Evaluation of laboratory methods for diagnosis of varicella.

BACKGROUND: The incidence of varicella disease is declining as a result of vaccination, making clinical diagnosis more challenging, particularly for vaccine-modified cases. We conducted a comprehensive evaluation of laboratory tests and specimen types to assess diagnostic performance and determine what role testing can play after skin lesions have resolved. METHODS: We enrolled patients with suspected varicella disease in 2 communities. Enrollees were visited at the time of rash onset and 2 weeks later. Multiple skin lesion, oral, urine, and blood or serum specimens were requested at each visit and tested for varicella zoster virus (VZV) immunoglobulin (Ig) G, IgM, and IgA antibody by enzyme-linked immunoassay; for VZV antigen by direct fluorescent antibody; and/or for VZV DNA by polymerase chain reaction (PCR). Clinical certainty of the diagnosis of varicella disease was scored. PCR results from first-visit vesicles or scab specimens served as the gold standard in assessing test performance. RESULTS: Of 93 enrollees, 53 were confirmed to have varicella disease. Among 20 unmodified cases, PCR testing was 95%-100% sensitive for macular and/or papular lesions and for oral specimens collected at the first visit; most specimens from the second visit yielded negative results. Among 27 vaccine-modified cases, macular and/or papular lesions collected at the first visit were also 100% sensitive; yields from other specimens were poorer, and few specimens from the second visit tested positive. Clinical diagnosis was 100% and 85% sensitive for diagnosing unmodified and vaccine-modified varicella cases, respectively. CONCLUSIONS: PCR testing of skin lesion specimens remains convenient and accurate for diagnosing varicella disease in vaccinated and unvaccinated persons. PCR of oral specimens can sometimes aid in diagnosis of varicella disease, even after rash resolves.

Neurological and neuromuscular disease as a risk factor for respiratory failure in children hospitalized with influenza infection.

CONTEXT: The Advisory Committee on Immunization Practices (ACIP) recommends annual influenza vaccination for children with certain chronic medical conditions to prevent serious complications of influenza infection. Little is known about the relative contribution of each of these chronic medical conditions to the development of serious influenza-associated complications. OBJECTIVE: To identify chronic medical conditions that are associated with respiratory failure in children hospitalized with community-acquired laboratory-confirmed influenza. DESIGN, SETTING, AND PATIENTS: A retrospective cohort study of patients aged 21 years or younger hospitalized at The Children's Hospital of Philadelphia with community-acquired laboratory-confirmed influenza during 4 consecutive influenza seasons (June 2000 through May 2004). We examined 9 ACIP-designated high-risk chronic medical conditions and 3 additional chronic medical conditions (neurological and neuromuscular disease [NNMD], gastroesophageal reflux disease [GERD], and history of prematurity) that in recent studies have been associated with influenza hospitalization and severe influenza-related complications. MAIN OUTCOME MEASURES: Rate and odds ratio (OR) of respiratory failure, defined as need for mechanical ventilation. RESULTS: Of 745 children hospitalized with community-acquired laboratory-confirmed influenza, 322 (43%) had 1 or more ACIP-designated high-risk chronic medical conditions. Neurological and neuromuscular disease, GERD, and history of prematurity were present in 12%, 14%, and 3%, of children, respectively. Thirty-two children (4.3%) developed respiratory failure. In multivariate logistic regression analyses, conditions associated with respiratory failure included NNMD (OR, 6.0; 95% confidence interval [CI], 2.7-13.5), chronic pulmonary disease other than asthma (OR, 4.8; 95% CI, 1.5-15.1), and cardiac disease (OR, 4.0; 95% CI, 1.6-10.2). The predicted probabilities of respiratory failure derived from the multivariate model were 12% (95% CI, 7%-20%), 9% (95% CI, 3%-23%), and 8% (95% CI, 4%-18%) for children with NNMD, chronic pulmonary disease, and cardiac disease, respectively. CONCLUSIONS: These results support the ACIP's recent decision to add NNMD to the list of conditions for which annual influenza vaccine is recommended in children. Neurologists and primary care pediatricians should be alerted to the increased risk of respiratory failure and the importance of influenza vaccination in children with NNMD.

