Varicella Zoster Virus IgG Research Articles

PP04.3 – 2650: Varicella angiopathy: The current challenges of management

Stroke secondary to varicella angiopathy commonly occurs in healthy children presenting with hemiparesis with a history of Varicella Zoster Virus (VZV) infection less than 12 months earlier. It accounts for approximately 31% of all children presenting with arterial ischaemic strokes. With recent advances in intrathecal antibody testing clinicians are faced with novel challenges in the management of these children. We describe a 4-year-old child who presented to the emergency department with right arm and leg weakness, slurred speech, and right-sided facial weakness over the previous few hours. He had three episodes in the previous six months characterised by a sudden drop to the ground, without loss of consciousness or jerking. In thirty minutes he had returned to normal activity. MRI brain confirmed multiple focal areas of infarction in the left cerebral hemisphere. MRA showed significant abnormal narrowing of the terminal left internal carotid and proximal left middle cerebral artery. CSF testing confirmed active VZV infection with intrathecal antibody production. A literature search confirmed that in adults, characteristic ischaemic lesions in the setting of positive CSF markers are considered the consistent criteria for diagnosis of varicella angiopathy with no clear diagnostic guidelines for children. Equally there is no consensus in treatment with authors recommending combination of antiviral and immunosuppressive therapy, others anticoagulant and antiplatelet medication. In this case Infectious Disease and Virology consults were sought and a five-week course of intravenous Acyclovir was commenced with oral aspirin. Repeat CSF testing showed no improvement in VZV IgG levels. Following a 3-month course of oral valciclovir, repeat testing confirmed treatment of VZV infection. MRI and MRA showed persistent arterial narrowing and some resolution in areas of infarction. This case illustrates the challenges faced in diagnosis and treatment for children presenting with stroke suspected secondary to Varicella angiopathy and the benefits of multiprofessional working.

Arsenic exposure and prevalence of the varicella zoster virus in the United States: NHANES (2003-2004 and 2009-2010).

BackgroundArsenic is an immunotoxicant. Clinical reports observe the reactivation of varicella zoster virus (VZV) in people who have recovered from arsenic poisoning and in patients with acute promyelocytic leukemia that have been treated with arsenic trioxide.ObjectiveWe evaluated the association between arsenic and the seroprevalence of VZV IgG antibody in a representative sample of the U.S. population.MethodsWe analyzed data from 3,348 participants of the National Health and Nutrition Examination Survey (NHANES) 2003–2004 and 2009–2010 pooled survey cycles. Participants were eligible if they were 6–49 years of age with information on both VZV IgG and urinary arsenic concentrations. We used two measures of total urinary arsenic (TUA): TUA1 was defined as the sum of arsenite, arsenate, monomethylarsonic acid, and dimethylarsinic acid, and TUA2 was defined as total urinary arsenic minus arsenobetaine and arsenocholine.ResultsThe overall weighted seronegative prevalence of VZV was 2.2% for the pooled NHANES sample. The geometric means of TUA1 and TUA2 were 6.57 μg/L and 5.64 μg/L, respectively. After adjusting for age, sex, race, income, creatinine, and survey cycle, odds ratios for a negative VZV IgG result in association with 1-unit increases in natural log-transformed (ln)-TUA1 and ln-TUA2 were 1.87 (95% CI: 1.03, 3.44) and 1.40 (95% CI: 1.0, 1.97), respectively.ConclusionsIn this cross-sectional analysis, urinary arsenic was inversely associated with VZV IgG seroprevalence in the U.S. population. This finding is in accordance with clinical observations of zoster virus reactivation from high doses of arsenic. Additional studies are needed to confirm the association and evaluate causal mechanisms.CitationCardenas A, Smit E, Houseman EA, Kerkvliet NI, Bethel JW, Kile ML. 2015. Arsenic exposure and prevalence of the varicella zoster virus in the United States: NHANES (2003–2004 and 2009–2010). Environ Health Perspect 123:590–596; http://dx.doi.org/10.1289/ehp.1408731

Varicella zoster virus reactivation after autologous SCT is a frequent event and associated with favorable outcome in myeloma patients.

