an initial HepB vaccine series that consisted of doses of HepB-CpG or doses from a different manufacturer ( 11 ). HepB-CpG may also be used to revaccinate new health care personnel (including the challenge dose) initially vaccinated with a vaccine from a different manufacturer in the distant past who have anti-HBs <10 mIU/mL upon hire or matriculation ( 2 ). Precautions and contraindications. Before administering HepB-CpG, health care providers should consult the package insert for precautions, warnings, and contraindications. Adverse events occurring after administration of any vaccine should be reported to the Vaccine Adverse Event Reporting System (VAERS). Reports can be submitted to VAERS online, by fax, or by mail. Additional information about VAERS is available by telephone (1-800-822-7967) or online (https://vaers.hhs.gov). Future Considerations Postlicensure surveillance studies and additional data pertaining to the use of HepB-CpG will be reviewed by ACIP as they become available, and recommendations will be updated as needed. Future economic analyses might inform cost-effectiveness considerations of HepB-CpG, including its use among persons at an increased risk for vaccine nonresponse.
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              Update: Recommendations of the Advisory Committee on Immunization Practices for Use of Hepatitis A Vaccine for Postexposure Prophylaxis and for Preexposure Prophylaxis for International Travel

              Postexposure prophylaxis (PEP) with hepatitis A (HepA) vaccine or immune globulin (IG) effectively prevents infection with hepatitis A virus (HAV) when administered within 2 weeks of exposure. Preexposure prophylaxis against HAV infection through the administration of HepA vaccine or IG provides protection for unvaccinated persons traveling to or working in countries that have high or intermediate HAV endemicity. The Advisory Committee on Immunization Practices (ACIP) Hepatitis Vaccines Work Group conducted a systematic review of the evidence for administering vaccine for PEP to persons aged >40 years and reviewed the HepA vaccine efficacy and safety in infants and the benefits of protection against HAV before international travel. The February 21, 2018, ACIP recommendations update and supersede previous ACIP recommendations for HepA vaccine for PEP and for international travel. Current recommendations include that HepA vaccine should be administered to all persons aged ≥12 months for PEP. In addition to HepA vaccine, IG may be administered to persons aged >40 years depending on the provider’s risk assessment. ACIP also recommended that HepA vaccine be administered to infants aged 6–11 months traveling outside the United States when protection against HAV is recommended. The travel-related dose for infants aged 6–11 months should not be counted toward the routine 2-dose series. The dosage of IG has been updated where applicable (0.1 mL/kg). HepA vaccine for PEP provides advantages over IG, including induction of active immunity, longer duration of protection, ease of administration, and greater acceptability and availability. Introduction Postexposure prophylaxis (PEP) with hepatitis A (HepA) vaccine or immune globulin (IG) effectively prevents infection with hepatitis A virus (HAV) when administered within 2 weeks of exposure ( 1 , 2 ). The efficacy of IG or vaccine when administered >2 weeks after exposure has not been established. Previous ACIP* recommendations for PEP included HepA vaccine for persons aged 1–40 years and IG for persons outside this age range; if IG was not available for persons aged >40 years, HepA vaccine could be administered ( 1 ). Preexposure prophylaxis against HAV infection through the administration of HepA vaccine or IG is also recommended for unvaccinated persons traveling to or working in countries that have high or intermediate HAV endemicity ( 3 ). Because HepA vaccine is not licensed for use in children aged 40 years using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework (https://www.cdc.gov/vaccines/acip/recs/grade/table-refs.html). Quality of evidence related to the benefits and harms of administering HepA vaccine for preexposure prophylaxis to infants aged 6–11 months who will be traveling internationally was not evaluated using the GRADE framework; instead, studies of HepA vaccine efficacy and safety in infants ( 7 – 9 ) and the benefits of protection against HAV before international travel were considered ( 3 ). At the February 2018 ACIP meeting, the following proposed recommendations were presented to the committee: 1) HepA vaccines should be administered for PEP for all persons aged ≥12 months; in addition to HepA vaccine, IG may be administered to persons aged >40 years for PEP, depending on the provider’s risk assessment; and 2) HepA vaccine should be administered to infants aged 6–11 months traveling outside the United States when protection against hepatitis A is recommended. After a period for public comment, the recommendations were approved unanimously by the voting ACIP members. ¶ Summary of Key Findings Prevention of HAV infection with HepA vaccine following exposure. A randomized, double-blind clinical trial of HepA vaccine in 1,090 HAV-susceptible persons aged 2–40 years who were contacts of persons with HAV infection suggested that performance of HepA vaccine administered 40 years; available data indicate reduced response to HepA vaccine in older age groups compared with response in younger adults ( 11 ). GRADE quality of evidence summary for HepA vaccine for PEP in persons aged >40 years. The evidence assessing benefits and harms of administering a dose of HepA vaccine for PEP to prevent HAV infection in