Background: Neonatal herpes simplex virus (HSV) infection is rare but potentially devastating and can result in neonatal death or serious disability. National incidence was estimated at 1.65/100,000 ...live births in an earlier British Paediatric Surveillance Unit (BPSU) study of births 1986-1991.
Methods: A second surveillance study of neonatal HSV was undertaken through the BPSU 2004-2006, with follow-up information collected on surviving children in early childhood.
Results: Over the three-year period, 85 infants were reported with confirmed neonatal HSV, an estimated incidence of 3.58/100,000 live births (95% CI 2.86-4.42), about double that reported almost two decades earlier. Over 40% of infants were pre-term compared with 25% in the earlier period. Just over 70% had central nervous system (CNS) or disseminated infection, and among these 54% had no skin, eye or mouth lesions noted. Almost all received antivirals, but 22 (26%) neonates died, all with disseminated or CNS infection. All but six infections were typed, of which 57% involved HSV-2; the increased risk of adverse outcomes associated with HSV-2 in the earlier study was confirmed and strengthened, with twice as many deaths or long term disability in infants with HSV-2 than HSV-1. As before, a reported history or diagnosis of maternal HSV infection was rare prior to infant diagnosis. Likely timing of infant exposure to HSV could only be assigned in 43% of cases, of which just over half were probable postnatal transmissions.
Conclusions: Neonatal HSV infection remains rare although incidence doubled in the British Isles between the late 1990s and the mid-2000s. These findings suggest that future research should explore the relationship between pre-term delivery and infant susceptibility, and also the role of postnatal acquisition of infection. Healthcare professionals and new parents must continue to be aware of this rare condition in order to enable prompt investigation and instigation of treatment.
Neonatal herpes simplex virus (HSV) infection (HSV infection in infants less than 6 weeks of age) is rare but mortality and morbidity rates are high after disseminated disease and encephalitis. In ...France, the epidemiology is poorly described, and two decades ago, incidence was estimated to be 3 per 100,000 live births a year. We describe determinants, epidemiologic and clinical characteristics of neonatal HSV infection in a managed-care population attending in two major obstetric and paediatric centres, Paris, France, over a 10-year period. This retrospective case series study was conducted from 2013 to 2023, in infants less than 42 days of age who had virologically confirmed HSV infection. We report an overall rate of neonatal herpes of 5.5 per 100,000 live births a year and an incidence of symptomatic cases of 1.2 per 100,000 live births a year. HSV-1 was the major serotype involved (84.2%) and post-natal acquisition through the orolabial route reached 63.2%. All neonates who had neonatal HSV PCR screening (owing to clinical signs in parents) and who received prompt acyclovir treatment remained asymptomatic. Symptomatic forms accounted for 21.1% cases of the total and mortality was high (62.5% of symptomatic forms). Conclusion: This case series confirms that neonates at risk for HSV disease and poor outcome are those born to HSV-seronegative mothers, preterm infants, and those who received acyclovir after onset of symptoms (mainly because mothers did not present evidence of acute HSV infection). Our study confirms the major role of HSV-1 and the frequency of its early post-natal acquisition. What is known: • Neonatal herpes simplex virus infection is rare but motality and morbidity rates are high after disseminted disease and encephalitis. National recommendations exist worldwide but mangement of this disease is not always easy. What is new: • As in France epidemiology of neonatal herpes is poorly described, our report is potentially an important addition to the existing literature. Moreover, we describe local practice that may be useful to physicians.
Homozygous loss-of-function variants in Interferon induced with helicase C domain 1 (IFIH1) leads to immunodeficiency with early onset recurrent and severe viral respiratory infections ...(Immunodeficiency 95; MIM 619773). Severe respiratory infections with RNA viruses such as rhinovirus and respiratory syncytial virus (RSV) are most characteristic of IFIH1 deficiency. IFIH1 encodes melanoma differentiation-associated protein 5 (MDA5), an intracellular sensor of mainly long double-stranded RNA (ds-RNA), a viral replication intermediate. When activated, MDA5 triggers antiviral pathways including increased transcription of Type 1-interferon. The antiviral role of MDA5 is best described for positive (+) RNA viruses such as Picornavirus family which produce long ds-RNA as a replication intermediate. We present a patient with neonatal herpes simplex virus (HSV) encephalitis and recurrent retinitis with homozygous variant of unknown significance (VUS) in IFIH1, c.2062A>G (p.Lys688Glu).
