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Congenital cytomegalovirus (CMV) affects ~1 of 150 births and is a leading cause of hearing loss and intellectual disability. It has been suggested that transmission may occur via contaminated surfaces. CMV AD169 in filtered human saliva, applied to environmental surfaces, was recovered at various time points. Samples were evaluated by culture and real-time polymerase chain reaction. CMV was found viable on metal and wood to 1 hour, glass and plastic to 3 hours, and rubber, cloth, and cracker to 6 hours. CMV was cultured from 83 of 90 wet and 5 of 40 dry surfaces. CMV was more likely to be isolated from wet, highly absorbent surfaces at earlier time points. [ABSTRACT FROM AUTHOR]

The seroincidence of herpes simplex virus type 2 (HSV-2) infection was determined among 1766 patients attending sexually transmitted disease (STD) clinics and enrolled in a randomized, controlled trial of human immunodeficiency virus (HIV)/STD risk-reduction counseling (RRC). Arm 1 received enhanced RRC (4 sessions); arm 2, brief RRC (2 sessions); and arm 3, the control arm, brief informational messages. The overall incidence rate was 11.7 cases/100 person-years (py). Independent predictors of incidence of HSV-2 infection included female sex; black race; residence in Newark, New Jersey; <50% condom use with an occasional partner; and, in females, incident trichomoniasis and bacterial vaginosis. Only 10.8% of new HSV-2 infections were diagnosed clinically. Incidence rates were 12.9 cases/100 py in the control arm, 11.8 cases/100 py in arm 2, and 10.3 cases/100 py in arm 1 (hazard ratio, 0.8 [95% confidence interval, 0.6-1.1], vs. controls). The possible benefit of RRC in preventing acquisition of HSV-2 infection offers encouragement that interventions more specifically tailored to genital herpes may be useful and should be an important focus of future studies. Copyright © 2004 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Viruses that can persist in the host are of special concern in immunocompromised populations. Among 871 human immunodeficiency virus (HIV)-infected and 439 high-risk HIV-uninfected women, seroprevalences of cytomegalovirus, hepatitis B virus, hepatitis C virus, and herpes simplex virus types 1 and 2 and prevalence of human papillomavirus DNA in cervicovaginal lavage fluids were all >50% and were 2-30 times higher than prevalences in the general population. Prevalences were highest among HIV-infected women, of whom 44.2% had >or=5 other infections, and were relatively high even among the youngest women (age 16-25 years). In multivariate analyses, viral infections were independently associated not only with behaviors such as injection drug use and commercial sex but also with low income, low levels of education, and black race. Disadvantaged women and women who engage in high-risk behaviors are more likely to be coinfected with HIV and other viruses and, thus, may be at high risk of serious disease sequelae. Copyright © 2003 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

The seroprevalence of herpes simplex virus type 2 (HSV-2) infection was studied among 4128 patients from sexually transmitted disease (STD) clinics who were enrolled in a randomized controlled trial of human immunodeficiency virus and STD counseling efficacy. HSV-2 seroprevalence was 40.8% and was higher in women than in men (52.0% vs. 32.4%; P<.0001) and higher in blacks than in nonblacks (48.1% vs. 29.6%; P<.0001). Among 14-19-year-old patients, 36.8% of black women and 25.8% of nonblack women were infected with HSV-2. Independent predictors of HSV-2 seropositivity included female sex, black race, older age, less education, more lifetime sex partners, prior diagnosis of syphilis or gonorrhea, and lack of HSV-1 antibody. The majority of HSV-2-seropositive persons (84.7%) had never received a diagnosis of genital herpes. HSV-2 infection is common in STD clinic attendees in the United States, even among young age groups, especially among women. Efforts to prevent genital herpes should begin at an early age. The high rate of undiagnosed HSV-2 infection likely contributes to ongoing transmission. Copyright © 2002 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Background: This paper describes the seroprevalence and risk factors of Herpes simplex virus (HSV) infection in a group of female prostitutes from Mexico City.Methods: Women who consented to participate in the study voluntarily attended a sexually transmitted disease (STD) clinic during 1992. A standardized questionnaire was administered and a blood sample was obtained from each participant. Type-specific Western blot serology was performed to determine the serostatus of HSV-1 and HSV-2 for participants. Bivariate and multivariate analyses were applied to identify variables associated with an increased risk for HSV infection.Results: Prevalences of infection among the 997 prostitutes studied were 93.9% for HSV-1 and 60.8% for HSV-2. Only 1.8% of the women were seronegative for both viruses. The only variable associated with HSV-1 seropositivity was crowding index. The following variables were associated with an increased risk for infection with HSV-2: age, level of education, working site, born outside Mexico City and increasing time as a prostitute.Conclusions: This is the first assessment of HSV infection in Mexico and may be useful for the development and application of control and preventive measures among the prostitute population at risk of acquiring and transmitting human immunodeficiency virus (HIV) and other STD. [ABSTRACT FROM AUTHOR]

