Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic

Neonatal herpes simplex virus (HSV) infection is rare, with an estimated incidence of 3.58 per 100 000 live births in the UK and should be suspected in any newborn with fever and bacterial culture-negative sepsis. We describe a case of a previously well full-term male neonate who presented with persistent fever and elevated ferritin level that was carried out during the era of the COVID-19 pandemic as part of SARS-CoV-2 panel investigations. Despite the initial negative HSV serology, HSV-1 PCR from a scalp lesion returned positive. He made a full recovery after acyclovir therapy. This case highlights the importance of maintaining a high clinical index of suspicion of HSV infection in any febrile neonate even with absence of maternal history and negative serology, particularly if associated with hyperferritinaemia. We also address the challenge of interpreting inflammatory biomarkers’ results for SARS-CoV-2 infection in neonates.

HSV-pneumonitis in a patient with lung cancer receiving check point inhibitors – a case report

Background Herpes simplex virus (HSV) is commonly associated with oro-facial and genital manifestations. It rarely causes encephalitis and even less commonly, in heavily immunosuppressed patients, visceral disease or bronchopneumonitis. We present a case of cytologically-proven, PCR-positive HSV-1 tracheobronchitis and pneumonitis in a patient with less severe immunocompromise. Case presentation A 64 year old white man with steroid-induced diabetes mellitus and progressive small-cell bronchial carcinoma despite chemo- and immunotherapy with two checkpoint inhibitors presented with symptoms of lower respiratory tract infection. Community-acquired pneumonia was suspected and empirical broad-spectrum antibacterial treatment was initiated. Chest CT-scan revealed ground-glass opacities and tree-in bud lesions. Cytology of BAL showed extensive cytopathic effects typically caused by infection with herpes virus and PCR confirmation of HSV-1. Acute phase HSV serology was positive for IgG and borderline for IgM. The patient deteriorated clinically due to tumor progress and infection despite high-dose acyclovir therapy and died 2 weeks after admission. Conclusions We report an unusual case of fatal HSV-1 pneumonitis due to reactivation in a patient with lung cancer, steroid-induced diabetes and treatment with two checkpoint inhibitors. In immunosuppressed patients with non-improving pneumonia invasive diagnostic procedures are warranted including cytology and molecular diagnostics.

1407. Potential Impact of the Biofire® Film Array Meningitis and Encephalitis (ME) Panel in Reducing Repeat Lumbar Punctures in Patients with Meningitis and Encephalitis

Background The Biofire® FilmArray Meningitis Encephalitis (FAME) is a multiplex polymerase chain reaction (PCR) test can rapidly detect up to 14 pathogens that cause meningitis and encephalitis. The impact on preventing repeat lumbar punctures to obtain more diagnostic studies is currently unknown. Methods Patients admitted to Memorial Hermann Hospital (MHH) between July 2018-February 2019 with community-acquired symptoms of meningitis or encephalitis, CSF with white blood cell count >5 cells/mm3, and with leftover CSF at the MHH microbiology laboratory were eligible for the study. Testing FAME was performed after discharge for specimens that had not been centrifuged, had a volume of ≥200 μL, were appropriately stored, and were collected by lumbar puncture (LP) for evaluation of suspected meningitis/encephalitis. Results Of 1,382 CSF specimens screened, 70 (5.0%) met the criteria and were tested with FAME. The majority was adults (72.8%), non-Caucasian (68.6%), male (60%), immunocompetent (75.7%) and had a meningitis presentation (75.7%). Mean age was 36.9 years (1 mo-89 years). The mean duration between CSF collection and any PCR result done in the hospital was 60 hours. Fifteen patients (21.4%) required 25 repeat LPs [13 (86.6%) for additional testing (7 (53.8%) pediatric patients) and 2 (13.3%) for cryptococcal meningitis assessment]. The FAME could have prevented repeat LPs in 86.6% of patients. Five of the 13 repeat LP (38.4%) FA ME showed a pathogen [VZV (2), HSV 1 (1), HHSV-6 (1), Neisseria meningitidis (1)]. Of 46 tests with negative FA ME, acyclovir therapy was started in 22 (47.8%) with a mean of 6 doses dispensed. 38 (26.6%) patients were discharged with an unknown etiology of whom FA ME was positive in 8 (21%) [HSV2 (37.5%), VZV (25%), Enterovirus (25%) and HSV1 (12.5%)]. PCR was ordered in the hospital for only 4 (50%) of these patients. Conclusion The FAME identified an etiology in 21% of patients with meningitis and encephalitis symptoms discharged with an unknown etiology. A total of 18.5% of patients required a repeat LP for additional testing. FAME testing offers an avenue for reducing the burden of repeat LPs and duration of unnecessary anti-infective therapy while increasing diagnostic yield. Disclosures All authors: No reported disclosures.

