Search Results (40)

Background: Congenital cytomegalovirus (cCMV) infection is a leading cause of neonatal morbidity. This retrospective study aimed to evaluate the efficacy of valacyclovir in reducing vertical transmission after primary maternal CMV infection and to assess the diagnostic performance of amniocentesis and prenatal imaging. Methods: Eighty-two pregnant women with confirmed primary CMV infection were included. Maternal CMV serology and viral DNA were assessed in blood and urine, with standardized prenatal care including serial ultrasound examinations and fetal MRI when indicated. Amniocentesis was offered to confirm fetal infection. Valacyclovir (8 g/day) was administered before 24 weeks’ gestation, and neonatal infection was diagnosed by CMV DNA detection in urine at birth. Statistical analyses were performed using SPSS version 27.0. Results: Most infections (62.2%) were diagnosed in the first trimester. Valacyclovir was administered in 97.6% of cases, and amniocentesis was performed in 81.7%, with CMV DNA detected in 19.4%. Among 74 live births, 23% of neonates were CMV-positive and 6.8% symptomatic. Seven infected neonates had negative amniocentesis (false-negative rate, 13.2%). Prenatal ultrasound and MRI failed to detect abnormalities in symptomatic cases. Conclusions: Valacyclovir may reduce, but does not eliminate, the risk of cCMV transmission. Negative amniocentesis does not fully exclude fetal infection, highlighting postnatal follow-up. Full article

Cytomegalovirus (CMV) is the most common infectious cause of congenital malformations, often presenting with atypical clinical findings. Fetal damage is most severe following primary maternal infection during the first trimester of pregnancy, with the likelihood of transmission increasing with pregnancy advancement. CMV damage may continue to intensify during the early postnatal years. In this narrative review we summarized publications from the last 30 years addressing the epidemiology, diagnosis, prevention and treatment of CMV in pregnancy, with a special emphasis on embryonic and fetal damage. Substantial progress has been made in the diagnosis and treatment of CMV infection during pregnancy, warranting a reconsideration of current clinical approaches. Assessment of viral load enables prediction of fetal infection; its reduction by maternal treatment with valacyclovir may lower both the rate and severity of transmission. Confirmed fetal infection can be diagnosed by amniocentesis and viral DNA detection. Clinical manifestations in infants may be evident at birth (cCMV) or gradually emerge during the first years. The most common fetal damage is hearing loss alongside a variety of brain lesions resulting in significant neurological deficits, including intellectual impairment. Brain involvement is diagnosed by ultrasound or magnetic resonance imaging (MRI). Pharmacological treatment with ganciclovir or valganciclovir, if initiated early after birth, can slow the progression of hearing loss and may ameliorate other neurological and neurodevelopmental deficits. As of today, there is no approved CMV vaccine for prevention. The mRNA-1647’s vaccine, currently in phase 3 clinical trial, appears promising. These advances underscore the need for screening pregnant women in the first trimester and newborn infants of mothers suspected of having CMV infection. Neurodevelopmental follow up for several years, including hearing and visual assessment, is advised in all infants positive for CMV. Infants with clinical manifestations should be offered treatment as early as possible following diagnosis of cCMV. Full article

Background: To repurpose carbutamide (CBT), a discontinued sulfonylurea-class anti-diabetic drug, as an anti-inflammatory bowel disease (IBD) drug, CBT azo-linked with salicylic acid (CAA) was designed and synthesized as a colon-specific prodrug to co-release CBT and mesalazine (5-ASA) selectively in the large intestine. Methods: CAA exhibited reduced lipophilicity and decreased transintestinal transport compared to CBT, as shown in an ex vivo experiment using isolated rat jejunal segments. It also underwent cleavage into CBT and 5-ASA when incubated with cecal contents of rats. Additionally, oral administration of CAA and Sulfasalazine (SSZ), a colon-specific prodrug of 5-ASA currently used for IBD treatment, resulted in similar levels of 5-ASA accumulation in the rat cecal region. Results: In a dinitrobenzene sulfonic acid-triggered colitis model in rats, CAA produced a more pronounced improvement in colon injury and inflammation than SSZ. Furthermore, rectal co-administration of CBT and 5-ASA conferred enhanced protective outcomes compared to monotherapy with either agent alone, suggesting a combined anticolitic action. The two drugs also jointly suppressed valacyclovir uptake via peptide transporter 1 (PepT1) in the distal colon, supporting PepT1 as a target contributing to their combined anticolitic effect. Unlike CBT, which significantly reduced blood glucose following oral administration, equimolar administration of CAA did not alter glycemic levels, consistent with reduced systemic exposure to CBT. Conclusions: In conclusion, CAA functions as a colon-specific mutual prodrug that surpasses SSZ in anticolitic performance while minimizing hypoglycemia risk, thus facilitating the repurposing of CBT as a treatment for IBD. Full article

