Diagnostic value of anti-VZV IgG in neurological diseases among varicella unvaccinated individuals.

Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus that causes neurological manifestations either as a complication of primary infection or reactivation. VZV induced neurological diseases have a good prognosis when confirmed early and treated with anti-viral therapy. Myelitis, encephalitis, ventriculitis or meningitis can occur without a telltale rash in immunocompetent and immunocompromised individuals making the diagnosis difficult. We analyzed CSF and serum samples from 30 unvaccinated study participants (17 male and 13 female) to determine the presence of VZV DNA by PCR in CSF and to estimate serum and CSF anti-VZV IgG and albumin levels in participants with neurological manifestations with/without rash. Anti-VZV IgG was detected in CSF (n = 22, [73%]) and serum (n = 29, [97%]) of pediatric and adult participants. Anti-VZV IgG were detected in CSF of participants with varied clinical presentation altered sensorium (n = 8, [36%]), meningitis (n = 4, [18%]), acute febrile illness (n = 3, [14%], encephalopathy/meningoencephalitis (n = 2, [9%]), irritability (n = 2, [9%]) and each patient from cerebrovascular stroke, demyelinating disorder and febrile seizure (n = 1, [4.5%]). VZV DNA was detected from one participant and CSF serum albumin levels were elevated in 53% of study participants. VZV DNA is present up to 1-2 weeks post onset of disease, after which anti-VZV antibody may be the only indicator of disease and therefore both VZV DNA and anti-VZV IgG need to be tested for in CSF. As VZV DNA and VZV IgG antibody are both good indicators of VZV reactivation, routine testing would result in reduced morbidity and mortality by early detection of disease and antiviral treatment.

Long -term persistence of antibodies against varicella in fully immunized healthcare workers: an Italian retrospective cohort study.

BACKGROUND: Chickenpox is a highly contagious disease caused by the varicella zoster virus (VZV), and in infants, adolescents, adults, pregnant women, and the immunocompromised it can be serious. The best way to prevent chickenpox is immunization with the varicella vaccine. Protective levels of antibodies induced by the varicella vaccine decline over time, but there is currently no formal recommendation for testing anti-varicella zoster virus (VZV) IgG levels in immunized healthcare workers (HCWs). METHODS: The aims of this study were to evaluate the seroprevalence of circulating anti-VZV IgG in a sample a sample of students and residents of the medical school of the University of Bari, the long-term immunogenicity of the varicella vaccine, and the effectiveness of a strategy consisting of a third vaccine booster dose. The study population was screened as part of a biological risk assessment conducted between April 2014 and October 2020. A strategy for the management of non-responders was also examined. RESULTS: The 182 students and residents included in the study had a documented history of immunization (two doses of varicella vaccine). The absence of anti-VZV IgG was determined in 34% (62/182; 95%CI = 27.2-41.4%), with serosusceptibility more common among males than females (p < 0.05). After a third varicella dose, seroconversion was achieved in 100% of this previously seronegative group. No serious adverse events were recorded. CONCLUSIONS: One-third of the study population immunized against VZV lacked a protective antibody titer, but a third dose of vaccine restored protection. Since it is highly unlikely that VZV will be eliminated in the immediate future, the loss of immunity in a substantial portion of the population implies a risk of varicella outbreaks in the coming years. Screening for varicella immunity in routine assessments of the biological risk of medical students and HCWs may help to prevent nosocomial VZV infections.

Primary varicella infection in children with systemic juvenile idiopathic arthritis under tocilizumab therapy.

We report the clinical course and outcome of primary varicella infection in six children with systemic juvenile idiopathic arthritis (sJIA) receiving tocilizumab. None had disseminated or fatal varicella infection, but one patient developed macrophage activation syndrome (MAS) and another had an arthritis relapse. All patients had a significant elevation of serum IL-6 levels, and the two children who developed MAS or arthritis relapse showed high serum IL-18 levels, which could cause a sJIA flare-up.