Chickenpox or smallpox: the use of the febrile prodrome as a distinguishing characteristic.

BACKGROUND: The ability to differentiate chickenpox from smallpox is important for early recognition of bioterrorism events and prevention of false alarms. The febrile prodrome is a clinical feature used to differentiate these conditions. However, the prevalence of prodromal manifestations in chickenpox has not been well established. METHODS: We evaluated prodrome characteristics of all chickenpox cases identified through an active varicella surveillance program over a 21-month period. The frequencies of various prodromal manifestations among vaccinated and unvaccinated case patients were assessed, and the impact of other demographic features on these manifestations was evaluated. Data were analyzed to determine what proportion met the smallpox febrile prodrome criteria as elaborated in the Centers for Disease Control and Prevention algorithm for evaluating patients suspected of having smallpox. Finally, we compared our data with historical data on smallpox prodromes. RESULTS: Data on prodrome characteristics were available for 932 chickenpox cases. Prodromal fever was present in 37% of unvaccinated chickenpox case patients and in 25% of vaccinated case patients. Among unvaccinated case patients, adults were 70% more likely than children to have fever in the prodrome period. We found that prodromes are less common and less severe in chickenpox than in smallpox. Nevertheless, 7%-17% of unvaccinated chickenpox case patients meet the smallpox febrile prodrome criteria. CONCLUSIONS: Febrile prodromes occur in a significant proportion of patients with chickenpox, particularly among unvaccinated case patients and adults. Therefore, the febrile prodrome alone is not a sufficient marker of smallpox risk. All major and minor smallpox criteria should be considered together in assessing the likelihood of smallpox.

Do laws bring children in child care centers up to date for immunizations?

BACKGROUND: Pennsylvania state law requires licensed child care centers (CCCs) to document that each enrolled child is up to date (UTD) for routine immunizations within 60 days of enrollment. This study evaluates the law's impact on immunization coverage among children aged

Varicella immunity in vaccinated healthcare workers.

BACKGROUND: Nosocomial spread of varicella-zoster virus (VZV) infection can cause severe disease among vulnerable patient-populations and healthcare personnel (HCP). Limited data are available on duration of varicella vaccine-induced protection among adults and to what extent cell-mediated immunity (CMI) and antibody avidity contribute to protection. OBJECTIVE: Evaluate humoral and cell-mediated immune responses of HCP who received a 2-dose regimen of varicella vaccine, and observe the responses to a 3rd vaccine dose among HCP who were seronegative after vaccination. STUDY DESIGN: A convenience sample of HCP with documented 2 doses of varicella vaccine was used to assess acquired VZV immune parameters (cytokine production, IgG avidity). HCP seronegative after 2 doses of vaccine were offered a third dose and evaluated further. Vaccine recipients' immune responses were compared with responses from persons with history of wild-type VZV infection. RESULTS: The convenience sample consisted of 101 HCP with documented 2 doses of varicella vaccine; 12 (11.9%) were seronegative post-vaccination. 11.5% of 61 seropositive 2-dose recipients produced low avidity antibody, suggesting suboptimal response to vaccine. Seven 2-dose vaccinees who were VZV seronegative seroconverted after a third dose; however, 3/7 (42.9%) produced low avidity IgG. 142 persons with a history of varicella were all VZV IgG seropositive, and all had moderate to high avidity IgG. CONCLUSIONS: Measurements of serum IgG titers alone may not accurately reflect vaccine protection. Varicella vaccination of HCP remains important but further studies are needed to evaluate CMI and antibody avidity responses in HCP vaccinated with two doses of varicella vaccine.

Knowledge, attitudes, and practices for diagnosing breakthrough varicella in the outpatient setting.

