Jessica Leung

Herpes Zoster Incidence Among Insured Persons in the United States, 1993–2006: Evaluation of Impact of Varicella Vaccination

BACKGROUND herpes zoster (HZ) is caused by reactivation of latent varicella zoster virus and is often associated with substantial pain and disability. Baseline incidence of HZ prior to introduction of HZ vaccine is not well described, and it is unclear whether introduction of the varicella vaccination program in 1995 has altered the epidemiology of HZ. We examined trends in the incidence of HZ and impact of varicella vaccination on HZ trends using a large medical claims database. METHODS medical claims data from the MarketScan databases were obtained for 1993-2006. We calculated HZ incidence using all persons with a first outpatient service associated with a 053.xx code (HZ ICD-9 code) as the numerator, and total MarketScan enrollment as the denominator; HZ incidence was stratified by age and sex. We used statewide varicella vaccination coverage in children aged 19-35 months to explore the impact of varicella vaccination on HZ incidence. RESULTS HZ incidence increased for the entire study period and for all age groups, with greater rates of increase 1993-1996 (P < .001). HZ rates were higher for females than males throughout the study period (P < .001) and for all age groups (P < .001). HZ incidence did not vary by state varicella vaccination coverage. CONCLUSIONS HZ incidence has been increasing from 1993-2006. We found no evidence to attribute the increase to the varicella vaccine program.

An outbreak of varicella in elementary school children with two-dose varicella vaccine recipients--Arkansas, 2006.

Background: In June 2006, the Advisory Committee on Immunization Practices (ACIP) expanded its June 2005 recommendation for a second dose of varicella vaccine during outbreaks to a recommendation for routine school entry second dose varicella vaccination. In October 2006, the Arkansas Department of Health was notified of a varicella outbreak among students where some received a second dose during an outbreak-related vaccination campaign in February 2006. Methods: The outbreak was investigated using a school-wide parental survey with a follow-up survey of identified case patients. Vaccination status was verified using state and local immunization records. Limited laboratory testing confirmed circulation of wild-type varicella, including varicella in 2-dose vaccine recipients. Results: Vaccination information was available for 871 (99%) of the 880 children. Varicella vaccination coverage was 97% (2-dose, 39%; 1-dose, 58%). A review of the February vaccination clinic found no deficiencies; lot numbers did not differ between cases and noncases. Varicella was confirmed by PCR in 5 (42%) of 12 lesion specimens and by IgM in 1 (6%) of 16 serum specimens. Varicella was reported in 84 children, including 25 (30%) two-dose and 53 (63%) one-dose recipients. Attack rates among 2-dose recipients (10.4%) and 1-dose recipients (14.6%) were not significantly different (RR: 0.72, 95% CI: 0.44–1.15). All 2-dose recipients and 80% of 1-dose recipients reported having 50 or fewer skin lesions. Conclusion: This outbreak is the first to document varicella in both 1- and 2-dose vaccine recipients; both groups had mild disease. The vaccine effectiveness of 1 and 2 doses were similar.

Fatal varicella due to the vaccine-strain varicella-zoster virus

We describe a death in a 15-mo-old girl who developed a varicella-like rash 20 d after varicella vaccination that lasted for 2 mo despite acyclovir treatment. The rash was confirmed to be due to vaccine-strain varicella-zoster virus (VZV). This is the first case of fatal varicella due to vaccine-strain VZV reported from the United States. The patient developed severe respiratory complications that worsened with each new crop of varicella lesions; vaccine-strain VZV was detected in the bronchial lavage specimen. Sepsis and multi-organ failure led to death. The patient did not have a previously diagnosed primary immune deficiency, but her failure to thrive and repeated hospitalizations early in life (starting at 5 mo) for presumed infections and respiratory compromise treated with corticosteroids were suggestive of a primary or acquired immune deficiency. Providers should monitor for adverse reactions after varicella vaccination. If severe adverse events develop, acyclovir should be administered as soon as possible. The possibility of acyclovir resistance and use of foscarnet should be considered if lesions do not improve after 10 d of treatment (or if they become atypical [e.g., verrucous]). Experience with use of varicella vaccine indicates that the vaccine has an excellent safety profile and that serious adverse events are very rare and mostly described in immunocompromised patients. The benefit of vaccination in preventing severe disease and mortality outweigh the low risk of severe events occurring after vaccination.

