Human Herpesvirus Research Articles

Photodynamic Inactivation of Human Herpes Virus In Vitro with Ga(III) and Zn(II) Phthalocyanines

Photodynamic inactivation (PDI) has been revealed as a valuable approach against viral infections because of the fast therapeutic effect and low possibility of resistance development. The photodynamic inhibition of the infectivity of human herpes simplex virus type 1 (HSV-1) strain Victoria at different stages of its reproduction was studied. PDI activity was determined on extracellular virions, on the stage of their adsorption to the Madin-Darby bovine kidney (MDBK) cell line and inhibition of the viral replication stage by application of two tetra-methylpyridiloxy substituted gallium and zinc phthalocyanines (ZnPcMe and GaPcMe) upon 660 nm light exposure with a light-emitting diode (LED 660 nm). The PDI effect was evaluated on extracellular virions and virus adsorption by the terminal dilution method and the change in viral infectivity, which was compared to the untreated control group. The decrease in viral titer (Δlgs) was determined. The effect on the replicative cycle of the virus was determined using the cytopathic effect inhibition (CPE) assay. The direct influence on the virions showed a remarkable effect with a decrease in the viral titer more than 4 (Δlg > 4). The influence of the virus to the cell on the stage of adsorption was also significantly affected by the exposure time and the concentration of applied photosensitizers. A distinct inhibition was evaluated for ZnPcMe at the viral replication stage, which demonstrated a high photoinactivation index (PII = 33.0). This study suggested the high efficacy of PDI with phthalocyanines on HSV-1 virus, with full inhibition caused by the mechanism of singlet oxygen generation. These promising data are a good basis for further investigations on the PDI application against pathogenic viruses.

Clinical observations of skin Kaposi’s sarcoma

Kaposi's sarcoma is an angioproliferative disease of endothelial origin associated with human herpes virus-8 (HHV-8), or Kaposi's sarcoma herpesvirus. The disease was first described in 1872 by Moritz Kaposi as a pigmented cutaneous sarcoma localized on the lower extremities. The disease is considered quite rare, but at present there is an increase in the incidence worldwide, due to which there is a growing interest in this problem. Today, it remains the leading skin pathology among HIV-positive patients, occurring in 20%. However, the assessment of the pathological process can be difficult, and the diagnosis may not be made at all, due to atypical clinical manifestations (especially in HIV-negative patients), so the problem of Kaposi's sarcoma diagnostics remains relevant for doctors of any specialty, especially dermatovenerologists and oncologists. Kaposi's sarcoma can affect almost any organ, including the skin. The most common localization is on the skin of the extremities and face. Clinical manifestations are rashes in the form of spots, nodules, plaques, nodes. Kaposi's sarcoma is classified according to clinical and epidemiological forms: classical, endemic, epidemic and iatrogenic. Recently, a fifth form has been described, called non-epidemic Kaposi's sarcoma, which is observed in HIV-negative men who have sex with other men. The persistence of HHV-8 alone in the human body is not sufficient for Kaposi's sarcoma to occur, as the development of the disease is dependent on immunosuppressive conditions such as HIV infection, cytostatic drugs, and chronic systemic inflammatory diseases (e.g., rheumatoid arthritis). The interaction between human immune dysfunction and the local inflammatory response to herpesvirus creates a favourable environment for the onset and progression of the disease. These clinical cases demonstrate an atypical clinical course of Kaposi's sarcoma of the skin with the absence of HIV-1, HIV-2 and HHV-8 in the blood of the presented patients.

Comparison of IL-6, IL-10, and TNFα levels between PLWHIV with and without Kaposi Sarcoma and healthy controls.

