Varicella-zoster Virus Antibody Research Articles

Varicella-zoster virus-specific, cell-mediated immunity with interferon-gamma release assay after vaccination of college students with no or intermediate IgG antibody response.

This study measured Varicella-zoster virus (VZV) specific cell-mediated immunity (CMI) and antibodies to clarify immune response after vaccination in 68 college students with negative or intermediate IgG antibody status. The enrolled numbers of negative, intermediate, and positive VZV-IgG antibody were 27, 41, and 28 students, respectively. The positive rates of CMI were 3.7% (1/27), 41.5% (17/41), and 96.4% (27/28) before vaccination, respectively. After vaccination, the IgG antibody titers became significantly higher in the intermediate IgG group compared to those in the negative IgG group (P < 0.01), but CMI did not differ significantly between the two groups. Ninety-three percent (38/41) of the intermediate IgG antibody group and 41% (11/27) of the negative IgG antibody group became positive for the IgG antibody after vaccination (P < 0.0001). When subjects were divided into negative, intermediate, and positive CMI by interferon-gamma values before vaccination, the IgG antibody and interferon-gamma values increased significantly in the positive CMI group compared to the negative CMI group after vaccination (P < 0.01 and P < 0.01, respectively). All (17/17) of positive CMI group and 61% (27/44) of negative CMI group became positive for the IgG antibody after vaccination (P < 0.01). Ninety-four percent (16/17) of positive CMI group and 59% (28/44) of negative CMI group became positive for CMI after vaccination (P < 0.05). Ninety-six percent (22/23) of the subjects with a history of vaccination became IgG seropositive after a second dose of vaccination, but 22% (5/23) of them remained negative for CMI. CMI is valuable information to identify potential non-responders to vaccination and to predict risk of clinical VZV infection.

Detection of antibodies to varicella-zoster virus in recipients of the varicella vaccine by using a luciferase immunoprecipitation system assay.

A high-throughput test to detect varicella-zoster virus (VZV) antibodies in varicella vaccine recipients is not currently available. One of the most sensitive tests for detecting VZV antibodies after vaccination is the fluorescent antibody to membrane antigen (FAMA) test. Unfortunately, this test is labor-intensive, somewhat subjective to read, and not commercially available. Therefore, we developed a highly quantitative and high-throughput luciferase immunoprecipitation system (LIPS) assay to detect antibody to VZV glycoprotein E (gE). Tests of children who received the varicella vaccine showed that the gE LIPS assay had 90% sensitivity and 70% specificity, a viral capsid antigen enzyme-linked immunosorbent assay (ELISA) had 67% and 87% specificity, and a glycoprotein ELISA (not commercially available in the United States) had 94% sensitivity and 74% specificity compared with the FAMA test. The rates of antibody detection by the gE LIPS and glycoprotein ELISA were not statistically different. Therefore, the gE LIPS assay may be useful for detecting VZV antibodies in varicella vaccine recipients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00921999.).

Varicella zoster immune status in children treated for acute leukemia.

Children treated for acute leukemia are at increased risk of severe infection with varicella zoster virus (VZV). We studied the VZV sero-status of children with acute leukemia prior to starting chemotherapy and after completion of chemotherapy. VZV sero-status was assessed using time resolved fluorescence immunoassay (TRFIA) before starting treatment and 6 months after completion of treatment. Prior to starting treatment for acute leukemia, a significant proportion of children (35%) are VZV seronegative. On completion of treatment most patients maintained protective VZV antibody levels; however, 35% had reduced/loss VZV antibody to a level considered non-protective and susceptible to VZV infection.

Evaluation of Measles, Rubella, Mumps, Hepatitis B and Varicella Zoster Antibodies in Medical and Dental Students in Shiraz, Iran

Measles, rubella, mumps, hepatitis B virus (HBV) and varicella zoster virus (VZV) cause infectious diseases that can be effectively prevented by vaccination. Vaccination of medical students is important, because they are more likely to become exposed and infected by these viruses. A total of 180 students, consisting of 90 women and 90 men, were serologically screened for measles, rubella and mumps, HBV and VZV antibodies. Their sera were examined for Immunoglobulin G (IgG) antibody against these viruses by using ELISA IgG kits. Total antibody against measles, rubella, mumps, HBV and VZV were 52%, 100%, 76%, 68% and 15% respectively. There was no significant difference in antibodies level according to gender. The results of this study indicate vaccination is vital for medical student prior to hospital training.

