Maternally transferred monoclonal antibodies protect neonatal mice from herpes simplex virus-induced mortality and morbidity

Neonatal herpes simplex virus (HSV) infections often result in significant mortality and neurological morbidity despite antiviral drug therapy. Maternally-transferred HSV-specific antibodies reduce the risk of clinically-overt neonatal HSV (nHSV), but this observation has not been translationally applied. Using a neonatal mouse model, we tested the hypothesis that passive transfer of HSV-specific human monoclonal antibodies (mAbs) can prevent mortality and morbidity associated with nHSV. The mAbs were expressed in vivo by vectored immunoprophylaxis, or administered in vivo following recombinant expression in vitro. Through these maternally-derived routes or through direct administration to pups, diverse mAbs to HSV glycoprotein D protected against neonatal HSV-1 and HSV-2 infection. Using in vivo bioluminescent imaging, both pre- and post-exposure mAb treatment significantly reduced viral load. Administration of mAb also reduced nHSV-induced behavioral morbidity, as measured by anxiety-like behavior. Together these studies support the notion that HSV-specific mAb-based therapies may prevent or improve HSV infection outcomes in neonates.

A Preterm With Disseminated Neonatal Herpes Simplex Virus (HSV) After Kangaroo Mother Care: Role of Prevention and Early Treatment

Disseminated neonatal herpes simplex virus (HSV) infection represents the most severe form of neonatal herpes, which is associated with high morbidity and mortality. It can be completely prevented and early antiviral treatment can significantly reduce its adverse outcomes. Its early recognition in the neonate can be difficult, since the clinical presentation often mimics bacterial sepsis especially in absence of cutaneous vesicles. We report a case of preterm (twin 1) baby who during the hospital stay developed disseminated neonatal HSV type 1 infection, possibly acquired during kangaroo mother care, as on examination mother was noticed to have herpes labialis. The other twin 2 baby also developed few macular papular rash and was immediately started on antiviral treatment. The purpose of this report is to alert healthcare providers to this potential route of transmission. Furthermore, it is essential to consider neonatal HSV infection in any sick infant who is not responding to standard empirical antibiotic management, even in the absence of herpetic lesions.

Australian Paediatric Surveillance Unit (APSU) Annual Surveillance Report 2020

For 27 years, national prospective data on selected rare childhood diseases have been collected monthly by the Australian Paediatric Surveillance Unit (APSU) from paediatricians and other clinical specialists who report cases in children aged up to 16 years. We report here the annual results of APSU surveillance in 2020 for ten rare communicable diseases and complications of communicable diseases, namely: acute flaccid paralysis (AFP); congenital cytomegalovirus (CMV) infection; neonatal herpes simplex virus (HSV) infection; perinatal exposure to human immunodeficiency virus (HIV); paediatric HIV infection; severe complications of seasonal influenza; juvenile onset recurrent respiratory papillomatosis (JoRRP); congenital rubella syndrome; congenital varicella syndrome; and neonatal varicella infection. We describe the results for each disease in the context of the total period of study, including demographics, clinical characteristics, treatment and short-term outcomes. Despite challenges presented by the coronavirus disease 2019 (COVID-19) pandemic in 2020, more than 1,400 paediatricians reported regularly to the APSU and an overall monthly reporting rate of > 90% was achieved. The minimum AFP target of 1 case per 100,000 children aged less than 15 years was achieved and there were few cases of vaccine-preventable diseases (JoRRP, rubella, varicella). However, high cases of congenital CMV, neonatal HSV and perinatal exposure to HIV persist. There were no severe complications of seasonal influenza reported for the first time in 13 years. This is consistent with other surveillance data reporting a decline of influenza and other communicable diseases in 2020, and likely reflects the wider effects of public health measures to reduce transmission of SARS-CoV-2 in the Australian community.

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.

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.