Sex: U
Vaccine: VARCEL
Symptoms: Vaccination failure
Clinical narrative: This literature study report was received from the authors. The main aim of this study was to evaluate the 2-dose varicella vaccine effectiveness (VE) by conducting a matched case-control study to examine the overall and incremental VE of the 2-dose varicella vaccination regimen in preventing varicella among school-aged children (4-18 years) in 2 geographically and demographically diverse areas under active surveillance for varicella. Secondary study objectives were to estimate 1-dose VE among children aged 1 to 18 years during the 2-dose era and determine risk factors associated with breakthrough varicella among 2-dose recipients. The study authors from May 2009 through June 2011, conducted matched case-control study in collaboration with the Centers for Disease Control and Prevention (CDC) at 2 different centers. Institutional review boards approved the study protocol. The target populations for case and control subject recruitment were residents aged 1 to 18 years. During the 2010 to 2011 academic active surveillance was expanded. Eligible case subjects were also identified through citywide passive surveillance. All case reports were investigated with the standardized questionnaire. In May 2009 through July 2010, enrollment was limited to children aged 5 to 14 years with laboratory confirmation of varicella-zoster virus (VZV) by polymerase chain reaction (PCR) testing. During August 2010 through June 2011, enrollment was expanded to include people 1 to 18 years of age with laboratory or clinical diagnosis of varicella by a health care provider. Control subjects were selected. The department of Public Health immunization registry has used health department birth records and vaccine administration reporting from health care providers to establish and maintain immunization records for all children aged = (or) < 6 years in city since 1995. The registry expanded to include children aged = (or) < 6 years in 2007. For each varicella case identified that met study inclusion criteria, authors selected potential controls using incidence density sampling by extracting age-matched (plus or minus 2 years) records for all children from the pool of eligible controls aged 1 to 18 years who did not have a previous varicella history documented in historic surveillance data or immunization registry. A 2-year age range for controls was chosen, because the routine 2-dose varicella vaccination recommendation spans ages 4 to 6 years. Moreover, because routine 1-dose coverage reached higher levels (>80%), protection from 1-dose varicella vaccination appears to remain consistent during the first few years after vaccination. Between 5 and 60 potential control subjects were randomly selected from the corresponding control pool for each incident case. To be able to analyze vaccine effectiveness (VE) among the age groups for which the first and second doses of varicella vaccine are recommended, controls selected for cases aged 1 to 3 years had to be < 4 years of age, and controls selected for cases > (or) = 4 years of age had to be > (or) = 4 years of age. Study staff obtained data through verbal consent and collected data from a parent or guardian of each subject by telephone by using a standard questionnaire. The staff used data from clinically diagnosed and laboratory confirmed varicella. Varicella severity was categorized based on the number of lesions reported as mild (<50 lesions), moderate (50-500 lesions), or severe (>500 lesions). All VE estimates were calculated with Greenwood and Yule's formula: VE = 1 - relative risk. The distribution of categorical or continuous variables between cases and controls was examined with Mantel-Haenszel, x2 test, Fisher's exact test, MannWhitney Utest, or Kruskal-Wallis test where appropriate. A total of 125 clinically diagnosed varicella cases and 408 matched controls were enrolled. Of the 44 (35.2%) cases that had lesion specimens tested for VZV, 29 were laboratory-confirmed cases (all PCR positive), 11 were PCR negative (median lesion collection day: 5 [range: 2-21]), 2 had inadequate specimens, and 2 were culture negative. The distribution of demographic characteristics did not differ significantly between clinically diagnosed case and control subjects, except day care attendance among those aged > (or) = 4 years (P = .03). Most controls aged > (or) = 4 years from AV and city had received > (or) = 1 of varicella vaccine (98.8% vs 95.5%, P = .05), and