RARE DISEASE
Congenital varicella syndrome
Congenital varicella syndrome
Congenital varicella syndrome
Synonyms: Antenatal varicella virus infection, Mother-to-child transmission of varicella syndrome
Synonyms: Antenatal varicella virus infection, Mother-to-child transmission of varicella syndrome
Synonyms: Antenatal varicella virus infection, Mother-to-child transmission of varicella syndrome
Drug discovery
1
drug
With orphan designation
Overview
Congenital varicella syndrome (CVS) is a rare embryopathy caused by maternal varicella-zoster virus (VZV) infection during the first 20 weeks of gestation. It manifests with dermatomal skin scarring, limb hypoplasia, neurological defects, ocular anomalies, and visceral organ damage. Diagnosis combines maternal infection history, fetal ultrasound findings, and VZV PCR testing. Prevention through pre-pregnancy vaccination and post-exposure prophylaxis with varicella-zoster immune globulin (VariZIG) remains critical [1][2][16].
Burden
30% mortality in neonates ≤1 month from pulmonary/GI complications [6][16]
Survivors face lifelong disabilities: 60% neurological deficits, 51% ocular damage, 49% skeletal anomalies [5][13]
Preventable through vaccination programs, with 97% reduction in pediatric varicella cases since 1995 in vaccinated populations [18]
Therapies
Prophylaxis: VariZIG within 10 days of maternal VZV exposure [3][8]
Antivirals: IV acyclovir (30 mg/kg/day) for neonates with active infection; maternal oral acyclovir for third-trimester infections [6][8][13]
Supportive care: Multidisciplinary management of limb defects, neurological complications, and ophthalmic sequelae [1][7]
Categories: rare developmental anomalies during embryogenesis, rare infectious diseases, rare ophthalmic disorders, rare teratologic disorders
Research Papers
94 drug discovery papers about Congenital varicella syndrome, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
94 drug discovery papers about Congenital varicella syndrome, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2025-02-26 | Varicella Zoster Virus Infection and Pregnancy: An Optimal Management Approach.
Varicella-zoster virus is an α-herpes virus with a double-stranded DNA genome, which causes two main clinical pictures: varicella or chickenpox and herpes zoster. Chickenpox is the primary infection, predominantly affecting children, and it presents with fever and a cutaneous eruption consisting of a vesicular, pruritic, and painful rash. Herpes zoster is a viral infection that typically develops in adulthood as a result of the reactivation of the varicella-zoster virus. If acquired during pregnancy, chickenpox may be responsible for serious complications for the mother, the fetus, or the newborn. The most frequent complication of primary varicella-zoster virus infection in mothers is varicella pneumonia, while encephalitis and hepatitis are rare. The effects on the fetus due to chickenpox infection depend on the stage of pregnancy when the mother becomes infected. If the infection occurs during the first trimester, it does not increase the risk of miscarriage. However, if the infection occurs during the first or second trimester, it may cause fetal varicella syndrome or congenital varicella syndrome. During pregnancy, if the varicella-zoster virus reactivates, it usually does not cause harm to the fetus or lead to any birth defects. However, it may increase maternal morbidity due to herpes zoster and its complications. In the case of primary varicella-zoster virus infection in pregnant women, about 20% of newborns may get neonatal or infantile herpes zoster without any complications. However, it is recommended to start early treatment of herpes zoster in pregnant women as it is believed to accelerate the healing process of skin lesions and alleviate pain, reducing both its duration and severity. Through this narrative review, we discuss the approach to the optimal management of varicella-zoster virus infection during pregnancy.
