Use of genomic analysis of varicella-zoster virus to investigate suspected varicella-zoster transmission within a renal unit.

BACKGROUND: The source of hospital-acquired chickenpox infection may be presumed from a known exposure, but has not been previously proven using genomic analysis. OBJECTIVE: Investigation of suspected VZV transmission was done using single nucleotide polymorphism genomic analysis. STUDY DESIGN: Comparison was made of viral isolates from two patients with chickenpox on the same ward who were not known to have had direct contact. RESULTS: An identical genotype in the variable R1 region of the VZV was isolated from the two patients. CONCLUSION: Inapparent hospital-acquired transmission was the most likely route of infection.     

Immunity to varicella zoster virus in children with leukaemia

A total of 46% (32/70) of children with acute lymphoblastic leukaemia presenting to the Hospital for Sick Children had a past history of chickenpox. When their immunity to varicella zoster virus (VZV) was assessed, 75% (24/32) had a positive lymphocyte transformation response to VZV antigen in tissue culture while 78% (25/32) possessed IgG antibody against VZV. Therefore, at least 22% of the children were probably susceptible to infection with VZV inspite of having a history suggestive of chickenpox.Of those with a negative or uncertain history 34% had a positive lymphocyte transformation response, while 55% (21/38) had IgG antibody against VZV. Therefore, about one in two of those with a negative history to VZV had some form of immunity to VZV. Hence, regardless of their VZV infection history, children with leukaemia would need to undergo both cell mediated and humoral immunity tests before they may be considered for immunisation with the live varicella vaccine. From our studies, 34% (24/70) of our patients did not have any evidence of immunity to VZV by either test method. These would be considered for immunisation with the live varicella vaccine.     

Chickenpox and multiple sclerosis: A Mendelian randomization study

Observational studies have suggested a suspected association between varicella-zoster virus (VZV) infection and multiple sclerosis (MS), but the connection has remained unclear. The aim of the present study is to evaluate the causal relationship between chickenpox which is caused by VZV infection and MS. We performed a two‑sample Mendelian randomization analysis to investigate the association of chickenpox with MS using summary statistics from genome‑wide association studies (GWAS). The GWAS summary statistics data for chickenpox was from the 23andMe cohort including 107 769 cases and 15 982 controls. A large summary of statistical data from the International Multiple Sclerosis Genetics Consortium (IMSGC) was used as the outcome GWAS data set, including 14 802 MS cases and 26 703 controls. We found evidence of a significant association between genetically predicted chickenpox and risk of MS (odds ratio [OR] = 35.27, 95% confidence interval [CI] = 22.97–54.17, p = 1.46E−59). Our findings provided evidence indicating a causal effect of chickenpox on MS. Further elucidations of this association and underlying mechanisms are needed for identifying feasible interventions to promote MS prevention.     

Low antibody avidity in elderly chickenpox patients.

A small outbreak of chickenpox confirmed serologically in 3 elderly patients from a geriatric home is described. Disease was probably due to exogenous reinfection, yet nevertheless the avidity of specific antibodies measured by the urea denaturation test was even lower than in primary chickenpox controls, which themselves were, as expected, significantly lower than zoster controls. In elderly individuals susceptibility to reinfection with varicella-zoster virus (VZV) with clinical manifestation such as chickenpox may well be associated with the decay of specific humoral immunity detectable by antibodies of particularly low avidity, in contrast to reactivation of latent VZV presenting clinically as zoster, which is related to deficiencies in specific cellular immunity.     