The occurrence of varicella zoster virus (VZV) reactivation is increased after allogeneic transplantation, whereas limited data are available for herpes zoster (HZ) after autologous SCT (ASCT). We determined the incidence and the prognostic significance of HZ and its correlation with VZV serology in 191 consecutive myeloma patients undergoing high-dose melphalan chemotherapy with ASCT. We found that VZV reactivation occurred in 57 (30%) patients, in 8.5% during induction and in 21.5% after ASCT peaking at 8 months after ASCT. Disease burden due to HZ was assessed as high or rather high in 70% of the patients. By immune fluorescence and Serion Elisa VZV IgG assessment, 90.8% of all patients had specific anti-VZV antibodies at ASCT. Lower specific antibody titers at transplantation were observed in patients with HZ after ASCT than in those without reactivation (P=0.009). Finally, OS was better in myeloma patients with HZ after ASCT compared with patients without HZ (P=0.007). Our data indicate that VZV reactivation after ASCT is a frequent event carrying a significant disease burden and it is associated with improved survival. Low levels of specific VZV antibodies at ASCT suggest increased vulnerability for VZV reactivation.

The association of Varicella zoster virus reactivation with Bell's palsy in children

ObjectivesBell's palsy is considered the most common cause of facial nerve paralysis in children. Although different theories have been postulated for its diagnosis, reactivation of the Varicella zoster virus (VZV) has been implicated as one of the causes of Bell's palsy. The aim of the study was to evaluate the association of Varicella-zoster virus infection with Bell's palsy and its outcome in children. MethodsA total of 30 children with Bell's palsy were recruited and were assayed for evidence of VZV infection. The severity of facial nerve dysfunction and the recovery rate were evaluated according to House–Brackmann Facial Nerve Grading Scale (HB FGS). Paired whole blood samples from all patients were obtained at their initial visit and 3 weeks later, and serum samples were analyzed for VZV IgG and IgM antibodies using ELISA. ResultsA significantly higher percentage of Bell's palsy patients were seropositive for VZV IgM antibodies than controls (36.6% of patients vs 10% of controls) while for VZV IgG antibodies the difference was statistically nonsignificant. HB FGS in Bell's palsy patients with serologic evidence of VZV recent infection or reactivation showed a statistiacally significant less cure rate than other patients. ConclusionsVZV reactivation may be an important cause of acute peripheral facial paralysis in children. The appropriate diagnosis of VZV reactivation should be done to improve the outcome and the cure rate by the early use of antiviral treatment.

Arsenic Exposure and Seroprevalence of the Varicella- Zoster Virus Igg Antibody in the US Population

Background: There is evidence from experimental models that exposure to inorganic arsenic causes immunosuppression. Clinical case-reports frequently observe the reactivation of the Varicella-Zoster Virus (VZV) in people who have recovered from acute and chronic arsenic poisoning, as well as in patients with acute promyelocytic leukemia that have received therapeutic treatment with arsenic trioxide. Aim: Examine the association between urinary arsenic exposure and the seronegative prevalence of VZV IgG in a representative sample of the US population. Methods: Cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) for the 2003-2004 (N=1653) and 2009-2010 (N=1727) cycles. Participants were eligible if they were 6-49 years of age sampled for both VZV IgG and urinary arsenic speciation. Results: The weighted seronegative prevalence of VZV was 2.63% in 2003-2004 and 1.28% in 2009-2010 for the selected samples. The geometric mean of total urinary arsenic, defined as the sum of arsenite, arsenate, monomethylarsonate and dimethylarsinate, was 6.60 µg/L in 2003-2004 and 6.51 µg/L in 2009-2010. After adjusting for age and creatinine, the odds of a negative VZV result approximately doubled for each increase in log-transformed urinary arsenic in 2003-2004 (OR: 2.27, 95% CI: 1.04-4.93) and 2009-2010 (OR: 2.14, 95% CI:1.50-3.06). Conclusions: Data from this cross-sectional analysis show a positive association between arsenic exposure and seronegative prevalence of VZV IgG in the US population. These findings are in accordance with clinical observations of zoster virus reactivation from high doses. A prospective cohort study is needed to establish if the observed association leads to any negative health outcomes and evaluate the causality of this relationship.