Patient is a 10-year-old male, born of consanguineous parents from the United Arab Emirates. Past medical history is notable for neonatal HSV encephalitis, grade 3 intraventricular hemorrhage, cerebral palsy, epilepsy, optic atrophy and recurrent HSV retinitis. Patient has no additional history of severe or recurrent infections. No family history of recurrent or severe infections, malignancy, autoimmunity or autoinflammation.
Immune evaluation demonstrated anemia with elevated mean corpuscular volume and mild elevation of platelets and monocytes. Patient had normal lymphocyte subsets, normal T and B cell subset distributions, protective vaccine titers and normal immunoglobins apart from mildly elevated immunoglobulin G. An Invitae primary immunodeficiency panel demonstrated homozygous VUS in IFIH1, c.2062A>G (p.Lys688Glu). This variant is not found in gnomAD or ClinVar and has a Combined Annotation Dependent Depletion score of 22.6. Functional testing demonstrated decreased interferon induction after stimulation with intracellular RNA, intracellular DNA and agonists of both Toll-like receptor 7 and 9. These findings are consistent with MDA5 deficiency given decreased interferon response with known MDA5 agonists.
In summary, we describe a patient with recurrent and severe infections with a DNA virus and no known infections with respiratory RNA viruses. Both DNA and RNA viruses produce long ds-RNA as replication intermediates, an MDA5 agonist. This patient highlights the anti-viral role of MDA5 for both DNA and RNA viruses.
Neonatal herpes simplex virus infection (nHSV) leads to severe morbidity and mortality, but national incidence is uncertain. Florida regulations require that healthcare providers report cases, and ...clinical laboratories report test results when herpes simplex virus (HSV) is detected. We estimated nHSV incidence using laboratory-confirmed provider-reported cases and electronic laboratory reports (ELR) stored separately from provider-reported cases. Mortality was estimated using provider-reported cases, ELR, and vital statistics death records.
For 2011-2017, we reviewed: provider-reported cases (infants ≤ 60 days of age with HSV infection confirmed by culture or polymerase chain reaction PCR), ELR of HSV-positive culture or PCR results in the same age group, and death certificates containing International Classification of Disease, Tenth Revision, codes for herpes infection: P35.2, B00.0-B00.9, and A60.0-A60.9. Provider-reported cases were matched against ELR reports. Death certificates were matched with provider and ELR reports. Chapman's capture-recapture method was used to estimate nHSV incidence and mortality. Mortality from all 3 sources was estimated using log-linear modeling.
Providers reported 114 nHSV cases, and ELR identified 197 nHSV cases. Forty-six cases were common to both datasets, leaving 265 unique nHSV reports. Chapman's estimate suggests 483 (95% confidence interval CI, 383-634) nHSV cases occurred (31.5 infections per 100 000 live births). The nHSV deaths were reported by providers (n = 9), ELR (n = 18), and vital statistics (n = 31), totaling 34 unique reports. Log-linear modeling estimates 35.8 fatal cases occurred (95% CI, 34-40).
Chapman's estimates using data collected over 7 years in Florida conclude nHSV infections occurred at a rate of 1 per 3000 live births.
Neonatal Herpes Simplex Virus Infection James, Scott H; Kimberlin, David W
Infectious disease clinics of North America,
09/2015, Letnik:
29, Številka:
3
Journal Article
Recenzirano
Herpes simplex virus (HSV) 1 and HSV-2 infections are highly prevalent worldwide and are characterized by establishing lifelong infection with periods of latency interspersed with periodic episodes ...of reactivation. Acquisition of HSV by an infant during the peripartum or postpartum period results in neonatal HSV disease, a rare but significant infection that can be associated with severe morbidity and mortality, especially if there is dissemination or central nervous system involvement. Diagnostic and therapeutic advances have led to improvements in mortality and, to a lesser extent, neurodevelopmental outcomes, but room exists for further improvement.
Abstract
Though primarily used to improve neurodevelopmental outcomes, suppressive oral acyclovir therapy following neonatal herpes simplex virus disease also decreases cutaneous recurrences. Skin ...recurrences can still occur, however, and understanding their frequency is helpful in managing patients with this rare disease.
