Materiały źródłowe

• #1 Laboratory Diagnosis of Neonatal Herpes Simplex Virus Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6498033/

  Herpes simplex virus (HSV) is a common and often benign infection in humans; although it less commonly affects newborns, infection in this age group can be devastating. Newborns often present with nonspecific clinical findings, making timely and accurate diagnosis of infection critical. […] A wide variety of tests are available for detecting herpes simplex virus infection, but only a subset are useful and validated in the newborn population. The current review summarizes available diagnostic testing for neonatal disease, including discussing limitations, unmet needs, and emerging data on molecular testing methods. […] A thorough evaluation and accurate clinical diagnostic testing are critical to making this diagnosis and guiding appropriate treatment. […] The importance of a reliable and prompt etiologic laboratory diagnosis of neonatal HSV is underscored by its nonspecific clinical presentation and the fact that early antiviral therapy can reduce severity and improve outcomes.

• #2 Neonatal Herpes Simplex Virus (HSV) Infection – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/infections-in-neonates/neonatal-herpes-simplex-virus-hsv-infection

  Neonatal herpes simplex virus infection is usually transmitted during delivery. Diagnosis is by viral culture, polymerase chain reaction testing, immunofluorescence, or electron microscopy. […] Rapid diagnosis by viral culture or HSV PCR is essential. The most common site of retrieval is skin vesicles. […] All infants with HSV disease should have an ophthalmologic examination and neuroimaging. […] Acyclovir should be started immediately and presumptively in suspected cases while awaiting confirmatory diagnostic tests. […] The mortality rate of untreated disseminated herpes simplex disease is 85%; among neonates with untreated encephalitis, it is approximately 50%. […] To prevent neonatal herpes infection, pregnant patients with a history of genital herpes should be offered suppressive viral therapy at or beyond 36 weeks gestation. […] In suspected cases, presumptive therapy and rapid diagnosis by HSV PCR of cerebrospinal fluid, blood, or lesions are essential to optimize outcomes.

• #3 Neonatal Herpes Simplex Virus Infections | AAFP

  https://www.aafp.org/pubs/afp/issues/2002/0315/p1138.html

  Neonatal herpes simplex virus infections can result in serious morbidity and mortality. […] The diagnosis of neonatal HSV can be difficult, but it should be suspected in any newborn with irritability, lethargy, fever or poor feeding at one week of age. Diagnosis is made by culturing the blood, cerebrospinal fluid, urine and fluid from eyes, nose and mucous membranes. […] The diagnosis of neonatal HSV can be difficult initially. The presentation is nonspecific, with signs and symptoms such as irritability, lethargy, fever or failure to feed at about one week of age. […] Diagnosis of an HSV infection in an infant requires a high index of suspicion because the history of an active infection, primary or secondary, in a mother is often not given. HSV infections should be considered in all neonates who present in the first month of life with nonspecific symptoms such as fever, poor feeding, lethargy or seizure.

• #4 Neonatal Herpes Simplex Virus Infections | AAFP

  https://www.aafp.org/pubs/afp/issues/2002/0315/p1138.html

  Neonatal herpes simplex virus infections can result in serious morbidity and mortality. […] The diagnosis of neonatal HSV can be difficult, but it should be suspected in any newborn with irritability, lethargy, fever or poor feeding at one week of age. Diagnosis is made by culturing the blood, cerebrospinal fluid, urine and fluid from eyes, nose and mucous membranes. […] The diagnosis of neonatal HSV can be difficult initially. The presentation is nonspecific, with signs and symptoms such as irritability, lethargy, fever or failure to feed at about one week of age. […] Diagnosis of an HSV infection in an infant requires a high index of suspicion because the history of an active infection, primary or secondary, in a mother is often not given. HSV infections should be considered in all neonates who present in the first month of life with nonspecific symptoms such as fever, poor feeding, lethargy or seizure.

• #5 Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic | BMJ Case Reports

  https://casereports.bmj.com/content/14/3/e241405

  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. […] Despite the initial negative HSV serology, HSV-1 PCR from a scalp lesion returned positive. […] 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. […] Neonatal HSV infection still poses a diagnostic dilemma for clinicians considering advances in diagnostic methods. […] It is challenging to diagnose neonatal herpes infection when typical skin lesions are absent. […] Neonatal HSV infection can be classified into three main types: localised skin, eye and mouth (SEM); Central Nervous System (CNS) with or without SEM and disseminated infection.

• #6 Neonatal herpes – Don’t Forget the Bubbles

  https://dontforgetthebubbles.com/neonatal-herpes/

  Disease caused by Herpes Simplex Virus (HSV) types 1 and 2 can have devastating consequences. […] Neonatal herpes can present with various symptoms, and diagnosis can be challenging. […] The standard diagnosis of neonatal herpes is by PCR (on both HSV types), performed on swabs (cutaneous, nasopharyngeal mucosa, ocular, rectal), serum, and liquor. […] Be aware that typical cutaneous signs are only present in 50% of cases in neonates, so testing for herpes is also important when symptoms are less clear-cut. […] When testing is done immediately after birth, for example, if a woman has symptoms during delivery, swab results can be false-positive due to left-over HSV of maternal origin. […] Liquor PCR can be false-negative in an early disease stage and may have to be repeated if suspicion is high and no other organisms were identified the first time.

• #7 Neonatal Herpes Infection: A Review – Page 3

  https://www.medscape.com/viewarticle/472408_3

  The clinical presentation of neonatal herpes infection differs according to the type of infection. Vesicular skin lesions are the most predominant symptom consistent with neonatal herpes infection and, when lesions are present, herpes infection must be presumed until proven otherwise. […] Although vesicular lesions are the most frequent presentation, the absence of lesions should not preclude the consideration of neonatal HSV infection. […] Those infants with SEM disease are the most easily diagnosed since they usually present with obvious vesicular lesions. […] Infants with CNS disease present with acute symptoms of meningitis, including a bulging fontanel, irritability, abnormal movements or positioning, and most commonly seizure activity. […] Finally, infants presenting with disseminated herpes disease typically present with symptoms very similar to those associated with bacterial infection.

• #8 Laboratory Diagnosis of Neonatal Herpes Simplex Virus Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6498033/

  Although HSV can be detected by various methodologies, selection of the appropriate assays specific in this setting enhances the quality of the results and avoids delaying reporting. […] The following assays are available for consideration. […] The clinical syndrome will be based on the results of these tests, with isolated SEM disease diagnosed if all testing is negative other than the surface swabs and/or vesicles, and CNS disease diagnosed if CSF PCR is positive (whether or not surface or vesicle samples are positive) but there is no evidence of visceral involvement (e.g., pneumonia or abnormal liver function) to suggest disseminated disease. […] Although resistance to acyclovir is rare in neonatal HSV infection, it has been described in patients whose mothers previously received suppressive acyclovir treatment.

• #9 Laboratory Diagnosis of Neonatal Herpes Simplex Virus Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6498033/

  Testing HSV DNA on blood samples by PCR has recently been shown to be beneficial for laboratory diagnosis of neonatal infection. […] Although HSV PCR performed on CSF is the most sensitive test for virologic confirmation of CNS disease, a negative result does not rule out the possibility of CNS infection. […] Mortality from neonatal HSV disease was dramatically improved by the introduction of high-dose acyclovir treatment as standard care. […] Even with appropriate treatment, survivors of neonatal HSV disease remain at risk for recurrent skin lesions, recurrent CNS disease, and neurodevelopmental impairment. […] Current guidelines recommend virus culture and/or PCR assays on multiple samples, including surface samples (eye, mouth, nasopharynx, and anus), skin lesions, blood, and CSF samples.

