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Open Forum Infectious Diseases May 2024We present an immunocompromised patient with a multiresistant herpes simplex virus-1 reactivation with a rare mutation (A605V) in the viral DNA polymerase gene....
Reactivation of Multidrug-Resistant HSV-1 in a Post-Allogenic Hematopoietic Stem Cell Transplant Patient: Dynamic Detection of the Rare A605V Mutation by Next-Generation Sequencing.
We present an immunocompromised patient with a multiresistant herpes simplex virus-1 reactivation with a rare mutation (A605V) in the viral DNA polymerase gene. Next-generation sequencing suggests the presence of multiple drug-resistant strains before treatment and altered ratios during treatment, affecting the clinical response to aciclovir and foscarnet.
PubMed: 38798899
DOI: 10.1093/ofid/ofae250 -
Narra J Apr 2024Numerous prior studies have identified therapeutic targets that could effectively combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection,...
Numerous prior studies have identified therapeutic targets that could effectively combat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, including the angiotensin-converting enzyme 2 (ACE2) receptor, RNA-dependent RNA polymerase (RdRp), and Main protease (Mpro). In parallel, antiviral compounds like abacavir, acyclovir, adefovir, amantadine, amprenavir, darunavir, didanosine, oseltamivir, penciclovir, and tenofovir are under investigation for their potential in drug repurposing to address this infection. The aim of the study was to determine the effect of modifying the functional groups of the aforementioned antivirals in silico. Using the genetic optimization for ligand docking algorithm on software Maestro (version 11.1), the modified antivirals were docked onto ACE2 receptor, RdRp, and Mpro. Using QuickProp (Maestro v11.1), PASS (prediction of activity spectra for the substances), and altogether with SwissADME, the ADMET (absorption, distribution, metabolism, excretion, and toxicity) of the modified antivirals, as well as their bioavailability and the predicted activity spectra, were determined. Discovery studio software was used to undertake post-docking analysis. Among the 10 antivirals, N(CH) derivative of darunavir, N(CH) derivative of amprenavir and NCH derivative of darunavir exhibited best binding affinities with ACE2 receptor (docking scores: -10.333, -9.527 and -9.695 kJ/mol, respectively). Moreover, NCH derivative of abacavir (-6.506 kJ/mol), NO derivative of didanosine (-6.877 kJ/mol), NCH derivative of darunavir (-7.618 kJ/mol) exerted promising affinity to Mpro. In conclusion, the results of the in silico screenings can serve as a useful information for future experimental works.
Topics: Antiviral Agents; Humans; Molecular Docking Simulation; SARS-CoV-2; Drug Repositioning; COVID-19 Drug Treatment; Models, Molecular; COVID-19; Angiotensin-Converting Enzyme 2; Pneumonia, Viral; Pandemics
PubMed: 38798846
DOI: 10.52225/narra.v4i1.319 -
Viruses May 2024Epidemiological studies have shown that HPV-related diseases are the most prevalent sexually transmitted infections. In this context, this report will present various... (Review)
Review
Epidemiological studies have shown that HPV-related diseases are the most prevalent sexually transmitted infections. In this context, this report will present various clinical cases demonstrating the effectiveness of Acyclovir (ACV) or its prodrug Valaciclovir (VCV), both acyclic guanosine analogs commonly used for the treatment of HHV-1 and HHV-2, for the treatment of HPV-related diseases. The report shows the remission of five cases of penile condyloma and a case of remission in a woman affected by cervical and vaginal condylomas and a vulvar giant condyloma acuminate of Buschke and Lowenstein. The literature review shows that ACV is effective in treating skin warts when administered orally, topically, and intralesionally, suggesting its therapeutic potential in other diseases associated with HPV. ACV was also used successfully as an adjuvant therapy for juvenile and adult forms of laryngeal papillomatosis, also known as recurrent respiratory papillomatosis, prolonging the patient's symptom-free periods. Although the prevention of HPV infections is certainly achieved with the HPV vaccine, ACV and VCV have shown to be effective even against genotypes not included in the current vaccine and can be helpful for those problematic clinical cases involving unvaccinated individuals, immunocompromised patients, people who live with HIV, or non-responders to the vaccine. We and others concluded that randomized clinical trials are necessary to determine the efficacy of ACV and VCV for HPV-related diseases.
