Search Results (416)

Background: Herpes zoster (HZ) is uncommon in children and is typically considered a mild disease. However, hospitalized cases may be associated with complications. Data on herpes zoster in children in Eastern Europe are limited. This study aimed to describe the clinical features, complications, and factors associated with severity in hospitalized pediatric HZ. Methods: We conducted a retrospective cohort study including children (<18 years) hospitalized with HZ between January 2015 and December 2025, at a tertiary infectious diseases center in Bucharest, Romania. Demographic, clinical, laboratory, and outcome data were extracted from medical records. Univariable and multivariable analyses were performed to identify factors associated with complications and prolonged hospital stay. Results: Among 612 pediatric HZ cases, 92 (15.0%) required hospitalization. The median age was 8.8 years (IQR 4.8–13.2), and 52.2% were male. Overall, 43.5% developed complications, most commonly bacterial superinfection (30.4%), followed by neurological and ophthalmological involvement. Herpes zoster sine herpete was identified in 4.3% of cases and was associated with central nervous system involvement. Headache (OR = 4.34, p = 0.025) and lymphopenia (OR = 3.01, p = 0.020) were independently associated with complications. Patients with complications had longer hospital stays (median of 6 vs. 4 days, p = 0.002). In multivariable analysis, complications, immunocompromised status, and chronic conditions were associated with prolonged hospitalization. Conclusions: Herpes zoster in children is generally mild and has a favorable prognosis; however, hospitalized cases are often associated with complications, especially bacterial superinfections and neurological involvement. These findings derive from a selected population and highlight the role of clinical and host-related factors in shaping outcomes in hospitalized pediatric herpes zoster. Full article

Background/Objectives: Herpes zoster is caused by varicella-zoster virus reactivation, which often leads to a chronic pain condition named postherpetic neuralgia (PHN). Patients with immunosuppressive conditions face a heightened risk of developing PHN. This study aims to identify factors contributing to PHN development in immunosuppressive patients. Methods: This retrospective cohort study was conducted involving 219 immunosuppressive patients from two centers and split into training and test cohorts. Participants were divided into PHN (n = 88) and acute phase pain (ACP, n = 131) groups. Univariate and multivariate logistic regression analyses were used to identify clinical predictors of PHN. A nomogram was constructed to predict PHN risk by integrating significant predictors. The discrimination, calibration and clinical usefulness of the nomogram were evaluated. Results: Multivariate analysis revealed metabolic syndrome, older age, higher lactate dehydrogenase (LDH), and higher neutrophil-to-lymphocyte ratio (NLR) as significant PHN predictors. The nomogram showed good discrimination in both training (AUC of 0.83 [95% CI 0.77–0.90] with a specificity of 0.78, sensitivity of 0.87, NPV of 0.90, and PPV of 0.73) and test cohorts (AUC of 0.85 [95% CI 0.75–0.96] with a specificity of 0.82, sensitivity of 0.85, NPV of 0.89, and PPV of 0.76). Clinical decision curve analysis confirmed the practical utility of the nomogram. Conclusions: The nomogram incorporating age, metabolic syndrome, LDH, and NLR are useful in estimating PHN risk among immunosuppressed patients. Full article

Anti-inflammatory agents, antipyretics, and antibiotics are commonly used to manage fever and pain associated with infectious diseases in both adults and children. Despite their effectiveness, inappropriate and unnecessary prescriptions remain widespread, leading to adverse patient outcomes and, in the case of antibiotics, contributing to antimicrobial resistance. Addressing these issues requires effective stewardship programs focused on educating healthcare professionals and the public on evidence-based guidelines for optimal prescribing practices. This paper explores the five “A”s fundamental to infection management in pediatric and adult patients: appropriateness, abuse, antipyretics, anti-inflammatory agents, and antibiotics. Through a comprehensive literature review, expert perspectives, and clinical guidelines, the study evaluates the roles of anti-inflammatory agents (e.g., ibuprofen), antipyretics (e.g., paracetamol), and antibiotics in clinical practice, highlighting best practices for their use. Current guidelines emphasize that antipyretics should only be administered when fever is accompanied by significant discomfort or pain, as fever itself plays a role in the immune response. Based on the available literature, experts also suggest that paracetamol should be preferred as a first-line antipyretic due to its favorable safety profile, while ibuprofen should be used with caution, particularly during respiratory infections, varicella, and severe bacterial infections, due to its potential to exacerbate complications. According to experts, special consideration is also required for patients with renal or gastrointestinal comorbidities to prevent toxicity. Regarding antibiotics, prescriptions should be limited to clear evidence of bacterial infection to avoid unnecessary patient exposure and the development of antimicrobial resistance. Stewardship programs underscore the importance of selecting the right agent, optimizing dosing, and introducing shorter treatment regimens where supported by evidence, to improve therapeutic outcomes while minimizing resistance risks. Ultimately, this paper provides practical, evidence-based recommendations to support rational prescribing of antipyretics, anti-inflammatory drugs, and antibiotics, aiming to optimize patient outcomes, prevent unnecessary toxicity, and contribute to global efforts against antimicrobial resistance. Full article