Varicella and Varicella Vaccination in South Korea

With continuing occurrence of varicella despite increasing vaccine coverage for the past 20 years, a case-based study, a case-control study, and an immunogenicity and safety study were conducted to address the impact of varicella vaccination in South Korea. Varicella patients under the age of 16 years were enrolled for the case-based study. For the case-control study, varicella patients between 12 months and 15 years of age were enrolled with one control matched for each patient. For the immunogenicity and safety study, otherwise healthy children from 12 to 24 months old were immunized with Suduvax (Green Cross, South Korea). Fluorescent antibody to membrane antigen (FAMA) varicella-zoster virus (VZV) antibody was measured before and 6 weeks after immunization. In the case-based study, the median age of the patients was 4 years. Among 152 patients between 1 and 15 years of age, 139 children received varicella vaccine and all had breakthrough infections. Clinical courses were not ameliorated in vaccinated patients, but more vaccinated patients received outpatient rather than inpatient care. In the case-control study, the adjusted overall effectiveness of varicella vaccination was 54%. In the immunogenicity and safety study, the seroconversion rate and geometric mean titer for FAMA antibody were 76.67% and 5.31. Even with increasing varicella vaccine uptake, we illustrate no upward age shift in the peak incidence, a high proportion of breakthrough disease, almost no amelioration in disease presentation by vaccination, and insufficient immunogenicity of domestic varicella vaccine. There is need to improve the varicella vaccine used in South Korea.

Susceptibility to varicella zoster of children with cystic fibrosis

Varicella zoster virus (VZV) infection can result in significant morbidity in patients with cystic fibrosis (CF), and the risk of severe pulmonary complications rises with age [[1]MacDonald N.E. Morris R.F. Beaudry P.H. Varicella in children with cystic fibrosis.Pediatr Infect Dis J. 1987; 6: 414-416Crossref PubMed Scopus (10) Google Scholar]. This is a greater concern in those receiving systemic corticosteroids, which in the case of CF is most often given for acute allergic bronchopulmonary aspergillosis (ABPA). Severe complications such as pneumonitis, secondary bacterial infections, and liver failure may occur despite prompt treatment with antiviral agents. The seroprevalence of VZV antibodies in CF children is unknown, although in the general population >80% of children over 6 years of age have evidence of immunity [[2]Vyse A.J. Gay N.J. Hesketh L.M. Morgan-Capner P. Miller E. Seroprevalence of antibody to varicella zoster virus in England and Wales in children and young adults.Epidemiol Infect. 2004; 132: 1129-1134Crossref PubMed Scopus (60) Google Scholar]. We aimed to investigate the seroprevalence of VZV antibodies in children attending our large paediatric specialist CF centre, whether or not there was a history of chicken pox. In 2011 we started routine testing for VZV antibodies in 6 year olds at their annual review. This age was selected in view of the low prevalence of ABPA under that age and the chance that children would already have had chicken pox. Evidence of immunity to VZV was determined by VZV IgG antibodies ≥0.9 IU/L (measured by a VIDAS VZV IgG enzyme-linked fluorescent immunoassay). In 2012 the prevalence of ABPA in our CF clinic was 9%, 96% of which was aged 6 and above. As this was a new policy, we also tested older children in order to cover the whole clinic. We identified all children in our CF clinic aged ≥6 years at August 2012, and collected data on VZV immunity 12 months later, thus ensuring that children aged ≥6 years at the initial time-point would have had an annual review. We asked general practitioners to vaccinate patients with a negative result. There were 232 patients aged ≥6 years. 178 patients (77%) in this cohort had been tested for evidence of VZV immunity within the year. Of these, n = 22 (12%) had no evidence of VZV antibodies and were therefore susceptible to chickenpox (Fig. 1). In our paediatric CF population, the prevalence of VZV antibodies was similar to that reported for the general population. However, unlike the general population, children with CF are at greater risk of serious complications from varicella infection. In contrast to other groups of patients with chronic diseases whose treatment may result in immunosuppression, there is no UK-wide specific recommendation for VZV immunization in CF. Vaccination against VZV before immune compromise has been used as a strategy to prevent VZV complications in patients starting immunosuppressive therapy [[3]Levin M.J. Varicella vaccination of immunocompromised children.J Infect Dis. 2008; 197: S200-S206Crossref PubMed Scopus (47) Google Scholar]. We suggest screening for VZV antibodies in children with CF at 6 years and offering vaccination for those found to be seronegative.