2022-04-26 | Effectiveness of oral aciclovir in preventing maternal chickenpox: A comparison with VZIG
Abstract Objectives Although often presenting as a self-limiting childhood disease, chickenpox can have serious consequences if acquired in pregnancy. The UK recommendations are that varicella immunoglobulin (VZIG) is administered intramuscularly to susceptible pregnant women exposed to chickenpox prior to 20 weeks gestation. Oral aciclovir or VZIG is recommended if exposure occurs at 20+ weeks gestation. Our objective was to compare the effectiveness of oral aciclovir to VZIG in preventing maternal and neonatal chickenpox. Methods We identified and followed up 186 pregnant women who were exposed to chickenpox and compared their outcomes. Results 171/186 (91.9%) of these women received either VZIG or oral aciclovir. 53 of the 145 (36.6%) women who received VZIG went on to develop chickenpox compared to 8 of the 26 (30.8%) women who received oral aciclovir (p=0.32). No statistical difference was found between the oral aciclovir and VZIG groups even after controlling for maternal age, gestational stage, type of exposure and IgG titre (adjusted OR:0.83; 95%CI:0.26-2.65; p=0.751). Conclusions These findings support the use of oral aciclovir as first-line prophylaxis in pregnant women exposed at 20+ weeks, (and possibly second-line <20 weeks) as they suggest its effectiveness at preventing maternal chickenpox is either better or equal to VZIG.
2021-03-04 | Modulation of Endosome Function, Vesicle Trafficking and Autophagy by Human Herpesviruses
Human herpesviruses are a ubiquitous family of viruses that infect individuals of all ages and are present at a high prevalence worldwide. Herpesviruses are responsible for a broad spectrum of diseases, ranging from skin and mucosal lesions to blindness and life-threatening encephalitis, and some of them, such as Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein–Barr virus (EBV), are known to be oncogenic. Furthermore, recent studies suggest that some herpesviruses may be associated with developing neurodegenerative diseases. These viruses can establish lifelong infections in the host and remain in a latent state with periodic reactivations. To achieve infection and yield new infectious viral particles, these viruses require and interact with molecular host determinants for supporting their replication and spread. Important sets of cellular factors involved in the lifecycle of herpesviruses are those participating in intracellular membrane trafficking pathways, as well as autophagic-based organelle recycling processes. These cellular processes are required by these viruses for cell entry and exit steps. Here, we review and discuss recent findings related to how herpesviruses exploit vesicular trafficking and autophagy components by using both host and viral gene products to promote the import and export of infectious viral particles from and to the extracellular environment. Understanding how herpesviruses modulate autophagy, endolysosomal and secretory pathways, as well as other prominent trafficking vesicles within the cell, could enable the engineering of novel antiviral therapies to treat these viruses and counteract their negative health effects.
2020-04-01 | Kallikrein-Mediated Cytokeratin 10 Degradation Is Required for Varicella Zoster Virus Propagation in Skin
Varicella zoster virus (VZV) is a skin-tropic virus that infects epidermal keratinocytes and causes chickenpox. Although common, VZV infection can be life-threatening, particularly in the immunocompromized. Therefore, understanding VZV-keratinocyte interactions is important to find new treatments beyond vaccination and antiviral drugs. In VZV-infected skin, kallikrein 6 and the ubiquitin ligase MDM2 are upregulated concomitant with keratin 10 (KRT10) downregulation. MDM2 binds to KRT10, targeting it for degradation via the ubiquitin-proteasome pathway. Preventing KRT10 degradation reduced VZV propagation in culture and prevented epidermal disruption in skin explants. KRT10 knockdown induced expression of NR4A1 and enhanced viral propagation in culture. NR4A1 knockdown prevented viral propagation in culture, reduced LC3 levels, and increased LAMP2 expression. We therefore describe a drug-able pathway whereby MDM2 ubiquitinates and degrades KRT10, increasing NR4A1 expression and allowing VZV replication and propagation.
2011-04-29 | [Skin infections in pregnancy].
The article outlines examples of a viral (varicella-zoster virus, VZV), a bacterial (Lyme borreliosis) and a parasitic (scabies) infection in pregnancy with their risk for the mother and/or child as well as their management. VZV infections cause various clinical scenarios depending on the maternal immune status and the time of infection. Herpes zoster usually poses no risk to the pregnant woman and there is no need for antiviral therapy. VZV infection of a seronegative mother, however, may lead to severe varicella in the pregnant woman and to congenital malformations (congenital varicella syndrome) in case of early infection or neonatal varicella in case of perinatal infection. Prompt therapy with acyclovir or administration of VZV immunoglobulin for prophylaxis is mandatory in those patients. In case of Lyme borreliosis of the mother, adequate antibiotic therapy with amoxicillin prevents harm to the fetus. Doxycycline is contraindicated during pregnancy. Scabies represents an important differential diagnosis of pruritic dermatoses in pregnancy and should be treated with permethrin 5% cream.