Topics: Adult; Female; Humans; Male; Acyclovir; Antiviral Agents; Papillomavirus Infections; Treatment Outcome; Valacyclovir
PubMed: 38793636
DOI: 10.3390/v16050756 -
Viruses May 2024Equid herpesvirus 4 (EHV-4) is a common respiratory pathogen in horses. It sporadically induces abortion or neonatal death. Although its contribution in neurological...
Equid herpesvirus 4 (EHV-4) is a common respiratory pathogen in horses. It sporadically induces abortion or neonatal death. Although its contribution in neurological disorders is not clearly demonstrated, there is a strong suspicion of its involvement. Despite preventive treatments using vaccines against EHV-1/EHV-4, the resurgence of alpha-EHV infection still constitutes an important threat to the horse industry. Yet very few studies have been conducted on the search for antiviral molecules against EHV-4. A screening of 42 antiviral compounds was performed in vitro on equine fibroblast cells infected with the EHV-4 405/76 reference strain (VR2230). The formation of cytopathic effects was monitored by real-time cell analysis (RTCA), and the viral load was quantified by quantitative PCR. Aciclovir, the most widely used antiviral against alpha-herpesviruses in vivo, does not appear to be effective against EHV-4 in vitro. Potential antiviral activities were confirmed for eight molecules (idoxuridine, vidarabine, pritelivir, cidofovir, valganciclovir, ganciclovir, aphidicolin, and decitabine). Decitabine demonstrates the highest efficacy against EHV-4 in vitro. Transcriptomic analysis revealed the up-regulation of various genes implicated in interferon (IFN) response, suggesting that decitabine triggers the immune antiviral pathway.
Topics: Animals; Antiviral Agents; Horses; Decitabine; Immunity, Innate; Herpesvirus 4, Equid; Fibroblasts; Herpesviridae Infections; Horse Diseases; Viral Load; Cell Line; Virus Replication; Drug Evaluation, Preclinical
PubMed: 38793627
DOI: 10.3390/v16050746 -
Transplant International : Official... 2024Valganciclovir (VGC) is administered as prophylaxis to kidney transplant recipients (KTR) CMV donor (D)+/recipient (R)- and CMV R+ after thymoglobulin-induction (R+/TG).... (Observational Study)
Observational Study
Valganciclovir (VGC) is administered as prophylaxis to kidney transplant recipients (KTR) CMV donor (D)+/recipient (R)- and CMV R+ after thymoglobulin-induction (R+/TG). Although VGC dose adjustments based on renal function are recommended, there is paucity of real-life data on VGC dosing and associations with clinical outcomes. This is a retrospective Swiss Transplant Cohort Study-embedded observational study, including all adult D+/R- and R+/TG KTR between 2010 and 2020, who received prophylaxis with VGC. The primary objective was to describe the proportion of inappropriately (under- or over-) dosed VGC week-entries. Secondary objectives included breakthrough clinically significant CMV infection (csCMVi) and potential associations between breakthrough-csCMVi and cytopenias with VGC dosing. Among 178 KTR, 131 (73.6%) patients had ≥2 week-entries for the longitudinal data of interest and were included in the outcome analysis, with 1,032 VGC dose week-entries. Overall, 460/1,032 (44.6%) were appropriately dosed, while 234/1,032 (22.7%) and 338/1,032 (32.8%) were under- and over-dosed, respectively. Nineteen (14.5%) patients had a breakthrough-csCMVi, without any associations identified with VCG dosing ( = 0.44). Unlike other cytopenias, a significant association between VGC overdosing and lymphopenia (OR 5.27, 95% CI 1.71-16.22, = 0.004) was shown. VGC prophylaxis in KTR is frequently inappropriately dosed, albeit without meaningful clinical associations, neither in terms of efficacy nor safety.