As with most live attenuated viral vaccines, varicella vaccine comprises a mixture of variant strains. Knowledge about the pathogenic potential of individual strains in the varicella vaccine is limited. Vaccination against chickenpox causes a usually modified varicella-like rash in a small percentage of healthy children, and vaccine virus reactivates on rare occasions to cause herpes zoster (HZ). In several published studies, our respective laboratories have analyzed genomic variation among specimens from cases of postvaccination rash and HZ in vaccine recipients, focusing on polymorphisms between vaccine Oka strains and the parental Oka strain. In most respects, these studies were in close agreement, identifying the set of wild-type markers among vaccine adverse event isolates, each occurring at similar frequencies. The same 3 universally present vaccine markers, at positions 106262, 107252, and 108111, were also identified by both laboratories. One notable difference has been the observation of mostly clonal vaccine virus among isolates examined by one laboratory and mostly mixed viruses in isolates examined by the other. In addition to reviewing and comparing our combined observations, we propose possible explanations for our contrasting findings and propose future studies to reconcile them. Copyright © 2008 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Widespread use of varicella vaccine in the United States could enable detection of rare adverse events not identified previously. We reviewed data from 1995 to 2005 from the Vaccine Adverse Event Reporting System, including data from laboratory analyses, to distinguish adverse events associated with wild-type varicella-zoster virus (VZV) versus those associated with vaccine strain. Almost 48 million doses of varicella vaccine were distributed between 1995 and 2005. There were 25,306 adverse events reported (52.7/100,000 doses distributed); 5.0% were classified as serious (2.6/100,000 doses distributed). Adverse events associated with evidence of vaccine-strain VZV included meningitis in patients with concurrent herpes zoster. Patients with genetic predispositions may rarely have disease triggered by receipt of varicella vaccine. Overall, serious adverse events reported after varicella vaccination continue to be rare and must be considered relative to the substantial benefits of varicella vaccination. Ongoing safety surveillance and further studies may shed light on some of the hypothesized associations. Copyright © 2008 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

In June 2005, the Advisory Committee on Immunization Practices (ACIP) recommended administering a second dose of varicella vaccine during outbreaks, supplementing the routine 1-dose requirement. From October 2005 to January 2006, a varicella outbreak occurred in Maine in a highly vaccinated elementary school population. We investigated the outbreak, held a school-based vaccination clinic, and assessed costs in implementing ACIP's outbreak-response recommendation. Parents completed questionnaires and case investigation interviews. Personnel at the Maine Center for Disease Control and Prevention, the school in which the outbreak occurred ('school A'), and physician offices completed economic surveys. Forty-eight cases occurred, with no hospitalizations or deaths. Vaccine effectiveness was 86.6% (95% confidence interval, 82.0%-90.1%). Of 240 eligible students, 132 (55.0%) received second-dose vaccination. Implementing ACIP's outbreak-response recommendation was challenging and cost approximately $26,875. Additionally, the routine 1-dose varicella vaccination policy did not confer adequate population immunity to prevent this outbreak. These findings support ACIP's June 2007 recommendation for a routine 2-dose varicella vaccination program. Copyright © 2008 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Thirty-three long-term care residents (mean age 76.5 years), who were participating in a study in which they were randomized to receive either oral daily standard dose (400-1000 IU/day) 25-hydroxy vitamin D (vitamin D3) (SD) or high dose (3000-4000 IU/day) (HD) vitamin D3, were vaccinated with the live, attenuated herpes zoster vaccine. Blood was drawn at vaccination and three weeks later to determine varicella-zoster virus (VZV) antibody and T-cell mediated immune responses. ELISA and neutralizing antibodies increased significantly, but to the same extent, in both groups. The antibody avidity significantly increased from pre- to post-vaccination only in the HD group. VZV-CMI, as measured by FLUOROSPOT significantly increased post-vaccination in both groups, but the difference in interferon-γ spot-forming cells (SFC) and interleukin-2 SFC was lower in the HD than SD group. The increase in VZV-CMI correlated inversely with circulating regulatory T cells in the HD group. We conclude that pre-treatment with HD vitamin D3 does not appreciably enhance the antibody response to a live vaccine and that VZV-CMI responses were diminished in HD vitamin D3 recipients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.J.L. is a consultant for Moderna, Pfizer, Merck, GSK, and Curevo; N. L., R.S.S., J.C., A.A.G., D.S.S. No disclosures; A. W. is a consultant for Pfizer, Curevo, GSK, and Merck., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Fatigue is the most prevalent Long-COVID symptom. Individuals who are affected have to learn to organize and manage daily activities according to the subjectively perceived energy reserves. Our objective was to develop an application, Fading Fatigue, that supports patients in their energy management, in particular after an initial therapy guided by health professionals. Fading Fatigue was developed in an iterative approach and implemented as a client-server application. Interviews and a literature search were conducted to identify limitations and challenges of the current treatment. Fading Fatigue offers several tools for energy management: a daily energy planner, a documentation aid for well-being and a progress view. Future work should study usability. Inclusion of additional features increasing the adherence such as providing feedback could be considered.