vaccines
2026-08-08 | Varicella–Zoster Virus Infection in Pregnancy: Maternal, Fetal, and Neonatal Implications in the Vaccination Era
Infection by the varicella–zoster virus (VZV) during pregnancy is uncommon but clinically relevant, since it may compromise both the mother and the fetus. Although varicella is generally benign and self-limited in childhood, the physiological and immunological changes in pregnancy predispose individuals to more severe forms of the disease, with pneumonia representing the main maternal complication and a leading cause of morbidity and mortality. Vertical transmission may result in congenital varicella syndrome, the most severe fetal consequence, whose risk is greatest between the 13th and 20th weeks of gestation, or in severe neonatal varicella when maternal infection occurs in the peripartum period. This article presents a narrative review of the literature. To enhance methodological transparency and reproducibility, key principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were applied to the literature search and study selection process. Searches were conducted in the PubMed/MEDLINE and SciELO databases, and 32 studies were included in the narrative synthesis. The review addresses the virology, pathophysiology, and epidemiology of VZV infection, including differences between temperate and tropical regions, as well as its clinical manifestations and maternal, fetal, and neonatal complications. Diagnosis is predominantly clinical, with the polymerase chain reaction being the most sensitive and specific confirmatory method and serology being useful mainly for the assessment of maternal immunity. Management encompasses the assessment of susceptibility, post-exposure prophylaxis according to current guideline recommendations, and early antiviral treatment of established infection. Preconception and postpartum vaccination remain the main preventive strategies. Despite recent advances, important gaps persist regarding prophylactic strategies and the long-term safety of antivirals during pregnancy.
2025-12-31 | TORCH – Current state of knowledge as of 2025
The acronym TORCH designates a group of pathogens that can lead to serious pregnancy complications, such as miscarriage, fetal growth restriction, and congenital infections. This review summarizes current insights into these infections, offering practical guidance primarily for obstetricians, infectious disease specialists, and general practitioners involved in prenatal care. The TORCH complex includes Toxoplasma gondii, Rubella virus, Cytomegalovirus (CMV), and Herpes simplex virus (HSV). The definition may be extended to encompass additional (other) pathogens such as Hepatitis B and C viruses (HBV, HCV), Human immunodeficiency virus (HIV), Varicella-zoster virus (VZV), Treponema pallidum (syphilis), Parvovirus B19, and Zika virus. Screening practices for TORCH infections during pregnancy vary significantly across countries. Despite widespread access to medical care and increasing awareness among women planning pregnancy, routine screening for TORCH pathogens is not universally implemented. In Poland, diagnostic procedures during pregnancy are defined by the Standard of Perinatal Care established by the Ministry of Health. This regulation- which replaced earlier recommendations of the Polish Society of Gynecologists and Obstetricians- does not distinguish between ,,mandatory” and ,,recommended” tests but specifies a unified set of investigations to be performed at defined stages of pregnancy. Screening conducted during pregnancy plays a crucial role in detecting previously unrecognized infections. In Poland , a substantial proportion of new diagnoses of HIV, HBV and HCV among young women are made during routine antenatal testing, underscoring the importance of standardized serological screening in prenatal care rather than relying on diagnosis before conception. However, due to their distinct epidemiological and clinical profiles, HIV, HBV, and HCV infections are not discussed in detail in this review.
2025-08-19 | Varicella-zoster virus seroprevalence among reproductive-age women in Iran: a meta-analysis and implications for targeted immunization.
