John X. Zhang

Changing Varicella Epidemiology in Active Surveillance Sites—United States, 1995–2005

Significant reductions in varicella incidence were reported from 1995 to 2000 in the varicella active surveillance sites of Antelope Valley (AV), California, and West Philadelphia (WP), Pennsylvania. We examined incidence rates, median age, and vaccination status of case patients for 1995-2005. Coverage data were from the National Immunization Survey. By 2005, coverage among children 19-35 months of age reached 92% (AV) and 94% (WP); 57% and 64% of case patients in AV and WP, respectively, were vaccinated; and varicella incidence declined by 89.8% in AV and 90.4% in WP. Incidence declined in all age groups, especially among children <10 years of age in both sites and among adolescents 10-14 years of age in WP. In AV, since 2000, the incidence among adolescents 10-14 and 15-19 years of age increased. Implementation of school requirements through 10th grade in WP may explain the differences in the decline in incidence among adolescents. Continued surveillance will be important to monitor the impact that the 2-dose vaccine policy in children has on varicella epidemiology.

Near Elimination of Varicella Deaths in the US After Implementation of the Vaccination Program

OBJECTIVE: Varicella has been preventable by vaccination in the United States since 1995. Previous studies reported a 66% decline in mortality rate during the first 6 years of the program. Since then, vaccination coverage has increased substantially. We updated the analysis of US varicella mortality for 2002–2007 and assessed the impact of the first 12 years of the US varicella vaccination program on varicella deaths. METHODS: National data on deaths for which varicella was listed as an underlying or contributing cause were obtained from the Mortality Multiple Cause-of-Death records from the US National Center for Health Statistics. We calculated the age-adjusted and age-specific mortality rates for 2002–2007 and trends since the prevaccine years. RESULTS: During the 12 years of the mostly 1-dose US varicella vaccination program, the annual average mortality rate for varicella listed as the underlying cause declined 88%, from 0.41 per million population in 1990–1994 to 0.05 per million population in 2005–2007. The decline occurred in all age groups, and there was an extremely high reduction among children and adolescents younger than 20 years (97%) and among subjects younger than 50 years overall (96%). In the last 6 years analyzed (2002–2007), a total of 3 deaths per age range were reported among children aged 1 to 4 and 5 to 9 years, compared with an annual average of 13 and 16 deaths, respectively, during the prevaccine years. CONCLUSIONS: The impressive decline in varicella deaths can be directly attributed to successful implementation of the 1-dose vaccination program. With the current 2-dose program, there is potential that these most severe outcomes of a vaccine-preventable disease could be eliminated.

Varicella among Adults: Data from an Active Surveillance Project, 1995–2005

We report detailed population-based data on varicella among adults. In 2 US varicella active surveillance sites with high vaccine coverage among young children, the incidence of varicella among adults declined 74% during 1995-2005. A low proportion (3%) of adults with varicella had been vaccinated, with no improvement over the decade of program implementation, suggesting that the decline was likely secondary to herd-immunity effects. Compared with children, adults had more severe varicella in terms of both clinical presentation and frequency of complications. However, <30% of adults with varicella were treated with acyclovir. Among adolescents, illness severity was intermediate between that in children and adults. Varicella cases are preventable through vaccination. As we enter the second decade of the varicella vaccination program in the United States, we need to ensure that susceptible adolescents and adults are adequately protected from varicella by vaccination and that those who acquire varicella are appropriately treated with effective antiviral treatment.

Varicella-Related Hospitalizations in the United States, 2000–2006: The 1-Dose Varicella Vaccination Era