High Incidence of Herpes Zoster After Lung Transplantation.

Primary varicella zoster virus (VZV) infection causes varicella and subsequently lifelong latent infection in ganglia from which it may reactivate leading to herpes zoster (HZ). Recently, we reported that VZV-reactive memory T-cells are significantly lower in transplant recipients than controls. In addition, the VZV-specific IgG titres after transplantation were significantly lower than before transplantation. Data on the incidence and timing of VZV reactivation after lung transplantation is limited. Therefore, we investigated the incidence of HZ after lung transplantation. Additionally, we questioned whether the VZV-specific T-cell and B-cell memory responses are recovered after VZV reactivation. The records of 101 patients (median age: 54 years) who underwent lung transplantation between April 2002 and April 2013 were analysed for VZV-PCR DNA till October 2013. VZV infection was clinically diagnosed and confirmed by PCR in 15 patients. One patient who was VZV IgG negative before transplantation, developed primary VZV infection 1.2 years after transplantation. Fifteen patients developed HZ: one patient had systemic dissemination, one patient developed disseminated vesicular rash in C2-C5 and died 6 days later, and 13 patients had uncomplicated cutaneous HZ involving 1-3 dermatomes. The median time to HZ was 1.4 years after transplantation. The overall incidence rate of HZ after transplantation (38 cases/1000 PY) was significantly higher than the age-matched healthy population (7-8 cases/1000 PY). The VZV-specific B and T-cell memory responses of 5 patients before and after HZ were compared with 5 patients without HZ. In 4 out of 5 patients the number of VZV-specific IgG producing B-cells increased after HZ to higher frequencies than those without HZ (p=0.06). The percentage of VZV-reactive CD4 and CD8 central and effector memory T-cells increased in all patients after HZ to significantly higher frequencies compared to those without HZ (p=0.03).In conclusion, HZ is a frequent complication after lung transplantation and increases VZV-specific T- and B-cell memory responses. Boosting the VZV adaptive immune response by prophylactic VZV vaccination before transplantation may limit the incidence of HZ after transplantation.

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.

Seroprevalence of Cytomegalovirus, Epstein Barr Virus and Varicella Zoster Virus among Pregnant Women in Bradford: A Cohort Study

ObjectiveTo estimate the seroprevalence of cytomegalovirus (CMV), Epstein Barr virus (EBV) and varicella zoster virus (VZV) among pregnant women in Bradford by ethnic group and country of birth.MethodsA stratified random sample of 949 pregnant women enrolled in the Born in Bradford birth cohort was selected to ensure sufficient numbers of White UK born women, Asian UK born women and Asian women born in Asia. Serum samples taken at 24-28 weeks’ gestation were tested for CMV IgG, EBV IgG and VZV IgG. Each woman completed a questionnaire which included socio-demographic information.ResultsCMV seroprevalence was 49% among the White British women, 89% among South Asian UK born women and 98% among South Asian women born in South Asia. These differences remained after adjusting for socio-demographic factors. In contrast, VZV seroprevalence was 95% among women born in the UK but significantly lower at 90% among South Asian women born in Asia. EBV seroprevalence was 94% overall and did not vary by ethnic group/country of birth. ConclusionsAlthough about half of White British women are at risk of primary CMV infection in pregnancy and the associated increased risk of congenital infection, most congenital CMV infections are likely to be in children born to South Asian women with non-primary infection during pregnancy. South Asian women born in South Asia are at risk of VZV infection during pregnancy which could produce congenital varicella syndrome or perinatal chickenpox. Differences in CMV and VZV seroprevalence by ethnic group and country of birth must be taken into account when universal immunisation against these viruses is contemplated.