The fraction of varicella zoster virus-specific antibodies among all intrathecally-produced antibodies discriminates between patients with varicella zoster virus reactivation and multiple sclerosis

BackgroundPrimary infection with or reactivation of varicella zoster virus (VZV) can cause neurologic complications, which typically result in an intrathecal production of VZV-specific antibodies. Intrathecal antibodies to VZV are detectable by an elevated antibody index (AI). However, elevated VZV AIs are also found in more than half of patients with multiple sclerosis (MS), where they are thought to be part of a polyspecific intrathecal immune response. Determination of the fraction of intrathecally-produced virus-specific antibodies among all intrathecally produced antibodies may discriminate between virus-specific and polyspecific intrathecal immune responses, but the fraction of intrathecally-produced VZV-specific immunoglobulin (Ig)G of the total intrathecally produced IgG (FS anti-VZV) in patients with MS and VZV reactivation has hitherto not been compared.FindingsFS anti-VZV was calculated in patients with a clinically isolated syndrome suggestive of multiple sclerosis (MS) or MS (n = 20) and in patients with VZV reactivation (7 samples from 5 patients), which all had elevated VZV AIs. The median FS anti-VZV was 35-fold higher in patients with VZV reactivation (45.1%, range 13.5-73%) than in patients with CIS/MS (1.3%, range 0.3-5.3%; p = 0.0001). While there was thus no overlap of FS anti-VZV values between groups, VZV AIs completely overlapped in patients with CIS/MS (1.6-14.8) and VZV reactivation (2.1-8.1).ConclusionsThe fraction of intrathecally-produced VZV-specific IgG of the total intrathecally produced IgG discriminates between patients with VZV reactivation and MS. Our results provide further evidence that intrathecally-produced VZV antibodies are part of the polyspecific immune response in patients with MS.

Seroepidemiology of Varicella and value of self-reported history of Varicella infection in Iranian medical students

We conducted this study to assess the seroprevalence of Varicella zoster virus (VZV) antibodies in a group of Iranian medical sciences students that were at risk of Varicella and the value of self-reported history as a predictor of immunity. 255 medical, nursing and obstetrics students who had not entered as a student or worked in a hospital from 3 different schools were enrolled in the study in 2012 (Qazvin province, Iran). Demographics and other information as well as the history of Varicella were obtained through a self-administered questionnaire. Blood samples were collected to determine the Varicella IgG levels via an enzyme-linked immunosorbent assay. A statistical analysis was performed by calculating prevalences and their 95% confidence intervals. Sensitivity, specificity, positive and negative predictive values, Cohen's kappa and positive and negative likelihood ratios of recalled history were determined. p < 0.05 was considered statistically significant. The mean age of participants was 21.3 ± 4.3 years. Seropositivity rate was 74.5%. The relationships between marital status, number of family members, and acquired VZV history with immunity against the virus were statistically significant. The overall rate of reported history was 57%. The positive and negative predictive values of self-reported history of Varicella were 91% and 47.3%, respectively. Immunization of students of Iranian medical sciences seems logical in the near future. Also, they should be tested for Varicella immunity regardless of the history of previous infection.

The Significance of Varicella Exposure History and Correlation with Serology among Patients with Inflammatory Bowel Disease: Presidential Poster