Simultaneous infection of measles and varicella-zoster virus in a child in India

Simultaneous occurrence of measles and chickenpox in a single individual is a rare event despite the fact that each of these infections alone is very common. The clinical presentation and molecular characterization of a dual infection caused by measles and Varicella-Zoster virus (VZV) in a 3-year female child is reported for the first time from India. The child presented with high fever, cough, cervical lymphadenopathy, and maculopapular rash followed by vesicular skin rash. The child was not immunized against measles and chickenpox. The viral nucleic acids extracted from the clinical specimen were subjected to PCR-Sequencing for confirmation of a dual infection with measles and VZV. The PCR and sequence analysis from the throat swab samples confirmed the coinfection of wild-type measles (genotype D4) and Varicella-Zoster virus (PstI(+) BglI(+)). The measles virus RNA and VZV DNA could be detected successfully from a single specimen of a throat swab. The case recovered uneventfully. Dual infection with measles and VZV does occur but may be underreported in the literature.     

Acute central nervous system complications in varicella zoster virus infections.

BACKGROUND: In a previous multicenter study on central nervous system (CNS) viral infections varicella zoster virus (VZV) appeared the most frequent etiologic agent and appeared often without rash. OBJECTIVE: To evaluate the appearance and diagnostics of VZV in CNS more thoroughly, we studied the cases systematically by using sensitive and specific methods to learn the best diagnostic approach in order to start specific therapy. STUDY DESIGN: We analyzed all serum and cerebrospinal fluid samples of 174 patients, 88 females and 86 males, with acute CNS symptoms associated with VZV infection diagnosed in the multicenter study on viral CNS infections. RESULTS: About 38 patients (22%) had chickenpox, 59 (34%) had shingles, and 77 (44%) had no cutaneous symptoms at all. The mean age of chickenpox patients was 8.6 years, of the others 46.6 and 41.4 years. VZV-specific nucleic acid was detected in the CSF in one fourth of the patients in all groups, primarily during the first week of illness. In serum specimens, specific IgM was present in two thirds of the patients with chickenpox, whereas in the others in one third of the cases. In CSF, specific IgM was present in 15-17% of patients with skin manifestations, compared with 6% of those without rash. CONCLUSIONS: The role of VZV infections in CNS complications seems remarkable, often presenting without rash. Even these cases should be promptly recognized in order to conduct proper antiviral therapy. In children, a combination of PCR and IgM tests is the best approach. In adults, PCR, together with the measurement of intrathecal antibody production yields best results.     

Asymptomatic reactivation and shed of infectious varicella zoster virus in astronauts

Varicella zoster virus (VZV) causes varicella (chickenpox), after which virus becomes latent in ganglia along the entire neuraxis. Virus reactivation produces zoster (shingles). Infectious VZV is found in vesicles of patients with zoster and varicella, but virus shed in the absence of disease has not been documented. VZV DNA was previously detected in saliva of astronauts during and after spaceflight, a uniquely stressful environment in which cell mediated immunity (CMI) is temporally dampened. The decline in CMI to VZV associated with zoster led to the hypothesis that infectious VZV would also be present in the saliva of astronauts subjected to stress of spaceflight. Herein, not only was the detection of salivary VZV DNA associated with spaceflight validated, but also infectious virus was detected in saliva from 2 of 3 astronauts. This is the first demonstration of shed of infectious VZV in the absence of disease.     

Comparison of the performance of the LIAISON VZV-IgG and VIDAS automated enzyme linked fluorescent immunoassays with reference to a VZV-IgG time-resolved fluorescence immunoassay and implications of choice of cut-off for LIAISON assay