Seroprevalence of Varicella-Zoster Virus in Five US-Bound Refugee Populations

Little is known about varicella-zoster virus (VZV) susceptibility in US-bound refugee populations, although published data suggest that VZV seroprevalence in these refugee populations may be lower than US populations. We describe VZV seroprevalence in five US-bound refugee groups: (1) Bhutanese in Nepal, (2) Burmese on the Thailand-Burma (Myanmar) border, (3) Burmese in Malaysia, (4) Iraqi in Jordan, and (5) Somali in Kenya. Sera were tested for presence of VZV IgG antibodies among adults aged 18-45 years. Overall VZV seroprevalence was 97% across all refugee groups. VZV seroprevalence was also high across all age groups, with seroprevalence ranging from 92-100% for 18-26 year-olds depending on refugee group and 93-100% for 27-45 year-olds. VZV seroprevalence was unexpectedly high in these five US-bound refugee groups, though may not reflect seroprevalence in other refugee groups. Additional studies are needed to better understand VZV seroprevalence in refugee populations over time and by region.

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.

Complications of varicella zoster virus reactivation.

Varicella zoster virus (VZV) is an exclusively human neurotropic alphaherpesvirus. Primary infection causes varicella (chickenpox), after which virus becomes latent in ganglionic neurons along the entire neuraxis. With advancing age or immunosuppression, cell-mediated immunity to VZV declines and virus reactivates to cause zoster (shingles), which can occur anywhere on the body. Skin lesions resolve within 1-2 weeks, while complete cessation of pain usually takes 4-6 weeks. Zoster can be followed by chronic pain (postherpetic neuralgia), cranial nerve palsies, zoster paresis, meningoencephalitis, cerebellitis, myelopathy, multiple ocular disorders and vasculopathy that can mimic giant cell arteritis. All of the neurological and ocular disorders listed above may also develop without rash. Diagnosis of VZV-induced neurological disease may require examination of cerebrospinal fluid (CSF), serum and/ or ocular fluids. In the absence of rash in a patient with neurological disease potentially due to VZV, CSF should be examined for VZV DNA by PCR and for anti-VZV IgG and IgM. Detection of VZV IgG antibody in CSF is superior to detection of VZV DNA in CSF to diagnose vasculopathy, recurrent myelopathy, and brainstem encephalitis. Oral antiviral drugs speed healing of rash and shorten acute pain. Immunocompromised patients require intravenous acyclovir. First-line treatments for post-herpetic neuralgia include tricyclic antidepressants, gabapentin, pregabalin, and topical lidocaine patches. VZV vasculopathy, meningoencephalitis, and myelitis are all treated with intravenous acyclovir.

Varicella zoster virus quantitation in blood from symptomatic and asymptomatic individuals

Primary infection with varicella zoster virus (VZV) occurs in immunocompromised and immunocompetent individuals. Clinical and asymptomatic reactivation with shedding of infectious virus and viremia may occur. The prevalence of VZV viremia is unknown. The aim of this study was to detect VZV viremia and quantify VZV DNA using quantitative polymerase chain reaction (qPCR) in blood from different populations. A qPCR-based method using EvaGreen® was used to quantify VZV DNA in 491 samples, including whole blood, plasma and buffy-coat, from patients hospitalized with varicella-associated disease (Group 1, n=10) and three groups with no VZV disease: individuals with a first clinical diagnosis of central nervous system demyelination (Group 2, n=213) with their age and sex-matched controls (Group 3, n=218); and HIV-infected individuals (Group 4, n=50). VZV-specific IgG antibody titres were measured in Group 3. The proportion positive for viremia and mean detectable VZV DNA load (copies/ml) were: Group 1: 100% (10/10) and 4.6 × 10(6) ± 1.4 × 10(7) ; Group 2: 4% (9/213) and 1.5 × 10(3) ± 1.8 × 10(4) ; Group 3: 8% (17/218) and 1.1 × 10(3) ± 7.8 × 10(3) ; Group 4: 12% (6/50) and 7.7 × 10(1) ± 2.8 × 10(2) . VZV DNA load and IgG titres were not significantly correlated (Group 3 only). VZV load in Group 1 was significantly elevated compared to Groups 2-4 (P<0.001); the latter were not significantly different from each other (P=0.05). VZV genotypes from clades 1-5 were identified in Group 1. VZV DNA was detected but at low frequency and viral load in both immunocompetent and immunocompromised individuals asymptomatic for VZV infection, compared to individuals with active VZV infection.

