Doug Campos-Outcalt, MD, ACIP update MPA Department of Family and Community Medicine, University of Arizona College Here’s what you need to know to keep your patients’ of Medicine, Phoenix up to date. [email protected]

he Advisory Committee on Immuniza- ❚ In response to these data, the most tion Practices (ACIP) made a number recent ACIP recommendation expands in- T of major new recommendations last dications for HAV to include anyone year. Th ese new recommendations address: who will be in close personal contact—living in the same household or providing regular • expanded use of hepatitis A virus (HAV) babysitting—with an adoptee from any coun- vaccine try with high or intermediate endemic rates Anyone who • preferences for combination of HAV. Th e vaccine should be given within will be in close • timing of poliovirus vaccine doses the fi rst 60 days of the adoptee’s arrival in the personal contact • resumption of the normal Haemophi- United States.1 Th e fi rst dose of the 2-dose se- with an adoptee lus infl uenzae Type b (Hib) schedule, as ries should be given as soon as the adoption is from any country shortages have resolved planned, ideally 2 or more weeks before expo- with high or • the use of a new bivalent human papil- sure to the adoptee. intermediate loma virus (HPV2) vaccine in women and Th is new recommendation adds to ear- endemic rates quadrivalent (HPV4) vaccine in men lier expansions of indications for HAV vaccine, of hepatitis A • a reduced-dose schedule for post- which include universal use in children, use in should receive exposure prophylaxis postexposure prophylaxis, and preexposure the HAV vaccine. • proof of immunity against mumps, mea- protection for travelers.2,3 sles, and rubella for health care workers • recommendations for boosters. ACIP still prefers combination vaccines, with caveats Increasing numbers of vaccine products with Adoptive families need more multiple antigens have reduced the number protection against HAV of injections needed to complete the recom- Each year, approximately 18,000 children mended childhood immunization schedule. are adopted from foreign countries, almost Th ese new products also create a situation in all of them born in countries with high or in- which parents and physicians have to choose termediate rates of HAV, 85% of them under between using the combination products or 5 years of age.1 Identifying adoptees with an staying with component vaccines that contain acute HAV is problematic, because fewer antigens, but necessitate a larger num- in this age group, fewer than 10% of infected ber of injections. children manifest jaundice.1 Th e Centers for When ACIP considered this dilemma, Disease Control and Prevention (CDC) has re- committee members gave the general prefer- corded a small number of cases of acute HAV ence to combination vaccines. At the same infection traced back to exposure to adoptees, time, the committee acknowledged that many and there is some evidence that 1% to 6% of considerations—storage, costs, number of new international adoptees have acute, and injections, vaccine availability, infectious, HAV.1 status, likelihood of improved coverage, likeli-

JFPONLINE.COM VOL 59, NO 3 | MARCH 2010 | THE JOURNAL OF FAMILY PRACTICE 155 TABLE HPV vaccines: A side-by-side comparison