Factors Associated With HSV PCR CSF Testing and Empiric Acyclovir Therapy in Young Febrile Infants

Herpes simplex virus (HSV) infection in infants is a devastating disease with an often subtle presentation. We examined cerebrospinal fluid (CSF) HSV PCR (polymerase chain reaction) testing and empiric acyclovir therapy in young febrile infants. Chart review identified hospitalized infants aged ≤60 days with fever ≥38°C who had undergone lumbar puncture. Previously published criteria were used to define patients at high risk for HSV. Primary outcomes were CSF HSV PCR testing and empiric acyclovir therapy. Of 536 febrile infants, 23% had HSV testing; empiric acyclovir was started in 15%. HSV testing and therapy were associated with younger age, seizure, maternal vaginal lesions, postnatal HSV contact, vesicles, poor tone, CSF pleocytosis, and enteroviral testing. Sixty-two percent of high-risk infants did not undergo HSV testing, and 75% did not receive acyclovir. High-risk infants were untested and untreated at relatively high rates. Evidence-based criteria to guide HSV testing and treatment are needed.

Varicella Retinal Vasculopathy: Unilateral Cilioretinal Artery Occlusion Despite Acyclovir Therapy Caught Using Optical Coherence Tomography-Angiography (OCTA)

Varicella zoster is known to be associated with vaso-occlusive pathologies, vasculitis, or optic neuritis, leading to profound visual loss. We report a case where a 13-year-old boy who initially presented to us with on and off diminution of vision in his right eye since 3 days and had normal ocular and OCT angiography findings followed up in 5 days with sudden painless diminution of vision in the same eye since one day this time revealing a pale macular region with rest of the retina being normal. Repeated OCT angiography showed loss of the capillary network around the perifoveal region suggesting cilioretinal artery occlusion.

Bilateral herpes simplex keratitis: lactation a trigger for recurrence!

A young lactating woman presenting to us with simultaneous bilateral corneal lesions was clinically diagnosed to have herpes simplex keratitis, which was confirmed by herpes simplex virus (HSV) PCR. The patient was administered topical and systemic acyclovir therapy and therapeutic penetrating keratoplasty was done in right eye. She was advised to continue breast feeding under strict hygienic conditions. Diagnosis and management of HSV keratitis in a lactating patient can be particularly challenging for both clinician and patient and adoption of a multidisciplinary approach is necessary to ensure safety of mother and child. At 3 months follow-up, the baby was clinically healthy, there were no side effects of acyclovir therapy in the mother or the baby and the patient showed no evidence of recurrence in either eye.

Herpes zoster - is there a need for new treatment recommendations?

Background/Aim. The reactivation of the varicella zoster virus results in herpes zoster. Acyclovir is currently recommended over 7 to 10 days for herpes zoster treatment and should be started within 72 hours of rash eruption. This study analyses whether a therapy delay and/or shorter courses of treatment are associated with adverse outcomes. Methods. We identified 292 patients treated at the Clinic for Infectious and Tropical Diseases in Belgrade for herpes zoster in a five-years period. The data on these patients were analyzed using the descriptive statistics, the ?2 test, the Mann-Whitney U-test and the multiple logistic regression analysis. Results. The average time from rash eruption to the first dose of acyclovir was 4.07 ? 2.64 days. The patients received acyclovir for 6.83 ? 2.45 days. Seventy-one patients had disseminated herpes zoster, 100 had cranial nerve involvement, 86 had complications other than postherpetic neuralgia and one patient died. In cases where therapy was delayed there was no significant association with complications (?2 = 0.031; p = 0.86). Our logistic regression model was not able to predict who was treated less than 7 days. An association between the HZ complications and abbreviated acyclovir regimens was not demonstrated (?2 = 1.109; p = 0.326). We conducted the PubMed search on February 1st, 2017 and found no proof for the need to apply at least 7 days of acyclovir therapy for herpes zoster in the studies that have been published so far. Conclusion. We were unable to prove an association between therapy delay and unfavorable outcomes. The same was true for shorter than recommended acyclovir courses.

Impact of a Rapid Herpes Simplex Virus PCR Assay on Duration of Acyclovir Therapy

ABSTRACTHerpes simplex virus (HSV) infections of the central nervous system (CNS) are associated with significant morbidity and mortality rates in children. This study assessed the impact of a direct HSV (dHSV) PCR assay on the time to result reporting and the duration of acyclovir therapy for children with signs and symptoms of meningitis and encephalitis. A total of 363 patients with HSV PCR results from cerebrospinal fluid (CSF) samples were included in this retrospective analysis, divided into preimplementation and postimplementation groups. For the preimplementation group, CSF testing was performed using a laboratory-developed real-time PCR assay; for the postimplementation group, CSF samples were tested using a direct sample-to-answer assay. All CSF samples were negative for HSV. Over 60% of patients from both groups were prescribed acyclovir. The average HSV PCR test turnaround time for the postimplementation group was reduced by 14.5 h (23.6 h versus 9.1 h;P< 0.001). Furthermore, 79 patients (43.6%) in the postimplementation group had dHSV PCR results reported <4 h after specimen collection. The mean time from specimen collection to acyclovir discontinuation was 17.1 h shorter in the postimplementation group (31.1 h versus 14 h;P< 0.001). The median duration of acyclovir therapy was also significantly reduced in the postimplementation group (29.2 h versus 14.3 h;P= 0.01). Our investigation suggests that implementation of rapid HSV PCR testing can decrease turnaround times and the duration of unnecessary acyclovir therapy.