Postexposure Management of Vaccine-Preventable Diseases

      Abstract

      Because some parents are choosing to not vaccinate or only partially vaccinate their children, vaccine-preventable diseases that once were rarely seen in pediatric practice must now be considered part of the differential diagnosis when caring for these children. Measles, mumps, varicella, meningococcal disease, pertussis, and influenza are reviewed. Recommendations for prevention and treatment of these vaccine-preventable diseases are discussed.

      Key Words

      Teri Moser Woo, PhD, RN, ARNP, CNL, CPNP, FAANP
      Corresponding Editor
      Pacific Lutheran University
      Tacoma, Washington
      Elizabeth Farrington, PharmD, FCCP, FCCM, FPPAG, BCPS
      University of North Carolina, Eshelman School of Pharmacy
      Chapel Hill, North Carolina
      New Hanover Regional Medical Center
      Wilmington, North Carolina
      Leah Molloy, PharmD
      Children's Hospital of Michigan
      Detroit, Michigan
      • 1.
        Review current child and adolescent vaccination rates in the United States.
      • 2.
        Discuss vaccine-preventable diseases currently experiencing outbreaks in the United States.
      • 3.
        Review management of vaccine-preventable diseases.
      In 2000, measles was declared eliminated in the United States as a result of high two-dose measles vaccine immunization rates, yet in 2014, 600 cases of measles were reported in the United States, and in 2015, 189 cases were reported through October 15 (
      • Centers for Disease Control and Prevention
      Measles cases and outbreaks.
      ). In 2014 there were 1,223 confirmed cases of mumps in the United States (
      • Centers for Disease Control and Prevention
      Mumps cases and outbreaks.
      ), including an outbreak that affected six National Hockey League teams (). Outbreaks of serotype B meningococcal disease on multiple college campuses in 2014 and 2015 created the need for a U.S.-approved vaccine to provide immunity. It is clear that when children and adolescents are not vaccinated, outbreaks of vaccine-preventable diseases will occur. Current immunization rates in the United States, recent vaccine-preventable disease outbreaks, and care of children and adolescents exposed during an outbreak will be reviewed.
      It is clear that when children and adolescents are not vaccinated, outbreaks of vaccine-preventable diseases will occur.

      Current Immunization Coverage

      Healthy People 2020 set goals for vaccination coverage levels for universally recommended vaccines among young children ages 19 to 35 months of age, children in kindergarten, and adolescents (
      • Office of Disease Prevention and Health Promotion
      2020 Topics & objectives: Immunization and infectious diseases, Healthy People 2020.
      ). Healthy People 2020 set a vaccine coverage goal of 90% of children aged 19 to 35 months to receive four doses of diphtheria-tetanus-acellular pertussis (DTaP) vaccine, three or four doses of Haemophilus influenzae type b (Hib) vaccine, three doses of polio vaccine, three doses of hepatitis B (HBV) vaccine, one dose of measles-mumps-rubella (MMR) vaccine, one dose of varicella vaccine, and four doses of pneumococcal conjugate vaccine. For children entering kindergarten, Healthy People 2020 set a goal of 95% vaccine coverage for four doses of DTaP vaccine, three doses of polio vaccine, three doses of HBV vaccine, and two doses each of MMR and varicella vaccine. The goal for adolescents aged 13 to 15 years is for 80% to receive one dose of tetanus-diphtheria-acellular pertussis (Tdap) vaccine, one dose of meningococcal conjugate vaccine, and three doses of human papillomavirus (HPV) vaccine and for 90% to receive two doses of varicella vaccine (
      • Office of Disease Prevention and Health Promotion
      2020 Topics & objectives: Immunization and infectious diseases, Healthy People 2020.
      ).

      Current Coverage in Children Ages 19 to 35 Months

      Since 1994, vaccination coverage among U.S. children ages 19 to 35 months has been monitored annually via the National Immunization Survey. In 2014, 71.4% of children received the combined (4:3:1:3:3:1:4) vaccine series, which includes four doses of DTaP vaccine, three doses of poliovirus vaccine, one dose of measles-containing vaccine, the full series of Hib vaccine (three or four doses, depending on product type), three doses of HBV vaccine, one dose of varicella vaccine, and four doses of pneumococcal conjugate vaccine (
      • Hill H.A.
      • Elam-Evans L.D.
      • Yankey D.
      • Singleton J.A.
      • Kolasa M.
      National, state, and selected local area vaccination coverage among children aged 19-35 months—United States, 2014.
      ). Healthy People 2020 coverage goals of 90% were achieved for polio, hepatitis B, one dose of MMR, and varicella. Of children aged 19 to 25 months, 94.7% had received three doses of DTaP vaccine, but only 84.2% were fully immunized with four doses. Likewise, 93.3% of preschoolers had received the primary series of Hib, and 82% were fully vaccinated for Hib (
      • Hill H.A.
      • Elam-Evans L.D.
      • Yankey D.
      • Singleton J.A.
      • Kolasa M.
      National, state, and selected local area vaccination coverage among children aged 19-35 months—United States, 2014.
      ). Only 0.8% of U.S. children had received no vaccines by age 35 months (
      • Hill H.A.
      • Elam-Evans L.D.
      • Yankey D.
      • Singleton J.A.
      • Kolasa M.
      National, state, and selected local area vaccination coverage among children aged 19-35 months—United States, 2014.
      ).

