Varicella-zoster Virus Infection Research Articles

Immunogenicity to Herpes Zoster recombinant subunit vaccine in immune-mediated rheumatic patients under treatment with JAK inhibitors.

Patients with immune-mediated rheumatic diseases (IMRDs) face an elevated risk of varicella-zoster virus infection (VZV), and herpes zoster (HZ). Treatment with immunosuppressors further increases the risk. A new recently approved adjuvant recombinant inactive vaccine, offers safe protection against HZ. However, limited data exist on the efficacy of this new vaccine in patients with IMRDs treated with JAK inhibitors. We aimed to characterize B cell and T cell immune responses elicited by the HZ recombinant subunit vaccine in patients with IMRDs under treatment with JAK inhibitors, and to identify factors that might be associated with reduced immunogenicity, and therefore reduced protection. We investigated humoral, and cellular CD4 and CD8 immune responses following a two-dose regimen of the recombinant inactive vaccine in 43 patients with rheumatic diseases treated with different JAK inhibitors. The responses were compared with age, gender and disease-matched healthy controls. Patients with IMRDs treated with JAK inhibitors showed reduced seroconversion rate (63% vs 100% and lower VZV IgG titers (1222 ± 411 vs 3048 ± 556, p< 0.0001) as compared with healthy controls. Functional T CD4 (IL-2 plus IFN-γ secretion) and T CD8 (Granzyme A and/or Granzyme B secretion) immune responses were also significantly diminished in IMRDs patients. Negative correlation was found between VZV antibody titers and age, specific treatments (baricitinib, tofacitinib, upadacitinib), cumulative methotrexate and glucocorticoid doses, history of multiple DMARDs, and treatment duration with JAK inhibitors. Functional T-CD4 responses but not functional T-CD8 responses also showed similar negative correlations. Positive associations were observed between functional T-CD4 and T-CD8 responses. Our study provides valuable insights into the immune responses elicited by the recombinant inactive vaccine in patients with IMRDs treated with JAK inhibitors. In these patients we have observed a broad impact on the adaptive humoral and cellular immune responses, suggesting a potential reduction in protection against herpes zoster infection and VHZ reactivation.

Upregulation of keratin 15 is required for varicella-zoster virus replication in keratinocytes and is attenuated in the live attenuated vOka vaccine strain

Varicella-zoster virus (VZV) is the etiological agent of chickenpox and shingles, diseases characterised by epidermal virus replication in skin and mucosa and the formation of blisters. We have previously shown that VZV infection has a profound effect on keratinocyte differentiation, altering the normal pattern of epidermal gene expression. In particular, VZV infection reduces expression of suprabasal keratins 1 and 10 and desmosomal proteins, disrupting epidermal structure to promote expression of a blistering phenotype. Here, we extend these findings to show that VZV infection upregulates the expression of keratin 15 (KRT15), a marker expressed by basal epidermal keratinocytes and hair follicles stem cells. We demonstrate that KRT15 is essential for VZV replication in the skin, since downregulation of KRT15 inhibits VZV replication in keratinocytes, while KRT15 exogenous overexpression supports viral replication. Importantly, our data show that VZV upregulation of KRT15 depends on the expression of the VZV immediate early gene ORF62. ORF62 is the only regulatory gene that is mutated in the live attenuated VZV vaccine and contains four of the five fixed mutations present in the VZV Oka vaccine. Our data indicate that the mutated vaccine ORF62 is not capable of upregulating KRT15, suggesting that this may contribute to the vaccine attenuation in skin. Taken together our data present a novel association between VZV and KRT15, which may open a new therapeutic window for a topical targeting of VZV replication in the skin via modulation of KRT15.

Chimeric antigen receptor-T-cell therapies going viral: latent and incidental viral infections.

