Two live, attenuated varicella zoster virus-containing vaccines are available in the United States for prevention of varicella: 1) a single-antigen varicella vaccine (VARIVAX, Merck & Co., Inc., Whitehouse Station, New Jersey), which was licensed in the United States in 1995 for use among healthy children aged > or = 12 months, adolescents, and adults; and 2) a combination measles, mumps, rubella, and varicella vaccine (ProQuad, Merck & Co., Inc., Whitehouse Station, New Jersey), which was licensed in the United States in 2005 for use among healthy children aged 12 months-12 years. Initial Advisory Committee on Immunization Practices (ACIP) recommendations for prevention of varicella issued in 1995 (CDC. Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 1996;45 [No. RR-11]) included routine vaccination of children aged 12-18 months, catch-up vaccination of susceptible children aged 19 months-12 years, and vaccination of susceptible persons who have close contact with persons at high risk for serious complications (e.g., health-care personnel and family contacts of immunocompromised persons). One dose of vaccine was recommended for children aged 12 months-12 years and 2 doses, 4-8 weeks apart, for persons aged > or = 13 years. In 1999, ACIP updated the recommendations (CDC. Prevention of varicella: updated recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 1999;48 [No. RR-6]) to include establishing child care and school entry requirements, use of the vaccine following exposure and for outbreak control, use of the vaccine for certain children infected with human immunodeficiency virus, and vaccination of adolescents and adults at high risk for exposure or transmission. In June 2005 and June 2006, ACIP adopted new recommendations regarding the use of live, attenuated varicella vaccines for prevention of varicella. This report revises, updates, and replaces the 1996 and 1999 ACIP statements for prevention of varicella. The new recommendations include 1) implementation of a routine 2-dose varicella vaccination program for children, with the first dose administered at age 12-15 months and the second dose at age 4-6 years; 2) a second dose catch-up varicella vaccination for children, adolescents, and adults who previously had received 1 dose; 3) routine vaccination of all healthy persons aged > or = 13 years without evidence of immunity; 4) prenatal assessment and postpartum vaccination; 5) expanding the use of the varicella vaccine for HIV-infected children with age-specific CD4+ T lymphocyte percentages of 15%-24% and adolescents and adults with CD4+ T lymphocyte counts > or = 200 cells/microL; and 6) establishing middle school, high school, and college entry vaccination requirements. ACIP also approved criteria for evidence of immunity to varicella.

Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP).

We performed a longitudinal analysis of antibody titers specific for viral antigens (vaccinia, measles, mumps, rubella, varicella–zoster virus, and Epstein–Barr virus) and nonreplicating antigens (tetanus and diphtheria) in 45 subjects for a period of up to 26 years. In addition, we measured antigen-specific memory B cells by means of limiting-dilution analysis, and we compared memory B-cell frequencies to their corresponding serum antibody levels. Results Antiviral antibody responses were remarkably stable, with half-lives ranging from an estimated 50 years for varicella–zoster virus to more than 200 years for other viruses such as measles and mumps. Antibody responses against tetanus and diphtheria antigens waned more quickly, with estimated half-lives of 11 years and 19 years, respectively. B-cell memory was long-lived, but there was no significant correlation between peripheral memory B-cell numbers and antibody levels for five of the eight antigens tested. Conclusions These studies provide quantitative analysis of serologic memory for multiple antigens in subjects followed longitudinally over the course of more than one decade. In cases in which multiple exposures or repeated vaccinations were common, memory B-cell numbers did not correlate with antibody titers. This finding suggests that peripheral memory B cells and antibody-secreting plasma cells may represent independently regulated cell populations and may play different roles in the maintenance of protective immunity.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa066092

Duration of humoral immunity to common viral and vaccine antigens.

In low-income countries, infectious diseases still account for a large proportion of deaths, highlighting health inequities largely caused by economic differences. Vaccination can cut health-care costs and reduce these inequities. Disease control, elimination or eradication can save billions of US dollars for communities and countries. Vaccines have lowered the incidence of hepatocellular carcinoma and will control cervical cancer. Travellers can be protected against "exotic" diseases by appropriate vaccination. Vaccines are considered indispensable against bioterrorism. They can combat resistance to antibiotics in some pathogens. Noncommunicable diseases, such as ischaemic heart disease, could also be reduced by influenza vaccination. Immunization programmes have improved the primary care infrastructure in developing countries, lowered mortality in childhood and empowered women to better plan their families, with consequent health, social and economic benefits. Vaccination helps economic growth everywhere, because of lower morbidity and mortality. The annual return on investment in vaccination has been calculated to be between 12% and 18%. Vaccination leads to increased life expectancy. Long healthy lives are now recognized as a prerequisite for wealth, and wealth promotes health. Vaccines are thus efficient tools to reduce disparities in wealth and inequities in health.

https://www.who.int/bulletin/volumes/86/2/07-040089.pdf

Vaccination greatly reduces disease, disability, death and inequity worldwide.

Statistical physics of vaccination

Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of parents. Anti-vaccination movements have been implicated in lowered vaccine acceptance rates and in the increase in vaccine-preventable disease outbreaks and epidemics. In this review, we will look at determinants of parental decision-making about vaccination and provide an overview of the history of anti-vaccination movements and its clinical impact.