adults aged >40 years was determined to be GRADE evidence type 4 (i.e., evidence from clinical experience and observations, observational studies with important limitations, or randomized controlled trials with several major limitations) for benefits and type 3 (i.e., evidence from observational studies, or randomized controlled trials with notable limitations) for harms (https://www.cdc.gov/vaccines/acip/recs/grade/table-refs.html). Prevention of HAV infection among infants aged 6–11 months who received HepA vaccine before travel. HepA vaccine was demonstrated to be safe and efficacious for infants as young as age 2 months ( 2 , 7 – 9 ), although vaccination of infants aged 40 years were based on the premise that IG is more efficacious in this group; however, evidence of decreased IG potency (i.e., reduced titers of anti-HAV antibodies) ( 12 ) led to a recommendation for an increase in the IG dosage (0.1 mL/kg) for hepatitis A PEP in 2017, with a consequent increase in IG administration volume ( 6 ). In addition, when HAV exposure, and thus the need for PEP, is not clear (i.e., consumer of recalled food product or patron at a restaurant where a notification occurred), the benefit of IG compared with vaccine, which provides long-term protection, is less certain. Before travel administration of HepA vaccine to infants aged 6–11 months. IG cannot be administered simultaneously with MMR vaccine because antibody-containing products such as IG can inhibit the immune response to measles and rubella vaccines for 3 months ( 4 , 6 ). However, because MMR vaccine is recommended for all infants aged 6–11 months traveling internationally from the United States and because measles in infancy is more severe than HAV infection in infancy, MMR vaccine should be administered preferentially to preexposure prophylaxis with IG for prevention of HAV infection. Administration of HepA vaccine (indication for off-label use) and MMR vaccine to infants aged 6–11 months ( 7 – 9 ) provides protection against both HAV and measles and allows for simultaneous prophylactic administration ( 4 , 13 ). Recommendations for Postexposure Prophylaxis Against HAV Infection HepA vaccine should be administered to all persons aged ≥12 months for PEP. In addition to HepA vaccine, IG may be administered to persons aged >40 years, depending on the provider’s risk assessment (Supplementary Text 1, https://staging-stacks.cdc.gov/view/cdc/59777). Recommendations for PEP have been updated to include HepA vaccine for all unvaccinated persons aged ≥12 months, regardless of risk group, and co-administration of IG when indicated (Table 1). The dosage of GamaSTAN S/D human IG for PEP (0.1 mL/kg) also has been updated ( 6 ). Persons who have recently been exposed to HAV and who have not received HepA vaccine previously should receive PEP as soon as possible, within 2 weeks of exposure ( 1 ). TABLE 1 Recommendations for postexposure prophylaxis and preexposure protection, by age group and risk category Indication/Age group Risk category/Health status Hepatitis A vaccine Immune globulin Postexposure prophylaxis 40 yrs Healthy 1 dose† 0.1 mL/kg§ ≥12 mos Immunocompromised or chronic liver disease 1 dose† 0.1 mL/kg¶ ≥12 mos Vaccine contraindicated** No 0.1 mL/kg Preexposure protection†† 40 yrs Healthy 1 dose*** 0.1–0.2 mL/kg§§,††† All ages Immunocompromised or chronic liver disease 1 dose*** 0.1–0.2 mL/kg§§,††† >6 mos Persons who elect not to receive vaccine or for whom vaccine is contraindicated** No 0.1–0.2 mL/kg§§ * Measles, mumps, and rubella vaccine should not be administered for at least 3 months after receipt of IG. † A second dose is not required for postexposure prophylaxis; however, for long-term immunity, the hepatitis A vaccination series should be completed with a second dose at least 6 months after the first dose. § The provider’s risk assessment should determine the need for immune globulin administration. If the provider’s risk assessment determines that both vaccine and immune globulin are warranted, HepA vaccine and immune globulin should be administered simultaneously at different anatomic sites ¶ Vaccine and immune globulin should be administered simultaneously at different anatomic sites. ** Life-threatening allergic reaction to a previous dose of hepatitis A vaccine, or allergy to any vaccine component. †† IG should be considered before travel for persons with special risk factors for either HAV infection or increased risk for complications in the event of exposure to HAV. §§ 0.1 mL/kg for travel up to 1 month; 0.2 mL/kg for travel up to 2 months, 0.2mL/kg every 2 months for travel of ≥2 months’ duration. ¶¶ This dose should not be counted toward the routine 2-dose series, which should be initiated at age 12 months. *** For persons not previously vaccinated with HepA vaccine, administer dose as soon as travel is considered, and complete series according to routine schedule. ††† May be administered, based on providers’ risk assessment. Infants aged 40 years depending on the providers’ risk assessment (Supplementary Text 1, https://staging-stacks.cdc.gov/view/cdc/59777). For long-term immunity, the HepA vaccine series should be completed with a second dose at least 6 months after the first dose; however, the second dose is not necessary for PEP. A second dose should not be administered any sooner than 6 months after the first dose, regardless of HAV exposure risk. TABLE 2 Vaccines used to prevent hepatitis A virus (HAV) infection Vaccine Trade name (manufacturer) Age group (yrs) Dosage Route Schedule Booster Hepatitis A vaccine, inactivated Havrix (GlaxoSmithKline) 1–18 0.5 mL (720 ELU) IM 0, 6–12 mo None ≥19 1 mL (1,440 ELU) IM 0, 6–12 mo None Hepatitis A