The unprecedented success of mRNA vaccines in managing the COVID-19 pandemic raises the prospect of applying the mRNA platform to other viral diseases of humans and domesticated animals, which may lead to more efficacious vaccines for some agents. We briefly discuss reasons why mRNA vaccines achieved such success against COVID-19 and indicate what other virus infections and disease conditions might also be ripe for control using mRNA vaccines. We also evaluate situations where mRNA could prove valuable to rebalance the status of immune responsiveness and achieve success as a therapeutic vaccine approach against infections that induce immunoinflammatory lesions., Competing Interests: Declaration of competing interest The authors declare no conflict of financial interest., (Copyright © 2022 Institut Pasteur. All rights reserved.)

Herpes zoster is a localized skin infection caused by reactivation of latent varicella-zoster virus. Tissue-resident T cells likely control skin infections. Zoster provides a unique opportunity to determine if focal reinfection of human skin boosts local or disseminated antigen-specific tissue-resident T cells. Here, we show virus-specific T cells are retained over one year in serial samples of rash site and contralateral unaffected skin of individuals recovered from zoster. Consistent with zoster resolution, viral DNA is largely undetectable on skin from day 90 and virus-specific B and T cells decline in blood. In skin, there is selective infiltration and long-term persistence of varicella-zoster virus-specific T cells in the rash site relative to the contralateral site. The skin T cell infiltrates express the canonical tissue-resident T cell markers CD69 and CD103. These findings show that zoster promotes spatially-restricted long-term retention of antigen-specific tissue-resident T cells in previously infected skin., (© 2022. The Author(s).)

Zoster vaccines generate antibody responses against varicella-zoster virus (VZV). We compared antibody-dependent cell cytotoxicity (ADCC) elicited by zoster vaccine live (ZVL) and recombinant zoster vaccine (RZV). ADCC mediated by antibodies against VZV lysate (VZV-ADCC) and recombinant glycoprotein E (gE-ADCC) was measured using plasma from 20 RZV- and 20 ZVL-recipients, including half 50-60-years-old and half ≥70-years-old. Solid phase-bound anti-VZV antibodies stimulated TNFα in NK cells as measured by flow cytometry or ELISA. VZV-ADCC pre- and post-immunization was higher in younger vaccinees. ZVL did not appreciably increase VZV-ADCC, whereas RZV increased VZV-ADCC in older vaccinees. ELISA-measured gE-ADCC was similar across groups pre-immunization; significantly increased after ZVL; and RZV and was higher in younger RZV than ZVL recipients. IgG3 antibodies increased after RZV and ZVL, with greater anti-gE than anti-VZV responses. Moreover, gE-ADCC strongly correlated with anti-gE antibody avidity, but there were no appreciable correlations between VZV-ADCC and avidity. NK cells stimulated by anti-gE antibodies showed increased IFNγ and CD107a expression, which was not observed with anti-VZV antibodies. In conclusion, anti-gE antibodies generated more robust ADCC than anti-VZV antibodies. RZV induced higher ADCC antibodies than ZVL depending on the antigen and age of vaccinees. Older adults had lower ADCC antibodies before and after vaccination than younger adults., (© 2022. The Author(s).)