Infectious agents account for millions of deaths every year. The Herpes Simplex Viruses (HSVs) are large double-stranded DNA viruses that infect more than 90% of the human population and can establish life-long latency in human hosts. Currently, effective FDA approved anti-herpetic drugs include acyclovir and later-generation derivatives (valacyclovir and famciclovir), which inhibit viral DNA synthesis. In previous work, we demonstrated that the small molecule Ruvidar^® could inhibit numerous pathogenic human viruses when added to solutions of viruses both with and without light activation. In these experiments, we evaluated the ability of Ruvidar^® to restrict HSV-1 replication in Vero cells, both by itself and in combination with acyclovir and metformin in the absence of light activation to mimic deep tissue. Ruvidar^® successfully inhibited HSV-1 replication at significantly lower concentrations and more effectively than either acyclovir or metformin alone. We also discovered additive and synergistic anti-HSV-1 effects when combinational therapy was tested. Ruvidar^® also restricted HSV-1 replication in human U251 glioblastoma astrocytoma cells, remained highly effective against acyclovir-resistant HSV-1 mutants, and protected infected cells from virus-induced cytopathology. Full article

Herpes Simplex Virus (HSV) infections, caused primarily by HSV-1 and HSV-2, are among the most prevalent viral diseases worldwide, with recurrent manifestations that significantly affect quality of life. Therapeutic strategies include both topical and systemic interventions, each with distinct goals. This systematic review was conducted according to PRISMA guidelines. A comprehensive search of PubMed, Scopus, and Web of Science (2005–2025) identified studies evaluating topical or systemic treatments for HSV. Eligible studies included randomized controlled trials and observational studies reporting validated clinical outcomes. Topical treatments, including acyclovir cream, docosanol, and newer formulations, primarily reduce lesion duration and alleviate local symptoms when applied early. These interventions have limited systemic absorption and generally do not influence recurrence frequency. Novel delivery methods and combination strategies, such as acyclovir–hydrocortisone formulations or photodynamic therapy, may enhance local efficacy and symptom control. Systemic Therapies: Systemic antivirals, such as acyclovir, valacyclovir, and famciclovir, target both lesion resolution and recurrence prevention. Evidence from randomized trials supports their use for episodic and suppressive therapy, including short-course, high-dose regimens that improve adherence while controlling symptoms. Systemic therapy is particularly indicated for recurrent, disseminated, or high-risk infections. Topical and systemic therapies serve complementary roles in HSV management. Topical agents are useful for localized or initial episodes, while systemic therapy addresses broader clinical objectives, including recurrence reduction. Future research should focus on mechanism-based therapies, novel delivery systems, and standardized outcome measures to guide personalized treatment strategies. Emerging therapies targeting viral latency, immune modulation, and gene-editing technologies hold promise for long-term suppression and personalized management of HSV infections. Full article

Herpesviruses are prevalent pathogens affecting lactating women, yet the safety and efficacy of antiviral therapies in this population remain underexplored. This systematic review evaluates the safety and efficacy of antiviral therapies for Herpesviridae infections, including CMV, VZV, EBV, and HSV, in lactating mothers. A comprehensive literature search was conducted using PubMed, Cochrane Library, and Scopus, alongside specialized databases like LactMed. Twelve studies were included, comprising three randomized control trials, five observational studies, and four case reports. Quality assessment using Joanna Briggs Institute tools indicated moderate-to-high methodological quality for the trials and consistent strengths in case reports, though some limitations were noted. Results suggest that antiviral agents, particularly acyclovir and valacyclovir, are generally safe for breastfeeding mothers, with minimal infant exposure and low risk of adverse effects. However, the virologic benefits appear modest, and most studies focused on HIV co-infected populations, limiting generalizability to lactating women without HIV. In conclusion, while current evidence supports the use of specific antivirals during lactation, there is a critical need for further research to address existing knowledge gaps and optimize treatment strategies for both mothers and infants. Full article

