Barbara Watson

Ten year follow-up of healthy children who received one or two injections of varicella vaccine.

Background. The rate of varicella and persistence of varicella antibody after a one dose vs. a two dose regimen of varicella virus vaccine live Oka/Merck (VARIVAX®; Merck & Co., Inc., West Point, PA) in ∼2000 children were compared during a 9- to 10-year follow-up period. Methods. Children 12 months to 12 years of age with a negative history of varicella were randomized in late 1991 to early 1993 to receive either one or two injections of varicella vaccine given 3 months apart. Subjects were actively followed for varicella, any varicella-like illness or zoster and any exposures to varicella or zoster on a yearly basis for 10 years after vaccination. Persistence of varicella antibody was measured yearly for 9 years. Results. Most cases of varicella reported in recipients of one or two injections of vaccine were mild. The risk of developing varicella >42 days postvaccination during the 10-year observation period was 3.3-fold lower (P < 0.001) in children who received two injections than in those who received one injection (2.2%vs. 7.3%, respectively). The estimated vaccine efficacy for the 10-year observation period was 94.4% for one injection and 98.3% for two injections (P < 0.001). Measurable serum antibody persisted for 9 years in all subjects. Conclusions. Administration of either one or two injections of varicella vaccine to healthy children results in long term protection against most varicella disease. The two dose regimen was significantly more effective than a single injection.

Oka/Merck varicella vaccine in healthy children: final report of a 2-year efficacy study and 7-year follow-up studies

A large double-blind, randomized, placebo-controlled trial of live attenuated Oka/Merck varicella vaccine was conducted among healthy children, 1-14 years of age. During the first varicella season, the efficacy of the vaccine among susceptible children was 100%1. During the second varicella season, 22 children were diagnosed with varicella; 21 cases in placebo recipients and one in a vaccine recipient. The overall efficacy of the vaccine through two varicella seasons was 98%. After the code for the study was broken, the original group of vaccine recipients continued to be followed for development of varicella. The estimated proportion of vaccine recipients who remained varicella-free at the end of 7 years was 95%. The 23 cases of varicella that occurred in vaccine recipients over the 7-year period were considerably milder than natural varicella. The average number of lesions was 53, 50% of the children had non-vesicular rashes, and 14% of the children had a temperature greater than or equal to 38.9 degrees C (102 degrees F), oral. The persistence of antibody in a subset of vaccine recipients followed for 6 years was 100%.

Incidence, complications, and risk factors for prolonged stay in children hospitalized with community-acquired influenza

OBJECTIVES. Few studies have examined the characteristics and clinical course of children hospitalized with laboratory-confirmed influenza. We sought to (1) estimate the age-specific incidence of influenza-related hospitalizations, (2) describe the characteristics and clinical course of children hospitalized with influenza, and (3) identify risk factors for prolonged hospitalization. PATIENTS AND METHODS. Children ≤21 years of age hospitalized with community-acquired laboratory-confirmed influenza at a large urban childrens hospital were identified through review of laboratory records and administrative data sources. A neighborhood cohort embedded within our study population was used to estimate the incidence of community-acquired laboratory-confirmed influenza hospitalizations among children <18 years old. Risk factors for prolonged hospitalization (>6 days) were determined by using logistic regression. RESULTS. We identified 745 children hospitalized with community-acquired laboratory-confirmed influenza during the 4-year study period. In this urban cohort, the incidence of community-acquired laboratory-confirmed influenza hospitalization was 7 per 10000 child-years of observation. The median age was 1.8 years; 25% were infants <6 months old, and 77% were children <5 years old. Many children (49%) had a medical condition associated with an increased risk of influenza-related complications. The incidence of influenza-related complications was higher among children with a preexisting high-risk condition than for previously healthy children (29% vs 21%). However, only cardiac and neurologic/neuromuscular diseases were found to be independent risk factors for prolonged hospitalization. CONCLUSIONS. Influenza is a common cause of hospitalization among both healthy and chronically ill children. Children with cardiac or neurologic/neuromuscular disease are at increased risk of prolonged hospitalization; therefore, children with these conditions and their contacts should be a high priority to receive vaccine. The impact on pediatric hospitalization of the new recommendation to vaccinate all children 6 months to <5 years old should be assessed.