Background and Purpose: A large proportion of ischemic stroke patients lack a definitive stroke etiology despite extensive diagnostic testing. Varicella-Zoster Virus (VZV) can directly invade blood vessels causing vasculitis and may be associated with cryptogenic stroke (CS)., Methods: We conducted a retrospective cross-sectional study of CS patients tested for VZV. The following were considered evidence of VZV reactivation (VZV+): positive CSF VZV PCR, anti-VZV IgM in CSF, or anti-VZV IgG CSF/serum ratio of 1:10 or higher. We describe the cohort, report VZV+ proportion with 95% confidence intervals (CI) determined with the Wald method, and compare patient groups using standard statistical tests., Results: A total of 72 CS patients met full study inclusion criteria. Most of the patients were <65 years old, had few traditional vascular risk factors, and had multifocal infarcts. Mean age was 49 years (SD ±13) and 47% were women. A total of 14 patients (19.4%; CI: 11.4-30.8%) had evidence of CNS VZV reactivation. There was no difference in evaluated demographic or radiographic features between those with versus without evidence of VZV reactivation. History of ischemic stroke in the past year (11/14 vs 25/43, P <.05) and hypertension (13/14 vs 35/58 and P <.05) were associated with VZV+., Conclusion: We found a high proportion of CNS VZV reactivation in a cross-sectional cohort of CS patients selected for CSF testing. Testing for VZV might be reasonable in CS patients who are young, have multifocal infarcts, or had an ischemic stroke within the past year, but additional research is needed., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Although the establishment, maintenance and reactivation from alphaherpesvirus latency is far from fully understood, some things are now manifestly clear: Alphaherpesvirus latency occurs in neurons of the peripheral nervous system and control of the process is multifactorial and complex. This includes components of the immune system, contributions from non-neuronal cells surrounding neurons in ganglia, specialized nucleic acids and modifications to the viral DNA to name some of the most important. Efficacious vaccines have been developed to control both acute varicella and zoster, the outcome of reactivation, but despite considerable effort vaccines for acute herpes simplex virus (HSV) infection or reactivated lesions have thus far failed to materialize despite considerable effort. Given the relevance of the immune system to establish and maintain HSV latency, a vaccine designed to tailor the HSV response to maximize the activity of components most critical for controlling reactivated infection might limit the severity of recurrences and hence reduce viral transmission. In this review, we discuss the current understanding of immunological factors that contribute to HSV and VZV latency, identify differences between varicella-zoster virus (VZV) and HSV that could explain why vaccines have been valuable at controlling VZV disease but not HSV, and finish by outlining possible strategies for developing effective HSV vaccines.

Monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) are clonal B-cell disorders associated with an increased risk of infections and impaired vaccination responses. We investigated the immunogenicity of recombinant zoster vaccine (RZV) in these patients. Individuals with MBL/untreated CLL and Bruton tyrosine kinase inhibitor (BTKi)-treated CLL patients were given two doses of RZV separated by 2 months. Responses assessed at 3 and 12 months from the first dose of RZV by an anti-glycoprotein E ELISA antibody assay and by dual-color Interferon-γ and Interleukin-2FLUOROSPOT assays were compared to historic controls matched by age and sex. About 62 patients (37 MBL/untreated CLL and 25 BTKi-treated CLL) were enrolled with a median age of 68 years at vaccination. An antibody response at 3 months was seen in 45% of participants, which was significantly lower compared to historic controls (63%, p = .03). The antibody response did not significantly differ between MBL/untreated CLL and BTKi-treated CLL (51% vs. 36%, respectively, p = .23). The CD4+ T-cell response to vaccination was significantly lower in study participants compared to controls (54% vs. 96%, p < .001), mainly due to lower responses among BTKi-treated patients compared to untreated MBL/CLL (32% vs. 73%, p = .008). Overall, only 29% of participants achieved combined antibody and cellular responses to RZV. Among participants with response assessment at 12 months (n = 47), 24% had antibody titers below the response threshold. Hypogammaglobulinemia and BTKi therapy were associated with reduced T-cell responses in a univariate analysis. Strategies to improve vaccine response to RZV among MBL/CLL patients are needed., (© 2021 Wiley Periodicals LLC.)

Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125-241 kbp contain 70-170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae , which is available at ictv.global/report/herpesviridae.