• #10 Neonatal Herpes Simplex Virus Infections | AAFP

  https://www.aafp.org/pubs/afp/issues/2002/0315/p1138.html

  Any vesicular rash in an infant up to eight weeks of age should be cultured and the infant immediately started on antiviral therapy with acyclovir (Zovirax) pending culture results. […] All infants suspected to have or who are diagnosed with an HSV infection should be treated with parenteral antiviral therapy. The duration of disease before antiviral therapy is initiated is significantly correlated with morbidity and mortality. Currently, suggested therapy is acyclovir 60 mg per kg per day in three divided doses intravenously for 14 days for disease limited to skin, eyes and mucous membranes, and 21 days for central nervous system or disseminated disease. […] The HSV-exposed neonate should be monitored closely for any signs of infection. Initial cultures should be performed at 24 to 48 hours, then weekly cultures of conjunctiva, nose, mouth, urine and rectum for HSV-1 or HSV-2 have been suggested. […] Any exposed infant with clinical signs of HSV should be cultured (conjunctiva, nose, mouth, urine, rectum, CSF, blood buffy coat), CSF should be sent for PCR analysis, and the infant should be immediately started on intravenous acyclovir therapy.

• #11 NEONATAL HSV INFECTION

  https://guidelines.stief.org.nz/herpes-neonatal-hsv-infection

  About 6080% of infants with neonatal HSV disease are born to women with unrecognised infection. […] The risk is greatest when a previously seronegative woman acquires genital herpes (HSV-1 or HSV-2) at or near the time of delivery. […] In this case, the risk of neonatal HSV infection is 50%, while vertical transmission rates of 25% are found in those with a non-primary first episode. […] The usual age of symptom onset in neonatal HSV infection is between 5 and 21 days, but there may be a delay in diagnosis if the significance of the symptoms is not initially recognised. […] Physicians caring for sick infants in the first 6 weeks of life should always be aware that neonatal HSV infection remains a possibility, even when no parental history of HSV infection is given. […] If vesicular lesions are present, the base of the lesion should be scraped and sent for PCR.

• #12 NEONATAL HSV INFECTION

  https://guidelines.stief.org.nz/herpes-neonatal-hsv-infection

  Given that neonatal HSV infection can be present even in the absence of skin lesions, other diagnostic specimens are also required. […] Therefore, swabs should be taken from the nasopharynx/mouth, conjunctiva, umbilicus, rectum and urine. […] A CSF sample should be taken for HSV PCR testing, and evaluation of other parameters such as cell count, protein and glucose. […] PCR is a rapid, highly sensitive and specific technique that detects tiny quantities of viral DNA. […] It is more reliable than viral culture for CNS infections. […] However, although a positive PCR result is highly predictive of infection, a negative result does not eliminate the possibility of disease. […] A negative PCR finding from a CSF sample should be evaluated in conjunction with the overall clinical picture, including other diagnostic modalities, and should not be used on its own to exclude CNS HSV infection.

• #13 Congenital Herpes Simplex – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507897/

  Congenital HSV infection can be clinically challenging due to the early manifestations often being subtle and nonspecific. […] Prompt treatment requires early consideration of congenital HSV as a possibility in neonates with mucocutaneous lesions, CNS abnormalities, or a sepsis-like picture. […] Given that HSV grows readily in cell culture, cultures of vesicular lesions and affected sites are preferred for diagnosing congenital HSV. […] A polymerase chain reaction (PCR) assay can often detect HSV DNA in CSF from neonates with CNS infection and older children and adults with HSV encephalitis (HSE); PCR is the diagnostic method of choice for CNS HSV involvement. […] Parenteral acyclovir is the standard of care in treating congenital HSV infection. […] All infants with CNS involvement should have a repeat lumbar puncture performed near the end of therapy to document that the CSF is negative for HSV DNA on PCR assay.

• #14 Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic | BMJ Case Reports

  https://casereports.bmj.com/content/14/3/e241405

  Hyperferritinaemia can be found in particular inflammatory disorders such as haemophagocytic lymphohistiocytosis (HLH) that could be induced by infection with HSV. […] Our infant had substantially elevated levels of ferritin, lactate dehydrogenase and D-dimers in this context. […] Although the scaly spots were not consistent with probable HSV skin lesions, they were scraped for viral PCR and samples from one lesion were obtained for HSV DNA PCR testing (nucleic acid amplification). […] Seven days later, PCR results for HSV type 1 returned positive from the lesion. […] The case was discussed with the tertiary infectious diseases team who advised treatment of disseminated HSV infection based on evidence of hepatitis with raised ALT level and positive HSV-1 PCR. […] Neonatal HSV infection is lifelong with need for ongoing vigilance concerning recurrent infection.

• #15 Prevention and management of neonatal herpes simplex virus infections | Canadian Paediatric Society

  https://cps.ca/documents/position/prevention-management-neonatal-herpes-simplex-virus-infections

  Human herpes simplex virus (HSV) infection in neonates can result in devastating outcomes, including mortality and significant morbidity. […] It considers diagnosis and prognosis according to infection category, along with testing modalities and limitations. […] The most common and important category of NHSV acquisition is intrapartum. […] Newborns may also acquire HSV infection through in utero or postnatal transmission. […] The absence of skin lesions does not negate the possibility of an NHSV diagnosis. […] NHSV infection should be considered in neonates with sepsis syndrome, particularly when this condition is accompanied by liver dysfunction and even when there is no known history of maternal HSV and the infant has no skin vesicles. […] Caution should be exercised when using a negative CSF HSV PCR to rule out CNS HSV, particularly when the sample is obtained in the early stages of illness (the first 24 h to 48 h).

• #16 Herpes Simplex Virus (HSV) in the newborn – Good practice points | Safer Care Victoria

  https://www.safercare.vic.gov.au/councils/ccopmm/good-practice-points/HSV-newborn

  Perinatally acquired HSV can be lethal if not treated early with anti-viral therapy. Diagnosis is impossible to rule out on clinical history alone and routine tests such as CSF HSV DNA PCR or “Biofire” may give false negatives especially if collected early in the illness. […] The aim of this good practice point is to remind clinicians that a negative cerebrospinal fluid (CSF) HSV DNA polymerase chain reaction (PCR) or “BioFire” have false negatives, especially if collected early in the illness. […] Infants may be tested for the presence of HSV by sending CSF or other specimens for detection of HSV1 or 2 related nucleic acid. […] Biofire testing can be falsely negative for a number of reasons i.e. there may be insufficient nucleic acid in the specimen to be detected, there may be strain variation making the nucleic acid sequences unrecognisable, or there can be contamination of the specimen.

• #17 Congenital Herpes Simplex – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507897/

  Congenital HSV infection can be clinically challenging due to the early manifestations often being subtle and nonspecific. […] Prompt treatment requires early consideration of congenital HSV as a possibility in neonates with mucocutaneous lesions, CNS abnormalities, or a sepsis-like picture. […] Given that HSV grows readily in cell culture, cultures of vesicular lesions and affected sites are preferred for diagnosing congenital HSV. […] A polymerase chain reaction (PCR) assay can often detect HSV DNA in CSF from neonates with CNS infection and older children and adults with HSV encephalitis (HSE); PCR is the diagnostic method of choice for CNS HSV involvement. […] Parenteral acyclovir is the standard of care in treating congenital HSV infection. […] All infants with CNS involvement should have a repeat lumbar puncture performed near the end of therapy to document that the CSF is negative for HSV DNA on PCR assay.