Primary varicella-zoster virus (VZV) infection during pregnancy poses significant risks to both mother and fetus, including congenital varicella syndrome (CVS) and serious maternal complications. In Iran, the absence of varicella vaccination in the national immunization program leaves many women susceptible. This systematic review and meta-analysis aimed to determine the overall seroprevalence of VZV antibodies among reproductive-age women in Iran. A comprehensive search was conducted in both international and Iranian databases for studies published up to November 15, 2024. Eligible studies reporting VZV seroprevalence among Iranian women aged 15-49 years were identified. Screening, data extraction, and risk of bias assessment were independently performed by two reviewers. Pooled seroprevalence was estimated using a random-effects meta-analysis in STATA version 18. Heterogeneity was evaluated with the Cochrane Q test and I² statistic. Subgroup analyses and meta-regression explored sources of heterogeneity. Sensitivity analyses (leave-one-out) and publication bias (Doi plot, LFK index) were also performed. The protocol was registered in PROSPERO (CRD42025647813). Data from 20 studies, including 5,629 participants, were analyzed. A pooled VZV seroprevalence of 81% (95% CI: 77-85%) was found, indicating that approximately 19% of reproductive-age women in Iran remain susceptible. Higher seroprevalence was observed in pregnant women (88%) compared with non-pregnant women (79%), with the lowest rates among medical students (74%). Despite subgroup and meta-regression analyses, substantial heterogeneity remained unexplained. Sensitivity analyses supported the robustness of the results, while possible publication bias was suggested. Nearly one in five reproductive-age women in Iran lack immunity to VZV. Targeted vaccination, especially among non-pregnant women and students, may reduce susceptibility. Preconception screening for VZV immunity could help prevent maternal and fetal complications. However, given the high unexplained heterogeneity, results should be interpreted with caution.
2023-07-14 | Immunogenicity and Safety of a Newly Developed Live Attenuated Varicella Vaccine in Healthy Children: A Multi-National, Randomized, Double-Blinded, Active-Controlled, Phase 3 Study
Korean manufacturers have developed a new varicella vaccine, NBP608. This phase 3, randomized, double-blind, multicenter study aimed to compare the immunogenicity and safety of NBP608 among healthy children to those of VarivaxTM (control). Children aged 12 months to 12 years were randomized 1:1 to receive either NBP608 or control vaccine. Serum samples were obtained before vaccination and within six to eight weeks after vaccination. A total of 499 participants (NBP608, n = 251; control, n = 248) was enrolled. The seroconversion rate (SCR) measured using FAMA assay was 99.53% in the NBP608 group, and the lower limit of the 95% confidence interval (95% LCL) for SCR difference (NBP608 minus control) was 0.52%. This 95% LCL for the difference was higher than the specified non-inferiority margin of –15%. In assessment by gpELISA, the SCR was 99.53% in the NBP608 group; and the 95% LCL for SCR difference was 6.5%, which was higher than the specified non-inferiority margin of –15%. There were no significant differences between the NBP608 and control group with respect to proportions of participants who demonstrated local and systemic solicited AEs. This study indicated that NBP608 had a clinically acceptable safety profile and was not immunologically inferior to VarivaxTM.
2023-04-20 | Live attenuated vaccines in patients receiving immunosuppressive agents
The use of live attenuated vaccines in patients with immunosuppressive agents is contraindicated in package inserts and guidelines in Japan and other countries. However, patients receiving immunosuppressants have a high risk of infectious disease becoming severe, and the necessity to prevent infectious disease is high. To date, 2,091 vaccinations have been reported in 25 reports of live attenuated vaccines in people receiving immunosuppressants. Twenty-three patients (1.1%) became infected with the virus strain used in the vaccine, which was varicella virus in 21 patients. No reports have described life-threatening complications. A prospective study at the National Center for Child Health and Development conducted under certain immunological conditions (CD4 cell count ≥ 500/mm3, stimulation index of lymphocyte blast transformation by phytohemagglutinin (PHA) ≥ 101.6, serum immunoglobulin G ≥ 300 mg/dL) confirmed the serological effectiveness and safety. The evidence suggests that live attenuated vaccines can be used even in combination with immunosuppressants. Further evidence must be gathered and immunological criteria investigated to determine the conditions for safe use. Depending on the results of these investigations, the wording in package inserts and guidelines may need to be revised.