Purpose: Varicella zoster virus (VZV) infection is a significant concern in immunosuppressed IBD patients with reports of severe, disseminated, and occasionally fatal infection. The European Crohn's and Colitis Organization (ECCO) guidelines on IBD immunization recommend using patient-reported varicella exposure history as an indicator to VZV immunity, and immunization of those with a negative exposure or vaccination history. Data on accurate recall of infection with corroborative serology are scarce. We analysed the significance of prior varicella exposure in predicting VZV seroprotection in IBD patients. Methods: We conducted a retrospective review of 220 consecutive patients attending our IBD clinic from October, 2012 to May, 2013. Data including patient demographics, disease phenotype, and prior VZV exposure (infection or vaccination), including VZV antibody titres, was obtained from electronic or case notes review. Ongoing medical therapy for IBD at the time of testing was also recorded. Results: Data for VZV exposure status and tests for VZV titres was available in 71 IBD patients (Crohn's disease n=39, ulcerative colitis n=32). Of these, 55% were females, the median age was 42 years (range 21-79), and mean disease duration was 8.7 years.Twenty-seven percent of patients were on no treatment, 24% were on aminosalicylates, and 49% were on effective immunosuppression. This included 16 (46%) patients on thiopurines, one (3%) on methotrexate, five (14%) on infliximab, two (6%) on adalimumab, three (8%) on infliximab + thiopurine combination, one (3%) on infliximab + methotrexate, six (17%) on corticosteroids, and one (3%) on infliximab + prednisolone. Two-third of patients (69%) were uncertain about a prior exposure to varicella; 28% gave a definitive history, and 3% stated no previous exposure. The overall prevalence of seropositivity for VZV IgG was 62/71 (87%), with 85% seropositivity in patients receiving immunosuppressive treatment. Despite definitive VZV exposure history, 10% patients were seronegative; these patients were on combined immunosuppressive therapy with infliximab and thiopurine. A total of 14% patients on immunomodulation were VZV IgG seronegative; 40% of these on bi-modal immunosuppressive therapy. Conclusion: A significant number of patients are seronegative, despite a positive history for varicella exposure, suggesting a loss of seroprotection possibly from immunosuppression. A strategy combining varicella exposure history with serology may identify history-positive yet seronegative individuals who merit vaccination, but arguably also identify history-negative yet seropositive individuals, resulting in a lower rate of unnecessary vaccination. There is an urgent need for more data, which could influence guideline development in this area.

Serology indicates cytomegalovirus infection is associated with varicella‐zoster virus reactivation

Varicella-zoster virus (VZV) causes chickenpox after which the virus remains latent in neural ganglia. Subsequent reactivation episodes occur, leading mainly to subclinical detection of VZV, but also to the clinical entity herpes zoster. These reactivations are known to occur most frequently amongst immunocompromised individuals, but the incidence of herpes zoster is also known to increase with age, supposedly as a consequence of immunosenescence. Our analysis aims to explore associations between cytomegalovirus (CMV) infection and VZV reactivation by analyzing VZV-specific antibody titers as a function of age, gender, and CMV serostatus. The analysis was repeated on measles and parvovirus B19 antibody titers. At the time of the observations, measles virus circulation was virtually eliminated, whereas parvovirus B19 circulated at lower levels than VZV. Multiple linear regression analyses, using the log-transformed antibody titers, identified a positive association between ageing and VZV antibody titers suggesting that ageing increasingly stimulates VZV reactivation. CMV infection further amplified the positive association between ageing and the reactivation rate. A negative association between CMV infection and VZV antibody titers was found in young individuals, thereby supporting the hypothesis that CMV infection may have a negative effect on the number of B-cells. However, no associations between CMV infection and measles or parvovirus B19 antibody titers occurred, but ageing tended to be associated with a decrease in the antibody titer against parvovirus B19. The combined results thus suggest that both CMV-dependent and CMV-independent immunosenescence occurs. This is supported by an in-depth analysis of VZV, measles and parvovirus B19 antibody titers.

Safety and Immunogenicity of Heat-Treated Zoster Vaccine (ZVHT) in Immunocompromised Adults

Safety and immunogenicity of heat-treated zoster vaccine (ZVHT) were assessed in immunocompromised adults. In a randomized, double-blind, placebo-controlled, multicenter study, 4 doses ZVHT or placebo were administered approximately 30 days apart to adults with either solid tumor malignancy (STM); hematologic malignancy (HM); human immunodeficiency virus (HIV) with CD4(+) ≤200; autologous hematopoietic stem-cell transplant (HCT) or allogeneic-HCT recipients. Varicella-zoster virus (VZV) T-cell responses by interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT) and VZV antibody concentrations by glycoprotein enzyme-linked immunosorbent assay (gpELISA) were measured at baseline and approximately 28 days after each dose. No safety signals were found in any group. IFN-γ ELISPOT geometric mean fold rises (GMFR) after dose 4 in STM, HM, HIV, and autologous-HCT patients were 3.00 (P < .0001), 2.23 (P = .004), 1.76 (P = .026), and 9.01 (P = NA), respectively. Similarly, antibody GMFR were 2.35 (P < .0001), 1.28 (P = .003), 1.37 (P = .017), and 0.90 (P = NA), respectively. T-cell and antibody responses were poor after 4 doses of ZVHT in allogeneic-HCT patients. ZVHT was generally safe and immunogenic through 28 days post-dose 4 in adults with STM, HM, and HIV. Autologous-HCT but not allogeneic-HCT patients had a rise in T-cell response; antibody responses were not increased in either HCT population. Study identification. V212-002 Clinical Trials Registration. NCT00535236.