Background: Immunization of varicella-zoster virus (VZV)-seronegative solid organ transplant (SOT) patients using the live-attenuated varicella vaccine is generally contraindicated, leaving no widely applicable immunization option. The recombinant subunit herpes zoster vaccine (RZV) is indicated for VZV-seropositive persons to prevent shingles but could potentially also protect VZV-seronegative persons against varicella. We performed a safety and immunogenicity evaluation of RZV in VZV-seronegative SOT recipients as an option for protection., Methods: VZV-seronegative adult SOT patients with no history of varicella/shingles vaccine or disease were given 2 doses of RZV vaccine 2-6 mo apart. Blood was drawn prevaccination (V1), before the second dose (V2), and 4 wk after the second dose (V3). Humoral immunity (anti-glycoprotein E) and cell-mediated immunity were evaluated, with polyfunctional cells defined as cells producing ≥2 cytokines., Results: Among 31 eligible VZV-seronegative SOT patients screened, 23 were enrolled. Median age was 38 y and median time since transplant procedure was 3.8 y. The most frequent transplant types were liver (35%) and lung (30%). Median anti-glycoprotein E levels significantly increased from V1 to V3 (P = 0.001) and V2 to V3 (P < 0.001), even though only 55% had a positive seroresponse. Median polyfunctional CD4 T-cell counts increased from V1 to V2 (54/106 versus 104/106 cells; P = 0.041) and from V2 to V3 (380/106; P = 0.002). Most adverse events were mild with no rejection episodes., Conclusions: RZV was safe and elicited significant humoral and cellular responses in VZV-seronegative SOT patients and has the potential to be considered as a preventive strategy against primary varicella., Competing Interests: D.K. has received clinical trials grant and consulting fees from GSK. The other authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Monkeypox is a poorly described emerging zoonosis endemic to Central and Western Africa., Methods: Using surveillance data from Tshuapa Province, Democratic Republic of the Congo during 2011-2015, we evaluated differences in incidence, exposures, and clinical presentation of polymerase chain reaction-confirmed cases by sex and age., Results: We report 1057 confirmed cases. The average annual incidence was 14.1 per 100 000 (95% confidence interval, 13.3-15.0). The incidence was higher in male patients (incidence rate ratio comparing males to females, 1.21; 95% confidence interval, 1.07-1.37), except among those 20-29 years old (0.70; .51-.95). Females aged 20-29 years also reported a high frequency of exposures (26.2%) to people with monkeypox-like symptoms.The highest incidence was among 10-19-year-old males, the cohort reporting the highest proportion of animal exposures (37.5%). The incidence was lower among those presumed to have received smallpox vaccination than among those presumed unvaccinated. No differences were observed by age group in lesion count or lesion severity score., Conclusions: Monkeypox incidence was twice that reported during 1980-1985, an increase possibly linked to declining immunity provided by smallpox vaccination. The high proportion of cases attributed to human exposures suggests changing exposure patterns. Cases were distributed across age and sex, suggesting frequent exposures that follow sociocultural norms., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Lung transplant recipients are at high risk for herpes zoster and preventive measures are a significant unmet need. We investigated the safety and immunogenicity of two doses of a recombinant zoster vaccine (RZV) in lung transplant recipients (≥50 years). We enrolled 50 patients of which 49 received at least one vaccine dose. Anti-glycoprotein E (gE) antibody levels (n = 43) increased significantly compared to baseline (median optical density [OD] 1.96; interquartile range [IQR]: 1.17-2.89) after the first (median OD 3.41, IQR 2.54-3.81, p < .0001) and second vaccine dose (median OD 3.63, IQR 3.39-3.86, p < .0001). gE-specific polyfunctional CD4+ T cell frequencies (n = 38) also increased from baseline (median 85 per 10 6 CD4+ T cells; IQR: 46-180) to the first (median 128 per 10 6 CD4+ T cells; IQR: 82-353; p = .023) and after the second dose (median 361 per 10 6 CD4+ T cells; IQR: 146-848; p < .0001). Tenderness (83.0%; 95%CI: 69.2-92.4%) and redness (31.9%; 95%CI: 19.1-47.1%) at injection site were common. One rejection episode within 3 weeks of vaccination was observed. This is the first study demonstrating that RZV was safe and elicited significant humoral and cell-mediated immunity in lung transplant recipients. RZV is a new option for the prevention of shingles in this population., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Two herpes zoster (HZ) vaccines licensed in the United States are recommended by the Advisory Committee on Immunization Practices (ACIP): (i) live-attenuated vaccine (ZVL) using vOka strain varicella-zoster virus (VZV) and (ii) recombinant adjuvanted vaccine (RZV) containing recombinant varicella-zoster virus (VZV) glycoprotein E (gE). Two phase 3 clinical trials of RZV led the Advisory Committee on Immunization Practices (ACIP) to recommend it with preferred status. VZV T cell-mediated immunity (CMI), but not humoral immunity, is considered essential for protection against HZ. Published studies of humoral immunity focused on VZV-specific IgG concentration. To complement reports comparing the CMI responses to these vaccines, we compared humoral responses in ZVL and RZV recipients, emphasizing functional qualities (avidity and neutralization). Baseline avidities to a VZV glycoprotein mixture (gp) were near the upper limit of detection, but avidity to gE was much lower. Small increases in gp avidity were observed for both RZV and ZVL vaccination (19 and 12 avidity index units [AIU], respectively). RZV boosted both gE avidity and VZV neutralizing antibody significantly more than ZVL (mean gE avidity boost, 47 AIU versus 22 AIU; mean neutralizing antibody boost, 22-fold versus 8-fold). Increases in neutralizing antibodies strongly correlated with gE avidity increases ( r  = 0.5) and moderately with gp avidity increases ( r  = 0.23). After 1 year, 81% of RZV recipients and only 18% of ZVL recipients retained >50% of their peak avidity boosts. These results are consistent with the CMI responses to these vaccines: RZV responses are skewed to long-term memory, whereas ZVL preferentially induces transient effector responses. IMPORTANCE These observations further distinguish the immunogenicity and duration of the immune response of the two vaccines. In addition, measurements of functional humoral immunity (IgG avidity and neutralizing antibody) in response to zoster immunization, alone or combined with other immune markers, might contribute to practical in vitro correlates of protection. Combined with previous observations of the cell-mediated response to these vaccines, this study suggests that vaccine development will benefit from more expansive and granular assessments of acquired immunity during early phase 1 immunogenicity trials., (Copyright © 2021 American Society for Microbiology.)