BACKGROUND: Determination of Varicella Zoster virus (VZV) immune status in pregnant women without history of chickenpox is important in identifying those who genuinely need VZV immune globulin prophylaxis following significant exposure to chickenpox or shingles. Immune status testing requires highly sensitive and specific immunoassays for timely and accurate results. OBJECTIVES: To compare the performance of DiaSorin LIAISON and Biomerieux VIDAS VZV-IgG assays with reference to a VZV-IgG time-resolved fluorescence immunoassay (TRFIA). STUDY DESIGN: A panel of sera collected from 65 pregnant contacts of VZV and 62 individuals tested for VZV immunity was tested in all three assays. Dose-response curves were generated using International Standards W1044 and 90/690. RESULTS: Sensitivity and specificity of VIDAS compared to VZV-TRFIA was 54.5% and 97.9% respectively and for LIAISON compared to VZV-TRFIA was 67% and 100% respectively. Both assays correlated well with TRFIA with R2 correlation coefficients of 0.79 and 0.76 respectively. Dose-response curves showed both Standards behaved in a similar manner in each assay. For VIDAS, the test cut-off value of 0.9 correlated with 275-280mIU/ml and for LIAISON a cut-off value of 150mIU/ml correlated with 208-219mIU/ml. CONCLUSIONS: By dose-response data and in comparison with TRFIA, LIAISON is more sensitive and specific than VIDAS.     

Detection of IgE anti-parvovirus antibodies in human breast milk

Breast milk is a complex fluid, rich in nutrients and non-nutritional bioactive components, including antimicrobial factors, immunoglobulins, cytokines, and anti-inflammatory substances. Although IgE is implicated in viral immunity, its role in breast milk in parvovirus B19 immunity has not been studied. Total immunoglobulin levels of IgE, IgG, and IgE anti-parvovirus B19 antibodies were determined by ELISA and Western blot analysis in breast milk and in sera from a mother and her nursing infant (female, 10 mo). For specific IgE protein determination, breast milk was fractionated by chromatography on G-100 Sephadex; 3 peaks were collected and separated by SDS PAGE. The levels of total IgE in breast milk and its fractions were low (<2.4 ng/ml), and those of maternal and infant serum were negligible (18 and 4.3 IU/ml, respectively). Nevertheless, the breast milk and maternal and infant sera contained IgE anti-parvovirus B19 antibodies, even though the infant was never infected with parvovirus B19. Total serum levels of maternal IgG were within the normal range and those of infant IgG were low (473 mg/dl); total IgG in breast milk was not determined. Maternal serum contained some detectable IgG anti-parvovirus antibodies that were not present in infant serum or breast milk. Total maternal and infant serum levels of IgM and IgA were within the normal ranges. The presence of IgE anti-parvovirus B19 antibodies in breast milk suggests that IgE anti-viral antibodies are transmitted in breast milk and may provide protective responses in nursing children.     

Clinical and molecular pathogenesis of varicella virus infection

Varicella zoster virus (VZV) is a neurotropic human herpesvirus that infects nearly all humans and causes chickenpox (varicella). After chickenpox, VZV becomes latent in cranial nerve, dorsal root, and autonomic nervous system ganglia along the entire neuraxis. Virus reactivation produces shingles (zoster), characterized by pain and rash usually restricted to 1-3 dermatomes. Zoster is often complicated by postherpetic neuralgia (PHN), pain that persists for months to years after rash resolves. Virus may also spread to the spinal cord and blood vessels of the brain, producing a unifocal or multifocal vasculopathy, particularly in immunocompromised individuals. The increased incidence of zoster in elderly and immunocompromised individuals appears to be due to a VZV-specific host immunodeficiency. PHN may reflect a chronic VZV ganglionitis, and VZV vasculopathy is due to productive virus infection in cerebral arteries. Strategies that might boost host cell-mediated immunity to VZV are discussed, as well as the physical state of viral nucleic acid during latency and the possible mechanisms by which herpesvirus latency is maintained and virus is reactivated. A current summary of varicella latency and pathogenesis produced by simian varicella virus (SVV), the counterpart of human VZV, points to the usefulness of a primate model of natural infection to study varicella latency, as well as the experimental model of intratracheal inoculation to study the effectiveness of antiviral agents in driving persistent varicella virus into a latent state.     