• #18 Neonatal herpes – Knowledge and References – Taylor & Francis

  https://taylorandfrancis.com/knowledge/Medicine_and_healthcare/Perinatal_%26_neonatal_medicine/Neonatal_herpes/

  If the baby presents with CNS symptomatology, neuroimaging and HSV PCR on CSF will provide a rapid diagnosis. […] Virus culture should also be performed on these specimens but could require anywhere from two to seven days to produce positive results. […] It is important to note that HSV subtyping is important in the diagnosis of neonatal HSV, because it helps with both epidemiology and prognostication. […] Neonatal herpes simplex virus (HSV) infection is commonly acquired from the genital tract at birth, and infrequently acquired through transplacental transmission of the HSV virus.

• #19 Congenital Herpes Simplex – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507897/

  Congenital herpes simplex is a rare but potentially devastating viral infection that occurs in newborns and is transmitted from mother to baby during childbirth. […] Despite its infrequency, the consequences of congenital herpes simplex underscore the importance of staying informed and up-to-date on best practices in diagnosis and treatment. […] Newborns often present with nonspecific clinical findings, making timely and accurate diagnosis of infection critical. […] However, diagnosing neonatal HSV infection can be challenging when skin lesions are absent. […] Diagnostic confirmation methods include fluorescent antibody staining, enzyme immunoassays (EIAs), and monolayer culture with typing. […] The most common treatment for congenital HSV infection is parenteral acyclovir, which should be administered to all neonates with HSV disease, regardless of the specific manifestations and clinical findings.

• #20 Case Report: Disseminated HSV Infection in a Well-Appearing Neonate | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/1000/p332.html

  A 12-day-old infant with no significant birth history presented with several 1-mm grouped pustular lesions on erythematous bases on the back and right axilla, and vesicular lesions on the umbilicus. […] Swabs were collected for a bacterial culture and herpes simplex virus (HSV) polymerase chain reaction (PCR). […] The HSV PCR of skin and plasma was positive for HSV-1. […] Neonatal HSV infections are classified into three subtypes: localized with skin, eye, or mouth disease; localized central nervous system disease; and disseminated multi-organ involvement. […] Early diagnosis of neonatal HSV and adequate antiviral treatment have lowered the percentage of patients with a developmental delay because of skin, eye, or mouth disease from 25% to less than 2%. […] Tzanck smear with Giemsa stain is an inexpensive test for rapid detection of HSV infection. […] A positive Tzanck smear with multinucleated giant cells and viral cytopathic changes is 100% specific for HSV infection.

• #21 What Are the Causes of Neonatal HSV Infection?

  https://www.icliniq.com/articles/infectious-diseases/neonatal-herpes-simplex-infection

  All three techniques are helpful for accurately diagnosing neonatal herpes simplex infection. However, PCR and immunofluorescence testing are considered more reliable because they can detect trace amounts of the virus. […] Early diagnosis and prompt treatment can significantly reduce the risk of serious complications or death. […] In addition, treatment may involve antiviral medications and supportive care, depending upon the infections severity. […] When it comes to neonatal herpes simplex infection, early diagnosis is critical.

• #22 Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic | BMJ Case Reports

  https://casereports.bmj.com/content/14/3/e241405

  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. […] Despite the initial negative HSV serology, HSV-1 PCR from a scalp lesion returned positive. […] 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. […] Neonatal HSV infection still poses a diagnostic dilemma for clinicians considering advances in diagnostic methods. […] It is challenging to diagnose neonatal herpes infection when typical skin lesions are absent. […] Neonatal HSV infection can be classified into three main types: localised skin, eye and mouth (SEM); Central Nervous System (CNS) with or without SEM and disseminated infection.

• #23 Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic | BMJ Case Reports

  https://casereports.bmj.com/content/14/3/e241405

  Hyperferritinaemia can be found in particular inflammatory disorders such as haemophagocytic lymphohistiocytosis (HLH) that could be induced by infection with HSV. […] Our infant had substantially elevated levels of ferritin, lactate dehydrogenase and D-dimers in this context. […] Although the scaly spots were not consistent with probable HSV skin lesions, they were scraped for viral PCR and samples from one lesion were obtained for HSV DNA PCR testing (nucleic acid amplification). […] Seven days later, PCR results for HSV type 1 returned positive from the lesion. […] The case was discussed with the tertiary infectious diseases team who advised treatment of disseminated HSV infection based on evidence of hepatitis with raised ALT level and positive HSV-1 PCR. […] Neonatal HSV infection is lifelong with need for ongoing vigilance concerning recurrent infection.

• #24 Neonatal herpes simplex virus (HSV) infection: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/neonatal-herpes-simplex-virus-hsv-infection-clinical-features-and-diagnosis

  Neonatal herpes simplex virus (HSV) infection: Clinical features and diagnosis […] Herpes simplex virus (HSV) infection during pregnancy poses a significant risk to the developing fetus and newborn. Neonates can acquire HSV infection by intrauterine, perinatal, or postnatal transmission of the virus. Neonatal HSV infection causes serious morbidity and mortality and leaves many survivors with permanent sequelae. Strong clinical suspicion, timely diagnosis, and early antiviral treatment are critical to improving outcome. […] The clinical features and diagnosis of neonatal HSV infection will be reviewed here. […] […] EVALUATION AND DIAGNOSIS […] Clinical suspicion […] Detection of HSV […] – Specimens to collect […] – Viral culture […] – Polymerase chain reaction […] – Cerebrospinal fluid

• #25 Neonatal herpes simplex virus (HSV) infection: Clinical features and diagnosis – UpToDate

  https://www.uptodate.com/contents/neonatal-herpes-simplex-virus-hsv-infection-clinical-features-and-diagnosis

  – Blood […] – Skin and mucous membrane […] – Other sites […] – DFA and EIA […] – Serology […] – Interpretation/diagnosis […] Additional studies […] – Laboratory evaluation […] – Eye examination […] – Electroencephalogram […] – Diagnostic imaging […] – Neuroimaging […] – Chest radiograph […] – Abdominal ultrasonography

• #26 Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic | BMJ Case Reports

  https://casereports.bmj.com/content/14/3/e241405

  Hyperferritinaemia can be found in particular inflammatory disorders such as haemophagocytic lymphohistiocytosis (HLH) that could be induced by infection with HSV. […] Our infant had substantially elevated levels of ferritin, lactate dehydrogenase and D-dimers in this context. […] Although the scaly spots were not consistent with probable HSV skin lesions, they were scraped for viral PCR and samples from one lesion were obtained for HSV DNA PCR testing (nucleic acid amplification). […] Seven days later, PCR results for HSV type 1 returned positive from the lesion. […] The case was discussed with the tertiary infectious diseases team who advised treatment of disseminated HSV infection based on evidence of hepatitis with raised ALT level and positive HSV-1 PCR. […] Neonatal HSV infection is lifelong with need for ongoing vigilance concerning recurrent infection.

• #27 Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic | BMJ Case Reports

  https://bibliotheek.ehb.be:2635/content/14/3/e241405

  Hyperferritinaemia can be found in particular inflammatory disorders such as haemophagocytic lymphohistiocytosis (HLH) that could be induced by infection with HSV. […] Our infant had substantially elevated levels of ferritin, lactate dehydrogenase and D-dimers in this context. […] Although the scaly spots were not consistent with probable HSV skin lesions, they were scraped for viral PCR and samples from one lesion were obtained for HSV DNA PCR testing (nucleic acid amplification). […] Seven days later, PCR results for HSV type 1 returned positive from the lesion. […] Our patient had negative HSV serology, however, if there is hepatic dysfunction of unclear aetiology, empiric therapy with acyclovir is reasonable to be initiated due to the possible severity of HSV hepatitis. […] Elevated ferritin level has a number of causes, including neonatal HLH.