Infections are the leading cause of non-relapse mortality following chimeric antigen receptor (CAR)-T-cell therapy, with viral infections being frequent both in the early and late phases post-infusion. We review the epidemiology of viral infections and discuss critical approaches to prevention and management strategies in this setting. Herpesviruses dominate the early period. herpes simplex virus and varicella zoster virus infections are rare due to widespread antiviral prophylaxis, but cytomegalovirus (CMV) reactivation is increasingly observed, particularly in high-risk groups including B cell maturation antigen (BCMA)-CAR-T-cell therapy recipients and patients receiving corticosteroids. While CMV end-organ disease is rare, CMV is associated with increased mortality, emphasizing the need to evaluate the broader impact of CMV on long-term hematological, infection, and survival outcomes. Human herpesvirus-6 (HHV-6) has also emerged as a concern, with its diagnosis complicated by overlapping symptoms with neurotoxicity, underscoring the importance of considering viral encephalitis in differential diagnoses. Respiratory viruses are the most common late infections with a higher incidence after BCMA CAR-T-cell therapy. Vaccination remains a critical preventive measure against respiratory viruses but may be less immunogenic following CAR-T-cell therapy. The optimal timing, type of vaccine, and dosing schedule require further investigation. A better understanding of viral epidemiology and preventive trials are needed to improve infection prevention practices and outcomes following CAR-T-cell therapies.

MR imaging of varicella zoster virus infection of the central and peripheral nervous system - From Ramsay-Hunt to Elsberg

MR imaging of varicella zoster virus infection of the central and peripheral nervous system - From Ramsay-Hunt to Elsberg

Ambispective epidemiological observational study of varicella-zoster virus infection: An 18 year-single-center Bulgarian experience.

Varicella (chickenpox) and herpes zoster (shingles) are outcomes of varicella-zoster virus (VZV) infection, and understanding their incidence trends is vital for public health planning. To conduct an ambispective epidemiological study by analyzing the main epidemiological characteristics of VZV infection during an 18 year-period (2000-2018). We used descriptive and epidemiological methods to characterize chickenpox in Bulgaria, the city of Plovdiv and the region for a period of 18 years (2000-2018). The average incidence of varicella-zoster infection for the period 2000-2018 in the Plovdiv region was estimated at 449.58‰. The highest relative share of the infection was assessed in the month of January at 13.6%, and the lowest in the months of August and September at 2.9% (both months). The age group most affected by the infection was 1-4 years, followed by 5-9 years. This corresponds to the so-called "pro-epidemic population" - a phenomenon typical for airborne infections, confirming their mass impact on the perpetuation of VZV infection. Our findings reveal significant insights into VZV epidemiology, including age-specific incidence rates, clinical manifestations, and vaccination impact. This comprehensive analysis contributes to the broader understanding of VZV infection dynamics and may inform evidence-based preventive measures.

Varicella-zoster virus recapitulates its immune evasive behaviour in matured hiPSC-derived neurospheroids.

Varicella-zoster virus (VZV) encephalitis and meningitis are potential central nervous system (CNS) complications following primary VZV infection or reactivation. With Type-I interferon (IFN) signalling being an important first line cellular defence mechanism against VZV infection by the peripheral tissues, we here investigated the triggering of innate immune responses in a human neural-like environment. For this, we established and characterised 5-month matured hiPSC-derived neurospheroids (NSPHs) containing neurons and astrocytes. Subsequently, NSPHs were infected with reporter strains of VZV (VZVeGFP-ORF23) or Sendai virus (SeVeGFP), with the latter serving as an immune-activating positive control. Live cell and immunocytochemical analyses demonstrated VZVeGFP-ORF23 infection throughout the NSPHs, while SeVeGFP infection was limited to the outer NSPH border. Next, NanoString digital transcriptomics revealed that SeVeGFP-infected NSPHs activated a clear Type-I IFN response, while this was not the case in VZVeGFP-ORF23-infected NSPHs. Moreover, the latter displayed a strong suppression of genes related to IFN signalling and antigen presentation, as further demonstrated by suppression of IL-6 and CXCL10 production, failure to upregulate Type-I IFN activated anti-viral proteins (Mx1, IFIT2 and ISG15), as well as reduced expression of CD74, a key-protein in the MHC class II antigen presentation pathway. Finally, even though VZVeGFP-ORF23-infection seems to be immunologically ignored in NSPHs, its presence does result in the formation of stress granules upon long-term infection, as well as disruption of cellular integrity within the infected NSPHs. Concluding, in this study we demonstrate that 5-month matured hiPSC-derived NSPHs display functional innate immune reactivity towards SeV infection, and have the capacity to recapitulate the strong immune evasive behaviour towards VZV.

