OBJECTIVE: This study aims to analyse the clinical presentation caused by enterovirus (EV) and/or human parechovirus (HPeV) infection in children, as well as the management of such cases admitted to a regional hospital in Australia.
METHODS: Retrospective study reviewing medical records.
METHODS: Single hospital in regional Australia.
METHODS: All children under 18 years admitted over the 5-year period beginning from 1 January 2017 with confirmed EV and/or HPeV infection. Cases with clinically insignificant EV/HPeV isolation were excluded.
METHODS: Data collected included demographic data, signs and symptoms present, specimens of EV/HPeV isolation, co-occurring pathogens, peak C-reactive protein (CRP), antibiotic therapy, discharge diagnosis and follow-up after discharge.
RESULTS: Overall, 27 patients fulfilled the inclusion criteria; 81.5% of the patients were ≤3 months of age with a median of 2 months (interquartile range 1-3); 74.1% were males. The most common clinical features were a fever ≥38°C and irritability/lethargy/high-pitched cry. 29.6% of the patients had co-occurring pathogens detected, and a CRP ≤10 mg/L was observed in 77.8% of cases. All but two children were treated with antibiotics while awaiting polymerase chain reaction results. The most common discharge diagnosis was meningitis. In all, 74.1% of the children attended follow-up appointments.
CONCLUSIONS: EV and HPeV should be considered as a possible aetiology of fever and irritability/lethargy/high-pitched cry in children under 3 months.

Ramsay Hunt syndrome (RHS) is a manifestation of reactivated varicella-zoster virus (VZV) from the geniculate ganglion. Data on clinical features and outcomes of patients with RHS and concurrent VZV meningitis (henceforth RHS meningitis) are limited. Thus, we conducted a nationwide population-based cohort study of all adults hospitalized for RHS meningitis at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with VZV meningitis without cranial nerve palsies were included for comparison. In total, 37 patients with RHS meningitis (mean annual incidence: 1.6/1 000 000 adults) and 162 with VZV meningitis without cranial nerve palsies were included. In RHS meningitis, the median age was 52 years (interquartile range: 35-64), and in addition to peripheral facial nerve palsy (100%), dizziness (46%), and hearing loss (35%) were common symptoms. The triad of headache, neck stiffness, and photophobia/hyperacusis was less common in RHS meningitis than in VZV meningitis without cranial nerve palsies (0/27 [0%] vs. 24/143 [17%]; p = 0.02). At 30 days after discharge, 18/36 (50%) patients with RHS meningitis had persistent peripheral facial nerve palsy, with no statistically significant difference between those treated with and without adjuvant glucocorticoids (6/16 [38%] vs. 12/20 [60%]; p = 0.18). Additional sequelae of RHS meningitis included dizziness (29%), neuralgia (14%), tinnitus/hyperacusis (11%), hearing loss (9%), headache (9%), fatigue (6%), and concentration difficulties (3%). In conclusion, clinical features and outcomes of RHS meningitis were primarily related to cranial neuropathies.

Data on clinical features and outcomes of benign recurrent lymphocytic meningitis (BRLM) are limited.
This was a nationwide population-based cohort study of all adults hospitalized for BRLM associated with herpes simplex virus type 2 (HSV-2) at the departments of infectious diseases in Denmark from 2015 to 2020. Patients with single-episode HSV-2 meningitis were included for comparison.
Forty-seven patients with BRLM (mean annual incidence 1.2/1,000,000 adults) and 118 with single-episode HSV-2 meningitis were included. The progression risk from HSV-2 meningitis to BRLM was 22% (95% confidence interval [CI] 15%-30%). The proportion of patients with the triad of headache, neck stiffness and photophobia/hyperacusis was similar between BRLM and single-episode HSV-2 meningitis (16/43 [37%] vs. 46/103 [45%]; p = 0.41), whilst the median cerebrospinal fluid leukocyte count was lower in BRLM (221 cells vs. 398 cells; p = 0.02). Unfavourable functional outcomes (Glasgow Outcome Scale score of 1-4) were less frequent in BRLM at all post-discharge follow-up visits. During the study period, 10 (21%) patients with BRLM were hospitalized for an additional recurrence (annual rate 6%, 95% CI 3%-12%). The hazard ratio for an additional recurrence was 3.93 (95% CI 1.02-15.3) for patients with three or more previous episodes of meningitis.
Clinical features of BRLM were similar to those of single-episode HSV-2 meningitis, whilst post-discharge outcomes were more favourable. Patients with three or more previous episodes of meningitis had higher risk of an additional recurrence.