• #28 Neonatal Herpes: Can You Be Born With Herpes?

  https://my.clevelandclinic.org/health/diseases/neonatal-herpes-simplex

  If providers suspect herpes, they do testing right away to check for the presence of the herpes simplex virus in your baby’s body. […] If healthcare providers suspect your baby has neonatal herpes, it’s very likely that your baby will be admitted to the hospital for treatment. […] Providers use an antiviral medication called acyclovir to treat neonatal herpes. Your baby will receive this treatment through an IV and then by mouth (as a liquid). […] If lab testing confirms your baby has herpes, then their care team will likely do: A chest X-ray. An abdominal X-ray. Brain imaging, like a brain MRI scan (magnetic resonance imaging scan). A detailed eye exam. […] If your baby has any signs of neonatal herpes, contact a healthcare provider right away. Neonatal herpes needs quick treatment. The sooner your baby gets treatment, the better their chances of survival and of recovery with minimal or no long-term effects.

• #29 Neonatal Meningitis & Herpes Encephalitis | Birth Injuries

  https://www.malpracticeohio.com/birth-injuries/neonatal-intensive-care-errors/meningitis-herpes-encephalitis/

  HSV-2 causes 70-90% of encephalitis cases in infants, most of which stem from exposure to HSV-2 in genital secretions during delivery. […] Encephalitis is an infection or inflammation of the brain, while meningitis is an infection or inflammation of the layers of thin tissue that cover the brain. These can occur together, and both are medical emergencies, as symptoms can appear suddenly and the virus can progress rapidly. Left untreated, death occurs within 10–14 days. […] The overall mortality rate for neonatal HSV-2 encephalitis is 15-57%; […] A DIS infection is lethal in 31% of cases, and leaves approximately 17% of babies with permanent disabilities. […] Symptoms of encephalitis and meningitis usually appear 4-11 days after birth and may include: Fever, Lethargy, Poor feeding, Vomiting, Body stiffness, Unexplained or unusual irritability, Seizures, Tremors, Full or bulging fontanel (soft spot on the top of the head).

• #30 Neonatal Herpes Simplex Virus (HSV) Infection – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/infections-in-neonates/neonatal-herpes-simplex-virus-hsv-infection

  Neonatal herpes simplex virus infection is usually transmitted during delivery. Diagnosis is by viral culture, polymerase chain reaction testing, immunofluorescence, or electron microscopy. […] Rapid diagnosis by viral culture or HSV PCR is essential. The most common site of retrieval is skin vesicles. […] All infants with HSV disease should have an ophthalmologic examination and neuroimaging. […] Acyclovir should be started immediately and presumptively in suspected cases while awaiting confirmatory diagnostic tests. […] The mortality rate of untreated disseminated herpes simplex disease is 85%; among neonates with untreated encephalitis, it is approximately 50%. […] To prevent neonatal herpes infection, pregnant patients with a history of genital herpes should be offered suppressive viral therapy at or beyond 36 weeks gestation. […] In suspected cases, presumptive therapy and rapid diagnosis by HSV PCR of cerebrospinal fluid, blood, or lesions are essential to optimize outcomes.

• #31 Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic | BMJ Case Reports

  https://casereports.bmj.com/content/14/3/e241405

  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. […] Despite the initial negative HSV serology, HSV-1 PCR from a scalp lesion returned positive. […] 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. […] Neonatal HSV infection still poses a diagnostic dilemma for clinicians considering advances in diagnostic methods. […] It is challenging to diagnose neonatal herpes infection when typical skin lesions are absent. […] Neonatal HSV infection can be classified into three main types: localised skin, eye and mouth (SEM); Central Nervous System (CNS) with or without SEM and disseminated infection.

• #32 Neonatal herpes – Knowledge and References – Taylor & Francis

  https://taylorandfrancis.com/knowledge/Medicine_and_healthcare/Perinatal_%26_neonatal_medicine/Neonatal_herpes/

  Neonatal herpes is a viral infection that is highly dangerous and often fatal, and is typically contracted during or shortly after delivery through contact with infected genital secretions. […] The diagnosis of neonatal herpes is confirmed by viral culture or preferably immediate direct fluorescent antibody (DFA) staining of material from skin or ocular lesions. CNS involvement is detected by polymerase chain reaction (PCR) of the cerebrospinal fluid (CSF). […] Neonatal herpes infection is serious but extremely rare, occurring in less than two per 100 000 live births. […] Infants with neonatal HSV can be divided into three groups: (a) skin, eye, or mouth (SEM) involvement only, (b) encephalitis with or without SEM, (c) disseminated infection. […] The laboratory diagnostic techniques useful for neonatal HSV infection are dependent on disease presentation.

• #33 Neonatal Herpes Infection: A Review – Page 3

  https://www.medscape.com/viewarticle/472408_3

  The clinical presentation of neonatal herpes infection differs according to the type of infection. Vesicular skin lesions are the most predominant symptom consistent with neonatal herpes infection and, when lesions are present, herpes infection must be presumed until proven otherwise. […] Although vesicular lesions are the most frequent presentation, the absence of lesions should not preclude the consideration of neonatal HSV infection. […] Those infants with SEM disease are the most easily diagnosed since they usually present with obvious vesicular lesions. […] Infants with CNS disease present with acute symptoms of meningitis, including a bulging fontanel, irritability, abnormal movements or positioning, and most commonly seizure activity. […] Finally, infants presenting with disseminated herpes disease typically present with symptoms very similar to those associated with bacterial infection.

• #34 Laboratory Diagnosis of Neonatal Herpes Simplex Virus Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6498033/

  Although HSV can be detected by various methodologies, selection of the appropriate assays specific in this setting enhances the quality of the results and avoids delaying reporting. […] The following assays are available for consideration. […] The clinical syndrome will be based on the results of these tests, with isolated SEM disease diagnosed if all testing is negative other than the surface swabs and/or vesicles, and CNS disease diagnosed if CSF PCR is positive (whether or not surface or vesicle samples are positive) but there is no evidence of visceral involvement (e.g., pneumonia or abnormal liver function) to suggest disseminated disease. […] Although resistance to acyclovir is rare in neonatal HSV infection, it has been described in patients whose mothers previously received suppressive acyclovir treatment.

• #35 Neonatal Herpes Infection: A Review – Page 3

  https://www.medscape.com/viewarticle/472408_3

  The clinical presentation of neonatal herpes infection differs according to the type of infection. Vesicular skin lesions are the most predominant symptom consistent with neonatal herpes infection and, when lesions are present, herpes infection must be presumed until proven otherwise. […] Although vesicular lesions are the most frequent presentation, the absence of lesions should not preclude the consideration of neonatal HSV infection. […] Those infants with SEM disease are the most easily diagnosed since they usually present with obvious vesicular lesions. […] Infants with CNS disease present with acute symptoms of meningitis, including a bulging fontanel, irritability, abnormal movements or positioning, and most commonly seizure activity. […] Finally, infants presenting with disseminated herpes disease typically present with symptoms very similar to those associated with bacterial infection.

• #36 Neonatal herpes – Knowledge and References – Taylor & Francis

  https://taylorandfrancis.com/knowledge/Medicine_and_healthcare/Perinatal_%26_neonatal_medicine/Neonatal_herpes/

  If the baby presents with CNS symptomatology, neuroimaging and HSV PCR on CSF will provide a rapid diagnosis. […] Virus culture should also be performed on these specimens but could require anywhere from two to seven days to produce positive results. […] It is important to note that HSV subtyping is important in the diagnosis of neonatal HSV, because it helps with both epidemiology and prognostication. […] Neonatal herpes simplex virus (HSV) infection is commonly acquired from the genital tract at birth, and infrequently acquired through transplacental transmission of the HSV virus.