proteins
2023-09-24 | An Algorithm for the Development of a Recombinant Antiherpetic Subunit Vaccine Combining the Crystal Structure Analysis, AlphaFold2-Based Modeling, and Immunoinformatics
Using the envelope glycoprotein B (gB) crystal structure and digital prediction algorithm, the B- and T-cell antigenic determinants (epitopes) of human herpesvirus 1 (HHV-1), also known as herpes simplex virus 1 (HSV-1), were generated, and the method for their production in the form of recombinant proteins was proposed. First, the structure of the surface topological domain (ectodomain or spike) of gB with mapped epitopes was analyzed, and the most stable and immunogenic (due to their enrichment with B-and T-cell epitopes) subdomains were selected for the modeling of subunit vaccine prototypes using the AlphaFold2 (Google DeepMind, London, UK) artificial intelligence system. The proposed candidate vaccines included both small (about 100 amino acids) monomeric polypeptides, which were ideal for recombinant expression as fusion proteins, and a more complex polypeptide, which, due to its trimeric fold, looks like a miniature analog of the gB ectodomain. In this miniature analog, the ectodomain regions with the potential to interfere efficacious expression of soluble recombinant protein in Escherichia coli have been removed. The structural stability of the modeled proteins, confirmed by molecular dynamics simulation and host immune responses, predicted in silico, indicates the suitability of the two suggested polypeptides for generating subunit vaccines using recombinant DNA technology.
small molecules
2025-02-26 | Varicella Zoster Virus Infection and Pregnancy: An Optimal Management Approach.
Varicella-zoster virus is an α-herpes virus with a double-stranded DNA genome, which causes two main clinical pictures: varicella or chickenpox and herpes zoster. Chickenpox is the primary infection, predominantly affecting children, and it presents with fever and a cutaneous eruption consisting of a vesicular, pruritic, and painful rash. Herpes zoster is a viral infection that typically develops in adulthood as a result of the reactivation of the varicella-zoster virus. If acquired during pregnancy, chickenpox may be responsible for serious complications for the mother, the fetus, or the newborn. The most frequent complication of primary varicella-zoster virus infection in mothers is varicella pneumonia, while encephalitis and hepatitis are rare. The effects on the fetus due to chickenpox infection depend on the stage of pregnancy when the mother becomes infected. If the infection occurs during the first trimester, it does not increase the risk of miscarriage. However, if the infection occurs during the first or second trimester, it may cause fetal varicella syndrome or congenital varicella syndrome. During pregnancy, if the varicella-zoster virus reactivates, it usually does not cause harm to the fetus or lead to any birth defects. However, it may increase maternal morbidity due to herpes zoster and its complications. In the case of primary varicella-zoster virus infection in pregnant women, about 20% of newborns may get neonatal or infantile herpes zoster without any complications. However, it is recommended to start early treatment of herpes zoster in pregnant women as it is believed to accelerate the healing process of skin lesions and alleviate pain, reducing both its duration and severity. Through this narrative review, we discuss the approach to the optimal management of varicella-zoster virus infection during pregnancy.
2022-04-26 | Effectiveness of oral aciclovir in preventing maternal chickenpox: A comparison with VZIG
Abstract Objectives Although often presenting as a self-limiting childhood disease, chickenpox can have serious consequences if acquired in pregnancy. The UK recommendations are that varicella immunoglobulin (VZIG) is administered intramuscularly to susceptible pregnant women exposed to chickenpox prior to 20 weeks gestation. Oral aciclovir or VZIG is recommended if exposure occurs at 20+ weeks gestation. Our objective was to compare the effectiveness of oral aciclovir to VZIG in preventing maternal and neonatal chickenpox. Methods We identified and followed up 186 pregnant women who were exposed to chickenpox and compared their outcomes. Results 171/186 (91.9%) of these women received either VZIG or oral aciclovir. 53 of the 145 (36.6%) women who received VZIG went on to develop chickenpox compared to 8 of the 26 (30.8%) women who received oral aciclovir (p=0.32). No statistical difference was found between the oral aciclovir and VZIG groups even after controlling for maternal age, gestational stage, type of exposure and IgG titre (adjusted OR:0.83; 95%CI:0.26-2.65; p=0.751). Conclusions These findings support the use of oral aciclovir as first-line prophylaxis in pregnant women exposed at 20+ weeks, (and possibly second-line <20 weeks) as they suggest its effectiveness at preventing maternal chickenpox is either better or equal to VZIG.