Immune evasion as a pathogenic mechanism of varicella zoster virus

Varicella zoster virus (VZV) is a human herpesvirus that causes varicella (chickenpox) during primary infection, establishes latency in dorsal root ganglia and may reactivate years later, producing herpes zoster. VZV must evade antiviral immunity during three important stages of viral pathogenesis, including the cell-associated viremia characteristic of primary infection, persistence in dorsal root ganglia during latency and the initial period of VZV reactivation. Our observations about the immunomodulatory effects of VZV document its capacity to interfere with adaptive immunity mediated by CD4 as well as CD8 T cells, ensuring the survival of the virus in the human population from generation to generation.     

Temporal and lateral dynamics of HIV shedding and elevated sodium in breast milk among HIV-positive mothers during the first 4 months of breast-feeding

OBJECTIVE: To better understand the dynamics of breast milk HIV shedding and its relation to postnatal HIV transmission, we investigated the temporal and lateral relations of breast milk viral shedding and sodium concentrations in HIV-positive women. DESIGN: This was a longitudinal cohort study in Lusaka, Zambia. METHOD: We examined patterns of HIV shedding in breast milk over the first 4 months of breast-feeding and their correlations with postnatal HIV transmission among 138 breast-feeding mothers. Sodium concentration in breast milk was also examined in the same samples and in breast milk from 23 HIV-negative controls. RESULTS: Higher breast milk viral load at 1 week, 1 month, and 4 months and consistent viral shedding in breast milk were significantly associated with increased risk of HIV transmission. Elevated breast milk sodium concentration (> or =13 mmol/L) at 4 months was associated with HIV transmission, low maternal CD4 cell count, and high maternal plasma viral load. Elevated sodium concentration at 1 week postpartum was common and was not associated with any of these parameters. CONCLUSIONS: Consistent viral shedding and high breast milk viral load are strong predictors of mother-to-child HIV transmission. Although sodium concentrations later in breast-feeding correlate with breast milk viral load, increased breast milk sodium is normal in early lactation and does not predict HIV transmission.     

Direct and indirect effects of breast milk on the neurobehavioral and cognitive development of premature infants

Eighty-six premature infants were tested to examine the effects of maternal breast milk on infant development. Infants were classified by breast-milk consumption during the hospitalization period (M = 57.4 days) into three groups: those receiving minimal (<25% of nutrition), intermediate (25-75%), and substantial (>75%) amounts of breast milk. Infants in the three groups were matched for birth weight, gestational age (GA), medical risk, and family demographics. At 37 weeks GA, mother-infant interaction was videotaped, maternal depression self-reported, and neurobehavioral maturation assessed by the Neonatal Behavior Assessment Seale (Brazelton, 1973). At 6 months corrected age, infants were tested with the Bayley II (Bayley, 1993). Infants receiving substantial amounts of breast milk showed better neurobehavioral profiles-in particular, motor maturity and range of state. These infants also were more alert during social interactions, and their mothers provided more affectionate touch. Higher maternal depression scores were associated with lower quantities of breast milk, longer latencies to the first breast-milk feeding, reduced maternal affectionate touch, and lower infant cognitive skills. Maternal affectionate touch moderated the relations between breast milk and cognitive development, with infants receiving a substantial amount of breast milk and frequent touch scoring the highest. In addition to its nutritional value, breast milk may be related to improved maternal mood and interactive behaviors, thereby indirectly contributing to development in premature infants.     

Management of chickenpox in pregnant women: an Italian perspective

Chickenpox is a highly contagious disease caused by primary infection of varicella zoster virus (VZV). The disease is spread worldwide and is usually benign but, in some groups of population like pregnant women, can have a severe outcome. Due to a not optimal vaccination coverage, a relatively high number of childbearing-aged women in a European country such as Italy tested seronegative for VZV and so are currently at risk of acquiring chickenpox during pregnancy, especially if they live in contact with children for family or work reasons. Only few data are available about the risk of infection in this setting: the incidence of chickenpox may range from 1.5 to 4.6 cases/1000 childbearing females and from 1.21 to 6 cases/10,000 pregnant women, respectively. This review is aimed to focus on the epidemiology and the clinical management of exposure to chickenpox during pregnancy. Particular emphasis is given to the accurate screening of childbearing women at the time of the first gynecological approach — the females who tested susceptible to infection can be counseled about the risks and instructed on procedure should contact occur — and to the early prophylaxis of the at-risk exposure. Lastly, the achievement of adequate vaccination coverage of the Italian population remains a cornerstone in the prevention of chickenpox in pregnancy.     