Glycoprotein E-Displaying Nanoparticles Induce Robust Neutralizing Antibodies and T-Cell Response against Varicella Zoster Virus.

The Varicella zoster virus (VZV), responsible for both varicella (chickenpox) and herpes zoster (shingles), presents significant global health challenges. While primary VZV infection primarily affects children, leading to chickenpox, reactivation in later life can result in herpes zoster and associated post-herpetic neuralgia, among other complications. Vaccination remains the most effective strategy for VZV prevention, with current vaccines largely based on the attenuated vOka strains. Although these vaccines are generally effective, they can induce varicella-like rashes and have sparked concerns regarding cell virulence. As a safer alternative, subunit vaccines circumvent these issues. In this study, we developed a nanoparticle-based vaccine displaying the glycoprotein E (gE) on ferritin particles using the SpyCatcher/SpyTag system, termed FR-gE. This FR-gE nanoparticle antigen elicited substantial gE-specific binding and VZV-neutralizing antibody responses in BALB/c and C57BL/6 mice-responses that were up to 3.2-fold greater than those elicited by the subunit gE while formulated with FH002C, aluminum hydroxide, or a liposome-based XUA01 adjuvant. Antibody subclass analysis revealed that FR-gE produced comparable levels of IgG1 and significantly higher levels of IgG2a compared to subunit gE, indicating a Th1-biased immune response. Notably, XUA01-adjuvanted FR-gE induced a significant increase in neutralizing antibody response compared to the live attenuated varicella vaccine and recombinant vaccine, Shingrix. Furthermore, ELISPOT assays demonstrated that immunization with FR-gE/XUA01 generated IFN-γ and IL-2 levels comparable to those induced by Shingrix. These findings underscore the potential of FR-gE as a promising immunogen for the development of varicella and herpes zoster vaccines.

Visceral disseminated varicella zoster virus infection masquerading as lupus mesenteric vasculitis recurrence.

Visceral disseminated varicella zoster virus infection masquerading as lupus mesenteric vasculitis recurrence.

Mpox Epidemiology and Risk Factors, Nigeria, 2022.

To investigate epidemiology of and risk factors for laboratory-confirmed mpox during the 2022 outbreak in Nigeria, we enrolled 265 persons with suspected mpox. A total of 163 (61.5%) were confirmed to have mpox; 137 (84.0%) were adults, 112 (68.7%) male, 143 (87.7%) urban/semi-urban dwellers, 12 (7.4%) self-reported gay men, and 3 (1.8%) female sex workers. Significant risk factors for adults were sexual and nonsexual contact with persons who had mpox, as well as risky sexual behavior. For children, risk factors were close contact with an mpox-positive person and prior animal exposure. Odds of being mpox positive were higher for adults with HIV and lower for those co-infected with varicella zoster virus (VZV). No children were HIV-seropositive; odds of being mpox positive were higher for children with VZV infection. Our findings indicate mpox affects primarily adults in Nigeria, partially driven by sexual activity; childhood cases were driven by close contact, animal exposure, and VZV co-infection.

Zoster vaccination

Herpes zoster (HZ) is a sequela of the reactivation of a latent varicella zoster virus (VZV) infection of the sensory dorsal root ganglia and cranial nerves due to adecrease in specific Tcell-mediated immunity as aresult of immunosenescence, immunodeficiency diseases, e.g., human immunodeficiency virus (HIV) infection or immunosuppressive therapy. The disease burden of HZ greatly increases with age; however, younger patients with, e.g., inflammatory rheumatic diseases, also have an increased risk of HZ, which is higher under certain immunosuppressive drugs, e.g., Janus kinase (JAK) inhibitors or glucocorticoids. The risk of complications, e.g., postherpetic neuralgia (PHN) is also increased in this patient group. Of the two vaccines licensed in Germany, the Standing Committee on Vaccination (STIKO) at the Robert Koch Institute recommends the recombinant adjuvanted HZ subunit vaccine for the standard vaccination of all persons ≥ 60years and for persons ≥ 50years with an increased HZ risk for prevention of HZ and PNH due to its better efficacy and longer duration of effectiveness. Clinical trials have demonstrated a 90-97% efficacy in preventing HZ in immune healthy adults aged ≥ 50 years, with a much higher reactogenicity in the vaccine group compared to placebo. Adequate efficacy, immunogenicity and safety have also been demonstrated in clinical trials in immunocompromised and immunosuppressed patients. An extension of the STIKO vaccination recommendation to all adults with an increased HZ risk in line with the approval would be welcome.