Varicella poses an occupational risk and a nosocomial risk for susceptible healthcare personnel and patients, respectively. Patients with varicella are thought to be infectious from 1 to 2 days before rash onset until all lesions are crusted, typically 4-7 days after onset of rash. We searched Medline, Embase, Cochrane Library and CINAHL databases to assess evidence of varicella-zoster virus (VZV) transmission before varicella rash onset. Few articles (7) contributed epidemiologic evidence; no formal studies were found. Published articles reported infectiousness at variable intervals before rash onset, between <1 day to 4 days prior to rash, with 1-2 patients for each interval. Laboratory assessment of transmission before rash was also limited (10 articles). No culture-positive results were reported. VZV DNA was identified by PCR before rash onset in only one study however, PCR does not indicate infectivity of the virus. Based on available medical literature, VZV transmission before rash onset seems unlikely, although the possibility of pre-rash, respiratory transmission cannot be entirely ruled out.

Background: Varicella zoster virus (VZV) vasculopathy is characterized by persistent arterial inflammation leading to stroke. Studies show that VZV induces amyloid formation that may aggravate vasculitis. Thus, we determined if VZV central nervous system infection produces amyloid., Methods: Aβ peptides, amylin, and amyloid were measured in cerebrospinal fluid (CSF) from 16 VZV vasculopathy subjects and 36 stroke controls. To determine if infection induced amyloid deposition, mock- and VZV-infected quiescent primary human perineurial cells (qHPNCs), present in vasculature, were analyzed for intracellular amyloidogenic transcripts/proteins and amyloid. Supernatants were assayed for amyloidogenic peptides and ability to induce amyloid formation. To determine amylin's function during infection, amylin was knocked down with small interfering RNA and viral complementary DNA (cDNA) was quantitated., Results: Compared to controls, VZV vasculopathy CSF had increased amyloid that positively correlated with amylin and anti-VZV antibody levels; Aβ40 was reduced and Aβ42 unchanged. Intracellular amylin, Aβ42, and amyloid were seen only in VZV-infected qHPNCs. VZV-infected supernatant formed amyloid fibrils following addition of amyloidogenic peptides. Amylin knockdown decreased viral cDNA., Conclusions: VZV infection increased levels of amyloidogenic peptides and amyloid in CSF and qHPNCs, indicating that VZV-induced amyloid deposition may contribute to persistent arterial inflammation in VZV vasculopathy. In addition, we identified a novel proviral function of amylin., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Recent enhanced monkeypox (MPX) surveillance in the Democratic Republic of Congo, where MPX is endemic, has uncovered multiple cases of MPX and varicella zoster virus (VZV) coinfections. The purpose of this study was to verify if coinfections occur and to characterize the clinical nature of these cases. Clinical, epidemiological, and laboratory results were used to investigate MPX/VZV coinfections. A coinfection was defined as a patient with at least one Orthopoxvirus/MPX-positive sample and at least one VZV-positive sample within the same disease event. Between September 2009 and April 2014, 134 of the 1,107 (12.1%) suspected MPX cases were confirmed as MPX/VZV coinfections. Coinfections were more likely to report symptoms than VZV-alone cases and less likely than MPX-alone cases. Significantly higher lesion counts were observed for coinfection cases than for VZV-alone but less than MPX-alone cases. Discernible differences in symptom and rash severity were detected for coinfection cases compared with those with MPX or VZV alone. Findings indicate infection with both MPX and VZV could modulate infection severity. Collection of multiple lesion samples allows for the opportunity to detect coinfections. As this program continues, it will be important to continue these procedures to assess variations in the proportion of coinfected cases over time.

The varicella-zoster virus (VZV) genome, comprises both unique and repeated regions. The genome also includes reiteration regions, designated R1 to R5, which are tandemly repeating sequences termed elements. These regions represent an understudied feature of the VZV genome. The R4 region is duplicated, with one copy in the internal repeat short (IRs) which we designated R4A and a second copy in the terminal repeat short (TRs) termed R4B. We developed primers to amplify and Sanger sequence these regions, including independent amplification of both R4 regions. Reiteration regions from >80 cases of PCR-confirmed shingles were sequenced and analyzed. Complete genome sequences for the remaining portions of these viruses were determined using Illumina MiSeq. We identified 28 elements not previously reported, including at least one element for each R region. Length heterogeneity was substantial in R3, R4A and R4B. Length heterogeneity between the two copies of R4 was common., Competing Interests: Declaration of competing interest The authors report no conflicts of interest related to this work., (Copyright © 2020. Published by Elsevier Inc.)