BACKGROUND: Zostavax, the live-attenuated vaccine used to prevent herpes zoster (HZ), has been available to individuals aged 70 and 71-79 years (phased catch-up) via Australia\'s National Immunisation Program (NIP) since 2016. There are limited data characterising the incidence of HZ at the level of the Australian population. National prescription data for antivirals used to treat HZ may be used as a proxy for HZ incidence. We aimed to examine trends in antiviral prescriptions supplied for the treatment of HZ in Australia pre- and post-2016, and to assess whether Zostavax\'s inclusion on the NIP correlated with a reduction in HZ antiviral prescription rates.
METHODS: Using the Australian Pharmaceutical Benefits Scheme and Repatriation Pharmaceutical Benefits Scheme prescribing data, we analysed antiviral prescriptions supplied for the treatment of HZ Australia-wide between 1994 and 2019. Annual prescription rates were calculated, and trends and changes in HZ antiviral use were explored descriptively and using Poisson models.
RESULTS: HZ antiviral prescription rates increased 2.6-fold (160%) between 1995 and 2015 [25.4 (95% CI 25.2, 25.6) and 65.3 (95% CI 64.9, 65.6) prescriptions per 10,000 people, respectively], and then decreased 0.45-fold (55%) between 2016 and 2018 [60.9 (95% CI 60.6, 61.2) and 27.5 (95% CI 27.3, 27.9) prescriptions per 10,000 people, respectively]. The prescription rate for the antiviral famciclovir restricted specifically for treating HZ in immunocompromised individuals increased 8.5-fold (750%) between 2006 (year first listed) and 2019 [0.3 (95% CI 0.3, 0.3) and 2.5 (95% CI 2.4, 2.6) prescriptions per 10,000 people, respectively].
CONCLUSIONS: The introduction of the live-attenuated HZ vaccine on Australia\'s formal national vaccination program was associated with a reduction in HZ antiviral prescription rates within the Australian population. The data suggest that the introduction of Shingrix, the non-live subunit zoster vaccine, may also be associated with a similar reduction in HZ antiviral prescriptions used to treat the immunocompromised, as well as the general population, given its accepted greater efficacy over Zostavax.

Herpes simplex keratitis is an important infectious cause of blindness worldwide. The mainstay of antiviral therapy is treatment with long-established nucleoside analogues orally or topically. However, the emergence of resistant strains may become a major health concern in the future. Therefore, the development of backup antiherpetic medicines is urgently needed. Small molecule PDSTP is known to be active against herpes simplex type 1 strains in vitro, affecting early host-pathogen interactions. Here, we evaluated its preclinical efficacy in a rabbit model of herpes simplex epithelial keratitis. The mean course of keratitis and the corneal lesions in the 1.0% PDSTP gel group was statistically significantly less than in the negative control group and was comparable to that in the aciclovir group. These findings open up new opportunities for the development of antiherpetic drugs with an original mechanism of action.

BACKGROUND: Antivirals and occlusive lip patches are key treatments for cold sores. Additional therapeutic options, and validated methods to evaluate these, are needed.
METHODS: This exploratory, double-blind, single-center study aimed to evaluate a novel lip patch containing the antiviral aciclovir (ACV) using noninvasive methods for measuring cold sore-associated inflammation. Healthy subjects with ultraviolet radiation (UVR)-induced cold sores were randomized to 10 days\' treatment with a lip patch containing ACV (N = 12) or without ACV (N = 13). Outcome measures included blood flux (field laser perfusion imaging, FLPI), skin temperature (thermography), and skin redness (high-resolution color photography, HRCP).
RESULTS: Mean blood flux (in perfusion units) and skin temperature (in °C/pixel) were higher for cold sores versus intrasubject control regions. For ACV versus placebo patches, skin temperature was higher for ACV with total day 1-5 mean values of 2.6 versus 0.5 (p = 0.036) and day 1-10 mean values of 3.2 versus 0.8 (p = 0.049). Conversely, mean total episode blood flux values over days 1-5 were lower for ACV versus placebo patch (flux 2227 versus 2939, p = 0.340) and remained lower over days 1-10 (flux ACV 810 versus placebo 961, p = 0.404). HRCP failed to discriminate cold sores from control regions or between treatments. Subject-reported pain/soreness, itching, and burning were generally lower with ACV patch.
CONCLUSIONS: FLPI reliably measures cold sore-related inflammation and thermography heat radiating from the skin. HRCP was of little value.
BACKGROUND: NCT01653509.