Exploring Varicella Vaccine Coverage and Influencing Factors in Rural and Pastoral Children of Qinghai Province: A Cross-Sectional Catch-Up Vaccination Study

&amp;lt;i&amp;gt;Background: &amp;lt;/i&amp;gt;Varicella is a respiratory infectious disease caused by varicella-zoster virus (VZV) infection. Varicella vaccine has been shown to be highly effective in preventing varicella disease, however it is not included in Qinghai Province’s local immunization planning program and must be paid for by families. Its use in local areas is options instead of compulsory, so high coverage is difficult to guarantee. Starting in October 2021, one dose of live attenuated varicella vaccine was recommended at lest for 3-17-year-old children in Qinghai. In 2022, it was conducted that an investigation of varicella vaccine coverage and factors influencing coverage among children in rural rural and pastoral areas to determine the impact of this VarV catch-up policy. &amp;lt;i&amp;gt;Objective: &amp;lt;/i&amp;gt; To explore varicella vaccine coverage and factors influencing caverage among 3-17-year-old children in rural and pastoral areas of Qinghai province. &amp;lt;i&amp;gt;Methods:&amp;lt;/i&amp;gt; A stratified cluster sampling method was used to select children aged 3-17 years from kindergartens and primary /secondary schools in rural and pastoral areas of Qinghai province for a questionnaire-based survey of their guardians. Coverage levels of one and two doses of VarV (VarV&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; and VarV&amp;lt;sub&amp;gt;2&amp;lt;/sub&amp;gt;) before and after a catch-up vaccination activity initiated in October 2021, and identified factors influenceing VarV&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; coverage. &amp;lt;i&amp;gt;Results:&amp;lt;/i&amp;gt; VarV&amp;lt;sub&amp;gt;1&amp;lt;/sub&amp;gt; and VarV&amp;lt;sub&amp;gt;2 &amp;lt;/sub&amp;gt;coverage levels after the catch-up activity were 79.06% (676/855) and 43.79% (363/829), respectively, and increased by 34.38 and 24.13 percentage points compared with before the catch-up activity. Multivariate logistic regression showed that VarV&amp;lt;sub&amp;gt;1 &amp;lt;/sub&amp;gt;coverage was higher in rural areas than in pastoral areas (OR=4.63, 95%&amp;lt;I&amp;gt;CI&amp;lt;/I&amp;gt;: 2.91-7.39), and higher among children whose guardians scored 4-6 or 7-10 points on knowledge about varicella and VarV than among children whose guardians scored 0-3 points (OR=8.61, 95%&amp;lt;I&amp;gt;CI&amp;lt;/I&amp;gt;: 4.73-15.69, OR=2.86, 95%&amp;lt;I&amp;gt;CI&amp;lt;/I&amp;gt;: 1.69-4.84). the main reasons for non-vaccination were guardians’ lack of understanding of VarV (48.6%, 87 children), guardians’ unawarness of the need for VarV vaccination (43.6%, 78 children), and unavailability of VarV at vaccination centers (31.3%, 56 children). &amp;lt;i&amp;gt;Conclusions: &amp;lt;/i&amp;gt;The catch-up activity significantly increased VarV coverage among children in the surveyed areas. It should been strengthened that health education on knowledge about varicella and VarV among guardians of children in Qinghai, especially in pastoral areas, to promote VarV vaccination of age-eligible children.

Suppression of the host antiviral response by non-infectious varicella zoster virus extracellular vesicles.