A Randomized Trial of Alternative Two- and Three-Dose Hepatitis B Vaccination Regimens in Adolescents: Antibody Responses, Safety, and Immunologic Memory

Objectives. Hoping to increase hepatitis B (HB) vaccination of adolescents, we did the following: 1) studied if modified regimens of the recombinant HB vaccine, Recombivax HB (2 or 3 doses of 5 or 10 μg given over 4 or 6 months), induce protective anti-hepatitis B surface antibody [anti-HBsAb] levels (≥10 mIU/mL) comparable to the recommended regimen (5 μg at 0 and 1, and 6 months); 2) measured early antibody response after a single dose; and 3) assessed immunologic memory after 2- and 3-dose regimens. Design. One thousand twenty-six adolescents were randomized to 1 of 5 treatment groups (10 μg at 0 and 4 or 0 and 6 months; 5 μg at 0 and 6 or 0, 2, and 4 or 0, 1, and 6 months) in an open trial. Anti-HBsAb was measured in all participants just before and 1 month after the last dose, and at several other times in a subset of vaccinees. Anti-HBsAb response to a booster dose 2 years later was examined to assess immunologic memory in participants vaccinated with 5 μg at 0 and 6 or 0, 1, and 6 months. Results. All regimens induced ≥10 mIU/mL of anti-HBs in ≥95% of vaccinees. Geometric mean titers ranged from 674.8 to 3049.4 mIU/mL. Geometric mean titers were higher with regimens using the following: 1) 10 versus 5 μg; 2) 3 versus 2 doses; and 3) vaccination intervals of 6 versus 4 months. After 6 months, 63.8% of vaccinees given one 10-μg dose had ≥10 mIU/mL of anti-HBsAb versus 41.6% after one 5-μg dose. Participants vaccinated with either two or three 5-μg doses retained robust immunologic memory. Conclusions. The results of this study show that a 2-dose regimen of Recombivax HB is as immunogenic and induces immunologic memory as effectively as the recommended 3-dose regimen. A regimen of two 10-μg doses may be of significant benefit for vaccinees who are poorly compliant or deviate from the intended vaccination schedule.

Postexposure effectiveness of varicella vaccine.

Objective. 1) To describe the postexposure effectiveness of varicella vaccine in a homeless shelter; and 2) to demonstrate an effective public health intervention and its implications. Design. A prospective observational study. Setting. A women and childrens shelter in Philadelphia with 2 cases of varicella before intervention. Outcome Measures. Varicella in vaccinated and unvaccinated shelter residents; vaccine effectiveness for prevention of varicella when administered after exposure among children <13 years of age. Results. Sixty-seven shelter residents received varicella vaccine after exposure, including 42 children <13 years of age. One child who was unvaccinated developed varicella, but no vaccinated child developed typical disease. Vaccine effectiveness was 95.2% (95% CI, 81.6%–98.8%) for prevention of any disease and 100% for prevention of moderate or severe disease among the children <13 years of age. Conclusion. When used within 36 hours after exposure to varicella in a setting where close contact occurred, varicella vaccine was highly effective in preventing further disease. This study provides support for the recent recommendation by the Advisory Committee on Immunization Practices to administer varicella vaccine after exposure: this practice should minimize the number of moderate or severe cases of disease and prevent prolonged outbreaks.