• #37 Neonatal Herpes Infection: A Review – Page 3

  https://www.medscape.com/viewarticle/472408_3

  The clinical presentation of neonatal herpes infection differs according to the type of infection. Vesicular skin lesions are the most predominant symptom consistent with neonatal herpes infection and, when lesions are present, herpes infection must be presumed until proven otherwise. […] Although vesicular lesions are the most frequent presentation, the absence of lesions should not preclude the consideration of neonatal HSV infection. […] Those infants with SEM disease are the most easily diagnosed since they usually present with obvious vesicular lesions. […] Infants with CNS disease present with acute symptoms of meningitis, including a bulging fontanel, irritability, abnormal movements or positioning, and most commonly seizure activity. […] Finally, infants presenting with disseminated herpes disease typically present with symptoms very similar to those associated with bacterial infection.

• #38 Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic | BMJ Case Reports

  https://casereports.bmj.com/content/14/3/e241405

  Hyperferritinaemia can be found in particular inflammatory disorders such as haemophagocytic lymphohistiocytosis (HLH) that could be induced by infection with HSV. […] Our infant had substantially elevated levels of ferritin, lactate dehydrogenase and D-dimers in this context. […] Although the scaly spots were not consistent with probable HSV skin lesions, they were scraped for viral PCR and samples from one lesion were obtained for HSV DNA PCR testing (nucleic acid amplification). […] Seven days later, PCR results for HSV type 1 returned positive from the lesion. […] The case was discussed with the tertiary infectious diseases team who advised treatment of disseminated HSV infection based on evidence of hepatitis with raised ALT level and positive HSV-1 PCR. […] Neonatal HSV infection is lifelong with need for ongoing vigilance concerning recurrent infection.

• #39 Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic | BMJ Case Reports

  https://bibliotheek.ehb.be:2635/content/14/3/e241405

  Hyperferritinaemia can be found in particular inflammatory disorders such as haemophagocytic lymphohistiocytosis (HLH) that could be induced by infection with HSV. […] Our infant had substantially elevated levels of ferritin, lactate dehydrogenase and D-dimers in this context. […] Although the scaly spots were not consistent with probable HSV skin lesions, they were scraped for viral PCR and samples from one lesion were obtained for HSV DNA PCR testing (nucleic acid amplification). […] Seven days later, PCR results for HSV type 1 returned positive from the lesion. […] Our patient had negative HSV serology, however, if there is hepatic dysfunction of unclear aetiology, empiric therapy with acyclovir is reasonable to be initiated due to the possible severity of HSV hepatitis. […] Elevated ferritin level has a number of causes, including neonatal HLH.

• #40 Neonatal Herpes Infection: A Review – Page 3

  https://www.medscape.com/viewarticle/472408_3

  Due to the increasing incidence of neonatal herpes infection and the exceptionally high mortality and morbidity of this disease, a high index of suspicion is imperative in all clinicians caring for neonatal patients. […] The clinical presentation of neonatal herpes may be very nonspecific, therefore a high index of suspicion must be present to reduce the mortality and morbidity associated with a delay in diagnosis. […] Any delay in the diagnosis of neonatal HSV infection can have disastrous consequences. While the presence of SEM infection is associated with a 0% mortality rate, without prompt treatment, up to 70% of infants with SEM disease will progress to either CNS or disseminated disease both of which have an increased risk of death or permanent sequelae. […] The diagnosis of herpes infection must be entertained in any infant presenting with seizures with no underlying etiology.

• #41 Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic | BMJ Case Reports

  https://casereports.bmj.com/content/14/3/e241405

  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. […] Despite the initial negative HSV serology, HSV-1 PCR from a scalp lesion returned positive. […] 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. […] Neonatal HSV infection still poses a diagnostic dilemma for clinicians considering advances in diagnostic methods. […] It is challenging to diagnose neonatal herpes infection when typical skin lesions are absent. […] Neonatal HSV infection can be classified into three main types: localised skin, eye and mouth (SEM); Central Nervous System (CNS) with or without SEM and disseminated infection.

• #42 Congenital Herpes Simplex – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507897/

  Congenital HSV infection can be clinically challenging due to the early manifestations often being subtle and nonspecific. […] Prompt treatment requires early consideration of congenital HSV as a possibility in neonates with mucocutaneous lesions, CNS abnormalities, or a sepsis-like picture. […] Given that HSV grows readily in cell culture, cultures of vesicular lesions and affected sites are preferred for diagnosing congenital HSV. […] A polymerase chain reaction (PCR) assay can often detect HSV DNA in CSF from neonates with CNS infection and older children and adults with HSV encephalitis (HSE); PCR is the diagnostic method of choice for CNS HSV involvement. […] Parenteral acyclovir is the standard of care in treating congenital HSV infection. […] All infants with CNS involvement should have a repeat lumbar puncture performed near the end of therapy to document that the CSF is negative for HSV DNA on PCR assay.

• #43 Neonatal herpes – Don’t Forget the Bubbles

  https://dontforgetthebubbles.com/neonatal-herpes/

  Disease caused by Herpes Simplex Virus (HSV) types 1 and 2 can have devastating consequences. […] Neonatal herpes can present with various symptoms, and diagnosis can be challenging. […] The standard diagnosis of neonatal herpes is by PCR (on both HSV types), performed on swabs (cutaneous, nasopharyngeal mucosa, ocular, rectal), serum, and liquor. […] Be aware that typical cutaneous signs are only present in 50% of cases in neonates, so testing for herpes is also important when symptoms are less clear-cut. […] When testing is done immediately after birth, for example, if a woman has symptoms during delivery, swab results can be false-positive due to left-over HSV of maternal origin. […] Liquor PCR can be false-negative in an early disease stage and may have to be repeated if suspicion is high and no other organisms were identified the first time.

• #44 Neonatal Herpes Infection: A Review – Page 3

  https://www.medscape.com/viewarticle/472408_3

  The clinical presentation of neonatal herpes infection differs according to the type of infection. Vesicular skin lesions are the most predominant symptom consistent with neonatal herpes infection and, when lesions are present, herpes infection must be presumed until proven otherwise. […] Although vesicular lesions are the most frequent presentation, the absence of lesions should not preclude the consideration of neonatal HSV infection. […] Those infants with SEM disease are the most easily diagnosed since they usually present with obvious vesicular lesions. […] Infants with CNS disease present with acute symptoms of meningitis, including a bulging fontanel, irritability, abnormal movements or positioning, and most commonly seizure activity. […] Finally, infants presenting with disseminated herpes disease typically present with symptoms very similar to those associated with bacterial infection.

• #45 Prevention and management of neonatal herpes simplex virus infections | Canadian Paediatric Society

  https://cps.ca/documents/position/prevention-management-neonatal-herpes-simplex-virus-infections

  Human herpes simplex virus (HSV) infection in neonates can result in devastating outcomes, including mortality and significant morbidity. […] It considers diagnosis and prognosis according to infection category, along with testing modalities and limitations. […] The most common and important category of NHSV acquisition is intrapartum. […] Newborns may also acquire HSV infection through in utero or postnatal transmission. […] The absence of skin lesions does not negate the possibility of an NHSV diagnosis. […] NHSV infection should be considered in neonates with sepsis syndrome, particularly when this condition is accompanied by liver dysfunction and even when there is no known history of maternal HSV and the infant has no skin vesicles. […] Caution should be exercised when using a negative CSF HSV PCR to rule out CNS HSV, particularly when the sample is obtained in the early stages of illness (the first 24 h to 48 h).