Cytomegalovirus (CMV) infection during pregnancy poses significant maternal and fetal health risks. Valacyclovir, an antiviral drug, has been explored as a therapeutic option for managing primary CMV infections in pregnant women. This study investigates the effects of valacyclovir therapy on immune response maturation against CMV, maternal antibody levels, and viral replication during treatment. We conducted a retrospective observational study involving pregnant women diagnosed with primary CMV infection and presenting in utero infection who received high-dose valacyclovir therapy (8 g/day). A group started the therapy at diagnosis, while another group started only after positive amniocentesis. Maternal antibody levels (IgM, IgG, and IgG avidity) and PCR for CMV testing (in blood, urine, and saliva) were measured longitudinally during the second and third trimesters. Our findings indicate that early valacyclovir therapy is related to lower avidity levels over time and a delay in reaching a high IgG avidity level (18.22 ± 1.21 weeks) compared to the patients who started Valacyclovir during the second trimester after positive amniocentesis (14.52 ± 1.64 weeks; p = 0.066). The therapy does not condition the overall concentration of maternal CMV-specific IgM and IgG. While high-dose VCV does not directly target the mechanism of IgG avidity maturation, it can interfere with this process by reducing the viral load and antigen presentation, influencing IgG avidity maturation. Further research is needed to elucidate the long-term implications of potential immunological modulation induced by Valacyclovir and to optimize early diagnosis and the right treatment protocol during pregnancy. Full article

Our previous study showed that the Epstein–Barr virus (EBV) may be the etiology for some patients with interstitial cystitis/bladder pain syndrome (IC/BPS); hence, the current study aimed to investigate the urinary viral spectrum in patients with IC/BPS and the clinical efficacy of valacyclovir. Twenty-eight patients were prospectively enrolled for valacyclovir 500 mg twice a day for 4 weeks. Urine samples were collected from IC/BPS patients and 30 controls. The primary outcome was the difference in the visual analog scale (VAS) pain score, and secondary outcomes included changes in the urinary viral spectrum and urinary inflammatory cytokine level (ClinicalTrials.gov Identifier: NCT05094414). Urinary EBV was detected in 14.2% IC/BPS patients but not in the controls. Urinary John Cunningham virus and BK virus were detected in 18 (64.3%) and 2 (7.1%) patients with IC/BPS, respectively, with similar prevalences noted for the controls. No cytomegalovirus, varicella-zoster virus, or herpes simplex virus was detected in the urine samples. The VAS pain score in patients with IC/BPS significantly decreased after 4 weeks (from 7.5 [5.52–9.0] to 5 [1.5–6.0], p = 0.0003). Urinary EBV was undetectable in any sample after valacyclovir treatment, and the decreases in urinary interleukin (IL)-1β (from 0.66 [0.55–0.82] pg/mL to 0.58 [0.55–0.64] pg/mL, p = 0.0034), IL-8 (from 6.81 [2.38 to 29.1] pg/mL to 4.33 [1.53–11.04] pg/mL, p = 0.0361), IL-10 (from 1.06 [0.94–1.18] pg/mL to 0.92 [0.88–1.02], p = 0.0086), and tumor necrosis factor-α (from 1.61 [1.50–1.72] pg/mL to 1.50 [1.44–1.55] pg/mL, p = 0.0079) were significant. Valacyclovir could relieve bladder pain, eliminate urinary EBV, and reduce bladder inflammation. Full article

Cytomegalovirus (CMV) infection is the most common congenital infection worldwide, affecting between 0.7% and 1% of all live births. Approximately 11% of infected newborns are symptomatic at birth, and between 30% and 40% of these are at risk of developing long-term neurological sequelae. Until recently, the lack of an effective treatment did not justify universal testing of pregnant women. In recent years, however, valacyclovir at a dose of 8 g/day has been shown to be effective in preventing vertical transmission, and ganciclovir has been shown to be effective in preventing long-term sequelae in the treatment of symptomatic neonates. The aim of this article is to review congenital CMV infection, from its epidemiology to its treatment, using the most recent studies in the literature, and to help in the decision to modify protocols for universal testing of pregnant women according to the possibilities of each locality. Full article