OBJECTIVE: To describe the effect of the mature 1-dose varicella vaccination program on varicella morbidity, we analyzed 2 national databases for varicella-related hospitalizations in the United States since implementation of the varicella vaccination program in 1995. PATIENTS AND METHODS: Data from the National Hospital Discharge Survey and Nationwide Inpatient Sample were analyzed to describe trends in varicella-related hospitalizations during the 1-dose vaccination era (2000–2006) compared with those in the prevaccination era (1988–1995). Varicella-related hospitalizations were defined by using International Classification of Diseases, Ninth Revision codes. Results were extrapolated to represent national estimates. RESULTS: Using National Hospital Discharge Survey data, 24 488 varicella-related hospitalizations were estimated to occur in the United States during the 1-dose vaccination era. The varicella-related hospitalization rate was 0.12 per 10 000 population during the 1-dose vaccination era versus 0.42 per 10 000 population in the prevaccination era (P < .01). During the 1-dose vaccination era, the estimated annual average number of varicella-related hospitalizations was significantly lower and decreased by ≥65% in all age groups compared with those in the prevaccination era (P < .001 in all age groups). The varicella-related hospitalization rate during the 1-dose vaccination era estimated from the Nationwide Inpatient Sample was 0.09 per 10 000 population. CONCLUSIONS: Varicella-related hospitalization numbers and rates declined significantly during the 1-dose varicella vaccination era. Assuming declines in varicella-related hospitalizations are due, mainly, to the routine childhood varicella vaccination program, these data suggest that varicella vaccination prevented ∼50 000 varicella-related hospitalizations in the United States from 2000 to 2006.

Epidemiology of Varicella Hospitalizations in the United States, 1995–2005

To describe the impact of the varicella vaccination program on varicella-related hospitalizations (VRHs) in the United States, data from the Varicella Active Surveillance Project (VASP) were used to compare rates of hospitalization and rates of complications among patients hospitalized for varicella-related conditions from 1995 to 2005. Of the 26,290 varicella cases reported between 1995 and 2005, 170 cases resulted in VRHs, including 1 case that resulted in death. Both VRH rates per 100,000 population and complications during VRH per 100,000 population decreased significantly between the early vaccination period (1995-1998) and the middle/late vaccination period (1999-2005). Infants and adults were at highest risk for VRH, and having been vaccinated against varicella was a protective factor. Varicella vaccination may have prevented a significant number of VRHs. The fact that 4 vaccinated children required hospitalization for varicella-related complications demonstrates that 1 dose of varicella vaccine does not prevent serious disease in all cases, even among previously healthy children.

Epidemiology of Varicella During the 2-Dose Varicella Vaccination Program - United States, 2005-2014.

Before availability of varicella vaccine in the United States, an estimated 4 million varicella cases, 11,000-13,500 varicella-related hospitalizations, and 100-150 varicella-related deaths occurred annually. The varicella vaccination program was implemented in the United States in 1996 as a 1-dose routine childhood program. Based on data from two varicella active surveillance sites, the varicella vaccination program led to 90% decline in incidence over the next decade (1). However, because of continued varicella outbreaks, a routine 2-dose schedule (at ages 12-15 months and 4-6 years) was recommended and has been in place since 2006 (2). The declines in incidence (1,3-6) made it feasible for states to implement varicella case-based surveillance and to report varicella data to CDC through the National Notifiable Diseases Surveillance System (NNDSS). State data have become the primary source for monitoring trends in varicella incidence nationally (7). Using NNDSS data, CDC previously reported nationwide declines in varicella incidence of 72% from the end of the 1-dose to the early years of the 2-dose varicella vaccination program (2006-2010) (7). This report updates varicella incidence trends to include the most recent years in the 2-dose varicella vaccination program. Between the period 2005-2006 (before the 2-dose recommendation) and 2013-2014, overall varicella incidence declined 84.6%, with the largest declines reported in children aged 5-9 years (89.3%) and 10-14 years (84.8%). The availability of varicella-specific data varied over time. During the last 2 years examined (2013 and 2014), completeness of reporting of two critical variables monitored by CDC, vaccination status (receipt of at least 1 dose of varicella vaccine) of cases and severity of disease based on number of lesions, were 54.2% and 39.1%, respectively. State and local health departments, in collaboration with CDC, should continue working to improve reporting of cases and completeness of critical varicella-specific variables to better monitor impact of the varicella vaccination program.

Varicella Outbreak Epidemiology in an Active Surveillance Site, 1995-2005

We describe trends and characteristics of varicella outbreaks identified in an active surveillance site from 1995 to 2005. Cases of varicella were reported to the active surveillance project, and outbreaks were defined retrospectively as > or =5 varicella cases epidemiologically linked to a common setting that occurred within 1 incubation period. Outbreaks were grouped by calendar year. From 1995-1998 to 2002-2005, varicella outbreaks significantly decreased in number, from 236 to 46 (P< .001); in size, from a median of 15 cases/outbreak to 9 cases/outbreak (P< .001); and in duration, from 44.5 days to 30 days (P< .001). The median age of case patients with outbreak-related varicella increased from 6 to 9 years (P< .001). The 1-dose varicella vaccination program has been successful in decreasing the number of outbreaks and cases; however, challenges remain with regard to controlling outbreaks among vaccinated persons and targeting vaccination efforts to susceptible persons in older age groups.