Background: Varicella burden is closely linked to national socioeconomic development, yet systematic analyses of its non-linear relationship with the Socio-demographic Index (SDI) are lacking. This study aims to elucidate this relationship and inform equitable, context-specific strategies. Methods: Based on data from the Global Burden of Diseases 2021 study, we analyzed global trends (1990–2021) in the incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) of varicella. Joinpoint regression was used to identify trend transition points, and an autoregressive integrated moving average (ARIMA) model was applied to forecast the disease burden through 2035. Analyses were conducted, and countries and territories were stratified into five SDI groups: high (SDI > 0.81), high–middle (0.70–0.81), middle (0.61–0.69), low–middle (0.46–0.60), and low (SDI < 0.46). These approaches aimed to systematically elucidate the socioeconomic gradient of the varicella burden and to specifically investigate its potential non-linear relationship with SDI. Results: From 1990 to 2021, global age-standardized mortality and DALYs declined by −45.71% (95% UI: −48.32% to −42.95%) and −36.15% (95% UI: −39.04% to −33.01%), respectively, while incidence and prevalence rates slightly increased. A significant U-shaped relationship emerged between burden and SDI, with rates highest in low- and high-SDI regions. The rise in high-SDI regions was driven by increasing incidence and prevalence from 1996 to 2015. Projections to 2035 indicate continued global decline but persistent disparities. Conclusions: The varicella burden follows a U-shaped socioeconomic gradient. Rising incidence in high-SDI regions highlights that economic development and routine pediatric vaccination alone are insufficient. Precision strategies tailored to SDI levels—closing adult immunity gaps in high-SDI, sustaining gains in middle-SDI, and expanding vaccine access in low-SDI regions—are essential. Full article

Background: Despite the introduction in 2017 of mandatory vaccination for the hexavalent and the measles–mumps–rubella–varicella vaccines, childhood vaccination coverage in Sicily (Italy) remains below the recommended and safety threshold of 95%. A catch-up vaccination intervention was implemented for the pediatric population of the 2022–2023 birth cohorts residing in a health district of Palermo (Bagheria) where in 2024, 24-month coverage for polio and measles was 77.29% and 77.62%, respectively. Methods: A cross-sectional study with a before–after component was conducted between June 2025 and December 2025, with the aim of evaluating the increase in vaccination coverage. A questionnaire was administered to the parents of non-compliant children to investigate the determinants of infant vaccine hesitancy. Results: Collaboration with primary care pediatricians and the organization of active call sessions and extra vaccination sessions resulted in an increase in vaccination coverage of approximately 10–12 percentage points in both birth cohorts. The investigation of the determinants of vaccination adherence showed some significant associations: “perception of infectious disease risk” (OR: 7.91; p = 0.009) and “expectations of a positive outcome from vaccination” (OR: 8.62; p = 0.003). Vaccine information sources such as the internet and media were associated with refusal of catch-up vaccination (OR: 0.47, p < 0.001; and OR: 0.13, p = 0.026, respectively). Conclusions: Despite methodological limitations, such as the self-reported nature of the survey data, the study demonstrated the usefulness of local strategies aimed at vaccination catch-up, representing a valuable example of local public health practice and effectively contributing to improved vaccination coverage in the pediatric population. Full article

Background: Oral lesions, particularly enanthema, may accompany chickenpox and represent an important but often underrecognized component of the clinical presentation. Their timely identification is especially relevant in dental practice, as oral manifestations may be more frequent in patients with a more severe clinical course. This study aimed to describe characteristic oral cavity changes in hospitalized and outpatient patients with chickenpox, to identify patterns in the occurrence of oral findings in relation to disease severity, and to support clinical assessment in practice. Methods: A retrospective review of medical records was conducted for patients diagnosed with chickenpox in Bulgaria between December 2023 and May 2025. Data from hospitalized patients and outpatient cases were analyzed and compared to evaluate the distribution of oral manifestations and their association with clinical severity. Results: A total of 144 patients were included, of whom 32.6% required hospitalization. Oral enanthema was more frequently observed among hospitalized patients (48.8%). In univariate analyses, oral enanthema and tongue changes were associated with hospitalization. Multivariable logistic regression identified age and body temperature as independent factors associated with hospitalization, while oral manifestations did not retain independent predictive significance. Conclusion: Oral enanthema was more frequently observed among hospitalized patients and was associated with a more severe clinical presentation in univariate analyses. Although oral findings should not be interpreted as independent predictors of disease severity, their recognition may support clinical assessment, dental treatment planning, and appropriate infection control measures. Full article