• #46 Herpes Simplex Virus (HSV) in the newborn – Good practice points | Safer Care Victoria

  https://www.safercare.vic.gov.au/councils/ccopmm/good-practice-points/HSV-newborn

  Perinatally acquired HSV can be lethal if not treated early with anti-viral therapy. Diagnosis is impossible to rule out on clinical history alone and routine tests such as CSF HSV DNA PCR or “Biofire” may give false negatives especially if collected early in the illness. […] The aim of this good practice point is to remind clinicians that a negative cerebrospinal fluid (CSF) HSV DNA polymerase chain reaction (PCR) or “BioFire” have false negatives, especially if collected early in the illness. […] Infants may be tested for the presence of HSV by sending CSF or other specimens for detection of HSV1 or 2 related nucleic acid. […] Biofire testing can be falsely negative for a number of reasons i.e. there may be insufficient nucleic acid in the specimen to be detected, there may be strain variation making the nucleic acid sequences unrecognisable, or there can be contamination of the specimen.

• #47 Herpes Simplex Virus (HSV) in the newborn – Good practice points | Safer Care Victoria

  https://www.safercare.vic.gov.au/councils/ccopmm/good-practice-points/HSV-newborn

  HSV has long been identified as occurring in infants whose mothers have no history of clinical HSV, making diagnosis impossible to rule out on clinical history alone (Pinninti and Kimberlin, 2014). […] In cases where HSV needs to be ruled out, relying solely on a negative CSF result is insufficient and further tests need to be employed- specifically swabs from mouth, conjunctiva, nasopharynx, rectum, any vesicles (if present) and blood for HSV DNA PCR and LFT (Especially ALT). Repeating CSF two to three days later may also be helpful.

• #48 NEONATAL HSV INFECTION

  https://guidelines.stief.org.nz/herpes-neonatal-hsv-infection

  About 6080% of infants with neonatal HSV disease are born to women with unrecognised infection. […] The risk is greatest when a previously seronegative woman acquires genital herpes (HSV-1 or HSV-2) at or near the time of delivery. […] In this case, the risk of neonatal HSV infection is 50%, while vertical transmission rates of 25% are found in those with a non-primary first episode. […] The usual age of symptom onset in neonatal HSV infection is between 5 and 21 days, but there may be a delay in diagnosis if the significance of the symptoms is not initially recognised. […] Physicians caring for sick infants in the first 6 weeks of life should always be aware that neonatal HSV infection remains a possibility, even when no parental history of HSV infection is given. […] If vesicular lesions are present, the base of the lesion should be scraped and sent for PCR.

• #49 Neonatal Herpes: When a Baby Catches the Infection

  https://flo.health/being-a-mom/your-baby/baby-health-and-safety/neonatal-herpes

  When it comes to neonatal herpes, its important to notice any symptoms as early as you can. The disease usually develops fast and can have serious consequences on a newborns health. The neonatal herpes symptoms might be as follows: A baby may look irritated without any special reason. Your baby may seem lethargic while reacting slowly. Your baby refuses to eat. They might get a fever. […] If you have an active infection, your doctor will take precautionary measures to help you give birth to a healthy infant. Most likely, youll get acyclovir, an antiviral medicine that has demonstrated the best results in suppressing HSV. […] Medical experts claim that almost 80 percent of babies with neonatal herpes are born from mothers with unrecognized oral and genital HSV infection. […] The majority of women with active HSV infection during the six weeks before birth undergo a cesarean section. Medical experts consider this procedure the safest way to prevent spreading the infection. […] In many cases, neonatal herpes doesnt show any symptoms. Neither infected babies nor their mothers show neonatal herpes symptoms during the first stage of the disease.

• #50 Laboratory Diagnosis of Neonatal Herpes Simplex Virus Infections

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6498033/

  Herpes simplex virus (HSV) is a common and often benign infection in humans; although it less commonly affects newborns, infection in this age group can be devastating. Newborns often present with nonspecific clinical findings, making timely and accurate diagnosis of infection critical. […] A wide variety of tests are available for detecting herpes simplex virus infection, but only a subset are useful and validated in the newborn population. The current review summarizes available diagnostic testing for neonatal disease, including discussing limitations, unmet needs, and emerging data on molecular testing methods. […] A thorough evaluation and accurate clinical diagnostic testing are critical to making this diagnosis and guiding appropriate treatment. […] The importance of a reliable and prompt etiologic laboratory diagnosis of neonatal HSV is underscored by its nonspecific clinical presentation and the fact that early antiviral therapy can reduce severity and improve outcomes.

• #51 Congenital Herpes Simplex – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507897/

  The prognosis of congenital HSV infection is contingent upon several factors, including the timing of maternal infection, the promptness of diagnosis, and the extent of neonatal organ involvement. […] Early initiation of antiviral therapy (eg, acyclovir) is paramount to improving outcomes, and prompt intervention is associated with a better prognosis. […] Congenital HSV infection can lead to a spectrum of complications, reflecting the virus’s propensity for neural tissue and its capacity to disseminate to various organs. […] Despite advances in antiviral therapy, the risk of mortality and long-term morbidity remains substantial, necessitating early intervention, comprehensive management strategies, and vigilant follow-up care to address the diverse complications associated with congenital HSV infection.

• #52 Neonatal Herpes Simplex Virus (HSV) Infection – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/infections-in-neonates/neonatal-herpes-simplex-virus-hsv-infection

  Neonatal herpes simplex virus infection is usually transmitted during delivery. Diagnosis is by viral culture, polymerase chain reaction testing, immunofluorescence, or electron microscopy. […] Rapid diagnosis by viral culture or HSV PCR is essential. The most common site of retrieval is skin vesicles. […] All infants with HSV disease should have an ophthalmologic examination and neuroimaging. […] Acyclovir should be started immediately and presumptively in suspected cases while awaiting confirmatory diagnostic tests. […] The mortality rate of untreated disseminated herpes simplex disease is 85%; among neonates with untreated encephalitis, it is approximately 50%. […] To prevent neonatal herpes infection, pregnant patients with a history of genital herpes should be offered suppressive viral therapy at or beyond 36 weeks gestation. […] In suspected cases, presumptive therapy and rapid diagnosis by HSV PCR of cerebrospinal fluid, blood, or lesions are essential to optimize outcomes.

• #53 Herpes Simplex Virus (HSV) Infection in Newborns – Children’s Health Issues – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/children-s-health-issues/infections-in-newborns/herpes-simplex-virus-hsv-infection-in-newborns

  Herpes simplex virus infection usually causes only annoying, recurring blisters in healthy adults but can cause severe infection in newborns. […] The diagnosis is typically based on tests of samples taken from the blisters. […] To diagnose herpes simplex virus infection, doctors take samples of material from the blisters and other body fluids and send the samples to a laboratory to grow (culture) the virus and identify the herpes simplex virus. […] Newborns who have a widespread infection are given the antiviral medication acyclovir by vein (intravenously) for 3 weeks and then by mouth for 6 months. […] If herpes simplex virus infection of the newborn is not treated, it usually progresses to severe problems. The infection is fatal in approximately 85% of babies with untreated widespread infection and in approximately 50% of newborns with untreated brain infection.