Impact of a Routine Two-Dose Varicella Vaccination Program on Varicella Epidemiology

OBJECTIVE: One-dose varicella vaccination for children was introduced in the United States in 1995. In 2006, a second dose was recommended to further decrease varicella disease and outbreaks. We describe the impact of the 2-dose vaccination program on varicella incidence, severity, and outbreaks in 2 varicella active surveillance areas. METHODS: We examined varicella incidence rates and disease characteristics in Antelope Valley (AV), CA, and West Philadelphia, PA, and varicella outbreak characteristics in AV during 1995–2010. RESULTS: In 2010, varicella incidence was 0.3 cases per 1000 population in AV and 0.1 cases per 1000 population in West Philadelphia: 76% and 67% declines, respectively, since 2006 and 98% declines in both sites since 1995; incidence declined in all age groups during 2006–2010. From 2006–2010, 61.7% of case patients in both surveillance areas had been vaccinated with 1 dose of varicella vaccine and 7.5% with 2 doses. Most vaccinated case patients had <50 lesions with no statistically significant differences among 1- and 2-dose cases (62.8% and 70.3%, respectively). Varicella-related hospitalizations during 2006–2010 declined >40% compared with 2002–2005 and >85% compared with 1995–1998. Twelve varicella outbreaks occurred in AV during 2007–2010, compared with 47 during 2003–2006 and 236 during 1995–1998 (P < .01). CONCLUSIONS: Varicella incidence, hospitalizations, and outbreaks in 2 active surveillance areas declined substantially during the first 5 years of the 2-dose varicella vaccination program. Declines in incidence across all ages, including infants who are not eligible for varicella vaccination, and adults, in whom vaccination levels are low, provide evidence of the benefit of high levels of immunity in the population.

Comparison of acellular and whole-cell pertussis-component diphtheria-tetanus-pertussis vaccines in infants

In a multicenter, double-blind, randomized, longitudinal study, 252 children received licensed Lederle diphtheria-tetanus toxoids and pertussis vaccine adsorbed (DTP) at 2, 4, and 6 months of age, and 245 children received a DTP vaccine with the Lederle/Takeda acellular pertussis component (APDT) at the same ages. Both groups of children received APDT vaccine at 18 months of age. After each of the first three immunizations, APDT vaccine recipients had fewer local and systemic reactions than did DTP vaccinees. Reactions after the 18-month APDT vaccination were minimal in severity regardless of the vaccine previously received. Antibody responses to lymphocytosis-promoting factor and agglutinogens were more pronounced in DTP recipients; however, APDT recipients had a better serologic response to filamentous hemagglutinin, and responses to the 69K protein were equivalent. This APDT vaccine produces fewer reactions than the standard whole-cell DTP vaccine. The protective significance of the serologic responses to the APDT vaccine is unknown, but the greater response to filamentous hemagglutinin and equivalent response to the 69K protein compared with those to DTP vaccine seem promising.

Routine laboratory testing data for surveillance of rotavirus hospitalizations to evaluate the impact of vaccination.

Objective: The recent implementation of a rotavirus vaccination program in the United States makes it imperative to assess the impact of immunization on the incidence of severe rotavirus disease leading to hospitalization. Active surveillance for laboratory-confirmed rotavirus hospitalizations is the ideal approach for surveillance, but requires substantial resources to implement. We examined laboratory and hospital discharge data for 2 tertiary care pediatric hospitals to assess the utility of routine laboratory testing data for surveillance of rotavirus gastroenteritis and to estimate rotavirus disease burden. Design: We obtained all discharge records of hospitalizations for acute gastroenteritis among children <5 years of age at Childrens Mercy Hospital (CMH), Kansas City, from July 2000 to June 2005 and at Childrens Hospital of Philadelphia (CHOP) from July 2004 to June 2006. We linked these discharge records to laboratory results of rotavirus testing to evaluate epidemiologic differences in children who were tested and not tested for rotavirus and to estimate overall rotavirus burden by extrapolating clinical testing results to the untested group. Results: At CMH, of the 3702 children with acute gastroenteritis, 69% (n = 2552) were discharged during the winter (January through May) months, when rotavirus is most common. Similarly, at CHOP, 62% (n = 779) of the 1261 gastroenteritis discharges occurred during the winter months. During these months, 47% (n = 1197 of 2552) of the discharges at CMH and 56% (n = 438 of 779) of the discharges at CHOP were tested for rotavirus and of those tested, 71% (n = 853 of 1197) and 55% (n = 242 of 438) were positive, respectively. At both hospitals, children with and without rotavirus testing had similar gender and race/ethnicity, but the rate of testing differed by age at CHOP and by month of admission at CMH. After adjusting for these differences, we estimate that 56%–70% of winter and 34%–48% of year-round gastroenteritis in children <5 years can be attributable to rotavirus. Overall, 3%–5% of all hospitalizations in children <5 years of age were caused by rotavirus. Conclusions: Sentinel hospitals where a large proportion of children hospitalized for gastroenteritis are routinely tested for rotavirus could provide a useful and cost-efficient platform to complement ongoing active surveillance efforts to evaluate the impact of rotavirus vaccination. The data reaffirm the substantial burden of rotavirus hospitalizations in US children and the potential health benefits of vaccination.

