Characteristics of neonatal herpes simplex virus infections in Germany: results of a 2-year prospective nationwide surveillance study

ObjectiveTo assess incidence and burden of neonatal herpes simplex virus (HSV) infections and to explore possible transmission routes.MethodsA 2-year prospective nationwide surveillance study performed in 2017 and 2018. All German paediatric departments (n=464 in 2017, n=441 in 2018) were contacted on a monthly basis to report potential cases of neonatal HSV infections. Infants with a postnatal age of ≤60 days and a positive HSV PCR or HSV culture from skin, mucous membrane, vesicles or conjunctival smear, blood or cerebrospinal fluid were included in the study.Results37 cases were analysed. 29 patients who exhibited no or only mild clinical symptoms were discharged home without organ damage or neurological abnormalities. Four patients showed significant neurological impairment, one patient required liver transplantation and two patients died during in-patient treatment. The 2-year incidence of neonatal HSV infections was 2.35 per 100 000 live births (95% CI 1.69 to 3.02) and disease-specific mortality was 0.13 per 100 000 live births (95% CI 0.04 to 0.21). Data on possible transmission routes were available in 23 cases. In 20 cases, an orofacial HSV infection was present in one or more family members. An active maternal genital HSV infection was reported in 3 cases.ConclusionNeonatal HSV infections are rare in Germany. Most infants have a benign clinical course, but some infants are severely affected. Postnatal HSV exposure may account for a considerable number of neonatal HSV infections.

A helicase-primase drug candidate with sufficient target tissue exposure affects latent neural herpes simplex virus infections

More than 50% of the world population is chronically infected with herpesviruses. Herpes simplex virus (HSV) infections are the cause of herpes labialis (cold sores), genital herpes, and sight-impairing keratitis. Less frequently, life-threatening disseminated disease (encephalitis and generalized viremia) can also occur, mainly in immunocompromised patients and newborns. After primary infection, HSV persists for life in a latent state in trigeminal or sacral ganglia and, triggered by diverse stimuli, disease recurs in more than 30% of patients up to several times a year. Current therapy with nucleoside analogs targeting the viral polymerase is somewhat effective but limited by poor exposure in the nervous system, and latent infections are not affected by therapy. Here, we report on an inhibitor of HSV helicase-primase with potent in vitro anti-herpes activity, a different mechanism of action, a low frequency of HSV resistance, and a favorable pharmacokinetic and safety profile. Improved target tissue exposure results in superior efficacy in preventing and treating HSV infection and disease in animal models as compared to standard of care. Therapy of primary HSV infections with drug candidate IM-250 {(S)-2-(2′,5′-difluoro-[1,1′-biphenyl]-4-yl)-N-methyl-N-(4-methyl-5-(S-methylsulfon-imidoyl)thiazol-2-yl)acetamide} not only reduces the duration of disease symptoms or time to healing but also prevents recurrent disease in guinea pigs. Treatment of recurrent infections reduces the frequency of recurrences and viral shedding, and, unlike nucleosidic drugs, IM-250 remains effective for a time after cessation of treatment. Hence, IM-250 has advantages over standard-of-care therapies and represents a promising therapeutic for chronic HSV infection, including nucleoside-resistant HSV.

Comparison of the Sensitivity and Specificity of Tzanck Smear and Immunofluorescence Assay for the Diagnosis of Cutaneous Herpes Simplex Virus and Varicella Zoster Virus Infections in a Real-life Clinical Setting

Objective: This research aim to compare (1) the sensitivities and specificities of Tzanck smears and indirect immunofluorescence assays (IFA) for cutaneous HSV and VZV infections in real-life settings; and (2) the detection rates of the tests for various patient types and lesion morphologies.Materials and Methods: This retrospective study reviewed 440 and 172 samples from patients with clinically suspicious cutaneous HSV and VZV infections, respectively. All patients underwent a Tzanck smear and IFA. The gold standard for the study was agreement of pre- and post-diagnostic coding (determined by a dermatologist) for cutaneous HSV and VZV infections.Results: For HSV infections, the respective sensitivity and specificity of Tzanck smears were 32.8% and 96.6%, whereas those for IFA were 60.7% and 100%. As to VZV infections, the sensitivity and specificity of Tzanck smears were 54.3% and 97.8%, respectively, while the corresponding IFA values were 71.7% and 100%. According to disease characteristics and lesion morphologies, the detection ability of cutaneous HSV by IFA was substantially higher than Tzanck smear especially in immunosuppressed condition. Tzanck smears and IFA demonstrated no statistical difference for early-onset ( 3 days) VZV infections.Conclusion: Tzanck smears and IFA had higher sensitivities for detecting VZV than HSV infections. IFA testing in suspected cutaneous HSV patients with immunosuppressed conditions should be recommended. Despite the overall sensitivity and specificity of IFA being greater than those for Tzanck smears especially in HSV infections, the latter test is a comparable option for early-onset VZV infections.