Although neonates are commonly exposed to vaginal herpes simplex virus (HSV)‐2, neonatal herpes is rare. Therefore, we analyzed paired infant and maternal HSV‐2 isolates from two cases of ...mother‐to‐infant transmission to identify viral factors contributing to vertical transmission. Sixteen infant isolates with neonatal herpes and 27 genital isolates in their third trimester were included. The infant isolates were significantly more temperature‐independent than the maternal isolates. Sequence comparison revealed viral UL13 protein kinase (UL13‐PK) mutation in the infant isolates in both cases. In the expanded cohort, infant isolates (5/18) had significantly more UL13‐PK mutations than genital isolates (1/29). Isolates within 8 days post‐birth (3/4) had a significantly higher frequency of UL13‐PK mutation than those after 9 days (2/14), suggesting a close association between UL13‐PK mutations and vertical transmission. Elongation factor 1‐delta was identified as a target of UL13‐PK by proteomic analysis of UL13‐PK‐positive and ‐negative HepG2 cells. The mixed infant isolates with the intact and mutated UL13‐PK conferred altered cell tropism, temperature independence adapting to fetal temperature, and better growth properties in Vero and hepatoblastoma HepG2 cells than in HSV‐2 with intact and mutated UL13‐PK alone, indicating that viral UL13‐PK mutation is essential for vertical HSV‐2 transmission.
A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 from South and Central America and the Caribbean. Although the full spectrum of ZIKV infection of the newborn has yet to be ...determined, other maternal viral infections resulting in transmission to the fetus provide instructive lessons that can be applied to the prospective evaluation of individuals with ZIKV infection. This review focuses on those other congenital infections, including rubella, congenital cytomegalovirus, human immunodeficiency virus, hepatitis B virus, and neonatal herpes simplex virus, from which lessons for the evaluation of ZIKV in the newborn can be applied.
Herpes simplex virus type 1/2 (HSV-1/2) seroprevalence was stable among pregnant women between 1999-2006 and 2007-2014. HSV-1/-2 seronegativity increased among those with ≤3 sex partners highlighting ...vulnerability to primary HSV infection and increased risk of neonatal herpes.
Abstract
Background
Neonatal herpes is a rare, devastating consequence of herpes simplex virus type 1 (HSV-1) or 2 (HSV-2) infection during pregnancy. The risk of neonatal infection is higher among pregnant women seronegative for HSV-1 or HSV-2 who acquire their first HSV infection near delivery.
Methods
We estimated HSV-1 and HSV-2 seroprevalence among pregnant women aged 20-39 years in 1999-2014, assessed HSV seroprevalence changes between 1999-2006 and 2007-2014, and compared HSV seroprevalence between pregnant women and sexually active, nonpregnant women aged 20-39 years in 2007-2014 using National Health and Nutrition Examination Survey data.
Results
Among pregnant women in 1999-2014, HSV-1 seroprevalence was 59.3%, HSV-2 seroprevalence was 21.1%, and HSV seronegativity was 30.6%. Between 1999-2006 and 2007-2014, HSV-1 and HSV-2 seroprevalence among pregnant women remained stable. However, among pregnant women with ≤3 sex partners (approximately 40% of all pregnant women), seronegativity for both HSV-1 and HSV-2 increased from 35.6% to 51.4% (P < .05). In 2007-2014, nonpregnant women who were (1) unmarried, (2) living below poverty level, or (3) had ≥4 sex partners were more likely than pregnant women to be seronegative for both HSV-1 and HSV-2 (P < .05).
Conclusions
HSV-1 and HSV-2 seroprevalence among US pregnant women remained stable between 1999 and 2014. However, pregnant women with fewer sex partners were increasingly seronegative for both HSV-1 and HSV-2, indicating an increasing proportion of pregnant women who are vulnerable to primary HSV acquisition in pregnancy, which confers an increased risk of transmitting HSV to their neonates.
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•Trivalent mRNA and protein vaccines produce robust neutralizing antibodies in dams and pups.•Trivalent mRNA and protein vaccines prevent infection of multiple organs.•Durability of ...vaccine protection extends into second-generation litters.
Neonatal herpes is a dreaded complication of genital herpes infection in pregnancy. We recently compared two vaccine platforms for preventing genital herpes in female mice and guinea pigs and determined that HSV-2 glycoproteins C, D and E expressed using nucleoside-modified mRNA in lipid nanoparticles provided better protection than the same antigens produced as baculovirus proteins and administered with CpG and alum. Here we evaluated mRNA and protein immunization for protection against neonatal herpes. Female mice were immunized prior to mating and newborns were infected intranasally with HSV-2. IgG binding and neutralizing antibody levels in mothers and newborns were comparable using the mRNA or protein vaccines. Both vaccines protected first and second litter newborns against disseminated infection based on virus titers in multiple organs. We conclude that both vaccines are efficacious at preventing neonatal herpes, which leaves the mRNA vaccine as our preferred candidate based on better protection against genital herpes.
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