To compare New Zealand medical grade kanuka honey with topical aciclovir for the treatment of herpes simplex labialis.
Prospective parallel randomised controlled open-label superiority trial.
76 community pharmacies across New Zealand between 10 September 2015 and 13 December 2017.
952 adults randomised within the first 72 hours of a herpes simplex labialis episode.
Random assignment 1:1 to either 5% aciclovir cream or medical grade kanuka honey (90%)/glycerine (10%) cream, both applied five times daily.
The primary outcome was time from randomisation to return to normal skin (stage 7). Secondary outcomes included time from randomisation to stage 4 (open wound), time from stage 4 to 7, maximal pain, time to pain resolution and treatment acceptability.
Primary outcome variable: Kaplan-Meier-based estimates (95% CI) for the median time in days for return to normal skin were 8 (8 to 9) days for aciclovir and 9 (8 to 9) for honey; HR (95% CI) 1.06 (0.92 to 1.22), p=0.56. There were no statistically significant differences between treatments for all secondary outcome variables. No related serious adverse events were reported.
There was no evidence of a difference in efficacy between topical medical grade kanuka honey and 5% aciclovir in the pharmacy-based treatment of herpes simplex labialis.
ACTRN12615000648527;Post-results.

A lip cream with special propolis extract GH 2002 at a concentration of 0.5% (199 patients) was tested against aciclovir 5% (198 patients) in the treatment of episodes of herpes labialis under double-blind conditions. Upon inclusion, all patients were in the vesicular phase. Application was five times daily of approximately 0.2 g of cream to the entire upper and lower lip. The primary parameter was the difference in time between groups to complete encrustation or epithelization of the lesions. Secondary endpoints were the course of typical herpes symptoms (pain, burning and itching, tension and swelling), the global assessment of efficacy and the safety of application. The predefined clinical situation was reached after a (median) 3 days with propolis and 4 days with aciclovir (p < 0.0001). Significant differences in favor of propolis were also found for all secondary parameters. No allergic reactions, local irritations or other adverse events occurred.

OBJECTIVE: This controlled single-blind trial compared the efficacy of a lip balm with propolis special extract GH 2002 at a concentration of 0.5% in the treatment of episodes of herpes labialis with that of 5% aciclovir cream.
METHODS: Patients in the erythematous/papular stage were randomized: 189 patients were treated with propolis cream, 190 patients were treated with aciclovir cream (intention-to-treat population). Application was 5 times daily. The primary parameter was the difference in median time to complete encrustation or epithelialization of lesions. Secondary parameters were the development of typical herpes symptoms (eg, pain, burning and itching, tension, and swelling), the global assessment of efficacy, and the safety of application.
RESULTS: The predefined clinical situation was reached after a median of 4 days with propolis and after 5 days with aciclovir (P < 0.0001). Significant differences in favor of the study preparation were found with all secondary parameters and symptoms. No allergic reactions, local irritations, or other adverse events were observed.
CONCLUSIONS: A formulation of 0.5% propolis GH 2002 extract lip balm was found to be superior in the treatment of episodes of herpes labialis over 5% aciclovir cream in patients in the papular/erythematous phase upon inclusion. EudraCT Registration No. 2006-001971-38.

BACKGROUND: Worldwide, about 90% of people are infected with the herpes simplex virus, 30% of whom will experience recurrent herpes simplex labialis, commonly referred to as \'cold sores\', which can last up to 10 days. The most common treatment is aciclovir cream which reduces healing time by just half a day compared with no specific treatment. This is a protocol for a randomised controlled trial (RCT) to determine the efficacy of medical grade kanuka honey-based topical treatment (Honevo) in reducing the healing time and pain of cold sores, compared with topical aciclovir treatment (Viraban).
METHODS: This open-label, parallel-group, active comparator superiority RCT will compare the efficacy of medical grade kanuka honey with 5% aciclovir cream in the treatment of cold sores in the setting of a pharmacy research network of 60 sites throughout New Zealand. Adults presenting with a cold sore (N=950) will be randomised by pharmacy-based investigators. The pharmacy-based investigators will dispense the investigational product to randomised participants and both study groups apply the treatment five times daily until their skin returns to normal or for 14 days, whichever occurs first. In response to a daily SMS message, participants complete an assessment of their cold sore healing, with reference to a visual guide, and transmit it to the investigators by a smartphone eDiary in real time. The primary outcome variable is time (in days) from randomisation to return to normal skin. Secondary endpoints include total healing time stratified by stage of the lesion at onset of treatment, highest pain severity and time to pain resolution.
BACKGROUND: New Zealand Ethics Registration 15/NTB/93. Results will be published in a peer-reviewed medical journal, presented at academic meetings and reported to participants.
BACKGROUND: Australia New Zealand Clinical Trials Registry: ACTRN12615000648527, pre-results.SCOTT Registration: 15/SCOTT/14 PROTOCOL VERSION: 4.0 (12 June 2017).