Impact of the Maturing Varicella Vaccination Program on Varicella and Related Outcomes in the United States: 1994–2012

BACKGROUND Although the 1-dose varicella vaccination program, introduced in 1996, has led to significant declines in varicella disease, outbreaks continued to occur, which led to the adoption of a 2-dose vaccination program in 2007. We previously reported an 88% decline in varicella-related hospitalizations and a 59% decline in outpatient visits during 1994-2002. We now update data on varicella healthcare utilization with 10 years of additional data, during a period of stabilizing first-dose coverage and rapidly increasing second-dose coverage. METHODS We performed a retrospective cohort study using claims data from 1994-2012 Truven Health MarketScan databases. We examined trends in rates of varicella-related outpatient visits and hospitalizations for MarketScan enrollees aged 0-49 years, including outpatient laboratory testing, outpatient antiviral use, and pediatric strokes, with 1994-1995 as the prevaccination period and 2006-2012 as the 2-dose varicella vaccination period. RESULTS Varicella outpatient visits declined 84% in 2012 versus the prevaccination period, with a 60% decline during the 2-dose period. Varicella hospitalizations declined 93% in 2012 versus the prevaccination period, with a 38% decline during the 2-dose period. The proportion of those with a varicella outpatient visit having varicella laboratory testing increased from 6% in 2003 to 17% in 2012. There were 21 445 (17%) with a claim for antivirals, which was relatively stable over time. There was no reduction in pediatric strokes during 1994-2012. CONCLUSIONS We document from our large study population that the varicella vaccination program has led to significant declines in outpatient visits and hospitalizations from the prevaccination period through 2012, with additional declines during the 2-dose varicella vaccination period.

Challenges in confirming a varicella outbreak in the two-dose vaccine era

BACKGROUND A second dose of varicella vaccine was recommended for U.S. children in 2006. We investigated a suspected varicella outbreak in School District X, Texas to determine 2-dose varicella vaccine effectiveness (VE). METHODS A varicella case was defined as an illness with maculopapulovesicular rash without other explanation with onset during April 1-June 10, 2011, in a School District X student. We conducted a retrospective cohort in the two schools with the majority of cases. Lesion, saliva, and environmental specimens were collected for varicella-zoster virus (VZV) PCR testing. VE was calculated using historic attack rates among unvaccinated. RESULTS In School District X, 82 varicella cases were reported, including 60 from Schools A and B. All cases were mild, with a median of 14 lesions. All 10 clinical specimens and 58 environmental samples tested negative for VZV. Two-dose varicella vaccination coverage was 66.4% in Schools A and B. Varicella VE in affected classrooms was 80.9% (95% CI: 67.2-88.9) among 1-dose vaccinees and 94.7% (95% CI: 89.2-97.4) among 2-dose vaccinees in School A, with a second dose incremental VE of 72.1% (95% CI: 39.0-87.3). Varicella VE among School B students did not differ significantly by dose (80.1% vs. 84.2% among 1-dose and 2-dose vaccinees, respectively). CONCLUSION Laboratory testing could not confirm varicella as the etiology of this outbreak; clinical and epidemiologic data suggests varicella as the likely cause. Better diagnostics are needed for diagnosis of varicella in vaccinated individuals so that appropriate outbreak control measures can be implemented.

Impact of the US Two-dose Varicella Vaccination Program on the Epidemiology of Varicella Outbreaks: Data from Nine States, 2005-2012.