A Cluster of Primary Varicella Cases Among Healthcare Workers With False-Positive Varicella Zoster Virus Titers

BACKGROUND Five cases of primary varicella zoster virus (VZV) we re diagnosed among hospital healthcare workers (HCWs). All had complied with a pre-employment VZV screening program and had been considered immune. OBJECTIVES To summarize the investigation of VZV among un-immunized HCWs and to provide recommendations for avoiding false-positive serologic tests. DESIGN Risk of transmission of VZV to susceptible HCWs is minimized through serologic screening. Varicella vaccine is recommended for susceptible HCWs. A commercially available latex bead agglutination assay (LA) is widely used because it is rapid and easy to perform. LA was compared with the whole-cell varicella ELISA standardized in the Centers for Disease Control and Prevention (CDC) National Herpes Laboratory. SETTING/POPULATION Large inner-city, tertiary-employee population. RESULTS In a year, 5 HCWs presented with laboratory-confirmed primary varicella infection. Four had VZV exposures 2 weeks prior to presentation. All had documented positive VZV titers by LA performed at hire. None were offered VZV vaccination. The original LAs were judged false-positives. INTERVENTION/FOLLOW-UP INVESTIGATION: Fifty-three consecutive VZV LA samples from the hospital laboratory were retested at the CDC. Forty-four samples concurred. Of the remaining 9, 4 were positive by hospital LA but negative by CDC IgG ELISA. Four were equivocal by hospital LA but negative by CDC IgG ELISA and LA. One was positive by hospital LA but negative by LA and equivocal by ELISA at the CDC. CONCLUSION LA may be prone to false-positive results and inappropriate for screening hospital HCWs.

Incremental effectiveness of second dose varicella vaccination for outbreak control at an elementary school in Philadelphia, pennsylvania, 2006.

Background: In 2006, the Philadelphia Department of Public Health conducted an investigation of a varicella outbreak at an elementary school in which second-dose vaccination for outbreak control (VOC) was implemented. We evaluated the effectiveness of this intervention. Methods: Self-administered questionnaires collected varicella disease and vaccination information. Students eligible for second-dose VOC were 1-dose vaccine recipients without prior varicella disease. A breakthrough varicella case was defined as a maculopapulovesicular rash in a student with onset >42 days after 1-dose vaccination without other apparent cause. Vaccine effectiveness was evaluated using survival analysis techniques and analyzed by vaccine status (first dose versus second dose). Multivariable Cox proportional hazard models were used to identify statistical interactions and adjust for confounders. Results: The questionnaire response rate was 92% (342/370). Of the 286 eligible students, 187 (65%) received a second-dose VOC. The crude attack rate was 9/187 (5%) among second-dose VOC recipients; 43/99 (43%) among 1-dose recipients, and 5/6 (83%) among unvaccinated students. Second-dose VOC recipients had milder rashes, compared with 1-dose or unvaccinated students. The adjusted incremental second-dose vaccine effectiveness was 76% (95% confidence interval: 44%–90%) for students with classroom exposure. Incremental effectiveness was similar (79%) when we extended the immune response time from 4 days to 7 days after second-dose VOC. Conclusions: Second-dose VOC resulted in a substantial reduction in varicella incidence for students with classroom exposure. Until high rates of routine second-dose vaccine coverage are achieved, clinicians should consider second-dose VOC an appropriate intervention to reduce disease transmission in institution-based outbreaks.