• #54 Case Report: Disseminated HSV Infection in a Well-Appearing Neonate | AAFP

  https://www.aafp.org/pubs/afp/issues/2021/1000/p332.html

  A 12-day-old infant with no significant birth history presented with several 1-mm grouped pustular lesions on erythematous bases on the back and right axilla, and vesicular lesions on the umbilicus. […] Swabs were collected for a bacterial culture and herpes simplex virus (HSV) polymerase chain reaction (PCR). […] The HSV PCR of skin and plasma was positive for HSV-1. […] Neonatal HSV infections are classified into three subtypes: localized with skin, eye, or mouth disease; localized central nervous system disease; and disseminated multi-organ involvement. […] Early diagnosis of neonatal HSV and adequate antiviral treatment have lowered the percentage of patients with a developmental delay because of skin, eye, or mouth disease from 25% to less than 2%. […] Tzanck smear with Giemsa stain is an inexpensive test for rapid detection of HSV infection. […] A positive Tzanck smear with multinucleated giant cells and viral cytopathic changes is 100% specific for HSV infection.

• #55 Neonatal herpes encephalitis | MedLink Neurology

  https://www.medlink.com/articles/neonatal-herpes-encephalitis

  Prompt institution of antiviral therapy is critical to minimize mortality and morbidity. […] Without specific antiviral therapy, most infected neonates will die, and survivors will have substantial neurologic sequelae. […] Specific antiviral therapy markedly reduces mortality in all clinical forms of infection. […] For disseminated and CNS disease, antiviral treatment reduces mortality to about one half to one third the rate that occurs when no therapy is given. […] The possibility of herpes simplex virus infection must be considered in any neonate with signs or symptoms of sepsis. Specific antiherpes simplex virus drug therapy instituted as early as possible, without waiting for confirmatory test results, is essential to prevent death and to minimize sequelae. […] Acyclovir is the drug of choice for herpes simplex virus.

• #56 Neonatal Herpes Infection: A Review – Page 3

  https://www.medscape.com/viewarticle/472408_3

  Due to the increasing incidence of neonatal herpes infection and the exceptionally high mortality and morbidity of this disease, a high index of suspicion is imperative in all clinicians caring for neonatal patients. […] The clinical presentation of neonatal herpes may be very nonspecific, therefore a high index of suspicion must be present to reduce the mortality and morbidity associated with a delay in diagnosis. […] Any delay in the diagnosis of neonatal HSV infection can have disastrous consequences. While the presence of SEM infection is associated with a 0% mortality rate, without prompt treatment, up to 70% of infants with SEM disease will progress to either CNS or disseminated disease both of which have an increased risk of death or permanent sequelae. […] The diagnosis of herpes infection must be entertained in any infant presenting with seizures with no underlying etiology.

• #57 Neonatal Herpes Simplex Virus (HSV) Infection – Pediatrics – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pediatrics/infections-in-neonates/neonatal-herpes-simplex-virus-hsv-infection

  Neonatal herpes simplex virus infection is usually transmitted during delivery. Diagnosis is by viral culture, polymerase chain reaction testing, immunofluorescence, or electron microscopy. […] Rapid diagnosis by viral culture or HSV PCR is essential. The most common site of retrieval is skin vesicles. […] All infants with HSV disease should have an ophthalmologic examination and neuroimaging. […] Acyclovir should be started immediately and presumptively in suspected cases while awaiting confirmatory diagnostic tests. […] The mortality rate of untreated disseminated herpes simplex disease is 85%; among neonates with untreated encephalitis, it is approximately 50%. […] To prevent neonatal herpes infection, pregnant patients with a history of genital herpes should be offered suppressive viral therapy at or beyond 36 weeks gestation. […] In suspected cases, presumptive therapy and rapid diagnosis by HSV PCR of cerebrospinal fluid, blood, or lesions are essential to optimize outcomes.

• #58 Neonatal Herpes Simplex Virus Infections | AAFP

  https://www.aafp.org/pubs/afp/issues/2002/0315/p1138.html

  Any vesicular rash in an infant up to eight weeks of age should be cultured and the infant immediately started on antiviral therapy with acyclovir (Zovirax) pending culture results. […] All infants suspected to have or who are diagnosed with an HSV infection should be treated with parenteral antiviral therapy. The duration of disease before antiviral therapy is initiated is significantly correlated with morbidity and mortality. Currently, suggested therapy is acyclovir 60 mg per kg per day in three divided doses intravenously for 14 days for disease limited to skin, eyes and mucous membranes, and 21 days for central nervous system or disseminated disease. […] The HSV-exposed neonate should be monitored closely for any signs of infection. Initial cultures should be performed at 24 to 48 hours, then weekly cultures of conjunctiva, nose, mouth, urine and rectum for HSV-1 or HSV-2 have been suggested. […] Any exposed infant with clinical signs of HSV should be cultured (conjunctiva, nose, mouth, urine, rectum, CSF, blood buffy coat), CSF should be sent for PCR analysis, and the infant should be immediately started on intravenous acyclovir therapy.

• #59 Neonatal Herpes Simplex Virus Infections | AAFP

  https://www.aafp.org/pubs/afp/issues/2002/0315/p1138.html

  Any vesicular rash in an infant up to eight weeks of age should be cultured and the infant immediately started on antiviral therapy with acyclovir (Zovirax) pending culture results. […] All infants suspected to have or who are diagnosed with an HSV infection should be treated with parenteral antiviral therapy. The duration of disease before antiviral therapy is initiated is significantly correlated with morbidity and mortality. Currently, suggested therapy is acyclovir 60 mg per kg per day in three divided doses intravenously for 14 days for disease limited to skin, eyes and mucous membranes, and 21 days for central nervous system or disseminated disease. […] The HSV-exposed neonate should be monitored closely for any signs of infection. Initial cultures should be performed at 24 to 48 hours, then weekly cultures of conjunctiva, nose, mouth, urine and rectum for HSV-1 or HSV-2 have been suggested. […] Any exposed infant with clinical signs of HSV should be cultured (conjunctiva, nose, mouth, urine, rectum, CSF, blood buffy coat), CSF should be sent for PCR analysis, and the infant should be immediately started on intravenous acyclovir therapy.

• #60 Prevention and management of neonatal herpes simplex virus infections | Canadian Paediatric Society

  https://cps.ca/documents/position/prevention-management-neonatal-herpes-simplex-virus-infections

  The evaluation of HSV viremia using PCR is less well established than CSF PCR testing. […] Early therapy with intravenous (IV) ACV improves the prognosis for all three presentations of NHSV. […] The dose is 60 mg/kg/day in three divided doses administered every 8 h, assuming that renal function is normal. […] Treatment duration should be 14 days if the disease is limited to the skin, eyes or mouth, and a minimum of 21 days if the infection involves the CNS or is disseminated. […] Follow-up is necessary to detect and manage adverse effects related to suppressive ACV treatment as well as for the neurodevelopmental sequelae of NHSV.

• #61 Prevention and management of neonatal herpes simplex virus infections | Canadian Paediatric Society

  https://cps.ca/documents/position/prevention-management-neonatal-herpes-simplex-virus-infections

  The evaluation of HSV viremia using PCR is less well established than CSF PCR testing. […] Early therapy with intravenous (IV) ACV improves the prognosis for all three presentations of NHSV. […] The dose is 60 mg/kg/day in three divided doses administered every 8 h, assuming that renal function is normal. […] Treatment duration should be 14 days if the disease is limited to the skin, eyes or mouth, and a minimum of 21 days if the infection involves the CNS or is disseminated. […] Follow-up is necessary to detect and manage adverse effects related to suppressive ACV treatment as well as for the neurodevelopmental sequelae of NHSV.

