Neonatal Herpes Simplex Virus Infection: Epidemiology and Treatment

In this study, a highly efficient sensing platform based on metal-organic framework-derived porous carbon (MOF-PC) and bio-gatekeeper strategy was designed for the sensitive detection of Herpes simplex virus type 1 (HSV-1). To realize the aim above, MOF-PC was obtained through the carbonization of the zeolitic imidazolate framework (ZIF-8). The electroactive dye methylene blue (MB) was then captured as a signal probe in the MOF-PC pores. Specifically, HSV-1 highly specific antisense ssDNA oligonucleotide was connected to MOF-PC through π-stacking interaction as a gatekeeper and sealed up the pores of MOF-PC. By adding the targets (synthetic ssDNA target or total genome HSV-1 DNA) and hybridization between the immobilized specific antisense ssDNA oligonucleotides and the targets, the double-stranded DNA (dsDNA) was separated from the MOF-PC surface due to the low affinity of the MOF-PC to the dsDNA. Meanwhile, MBs were released from the opened holes of MOF-PC. Therefore, the intensity of MB peak current in the absence of a target was high and then decreased by releasing and washing of MB molecules. The MB@MOF-PC responded linearly to synthetic ssDNA target in the range from 10⁻¹⁸ to 10⁻⁸ M and isolated total genome HSV-1 DNA in the range from 10² to 10⁸ copies/mL. The detection limits of 0.79 aM and 83.4 copies/mL were obtained for the synthetic ssDNA target and total genome HSV-1 DNA, respectively.

The ocular and periocular manifestations of sexually transmitted infections are heterogeneous in etiology, manifestations, and complications. Etiologic agents include bacteria, viruses, parasites, and protozoa, which are most frequently transmitted via direct ocular contact with an active lesion or infected bodily fluid, autoinoculation, or dissemination from a distant site. Vertical transmission most commonly occurs perinatally during vaginal delivery. The complications of ophthalmia neonatorum can be severe, with the potential for permanent blindness or life-threatening systemic involvement if untreated. Clinical features, diagnostic modalities, and therapeutic regimens vary based on etiology and are summarized in this review. Prompt diagnosis is imperative, given the severe sequelae that may result from ocular involvement in these infections, including permanent vision loss. A multidisciplinary approach, involving both ophthalmology and dermatology, to diagnosis and management is essential to mitigate the risk of morbidity associated with sexually transmitted infections resulting in eye disease.

Primary infection or reactivation of latent human cytomegalovirus (HCMV) or herpes simplex viruses (HSV) 1 or 2 during pregnancy can transmit the virus in utero or during natural childbirth to the fetus. The majority of these infections are asymptomatic at birth but may present later with potentially lethal disseminated infection or meningitis (HSV), or long-term neurodevelopmental sequelae including sensorineural hearing loss or neurodevelopmental impairments (HCMV). Unfortunately, early signs and symptoms of disseminated viral infections may be misdiagnosed as bacterial sepsis. Therefore, immediate testing for viral etiologies may not be ordered or even considered by skilled clinicians. In asymptomatic HCMV infections, early detection is necessary to monitor for and treat future neurologic sequelae. In acutely ill-appearing infants, specific detection of viruses against other disease-causing agents is vital to inform correct patient management, including early administration of the correct antimicrobial(s). An ideal test should be rapid, inexpensive, require low sample volumes, and demonstrate efficacy in multiple tissue matrices to aid in timely clinical decision-making for neonatal infections. This work discusses the development of a rapid probe-free qPCR assay for HSV and HCMV that enables early and specific detection of these viruses in neonates. The assay’s probe free chemistry would allow easier extension to a broad-based multiplexed pathogenic panel as compared to assays utilizing sequence-specific probes or nested PCR.

Antibody-dependent cellular cytotoxicity (ADCC) is associated with protection against neonatal herpes. We hypothesized that placental transfer of ADCC-mediating herpes simplex virus (HSV) immunoglobulin G (IgG) is influenced by antigenic target, function, glycans, gestational age, and maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Maternal and cord blood were collected from HSV-seropositive (HSV+) mothers pre-COVID and HSV+/SARS-CoV-2+ mothers during the pandemic. Transfer of HSV neutralizing IgG was significantly lower in preterm versus term dyads (transfer ratio [TR] 0.84 vs. 2.44) whereas the TR of ADCC-mediating IgG was <1.0 in both term and preterm pre-COVID dyads. Anti-glycoprotein D IgG, which had only neutralizing activity, and anti-glycoprotein B (gB) IgG, which displayed neutralizing and ADCC activity, exhibited different relative affinities for the neonatal Fc receptor (FcRn) and expressed different glycans. The transfer of ADCC-mediating IgG increased significantly in term SARS-CoV-2+ dyads. This was associated with greater placental colocalization of FcRn with FcγRIIIa. These findings have implications for strategies to prevent neonatal herpes.

This chapter describes the histological features of non-hepatotropic viral, bacterial and parasitic infections of the liver and identifies infections for which ancillary testing is particularly useful.

Neonatal herpes simplex virus (HSV) disease has been treated with high-dose (20 mg/kg/dose) acyclovir since 1991.

Determine the safety of acyclovir in infants with neonatal HSV treated with high-dose acyclovir; examine the association between acyclovir dose and exposure with adverse events (AEs).

We obtained demographic information and acyclovir dosing via medical records. Acyclovir exposure was calculated using an established pharmacokinetic model.

Infants <120 days of age with neonatal HSV discharged from four academic children's hospitals.

We identified clinical and laboratory adverse events (AEs).

We identified 49 infants with neonatal HSV treated with acyclovir; 42 infants had complete 21-day dosing information. Median mean daily dose was 59 mg/kg/day. Clinical AEs were common among all gestational and postnatal age groups. Rash was the most common clinical AE (37 %). Mild laboratory AEs occurred in 2–37 % of infants. The median maximum doses (mg/kg/day) were higher among infants with hypokalemia, elevated blood urea nitrogen, and thrombocytosis. For all other laboratory AEs, the median maximum doses for infants without events were higher or equal to the median maximum dose of infants with the AE. The odds of experiencing any clinical or laboratory AE did not differ by predicted acyclovir exposure for either area under the curve (AUC) or maximum concentration (Cmax) (odds ratio [OR] = 1.00 [0.98, 1.03] and OR = 1.01 [0.93, 1.12], respectively). Although AEs were common with high-dose acyclovir exposure, severe AEs were rare. Acyclovir exposure was not associated with AEs.