2021-03-04 | Modulation of Endosome Function, Vesicle Trafficking and Autophagy by Human Herpesviruses
Human herpesviruses are a ubiquitous family of viruses that infect individuals of all ages and are present at a high prevalence worldwide. Herpesviruses are responsible for a broad spectrum of diseases, ranging from skin and mucosal lesions to blindness and life-threatening encephalitis, and some of them, such as Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein–Barr virus (EBV), are known to be oncogenic. Furthermore, recent studies suggest that some herpesviruses may be associated with developing neurodegenerative diseases. These viruses can establish lifelong infections in the host and remain in a latent state with periodic reactivations. To achieve infection and yield new infectious viral particles, these viruses require and interact with molecular host determinants for supporting their replication and spread. Important sets of cellular factors involved in the lifecycle of herpesviruses are those participating in intracellular membrane trafficking pathways, as well as autophagic-based organelle recycling processes. These cellular processes are required by these viruses for cell entry and exit steps. Here, we review and discuss recent findings related to how herpesviruses exploit vesicular trafficking and autophagy components by using both host and viral gene products to promote the import and export of infectious viral particles from and to the extracellular environment. Understanding how herpesviruses modulate autophagy, endolysosomal and secretory pathways, as well as other prominent trafficking vesicles within the cell, could enable the engineering of novel antiviral therapies to treat these viruses and counteract their negative health effects.
2020-04-01 | Kallikrein-Mediated Cytokeratin 10 Degradation Is Required for Varicella Zoster Virus Propagation in Skin
Varicella zoster virus (VZV) is a skin-tropic virus that infects epidermal keratinocytes and causes chickenpox. Although common, VZV infection can be life-threatening, particularly in the immunocompromized. Therefore, understanding VZV-keratinocyte interactions is important to find new treatments beyond vaccination and antiviral drugs. In VZV-infected skin, kallikrein 6 and the ubiquitin ligase MDM2 are upregulated concomitant with keratin 10 (KRT10) downregulation. MDM2 binds to KRT10, targeting it for degradation via the ubiquitin-proteasome pathway. Preventing KRT10 degradation reduced VZV propagation in culture and prevented epidermal disruption in skin explants. KRT10 knockdown induced expression of NR4A1 and enhanced viral propagation in culture. NR4A1 knockdown prevented viral propagation in culture, reduced LC3 levels, and increased LAMP2 expression. We therefore describe a drug-able pathway whereby MDM2 ubiquitinates and degrades KRT10, increasing NR4A1 expression and allowing VZV replication and propagation.
2011-04-29 | [Skin infections in pregnancy].
The article outlines examples of a viral (varicella-zoster virus, VZV), a bacterial (Lyme borreliosis) and a parasitic (scabies) infection in pregnancy with their risk for the mother and/or child as well as their management. VZV infections cause various clinical scenarios depending on the maternal immune status and the time of infection. Herpes zoster usually poses no risk to the pregnant woman and there is no need for antiviral therapy. VZV infection of a seronegative mother, however, may lead to severe varicella in the pregnant woman and to congenital malformations (congenital varicella syndrome) in case of early infection or neonatal varicella in case of perinatal infection. Prompt therapy with acyclovir or administration of VZV immunoglobulin for prophylaxis is mandatory in those patients. In case of Lyme borreliosis of the mother, adequate antibiotic therapy with amoxicillin prevents harm to the fetus. Doxycycline is contraindicated during pregnancy. Scabies represents an important differential diagnosis of pruritic dermatoses in pregnancy and should be treated with permethrin 5% cream.
vaccines
2026-08-08 | Varicella–Zoster Virus Infection in Pregnancy: Maternal, Fetal, and Neonatal Implications in the Vaccination Era
Infection by the varicella–zoster virus (VZV) during pregnancy is uncommon but clinically relevant, since it may compromise both the mother and the fetus. Although varicella is generally benign and self-limited in childhood, the physiological and immunological changes in pregnancy predispose individuals to more severe forms of the disease, with pneumonia representing the main maternal complication and a leading cause of morbidity and mortality. Vertical transmission may result in congenital varicella syndrome, the most severe fetal consequence, whose risk is greatest between the 13th and 20th weeks of gestation, or in severe neonatal varicella when maternal infection occurs in the peripartum period. This article presents a narrative review of the literature. To enhance methodological transparency and reproducibility, key principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were applied to the literature search and study selection process. Searches were conducted in the PubMed/MEDLINE and SciELO databases, and 32 studies were included in the narrative synthesis. The review addresses the virology, pathophysiology, and epidemiology of VZV infection, including differences between temperate and tropical regions, as well as its clinical manifestations and maternal, fetal, and neonatal complications. Diagnosis is predominantly clinical, with the polymerase chain reaction being the most sensitive and specific confirmatory method and serology being useful mainly for the assessment of maternal immunity. Management encompasses the assessment of susceptibility, post-exposure prophylaxis according to current guideline recommendations, and early antiviral treatment of established infection. Preconception and postpartum vaccination remain the main preventive strategies. Despite recent advances, important gaps persist regarding prophylactic strategies and the long-term safety of antivirals during pregnancy.