      Current Coverage Among Kindergartners

      The CDC monitors school vaccine data to determine vaccine coverage rates for children attending kindergarten. In the 2014-2015 academic school year, the median coverage for kindergarteners was 94% for three doses of MMR vaccine, 93.6% for two doses of varicella vaccine, and 94.2% for DTaP vaccine (
      • Seither R.
      • Calhoun K.
      • Knighton C.L.
      • Mellerson J.
      • Meador S.
      • Tippins A.
      • Dietz V.
      • et al.
      Vaccination coverage among children in kindergarten—United States, 2014-2015 school year.
      ). The Healthy People 2020 goal of 95% coverage at kindergarten entry was only achieved by 18 states in the 2014-2015 survey (
      • Seither R.
      • Calhoun K.
      • Knighton C.L.
      • Mellerson J.
      • Meador S.
      • Tippins A.
      • Dietz V.
      • et al.
      Vaccination coverage among children in kindergarten—United States, 2014-2015 school year.
      ). States with high rates of exemption from vaccines had lower vaccination rates. Mississippi, which does not allow exemptions (less than 0.1%), had the highest kindergarten vaccination rates at greater than 99.2% (
      • Seither R.
      • Calhoun K.
      • Knighton C.L.
      • Mellerson J.
      • Meador S.
      • Tippins A.
      • Dietz V.
      • et al.
      Vaccination coverage among children in kindergarten—United States, 2014-2015 school year.
      ).

      Current Coverage in Adolescents

      Adolescent immunization rates are derived from the National Immunization Survey–Teen. In 2014, 87.6% of adolescents had received one dose of Tdap vaccine, and 79.3% had received one dose of meningococcal conjugate vaccine (
      • Reagan-Steiner S.
      • Yankey D.
      • Jeyarajah J.
      • Elam-Evans L.D.
      • Singleton J.A.
      • Curtis R.
      • Stokley S.
      • et al.
      National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years—United States, 2014.
      ). Sixty percent of adolescent females and 41.7% of males had received one dose of HPV vaccine in 2014. The three-dose completion rate (i.e., the percentage of adolescents who received ≥3 HPV vaccine doses among those who had ≥1 HPV vaccine dose) in 2014 for HPV was 69.3% for females and 57.8% for males (
      • Reagan-Steiner S.
      • Yankey D.
      • Jeyarajah J.
      • Elam-Evans L.D.
      • Singleton J.A.
      • Curtis R.
      • Stokley S.
      • et al.
      National, regional, state, and selected local area vaccination coverage among adolescents aged 13-17 years—United States, 2014.
      ). The percentage of adolescents who had either received two doses of varicella vaccine or had a history of disease was 85.0% in 2015. The highest vaccination coverage rates in adolescents in 2014 were MMR (90.7% had received two doses) and hepatitis B (91.4% had received three doses).

      Management of Vaccine-Preventable Disease Outbreaks

      For a variety of reasons, including concerns regarding vaccine safety and immune system overload (
      • Hulsey E.
      • Bland T.
      Immune overload: Parental attitudes toward combination and single antigen vaccines.
      ), some parents are choosing to not fully vaccinate their children and adolescents. Low vaccination rates have led to outbreaks of vaccine-preventable diseases across the United States. Diseases that once were rarely seen in pediatric practice must now be part of the differential diagnosis when providing care for unvaccinated or partially vaccinated children.
      Diseases that once were rarely seen in pediatric practice must now be part of the differential diagnosis when providing care for unvaccinated or partially vaccinated children.