Varicella zoster virus (VZV) is a ubiquitous human virus that predominantly spreads by direct cell-cell contact and requires efficient and immediate host immune evasion strategies to spread. The mechanisms of immune evasion prior to virion entry have not been fully elucidated and represent a critical gap in our complete understanding of VZV pathogenesis. This study describes a previously unreported antiviral evasion strategy employed by VZV through the exploitation of the infected host cell's small extracellular vesicle (sEV) machinery. These findings suggest that non-infectious VZV sEVs could travel throughout the body, affecting cells remote from the site of infection and challenging the current understanding of VZV clinical disease, which has focused on local effects and direct infection. The significance of these sEVs in early VZV pathogenesis highlights the importance of further investigating their role in viral spread and secondary disease development to reduce systemic complications following VZV infections.

Decreased T-cell response against latentcytomegalovirus infection does not correlate with anti-IFN autoantibodies in patients with APECED.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an inborn error of immunity affecting both multiple endocrine organs and susceptibility to candidiasis, each with an autoimmune basis. Recently, high titer neutralizing anti-type I interferon (IFN) autoantibodies have been linked with increased severity of SARS-CoV-2 and varicella zoster virus infections in APECED patients. Examining immunity against cytomegalovirus (CMV), we found a higher prevalence of anti-CMV IgG antibodies in patients with APECED (N = 19) than in 44 healthy controls (90% vs 64%, p = 0.04); the similar difference in their IgG levels did not achieve significance (95 ± 74 vs 64 ± 35 IU/mL, ns.). In contrast, the frequency of CMV-specific Tcells was lower (804 ± 718/million vs 1591 ± 972/million PBMC p = 0.03). We saw no correlations between levels of anti-CMV IgG and anti-IFN antibodies in APECED patients or in a separate cohort of patients with thymoma (n = 70), over 60% of whom also had anti-IFN antibodies. Our results suggest a dysregulated response to CMV in APECED patients and highlight immunodeficiency to viral infections as part of the disease spectrum.

Herpes Zoster Awareness: A pilot centre analysis

Herpes zoster (HZ), or shingles, is caused by the reactivation of the varicella-zoster virus (VZV), which typically occurs years after a primary VZV infection (chickenpox). HZ is characterized by a painful, unilateral vesicular rash that usually affects a single dermatome, with common sites including thoracic, lumbar, cervical, and trigeminal regions. While HZ typically lasts 2-4 weeks, it can be particularly severe in elderly and immunocompromised individuals, leading to complications such as postherpetic neuralgia (PHN), cranial nerve palsy, and visual deficits. The incidence of HZ increases with age, and early antiviral treatment with acyclovir can reduce the severity of the acute phase and prevent serious eye complications in ophthalmic HZ cases. With an aging population, the prevalence of HZ is expected to rise, highlighting the need for effective vaccination strategies. Two types of vaccines are available: a live attenuated zoster vaccine (LZV) and a recombinant zoster vaccine (RZV), with the latter showing higher efficacy in preventing HZ. Despite this, awareness of HZ and its vaccine remains low. A survey conducted in Izmir, Turkey, revealed that while 59.2% of respondents were aware of HZ, only 18.3% knew about the vaccine. The study underscores the need for increased public health efforts to raise awareness and promote vaccination, especially among high-risk populations such as the elderly and immunocompromised individuals.

Anifrolumab for systemic lupus erythematosus with multi-refractory skin disease: A case series of 18 patients.