Kaposi sarcoma (KS) is an angioproliferative disease caused by human herpesvirus 8 (HHV-8) and is mediated by cytokines in an immunodeficient environment. This study aimed to compare IL-6, IL-10, and TNFα levels among AIDS patients with disseminated KS (DKS), treatment naïve patients living with HIV (PLWHIV) without DKS, and healthy controls. Secondary outcomes were to compare cytokines levels in patients with DKS and unfavorable outcomes, as well as an analysis of the behavior of cytokines over time. This cohort study was performed at two centers in Mexico City. Three groups were included. Group 1: HIV+ treatment naïve with DKS, Group 2: HIV+ treatment naïve without KS, and Group 3: HIV negative, healthy controls. Plasmatic IL-6, IL-10, and TNFα levels were measured at baseline and over time in Groups 1 and 2. Seventy-six patients were included: 39 (52%) in Group 1, 17 (22%) in Group 2, and 20 (26%) in Group 3. The median baseline IL-6, IL-10, and TNFα levels were significantly higher in group 1. In group 1, baseline IL-6 was higher in patients who died than in survivors (14.4 vs 5.8 pg/mL p=0.048). Patients with severe immune reconstitution inflammatory syndrome due to KS (S-IRIS-KS) had higher IL-6 values than those without it (14.4 vs 5.8 pg/mL p=0.004). In the repeated-measures model in group 1, IL-10 levels were higher in patients who died (p<0.001) and developed IRIS-KS (p=0.01). IL-6, IL-10, and TNF α levels were markedly higher in patients with DKS. IL-6 and IL-10 levels were higher in patients with unfavorable outcomes.

Viral Load Measurements for Kaposi Sarcoma Herpesvirus (KSHV/HHV8): Review and an Updated Assay.

"When you can measure what you are speaking about, and express it in numbers, you know something about it." is a famous quote attributed to Lord Kelvin. This sentiment puts viral load measurements at the center of virology. Viral load, or more precisely, DNA copy number measurements, are also used to follow infections with human herpesviruses, such as Kaposi sarcoma herpesvirus (KSHV) and Epstein-Barr Virus (EBV). EBV and KSHV are associated with human cancers, and determining their DNA copy numbers in the context of cancer prediction and progression on therapy is of fundamental scientific and translationalinterest. Yet, there is no generally accepted assay for KSHV DNA quantitation, and KSHV viral load is not used in clinical decision-making. Here, we review the history of KSHV DNA detection assays, explore factors that affect sensitivity and specificity, and describe an automated, high-throughput, real-time quantitative polymerase chain reaction (PCR) assay for KSHV and EBV. In conjunction with a digital PCR assay using the same primer/probe combination, we describe how to determine the absolute KSHV genome copy numbers in plasma, peripheral blood mononuclear cells, saliva, and other easily accessible body fluids.

Variabilities of salivary human herpesvirus 6, 7, and secretory immunoglobulin A levels from pre- to post-competition periods in baseball players.

Persistent physical fatigue (PPhF) accompanying daily intensive training often results in underperformance. While salivary secretory immunoglobulin A (SIgA) has been traditionally used as an immunological marker, salivary human herpesvirus 6 and/or 7 (HHV-6/7) have recently been presented as "microbiological" markers of PPhF. This study aimed to examine the monthly variabilities of salivary HHV-6/7 levels and the difference with SIgA along the training periodization. A total of 27 healthy male university baseball players (N.=17) and non-players (student staff, N.=10) were followed up for 4 months (August, pre-competition period; September and October, competition period; November, post-competition period). The main measures were subjective and objective fatigue parameters (questionnaires and performance tests), and salivary HHV-6/7 and SIgA levels. The fatigue parameters indicated a decrease in athletic performance from August to September due to PPhF during high intensity training in August. Two-way repeated analysis of variance showed that salivary HHV-6 and -7 levels were higher in players compared to non-players (P<0.05). Salivary HHV-6 levels gradually decreased (P<0.05), whereas HHV-7 levels remained unchanged (P>0.05). Salivary SIgA levels were higher in players rather than in non-players (P>0.05), and the levels did not change (P>0.05). Our findings suggest that salivary HHV-6/7 levels, specifically in HHV-6, reflect the degree of PPhF independently of SIgA levels. As saliva can be collected anywhere, periodic monitoring of salivary HHV-6/7 levels may be easily applicable for assessing PPhF beside sports field and allow appropriate conditioning.

Detection of HHV-5 HHV-6a HHV-6b and HHV-7 in the urine: potential use as a non-invasive diagnostic tool for immune profiling

Decline in immune function with age has been studied extensively, but approaches to immune restoration have been hampered by the lack of simple methods of identifying individuals whose immune system is in decline. Our approach has been to identify individuals whose immune decline has led to a loss of control of common latent viral infections and their consequent reactivation. Viruses excreted in urine were detected and quantified and we believe this approach could provide a 'surrogate marker' for identifying immune compromised individuals. Here we report the detection of human herpes virus (HHV) 5, 6a, 6b and 7 in the urine of healthy individuals over a wide age range and their correlation with T cell receptor excision circle (TREC) data. The results did not show a clear correlation between TREC values and the detection of individual specific viruses or viral load values when measured singly. However, a correlation was found between low TREC values and the detection of several different human herpes viruses in the urine in males. We present evidence suggesting that for males, the detection of three or more different human herpes viruses in the urine could identify individuals with declining immune function as evidenced by their significantly lower TREC levels.