Increased Carotid Intima-Media Thickness Associated with Antibody Responses to Varicella-Zoster Virus and Cytomegalovirus in HIV-Infected Patients

ObjectiveWe investigated the relationship of the Herpesviridiae with inflammation and subclinical atherosclerosis in HIV-infected patients.MethodsProspective study including virologically suppressed HIV-infected patients. IgG antibodies against herpesviruses, carotid intima-media thickness (cIMT), endothelial function through flow-mediated dilatation (FMD) of the brachial artery, and blood atherosclerosis biomarkers (hsCRP, TNF-α, IL-6, MCP-1, MDA, sCD14, sCD163, VCAM-1, ICAM-1, D-dimer, and PAI-1) were measured.Results136 patients with HIV viral load <200 copies/ml were included. 93.4% patients were infected with herpes simplex virus type-1, 55.9% with herpes simplex virus type-2, 97.1% with varicella-zoster virus, 65.4% with human herpesvirus-6, 91.2% with cytomegalovirus, and 99.3% with Epstein-Barr virus. Previous AIDS diagnosis was associated with higher cytomegalovirus IgG titers (23,000 vs 17,000 AU, P = 0.011) and higher varicella-zoster virus IgG titers (3.19 vs 2.88 AU, P = 0.047), and there was a positive correlation of the Framingham risk score with IgG levels against cytomegalovirus (Spearman's Rho 0.216, P = 0.016) and Herpes simplex virus-2 (Spearman's Rho 0.293, P = 0.001). IgG antibodies against cytomegalovirus correlated in adjusted analysis with the cIMT (P = 0.030). High seropositivity for varicella-zoster virus (OR 2.91, 95% CI 1.05–8.01, P = 0.039), and for cytomegalovirus (OR 3.79, 95% CI 1.20–11.97, P = 0.023) were predictors for the highest quartile of the cIMT in adjusted analyses. PAI-1 levels were independently associated with cytomegalovirus IgG titers (P = 0.041), IL-6 and ICAM-1 levels with varicella-zoster virus IgG (P = 0.046 and P = 0.035 respectively), and hsCRP levels with Herpes simplex virus-2 IgG (P = 0.035).ConclusionIn virologically suppressed HIV-infected patients, antibody responses against herpesviruses are associated with subclinical atherosclerosis, and with increased inflammation and coagulation biomarkers.

Varicella immunity in vaccinated healthcare workers

BackgroundNosocomial 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. ObjectiveEvaluate 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 designA 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. ResultsThe 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. ConclusionsMeasurements 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.

Immunological Responses to Varicella-Zoster Virus (VZV) in Basrah with Special Emphasis on the Pattern of Exposure

The study aimed on the study of pattern of exposure and immunological responses to varicella-zoster virus (VZV) infection. Methods: A seroepidemiological study was carried out on 92 blood samples collected from children in primary health care centers and outpatient clinics of Al-Sader Teaching and Basrah maternity and children hospital during the period from January 2007 till March 2008. Serological responses were investigated by an enzyme-linked immunosorbent assay (ELISA) to detect VZV IgG antibody and cellular responses was detected by Erythrocyte rosette (E-Rosette) formation test. Results: The overall VZV- antibody prevalence was 53.3% for both serologic and cellular responses. The degree and pattern of exposure to VZV cases plays important role in the seroconversion and responses to VZV infections. The greatest responses observed in those with direct contact (household) with chickenpox cases (68.6% and 74.3%) and the direct contact acquired from VZV infected mothers (80% for both serologic and cellular responses). Exposure to typical chickenpox cases confers higher serologic and cellular responses (75% and 94.4% respectively). Cellular responses to VZV infections lasted longer than that for serologic responses. Sever VZV infections confers significantly higher levels of immunity (100%) and the complication post VZV infections (Pneumonia and encephalitis) mostly associated with sever cases at earlier age groups rather than the mild VZV cases. The differences in immune responses to VZV infections between male and females was significant (P

Do HIV-positive adult immigrants need to be screened for measles–mumps–rubella and varicella zoster virus immunization?