Concomitant Administration of Pneumococcal-23 and Zoster Vaccines Provides Adequate Herpes Zoster Coverage

To determine whether concomitant administration of zoster vaccine and polysaccharide pneumococcal-23 vaccine (PPV23) provides sufficient protection against herpes zoster infections. Literature was retrieved through the Centers for Disease Control and Prevention (CDC) website, PubMed (inception-February 2013), and Scopus (inception-February 2013) using the key words herpes zoster, pneumococcal, vaccine, concomitant, simultaneous administration, Pneumovax, Zostavax, and barriers. In addition, reference citations from publications were used. All English-language articles identified from the data sources were evaluated. Two studies evaluating concomitant and nonconcomitant administration of zoster vaccine and PPV23 were included. Current product labeling recommends a 4-week interval between zoster vaccine and PPV23 administration; however, the Food and Drug Administration (FDA) and the CDC promote concomitant administration to prevent a missed opportunity to vaccinate. This has caused confusion among health care professionals regarding the appropriate timing of these vaccines. A randomized trial that evaluated the immunogenicity of zoster vaccine and PPV23 given together versus separated by at least 4 weeks demonstrated that the varicella zoster virus (VZV) antibody levels of concomitant versus nonconcomitant vaccination groups did not meet noninferiority requirements. However, a large retrospective cohort trial that compared the incidence of herpes zoster infections following concomitant versus nonconcomitant administration of PPV23 and zoster vaccine did not find a statistically significant between-group difference. Concomitant administration of zoster vaccine and PPV23 is advocated by the CDC and FDA to improve immunization rates among vaccine-eligible individuals. Since there is no direct evidence that simultaneous administration of zoster vaccine and PPV23 puts patients at increased risk of developing herpes zoster, the vaccines should be given during the same office visit to avoid a missed opportunity to vaccinate against 2 serious diseases.

Ramsay Hunt syndrome associated with tocilizumab therapy in rheumatoid arthritis: a case report

Ramsay Hunt syndrome associated with tocilizumab therapy in rheumatoid arthritis: a case report

Immunogenicity and safety of a live attenuated shingles (herpes zoster) vaccine (Zostavax®) in individuals aged ≥ 70 years: A randomized study of a single dose vs. two different two-dose schedules

Disease protection provided by herpes zoster (HZ) vaccination tends to reduce as age increases. This study was designed to ascertain whether a second dose of the HZ vaccine, Zostavax®, would increase varicella zoster virus (VZV)-specific immune response among individuals aged ≥ 70 y. Individuals aged ≥ 70 y were randomized to receive HZ vaccine in one of three schedules: a single dose (0.65 mL), two doses at 0 and 1 mo, or two doses at 0 and 3 mo. VZV antibody titers were measured at baseline, 4 weeks after each vaccine dose, and 12 mo after the last dose. In total, 759 participants (mean age 76.1 y) were randomized to receive vaccination. Antibody responses were similar after a single dose or two doses of HZ vaccine [post-dose 2/post-dose 1 geometric mean titer (GMT) ratios for the 1-mo or 3-mo schedules were 1.11, 95% confidence interval (CI) 1.02–1.22 and 0.78, 95% CI 0.73–0.85], respectively). The 12-mo post-dose 2/12-mo post-dose 1 GMT ratio was similar for the 1-mo schedule and for the 3-mo schedule (1.06, 95% CI 0.96–1.17 and 1.08, 95% CI 0.98–1.19, respectively). Similar immune responses were observed in participants aged 70–79 y and those aged ≥ 80 y. HZ vaccine was generally well tolerated, with no evidence of increased adverse event incidence after the second dose with either schedule. Compared with a single-dose regimen, two-dose vaccination did not increase VZV antibody responses among individuals aged ≥ 70 y. Antibody persistence after 12 mo was similar with all three schedules.