Analysis of sero-epidemiological characteristics of varicella in healthy children in Jiangsu Province, China.

BACKGROUND: In recent years, outbreaks of varicella have continued to occur, and the coverage rate of varicella vaccine in Jiangsu Province, China, remains unclear. This study aims to analyse the levels of immune antibody against varicella and obtain a comprehensive understanding of the varicella attenuated live vaccine (VarV) coverage rate in children aged 1-9 years in Jiangsu Province. METHODS: From June to October 2016, a cross-sectional survey was conducted to collect 3631 serum samples from healthy children aged 1-9 years in Jiangsu Province. The immunoglobulin G (IgG) antibody levels of varicella were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: The VarV coverage rate of healthy children was only 43.1% (95% CI: 41.1-44.7%). The seroprevalence after vaccination with a single dose of VarV was only 57.1%, and the overall seropositivity and geometric antibody titre (GMC) were 43.5% and 225.4 mU/ml, respectively. The seropositivity was significantly higher in girls than in boys (χ2 = 18.82, P < 0.001). The difference in seropositivity between the 5-9 age group and 1-4 age group was statistically significant (χ2 = 84.31, P < 0.001). The difference in seropositivity between different regions was statistically significant, with the highest seropositivity in the northern area, 53.7% (χ2 = 35.64, P < 0.001). The seropositivity in the group receiving one dose of VarV was significantly higher than that of the unvaccinated group (χ2 = 205.16, P < 0.001). Linear regression analysis suggested that the GMC of varicella antibodies wanes with the time since vaccination (F = 65.01, P = 0.002). CONCLUSION: The VarV coverage rate of healthy children in Jiangsu Province was low. Sero-conversion rates were also low after one dose of VarV, and the immune effectiveness of a single dose of VarV was limited. To control the spread of varicella, VarV should be included in the routine immunization program, and strengthened immunization measures for the varicella-susceptible population warrant additional consideration.

Interdiction of a blood donation containing varicella-zoster virus by donor self-report of chickenpox.

Nowadays, risk of transfusion-transmitted infection has been substantially minimized by stringent donor eligibility screening and infectious disease testing. However, we report an interdiction of a blood donation containing varicella-zoster virus (VZV) by donor self-reporting of chickenpox. The donor developed varicella infection shortly after blood donation despite vaccination. Varicella-zoster virus DNA was detected in her fresh-frozen plasma before the blood components were issued for clinical transfusion. The report indicates the importance of donors' education and awareness of their obligation to report any symptoms developed shortly after blood donation in order to further secure blood safety.

Molecular characterisation of varicella zoster virus genotypes in Sri Lanka.

INTRODUCTION: Genotyping of wild type of varicella zoster virus (VZV) in Sri Lanka would help to distinguish the VZV wild type infection from varicella vaccine associated infections. METHODS: PCR-RFLP analysis of VZV ORF 38, 54 and 62 was used for genotyping in VZV from blood or vesicular fluid from 31 patients with chickenpox or herpes zoster. The PstI restriction site of ORF 38, BglI restriction site of ORF 54 and SmaI restriction site of ORF 62 were analyzed using RFLP to determine the genotype. RESULTS: Except for one strain, all other VZV isolates had the genotype characteristic of the wild type VZV strain PstI+BglI+ SmaI-, which was characteristic of the Asian strain. None of the isolates had the American or the European VZV profile (PstI+BglI-) but were similar to isolates from Africa and Asia (PstI+BglI+). Interestingly, one of the VZV strains isolated from a patient with chickenpox had the characteristic genotype of the vaccine strain PstI- BglI+ SmaI+. CONCLUSIONS: The genotype of the VZV in Sri Lanka is similar to the Asian VZV genotype and can be easily distinguished from the VZV vaccine strain by using the polymorphisms in ORF 38, ORF 54 and ORF 62.

Latency of varicella zoster virus in dorsal root, cranial, and enteric ganglia in vaccinated children.