      Measles

      The measles vaccine was developed in 1963, and measles was declared eliminated from the United States in 2000 (). Although measles was considered eliminated from the United States, it remains endemic around the world, including Europe, Asia, and the Pacific. With international travel, measles is easily imported, and unvaccinated children are at risk of developing measles. The Philippines is thought to be the source of multiple U.S. measles outbreaks, including a large multistate outbreak linked to visits to Disneyland in December 2014 (
      • Centers for Disease Control and Prevention
      Measles cases and outbreaks.
      ). Because of the high risk of exposure to measles with international travel, it is recommended that all infants 6 months or older receive at least one dose of MMR vaccine before traveling internationally and that children older than 12 months receive two doses of MMR vaccine separated by 28 days (
      • McLean H.Q.
      • Fiebelkorn A.P.
      • Temte J.L.
      • Wallace G.S.
      Prevention of measles, rubella, congenital rubella syndrome, and mumps, 2013: Summary recommendations of the Advisory Committee on Immunization Practices (ACIP).
      ).
      Measles is a highly contagious respiratory virus characterized by fever (which may be as high as 40.5°C), cough, coryza, and conjunctivitis (known as “the three C's”), and a maculopapular rash. The incubation period is 7 to 14 days, with the rash appearing approximately 14 days after exposure. The period of contagiousness is from 4 days before to 4 days after the rash appears. Treatment of children with measles is symptomatic, although vitamin A is recommended for all infants and children with measles to decrease morbidity and mortality. Vitamin A (50,000 IU for infants younger than 6 months; 100,000 IU for infants ages 6 through 11 months; and 200,000 IU for children ages 12 months or older) is administered once daily for 2 days to all children with severe measles. Any patient who is not immune to measles should be offered postexposure prophylaxis to prevent or modify the disease severity.
      Postexposure prophylaxis may be either a dose of MMR vaccine or immunoglobulin (IG). MMR vaccine may be administered to immunocompetent patients aged 12 months or older within 72 hours of measles exposure. Immunocompromised patients, pregnant women, and infants younger than 12 months should receive IG (
      • American Academy of Pediatrics
      Measles.
      ). Infants younger than 12 months may receive intramuscular IG (0.5 ml/kg, maximum 3 ml). Pregnant women who do not have immunity against measles and immunocompromised patients should receive intravenous (IV) IG. Dosing of IG is provided in Table 1. If IG is administered, the measles vaccine should be administered 6 months after the IG dose if the child is at least 12 months of age (
      • American Academy of Pediatrics
      Measles.
      ).
      Table 1Postexposure prophylaxis treatment of vaccine-preventable diseases
      Data from Kimberlin, D. W., Brady, M. T., Jackson, M. A., & Long, S. S. (Eds.). (2015). Red book report of the Committee on Infectious Diseases. Elk Grove Village, IL: American Academy of Pediatrics.
      DiseaseVulnerable populationProphylaxisComments
      MeaslesUnvaccinated persons or those who have only had one dose of vaccine

      Infants < 12 months of age, pregnant women without evidence of immunity, immunocompromised persons, bone marrow transplant patients (until 12 months after finishing immunosuppressive treatment), patients receiving treatment for ALL (until 6 months after completion of chemotherapy), and patients with HIV or AIDS with severe immunosuppression
      Measles vaccine: if given within 72 hours of measles exposure

      IG: IG IM or IG IV can be administered within 6 days of exposure to prevent or modify measles; the recommended dose of IG IM is 0.5 ml/kg, given IM (maximum 15 ml)

      IG IV 400 mg/kg is recommended for pregnant women without evidence of immunity and those who are severely immunocompromised
      Immunization is the intervention of choice for most vaccine-eligible people 12 months or older; children who receive IG for prophylaxis should receive the measles vaccine 6 months after IG administration, after the child is 12 months of age

      Pregnant women should not be administered MMR vaccine
      Varicella-zoster diseaseHealthy people age 12 months or older who are unimmunized

      Immunocompromised children with no evidence of immunity
      Varicella vaccine: Administer one dose of varicella vaccine within 3 to 5 days of exposure

      VariZIG: Administer VariZIG as soon as possible (within 10 days of exposure)

      VariZIG IM dose:

      Weight ≤ 2 kg: 62.5 units (0.5 vial)

      Weight 2.1 to 10 kg: 125 units (1 vial)

      Weight 10.1 to 20 kg: 250 units (2 vials)

      Weight 20.1 to 30 kg: 375 units (3 vials)

      Weight 30.1 to 40 kg: 500 units (4 vials)

      Weight > 40 kg: 625 units (5 vials)
      A second dose of varicella vaccine is administered at an age appropriate interval

      IVIG may be administered if VariZIG is not available; dose is 400 mg/kg IV
      Meningococcal diseaseClose contacts of infected persons are considered high risk:

      Household contacts, especially children < 2 years of age

      People who frequently sleep in the same house as the initial contact in the 7 days prior to onset of illness

      Child care or preschool contacts within 7 days of onset of illness

      Unprotected mouth-to-mouth resuscitation or unprotected contact during intubation at any time 7 days before onset of illness

      Airline passenger seated next to index case on a flight > 8 hr
      Ceftriaxone:

      < 15 years: 125 mg IM × 1 dose

      > 15 years: 250 mg IM × 1 dose

      Rifampin:

      < 1 month of age: 5 mg/kg every 12 hr for 2 days

      ≥ 1 month of age: 10 mg/kg (maximum 600 mg) for 2 days

      Ciprofloxacin:

      ≥ 1 month of age: 20 mg/kg (maximum 500 mg) in a single dose

      Azithromycin:

      10 mg/kg (maximum 500 mg) in a single dose
      Ceftriaxone:

      Safe in most patients, including pregnant women

      Rifampin:

      Not recommended for pregnant women

      Drug interactions

      Ciprofloxacin:

      Not recommended for pregnant women

      Do not use if resistant Neisseria meningitides is prevalent in the local area

      Azithromycin:

      Not routinely recommended
      PertussisHigh-risk patients:

      Infants

      Women in the third trimester of pregnancy

      Persons with pre-existing health conditions that may be exacerbated by pertussis (e.g., moderate to severe asthma, immunocompromised)

      Contact of high-risk patients:

      Care providers

      All contacts in high-risk settings that include infants < 12 months or women in the third trimester of pregnancy (neonatal care units, child care settings, maternity wards)
      Azithromycin:

      Infants < 1 month through 5 months: 10 mg/kg/day for 5 days

      Children ≥ 6 months: 10 mg/kg on day 1 (maximum 500 mg), 5 mg/kg/day on days 2 to 5 (maximum 250 mg/day)

      Adolescents and adults: 500 mg on day 1, 250 mg daily on days 2 to 5

      Erythromycin:

      Infants aged ≥ 1 month and older children: 40-50 mg/kg per day (maximum: 2 g per day) in 4 divided doses for 14 days

      Adults: 2 g per day in 4 divided doses for 14 days

      Clarithromycin:

      Infants and children aged ≥ 1 month: 15 mg/kg per day (maximum: 1 g per day) in 2 divided doses each day for 7 days

      Adults: 1 g per day in two divided doses for 7 days

      TMP–SMZ (alternate agent):

      Infants aged < 2 months: contraindicated

      Infants aged ≥ 2 months and children: trimethoprim 8 mg/kg per day, sulfamethoxazole 40 mg/kg per day in 2 divided doses for 14 days

      Adults: trimethoprim 320 mg per day, sulfamethoxazole 1,600 mg per day in 2 divided doses for 14 days
      Contacts may be treated within 21 days of exposure to onset of cough in index case

      All unimmunized or underimmunized contacts should receive DTaP or Tdap vaccine
      Note. ALL, acute lymphocytic leukemia; IG, immunoglobulin; IM, intramuscular; IV, intravenous.

      Mumps

      The mumps vaccine was licensed in the United States in 1967 and is currently available only in combination with measles and rubella vaccines, in MMR and MMRV. The mumps vaccine is considered to be 78% effective after one dose and 88% effective after two doses (
      • American Academy of Pediatrics
      Mumps.
      ); therefore, if there is a mumps outbreak in the community, a number of cases will be seen even in those who are fully immunized. Routine two-dose vaccination with MMR vaccine has reduced mumps outbreaks 99% below prevaccine era numbers, but outbreaks are still seen in schools, colleges, camps, and, as seen in 2014, sports teams (
      • Centers for Disease Control and Prevention
      Mumps cases and outbreaks.
      ).
      The mumps virus is spread via respiratory secretions and saliva. Symptoms of mumps include fever, headache, anorexia, and swelling of the salivary glands, usually the parotid glands (parotitis;
      • American Academy of Pediatrics
      Mumps.
      ). Mumps may be asymptomatic or subclinical with no salivary gland swelling. Viral meningitis can develop in patients with mumps (in 10% of cases), and orchitis may develop in males (
      • American Academy of Pediatrics
      Mumps.
      ). Patients may have the mumps virus present in their saliva from 7 days prior to parotitis until 8 days after swelling of the salivary glands occurs. It is recommended that infected persons be isolated for 5 days after parotitis develops, and children should be excluded from day care and school during this time (
      • American Academy of Pediatrics
      Mumps.
      ).
      The incubation period of mumps is 16 to 18 days (
      • American Academy of Pediatrics
      Mumps.
      ). Unlike measles, the mumps vaccine is not effective in preventing infection if it is administered after exposure. It is recommended that the MMR vaccine be administered to protect against future exposures. IG is not effective in preventing postexposure mumps (
      • American Academy of Pediatrics
      Mumps.
      ).
      During a mumps outbreak, all unimmunized persons 12 months or older should be vaccinated with MMR vaccine, and a second dose of MMR vaccine should be offered to students and health care personnel born after 1957 who only received one dose of MMR (
      • American Academy of Pediatrics
      Mumps.
      ). A local outbreak may prompt a second dose to be administered to preschoolers depending on the epidemiology of the outbreak (
      • Fiebelkorn A.P.
      • Barskey A.
      • Hickman C.
      • Bellini W.
      Mumps (Chapter 9).
      ). A third dose of MMR vaccine may be recommended by the public health authorities in certain circumstances, including when there is a high two-dose vaccination rate (greater than 90%); intense exposure settings (e.g., schools, colleges, correctional facilities, group living facilities, or health care facilities); or high attack rates (more than 5 cases per 1,000 population) and evidence of ongoing transmission for at least 2 weeks in the population with high attack rates (
      • Fiebelkorn A.P.
      • Barskey A.
      • Hickman C.
      • Bellini W.
      Mumps (Chapter 9).
      ).