Antigenemia, RNAemia, and innate immunity in children with acute rotavirus diarrhea

Antigenemia is commonly detected in children with acute rotavirus diarrhea, but the prevalence of viremia has not been clearly defined. We examined antigenemia in plasma and RNAemia in peripheral blood mononuclear cells (PBMC) of children with acute diarrhea by EIA, RT-PCR, and Southern hybridization, using primers and a probe specific to rotavirus NSP4 gene. We detected the presence of rotavirus antigen in 33.3% and almost full-length NSP4 gene in 70.8% of the acute-phase plasma and PBMC, respectively. In contrast, antigenemia and RNAemia were detected in 0% and 4.2% of the convalescent-phase plasma and PBMC, respectively, which were similar to antigenemia (0%) and RNAemia (7.7%) in healthy controls. We demonstrated an increase in the proportions of activated myeloid dendritic cells (mDC) and activated plasmacytoid DC (pDC) in acute-phase PBMC of patients when compared to those in convalescent phase of patients and in PBMC of healthy controls. The activation of mDC peaked on days 2-4 after illness onset, and the activation of acute-phase pDC appeared to correlate with levels of antigenemia. High prevalence of NSP4 gene in acute-phase PBMC indicates possible rotavirus replication in white blood cells, and extraintestinal spread and the activation of DC may have implications for the prevention of rotavirus disease in children.

Association of Physical Trauma With Risk of Herpes Zoster Among Medicare Beneficiaries in the United States

Risk factors for herpes zoster (HZ) are poorly defined. An age-matched, case-control study was conducted to assess the effect of physical trauma on HZ, using Medicare data. HZ cases were 3.4 times as likely as controls to have experienced trauma in the week before HZ onset, but the magnitude of the association between trauma and HZ declined over time. Cases who had cranial HZ were >25 times as likely as controls to have had cranial trauma in the week before HZ onset. Therefore, recent trauma can be a trigger for HZ.

Update on Incidence of Herpes Zoster Among Children and Adolescents After Implementation of Varicella Vaccination, Antelope Valley, CA, 2000 to 2010.

Background: Changes in herpes zoster (HZ) epidemiology are expected with childhood varicella vaccination. We reported previously that during 2000 to 2006 HZ incidence decreased 55% in children <10 years of age, while among 10- to 19-year olds it increased by 63%. We update the analysis with 4 additional years of data. Methods: Population-based active surveillance was conducted for HZ in Antelope Valley, California. Structured telephone interviews and medical chart reviews collected data on demographics, varicella vaccinations, disease histories and clinical information. We calculated HZ incidence for 2007 to 2010 and assessed trends since 2000. Results: Among children <10 years of age, HZ incidence continued the decreasing trend previously reported. During 2007 to 2010, the average incidence was 12.8 cases/100,000 children compared with 41.6 cases/100,000 children during 2000 to 2006, a 69% decline (P < 0.0001). For the 10- to 19-year olds, during 2007 to 2010 HZ incidence did not continue the increasing trend reported from 2000 to 2006; lower rates than in 2006 were observed in 3 of the 4 additional years evaluated. During 2007 to 2010 the average incidence was 78.2 cases/100,000 children compared with 68.0 cases/100,000 children during 2000 to 2006, a 13% increase (P = 0.123), with substantial fluctuation in annual rates throughout the 11 years of surveillance. Conclusions: During the mature varicella vaccination program, declines in HZ incidence among children <10 years of age continued through 2010. Among the 10- to 19-year olds, the increase reported through 2006 did not continue further and lower rates than in 2006 were observed through 2010. Widespread use of varicella vaccine could reduce HZ incidence among vaccinated populations. Ongoing monitoring of HZ incidence is needed to detect and understand changes in HZ epidemiology in the varicella vaccine era.