Changes in the prevalence of the measles, rubella, varicella-zoster, and mumps virus antibody titers in Japanese pregnant women

In the present study, immunity against infectious diseases, which are capable of influencing both the mother and fetus during pregnancy and the infant in the postnatal period, were assessed in pregnant women to elucidate the necessity of vaccination during the childbearing age. It was determined that there was a trend of increases in the proportion of patients that had low antibody titers observed at a young age. Overall, after adjusting for age, low antibody titers of measles (≤4 via the neutralization test [NT]), rubella (≤16 via the hemagglutination inhibition [HI]), and varicella and mumps (plus minus or negative on the enzyme-linked immunosorbent assay [EIA]) indicated that the rates of necessity for vaccination against measles, rubella, varicella, and mumps were 27.6%, 16.1%, 3.9%, and 23.8%, respectively. In Japan, acquired immunity for measles, rubella, and mumps was dependent on vaccination, whereas acquired immunity for varicella was dependent on natural infection. We recommend that women be vaccinated after delivery, as these vaccines are live, and thereby, are contraindicated during pregnancy.

Transient Idiopathic Isolated Unilateral Hypoglossal Nerve Palsy

A 33-year-old woman presented with five days of dysarthria and dysphagia. Her past medical history included Graves’ disease treated with a partial thyroidectomy five years earlier. On examination, she had tongue mounding and deviation to the right (Figs. 1 and ​and2).2). Other neurological and otorhinolaryngological findings were normal. Titers of herpes simplex virus and varicella-zoster virus antibodies were positive, but did not differ between the acute and convalescent phase sera. Brain magnetic resonance imaging (MRI) and magnetic resonance angiogram (MRA) findings were normal, and laboratory tests showed no evidence of inflammation. Idiopathic isolated unilateral hypoglossal nerve palsy was diagnosed. Figure 1. Right tongue mounding at rest. Figure 2. Tongue deviation to the right. While cranial nerves III, IV, VI and VII are more prone to idiopathic palsy, idiopathic unilateral hypoglossal nerve palsy is rare. With the limited number of cases reported, the male-to-female ratio appears even, the age of onset is widely distributed (20–69 years) and the majority of cases self-resolve.1 In acute isolated hypoglossal nerve palsy, malignancy, vascular pathology, herpes infection, systemic lupus erythematosus, multiple sclerosis and diabetic mononeuropathy have been reported as causes.1–3 Although the paired sera failed to show acute herpes infection in this case, reactivation of the disease could still be possible. Eight weeks after symptom onset, this patient fully recovered without intervention.

Varicella Zoster Virus Disease After Pediatric Living Donor Liver Transplantation: Is It Serious?

ObjectivesThe aim of this study was to evaluate patients who developed varicella zoster virus (VZV) disease after pediatric living donor liver transplantation (PLDLT). MethodsTwo hundred fifty-five patients who underwent PLDLT between 1995 and 2010 were included in this study. Pretransplantation vaccination of VZV was performed for all recipients except emergency PLDLTs. Posttransplantation VZV vaccination was administered to the patients with a low VZV antibody titer 2 years or more after transplantation. The clinical course and outcomes of VZV disease in cases were reviewed with the transplant database and hospital medical records. ResultsSixty-three patients developed VZV disease (chicken pox in 61, herpes zoster in 2) at a median onset of 36 months after PLDLT and at a median age of 4 years old, with a cumulative incidence of 25%. All chicken pox occurred in VZV antibody-negative patients. The onset of herpes zoster in the two patients occurred within 3 months after PLDLT; in addition, these patients were VZV antibody-positive patients. The clinical presentations of most patients were not serious and there were no disseminated infections. Although only 3 patients (5%) were hospitalized, the other 60 patients (95%) all showed a good response to oral antiviral therapy. ConclusionsAlthough VZV disease is an infectious disease with a high morbidity rate after PLDLT, it can normally be successfully managed on an outpatient basis at home. Pre- and posttransplantation vaccinations are effective for delaying the onset of chicken pox after PLDLT and to prevent it from developing into a serious illness.