Topics: Humans; Valganciclovir; Kidney Transplantation; Male; Cytomegalovirus Infections; Female; Retrospective Studies; Middle Aged; Antiviral Agents; Adult; Aged; Kidney; Transplant Recipients
PubMed: 38784442
DOI: 10.3389/ti.2024.12712 -
Pharmacology Research & Perspectives Jun 2024Aciclovir is considered the first-line treatment against Herpes simplex virus (HSV) infections in new-borns and infants. As renal excretion is the major route of...
Aciclovir is considered the first-line treatment against Herpes simplex virus (HSV) infections in new-borns and infants. As renal excretion is the major route of elimination, in renally-impaired patients, aciclovir doses are adjusted according to the degree of impairment. However, limited attention has been given to the implications of immature renal function or dysfunction due to the viral disease itself. The aim of this investigation was to characterize the pharmacokinetics of aciclovir taking into account maturation and disease processes in the neonatal population. Pharmacokinetic data obtained from 2 previously published clinical trials (n = 28) were analyzed using a nonlinear mixed effects modeling approach. Post-menstrual age (PMA) and creatinine clearance (CL) were assessed as descriptors of maturation and renal function. Simulation scenarios were also implemented to illustrate the use of pharmacokinetic data to extrapolate efficacy from adults. Aciclovir pharmacokinetics was described by a one-compartment model with first-order elimination. Body weight and diagnosis (systemic infection) were statistically significant covariates on the volume of distribution, whereas body weight, CL and PMA had a significant effect on clearance. Median clearance varied from 0.2 to 1.0 L/h in subjects with PMA <34 or ≥34 weeks, respectively. Population estimate for volume of distribution was 1.93 L with systemic infection increasing this value by almost 3-fold (2.67 times higher). A suitable model parameterization was identified, which discriminates the effects of developmental growth, maturation, and organ function. Exposure to aciclovir was found to increase with decreasing PMA and renal function (CL), suggesting different dosing requirement for pre-term neonates.
Topics: Humans; Acyclovir; Infant, Newborn; Antiviral Agents; Herpes Simplex; Female; Male; Models, Biological; Creatinine; Dose-Response Relationship, Drug; Metabolic Clearance Rate; Computer Simulation
PubMed: 38775304
DOI: 10.1002/prp2.1193 -
BMC Ophthalmology May 2024Only seven cases of ocular Spiroplasma infection have been reported to date, all presenting as congenital cataracts with concomitant intraocular inflammation. We...
BACKGROUND
Only seven cases of ocular Spiroplasma infection have been reported to date, all presenting as congenital cataracts with concomitant intraocular inflammation. We describe the first case of Spiroplasma infection initially presenting as a corneal infiltrate.
CASE PRESENTATION
A 1-month-old girl was referred for a corneal infiltrate in the left eye. She presented in our hospital with unilateral keratouveitis. Examination showed a stromal corneal infiltrate and dense white keratic precipitates in the left eye. Herpetic keratouveitis was suspected and intravenous acyclovir therapy was initiated. Two weeks later, the inflammation in the left eye persisted and was also noticed in the right eye. Acute angle-closure glaucoma and a cataract with dilated iris vessels extending onto the anterior lens capsule developed in the left eye. The inflammation resolved after treatment with azithromycin. Iridectomy, synechiolysis and lensectomy were performed. Bacterial metagenomic sequencing (16 S rRNA) and transmission electron microscopy revealed Spiroplasma ixodetis species in lens aspirates and biopsy. Consequently, a diagnosis of bilateral Spiroplasma uveitis was made.
CONCLUSIONS
In cases of congenital cataract with concomitant intraocular inflammation, Spiroplasma infection should be considered. The purpose of this case report is to raise awareness of congenital Spiroplasma infection as a cause of severe keratouveitis, cataract and angle-closure glaucoma in newborns. Performing molecular testing on lens aspirates is essential to confirm diagnosis. Systemic macrolides are suggested as the mainstay of treatment.
Topics: Humans; Female; Eye Infections, Bacterial; Cataract; Uveitis; Spiroplasma; Keratitis; Infant, Newborn; Anti-Bacterial Agents; Infant
PubMed: 38773506
DOI: 10.1186/s12886-024-03480-z -
Cureus Apr 2024Neuroretinitis is a potentially vision-threatening condition distinguished by swelling of the optic disc followed by the emergence of a macular star pattern. The...