      Varicella

      In 1995, universal vaccination with varicella vaccine was implemented in the United States, leading to a 95% reduction in varicella disease between 1995 and 2005 (
      • American Academy of Pediatrics
      Varicella-zoster virus infections.
      ). The varicella vaccine provides approximately 86% effectiveness after one dose and 98% after two doses (
      • American Academy of Pediatrics
      Varicella-zoster virus infections.
      ). In 2006, the Advisory Committee on Immunization Practices (ACIP) recommended a second dose of varicella vaccine at age 4 to 6 years. The second dose may be administered at an earlier age during an outbreak if 3 months have passed since the first dose (
      • Marin M.
      • Guris D.
      • Chaves S.S.
      • Schmid S.
      • Seward J.F.
      Prevention of varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP).
      ). Breakthrough cases of varicella can occur in vaccinated children, but they are less likely to occur in children who have received two doses of vaccine.
      Varicella is highly contagious and spreads from human to human via contact with infected persons or via respiratory secretions. The symptoms of varicella infection, commonly known as chicken pox, are a prodromal period of fever, headache, and anorexia, followed by a pruritic, vesicular rash that has various stages, from vesicles to crusting. Immunocompromised patients, patients with HIV or AIDS, and pregnant women are at risk for severe disease. The incubation period for varicella is 14 to 16 days, and patients are contagious from 1 to 2 days before the rash appears until all lesions are crusted over (
      • American Academy of Pediatrics
      Varicella-zoster virus infections.
      ).
      High-risk patients with varicella may be treated with antiviral agents to modify the severity of disease, although the antiviral drugs need to be started in the first 72 hours of illness to be effective. Oral acyclovir or valacyclovir may reduce the severity of disease in unvaccinated persons older than 12 years, persons with chronic skin or pulmonary disorders, and persons receiving long-term aspirin therapy or who are taking corticosteroids, including short-term or aerosolized corticosteroids (
      • American Academy of Pediatrics
      Varicella-zoster virus infections.
      ). IV acyclovir is the drug of choice in immunocompromised patients. Antiviral agents generally are not recommended for use in otherwise healthy children.
      Prophylaxis for unvaccinated persons exposed to varicella consists of either varicella vaccine or varicella Ig (VariZIG, Cangene bioPharma, Inc., Baltimore, MD). After exposure to prevent varicella disease, the varicella vaccine may be administered within 3 days (when it is 90% effective) and for up to 5 days, when it is 70% effective (
      • Marin M.
      • Guris D.
      • Chaves S.S.
      • Schmid S.
      • Seward J.F.
      Prevention of varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP).
      ). VariZIG is recommended in unimmunized immunocompromised patients, newborn infants whose mothers have signs and symptoms of varicella around delivery (5 days before to 2 days after delivery), hospitalized premature infants born at 28 week's gestation or later whose mothers do not have immunity to varicella, hospitalized premature infants born at less than 28 week's gestation regardless of maternal immunity, and pregnant women without evidence of immunity. VariZIG should be administered as soon as possible after exposure, preferably within 96 hours, but it may be administered up to 10 days after exposure (
      • American Academy of Pediatrics
      Varicella-zoster virus infections.
      ). If VariZIG is not available, IV IG may be administered. See Table 1 for prophylaxis recommendations.