the majority in each site had received 2 doses (78.5% vs 83.6%, P = .31). Although the proportion of vaccinated cases aged > (or) = 4 years from each site was similar (91% to 92%), the proportion of cases aged > (or) = 4 years who were 2-dose recipients was slightly lower in AV than city (41.1% vs 59.5%, p = .08). Among clinically diagnosed cases > (or) = 4 years of age, rash severity and characteristics differed significantly by vaccination status, with the majority of breakthrough cases reporting mild and mostly maculopapular rashes, whereas most unvaccinated cases had 50-500 lesions that were mostly vesicular. There was no severe varicella among 2-dose cases. Only 2 cases had >500 lesions; both were otherwise healthy adolescents, of whom, 1 was a 1-dose recipient and the other unvaccinated. None of the cases were hospitalized due to varicella or developed complications of varicella. Among breakthrough cases aged > (or) = 4 years, 2-dose cases were more likely to have rashes that resolved in <1 week (P = .01) and were less likely to have vesicular rashes (P = .01) than 1-dose cases. Presence and duration of fever did not differ significantly between breakthrough and unvaccinated cases. Among all unvaccinated and 1-dose participants, the effectiveness of 1-dose of varicella vaccine compared with no vaccine was 75.6% (95% confidence interval [Cl], 38.7%-90.3%) against all clinically diagnosed varicella and 78.1% (95% Cl, 12.7%-94.5%) against moderate or severe disease. The effectiveness of doses of varicella vaccine compared with no vaccine among subjects aged > (or) = 4 years was 93.6% (95% Cl, 75.6%-98.3%) against all clinically diagnosed varicella and 97.9% (95% Cl, 83.0%-99.7%) against moderate or severe varicella. The incremental effectiveness of 2-dose varicella vaccination compared with 1-dose among participants > (or) = 4 years of age was 87.5% (95% Cl, 74.9%-93.7%) in preventing any clinically diagnosed varicella and 94.1% (95% Cl, 72.4%-98.8%) in preventing moderate or severe clinically diagnosed disease. VE estimates were higher but not significantly in AV than city. Among subjects aged > (or) = 4 years from AV, 2-dose VE and incremental VE against any clinically diagnosed varicella were 98.4% and 92.4%, respectively. In city, 2-dose VE and incremental VE among subjects > (or) = 4 years old were 92.7% and 79.8%, respectively. Two dose VE estimates did not differ significantly between sites (P = 0.20); however, the small number of unvaccinated cases < (or) = 5 and controls < (or) = 6 may have led to unstable VE estimates by site. Among the 26 laboratory-confirmed cases aged > (or) = 4 years and their matched controls, 2-dose varicella VE was 95.9% (95% Cl, 23.2%-99.8%), and incremental VE was 97.3% (95% Cl, 88.9%-100%). Because data were sparse, we could not assess effectiveness of 1-dose of varicella vaccine against laboratory-confirmed varicella. Among 2-dose varicella vaccine recipients, there was no association between time since receiving dose 2 and breakthrough varicella (P = .17). However, those who received the second dose after 6 years of age were 60% less likely to have breakthrough varicella than those who had received the second dose at an earlier age (P = .009). A longer time interval between receiving 1- and 2-dose varicella vaccine (>5 or < (or) 5 years) was associated with lower odds of developing breakthrough varicella (OR= 0.5, P = .03). Subjects receiving dose 2 after 6 years of age were older than those receiving the second dose varicella vaccine earlier (12.7 vs 7.0 years, P < .001), as were subjects with a time interval between 1- and 2-dose varicella vaccine > 5 years compared with those having a shorter interval between doses (13.0 vs 7.4 years, P < .001). This literature study report correspond to 22 children of unknown age and gender. The medical history of patients and their concurrent conditions were not reported. On an unknown date the patients were vaccinated with varicella virus vaccine (manufacturer unknown) dose 1, dosage regimen and route unknown. Concomitant medications were not reported. On an unknown date, the patients were clinically diagnosed with varicella after receiving first dose of vaccine (possible ineffective). The outcome of event was unknown. The reporter considered the event to be related to varicella virus vaccine (manufacturer unknown). This case is linked to 1605USA002976, 1605USA002977 and 1605USA000171 via same literature link. Additional information has been requested.