Skin involvement is common in systemic lupus erythematosus (SLE), but may be resistant to conventional treatment. We sought to evaluate the efficacy of anifrolumab (ANI) in refractory cutaneous manifestations of SLE. Case series of patients with refractory cutaneous SLE from three Rheumatology Departments in Greece. Outcome measures were improvement in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), physician global assessment (PGA) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Clinically relevant improvement in skin was defined as decrease ≥50% (CLASI50) from baseline values. Eighteen patients received ANI; all had active skin involvement at baseline. Mean (SD) SLEDAI and PGA at ANI initiation were 7.4 (2.7) and 1.4 (0.5), respectively, with a mean prednisone dose 4.9 (4.5) mg/day. Mean CLASI (Activity/Damage) at baseline was 13.9 (9.7)/2.9 (4.6). Patients were refractory to a mean 6.3 (1.5) immunomodulatory agents (including hydroxychloroquine and glucocorticoids) before the initiation of ANI. After a mean 8.5 (4.6) months, 89% (n = 16/18) of patients demonstrated significant improvement in general lupus and cutaneous disease activity, and glucocorticoid tapering. Mean SLEDAI and mean CLASI at last visit were 3.4 (1.9) and 2.1 (2.4)/1.4 (2.2), respectively, and mean daily prednisone dose decreased to 2.4 (2.2). Of note, in this group of highly refractory patients CLASI50 was achieved in 16/18 (89%) patients. One patient discontinued ANI after 4 infusions due to a varicella-zoster virus infection and one patient, who initially responded to treatment with ANI, experienced a skin flare due to temporary discontinuation due to Covid 19 infection. DORIS remission and LLDAS were attained in two (11.1%) and eleven (61.1%) patients, respectively. Anifrolumab is highly effective in various skin manifestations of SLE, even after prior failure to multiple treatments.

Cross-Sectional and Longitudinal Associations Between Treatment for Herpes Virus Infection and the Dispensing of Antidementia Medicines: An Analysis of the Australian Pharmaceutical Benefits Scheme Database.

Evidence from previous observational studies suggest that infection by herpes simplex virus (HSV) and varicella zoster virus (VZV) increase the risk of dementia. To investigate if older adults exposed to HSV treatment have lower risk of dementia than the rest of the population. We used the 10% Australian Pharmaceutical Benefits Scheme (PBS) database from 2013 to 2022 to ascertain the cross-sectional, time-series and longitudinal association between exposure to HSV treatment and the dispensing of antidementia medicines. Participants were men and women aged 60 years or older. We used Anatomical Therapeutic Chemical (ATC) codes to identify medicines dispensed for the treatment of HSV and dementia. During the year 2022 6,868 (1.2%) of 559,561 of participants aged 60 years or over were dispensed antidementia agent. The odds ratio (OR) of being dispensed an antidementia agent among individuals dispensed treatment for HSV was 0.73 (99% CI = 0.56-0.95). Multilevel logistic regression for the 2013-2022 period for those dispensed HSV treatment was 0.87 (99% CI = 0.75-1.00). Split-time span series from 2013 was associated with hazard ratio of 0.98 (99% CI = 0.89-1.07) for individuals dispensed relative to those not dispensed HSV treatment. All analyses were adjusted for age, sex, and the dispensing of medicines for the treatment of diabetes, hyperlipidemia, hypertension, and ischemic heart disease. The dispensing of antiviral medicines for the treatment of HSV and VZV is consistently, but not conclusively, associated with decreased dispensing of antidementia medicines. This suggests that treatment of HSV and VZV infections may contribute to reduce the risk of dementia.

Reduced unilateral sweating caused by varicella zoster virus infection: a case report

BackgroundHerpes zoster is an infectious skin disease caused by the reactivation of the varicella zoster virus (VZV), which has been latent in the posterior root ganglia of the spinal cord or cranial ganglia for an extended period. Neurological complications caused by herpes zoster include aseptic meningitis, white matter disease, peripheral motor neuropathy, and Guillain-Barré syndrome. However, reduced unilateral sweating caused by the VZV is very rare.Case PresentationThis article reports the case of a 34-year-old woman who was admitted to our hospital with sore throat, dizziness, and reduced sweating on the left side of her body. Physical examination found herpes lesions on the left upper lip and left external ear canal (scabbed) and reduced sweating on the left side of the body. Head magnetic resonance imaging (MRI) with contrast showed no abnormalities. After a lumbar puncture, the patient was diagnosed with viral meningitis by VZV infection. The electromyographic skin sympathetic reflex indicated damage to the left sympathetic nerve.ConclusionsSecondary unilateral sweating reduction is a rare neurological complication of herpes zoster, caused by damage to the autonomic nervous system. Literature review and comprehensive examination indicated that the reduced unilateral sweating was due to the activation of latent herpes zoster virus in the autonomic ganglia which has damaged the autonomic nervous system. For patients who exhibit acute hemibody sweat reduction, doctors should consider the possibility of secondary autonomic nervous system damage caused by herpes zoster.