Immune Response to Herpes Simplex Virus Infection and Vaccine Development

Herpes simplex virus (HSV) infections are among the most common viral infections and usually last for a lifetime. The virus can potentially be controlled with vaccines since humans are the only known host. However, despite the development and trial of many vaccines, this has not yet been possible. This is normally attributed to the high latency potential of the virus. Numerous immune cells, particularly the natural killer cells and interferon gamma and pathways that are used by the body to fight HSV infections have been identified. On the other hand, the virus has developed different mechanisms, including using different microRNAs to inhibit apoptosis and autophagy to avoid clearance and aid latency induction. Both traditional and new methods of vaccine development, including the use of live attenuated vaccines, replication incompetent vaccines, subunit vaccines and recombinant DNA vaccines are now being employed to develop an effective vaccine against the virus. We conclude that this review has contributed to a better understanding of the interplay between the immune system and the virus, which is necessary for the development of an effective vaccine against HSV.

Natural Products-Derived Chemicals: Breaking Barriers to Novel Anti-HSV Drug Development

Recently, the problem of viral infection, particularly the infection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), has dramatically increased and caused a significant challenge to public health due to the rising problem of drug resistance. The antiherpetic drug resistance crisis has been attributed to the overuse of these medications, as well as the lack of new drug development by the pharmaceutical industry due to reduced economic inducements and challenging regulatory requirements. Therefore, the development of novel antiviral drugs against HSV infections would be a step forward in improving global combat against these infections. The incorporation of biologically active natural products into anti-HSV drug development at the clinical level has gained limited attention to date. Thus, the search for new drugs from natural products that could enter clinical practice with lessened resistance, less undesirable effects, and various mechanisms of action is greatly needed to break the barriers to novel antiherpetic drug development, which, in turn, will pave the road towards the efficient and safe treatment of HSV infections. In this review, we aim to provide an up-to-date overview of the recent advances in natural antiherpetic agents. Additionally, this paper covers a large scale of phenolic compounds, alkaloids, terpenoids, polysaccharides, peptides, and other miscellaneous compounds derived from various sources of natural origin (plants, marine organisms, microbial sources, lichen species, insects, and mushrooms) with promising activities against HSV infections; these are in vitro and in vivo studies. This work also highlights bioactive natural products that could be used as templates for the further development of anti-HSV drugs at both animal and clinical levels, along with the potential mechanisms by which these compounds induce anti-HSV properties. Future insights into the development of these molecules as safe and effective natural anti-HSV drugs are also debated.

Marine Algae: A Potential Resource of Anti-HSV Molecules

Herpes simplex viruses (HSVs) are common human pathogens belonging to the subfamily alpha-herpesvirinae that trigger severe infections in neonates and immunocompromised patients. After primary infection, the HSVs establish a lifelong latent infection in the vegetative neural ganglia of their hosts. HSV infections contribute to substantial disease burden in humans as well as in newborns. Despite a fair number of drugs being available for the treatment of HSV infections, new, effective, and safe antiviral agents, exerting different mechanisms of action, are urgently required, mainly due to the increasing number of resistant strains. Accumulating pieces of evidence have suggested that structurally diverse compounds from marine algae possess promising anti-HSV potentials. Several studies have documented a variety of algal polysaccharides possessing anti-HSV activity, including carrageenan and fucan. This review aimed to compile previous anti-HSV studies on marine algae–derived compounds, especially sulfated polysaccharides, along with their mode of action, toward their development as novel natural anti-HSV agents for future investigations.

Resveratrol as a Novel Anti-Herpes Simplex Virus Nutraceutical Agent: An Overview

The herpes simplex virus (HSV) is a common human virus affecting many people worldwide. HSV infections manifest with lesions that occur in different parts of the body, including oral, ocular, nasal, and genital skin and mucosa. In rare cases, HSV infections can be serious and lethal. Several anti-HSV drugs have been developed, but the existence of mutant viruses resistant to these drugs led to the individuation of novel antiviral agents. Plant-derived bioactive compounds, and more specifically polyphenols, have been demonstrated to exert marked anti-HSV activity and, among these, resveratrol (RSV) would be considered a good candidate. The purpose of this manuscript is to review the available literature elucidating the efficacy of RSV against HSV and the main demonstrated mechanisms of action.