Childhood immunization with the live-attenuated varicella-zoster virus (VZV) vaccine induces protective immune responses. Routine VZV vaccination started only 2 decades ago, and thus, there are few studies examining the longevity of vaccine-induced immunity. Here, we analyzed the quantity of VZV-specific plasma cells (PCs) and CD4 T cells in the bone marrow (BM) of healthy young adults ( n  = 15) following childhood VZV immunization. Long-lived BM resident plasma cells constitutively secrete antibodies, and we detected VZV-specific PCs in the BM of all subjects. Anti-VZV plasma antibody titers correlated positively with the number of VZV-specific BM PCs. Furthermore, we quantified the number of interferon gamma (IFN-γ)-producing CD4 T cells specific for VZV glycoprotein E and all other structural and nonstructural VZV proteins in both BM and blood (peripheral blood mononuclear cells [PBMCs]). The frequency of VZV-specific IFN-γ-producing CD4 T cells was significantly higher in PBMCs than BM. Our study shows that VZV-specific PCs and VZV-specific CD4 memory T cells persist up to 20 years after vaccination. These findings indicate that childhood VZV vaccination can elicit long-lived immune memory responses in the bone marrow. IMPORTANCE Childhood varicella-zoster virus (VZV) immunization induces immune memory responses that protect against primary VZV infection, chicken pox. In the United States, routine childhood VZV vaccination was introduced only 2 decades ago. Hence, there is limited information on the longevity of B and CD4 T cell memory, which are both important for protection. Here, we showed in 15 healthy young adults that VZV-specific B and CD4 T cell responses are detectable in bone marrow (BM) and blood up to 20 years after vaccination. Specifically, we measured antibody-secreting plasma cells in the BM and VZV-specific CD4 T cells in BM and blood. These findings suggest that childhood VZV vaccination induces long-lived immunity., (Copyright © 2020 American Society for Microbiology.)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Human cytomegalovirus (HCMV) infections are among the most common complications arising in transplant patients, elevating the risk of various complications including loss of graft and death. HCMV infections are also responsible for more congenital infections worldwide than any other agent. Congenital HCMV (cCMV) infections are the leading nongenetic cause of sensorineural hearing loss and a source of significant neurological disabilities in children. While there is overlap in the clinical and laboratory approaches to diagnosis of HCMV infections in these settings, the management, follow-up, treatment, and diagnostic strategies differ considerably. As yet, no country has implemented a universal screening program for cCMV. Here, we summarize the issues, limitations, and application of diagnostic strategies for transplant recipients and congenital infection, including examples of screening programs for congenital HCMV that have been implemented at several centers in Japan, Italy, and the United States., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Herpes zoster (HZ) is caused by reactivation of varicella zoster virus (VZV) that established latency in sensory and autonomic neurons during primary infection. In the Shingles Prevention Study (SPS), a large efficacy trial of live attenuated Oka/Merck zoster vaccine (ZVL), PCR-confirmed second episodes of HZ occurred in two of 660 placebo and one of 321 ZVL recipients with documented HZ during a mean follow-up of 3.13 years. An additional two ZVL recipients experienced a second episode of HZ in the Long-Term Persistence Substudy. All episodes of HZ were caused by wild-type VZV. The first and second episodes of HZ occurred in different dermatomes in each of these five participants, with contralateral recurrences in two. Time between first and second episodes ranged from 12 to 28 months. One of the five participants, who was immunocompetent on study enrollment, was immunocompromised at the onset of his first and second episodes of HZ. VZV DNA isolated from rash lesions from the first and second episodes of HZ was used to sequence the full-length VZV genomes. For the unique-sequence regions of the VZV genome, we employed target enrichment of VZV DNA, followed by deep sequencing. For the reiteration regions, we used PCR amplification and Sanger sequencing. Our analysis and comparison of the VZV genomes from the first and second episodes of HZ in each of the five participants indicate that both episodes were caused by the same VZV strain. This is consistent with the extraordinary stability of VZV during the replication phase of varicella and the subsequent establishment of latency in sensory ganglia throughout the body. Our observations also indicate that VZV is stable during the persistence of latency and the subsequent reactivation and replication that results in HZ., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The live-attenuated varicella vaccine, a routine immunization in the United States since 1995, is both safe and effective. Like wild-type varicella-zoster virus, however, vaccine Oka (vOka) varicella can establish latency and reactivate as herpes zoster, rarely leading to serious disease, particularly among immunocompromised hosts. Previous cases of reactivated vOka resulting in meningitis have been described in young children who received a single dose of varicella vaccine; less is known about vOka reactivation in older children after the 2-dose vaccine series. We present 2 adolescents with reactivated vOka meningitis, 1 immunocompetent and 1 immunocompromised, both of whom received 2 doses of varicella vaccine many years before as children. Pediatricians should be aware of the potential of vOka varicella to reactivate and cause clinically significant central nervous system disease in vaccinated children and adolescents., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Dr Gershon has National Institutes of Health funding to study varicella-zoster virus and a service laboratory contract with Merck for study of the safety of varicella-zoster virus vaccines. Dr Englund has received research support from Merck and GlaxoSmithKline. The other authors have indicated they have no potential conflicts of interest to disclose. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Diseases Control and Prevention., (Copyright © 2019 by the American Academy of Pediatrics.)