OBJECTIVES: We assessed provider knowledge, attitudes, and practices for the management of breakthrough varicella and identified barriers to implementation of laboratory testing and reporting. METHODS: We surveyed 145 health-care providers (HCPs) from 30 pediatric practices in Philadelphia who did not have a history of laboratory testing for breakthrough varicella. The self-administered survey instrument collected information on clinicians' practices for management of children presenting with rash, infection-control strategies, reporting to public health agencies, and laboratory testing. RESULTS: Among the 144 HCPs who completed the survey, 73 (51%) had practiced for more than 10 years. While 115 HCPs (80%) would elect to evaluate a child with rash in the office, only 19 (13%) would submit diagnostics. When patients had a known recent exposure to varicella, 84 HCPs (58%) would use laboratory tests: 40% would use direct fluorescent antibody staining on a specimen from a cutaneous lesion, 24% would use polymerase chain reaction on a lesion specimen, 21% would use acute and convalescent serology, and 10% would use other tests. While waiting for test results, 82 HCPs (57%) would advise that the child be kept at home, 39 (27%) would notify the local health department, and 33 (23%) would inform the school nurse. CONCLUSION: As varicella becomes increasingly uncommon, laboratory confirmation becomes more critical for appropriate diagnosis, similar to poliomyelitis and measles. Our findings suggest that HCPs need further education regarding laboratory confirmation, containment, and reporting of breakthrough varicella.

Varicella disease among vaccinated persons: clinical and epidemiological characteristics, 1997-2005.

Approximately 1 in every 5 children who receives 1 dose of varicella vaccine may develop varicella disease, also known as breakthrough disease, if exposed to varicella-zoster virus. Currently, in communities with high vaccination coverage, varicella cases mostly occur in vaccinated individuals. We report on the first population-based description of the clinical and epidemiological characteristics of varicella in populations with increasing vaccine coverage between 1997 and 2005. In vaccinated children 1-14 years of age, varicella was most often mild and modified; the atypical disease presentation may result in diagnostic challenges to health care providers. However, despite the generally mild nature of these cases, approximately 25% caused >50 lesions, and some resulted in serious complications similar to those occurring in unvaccinated individuals. Continued surveillance of the risk and characteristics of breakthrough disease will be needed, to monitor the effect of the new 2-dose vaccine recommendation for children.

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.

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.

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.

Varicella disease after introduction of varicella vaccine in the United States, 1995-2000.

CONTEXT: Before licensure of varicella vaccine in 1995, varicella was a universal childhood disease in the United States, causing 4 million cases, 11,000 hospitalizations, and 100 deaths every year. OBJECTIVE: To examine population-based disease surveillance data in 3 communities to document the impact of the varicella vaccination program. DESIGN, SETTING, AND SUBJECTS: Active surveillance for varicella conducted among the populations of Antelope Valley, Calif; Travis County, Tex; and West Philadelphia, Pa; from January 1, 1995, to December 31, 2000. Reporting sites included child care centers, schools, universities, physicians, public health clinics, hospitals, emergency departments, and households. MAIN OUTCOME MEASURES: Trends in number and rate of varicella cases and hospitalizations; varicella vaccine coverage. RESULTS: From 1995 through 1998, in each surveillance area, the number of verified varicella cases varied from year to year with marked springtime seasonality. In 1999, the number and rates of varicella cases and hospitalizations declined markedly. From 1995 through 2000, in Antelope Valley, Travis County, and West Philadelphia, varicella cases declined 71%, 84%, and 79%, respectively. Cases declined to the greatest extent among children aged 1 to 4 years, but cases declined in all age groups, including infants and adults. In the combined 3 surveillance areas, hospitalizations due to varicella declined from a range of 2.7 to 4.2 per 100,000 population in 1995 through 1998 to 0.6 and 1.5 per 100,000 population in 1999 and 2000, respectively (P =.15). By 2000, vaccine coverage among children aged 19 to 35 months was 82.1%, 73.6%, and 83.8% in Los Angeles County, Texas, and Philadelphia County, respectively. CONCLUSIONS: Varicella disease has declined dramatically in surveillance areas with moderate vaccine coverage. Continued implementation of existing vaccine policies should lead to further reductions of varicella disease in these communities and throughout the United States.