      Meningococcal Disease

      Meningococcal disease is a bacterial disease caused by Neisseria meningitides, which has 13 serotypes. The serotypes or strains known to cause invasive disease include A, B, C, Y, and W (
      • American Academy of Pediatrics
      Varicella-zoster virus infections.
      ). Serotype A is found primarily in sub-Saharan Africa. Serotype B outbreaks have occurred in New Zealand, France, and Oregon (
      • American Academy of Pediatrics
      Varicella-zoster virus infections.
      ). Several outbreaks of serotype B meningococcal disease have occurred on college campuses in the United States in New Jersey (Princeton University), California (University of California–Santa Barbara), and Oregon (University of Oregon) in 2014 and 2015. In summer 2015, an outbreak of type C meningococcal disease occurred in Chicago among men who have sex with men (
      • Kamiya H.
      • MacNeil J.
      • Blain A.
      • Patel M.
      • Martin S.
      • Weiss D.
      • Misegades L.
      • et al.
      Notes from the field: Meningococcal disease among men who have sex with men—United States, January 2012-June 2015.
      ). The Hajj pilgrimage in Saudi Arabia has been associated with outbreaks of serotype W meningococcal disease. Serotype W outbreaks have also been reported in sub-Saharan Africa and South America (
      • American Academy of Pediatrics
      Varicella-zoster virus infections.
      ).
      Four meningococcal vaccines licensed in the United States are active against serotypes A, C, Y, or W. In 1981 a meningococcal polysaccharide vaccine (Menomune, Sanofi Pasteur Inc., Bridgewater, NJ) active against serotypes A, C, Y, and W was approved for use in children ages 2 years or older. Two meningococcal conjugate vaccines (MenACWY-D [Menactra, Sanofi Pasteur Inc.] and MenACWY-CRM [Menveo, Novartis Vaccines and Diagnostics Inc., Cambridge, MA]) have been approved for use in patients 9 to 55 years of age. HibMenCY-TT (MenHibrix, GlaxoSmithKline Biologicals, Rixensart, Belgium) a meningococcal conjugate vaccine, is approved for infants and children ages 6 weeks through 18 months of age (
      • American Academy of Pediatrics
      Meningococcal infections.
      ). In 2014, a serotype B vaccine, MenB-FHbp (Trumenba, Pfizer, New York, NY), was approved for use in persons ages 10 to 25 years (
      • MacNeil J.R.
      • Rubin L.
      • Folaranmi T.
      • Ortega-Sanchez I.R.
      • Patel M.
      • Martin S.W.
      Use of serotype B meningococcal vaccines in adolescents and young adults: Recommendations of the Advisory Committee on Immunization Practices, 2015.
      ). A second serotype B meningococcal vaccine, MenB-4C (Bexsero, Novartis Vaccines and Diagnostics Inc.), was approved for use in 10- to 25-year-olds in the United States in January 2015, although it had previously been approved in Australia, Canada, and Europe and was used as an investigational drug for the campus outbreaks in the United States in 2014 and 2015 (
      • American Academy of Pediatrics
      Meningococcal infections.
      ).
      In 2015 the ACIP issued recommendations for serotype B meningococcal (MenB) vaccines. The ACIP states that the MenB vaccine may be administered to adolescents and young adults ages 16 to 23 years and that the preferred age for MenB vaccination is 15 to 18 years (
      • MacNeil J.R.
      • Rubin L.
      • Folaranmi T.
      • Ortega-Sanchez I.R.
      • Patel M.
      • Martin S.W.
      Use of serotype B meningococcal vaccines in adolescents and young adults: Recommendations of the Advisory Committee on Immunization Practices, 2015.
      ). The two MenB vaccines are not interchangeable, and the vaccine series should be completed with the same vaccine. The MenB-FHbp vaccine (Trumenba) is administered in a three-dose series, and the MenB-4C vaccine (Bexsero) is administered in a two-dose series. The ACIP recommends that MenB also be administered to persons older than age 10 years who have increased risk for meningococcal disease, including persons with persistent complement component deficiencies, persons with anatomic or functional asplenia, persons at increased risk during a serotype B meningococcal disease outbreak, and microbiologists routinely exposed to Neisseria meningitidis (
      • Folaranmi T.
      • Rubin L.
      • Martin S.W.
      • Patel M.
      • MacNeil J.R.
      Use of serotype B meningococcal vaccines in persons ages >10 years at increased risk for serotype B meningococcal disease: Recommendations of the Advisory Committee on Immunization Practices, 2015.
      ).
      Invasive meningococcal disease typically has a sudden onset of fever, chills, malaise, myalgia, and a rash that may be maculopapular, petechial, or purpuric. Meningitis develops in 50% of patients with invasive meningococcal disease, and bacteremia develops in 35% to 40% (
      • American Academy of Pediatrics
      Meningococcal infections.
      ). Invasive meningococcal disease progresses rapidly, with limb ischemia, pulmonary edema, coagulopathies, shock, coma, and death occurring in a matter of hours (
      • American Academy of Pediatrics
      Meningococcal infections.
      ). Infected patients require rapid, intensive treatment with a broad-spectrum antibiotic such as ceftriaxone or cefotaxime, along with treatment of shock. Further discussion of invasive meningococcal disease is outside the scope of this article. It is recommended that close contacts of patients with meningococcal disease, regardless of the strain, to receive chemoprophylaxis to prevent contracting the disease; a single dose of ceftriaxone is the preferred drug (
      • American Academy of Pediatrics
      Meningococcal infections.
      ). See Table 1 for chemoprophylaxis recommendations.