Background/Objectives: Since 2023, a significant increase in measles cases has been reported worldwide, and Italy has been among the most affected European countries. In this context, the integration of laboratory and epidemiological data enables timely case classification and helps distinguish between imported and indigenous cases, supporting disease control. However, most studies address only selected aspects of surveillance. Therefore, this study aimed to provide an integrated analysis of virological and epidemiological surveillance activities conducted between November 2023 and December 2025 by the Regional Reference Laboratory in the Emilia-Romagna Region (ERR). Methods: A total of 806 clinical samples (269 urine, 267 oral fluids—saliva or oropharyngeal swabs—and 270 sera) from 291 suspected measles cases were tested by molecular and/or serological methods, and MV genotyping was performed. Samples from discarded cases were also analysed for parvovirus B19 (B19V), human herpesvirus 6 (HHV-6), enterovirus (EV), and varicella zoster virus (VZV), chikungunya virus (CHIKV) and dengue virus (DENV). Results: Of 291 suspected cases, 176 (60.5%) were confirmed. Median age was 33 years, with 46% in the 15–39 year group. Vaccination status was available for 165: 90.3% were unvaccinated, 5.4% had one dose, and 4.2% had two doses. Notably, over half of confirmed cases occurred in areas with vaccine-hesitant communities. MV strain characterisation was performed in 99.4% of MV-RNA positive cases, with 84.3% genotype D8 and 15.6% genotype B3; 83% of strains were of indigenous origin, suggesting an ongoing endemic circulation. Clinical data showed complications in 19.3%, mainly pneumonia and diarrhoea. Additionally, differential diagnosis enabled the identification of the etiological agent in 37.5% of measles/rubella discarded cases, and 37.6% (29/77) tested positive for B19V. Conclusions: The study results highlight that effective measles surveillance must be supported by integrating timely virological diagnosis, molecular and epidemiological investigations, and differential diagnosis, to achieve the WHO goals of eliminating measles transmission. Full article

Background/Objectives: Vaccinations are a cost-effective strategy to reduce morbidity and mortality from infectious diseases, particularly in individuals with diabetes mellitus (DM). Despite recommendations for routine vaccination, uptake among adults with DM remains suboptimal. This study evaluates the effectiveness of interventions aimed at increasing Herpes Zoster (HZ) vaccine coverage in diabetic patients. Methods: This study included diabetic patients residing in the Romagna Local Health Authority (1.2 million inhabitants). Two complementary strategies were implemented: patient-oriented interventions (reminders/recalls) and provider-focused actions to engage general practitioners and diabetologists. Vaccination coverage in December 2023 was compared with December 2024, stratified by age, sex, and nationality. Primary outcomes were changes in coverage and intervention impact. Multivariate logistic regression assessed sociodemographic determinants of adherence. Results: As of 31 December 2023, 5182 diabetic patients had received at least one dose of Herpes Zoster vaccine (7.4% coverage). In 2024, overall coverage (11.1%) increased across all sociodemographic groups. Coverage rose to 12.8% in males and 9.0% in females and to 11.7% among Italian citizens, while foreign citizens showed lower absolute levels but a greater proportional increase. By age, individuals born after 1958 exhibited the largest relative growth, whereas those born in 1952–1958 reached the highest absolute coverage in 2024. Male sex, the 1952–1958 birth cohort, and Italian citizenship were associated with a higher likelihood of vaccination in both years. Conclusions: Our findings show a positive trend in Herpes Zoster vaccination among diabetic patients in Romagna HLA, driven by patient reminders, provider engagement, and age-targeted campaigns, while persistent sociodemographic disparities underscore the need for tailored strategies to optimize coverage. Full article