HPV4 HPV2

Year licensed 2006 2009

Virus-like particle types 6, 11, 16, 18 16,18

Hypersensitivity-related contraindication Yeast Latex

Schedule 0, 2, 6 months 0, 1, 6 months

Age range 9-26 years 10-25 years

hood of return visits, patient preference, and 6 months of life should be used only for those the potential for adverse events—factor into traveling overseas.6 the decision.4 ❚ MMRV is a special case. One combi- nation product received special attention Resume normal Hib schedule because of the potential for increased rates With the licensure of a new Hib product (Hi- An ACIP- of febrile seizures. Combined measles, berix, GlaxoSmithKline) for the booster dose commissioned mumps, rubella, and varicella (MMRV) vac- of Hib starting at age 15 months, the supply study found that cine is currently in short supply, but when of has stabilized. Supply is now the 4-dose the supply improves it will provide 1 less adequate to resume all 4 doses in the routine rabies vaccine injection to immunize against 4 childhood schedule and to recall all children who had series achieved viral at each of 2 visits. However, their booster dose deferred. Children can be the same there is good evidence that in children 1 to 2 vaccinated with Hib through the age of 59 antibody levels years of age who are receiving the fi rst dose months (prior to their fi fth birthday).7 as the of MMRV, there is an additional incidence 5-dose series. of febrile seizures of 1 in every 2300 to 2600, compared with children receiving separate 2 HPV vaccines are now available doses of MMR and varicella vaccines.5 Th ere With the licensure of an HPV2 vaccine for is no increased risk for older children or for use in women in the United States (, the second dose. GlaxoSmithKline), 2 HPV vaccine products ACIP considered this risk and recom- are now available for use.8 An HPV4 vaccine mends discussing the benefi ts and risks of (, Merck & Co.) was licensed in 2006. MMR and varicella separately vs using the Th e TABLE compares the composition, dosing MMRV combination vaccine. Th e commit- schedules, and precaution for these 2 prod- tee notes: “Use of MMR and varicella vaccines ucts. Each requires 3 doses, but the age rang- avoids [the] increased risk for and febrile es and dosing schedules are slightly diff erent. seizures following MMRV vaccine.”5 Th e HPV4 vaccine contains antigens against HPV types 16 and 18, which cause 70% of cer- vical cancers and precancerous lesions, and IPV combination dosing is clarifi ed types 6 and 11, which cause 90% of anogeni- Th e inclusion of inactivated poliovirus (IPV) tal warts.9 antigen into new combination vaccine prod- Th e HPV2 vaccine contains antigens for ucts has caused some confusion over the HPV types 16 and 18 only and does not pro- recommended dosing schedule of polio vac- tect against warts. Th e bivalent product ap- cine. ACIP has now clarifi ed that for the rec- pears to produce a higher level of antibody ommended 4-dose IPV schedule, the fourth response and may provide better cross protec- dose should be administered after age 4 and tion against other HPV types. ACIP compared at least 6 months after dose 3. In addition, eff ectiveness studies of both vaccines and de- the minimal intervals (4 weeks) in the fi rst cided to show no preference for either vaccine

156 THE JOURNAL OF FAMILY PRACTICE | MARCH 2010 | VOL 59, NO 3 IMMUNIZATION UPDATE