Neuroretinitis is a potentially vision-threatening condition distinguished by swelling of the optic disc followed by the emergence of a macular star pattern. The majority of these clinical observations are typically linked to infections caused by bacteria, parasites, or viruses. We report a case of dual infections in neuroretinitis complicated with severe macular edema. A 49-year-old lady presented with sudden onset left eye blurring of vision of one-week duration. Visual acuity was 6/6 in the right eye and 6/60 in the left eye. There was a left positive relative afferent pupillary defect with impaired optic nerve functions. A fundoscopy of the left eye showed optic disc swelling with a macular star. The right optic disc was also swollen. Vasculitis changes were observed in both posterior poles. The ocular coherence tomography of the left eye revealed the existence of macular edema, subretinal fluids, and an epiretinal membrane that extended from the optic disc to the fovea. Serological examinations were positive for toxoplasma and herpes simplex virus type 1. The patient was started on oral azithromycin, oral acyclovir, and oral corticosteroids. Left macular edema persisted despite the treatment. The patient was given a trial of a single injection of intravitreal ranibizumab. A remarkable reduction of subretinal fluids was seen post-intravitreal injection and continuation of medications. Intravitreal ranibizumab has shown significant outcomes in neuroretinitis with severe macula edema.
PubMed: 38765323
DOI: 10.7759/cureus.58444 -
Cureus Apr 2024Atopic dermatitis (AD) characterized by pruritus and eczematous lesions makes individuals susceptible to various viral and bacterial infections. Eczema herpeticum (EH),...
Atopic dermatitis (AD) characterized by pruritus and eczematous lesions makes individuals susceptible to various viral and bacterial infections. Eczema herpeticum (EH), also known as Kaposi's varicelliform eruption, is a severe herpes simplex virus infection that can be observed in individuals with AD. EH manifests with monomorphic vesicles and "punched-out" erosions accompanied by hemorrhagic crusts, primarily affecting eczematous areas. Misdiagnosis, often as impetigo, can lead to severe complications and even death. Timely diagnosis and treatment with acyclovir are crucial to avert these outcomes. Here we present a case of a 19-year-old male with AD who presented with a monomorphic vesicular rash.
PubMed: 38738145
DOI: 10.7759/cureus.58102 -
Indian Pediatrics May 2024To describe the utility of film array meningoencephalitis (FAME) panel in the management of children with acute encephalitis syndrome (AES).
OBJECTIVE
To describe the utility of film array meningoencephalitis (FAME) panel in the management of children with acute encephalitis syndrome (AES).
METHODS
A retrospective audit was conducted between January 2017 to July 2022. We included children aged < 18 years with a diagnosis of AES for whom a CSF analysis study including FAME panel testing performed within 48 hours of admission was available. Electronic medical records were reviewed for details including demographic profile, clinical presentation, investigations and outcome.
RESULTS
Out of 157 CSF samples sent for FAME panel testing, 49 were positive (31.4%.) Viral pathogens were identified in 42 (Enterovirus: 31, Human herpes virus 6: 9, Varicella zoster virus: 1, and Cytomegalovirus: 1) Bacterial pathogens were identified in 6 (Streptococcus pneumoniae: 2, Streptococcus agalactiae: 2, Hemophilus influenzae: 1, and Escherischia coli: 1). Fungal etiology (Cryptococcus neoformans) was detected in one child. Antibiotics could be stopped within 72 hours of initiation in 42 children in whom a viral etiology was established. Acyclovir could be stopped in 21 out of 32 children within 72 hours after the FAME panel testing. FAME panel was presumed to be false positive in 4 children.
CONCLUSION
Etiology of AES could be established in nearly a third of children with AES using the rapid diagnostic FAME panel testing in CSF and it was found to be effective in reducing empirical antibiotic/antiviral therapy.
Topics: Humans; India; Retrospective Studies; Child; Child, Preschool; Female; Male; Infant; Acute Febrile Encephalopathy; Adolescent; Meningoencephalitis
PubMed: 38736224
DOI: No ID Found