      Pertussis

      More than 200,000 cases of pertussis or “whooping cough” were reported annually before routine pertussis vaccination was implemented in the 1940s (
      • Centers for Disease Control and Prevention
      Pertussis (whooping cough).
      ). Immunity wanes after active infection or immunization, leaving the person vulnerable to pertussis across their life span. In the postvaccine era, outbreaks occur every 3 to 5 years; the most recent outbreaks occurred in 2012 and 2014 with 48,227 and 32,971 cases, respectively, reported to the CDC (
      • Centers for Disease Control and Prevention
      Postexposure antimicrobial prophylaxis.
      ).
      In 1997, the acellular pertussis vaccine was licensed because of adverse effects (fever and discomfort) that sometimes occurred with the original whole-cell vaccine. Pertussis vaccine currently comes combined with tetanus and diphtheria (DTaP). It also may be combined with tetanus, diphtheria, Hib, and polio (Pentacel, Sanofi Pasteur Inc.); with tetanus, diphtheria, and polio (Quadracel, Sanofi Pasteur Inc.); and diphtheria, tetanus, hepatitis B, polio, and Hib (Hexaxim, Sanofi Pasteur Inc.). Pertussis vaccine efficacy during a pertussis outbreak in Oregon in 2012 was 95% in 15- to 47-month-olds and 47% in adolescents ages 13 to 16 years (
      • Liko J.
      • Robinson S.G.
      • Cieslak P.R.
      Pertussis vaccine performance in an epidemic year—Oregon, 2012.
      ). Pregnant women vaccinated during 27 to 36 week's gestation passively transfer pertussis antibodies that are measurable in their infant for the first 2 to 3 months after birth, around the time the infant is able to receive his or her first pertussis vaccine (
      • Vilajeliu A.
      • Gonce A.
      • Lopez M.
      • Costa J.
      • Rocamora L.
      • Rios J.
      • et al.
      PERTU Working Group
      Combined tetanus-diphtheria and pertussis vaccine during pregnancy: Transfer of maternal pertussis antibodies to the newborn.
      ).
      Bordetella pertussis infection often begins with mild upper respiratory tract symptoms similar to the common cold, known as the catarrhal stage, and progresses to the cough stage, which lasts for 6 to 10 weeks (
      • American Academy of Pediatrics
      Pertussis (whooping cough).
      ). The classic cough associated with pertussis involves a whoop upon inspiration and paroxysms of coughing. Patients often vomit with the paroxysms of coughing. Pertussis affects infants younger than 6 months more severely than older children, and may include gagging, gasping, bradycardia, and apnea. Young infants may not have the classic whoop sound with their coughing. Younger infants often need to be hospitalized as a result of hypoxia or apnea spells, and sudden, unexpected death may occur (
      • American Academy of Pediatrics
      Pertussis (whooping cough).
      ). If started early in the course of pertussis, antibiotics may decrease the severity of the illness. Antibiotics also decrease the spread of pertussis to others. A 5-day course of azithromycin is the first-line treatment for all ages (
      • American Academy of Pediatrics
      Pertussis (whooping cough).
      ).
      The incubation period for pertussis is 7 to 10 days (range, 5 to 21 days), and patients are most contagious during the catarrhal phase, which may resemble the common cold (
      • American Academy of Pediatrics
      Pertussis (whooping cough).
      ). Additionally, adolescents and adults may present with mild or asymptomatic pertussis rather than the classic symptoms of pertussis, leading to unknowing spread of the disease. Close contacts of patients with pertussis who are not immunized or are underimmunized should have the pertussis vaccine, including the use of Tdap off-label in children ages 7 years to 10 years (
      • American Academy of Pediatrics
      Pertussis (whooping cough).
      ). Prophylactic antibiotic treatment is recommended for all household and other close contacts of the index case, regardless of their immunization status. Close contacts are defined by the
      • American Academy of Pediatrics
      Pertussis (whooping cough).
      recommendations as children in day care; face-to-face exposure within 3 feet of the index case; direct contact with nasal or respiratory secretions of the infected person; or sharing close or confined space for 1 hour or longer with the index case. Postexposure prophylaxis should be provided within 21 days of exposure to persons at high risk of developing severe disease or who will have close contact with a person at risk of developing severe disease (
      • Centers for Disease Control and Prevention
      Postexposure antimicrobial prophylaxis.
      ). Persons considered high risk for developing severe disease include infants and patients with health conditions that would be worsened by pertussis, such as moderate to severe asthma or immunocompromised persons. Persons who are exposed to high-risk patients, particularly infants and pregnant women in the third trimester of pregnancy, should be given prophylaxis treatment. Providers need to balance the health and safety of high-risk patients with the potential for overuse of antibiotics. Table 1 provides recommendations for postexposure prophylaxis.

