- [The Spanish Society of Paediatric Infectious Diseases guidelines on the prevention, diagnosis and treatment of neonatal herpes simplex infections]. [Journal Article]
- APAn Pediatr (Barc) 2018 Feb 13
- Neonatal herpes simplex virus infections are rare, but are associated with significant morbidity and mortality. Most newborns acquire herpes simplex virus infection in the peripartum period. For peri...
Neonatal herpes simplex virus infections are rare, but are associated with significant morbidity and mortality. Most newborns acquire herpes simplex virus infection in the peripartum period. For peripartum transmission to occur, women must be shedding the virus in their genital tracts symptomatically or asymptomatically around the time of delivery. There are evidence-based interventions in pregnancy to prevent the transmission to the newborn. Caesarean section should be performed in the presence of herpetic lesions, and antiviral prophylaxis in the last weeks of pregnancy is recommended to suppress genital tract herpes simplex virus at the time of delivery. The diagnosis and early treatment of neonatal herpes simplex virus infections require a high index of suspicion, especially in the absence of skin lesions. It is recommended to rule out herpes simplex virus infections in those newborns with mucocutaneous lesions, central nervous system involvement, or septic appearance. The prognosis of newborns with skin, eye, and/or mouth disease in the high-dose acyclovir era is very good. Antiviral treatment not only improves mortality rates in disseminated and central nervous system disease, but also improves the rates of long-term neurodevelopmental impairment in the cases of disseminated disease. Interestingly, a 6-month suppressive course of oral acyclovir following the acute infection has improved the neurodevelopmental prognosis in patients with CNS involvement.
- Helicase-primase inhibitor amenamevir for herpesvirus infection: Towards practical application for treating herpes zoster. [Journal Article]
- DTDrugs Today (Barc) 2017; 53(11):573-584
- Valacyclovir and famciclovir enabled successful systemic therapy for treating herpes simplex virus (HSV) and varicella zoster virus (VZV) infection by their phosphorylation with viral thymidine kinas...
Valacyclovir and famciclovir enabled successful systemic therapy for treating herpes simplex virus (HSV) and varicella zoster virus (VZV) infection by their phosphorylation with viral thymidine kinase. Helicase-primase inhibitors (HPIs) inhibit the progression of the replication fork, an initial step in DNA synthesis to separate the double strand into two single strands. The HPIs amenamevir and pritelivir have a novel mechanism of action, once-daily administration with nonrenal excretory characteristics, and clinical efficacy for genital herpes. Amenamevir exhibits anti-VZV and anti-HSV activity while pritelivir only has anti-HSV activity. A clinical trial of amenamevir for herpes zoster has been completed, and amenamevir has been licensed and successfully used in 20,000 patients with herpes zoster so far in Japan. We have characterized the features of the antiviral action of amenamevir and, unlike acyclovir, the drug's antiviral activity is not influenced by the viral replication cycle. Amenamevir is opening a new era of antiherpes therapy.
- Modeling of Pharmaceutical Biotransformation by Enriched Nitrifying Culture under Different Metabolic Conditions. [Journal Article]
- ESEnviron Sci Technol 2018 Feb 15
- Pharmaceutical removal could be significantly enhanced through cometabolism during nitrification processes. So far pharmaceutical biotransformation models have not considered the formation of transfo...
Pharmaceutical removal could be significantly enhanced through cometabolism during nitrification processes. So far pharmaceutical biotransformation models have not considered the formation of transformation products associated with the metabolic type of microorganisms. Here we reported a comprehensive model to describe and evaluate the biodegradation of pharmaceuticals and the formation of their biotransformation products by enriched nitrifying cultures. The biotransformation of parent compounds was linked to the microbial processes via cometabolism induced by ammonium oxidizing bacteria (AOB) growth, metabolism by AOB, cometabolism by heterotrophs (HET) growth and metabolism by HET in the model framework. The model was calibrated and validated using experimental data from pharmaceuticals biodegradation experiments at realistic levels, taking two pharmaceuticals as examples, i.e., atenolol and acyclovir. Results demonstrated the good prediction performance of the established biotransformation model under different metabolic conditions, as well as the reliability of the established model in predicting different pharmaceuticals biotransformations. The linear positive correlation between ammonia oxidation rate and pharmaceutical degradation rate confirmed the major role of cometabolism induced by AOB in the pharmaceutical removal. Dissolved oxygen was also revealed to be capable of regulating the pharmaceutical biotransformation cometabolically and the substrate competition between ammonium and pharmaceuticals existed especially at high ammonium concentrations.