DEVELOPMENT AND VALIDATION FOR INTRA-SPECIES CLASSIFICATION OF HHV6A AND HHV6B MOLECULAR GENETIC DIVERSITY

Human herpesvirus 6A (HHV6A) and human herpesvirus 6B (HHV6) are ubiquitous viruses that infect more than 95% of the population. Clinical manifestations of HHV6 infection and associated diseases are diverse, which may depend on virus molecular genetic characteristics (genovariants). Estimating the significance of the molecular genetic diversity is complicated due to the lack of proper classification. The aim of the study was to develop an intraspecies HHV6A and HHV6B classification. Using 50 and 207 HHV6A and HHV6B full-genome sequences retrieved from the NCBI Nucleotide database, various fragments of virus genome were analyzed. Multiple sequence alignment was performed using MAFFT L-INS-i algorithm; F81 nucleotide substitution model and maximum likelihood method were used to construct dendrograms. Nucleotide substitutions were determined relative to reference sequences X83413 (HHV6A) and AF157706 (HHV6B). Genovariants were defined based on the nucleotide substitutions in variable positions of the genomic fragment. The results were confirmed by constructing dendrograms. An opportunity of using fragments of HHV6A and HHV6B genomes to construct an intraspecies classification was assessed. Fragments U90 (part206) and U90B(part431) were selected as optimal. Based on the nucleotide sequences of the fragments, the intraspecies classification for HHV6A and HHV6B was constructed, including seven genovariants of each virus. The genovariants were characterized by unique nucleotide composition in the signature positions. A minimum (0.001 or less for both viruses) nucleotide diversity within the isolated genovariants was established. The classification reflects the phylogenetic relationships of circulating and inherited chromosomally integrated forms of HHV6A and HHV6B: divergence of HHV6A genovariants depending on its persistence form and integration site and coevolution of two HHV6B forms within several genovariants. Further studies on virus molecular genetic diversity in different regions of Russia and abroad may supplement the classification. The method of HHV6A and HHV6B classification is characterized by simplicity, technological accessibility and can be implemented in laboratories of different levels of technical equipment. The classification can be used to analyze an effect of virus molecular genetic diversity on the clinical characteristics of associated diseases, optimize the epidemiological surveillance system and develop new approaches for diagnostics, prevention, and treatment of HHV6 infection.

Human Herpes Virus-8 Oral Shedding Heterogeneity is Due to Varying Rates of Reactivation from Latency and Immune Containment.

HHV8 shedding rate is mosty determined by rate of reactivation from latency while viral loads is mostly dteremined by peripheral immune responses.DAS performed all mathematical modeling and editied the paper; EMK performed statistical analysis and edited the paper; CB assisted with modeling; FO, JN and IM designed and implemented the clinical protocols; WP designed and implemented the clinical protocols and edited the paper; JTS conceived the study and write the paper.

Unveiling the truth: Pathogen infections linked to miscarriage: A STROBE-Compliant Mendelian randomization study

Miscarriage represents a prevalent yet insufficiently studied adverse pregnancy outcome. The definitive causal links between various pathogens and miscarriage remain to be established. To investigate the causal connections between pathogen infections and miscarriage, we utilized a two-sample bidirectional Mendelian randomization (MR) analysis. We sourced genome-wide association studies data on pathogen infections from the UK Biobank, which included serological markers for infectious diseases and comprehensive whole-genome genetic information from approximately 10,000 individuals. Additionally, genome-wide association studies data on miscarriages were collected from 3 distinct European populations for our analysis. The MR analysis was primarily conducted using the inverse variance weighted method, complemented by Bayesian weighted MR and the weighted median method for robustness. To ensure the reliability of our findings, we performed heterogeneity and pleiotropy tests, leave-one-out sensitivity analyses, and a meta-analysis. Our extensive research has identified a causal association between miscarriage and infections by several human herpesviruses (HHV-1, HHV-3, HHV-4, HHV-6, and HHV-7), polyomaviruses (BK, JC, and Merkel cell polyomaviruses), and Chlamydia trachomatis (inverse variance weighted, P &lt; .05). Notably, a meta-analysis of the integrated data highlighted the particularly high accuracy and consistency of the association with Merkel cell polyomavirus. Our MR analysis has clarified the causal relationships between specific pathogen infections and miscarriage, providing a critical foundation for the prevention and treatment of this adverse pregnancy outcome.