Objective: To describe varicella cases in Tshuapa Province of the Democratic Republic of the Congo identified during monkeypox surveillance., Methods: Demographic, clinical and epidemiological data were collected from each suspected monkeypox case 2009-2014. Samples were tested by PCR for both Orthopoxviruses and varicella-zoster virus (VZV); a subset of VZV-positive samples was genotyped. We defined a varicella case as a rash illness with laboratory-confirmed VZV., Results: There were 366 varicella cases were identified; 66% were ≤19 years old. Most patients had non-typical varicella rash with lesions reported as the same size and stage of evolution (86%), deep and profound (91%), on palms of hands and/or soles of feet (86%) and not itchy (49%). Many had non-typical signs and symptoms, such as lymphadenopathy (70%) and sensitivity to light (23%). A higher proportion of persons aged ≥20 years than persons aged ≤19 years had ≥50 lesions (79% vs. 65%, P = 0.007) and were bedridden (15% vs. 9%, P = 0.056). All VZV isolates genotyped from 79 varicella cases were clade 5. During the surveillance period, one possible VZV-related death occurred in a 7-year-old child., Conclusions: A large proportion of patients presented with non-typical varicella rash and clinical signs and symptoms, highlighting challenges identifying varicella in an area with endemic monkeypox. Continued surveillance and laboratory diagnosis will help in rapid identification and control of both monkeypox and varicella and improve our understanding of varicella epidemiology in Africa., (© 2019 John Wiley & Sons Ltd This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Introduction: Pain following herpes zoster (HZ) can persist for months and negatively impact quality of life. To evaluate the effect of zoster vaccine live (ZVL) on progression of pain following HZ, we conducted a prospective cohort study of HZ cases at Kaiser Permanente Southern California., Methods: ZVL vaccinated and unvaccinated members aged ≥60 years with laboratory-confirmed HZ from January 18, 2012 to February 26, 2015 were followed up within 5 days of HZ diagnosis, and at 30, 60, and 90 days after diagnosis. Pain was assessed with the Zoster Brief Pain Inventory (ZBPI) on a 0-10 scale, using cut-points of ≥3, ≥5, and ≥7, with postherpetic neuralgia (PHN) defined as pain ≥3 at 90 days. Log binomial regression was used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) associated with pain, comparing vaccinated versus unvaccinated HZ patients., Results: We interviewed 509 vaccinated and 509 unvaccinated HZ patients. ZVL was associated with significantly lower risks of HZ-related pain at all time-points. The risk of PHN in vaccinated and unvaccinated patients, respectively, was 9.2% and 15.4% (aRR = 0.594, 95% CI: 0.413, 0.854); 2.0% and 4.8% of these patients reported pain ≥7 (aRR = 0.332, 95% CI: 0.153, 0.721). Irrespective of vaccination, the risk of PHN was lower in adults aged <70 years versus those ≥70 years and was similar or lower in females versus males., Conclusion: We used laboratory confirmation of HZ cases and patient survey to show that aside from preventing HZ, ZVL reduced HZ-related pain and prevented PHN among vaccine recipients who experienced HZ. Observational studies will be needed to evaluate long-term effectiveness of the new recombinant zoster vaccine and its benefits in protecting patients against PHN., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Vaccination against varicella-zoster virus (VZV) has been effective and safe in countries that routinely administer the vaccine. Brazil began universal VZV vaccination in 2013. This study aimed to identify VZV genotypes present in Manaus, Brazil prior to widespread immunization., Methods: Vesicular lesions or cerebral-spinal-fluid samples were collected from patients diagnosed with VZV, herpes zoster, or meningitis/encephalitis. DNA was extracted, amplified, and sequenced., Results: Half the isolates were clade-5 viruses and the remaining were divided between the European clades 1 and 3., Conclusions: This study provides insights into the circulating VZV genotypes in Manaus prior to widespread vaccination.