A systematic screening for measles, mumps, rubella (MMR) and varicella zoster virus (VZV) in HIV-positive adult immigrants in Spain was evaluated, and factors associated with MMR and VZV vaccines' indication were studied. Every HIV-positive immigrant was tested for VZV and MMR-IgG. MMR vaccine was indicated to patients with lymphocytes CD4+ >200 cells/mm3 and a negative measles-IgG, a negative mumps-IgG and/or a negative rubella-IgG. VZV vaccine was indicated to every VZV-IgG negative patient with CD4+ >400 cells/mm3. In total, 289 patients were screened; seroprevalence was 95.2%, 92.2%, 70.3% and 89.3% for VZV, measles, mumps and rubella IgG, respectively. Having a negative VZV-IgG was statistically associated with coming from sub-Saharan Africa (prevalence ratio [PR]: 6.52; 95% CI: 1.71–24.84; p=0.006), while having secondary education was a protective factor (PR: 0.25; 95% CI: 0.07–0.97; p=0.045). Fourteen patients (4.8%) had indication of VZV vaccine; vaccination was feasible in 21.4% of them at first visit. Eighty-one patients (29.7%) had indication of MMR vaccine, most of them due to mumps-IgG negative (53.1%) or rubella-IgG negative (24.7%). Age < 30 years at first visit was the only factor statistically associated with MMR vaccine indication (PR: 1.47; 95% CI: 1.02–2.11; p=0.04). According to CD4+ cell counts, vaccination was feasible in 71.6% of patients at first visit. In conclusion, more than a third of HIV-infected immigrant patients are susceptible to at least one easily preventable infectious disease. Especial attention should be given to immigrant women of childbearing age.

Serologic Analysis of the IgG Antibody Response in Children With Varicella Zoster Virus Wild-type Infection and Vaccination

In contrast to varicella zoster virus (VZV) primary infection, VZV vaccination does not seem to provide lifelong immunity against varicella. Because more people get vaccinated every year, the development of sensitive serological test systems for the detection of protective anti-VZV IgG will become important in the future. We have previously developed a novel VZV line assay based on 5 different recombinant VZV antigens. In this study, we compared this novel assay with a commercially available glycoprotein enzyme immunoassay (RIDASCREEN VZV IgG) in detecting anti-VZV IgG of children with previous varicella infection and VZV vaccination. One hundred twenty-five children were included in this study, 72 with a history of varicella infection and 53 with VZV vaccination. Both assays detected anti-VZV IgG antibodies in both study groups with similar sensitivities. The VZV line assay revealed striking differences in the anti-VZV IgG composition against the VZV open reading frames, 4, 14 and 49, between both study groups, indicating that wild-type varicella infection causes a more diverse immune response against VZV than does vaccination. The exploitation of these results enabled the discrimination of both study groups with a sensitivity of 0.93 and a specificity of 0.83, indicating that the serologic differentiation of children with previous varicella infection and VZV vaccination might be possible. The VZV line assay enables the detection of anti-VZV IgG with sensitivities comparable to glycoprotein enzyme immunoassays and might be suitable for the serologic discrimination between children with a history of varicella infection and VZV vaccination.

Seroprevalence of varicella-zoster virus and predictors for seronegativity in the Amsterdam adult population