Despite vaccination, varicella-zoster virus (VZV) remains an important pathogen. We investigated VZV latency in autopsy specimens from vaccinees, in gastrointestinal tissue removed surgically, and in a guinea pig model. We propose that retrograde transport from infected skin and viremia deliver VZV to neurons in which it becomes latent. Wild type (WT) VZV was found to be latent in many ganglia of vaccinated children with no history of varicella, suggesting that subclinical infection with WT-VZV occurs with subsequent viremic dissemination. The 30% to 40% rate of WT-VZV zoster reported in vaccinees and occasional trigeminal zoster due to vaccine type VZV (vOka) are consistent with viremic delivery of VZV to multiple ganglia. Most human intestinal specimens contained latent VZV within neurons of the enteric nervous system (ENS). Induction of viremia in guinea pigs led to VZV latency throughout the ENS. The possibility VZV reactivation in the ENS is an unsuspected cause of gastrointestinal disease requires future investigation.

[Post-varicella cerebral thrombophlebitis with anti-protein S: report of a pediatric case]. / Thrombophlébite cérébrale post-varicelle avec anticorps anti-protéine S : à propos d'un cas pédiatrique.

Purpura fulminans and venous thrombosis are rare complications of chickenpox. We report the case of a 6 year old with no history individuals who experienced cerebral thrombophlebitis, 3 weeks after varicella. MRI, performed at admission, has objectified longitudinal sinus thrombosis and a frontal parenchymal hematoma law. Meanwhile, a recent varicella seroconversion was demonstrated. The assessment of thrombophilia, meanwhile, has objectified a significant decrease in free protein S and activity, without associated DIC. Origin acquired this deficit was confirmed by the detection of antibodies (IgG and IgM) against the total protein S by ELISA. After evaluation of the benefit/risk only anticoagulation was initiated. The clinical and biological evolution was favorable, with rapid normalization of the S protein and decrease of anti-protein S. Many studies report the presence of anti-protein S in young children at the waning of chickenpox, without their exact frequency is determined. The decrease in protein S they cause leads to a transient hypercoagulable state may result in different clinical pictures. Cases of purpura fulminans seem more frequent when venous thrombosis isolated post chickenpox, sometimes atypical, appear rare.

Little Italy: an agent-based approach to the estimation of contact patterns- fitting predicted matrices to serological data.

Knowledge of social contact patterns still represents the most critical step for understanding the spread of directly transmitted infections. Data on social contact patterns are, however, expensive to obtain. A major issue is then whether the simulation of synthetic societies might be helpful to reliably reconstruct such data. In this paper, we compute a variety of synthetic age-specific contact matrices through simulation of a simple individual-based model (IBM). The model is informed by Italian Time Use data and routine socio-demographic data (e.g., school and workplace attendance, household structure, etc.). The model is named "Little Italy" because each artificial agent is a clone of a real person. In other words, each agent's daily diary is the one observed in a corresponding real individual sampled in the Italian Time Use Survey. We also generated contact matrices from the socio-demographic model underlying the Italian IBM for pandemic prediction. These synthetic matrices are then validated against recently collected Italian serological data for Varicella (VZV) and ParvoVirus (B19). Their performance in fitting sero-profiles are compared with other matrices available for Italy, such as the Polymod matrix. Synthetic matrices show the same qualitative features of the ones estimated from sample surveys: for example, strong assortativeness and the presence of super- and sub-diagonal stripes related to contacts between parents and children. Once validated against serological data, Little Italy matrices fit worse than the Polymod one for VZV, but better than concurrent matrices for B19. This is the first occasion where synthetic contact matrices are systematically compared with real ones, and validated against epidemiological data. The results suggest that simple, carefully designed, synthetic matrices can provide a fruitful complementary approach to questionnaire-based matrices. The paper also supports the idea that, depending on the transmissibility level of the infection, either the number of different contacts, or repeated exposure, may be the key factor for transmission.