Vaccine hesitancy, vaccine refusal and the anti-vaccine movement: influence, impact and implications

BACKGROUND The widespread use of a second dose of mumps vaccine among U.S. schoolchildren beginning in 1990 was followed by historically low reports of mumps cases. A 2010 elimination goal was established, but in 2006 the largest mumps outbreak in two decades occurred in the United States. METHODS We examined national data on mumps cases reported during 2006, detailed case data from the most highly affected states, and vaccination-coverage data from three nationwide surveys. RESULTS A total of 6584 cases of mumps were reported in 2006, with 76% occurring between March and May. There were 85 hospitalizations, but no deaths were reported; 85% of patients lived in eight contiguous midwestern states. The national incidence of mumps was 2.2 per 100,000, with the highest incidence among persons 18 to 24 years of age (an incidence 3.7 times that of all other age groups combined). In a subgroup analysis, 83% of these patients reported current college attendance. Among patients in eight highly affected states with known vaccination status, 63% overall and 84% between the ages of 18 and 24 years had received two doses of mumps vaccine. For the 12 years preceding the outbreak, national coverage of one-dose mumps vaccination among preschoolers was 89% or more nationwide and 86% or more in highly affected states. In 2006, the national two-dose coverage among adolescents was 87%, the highest in U.S. history. CONCLUSIONS Despite a high coverage rate with two doses of mumps-containing vaccine, a large mumps outbreak occurred, characterized by two-dose vaccine failure, particularly among midwestern college-age adults who probably received the second dose as schoolchildren. A more effective mumps vaccine or changes in vaccine policy may be needed to avert future outbreaks and achieve the elimination of mumps.

/pdf/recent-resurgence-of-mumps-in-the-united-states-3vf4498zl7.pdf

Recent Resurgence of Mumps in the United States

Background Measles was declared eliminated from the United States in 2000 but remains endemic worldwide. In 2005, a 17-year-old unvaccinated girl who was incubating measles returned from Romania, creating the largest documented outbreak of measles in the United States since 1996. Methods We conducted a case-series investigation, molecular typing of viral isolates, surveys of rates of vaccination coverage, interviews regarding attitudes toward vaccination, and cost surveys. Results Approximately 500 persons attended a gathering with the index patient one day after her return home. Approximately 50 lacked evidence of measles immunity, of whom 16 (32 percent) acquired measles at the gathering. During the six weeks after the gathering, a total of 34 cases of measles were confirmed. Of the patients with confirmed measles, 94 percent were unvaccinated, 88 percent were less than 20 years of age, and 9 percent were hospitalized. Of the 28 patients who were 5 to 19 years of age, 71 percent were home-schooled. Vaccine failure occurred in two persons. The virus strain was genotype D4, which is endemic in Romania. Although containment measures began after 20 persons were already infectious, measles remained confined mostly to children whose parents had refused to have them vaccinated, primarily out of concern for adverse events from the vaccine. Seventy-one percent of patients were from four households. Levels of measles-vaccination coverage in Indiana were 92 percent for preschoolers and 98 percent for sixth graders. Estimated costs of containing the disease were at least 167,685 dollars, including 113,647 dollars at a hospital with an infected employee. Conclusions This outbreak was caused by the importation of measles into a population of children whose parents had refused to have them vaccinated because of safety concerns about the vaccine. High vaccination levels in the surrounding community and low rates of vaccine failure averted an epidemic. Maintenance of high rates of vaccination coverage, including improved strategies of communication with persons who refuse vaccination, is necessary to prevent future outbreaks and sustain the elimination of measles in the United States.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa060775

Implications of a 2005 Measles Outbreak in Indiana for Sustained Elimination of Measles in the United States

In June 2005, the Advisory Committee on Immunization Practices (ACIP) recommended administering a second dose of varicella vaccine during outbreaks, supplementing the routine 1-dose requirement. From October 2005 to January 2006, a varicella outbreak occurred in Maine in a highly vaccinated elementary school population. We investigated the outbreak, held a school-based vaccination clinic, and assessed costs in implementing ACIP's outbreak-response recommendation. Parents completed questionnaires and case investigation interviews. Personnel at the Maine Center for Disease Control and Prevention, the school in which the outbreak occurred ("school A"), and physician offices completed economic surveys. Forty-eight cases occurred, with no hospitalizations or deaths. Vaccine effectiveness was 86.6% (95% confidence interval, 82.0%-90.1%). Of 240 eligible students, 132 (55.0%) received second-dose vaccination. Implementing ACIP's outbreak-response recommendation was challenging and cost approximately $26,875. Additionally, the routine 1-dose varicella vaccination policy did not confer adequate population immunity to prevent this outbreak. These findings support ACIP's June 2007 recommendation for a routine 2-dose varicella vaccination program.

/pdf/challenges-to-implementing-second-dose-varicella-vaccination-4df3xansjs.pdf

Challenges to Implementing Second-Dose Varicella Vaccination during an Outbreak in the Absence of a Routine 2-Dose Vaccination Requirement—Maine, 2006

The authors reply: We obtained laboratory confirmation for at least one patient in 9 of 11 families infected with measles. Among these 9 families, 14 of 20 patients had disease that was confirmed by laboratory analysis. The remaining two families (with 10 and 4 patients, respectively) declined to have specimens collected from all family members. The parents of the patient who had measles despite receiving two doses of vaccine declined to have specimens collected from any of their children except one whose disease was confirmed by laboratory testing during hospitalization. All patients had classic clinical symptoms of measles that appeared after the appropriate incubation period after exposure to a patient with laboratoryconfirmed disease. The percentage of cases that 1.

Amy A. Parker

Papers

Recent Resurgence of Mumps in the United States

Implications of a 2005 Measles Outbreak in Indiana for Sustained Elimination of Measles in the United States

Challenges to Implementing Second-Dose Varicella Vaccination during an Outbreak in the Absence of a Routine 2-Dose Vaccination Requirement—Maine, 2006

Pay-for-Performance Programs in the United Kingdom