Prediction of high-risk events amongst patients with mental disorders is critical for personalized interventions. We developed DeepBiomarker2 by leveraging deep learning and natural language processing to analyze lab tests, medication use, diagnosis, social determinants of health (SDoH) parameters, and psychotherapy for outcome prediction. To increase the model’s interpretability, we further refined our contribution analysis to identify key features by scaling with a factor from a reference feature. We applied DeepBiomarker2 to analyze the EMR data of 38,807 patients from the University of Pittsburgh Medical Center diagnosed with post-traumatic stress disorder (PTSD) to determine their risk of developing alcohol and substance use disorder (ASUD). DeepBiomarker2 predicted whether a PTSD patient would have a diagnosis of ASUD within the following 3 months with an average c-statistic (receiver operating characteristic AUC) of 0.93 and average F1 score, precision, and recall of 0.880, 0.895, and 0.866 in the test sets, respectively. Our study found that the medications clindamycin, enalapril, penicillin, valacyclovir, Xarelto/rivaroxaban, moxifloxacin, and atropine and the SDoH parameters access to psychotherapy, living in zip codes with a high normalized vegetative index, Gini index, and low-income segregation may have potential to reduce the risk of ASUDs in PTSD. In conclusion, the integration of SDoH information, coupled with the refined feature contribution analysis, empowers DeepBiomarker2 to accurately predict ASUD risk. Moreover, the model can further identify potential indicators of increased risk along with medications with beneficial effects. Full article

Multiple sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system (CNS). Microbes, including bacteria and certain viruses, particularly Epstein–Barr virus (EBV), have been linked to the pathogenesis of MS. While there is currently no cure for MS, antibiotics and antivirals have been studied as potential treatment options due to their immunomodulatory ability that results in the regulation of the immune process. The current issue addressed in this systematic review is the effect of antimicrobials, including antibiotics, antivirals, and antiparasitic agents in animals and humans. We performed a comprehensive search of PubMed, Google Scholar, and Scopus for articles on antimicrobials in experimental autoimmune encephalomyelitis animal models of MS, as well as in people with MS (pwMS). In animal models, antibiotics tested included beta-lactams, minocycline, rapamycin, macrolides, and doxycycline. Antivirals included acyclovir, valacyclovir, and ganciclovir. Hydroxychloroquine was the only antiparasitic that was tested. In pwMS, we identified a total of 24 studies, 17 of them relevant to antibiotics, 6 to antivirals, and 1 relevant to antiparasitic hydroxychloroquine. While the effect of antimicrobials in animal models was promising, only minocycline and hydroxychloroquine improved outcome measures in pwMS. No favorable effect of the antivirals in humans has been observed yet. The number and size of clinical trials testing antimicrobials have been limited. Large, multicenter, well-designed studies are needed to further evaluate the effect of antimicrobials in MS. Full article

Herpes simplex virus 1 (HSV-1) is double-stranded DNA virus that belongs to the Orthoherpesviridae family. It causes serious neurological diseases of the central nervous system, such as encephalitis. The current U.S. Food and Drug Administration (FDA)-approved drugs for preventing HSV-1 infection include acyclovir (ACV) and valacyclovir; however, their long-term use causes severe side effects and often results in the emergence of drug-resistant strains. Therefore, it is important to discover new antiviral agents that are safe and effective against HSV-1 infection. Korean chestnut honey (KCH) has various pharmacological activities, such as antioxidant, antibacterial, and anti-inflammation effects; however, antiviral effects against HSV-1 have not yet been reported. Therefore, we determined the antiviral activity and mechanism of action of KCH after HSV-1 infection on the cellular level. KCH inhibited the HSV-1 infection of host cells through binding and virucidal steps. KCH decreased the production of reactive oxygen species (ROS) and calcium (Ca²⁺) following HSV-1 infection and suppressed the production of inflammatory cytokines by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-кB) activity. Furthermore, we found that KCH inhibited the expression of the nod-like receptor protein 3 (NLRP3) inflammasome during HSV-1 infection. Taken together, the antiviral effects of KCH occur through multiple targets, including the inhibition of viral replication and the ROS-mediated NLRP3 inflammasome pathway. Our findings suggest that KCH has potential for the treatment of HSV-1 infection and related diseases. Full article