for the prevention of cervical cancer and pre- Rabies vaccine: 4 doses cancerous lesions. are suffi cient Th e recommendation is for routine vac- Due to a threatened shortage of rabies vac- cination with an HPV product for all adoles- cine, ACIP commissioned a study to deter- cent girls ages 11 to 12, with catch-up through mine if a 4-dose series might be as eff ective age 26. If a female wants protection against as the licensed 5-dose series. Th e results anogenital warts, HPV4 is recommended. It is showed that a reduced-dose series achieved preferable to complete a 3-dose series with the equivalent antibody levels, so ACIP voted to same product, but if this is not possible, a series recommend 4 doses of vaccine at days 0, 3, can be completed with the other product. Th e 7, and 14 postexposure.12 Th e vaccine should HPV4 vaccine is made using yeast, and pre- be part of a 3-pronged approach to prevent fi lled HPV2 syringes contain latex. Hypersensi- rabies after an exposure, along with rabies tivity to these substances is a contraindication immune globulin administration and wound to their use. Patients who receive either vaccine cleaning.13 Th e 4-dose schedule diff ers from should be observed for 15 minutes after the in- the rabies vaccine package inserts and the jection to prevent injury from syncope. FDA licensure information. ❚ HPV4 in men. Th e HPV4 vaccine has now been licensed in the United States for use in males ages 9 to 26 to prevent anogeni- Tougher immunity criteria tal warts. It may also protect against HPV- for health care personnel ACIP now caused cancers (oral, genital, and anal), but Prior to 2009, criteria for proof of immunity recommends the proof of that is still lacking. ACIP debated to measles, mumps, or rubella among health that individuals whether to recommend HPV4 for boys rou- care workers included serologic testing, his- previously tinely at age 11 to 12 and decided against this. tory of 2 vaccines after age 1, physician-diag- vaccinated with Instead the group voted for a “permissive” nosed disease, or being born prior to 1957. Th e either MCV4 or recommendation that states HPV4 may be new criteria require laboratory confi rmation MPSV4 who are given to adolescents and young men ages 9 to of a physician diagnosis and add a footnote to at prolonged 26 to prevent warts and that protection is bet- the “born before 1957” criterion that states: In- increased risk ter if it is administered before exposure.10 Th is stitutions with unvaccinated health care work- be revaccinated allows vaccine use in young males to be pro- ers who lack laboratory evidence of immunity with MCV4. vided in the Vaccines for Children Program, should consider vaccinating them with 2 doses but falls short of including it in the routine of MMR (for measles and mumps) and 1 dose vaccine schedules. of MMR (for rubella). In an outbreak, the new Th e reasons for not recommending standards recommend inoculating unvacci- HPV4 routinely in young men were the cost nated health care personnel who do not have and the perception that anogenital warts are serological proof of immunity with 2 doses for primarily a cosmetic problem, although it outbreaks of measles or mumps and 1 dose was acknowledged that they can cause seri- during an outbreak of rubella.14,15 ous psychological morbidity. ACIP acknowl- edged that using HPV4 in men might lead to more protection for women because viral Meningococcal booster spread would be reduced, but stated that for those at high risk much more protection for women would ACIP now recommends quadrivalent meningo- be gained from a higher level of vaccination coccal (MCV4) for all teens among women. As the evidence of protec- ages 11 to 18 years and for anyone 2 to 55 years tion against HPV-related cancers in men of age who is at increased risk for meningococ- is gathered, ACIP will probably revisit this cal disease.16 MCV4 is licensed as a single dose. recommendation. Because of the high risk for meningococ- For a more detailed discussion of the is- cal disease among certain groups of people, sues posed by these 2 vaccines, see “Th e case as well as limited data on duration of protec- for HPV immunization” in the Journal of Fam- tion, ACIP now recommends that individu- ily Practice, December 2009.11 als previously vaccinated with either MCV4