Severe Varicella-Zoster virus pneumonia in a healthy young adult treated with acyclovir and extracorporeal membrane oxygenation: a case report

Purpose: Varicella-zoster virus (VZV) infection is common in children and is usually benign. In adults VZV infection can present as a severe primary viral pneumonia with acute respiratory failure. VZV infections in adult have a high mortality rate.Case report: A 32-year-old previously healthy male first presented to the emergency department with flulikesymptoms and no rash. Three days later he returned to the emergency department with a disseminatedskin rash and severe acute respiratory distress syndrome that required intubation and mechanical ventilation. A VZV infection was confirmed. Mechanical ventilation was insufficient and venovenous extracorporeal membrane oxygenation was introduced. In addition to supportive measures, he was treated with intravenousacyclovir. During hospitalisation he developed several complications, including severe cor pulmonale necessitating treatment with nitrous oxide and milrinone, disseminated intravascular coagulation necessitating an extracorporeal membrane change, and ventilator-associated pneumonia. He was discharged home in stable condition on hospital day 27.Conclusion: Primary VZV infection in adulthood is associated with several complications. Early recognition ofacute respiratory failure, ventilatory support, and early administration of acyclovir are crucial elements of VZVpneumonia treatment.

Ramsay Hunt Syndrome: A Rare Disease of Multiple Cranial Nerve Involvement

Ramsay Hunt Syndrome (RHS) also known as herpes zoster oticus is a viral disease, a member of the human herpes virus family, is a late complication of varicella-zoster virus infection that results in inflammation of the geniculate ganglion of cranial nerve VII. Ramsay Hunt is a clinical diagnosis. The hallmark of the condition is multiple unilateral erythematous vesicles, which are distributed over the auricle and preceded by severe otalgia. If these symptoms are associated with facial nerve palsy, the condition is called RHS which is usually accompanied by vestibulocochlear abnormalities. Diagnosis is often missed or delayed, which can lead to an increased incidence of long-term complications. The condition is self-limiting, but treatment is targeted at decreasing the total duration of the illness as well as providing analgesia and preventing the complications that can occur. This activity reviews the role of the inter professional team in the diagnosis and treatment of RHS. Mugda Med Coll J. 2024; 7(1): 48-52

Enantioselective Synthesis of β-l-5-[(E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl) Uracil)] (l-BHDU) via Chiral Pure l-Dioxolane.

β-l-5-((E)-2-Bromovinyl)-1-((2S,4S)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl) uracil (l-BHDU, 17) is a potent and selective inhibitor of the varicella-zoster virus (VZV). l-BHDU (17) has demonstrated excellent anti-VZV activity and is a preclinical candidate to treat chickenpox, shingles (herpes zoster), and herpes simplex virus 1 (HSV-1) infections. Its monophosphate prodrug (POM-l-BHDU-MP, 24) demonstrated an enhanced pharmacokinetic and antiviral profile. POM-l-BHDU-MP (24), in vivo, effectively reduced the VZV viral load and was effective for the topical treatment of VZV and HSV-1 infections. Therefore, a viable synthetic procedure for developing POM-l-BHDU-MP (24) is needed. In this article, an efficient approach for the synthesis of l-BHDU (17) from a readily available starting material is described in 7 steps. An efficient and practical methodology for both chiral pure l- & d-dioxolane 11 and 13 were developed via diastereomeric chiral amine salt formation. Neutralization of the amine carboxylate salt of l-dioxolane 10 provides enantiomerically pure l-dioxane 11 (ee ≥ 99%). Optically pure 11 was utilized to construct the final nucleoside l-BHDU (17) and its monophosphate ester prodrug (POM-l-BHDU-MP, 24). Notably, the reported process eliminates expensive chiral chromatography for the synthesis of chiral pure l- & d-dioxolane, which offers avenues for the development and structure-activity relationship studies of l- & d-dioxolane-derived nucleosides.