2025-12-31 | TORCH – Current state of knowledge as of 2025
The acronym TORCH designates a group of pathogens that can lead to serious pregnancy complications, such as miscarriage, fetal growth restriction, and congenital infections. This review summarizes current insights into these infections, offering practical guidance primarily for obstetricians, infectious disease specialists, and general practitioners involved in prenatal care. The TORCH complex includes Toxoplasma gondii, Rubella virus, Cytomegalovirus (CMV), and Herpes simplex virus (HSV). The definition may be extended to encompass additional (other) pathogens such as Hepatitis B and C viruses (HBV, HCV), Human immunodeficiency virus (HIV), Varicella-zoster virus (VZV), Treponema pallidum (syphilis), Parvovirus B19, and Zika virus. Screening practices for TORCH infections during pregnancy vary significantly across countries. Despite widespread access to medical care and increasing awareness among women planning pregnancy, routine screening for TORCH pathogens is not universally implemented. In Poland, diagnostic procedures during pregnancy are defined by the Standard of Perinatal Care established by the Ministry of Health. This regulation- which replaced earlier recommendations of the Polish Society of Gynecologists and Obstetricians- does not distinguish between ,,mandatory” and ,,recommended” tests but specifies a unified set of investigations to be performed at defined stages of pregnancy. Screening conducted during pregnancy plays a crucial role in detecting previously unrecognized infections. In Poland , a substantial proportion of new diagnoses of HIV, HBV and HCV among young women are made during routine antenatal testing, underscoring the importance of standardized serological screening in prenatal care rather than relying on diagnosis before conception. However, due to their distinct epidemiological and clinical profiles, HIV, HBV, and HCV infections are not discussed in detail in this review.
2025-08-19 | Varicella-zoster virus seroprevalence among reproductive-age women in Iran: a meta-analysis and implications for targeted immunization.
Primary varicella-zoster virus (VZV) infection during pregnancy poses significant risks to both mother and fetus, including congenital varicella syndrome (CVS) and serious maternal complications. In Iran, the absence of varicella vaccination in the national immunization program leaves many women susceptible. This systematic review and meta-analysis aimed to determine the overall seroprevalence of VZV antibodies among reproductive-age women in Iran. A comprehensive search was conducted in both international and Iranian databases for studies published up to November 15, 2024. Eligible studies reporting VZV seroprevalence among Iranian women aged 15-49 years were identified. Screening, data extraction, and risk of bias assessment were independently performed by two reviewers. Pooled seroprevalence was estimated using a random-effects meta-analysis in STATA version 18. Heterogeneity was evaluated with the Cochrane Q test and I² statistic. Subgroup analyses and meta-regression explored sources of heterogeneity. Sensitivity analyses (leave-one-out) and publication bias (Doi plot, LFK index) were also performed. The protocol was registered in PROSPERO (CRD42025647813). Data from 20 studies, including 5,629 participants, were analyzed. A pooled VZV seroprevalence of 81% (95% CI: 77-85%) was found, indicating that approximately 19% of reproductive-age women in Iran remain susceptible. Higher seroprevalence was observed in pregnant women (88%) compared with non-pregnant women (79%), with the lowest rates among medical students (74%). Despite subgroup and meta-regression analyses, substantial heterogeneity remained unexplained. Sensitivity analyses supported the robustness of the results, while possible publication bias was suggested. Nearly one in five reproductive-age women in Iran lack immunity to VZV. Targeted vaccination, especially among non-pregnant women and students, may reduce susceptibility. Preconception screening for VZV immunity could help prevent maternal and fetal complications. However, given the high unexplained heterogeneity, results should be interpreted with caution.
