Varicella immunoglobulin 250mg solution for injection vials

INTRODUCTION: Varicella zoster virus (VZV) is a human neurotropic herpesvirus that remains latent in the dorsal root ganglia and can reactivate to cause herpes zoster. In immunocompromised patients, reactivation may lead to severe neurological complications such as encephalitis, meningitis, myelitis, and neuropathy. However, varicella zoster virus-related myelitis (VZVM) is relatively rare, particularly in immunocompetent adults. The pathogenesis may involve direct viral invasion of the spinal cord parenchyma during the acute phase or a postinfectious immune-mediated inflammatory response. CASE PRESENTATIONS: This report describes three patients with VZVM(one woman ages 49 years and two men age 60 and 56 years), none of whom presented with a typical rash. Two patients (cases 1 and 2) developed encephalomyelitis at disease onset, characterized by fever, impaired consciousness, and long-segment spinal cord lesions. Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) detected VZV nucleic acid in both cases. In case 3, the patient initially developed VZVM complicated by cerebral venous sinus thrombosis. After an interval of approximately 40 days, delayed thoracic myelitis developed, and repeated CSF mNGS testing yielded negative results. All three patients received intravenous antiviral therapy; two additionally received low-dose corticosteroids combined with intravenous immunoglobulin, and one received intravenous methylprednisolone. During follow-up, one patient achieved full recovery of lower-limb motor function, whereas two patients remained paraplegic. CONCLUSIONS: VZVM presents with diverse clinical manifestations and may occur without the typical vesicular rash. It can develop either during the initial phase of VZV infection or as a delayed complication. Early magnetic resonance imaging and CSF molecular testing support timely diagnosis. Prompt and adequate antiviral therapy combined with immunomodulatory treatment may improve neurological outcomes.

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Abstract Background The immune response to infections could be largely driven by the individual’s genes, especially in the major histocompatibility complex (MHC) region. Varicella-zoster virus (VZV) is a highly communicable pathogen. In addition to infection, the reactivations of VZV can be a potential causal factor for multiple traits. Identification of VZV immune response-related health conditions can therefore help elucidate the aetiology of certain diseases. Methods A phenome-wide Mendelian randomization (MR) study of anti-VZV immunoglobulin G (IgG) levels with 1370 traits was conducted to explore the potential causal role of VZV-specific immune response on multiple traits using the UK Biobank cohort. For the robustness of the results, we performed MR analyses using five different methods. To investigate the impact of the MHC region on MR results, the analyses were conducted using instrumental variables (IVs) inside (IV mhc ) and outside (IV no.mhc ) the MHC region or all together (IV full ). Results Forty-nine single nucleotide polymorphisms (IV full ) were associated with anti-VZV IgG levels, of which five (IV mhc ) were located in the MHC region and 44 (IV no.mhc ) were not. Statistical evidence (false discovery rate < 0.05 in at least three of the five MR methods) for a causal effect of anti-VZV IgG levels was found on 22 traits using IV mhc , while no evidence was found when using IV no.mhc or IV full . The reactivations of VZV increased the risk of Dupuytren disease, mononeuropathies of the upper limb, sarcoidosis, coeliac disease, teeth problems and earlier onset of allergic rhinitis, which evidence was concordant with the literature. Suggestive causal evidence ( P < 0.05 in at least three of five MR methods) using IV full , IV mhc and IV no.mhc was detected in 92, 194 and 56 traits, respectively. MR results from IV full correlated with those from IV mhc or IV no.mhc . However, the results between IV mhc and IV no.mhc were noticeably different, as evidenced by causal associations in opposite directions between anti-VZV IgG and ten traits. Conclusions In this exploratory study, anti-VZV IgG was causally associated with multiple traits. IVs in the MHC region might have a substantial impact on MR, and therefore, could be potentially considered in future MR studies.

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BACKGROUND: Visceral disseminated varicella zoster virus (VZV) infection is a rare but life-threatening complication in immunosuppressed patients. Herein, we report a survival case of visceral disseminated VZV infection in a patient with systemic lupus erythematosus (SLE). CASE PRESENTATION: A 37-year-old woman was diagnosed as SLE and initial induction therapy was started. Two months after starting the immunosuppressive therapy consisting of 40 mg of prednisolone (PSL) and 1500 mg of mycophenolate mofetil (MMF) daily, she suddenly developed strong abdominal pain, which was required opioid analgesics, followed by systemic skin blisters, which were diagnosed as varicella. Laboratory findings showed rapid exacerbation of severe liver failure, coagulation abnormalities and increased numbers of blood VZV deoxyribonucleic acid (DNA). Therefore, she was diagnosed as visceral disseminated VZV infection. Multidisciplinary treatment with acyclovir, immunoglobulin and antibiotics was started, the dose of PSL was reduced, and MMF was withdrawn. By their treatment, her symptoms were resolved and she finally discharged. CONCLUSIONS: Our case highlights the importance of a clinical suspicion of visceral disseminated VZV infections, and the necessity of immediate administration of acyclovir and reduced doses of immunosuppressant to save patients with SLE.