- An off-target effect of BX795 blocks herpes simplex virus type 1 infection of the eye. [Journal Article]
- STSci Transl Med 2018 Feb 14; 10(428)
- Herpes simplex virus type 1 (HSV-1) causes recurrent mucocutaneous lesions in the eye that may advance to corneal blindness. Nucleoside analogs exemplified by acyclovir (ACV) form the primary class o...
Herpes simplex virus type 1 (HSV-1) causes recurrent mucocutaneous lesions in the eye that may advance to corneal blindness. Nucleoside analogs exemplified by acyclovir (ACV) form the primary class of antiherpetic drugs, but this class suffers limitations due to the emergence of viral resistance and other side effects. While studying the molecular basis of ocular HSV-1 infection, we observed that BX795, a commonly used inhibitor of TANK-binding kinase 1 (TBK1), strongly suppressed infection by multiple strains of HSV-1 in transformed and primary human cells, cultured human and animal corneas, and a murine model of ocular infection. Our investigations revealed that the antiviral activity of BX795 relies on targeting Akt phosphorylation in infected cells, leading to the blockage of viral protein synthesis. This small-molecule inhibitor, which was also effective against an ACV-resistant HSV-1 strain, shows promise as an alternative to existing drugs and as an effective topical therapy for ocular herpes infection. Collectively, our results obtained using multiple infection models and virus strains establish BX795 as a promising lead compound for broad-spectrum antiviral applications in humans.
- Retrospective Identification of Herpes Simplex 2 Virus-Associated Acute Liver Failure in an Immunocompetent Patient Detected Using Whole Transcriptome Shotgun Sequencing. [Journal Article]
- CRCase Reports Hepatol 2017; 2017:4630621
- Acute liver failure (ALF) is a severe condition in which liver function rapidly deteriorates in individuals without prior history of liver disease. While most cases result from acetaminophen overdose...
Acute liver failure (ALF) is a severe condition in which liver function rapidly deteriorates in individuals without prior history of liver disease. While most cases result from acetaminophen overdose or viral hepatitis, in up to a third of patients, no clear cause can be identified. Liver transplantation has greatly reduced mortality among these patients, but 40% of patients recover without liver transplantation. Therefore, there is an urgent need for rapid determination of the etiology of acute liver failure. In this case report, we present a case of herpes simplex 2 virus- (HSV-) associated ALF in an immunocompetent patient. The patient recovered without LT, but the presence of HSV was not suspected at the time, precluding more effective treatment with acyclovir. To determine the etiology, stored blood samples were analyzed using whole transcriptome shotgun sequencing followed by mapping to a panel of viral reference sequences. The presence of HSV-DNA in blood samples at the time of admission was confirmed using real-time polymerase chain reaction, and, at the time of discharge, HSV-DNA levels had decreased by a factor of 106.Conclusions. In ALF cases of undetermined etiology, uncommon causes should be considered, especially those for which an effective treatment is available.
- Well-Appearing Newborn With a Vesiculobullous Rash at Birth. [Journal Article]
- PedPediatrics 2018 Feb 06
- A term, appropriate-for-gestational-age, male infant born via normal spontaneous vaginal delivery presented at birth with a full-body erythematous, vesiculobullous rash. He was well-appearing with no...