Association between human herpesviruses infections and childhood neurodevelopmental disorders: insights from two-sample mendelian randomization analyses and systematic review with meta-analysis

BackgroundThe potential roles of viral infections in neurodevelopmental disorders (NDDs) have been suggested based on previous studies. Given the high prevalence of human herpesviruses (HHVs), the associations between HHVs infection and the risk of NDDs warrant explored.MethodsOur study employs a two-sample Mendelian randomization (MR) analysis and systematic review with meta-analysis to investigate whether genetically predicted HHVs infection are linked to three main childhood NDDs—autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS). We utilized genetic variants associated with HHV infections in genome-wide association study (GWAS) summary datasets of European populations to establish instrumental variables and statistics for three NDDs obtained from Psychiatric Genomics Consortium. MR analysis was performed using inverse-variance weighted, MR Egger, weighted median, simple median, weighted mode, and MR-PRESSO. In addition, publications associating HHVs infection with three NDDs were systematically searched using PubMed, Web of Science, and three Chinese databases for meta-analyses.ResultsThe MR results found no evidence to support a link between genetically predicted HHVs infection and the risk of NDDs based on existing datasets. Twenty-seven observational studies on children with HHVs infection and NDDs were considered eligible. Meta-analysis showed that cytomegalovirus and HHV-6 infection were related with ASD, while Epstein-Barr virus and cytomegalovirus infection were associated with TD in Chinese population. Conclusions: These results contribute to a comprehensive understanding of the possibilities underlying HHV infections in affecting childhood NDDs. Further research is necessary to include larger and more robust statistics of HHV infections and NDDs.Trial registrationThis systematic review was registered at PROSPERO as CRD42024554169. Retrospectively registered 26 July 2024.

Exploring the genetic associations and causal relationships between antibody responses, immune cells, and various types of breast cancer.

There may be potential associations between various pathogens, antibody immune responses, and breast cancer (BC), but the specific mechanisms and causal relationships remain unclear. First, multiple Mendelian randomization (MR) methods were used for univariable MR analysis to explore potential causal relationships between 34 antibody immune responses (related to 12 pathogens), 46 antibody immune responses (related to 13 pathogens), antibody responses post-COVID-19 vaccination, 731 immune cell types, and various BC subtypes (including overall BC, ER-positive, ER-negative, Luminal A, Luminal B, Luminal B HER2-negative, HER2-positive, and triple-negative BC). The primary results were then subjected to reverse MR analysis, heterogeneity testing using Cochran's Q, and horizontal pleiotropy testing. Robust findings were further used to design mediation pathways involving antibody immune responses, immune cells, and BC. After adjusting the effect estimates using multivariable MR (MVMR), a two-step mediation analysis was conducted to explore mediation pathways and mediation proportions. Finally, linkage disequilibrium score regression (LDSC) was applied to analyze the genetic correlation between phenotypes along mediation pathways, and cross-phenotype association analysis (CPASSOC) was performed to identify pleiotropic SNPs among three phenotypes along these pathways. Bayesian colocalization tests were conducted on pleiotropic SNPs using the multiple-trait-coloc (moloc). We identified potential causal relationships between 15 antibody immune responses to 8 pathogens (Hepatitis B virus, Herpes Simplex Virus 2, Human Herpesvirus 6, Polyomavirus 2, BK polyomavirus, Cytomegalovirus, Helicobacter pylori, Chlamydia trachomatis), 250 immune cell phenotypes, and various BC subtypes. MVMR-adjusted mediation analysis revealed four potential mediation pathways. LDSC results showed no significant genetic correlation between phenotypes pairwise. CPASSOC analysis identified two potential mediation pathways with common pleiotropic SNPs (rs12121677, rs281378, rs2894250). However, none of these SNPs passed the Bayesian colocalization test by moloc. These results excluded horizontal pleiotropy, stabilizing MR analysis results. This study utilized MR methods to analyze potential causal relationships between various antibody immune responses, immune cell types, and BC subtypes, identifying four potential regulatory mediation pathways. The findings of this study offer potential targets and research directions for virus-related and immunotherapy-related studies, providing a certain level of theoretical support. However, limitations such as GWAS sample size constraints and unclear specific pathophysiological mechanisms need further improvement and validation in future studies.