Objectives: Cytomegalovirus (CMV) infection is a significant health concern affecting numerous expectant mothers across the globe. CMV is the leading cause of health problems and developmental delays among infected infants. Notably, this study examines CMV infection in pregnancy, its management, prevention mechanisms, and treatment options. Methods: Specifically, information from the Cochrane Library, PUBMED, Wiley Online, Science Direct, and Taylor Francis databases were reviewed along with additional records identified through the register, the Google Scholar search engine. Based on the search, 21 articles were identified for systematic review. Results: A total of six randomized controlled trials (RCTs) were utilized for a meta-analytic review. As heterogeneity was substantial, the random effects model was used for meta-analysis. Utilizing the random-effects model, the restricted maximum likelihood (REML) approach, the estimate of effect size (d = −0.479, 95% CI = −0.977 to 0.019, p = 0.060) suggests the results are not statistically significant, so it cannot be inferred that the prevention methods used were effective, despite an inverse relationship between treatment and number of infected cases. The findings indicated that several techniques are used to prevent, diagnose, and manage CMV infection during pregnancy, including proper hygiene, ultrasound examination (US), magnetic resonance imaging (MRI), amniocentesis, viremia, hyperimmunoglobulin (HIG), and valacyclovir (VACV). Conclusions: The current review has significant implications for addressing CMV infection in pregnancy. Specifically, it provides valuable findings on contemporary management interventions to prevent and treat CMV infection among expectant mothers. Therefore, it allows relevant stakeholders to address these critical health concerns and understand the effectiveness of the proposed prevention and treatment options. Full article

Human Cytomegalovirus (HCMV) is a ubiquitous member of the Herpesviridae family, responsible for the most common congenital viral infection—congenital Cytomegalovirus (cCMV) infection. While a majority of HCMV infections in children and adults are asymptomatic, HCMV is well known to cause severe infections in the immunocompromised individual and maternal infections with variable long-term sequelae after maternal–fetal transmission with primary or nonprimary infections. HCMV seroprevalence and cCMV incidence vary by geographic area and demographic characteristics like race and socioeconomic status. While cCMV birth prevalence ranges from 0.2% to 6% in different parts of the world, it is influenced by regional HCMV seroprevalence rates. HCMV screening during pregnancy is not routinely offered due to lack of awareness, hurdles to accurate diagnosis, and lack of well-established effective treatment options during pregnancy. This review will focus on antiviral treatment options currently available for use during pregnancy and in the newborn period for the treatment of maternal and congenital HCMV infections. Full article

Valacyclovir (VACV) was developed as a prodrug of the most common anti-herpetic drug Acyclovir (ACV), aiming to enhance its bioavailability. Nevertheless, prolonged VACV oral treatment may lead to the development of important side effects. Nanotechnology-based formulations for vaginal administration represent a promising approach to increase the concentration of the drug at the site of infection, limiting systemic drug exposure and reducing systemic toxicity. In this study, VACV-loaded nanodroplet (ND) formulations, optimized for vaginal delivery, were designed. Cell-based assays were then carried out to evaluate the antiviral activity of VACV loaded in the ND system. The chitosan-shelled ND exhibited an average diameter of about 400 nm and a VACV encapsulation efficiency of approximately 91% and was characterized by a prolonged and sustained release of VACV. Moreover, a modification of chitosan shell with an anionic cyclodextrin, sulfobutyl ether β-cyclodextrin (SBEβCD), as a physical cross-linker, increased the stability and mucoadhesion capability of the nanosystem. Biological experiments showed that SBEβCD-chitosan NDs enhanced VACV antiviral activity against the herpes simplex viruses type 1 and 2, most likely due to the long-term controlled release of VACV loaded in the ND and an improved delivery of the drug in sub-cellular compartments. Full article