Background/Objectives: Varicella is a highly contagious childhood disease that may cause severe complications in susceptible populations. The SV-1 cell line-based varicella vaccine (VarV [SV-1]) has been increasingly used in routine immunization; however, safety and reporting patterns during the transition from partial use to full Expanded Program on Immunization (EPI) implementation remain poorly characterized. This study aimed to evaluate the safety profile and reporting dynamics of VarV (SV-1) before and after its incorporation into the Expanded Program on Immunization in Jiangsu Province, China. Methods: A retrospective observational study was conducted using data from the Jiangsu Provincial Immunization Integrated Service Management Information System and the Chinese National Adverse Event Following Immunization (AEFI) Information System (CNAEFIS), including all reported AEFI following VarV (SV-1) vaccination among children under 6 years of age during 2021–2023. Temporal trends, distribution characteristics, and factors associated with AEFI reporting were assessed using descriptive analyses, negative binomial (NB) regression models, and interrupted time series (ITS) analysis. Results: A total of 1,208,500 doses of VarV (SV-1) were administered, and 634 AEFI cases were reported, corresponding to an overall reporting rate of 52.46 per 100,000 doses. Most reported events were mild, self-limiting common reactions, predominantly pyrexia and injection-site reactions. No serious adverse events were identified. Although no immediate level change was observed at EPI implementation, a significant increasing post-EPI trend was detected, consistent with enhanced surveillance sensitivity rather than a change in intrinsic vaccine safety. Abnormal reactions were rare and resolved without sequelae. Conclusions: AEFI reporting rates following VarV (SV-1) vaccination in Jiangsu Province were within expected ranges, predominantly mild and reversible. Findings support the favorable safety profile of the VarV (SV-1) in routine childhood immunization programs and provide real-world evidence to support continued implementation of the two-dose varicella vaccination strategy within the EPI. Full article

Bispecific antibodies represent a pivotal advancement in treating relapsed/refractory B-cell lymphomas, addressing unmet needs for patients with limited conventional options. This review examines CD20 × CD3 bispecific antibodies (BsAbs) like mosunetuzumab, epcoritamab, odronextamab, and glofitamab, which link malignant B-cells and T-cells, thus inducing targeted tumor lysis. These IgG-like molecules activate T-cells, triggering proliferation and cytotoxic molecule release, bypassing MHC presentation. These agents have received regulatory approval for the treatment of various B-cell lymphomas and exhibit substantial efficacy, with high overall and complete response rates in diffuse large B-cell lymphoma and follicular lymphoma. However, their use is associated with immune-related toxicities. Cytokine Release Syndrome, which is a systemic inflammatory response due to a cytokine surge, and Immune Effector Cell-Associated Neurotoxicity Syndrome, linked to endothelial activation and blood–brain barrier disruption, are critical concerns. This review details their mechanisms, grading, and management, including the use of tocilizumab and corticosteroids. Furthermore, BsAb therapy carries an elevated susceptibility to viral, bacterial, and opportunistic infections, often exacerbated by hypogammaglobulinemia. Expert recommendations for antimicrobial prophylaxis, including herpes and varicella zoster virus, pneumocystis, and immunoglobulin supplements are crucial for mitigating these risks. While BsAbs offer an “off-the-shelf” advantage, balancing their efficacy with comprehensive toxicity management is crucial for maximizing patient outcomes. Full article

Kidney transplantation is considered the gold standard treatment for patients with end-stage kidney disease. Historically, outcomes in kidney transplantation have been focused on reducing rates of rejection as the dominant cause of graft loss. However, managing the risk of rejection with infection continues to be a delicate balancing act for transplant physicians. It has long been recognised that viruses are an important cause of morbidity and mortality in immunosuppressed patients with significant implications for kidney graft function and patient outcomes worldwide. This is a review article with literature selected from the PubMed database using relevant terms related to kidney transplantation and infectious diseases. This article focuses on the key viruses affecting kidney transplant recipients, including cytomegalovirus, polyoma virus, Epstein–Barr virus, varicella zoster virus, adenovirus, hepatitis B and C, and new emerging viruses. It examines differing epidemiology, diagnostic challenges, screening methods, and antiviral treatments. Key challenges for the international nephrology community include increased global mobility resulting in rapid shifts in viral epidemiology, increasing antimicrobial resistance, virus-associated malignancies, and suboptimal assays for screening donors and transplant recipients. Full article