The Development of Epilepsy Following CNS Viral Infections: Mechanisms.

This review examines the role of different viral infections in epileptogenesis, with a focus on Herpesviruses such as Human Herpesvirus 6 (HHV-6) and Epstein Barr Virus (EBV), Flaviviruses, Picornaviruses, Human Immunodeficiency Virus (HIV), Influenzavirus and Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2). A growing literature on animal models, such as the paradigmatic Theiler's murine encephalomyelitis virus (TMEV) model, and clinical investigations in patients with epilepsy have started to elucidate cellular mechanisms implicated in seizure initiation and development of epilepsy following viral infections. A central role of neuroinflammation has emerged, with evidence of activation of the innate and adaptive immunity, dysregulation of microglial and astrocytic activity and production of multiple cytokines and other inflammatory mediators. Several chronic downstream effects result in increased blood-brain barrier permeability, direct neuronal damage, and modifications of ion channels ultimately leading to altered neuronal excitability and seizure generation. Key findings underscore the complex interplay between initial viral infection, neuroinflammation, and later development of epilepsy. Further research is needed to elucidate these mechanisms and develop targeted interventions.

Abstract 4112775: Demographics and Cardiovascular Mortality Among Kaposi Sarcoma Patients in the United States: An Analysis of the SEER Database

Aims and Background: Kaposi sarcoma (KS) is a vascular neoplasm caused by human herpesvirus. Despite its significance, there is limited data regarding the causes and mortality factors associated with KS, particularly concerning cardiovascular mortality rates and specific influencing factors. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to gather data from 2000 to 2020. The primary endpoint was overall survival, assessed via log-rank analysis and Kaplan-Meier plots. Hazard ratios (HR) with 95% confidence intervals (CIs) were calculated using SAS v9.4, with significance set at p&lt;0.05. Results: We identified 8,247 patients with KS. Most were male (90.6%) and aged 40-59 years old (38.5%). Mortality data from KS showed that 56.3% of diagnosed patients were alive. Among those who died, 49.8% died of infectious causes, 11.4% died of cardiac causes, and the remaining died of other causes, such as leukemias and complications. Advanced age (&gt;80 years) vs. 0-19 year age group (HR: 2.263; 95% CI: 1.068-4.795; p=0.033), non-Hispanic Black race vs. non-Hispanic White race (HR 1.492; 95% CI: 1.369-1.627; p=0.001), and visceral involvement vs. cutaneous KS (HR 1.709; 95% CI: 1.487-1.963; p=0.001) were factors associated with increased mortality. Females had a slightly lower long-term survival than males (p&lt;0.001). Married individuals, higher incomes (≥$75,000), and urban areas of living had higher survival rates compared to widowed patients, lower-income patients (&lt;$75,000), and those in rural locations, respectively (p&lt;0.001, for all). In the subgroup analysis, females (24.3%; n=112) had significantly higher cardiac-related deaths than males (9.5%; n=297) (p&lt;0.0001). Cardiac-related deaths were highest in White patients (16.1%; n=279), followed by Hispanics (10.4%; n=79). Conclusions: Cardiac causes accounted for 11.4% of deaths. Various factors are associated with an increased mortality risk.

Combined effect of basic antiherpetic drugs with a new inhibitor of the terminase complex of herpes simplex virus type 1 in Vero cell culture

More than 90% of the world’s population are carriers of herpes simplex virus type 1 (HSV-1). The infection manifests itself in the formation of blisters and ulcers on the face or genitals, and can cause blindness, encephalitis, and generalized infection. All modern first- and second-line antiherpetic drugs selectively inhibit viral DNA-polymerase. The purine-benzoxazine conjugate LAS-131 [(S)-4-[6-(purin-6-yl)aminohexanoyl]-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine], which we described earlier, uses the large subunit of the HSV-1 terminase complex as a biotarget and selectively inhibits its reproduction in vitro. For the first time, we have obtained fundamentally new results on the combined effect of LAS-131 on human herpesvirus infection with practically significant antiviral compounds – nucleoside analogues (acyclovir [ACV], penciclovir [PCV], ganciclovir [GCV], brivudine [BVDU], iododeoxyuridine [IDU], adenine arabinoside [Ara-A], as well as a nucleoside phosphonate analogue (cidofovir [CDV]) and a pirophosphate analogue (foscarnet [FOS]). Using a inhibition assay of cytopathic effect (CPE) induced by a virus, it was shown that when combined with LAS-131, the concentrations of the compounds in combinations providing inhibition of HSV-1-induced CPE by 50%, decreased by 2 times (additive effect, FOS) or more (synergistic effect, ACV, PCV, GCV, IDU, BVDU, Ara-A, CDV). Reducing the concentrations of agents creates non-permissive conditions for the reproduction of HSV-1 and opens up new real possibilities for controlling human herpesvirus infection.