JFPONLINE.COM VOL 59, NO 3 | MARCH 2010 | THE JOURNAL OF FAMILY PRACTICE 157 or meningococcal polysaccharide vaccine New (MPSV4) who are at prolonged increased risk with more coverage be revaccinated with MCV4. A new pneumococcal conjugate vaccine Th ose who were previously vaccinated at (PCV13) for infants and children will be li- 7 years of age or older should be revaccinated censed soon. It will replace the PCV7 vac- 5 years after their previous meningococcal cine now recommended routinely. ACIP will vaccine; individuals who were previously make recommendations on how to introduce vaccinated at ages 2 to 6 years should be re- PCV13 into a schedule for infants and chil- vaccinated 3 years after their previous me- dren who are in the middle of a PCV7 series, ningococcal vaccine. and for catch-up vaccination for children Individuals at prolonged risk for menin- who have completed a PCV7 series. gococcal disease are those with complement Th e new vaccine will provide added component defi ciencies or anatomic or func- protection against an additional 6 types of tional asplenia, microbiologists who rou- pneumococcal bacteria, and will replace the tinely work with Neisseria meningitides, and older product immediately after licensure. It travelers to countries where meningococcal is unclear what will become of unused sup- disease is hyperendemic or epidemic. plies of PCV7. Physicians who need to order College freshmen living in dormitories PCV7 in this interim period before the new who were previously vaccinated with MCV4 vaccine is licensed will be faced with diffi cult A new do not need to be revaccinated. However, col- choices. Th e options include ordering only pneumococcal lege freshmen living in dormitories who were small quantities or trying to get an advance conjugate vaccinated with MPSV4 ≥5 years previously commitment from the manufacturers to take vaccine (PCV13) should be vaccinated with MCV4. back any unused vaccine. JFP for infants and children will be licensed References soon. It will 1. Centers for Disease Control and Prevention. Updated recom- 9. Centers for Disease Control and Prevention. Quadrivalent hu- replace the PCV7 mendations from the ACIP for use of in close man papillomavirus vaccine: recommendations of the Advi- contacts of newly arriving international adoptees. MMWR Morbid sory Committee on Immunization Practices (ACIP). MMWR vaccine now Mortal Wkly Rep. 2009;58:1006-1007. Available at: www.cdc.gov/ Morb Mortal Wkly Rep. 2007;56(RR-2):1-24. Available at: http:// recommended mmwr/preview/mmwrhtml/mm5836a4.htm. Accessed January www.cdc.gov/mmwr/pdf/rr/rr5602.pdf. Accessed February 19, 2010. 2, 2010. routinely. 2. Centers for Disease Control and Prevention. Update: prevention 10. Meeting of the Advisory Committee on Immunization Practices. of hepatitis A after exposure to hepatitis A virus and in interna- October 21-22, 2009, Atlanta, GA. Available at: www.cdc.gov/ tional travelers. Updated recommendations of the ACIP. MMWR vaccines/recs/ACIP/livemeeting-Oct09.htm#hpv. Accessed Jan- Morbid Mortal Wkly Rep. 2007;56:1080-1084. Available at: www. uary 21, 2010. cdc.gov/mmwr/preview/mmwrhtml/mm5641a3.htm. Accessed 11. Campos-Outcalt D. Th e case for HPV immunization.J Fam Pract. January 19, 2010. 2009;58:660-664. 3. Centers for Disease Control and Prevention. Prevention of hepa- 12. ACIP provisional recommendations for the prevention of human titis A through active or passive immunization: recommendation rabies. July 10, 2009. Available at: www.cdc.gov/vaccines/recs/ of the ACIP. MMWR Recomm Rep. 2006;55(RR-7):1-23. Available provisional/downloads/rabies-July2009-508.pdf. Accessed Janu- at: www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm. Ac- ary 28, 2010. cessed January 19, 2010. 13. Centers for Disease Control and Prevention. Human rabies pre- 4. ACIP provisional recommendations for the use of combination vention—United States, 2008: Recommendations of the ACIP. vaccines. August 28, 2009. Available at: www.cdc.gov/vaccines/ MMWR Morbid Mortal Wkly Rep. 2008;57(early release):1-26, recs/provisional/downloads/combo-vax-Aug2009-508.pdf. 28. Available at: www.cdc.gov/mmwr/preview/mmwrhtml/ Accessed January 18, 2010. rr57e507a1.htm. Accessed January 28, 2010. 5. ACIP provisional recommendations for use of measles, mumps, 14. Advisory Committee on Immunization Practices summary re- rubella and varicella (MMRV) vaccine. October 20, 2009. Avail- port. June 24-26, 2009. Available at: http://www.cdc.gov/vac- able at: www.cdc.gov/vaccines/recs/provisional/downloads/ cines/recs/ACIP/downloads/min-jun09.pdf. Accessed January mmrv-oct2009-508.pdf. Accessed January 19, 2010. 28, 2010. 6. Centers for Disease Control and Prevention. Update recom- 15. ACIP provisional recommendations for measles-mumps-rubella mendations of the ACIP regarding routine poliovirus vaccina- (MMR) “evidence of immunity” requirements for healthcare per- tion. MMWR Morbid Mortal Wkly Rep. 2009;58:829-830. Avail- sonnel. August 28, 2009. Available at: www.cdc.gov/vaccines/recs/ able at: www.cdc.gov/mmwr/preview/mmwrhtml/mm5830a3. provisional/downloads/mmr-evidence-immunity-Aug2009-508. htm?s-cid=mr. Accessed January 20, 2010. pdf. Accessed January 28, 2010. 7. Centers for Disease Control and Prevention. Provider letter, July 16. Centers for Disease Control and Prevention. Updated recom- 30, 2009. Available at: www.cdc.gov/vaccines/vac-gen/shortages/ mendation from ACIP for revaccination of persons at prolonged downloads/Hib-hcp-ltr-7-30-09.pdf. Accessed February 15, 2010. increased risk for meningococcal disease. MMWR Morb Mortal 8. ACIP provisional recommendations for HPV vaccine. December Wkly Rep. 2009;58:1042-1043. Available at: www.cdc.gov/mmwr/ 1, 2009. Available at: www.cdc.gov/vaccines/recs/provisional/ preview/mmwrhtml/mm5837a4.htm. Accessed January 20, downloads/hpv-vac-dec2009-508.pdf. Accessed January 18, 2010. 2010.

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