BackgroundIn the Netherlands, infection with varicella-zoster virus (VZV) is considered a benign common childhood illness and routine vaccination against VZV is not done. In 1995 it was estimated that 98-100% of the adult Dutch general population is immune, yet the estimate is based on a database in which a relative small number of people of non-Dutch ethnic origin were represented. As the city of Amsterdam has large immigrant communities originating from various subtropical and tropical countries, such as Morocco, Surinam, and Turkey with probably lower VZV transmission, this study aimed to estimate the seroprevalence of VZV IgG antibodies (anti-VZV) among various ethnic groups in Amsterdam, and identify factors associated with seronegative VZV status.MethodsThe study was a cross-sectional survey of the Amsterdam population (2004), and the study sample was stratified by age and ethnicity, with deliberate oversampling of minority ethnic groups. Serum samples obtained from 1,341 residents in 2004 were tested for antibodies to VZV. Basic demographic data (gender, age, country of birth, age at immigration and number of children) were also available.ResultsThe anti-VZV seroprevalence in the overall Amsterdam population was estimated to be 94% (95% confidence intervals; 92–96%). Regarding ethnic origin, first generation immigrants (Moroccan immigrants 90%, Surinamese or Antillean immigrants 91%, and Turkish 92%), especially those that migrated after the age of 11 years, were more likely to be anti-VZV seronegative compared to those arriving at an earlier age or those born in the Netherlands (97–98%). Both ethnic origin and generation of immigration were positive predictors for IgG seronegativity to VZV (p<0.015). No other predictors for seronegativity were found.ConclusionThe results of this study imply that about 4–8% of the general adult Amsterdam population is still susceptible to infection with VZV, and that susceptibility is even higher in some immigrant groups. When assessing the risk of infection after VZV exposure alertness is needed for vulnerable persons like pregnant women, patients with hematological malignancies or organ transplants in particular among first-generation immigrants.

Evaluation of Three Commercial Varicella-Zoster Virus IgG Enzyme-Linked Immunosorbent Assays in Comparison to the Fluorescent-Antibody-to-Membrane-Antigen Test

Commercial serologic assays for varicella-zoster virus (VZV), which enable reliable determination of VZV immune status and are amenable to automation, are needed. The present study compares the automated performance of the VZV whole-cell enzyme-linked immunosorbent assay (ELISA) Enzygnost anti-VZV/IgG, the Euroimmun anti-VZV ELISA (IgG) based on highly purified viral proteins, and the VZV glycoprotein (gp)-based Serion ELISA Classic VZV IgG. The fluorescent-antibody-to-membrane-antibody (FAMA) test was used as a reference. A total of 638 serum samples from VZV-negative children, blood donors, varicella vaccinees, and bone marrow transplant recipients were included. The Enzygnost anti-VZV/IgG and the Serion ELISA Classic VZV IgG showed sensitivities of 99.6% and 99.2%, respectively, and the Euroimmun anti-VZV ELISA (IgG) had a significantly lower sensitivity of 90.5%. Specificity was calculated as 100% for both the Euroimmun anti-VZV ELISA (IgG) and for the Enzygnost anti-VZV/IgG, and the Serion ELISA Classic VZV IgG had a significantly lower specificity of 89.4%. Quantitative results of all ELISAs correlated well, but there was a poor quantitative correlation between the ELISAs and FAMA. In conclusion, this study does not show any superiority of a gp- and a protein-based ELISA compared to a whole-cell ELISA for the automated detection of VZV-specific IgG. The automated performance of the Enzygnost anti-VZV/IgG assay correlated best with the FAMA reference assay.

Pneumonic varicella a in patient with inactive hepatitis B: Case report

Although rarely observed, varicella zoster virus (VZV)-related pneumonia is the most serious complication of the virus, which commonly affects adults and causes high mortality rates. In this study, we describe a case of VZV pneumonia in a 29-year-old male who is an inactive Hepatitis B virus carrier. The patient presented with a 5-day history of fatigue, sore throat, fever, cough and mild dyspnea. He also had an exanthematous vesicular rash. The rash had spread all over his body surface including the hairy skin. But he was not febrile and vital signs were normal. The skin examination exhibited a diffuse polymorphic rash with papules/vesicles, pustules and crusty lesions over the whole body. Serological findings were as follows: VZV IgM positive, VZV IgG positive and HBsAg positive. His chest X-ray showed bilateral pneumonic infiltrations. The patient was prescribed valacyclovir and clarithromycin. The skin lesions disappeared after ten days and the patient made a full recovery. We conclude that an early diagnosis of VZV pneumonia, which rarely occurs in adult patients and its effective treatment with antivirals may prevent the development of serious complications. J Microbiol Infect Dis 2012; 2(2): 68-71