Seroprevalence and detection of Human herpesvirus-8 (HHV-8) among healthy blood donors residing in Qatar

BackgroundHuman herpesvirus 8 (HHV-8) is a critical causative agent behind Kaposi sarcoma (KS), an oncogenic disease with profound consequences in immunocompromised individuals. Studies suggested HHV-8 seroprevalence in healthy populations is uncommon, but comprehensive investigations within the Middle East region remain scarce. This study aimed to bridge this knowledge gap by meticulously assessing HHV-8 seroprevalence among healthy blood donors in Qatar, leveraging serological methodologies and PCR. MethodsWe used sera samples collected from 621 healthy blood donors (median age = 36 years, IQR 30-43) from different nationalities residing in Qatar, mainly from the MENA region and Southeast Asia. All sera samples were tested for total anti-HHV-8 IgG antibodies using ELISA. The presence of lytic HHV-8 antibodies was confirmed by an immunofluorescence assay (IFA). Further, HHV-8 DNA was tested and quantitated by qRT-PCR. ResultsELISA detected anti-HHV-8 IgG total antibodies in 6.9% [43/621, 95%CI 5.2-9.2] of the tested samples. Subsequent testing by IFA revealed that 14% [6/43, 95%CI 3.6-24.3] of these anti-HHV-8 IgG were classified as HHV-8 lytic antibodies. This suggests that 0.97% [6/621, 95%CI 0.2-1.7] of these donors had a recent or ongoing active infection and viral replication. Only one seronegative Qatari blood donor had detectable HHV-8 DNA in his blood. No significant difference was observed between HHV-8 seropositivity and the demographic characteristics of the donors. ConclusionOur study showed that HHV-8 prevalence in Qatar aligns closely with global reports. Moreover, our findings raise considerations regarding HHV-8’s potential transmission via transfusion, which suggests the value of routine HHV-8 screening, particularly for immunocompromised patients vulnerable to KS.

Identification of stimuli that enhance human herpesvirus 6A (HHV-6A) replication and reconstitution.

HHV-6A is a betaherpesvirus that infects a wide range of human tissues and establishes lifelong latency in the host. Its reactivation has been implicated in several diseases, including multiple sclerosis, encephalitis, myocarditis, and chronic fatigue syndrome, although its pathogenetic role remains elusive. The efficacy of common antiviral drugs is limited, and no specific drugs target HHV-6A infection. The data of this study shed light on stimuli and potential pathways that influence HHV-6A replication and reconstitution. Our strategies not only simplify virus propagation and reconstitution to study HHV-6A biology but also provide the basis for the development of therapeutic strategies.

Infectious Disease as a Modifiable Risk Factor for Dementia: A Narrative Review.

This narrative review examines infectious diseases as modifiable risk factors for dementia, particularly in the context of an aging global population. As the prevalence of Alzheimer's disease and related dementias is expected to rise, prevention has become increasingly important due to the limited efficacy of current treatments. Emerging evidence links specific infectious diseases to increased dementia risk, possibly through mechanisms like neuroinflammation and disruption to normal cell function. Here, we review findings on how viral and bacterial infections contribute to dementia and explore potentially preventive measures, including vaccinations and antiviral treatments. Studies indicate that vaccinations against influenza, herpes zoster, and hepatitis, as well as antiviral treatments targeting human herpesvirus, could reduce the incidence of dementia. Additionally, non-pharmaceutical interventions during pandemics and in long-term care settings are highlighted as effective strategies for reducing the spread of infectious diseases, potentially lowering dementia risk. Putative mechanisms underlying the protective effects of these interventions suggest that reducing systemic inflammation may be important to their efficacy. While the currently available evidence suggests at best an association between some infectious diseases and dementia, this narrative review emphasizes the need to incorporate infectious disease prevention into broader public health strategies to potentially mitigate the growing burden of dementia. Further research is required to explore these preventive measures across diverse populations and to deepen our understanding of the biological mechanisms involved.