      Influenza

      Seasonal influenza outbreaks occur on an annual basis throughout the world. The influenza season in the United States is in the fall and winter, with peak flu season anytime from November to March (). A pandemic influenza outbreak is declared when a novel (nonhuman) influenza virus undergoes an antigenic shift and humans do not have immunity to the new influenza subtype. The last influenza pandemic was in 2009-2010, when the CDC estimates that 43 to 89 million persons had the H1N1 strain of influenza from April 2009 to April 2010, with 8,870 to 18,300 deaths attributed to the H1N1 strain ().
      The circulating strain(s) of influenza vary from year to year, and therefore the vaccine composition is reviewed annually. The influenza vaccine composition is determined by analyzing the prevailing strains of influenza gathered from national influenza centers in more than 100 countries. The national influenza centers send viral samples to five World Health Organization (WHO) Collaborating Centers in the United States (CDC, in Atlanta, Georgia), the United Kingdom, Australia, Japan, and China (
      • Centers for Disease Control and Prevention
      Selecting viruses for seasonal influenza vaccine.
      ). In February of each year, the WHO gathers information from the WHO Collaborating Centers and makes a recommendation regarding the composition of the Northern Hemisphere seasonal influenza vaccine. In the United States, the Vaccines and Related Biological Products Advisory Committee, a part of the U.S. Food and Drug Administration, makes the final decision regarding the composition of the U.S. vaccine (
      • Centers for Disease Control and Prevention
      Selecting viruses for seasonal influenza vaccine.
      ). The process of determining the circulating influenza strain is tricky, and a “good match” is 50% to 60% effective in preventing influenza, with a range in effectiveness since 2004 of 10% to 60% (
      • Centers for Disease Control and Prevention
      Seasonal influenza vaccine effectiveness, 2005-2012.
      ). The composition of the 2015-2016 trivalent influenza vaccine is A/California/7/2009 (H1N1)-like virus, an A/Switzerland/9715293/2013 (H3N2)-like virus, and a B/Phuket/3073/2013-like (Yamagata lineage) virus, with the quadrivalent vaccine additionally containing B/Brisbane/60/2008-like (Victoria lineage) virus (
      • Grohskopf L.A.
      • Sokolow L.Z.
      • Olsen S.J.
      • Bresee J.S.
      • Broder K.R.
      • Karron R.A.
      Prevention and control of influenza with vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 20115-2016 influenza season.
      ).
      The CDC monitors the seasonal influenza activity weekly throughout the influenza season and reports it in the Weekly FluView Report (www.cdc.gov/flu/weekly/). The weekly summary reports the circulating strains of influenza and the geographic spread of influenza. The CDC also tracks antiviral resistance and reports it in the Weekly FluView Report. If strains of influenza resistant to antiviral agents are circulating, the CDC will issue a recommendation for antiviral therapy and has been known to change recommendations mid influenza season when resistance is noted.
      The best protection against influenza is for all persons ages 6 months and older to be vaccinated by October of each year. Children ages 6 months through 8 years need two doses if they have received fewer than two doses of influenza vaccine before July 2015, and one dose if they have received two or more total doses of influenza vaccine before July 2015 (
      • American Academy of Pediatrics Committee on Infectious Diseases
      Recommendations for prevention and control of influenza in children, 2015-2016.
      ). High-risk patients who have confirmed influenza should be treated with antiviral agents. High-risk children are defined as children who are hospitalized; children younger than age 2 years; patients with chronic pulmonary, cardiac, renal, hepatic, hematologic, or metabolic disorders; children with neurodevelopment or neurologic disorders; immunosuppressed persons; pregnant women or women within 2 weeks postpartum; children and adolescents younger than 19 years treated with chronic aspirin therapy; and American Indian or Alaska Native peoples (
      • American Academy of Pediatrics Committee on Infectious Diseases
      Recommendations for prevention and control of influenza in children, 2015-2016.
      ). In children, oral oseltamivir (Tamiflu, Roche, Basel, Switzerland) is the drug of choice to treat influenza.
      Although immunization remains the best protection against influenza, certain children should receive chemoprophylaxis within 48 hours after exposure to influenza. Chemoprophylaxis with antiviral agents is recommended by the
      • American Academy of Pediatrics Committee on Infectious Diseases
      Recommendations for prevention and control of influenza in children, 2015-2016.
      as follows:
      • For children at high risk of complications from influenza for whom influenza vaccine is contraindicated
      • For children at high risk during the 2 weeks after influenza immunization (inactivated influenza virus)
      • For family members or health care providers who are unimmunized and are likely to have ongoing, close exposure to the following:
        • Unimmunized children at high risk; or
        • Unimmunized infants and toddlers who are younger than 24 months
      • For control of influenza outbreaks for unimmunized staff and children in a closed institutional setting with children at high risk (e.g., extended-care facilities)
      • As a supplement to immunization among children at high risk, including children who are immunocompromised and may not respond to the vaccine
      • As postexposure prophylaxis for family members and close contacts of an infected person if those people are at high risk of complications from influenza
      • For children at high risk and their family members and close contacts, as well as health care providers, when circulating strains of influenza virus in the community are not matched with seasonal influenza vaccine strains, on the basis of current data from the CDC and local health departments.
      Dosing of antiviral agents for treatment of influenza and chemoprophylaxis is provided in Table 2.
      Table 2Dosing of influenza antiviral medications for treatment or chemoprophylaxis
      Data from
      • Centers for Disease Control and Prevention
      Influenza antiviral medications: Summary for clinicians.
      .
      Antiviral agentUseChildrenAdults
      Oseltamivir (Tamiflu)Treatment (5 days)If < 1 year old: 3 mg/kg/dose twice daily

      If ≥ 1 year, dose varies by child's weight: ≤15 kg, the dose is 30 mg twice a day

      > 15 to 23 kg, the dose is 45 mg twice a day

      > 23 to 40 kg, the dose is 60 mg twice a day

      > 40 kg, the dose is 75 mg twice a day
      75 mg twice daily
      Oseltamivir (Tamiflu)Chemoprophylaxis (7 days)If child is < 3 months, use of oseltamivir for chemoprophylaxis is not recommended unless the situation is judged critical because of limited data in this age group

      If child is ≥ 3 months to < 1 year, 3 mg/kg/dose once daily

      If ≥ 1 year, dose varies by child's weight:

      ≤ 15 kg, the dose is 30 mg once a day

      > 15 to 23 kg, the dose is 45 mg once a day

      > 23 to 40 kg, the dose is 60 mg once a day

      > 40 kg, the dose is 75 mg once a day
      75 mg once daily
      Zanamivir (Relenza)Treatment (5 days)10 mg (two 5-mg inhalations) twice daily (FDA approved and recommended for use in children ≥ 7 years)10 mg (two 5-mg inhalations) twice daily
      Zanamivir (Relenza)Chemoprophylaxis (7 days)10 mg (two 5-mg inhalations) once daily (FDA approved for and recommended for use in children ≥ 5 years)10 mg (two 5-mg inhalations) once daily
      Note. FDA, Food and Drug Administration.

      Conclusion

      Vaccines provide protection against many diseases and have saved countless lives, yet we are in an era in which some parents are choosing not to vaccinate or to only partially vaccinate their children. Diseases that used to be rare when all children were fully vaccinated may now present in the pediatric primary care setting at any time. Pediatric providers need to keep vaccine-preventable diseases as a part of their differential diagnosis when examining children and maintain current knowledge on the management of vaccine-preventable diseases.

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      Biography

      Teri Moser Woo, Associate Professor, Associate Dean for Graduate Nursing Programs, Pacific Lutheran University, Tacoma, WA.

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