Background: A routine 2-dose varicella vaccination program was adopted in 2007 in the US to help further decrease varicella disease and prevent varicella outbreaks. We describe trends and characteristics of varicella outbreaks reported to the Centers for Disease Control and Prevention (CDC) during 2005–2012 from 9 states. Methods: Data on varicella outbreaks collected by 9 state health departments were submitted to CDC using the CDC outbreak reporting worksheet. Information was collected on dates of the outbreak, outbreak setting and number of cases by outbreak; aggregate data were provided on the numbers of outbreak-related cases by age group, vaccination status and laboratory confirmation. Results: Nine hundred and twenty-nine outbreaks were reported from the 6 states, which provided data for each year during 2005–2012. Based on data from these 6 states, the number of outbreaks declined by 78%, decreasing from 147 in 2005 to 33 outbreaks in 2012 (P = 0.0001). There were a total of 1015 varicella outbreaks involving 13,595 cases reported by the 9 states from 2005 to 2012. The size and duration of outbreaks declined significantly over time (P < 0.001). The median size of outbreaks was 12, 9 and 7 cases and median duration of outbreaks was 38, 35 and 26 days during 2005–2006, 2007–2009 and 2010–2012, respectively. Majority of outbreaks (95%) were reported from schools, declining from 97% in 2005–2006 to 89% in 2010–2012. Sixty-five percent of outbreak-related cases occurred among 5-year to 9-year olds, with the proportion declining from 76% in 2005–2006 to 45% during 2010–2012. Conclusions: The routine 2-dose varicella vaccination program appears to have significantly reduced the number, size and duration of varicella outbreaks in the US.

Trends in varicella mortality in the United States: Data from vital statistics and the national surveillance system

This manuscript describes trends in US varicella mortality using national vital statistics system data for 2008–2011, the first years of the routine 2-dose varicella vaccination program, and characteristics of varicella deaths reported to CDC during 1996–2013. We obtained data on deaths with varicella as underlying or contributing cause from the 2008–2011 Mortality Multiple Cause-of Death records and calculated rates to compare with the prevaccine and mature 1-dose varicella vaccination program eras. We also reviewed available records of varicella deaths reported to CDC through the national varicella death surveillance. The annual average age-adjusted mortality rate for varicella as the underlying cause was 0.05 per million population during 2008–2011, an 87% reduction from the prevaccine years. Varicella deaths among persons aged <20 y declined by 99% in 2008–2011 compared with prevaccine years. There was a 70% decline in varicella mortality rates among those <20 y in 2008–2011 compared to 2005–2007. Among the 83 deaths reported to CDC during 1996–2013 classified as likely due to varicella, 24 (29%) were among immunocompromised individuals. Five were among persons previously vaccinated with 1 dose of varicella vaccine. In conclusion, although the US varicella vaccination program has significantly reduced varicella disease burden, there are still opportunities to prevent varicella and its associated morbidity and mortality through routine varicella vaccination, catch-up vaccination, and ensuring that household contacts of immunocompromised persons have evidence of immunity.

Psychological Stress as a Trigger for Herpes Zoster: Might the Conventional Wisdom Be Wrong?

The causes for zoster remain largely unknown. Psychological stress is one commonly considered risk factor. We used self-controlled case series methods to look for increases in zoster following death or catastrophic health event occurring in a previously healthy spouse. We found no increase, although this stressor led to increased mental health visits.

Varicella Outbreak Reporting, Response, Management, and National Surveillance

Two national surveys were conducted to evaluate the status of varicella case-based surveillance and outbreak response. Although progress toward national surveillance has been significant, a large number of jurisdictions are still without case-based surveillance. For jurisdictions beginning case-based surveillance with limited resources, a staged approach is recommended. The national outbreak survey showed that a significant number of varicella outbreaks continue to occur. The majority of jurisdictions respond to these outbreaks, although the response varies considerably. Depending on the outbreak-response approach, costs per outbreak ranged from

Challenges With Controlling Varicella in Prison Settings Experience of California, 2010 to 2011

3000 for a typical, or passive, response to