Prevalence of Kaposi sarcoma in the United States: SEER cross-sectional study

Primary Kaposi sarcoma (KS) is a rare cancer caused by human herpesvirus-8 that most often affects people with compromised immune systems. Since knowledge of the relationship between disease and sociodemographic factors contributes to the development of precision medicine, we investigated the prevalence of KS within the US population. Using SEER, we found that the Black population had the highest prevalence rate in 2018 compared to other racial groups. Prevalence peaked in the 50 to 54 and 55 to 59 age groups, with another peak in the 80 to 84 age group.

Comparative Efficacy of Different Pharmacological Treatments for Pityriasis Rosea: A Network Meta-Analysis.

Background/Objectives: Pityriasis rosea (PR) is a self-limiting exanthematous disease associated with the endogenous reactivation of human herpesviruses (HHV)-6 and HHV-7. Classically, the lesions gradually resolve, leaving no sequelae. Therefore, the best treatment is reassuring the patient and suggesting a resting period. However, atypical PR cases characterized by extensive, persistent lesions and systemic symptoms may impact the patient's quality of life, and, therefore, a treatment can be prescribed. There is limited evidence on the comparative effectiveness of pharmacological treatments for PR; therefore, we performed a network meta-analysis to compare these interventions. Methods: Overall, 12 randomized control trials (RCTs) were identified. The outcomes were itch resolution and rash improvement. Results were expressed as risk ratio (RR) and 95% confidence interval (CI). We also calculated the relative ranking of the interventions for achieving the aforementioned outcomes as their surface under the cumulative ranking (SUCRA). Results: On network meta-analysis, only oral steroids and the combination of oral steroids+antihistamine resulted significantly superior to the placebo in terms of itch resolution (RR 0.44, CI 0.27-0.72 and RR 0.47, CI 0.22-0.99). Oral steroids resulted in the best treatment (SUCRA 0.90) for itch resolution. In terms of rash improvement, only acyclovir and erythromycin resulted significantly superior to placebo (RR 2.55, CI 1.81-3.58; and RR 1.69, CI 1.23-2.33), and acyclovir outperformed all the other tested interventions. Consequently, acyclovir ranked as the best intervention (SUCRA score 0.92). Conclusions: Acyclovir represents the best option for patients with PR that have extensive, persistent lesions or systemic symptoms. Steroids and antihistamines seemed the best treatment for itch resolution.

Challenges of Congenital HHV6 Infection Diagnosis and Treatment: Two Case Reports and Literature Review

Introduction: Congenital human herpesvirus 6 (HHV6) infection occurs in 1% of the general population and may result from the transmission of an inherited chromosomally integrated HHV6 (iciHHV6) or transplacental infection. It is mostly asymptomatic. Case reports: Case 1: a 29th-week-old female preterm newborn, admitted to the neonatal intensive care unit, became clinically unstable and irritable on the 20th day of hospitalization. Cranial ultrasound, revealed a significant posthemorrhagic tetraventricular dilation, with signs of ventriculitis. Investigations revealed HHV6 positivity on cerebrospinal fluid polymerase chain reaction multiplex panel testing and HHV6-DNA high viral loads in plasma samples. Case 2: a female late preterm newborn was admitted to the neonatal intensive care unit due to early-onset sepsis. Investigations revealed group B streptococcus positive blood cultures and cerebrospinal fluid HHV6 positivity on polymerase chain reaction multiplex panel testing, with negative bacterial culture. After 3 days of adequate antibiotic treatment, she maintained persistent moaning, which motivated a cranial ultrasound, revealing mild brain edema. Clinical improvement was observed only after beginning antiviral treatment in both newborns. Due to the persistency of high viral loads in both cases, despite antiviral treatment and clinical improvement, an iciHHV6 was suspected and posteriorly confirmed. Discussion/conclusion: Congenital iciHHV6 infection diagnosis is challenging because the presence of an iciHHV6 results in persistently high viral loads, even in the absence of active infection. Only a few diagnostic techniques can confirm active replication; unfortunately, these are not available in most countries. The decision to initiate antiviral treatment should be based on clinical judgment. Better ways for the diagnosis of active infection are needed.