vaccine, inactivated Vaqta (Merck and Co.) 1–18 0.5 mL (25 U) IM 0, 6–18 mo None ≥19 1 mL (50 U) IM 0, 6–18 mo None Combined hepatitis A and B vaccine* Twinrix (GlaxoSmithKline) ≥18 (primary) 1 mL (720 ELU HAV + 20 μg HBsAg) IM 0, 1, 6 mo None ≥18 (accelerated) 1 mL (720 ELU HAV + 20 μg HBsAg) IM 0, 7, 21–30 days 12 mo Abbreviations: ELU = ELISA units of inactivated HAV; HBsAg = hepatitis B surface antigen; IM = intramuscular; U = units of HAV antigen. * Combined hepatitis A and B vaccine (Twinrix) should not be used for postexposure prophylaxis. Persons aged ≥12 months who are immunocompromised or have chronic liver disease. Persons who are immunocompromised or have chronic liver disease and who have been exposed to HAV within the past 14 days and have not previously completed the 2-dose HepA vaccination series should receive both IG (0.1 mL/kg) and HepA vaccine simultaneously in a different anatomic site (e.g., separate limbs) as soon as possible after exposure ( 6 , 15 – 17 ) (Table 1). For long-term immunity, the HepA vaccination series should be completed with a second dose at least 6 months after the first dose; however, the second dose is not necessary for PEP. A second dose should not be administered any sooner than 6 months after the first dose, regardless of HAV exposure risk. In addition to HepA vaccine, IG should be considered for postexposure prophylaxis for persons with special risk factors for either HAV infection or increased risk of complications in the event of an exposure to HAV (Table 3) (Supplementary Text 1, https://staging-stacks.cdc.gov/view/cdc/59777). TABLE 3 Categories of persons with increased risk for hepatitis A virus (HAV) infection or increased risk for complications in the event of exposure to HAV Type of risk Risk category Examples Increased risk for HAV infection Close contacts of persons with HAV infection* Household contacts Caretakers Sexual contacts Occupational risk Persons working with nonhuman primates Persons working with HAV in a research laboratory Increased risk for HAV-associated complications Immunocompromised persons Congenital or acquired immunodeficiency HIV infection Chronic renal failure/Undergoing dialysis Solid organ, bone marrow, or stem cell transplant recipients Persons with diseases requiring treatment with immunosuppressive drugs/biologics (e.g., tumor necrosis alpha inhibitors), long-term systemic corticosteroids, radiation therapy Chronic liver disease Hepatitis B infection Hepatitis C infection Cirrhosis (any etiology) Fatty liver disease (hepatic steatosis) Alcoholic liver disease Autoimmune hepatitis Alanine aminotransferase (ALT) or aspartate amino transferase (AST) level more than twice the upper limit of normal or persistently elevated for 6 months Abbreviation: HIV = human immunodeficiency virus. * Excludes health care personnel using appropriate personal protective equipment. Recommendations for Preexposure Protection Against HAV Infection for Travelers Infants aged 6–11 months. HepA vaccine should be administered to infants aged 6–11 months traveling outside the United States when protection against HAV is recommended (Table 1). The travel-related dose for infants aged 6–11 months should not be counted toward the routine 2-dose series. Therefore, the 2-dose HepA vaccination series should be initiated at age 12 months according to the routine, age-appropriate vaccination schedule. Recommendations for preexposure protection against HAV for travelers aged 40 years, immunocompromised persons, and persons with chronic liver disease. Persons with chronic liver disease as well as adults aged >40 years, immunocompromised persons, and persons with other chronic medical conditions planning to depart to an area with high or intermediate HAV endemicity in 40 years, if indicated. The dosage of IG has been updated. Simultaneous administration of MMR and HepA vaccines is recommended for infants aged 6–11 months traveling internationally. What are the implications for public health practice? HepA vaccine for PEP provides advantages over IG, including induction of active immunity, longer duration of protection, ease of administration, and greater acceptability and availability.
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                Author and article information

                Journal
                MMWR Morb Mortal Wkly Rep
                MMWR Morb. Mortal. Wkly. Rep
                WR
                Morbidity and Mortality Weekly Report
                Centers for Disease Control and Prevention
                0149-2195
                1545-861X
                08 February 2019
                08 February 2019
                : 68
                : 5
                : 112-114
                Affiliations
                Immunization Services Division, National Center for Immunization and Respiratory Diseases, CDC; Zucker School of Medicine at Hofstra/Northwell and Cohen Children’s Medical Center, New Hyde Park, New York; University of Arkansas for Medical Sciences, Little Rock, Arkansas; Arkansas Children's Hospital, Little Rock, Arkansas; Department of Pediatrics, University of California Los Angeles, Los Angeles, California.
                Author notes
                Corresponding author: Candice L. Robinson, crobinson4@ 123456cdc.gov , 404-718-1400.
                Article
                mm6805a4
                10.15585/mmwr.mm6805a4
                6366676
                30730870
                f864b67d-07c3-4bac-898c-800ce4358a15

                All material in the MMWR Series is in the public domain and may be used and reprinted without permission; citation as to source, however, is appreciated.

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