Varicella in Infants After Implementation of the US Varicella Vaccination Program

To describe varicella disease in infants since implementation of the varicella vaccination program in the United States. From 1995 to 2008, demographic, clinical, and epidemiologic data on cases of varicella in infants were collected prospectively through a community-based active surveillance project. We examined disease patterns for infants in 2 age groups: 0 to 5 and 6 to 11 months. Infant varicella disease incidence declined 89.7% from 1995 to 2008. Infants aged 0 to 5 months had milder clinical disease than those aged 6 to 11 months: ≥50 lesions, 49% vs 58% (P = .038); fever (body temperature > 38°C), 12% vs 21% (P = .014); and varicella-related complications, 6% vs 14% (P = .009), respectively. Age was an independent predictor of the occurrence of complications. The varicella vaccination program has resulted in substantial indirect benefits for infants, who are not eligible for vaccination. Presence of maternal varicella-zoster virus antibodies might explain attenuated disease in very young infants likely born to mothers with history of varicella. Although varicella disease incidence has declined, exposure to varicella-zoster virus continues to occur. Improving varicella vaccination coverage in all age groups will further reduce the risk of varicella exposure and protect those not eligible for varicella vaccination.

Immunogenicity and safety of ZOSTAVAX® approaching expiry potency in individuals aged ≥50 years

Background: Age is a major risk factor for herpes zoster (HZ) and its potential long-term complication post-herpetic neuralgia (PHN). Due to the significant burden of HZ and PHN on patients’ quality of life, it is vital that effective and well-tolerated vaccines are available to prevent HZ in older adults. ZOSTAVAX® vaccine was developed to prevent HZ and PHN in individuals ≥50 years (y) of age, and its clinical efficacy and safety have been demonstrated.Aims and Methods: This phase 4, open-label, multicenter study was undertaken to assess the immunogenicity and safety of a single dose of ZOSTAVAX (refrigerator-stable formulation) given within 6 mo of its expiry date in individuals ≥50 y of age. The geometric mean fold rise (GMFR) from pre-vaccination to 4 weeks post-vaccination in varicella zoster virus (VZV) antibody titers was calculated. An acceptable antibody response was defined as a lower 95% confidence interval (CI) of GMFR >1.4. Solicited and unsolicited injection-site reactions and systemic adverse events were recorded.Results: The GMFR in VZV antibody titers was 3.1 (95% CI: 2.6, 3.8), satisfying the criterion for an acceptable VZV antibody response to ZOSTAVAX (minimum requirement: 1.4 GMFR). An acceptable rise in VZV antibody titers was observed in individuals of 50–59 y of age (GMFR 3.9; 95% CI: 2.9, 5.1) and in those ≥60 y of age (GMFR 2.5; 95% CI: 1.9, 3.2). ZOSTAVAX was well tolerated; no serious adverse events were reported.Conclusion: ZOSTAVAX elicits an acceptable immune response in immunocompetent individuals ≥50 y of age when stored as directed and administered during the 6 mo prior to expiration.

Impaired antibody memory to varicella zoster virus in HIV‐infected children: low antibody levels and avidity*

HIV-infected children have impaired antibody responses after exposure to certain antigens. Our aim was to determine whether HIV-infected children had lower varicella zoster virus (VZV) antibody levels compared with HIV-infected adults or healthy children and, if so, whether this was attributable to an impaired primary response, accelerated antibody loss, or failure to reactivate the memory VZV response. In a prospective, cross-sectional and retrospective longitudinal study, we compared antibody responses, measured by enzyme-linked immunosorbent assay (ELISA), elicited by VZV infection in 97 HIV-infected children and 78 HIV-infected adults treated with antiretroviral therapy, followed over 10 years, and 97 age-matched healthy children. We also tested antibody avidity in HIV-infected and healthy children. Median anti-VZV immunoglobulin G (IgG) levels were lower in HIV-infected children than in adults (264 vs. 1535 IU/L; P<0.001) and levels became more frequently unprotective over time in the children [odds ratio (OR) 17.74; 95% confidence interval (CI) 4.36-72.25; P<0.001]. High HIV viral load was predictive of VZV antibody waning in HIV-infected children. Anti-VZV antibodies did not decline more rapidly in HIV-infected children than in adults. Antibody levels increased with age in healthy (P=0.004) but not in HIV-infected children. Thus, antibody levels were lower in HIV-infected than in healthy children (median 1151 IU/L; P<0.001). Antibody avidity was lower in HIV-infected than healthy children (P<0.001). A direct correlation between anti-VZV IgG level and avidity was present in HIV-infected children (P=0.001), but not in healthy children. Failure to maintain anti-VZV IgG levels in HIV-infected children results from failure to reactivate memory responses. Further studies are required to investigate long-term protection and the potential benefits of immunization.