Acyclovir is an antiviral drug effective against infections caused by herpes simplex and varicella zoster viruses. It is given intravenously to treat serious infections such as herpes encephalitis. High acyclovir concentrations could cause toxicity, observed mainly as nephrotoxicity and, to a lesser extent, neurotoxicity. Acyclovir nephrotoxicity is primarily attributed to the crystallization of acyclovir within the renal tubules, although additional mechanisms may also contribute. However, the mechanism of acyclovir-induced neurotoxicity is unknown. Acyclovir is mainly eliminated from the body through renal excretion; however, around 15–20% of acyclovir is metabolized subsequently by alcohol and aldehyde dehydrogenase to the main metabolite 9-carboxymethoxymethylguanine (CMMG), and around 2% is metabolized by aldehyde oxidase to the minor metabolite, 8-hydroxyl acyclovir. It has been suggested that CMMG levels above 10 µmol/mL in the serum and 1 µmol/mL in the cerebrospinal fluid are highly associated with neurotoxicity. Studies have shown that there is a potential contribution of CMMG to acyclovir-induced neurotoxicity and of the acyclovir aldehyde to nephrotoxicity. In this narrative review, we approach the topic of acyclovir metabolites and their association with acyclovir toxicity. Moreover, we identify the research gap of the mechanisms by which these metabolites contribute to toxicity. Full article

Varicella-Zoster Virus (VZV) is one of the most important pathogens in ophthalmology. Reactivation may involve the adnexa (blepharoconjunctivitis, pseudomembranous conjunctivitis), cornea (dendritic keratitis, nummular and necrotizing stromal keratitis, disciform endotheliitis, neurotrophic ulcers, mucous-plaque keratitis) and sclera (episcleritis, anterior scleritis). Uveal inflammation ranges from anterior uveitis—with iris atrophy, trabeculitis-induced glaucoma and complicated cataract—to posterior necrotizing syndromes: acute retinal necrosis in immunocompetent hosts and progressive outer retinal necrosis in immunosuppressed patients, often complicated by occlusive vasculitis, macular edema, retinal detachment and phthisis. Optic nerve and cranial nerve involvement (optic neuritis, neuroretinitis, III/IV/VI palsies) and orbital inflammation may occur even without cutaneous signs (“zoster sine herpete”), making PCR-based intraocular diagnostics essential. Management relies on early, high-dose antivirals (acyclovir or valacyclovir), judicious corticosteroids and timely surgical intervention when required. Universal childhood varicella vaccination and recombinant zoster vaccination in adults ≥50 years have reduced VZV incidence and ocular complications in settings with high vaccine coverage, though rare post-vaccine keratitis or uveitis underscore the need for ongoing vigilance. In this review, we synthesize current knowledge on varicella-zoster virus ocular disease, with a focus on host–pathogen interactions that drive both injury and defense. Full article

To evaluate the epidemiology of herpetic keratitis over a 15-year period at a tertiary care center in Switzerland, focusing on the relative incidence of herpes simplex virus (HSV)-1, HSV-2, and varicella zoster virus (VZV), gender distribution, and co-infections, we conducted a retrospective single-center analysis of polymerase chain reaction (PCR) assays from corneal and conjunctival scrapings of suspected herpetic keratitis at a tertiary referral hospital. Patient demographics, viral spectra, and microbiological co-infections were assessed. Between 2010 and 2025, we identified 9954 PCR assays from 2892 patients, with 482 samples testing positive for herpesvirus. HSV-1 was the most frequent pathogen (328 of 3358, 9.8%), followed by VZV (143 of 3112, 4.6%), HSV-2 (9 of 3290, 0.27%), and CMV (2 of 194, 1.0%). Triplet testing (simultaneous HSV-1, HSV-2, and VZV-PCR) enabled direct comparisons of relative incidence rates. We found 2913 triplet testing results, with a relative distribution in positive results of 65.4% for HSV-1, 32.5% for VZV, and 2.1% for HSV-2. HSV-1 keratitis had a statistically significant higher incidence in men (58.9%, p = 0.0044), while no sex difference was detected for VZV (47.9%, p = 0.6683), HSV-2 (33.3%, p = 0.5078), or CMV (100%, p = 0.500). Bilateral infections were present in two patients, and co-infections were detected as follows: 8 cases of HSV-1/VZV co-detection, 3 cases of Acanthamoeba, and 15 of fungi. HSV-1 was the overwhelmingly dominant cause of herpetic keratitis at our institution, occurring more than twice as frequently as VZV and vastly outnumbering HSV-2. The statistically significant higher incidence in men in HSV-1 keratitis suggests possible biological or sociodemographic influences, whereas co-infections highlight the complexity of corneal pathology in a referral setting. These findings underscore the importance of multiplex PCR testing for accurate pathogen detection and provide insights into the epidemiologic landscape of herpetic keratitis. Full article