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Varicella zoster virus (VZV) causes childhood chickenpox, becomes latent in sensory ganglia and reactivates years later to cause shingles (Zoster) and postherpetic neuralgia in the elderly and immunosuppressed individuals. Serologic IgG tests can be used to determine if a person has antibodies to VZV from past varicella infection or had received varicella or zoster (shingles) vaccination. Commercial enzyme-linked immunosorbent assays (ELISAs) are currently used for the detection of VZV IgG antibodies in patient serum samples. However, ELISA tests require collection and processing of blood samples in a CLIA laboratory to separate serum or plasma for further testing. In this paper, we describe the development and testing of an antibody based Lateral Flow Immunochromatographic assay (LFA) device for the detection of VZV IgG in fingerstick whole blood. Analytical and clinical analyses were performed to compare the performance characteristics of the Viro VZV IgG LFA (VZV LFA) and the Diamedix VZV IgG ELISA. Analytical studies demonstrated the higher sensitivity of the VZV LFA compared to the ELISA by testing dilutions of the WHO VZV IgG serum International Standard. Clinical performance characteristics of the VZV LFA fingerstick whole blood assay were assessed at three point of care (POC) facilities by untrained users testing samples from 300 prospectively enrolled study subjects. VZV LFA results were compared with results obtained by testing serum samples obtained from the same study participants by the Diamedix VZV IgG ELISA. Two specimens with invalid results by the LFA assay were not included in the LFA performance calculations and nine equivocal ELISA results were included as positive for IgG results. The results from all three POC clinical sites demonstrated the higher sensitivity/positive percent agreement (PPA) (99.26%, 95% CI: 97.34-99.80) of the VZV LFA compared to the Diamedix VZV IgG ELISA (94.08%, 95% CI: 90.72-96.27). The specificity/negative percent agreement (NPA) of the VZV LFA compared to the ELISA test was calculated initially to be 39.29% (95% CI: 23.57-57.59) with 19 discordant test results out of 298 test results between the two assays (17 LFA positive/ELISA negative and two LFA negative/ELISA positive). The PPA and true NPA of the VZV LFA were determined by testing all 298 samples, including the discordant (19) and all concordant negative and positive (279) study subject serum samples, before and after blocking VZV gE antibody sites in the samples by spiking with VZV LFA gE capture antigen. The NPA improved to 100% (95% CI: 74.12-100) after the procedure when compared to the ELISA test results. The comparator ELISA PPA based on the spiking/blocking study remained as 94.08%, (95% CI: 90.72-96.27), comparable to test results from untreated samples. The VZV LFA has been demonstrated to be simple and sufficiently robust for use in CLIA-waived POC facilities by untrained healthcare professionals and to detect VZV IgG in 20 min from fingerstick whole blood. The VZV LFA therefore provides a fast, reliable, and highly sensitive method of determining prior VZV viral infection or varicella and zoster vaccination status.

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Neonatal varicella, arising from maternal infection with the varicella-zoster virus (VZV), is a rare but potentially severe condition with diverse clinical presentations. This case report highlights an instance where the mother developed a maculopapular rash seven days before delivery, indicating a possible transmission of VZV to the neonate. The patient's family history included recent diagnoses of herpes zoster and varicella among household members. On the second day of life, the newborn developed a discrete vesicular rash on an erythematous background, affecting the trunk and neck. Due to the unavailability of varicella zoster immunoglobulin (VZIG), intravenous immunoglobulin (IVIG) was administered along with a seven-day course of intravenous acyclovir. Despite the absence of VZIG, the combined treatment with IVIG and acyclovir proved effective in resolving the rash by the sixth day of life, without any ensuing complications. This case underscores the challenges of managing neonatal varicella in resource-limited settings and suggests that combination therapy may not prevent the occurrence of neonatal varicella but can mitigate serious complications and expedite clinical recovery.

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Background/Objectives: We aimed to determine in multiple sclerosis (MS) whether intrathecal immunoglobulin G (IgG) production against measles- (M), rubella- (R), and varicella zoster (Z) viruses, which is called MRZ reaction (MRZR) and considered the most specific soluble biomarker for MS, is associated with demographic and basic cerebrospinal fluid (CSF) parameters reflecting inflammation. Methods: We analyzed the presence of positive MRZR and associations with demographic and clinical routine CSF parameters in 513 patients with MS and 182 non-MS patients. Results: Comparing MS patients versus non-MS patients, positive MRZR (38.8% versus 2.2%; specificity 97.8%; positive likelihood ratio, PLR 17.7) had a better specificity and PLR for MS than CSF-specific OCB (89.5% versus 22.0%; specificity 78.0%; PLR 4.1). A positive MRZR in MS patients was associated with female sex ( p = 0.0001), pleocytosis ( p < 0.0001), higher frequency of presence of plasma cells in CSF ( p = 0.0248), normal CSF/serum albumin ratio ( p = 0.0005), and intrathecal production of total IgG or CSF-specific OCB (both p < 0.0001), but not with intrathecal production of total IgA or IgM. Conclusions: This study confirms the MRZR as a highly specific marker of MS and shows that MRZR-positive MS patients more frequently are female and show inflammatory changes of basic CSF parameters than MRZR-negative MS patients.

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