A term, appropriate-for-gestational-age, male infant born via normal spontaneous vaginal delivery presented at birth with a full-body erythematous, vesiculobullous rash. He was well-appearing with normal vital signs and hypoglycemia that quickly resolved. His father had a history of herpes labialis. His mother had an episode of herpes zoster during pregnancy and a prolonged rupture of membranes that was adequately treated. The patient underwent a sepsis workup, including 2 attempted but unsuccessful lumbar punctures, and was started on broad-spectrum antibiotics and acyclovir, given concerns about bacterial or viral infection. The rash evolved over the course of several days. Subsequent workup, with particular attention to his history and presentation, led to his diagnosis.
- [Trigeminal Herpes Zoster Presenting with High-intensity Signals for the Spinal Trigeminal Nucleus and Tract on Diffusion-weighted Image: A Case Report of Stroke Mimic]. [Journal Article]
- BNBrain Nerve 2018; 70(2):161-164
- A 50-year-old woman was admitted to our hospital with dysesthesia on the right upper portion of her face and a headache. Diffusion-weighted brain magnetic resonance imaging (MRI) revealed high-intens...
A 50-year-old woman was admitted to our hospital with dysesthesia on the right upper portion of her face and a headache. Diffusion-weighted brain magnetic resonance imaging (MRI) revealed high-intensity signals in the dorsolateral portion of the medulla oblongata. She was diagnosed with lateral medullary infarction and was intravenously treated with sodium ozagrel. On the second day of hospitalization, she had nausea and vomiting and showed nystagmus to all directions, suggesting damage to the vestibular nucleus. These manifestations coincided with partial symptoms of lateral medullary syndrome. On the third day of hospitalization, a rash appeared on the region of skin innervated by the first and second branches of the right trigeminal nerve. A reevaluation of the MRI findings indicated the presence of a lesion of the right spinal trigeminal nucleus and tract. She was treated with acyclovir for 14 days, and was discharged without any residual symptoms. Varicella zoster virus-DNA was detected in her cerebrospinal fluid. This disease mimics the presentation of a stroke and is important for differential diagnosis. (Received August 1, 2017; Accepted September 14, 2017; Published February 1, 2018).
- Herpes Zoster and Postherpetic Neuralgia: Prevention and Management. [Journal Article]
- AFAm Fam Physician 2017 Nov 15; 96(10):656-663
- Herpes zoster, or shingles, is caused by reactivation of varicella zoster virus, which causes chickenpox. There are an estimated 1 million cases in the Unites States annually, with an individual life...
Herpes zoster, or shingles, is caused by reactivation of varicella zoster virus, which causes chickenpox. There are an estimated 1 million cases in the Unites States annually, with an individual lifetime risk of 30%. Patients with conditions that decrease cell-mediated immunity are 20 to 100 times more likely to develop herpes zoster. Patients may present with malaise, headache, low-grade fever, and abnormal skin sensations for two to three days before the classic maculopapular rash appears. The rash is usually unilateral, confined to a single dermatome, and typically progresses to clear vesicles that become cloudy and crust over in seven to 10 days. Herpes zoster can be treated with acyclovir, valacyclovir, or famciclovir, ideally within 72 hours of the development of the rash. Postherpetic neuralgia is the most common complication, occurring in about one in five patients. It is defined as pain in a dermatomal distribution sustained for at least 90 days after acute herpes zoster. Treatment is focused on symptom control and includes topical lidocaine or capsaicin and oral gabapentin, pregabalin, or tricyclic antidepressants. The varicella zoster virus vaccine decreases the incidence of herpes zoster and is approved for adults 50 years and older. The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommends this vaccine for adults 60 years and older, except for certain immunosuppressed patients.
- ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an Infectious Diseases perspective (Immune checkpoint inhibitors, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors). [Review]
- CMClin Microbiol Infect 2018 Feb 07
- CONCLUSIONS: Clinicians should be aware of the risk of irAEs and PML in patients receiving immune checkpoint and cell adhesion inhibitors, respectively.
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- Multi-viral canaliculitis: case report and review of literature. [Journal Article]
- IOInt Ophthalmol 2018 Feb 09
- CONCLUSIONS: An encounter with an atypical canaliculitis with negative bacteriology work up, suboptimal response to routine therapies, and mid-canalicular obstructions should alert the physician to investigate for viral etiology.