• #62 #26: Neonatal HSV – Plain and Simplex – The Curbsiders

  https://thecurbsiders.com/cribsiders-podcast/26

  In the case of a symptomatic infant (trouble latching, hypothermic, irritable) prior to 24 hours of life: start evaluation for HSV and for bacterial infections. […] In Dr. Golden’s expert opinion, if a child is ill appearing and presenting within the first 30 days of life, he would keep HSV on the differential and start acyclovir empirically while awaiting testing. […] HSV infection is treated with 20mg/kg acyclovir IV every 8 hours. For SEM disease (negative CSF, AST/ALT), treatment course is 14 days. For disseminated disease or meningoencephalitis, treat for 21 days. […] If you have HSV on the differential, in Dr. Golden’s expert opinion you should initiate treatment—there is evidence that delayed treatment of HSV infection increases the risk of in-hospital mortality. […] Acyclovir prophylaxis for 6 months improves the neurodevelopmental outcomes of children who had neonatal HSV infection.

• #63 Congenital Herpes Simplex – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK507897/

  Congenital HSV infection can be clinically challenging due to the early manifestations often being subtle and nonspecific. […] Prompt treatment requires early consideration of congenital HSV as a possibility in neonates with mucocutaneous lesions, CNS abnormalities, or a sepsis-like picture. […] Given that HSV grows readily in cell culture, cultures of vesicular lesions and affected sites are preferred for diagnosing congenital HSV. […] A polymerase chain reaction (PCR) assay can often detect HSV DNA in CSF from neonates with CNS infection and older children and adults with HSV encephalitis (HSE); PCR is the diagnostic method of choice for CNS HSV involvement. […] Parenteral acyclovir is the standard of care in treating congenital HSV infection. […] All infants with CNS involvement should have a repeat lumbar puncture performed near the end of therapy to document that the CSF is negative for HSV DNA on PCR assay.

• #64 Neonatal herpes encephalitis | MedLink Neurology

  https://www.medlink.com/articles/neonatal-herpes-encephalitis

  Acyclovir is given intravenously at a dose of 20 mg/kg every 8 hours (60 mg/kg per day) for at least 21 days for neonatal herpes simplex virus encephalitis and disseminated herpes simplex virus disease. […] After 21 days of treatment with intravenous acyclovir, repeat CSF polymerase chain reaction for herpes simplex virus should be performed, and antiviral therapy should be continued for at least one more week, if still positive. […] The sequelae and complications of neonatal herpes infections lead to frequent emergency department visits and hospital readmissions.

• #65 #26: Neonatal HSV – Plain and Simplex – The Curbsiders

  https://thecurbsiders.com/cribsiders-podcast/26

  In the case of a symptomatic infant (trouble latching, hypothermic, irritable) prior to 24 hours of life: start evaluation for HSV and for bacterial infections. […] In Dr. Golden’s expert opinion, if a child is ill appearing and presenting within the first 30 days of life, he would keep HSV on the differential and start acyclovir empirically while awaiting testing. […] HSV infection is treated with 20mg/kg acyclovir IV every 8 hours. For SEM disease (negative CSF, AST/ALT), treatment course is 14 days. For disseminated disease or meningoencephalitis, treat for 21 days. […] If you have HSV on the differential, in Dr. Golden’s expert opinion you should initiate treatment—there is evidence that delayed treatment of HSV infection increases the risk of in-hospital mortality. […] Acyclovir prophylaxis for 6 months improves the neurodevelopmental outcomes of children who had neonatal HSV infection.

• #66 Genital Herpes in Pregnancy (Neonatal Herpes) | Doctor

  https://patient.info/doctor/genital-herpes-in-pregnancy

  Although rare in the UK, neonatal herpes is a severe condition and carries a high risk of morbidity and mortality. Neonatal herpes refers to infection acquired around the time of birth, whereas congenital herpes refers to infection acquired in utero and is extremely rare. […] Early diagnosis and prompt treatment are essential. Early recognition (and application of treatment protocols) is essential to improve prognosis. Remember there may not be obvious symptoms in the mother and HSV can be transmitted through asymptomatic viral shedding, and indeed this is most often the case. Consider the diagnosis in any infant in the first weeks of life who develops vesicles, seizures or sepsis. […] Prompt diagnosis and initiation of treatment are critical to neonatal outcome.

• #67 Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic | BMJ Case Reports

  https://casereports.bmj.com/content/14/3/e241405

  Unexplained fever should prompt a search for other diagnoses and not only sepsis in neonates and localised herpes infection should urge a search for features of disseminated disease. […] Hyperferritinaemia in feverish neonates can point to herpes simplex virus (HSV) infection even in the absence of suggestive maternal history. […] Empiric therapy with acyclovir in neonates with unexplained fever and elevated transaminases, while awaiting confirmatory HSV investigations, can mitigate the severe consequences of HSV hepatitis if left untreated.

• #68 Herpes Simplex Virus (HSV) in the newborn – Good practice points | Safer Care Victoria

  https://www.safercare.vic.gov.au/councils/ccopmm/good-practice-points/HSV-newborn

  HSV has long been identified as occurring in infants whose mothers have no history of clinical HSV, making diagnosis impossible to rule out on clinical history alone (Pinninti and Kimberlin, 2014). […] In cases where HSV needs to be ruled out, relying solely on a negative CSF result is insufficient and further tests need to be employed- specifically swabs from mouth, conjunctiva, nasopharynx, rectum, any vesicles (if present) and blood for HSV DNA PCR and LFT (Especially ALT). Repeating CSF two to three days later may also be helpful.

• #69 Prolonged fever and hyperferritinaemia: a puzzling diagnosis of neonatal herpes simplex virus infection during COVID-19 pandemic | BMJ Case Reports

  https://bibliotheek.ehb.be:2635/content/14/3/e241405

  Unexplained fever should prompt a search for other diagnoses and not only sepsis in neonates and localised herpes infection should urge a search for features of disseminated disease. […] Hyperferritinaemia in feverish neonates can point to herpes simplex virus (HSV) infection even in the absence of suggestive maternal history. […] Empiric therapy with acyclovir in neonates with unexplained fever and elevated transaminases, while awaiting confirmatory HSV investigations, can mitigate the severe consequences of HSV hepatitis if left untreated.

• #70

  https://www.autopsyandcasereports.org/article/doi/10.4322/acr.2018.050

  Herpes Simplex Virus infections (HSV) are ubiquitous. The neonatal HSV infection (NHSV) is rare. The incidence is estimated globally at only 10.3 per 100,000 births, but it can cause devastating disease in premature infants. […] We urge more awareness of this disease with continued surveillance; every effort should be taken to make an early diagnosis and thus prevent this devastating disease.

• #71 Herpes simplex ophthalmia neonatorum: a sight-threatening diagnosis | British Journal of General Practice

  https://bjgp.org/content/70/699/513

  Ophthalmia neonatorum or neonatal conjunctivitis refers to conjunctival inflammation with associated discharge. Onset is within the first 28 days of life and transmission is by delivery via an infected birth canal. […] Despite its rare occurrence, GPs must have a high suspicion of HSV conjunctivitis on initial presentation because misdiagnosis in a newborn with an immature immune system has sight-threatening consequences. […] Neonatal ocular HSV is diagnosed by polymerase chain reaction (PCR) of conjunctival swabs. Blood and cerebrospinal fluid (CSF) may also be taken for analysis to exclude CNS and disseminated disease. […] An ophthalmic referral should be sought urgently when HSV or any other keratitis is suspected in a neonate. […] The most important and commonly reiterated learning point would be vigilance and a high index of suspicion of HSV on the very first presentation, however infrequently these infections may occur in the developed world. Neonates have immature immune systems and should be treated in the same vein as immunocompromised patients. […] There is a clear trend between the progression to disseminated disease and higher morbidity and mortality, and untimely treatment can lead to lifelong devastating effects for the child that are entirely preventable.

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