Low induction of varicella-zoster virus-specific secretory IgA antibody after vaccination

Breakthrough after varicella vaccination occurs in approximately 2. 6% approximately 18.6% of immunocompetent children, but the reason has not been demonstrated clearly. As a first defense, specific secretory IgA antibody on the mucosa plays an important role in preventing invasion of microorganisms. To examine induction of varicella-zoster virus (VZV) specific secretory IgA after natural infection and vaccination and its booster mechanisms, 143 salivary samples were tested by ELISA. The VZV-secretory IgA values were significantly higher in the matched children after natural chickenpox than in those after vaccination, although the total secretory IgA did not differ between them. Two (7%) of the vaccinees lacked the sIgA antibody. In the elderly and in immunocompromised children, the VZV-secretory IgA values were no lower than those in healthy children, and they did not lack VZV-secretory IgA. The doctors and nurses taking care of patients with chickenpox had higher values than the other groups as did individuals who had had herpes zoster recently. VZV-secretory IgA was thought to be stimulated by exogenous and reactivated endogenous VZV to neutralize VZV with weak activity. These results suggest that low or no induction of VZV-secretory IgA antibody after vaccination may be one of the possible explanations for a breakthrough.     

Investigation of an Outbreak of Varicella in Chandigarh,North India,Using a Real-time Polymerase Chain Reaction Approach

Outbreaks of varicella are reported when susceptible population accumulates. This study reports a chickenpox outbreak in Burail in August 2014, wherein 20 laboratory-confirmed cases were identified by the detection of varicella zoster virus (VZV) DNA and VZV IgM antibodies. The viral load between vesicular swabs and serum samples from 8 patients with active lesions was found to have good correlation and further also related with disease severity. Real-time polymerase chain reaction can be useful for early diagnosis of an outbreak and vesicular swab can be used as a less invasive sample for assessing the disease severity.     

Factors affecting breast milk composition and potential consequences for development of the allergic phenotype

There is conflicting evidence on the protective role of breastfeeding in relation to allergic sensitization and disease. The factors in breast milk which influence these processes are still unclear and under investigation. We know that colostrum and breast milk contain a variety of molecules which can influence immune responses in the gut‐associated lymphoid tissue of a neonate. This review summarizes the evidence that variations in colostrum and breast milk composition can influence allergic outcomes in the infant, and the evidence that maternal and environmental factors can modify milk composition. Taken together, the data presented support the possibility that maternal dietary interventions may be an effective way to promote infant health through modification of breast milk composition.     

Varicella-zoster virus infection of a human CD4-positive T-cell line

Varicella-zoster virus (VZV) is a human alpha-herpesvirus that causes varicella (chickenpox) at primary infection and may reactivate as herpes zoster. VZV is a T-lymphotropic virus in vivo. To investigate the T-cell tropism of VZV, we constructed a recombinant virus expressing green fluorescent protein (VZV-GFP) under the CMV IE promoter. Coculture of VZV-GFP-infected fibroblasts with II-23 cells, a CD4-positive human T-cell hybridoma, resulted in transfer of virus to II-23 cells. II-23 cells are susceptible to VZV-GFP infection as demonstrated by expression of immediate/early (IE62), early (ORF4), and late (gE) genes. Recovery of infectious virus was limited, with only 1 to 3 in 10(6) cells releasing infectious virus by plaque assay, indicating that transfer of virus results in a limited productive infection. In vitro infection of II-23 cells will be useful for further analysis of VZV tropism for T-lymphocytes.