2023-07-14 | Immunogenicity and Safety of a Newly Developed Live Attenuated Varicella Vaccine in Healthy Children: A Multi-National, Randomized, Double-Blinded, Active-Controlled, Phase 3 Study
Korean manufacturers have developed a new varicella vaccine, NBP608. This phase 3, randomized, double-blind, multicenter study aimed to compare the immunogenicity and safety of NBP608 among healthy children to those of VarivaxTM (control). Children aged 12 months to 12 years were randomized 1:1 to receive either NBP608 or control vaccine. Serum samples were obtained before vaccination and within six to eight weeks after vaccination. A total of 499 participants (NBP608, n = 251; control, n = 248) was enrolled. The seroconversion rate (SCR) measured using FAMA assay was 99.53% in the NBP608 group, and the lower limit of the 95% confidence interval (95% LCL) for SCR difference (NBP608 minus control) was 0.52%. This 95% LCL for the difference was higher than the specified non-inferiority margin of –15%. In assessment by gpELISA, the SCR was 99.53% in the NBP608 group; and the 95% LCL for SCR difference was 6.5%, which was higher than the specified non-inferiority margin of –15%. There were no significant differences between the NBP608 and control group with respect to proportions of participants who demonstrated local and systemic solicited AEs. This study indicated that NBP608 had a clinically acceptable safety profile and was not immunologically inferior to VarivaxTM.
2023-04-20 | Live attenuated vaccines in patients receiving immunosuppressive agents
The use of live attenuated vaccines in patients with immunosuppressive agents is contraindicated in package inserts and guidelines in Japan and other countries. However, patients receiving immunosuppressants have a high risk of infectious disease becoming severe, and the necessity to prevent infectious disease is high. To date, 2,091 vaccinations have been reported in 25 reports of live attenuated vaccines in people receiving immunosuppressants. Twenty-three patients (1.1%) became infected with the virus strain used in the vaccine, which was varicella virus in 21 patients. No reports have described life-threatening complications. A prospective study at the National Center for Child Health and Development conducted under certain immunological conditions (CD4 cell count ≥ 500/mm3, stimulation index of lymphocyte blast transformation by phytohemagglutinin (PHA) ≥ 101.6, serum immunoglobulin G ≥ 300 mg/dL) confirmed the serological effectiveness and safety. The evidence suggests that live attenuated vaccines can be used even in combination with immunosuppressants. Further evidence must be gathered and immunological criteria investigated to determine the conditions for safe use. Depending on the results of these investigations, the wording in package inserts and guidelines may need to be revised.
proteins
2023-09-24 | An Algorithm for the Development of a Recombinant Antiherpetic Subunit Vaccine Combining the Crystal Structure Analysis, AlphaFold2-Based Modeling, and Immunoinformatics
Using the envelope glycoprotein B (gB) crystal structure and digital prediction algorithm, the B- and T-cell antigenic determinants (epitopes) of human herpesvirus 1 (HHV-1), also known as herpes simplex virus 1 (HSV-1), were generated, and the method for their production in the form of recombinant proteins was proposed. First, the structure of the surface topological domain (ectodomain or spike) of gB with mapped epitopes was analyzed, and the most stable and immunogenic (due to their enrichment with B-and T-cell epitopes) subdomains were selected for the modeling of subunit vaccine prototypes using the AlphaFold2 (Google DeepMind, London, UK) artificial intelligence system. The proposed candidate vaccines included both small (about 100 amino acids) monomeric polypeptides, which were ideal for recombinant expression as fusion proteins, and a more complex polypeptide, which, due to its trimeric fold, looks like a miniature analog of the gB ectodomain. In this miniature analog, the ectodomain regions with the potential to interfere efficacious expression of soluble recombinant protein in Escherichia coli have been removed. The structural stability of the modeled proteins, confirmed by molecular dynamics simulation and host immune responses, predicted in silico, indicates the suitability of the two suggested polypeptides for generating subunit vaccines using recombinant DNA technology.
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Drug Discovery Landscape
1 orphan drug designation for Congenital varicella syndrome, including 1 approved therapy.
1 orphan drug designation for Congenital varicella syndrome, including 1 approved therapy.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Varicella Zoster Immune Globulin (Human) [VARIZIG] | antibodies | FDA | Approved | Cangene bioPharma, Inc. |
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