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| __NOTOC__ | | __NOTOC__ |
| {{SI}}
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| {{CMG}} {{AE}} {{AKI}}
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| {{SK}} | | {{Roseola}} |
| ==Overview==
| | {{CMG}}:{{AE}}{{DAMI}} |
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| ==Historical Perspective==
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| *In 1935, the first case resembling neonatal HSV, was described with the presence of intranuclear inclusion bodies in a premature infant in the liver and the adrenals.<ref name="pmid19970188">{{cite journal| author=Hass GM| title=Hepato-Adrenal Necrosis with Intranuclear Inclusion Bodies: Report of a Case. | journal=Am J Pathol | year= 1935 | volume= 11 | issue= 1 | pages= 127-142.5 | pmid=19970188 | doi= | pmc=1910753 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19970188 }} </ref>
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| ==Classification== | | ==[[Roseola overview|Overview]]== |
| ===Neonatal Herpes Simplex Classification===
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| Neonatal herpes simplex is classified based on the organ system involvement in the neonate into the following:<ref name="pmid1988830">{{cite journal |vauthors=Whitley R, Arvin A, Prober C, Corey L, Burchett S, Plotkin S, Starr S, Jacobs R, Powell D, Nahmias A |title=Predictors of morbidity and mortality in neonates with herpes simplex virus infections. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group |journal=N. Engl. J. Med. |volume=324 |issue=7 |pages=450–4 |year=1991 |pmid=1988830 |doi=10.1056/NEJM199102143240704 |url=}}</ref>
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| *'''Disseminated herpes simplex:''' Involving visceral organs such as lung, liver, adrenal glands, skin, eye, and/or brain.
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| *'''Central nervous system disease:''' Involvement of the CNS with or without skin lesions.
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| *'''SEM Disease:''' Disease limited to the involvement of skin, eye and mouth.
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| ===Maternal Genital Herpes Classification=== | | ==[[Roseola historical perspective|Historical Perspective]]== |
| Maternal genital herpes is classified based on HSV type and maternal serology. It is essential to distinguish the type of maternal infection, as the type of infection influences the management approach.
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| *'''Primary Infection:''' It when a women has exposure to either HSV-1 or HSV-2 for the first time. The serology will be negative for antibodies against both the types.
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| *'''Recurrent Infection:''' It is when a women has clinical lesions demonstrating the same type of HSV to which the serology is positive.<ref name="pmid7081316">{{cite journal |vauthors=Vontver LA, Hickok DE, Brown Z, Reid L, Corey L |title=Recurrent genital herpes simplex virus infection in pregnancy: infant outcome and frequency of asymptomatic recurrences |journal=Am. J. Obstet. Gynecol. |volume=143 |issue=1 |pages=75–84 |year=1982 |pmid=7081316 |doi= |url=}}</ref>
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| *'''Non-primary first episode:''' It is the first clinically recognized episode and serology demonstrates either HSV-1 or HSV-2 antibodies indicating a prior exposure.
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| <small>
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| {| class="wikitable"
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| !Classification of maternal infection
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| !PCR / Culture from the genital lesion
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| !Maternal HSV-1/ HSV-2 Antibody status
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| |-
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| |First episode primary infection
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| |Positive for either virus
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| |Negative for both
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| |-
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| | rowspan="2" |Recurrent infection
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| |Positive for HSV-1
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| |Positive for HSV-1
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| |-
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| |Positive for HSV-2
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| |Positive for HSV-2
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| |-
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| | rowspan="2" |First episode Non-primary infection (Patient is immune to one type of HSV)
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| |Positive for HSV-1
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| |Positive for HSV-2
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| |-
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| |Positive for HSV-2
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| |Positive for HSV-1
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| |}
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| </small>
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| ==Pathophysiology== | | ==[[Roseola classification|Classification]]== |
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| ===Pathogenesis=== | | ==[[Roseola pathophysiology|Pathophysiology]]== |
| *Majority of infants with diagnosed neonatal herpes do not have maternal history of genital lesions because of asymptomatic shedding of the virus.<ref name="WaldZeh1995">{{cite journal|last1=Wald|first1=Anna|last2=Zeh|first2=Judith|last3=Selke|first3=Stacy|last4=Ashley|first4=Rhoda L.|last5=Corey|first5=Lawrence|title=Virologic Characteristics of Subclinical and Symptomatic Genital Herpes Infections|journal=New England Journal of Medicine|volume=333|issue=12|year=1995|pages=770–775|issn=0028-4793|doi=10.1056/NEJM199509213331205}}</ref><ref name="pmid1849612">{{cite journal |vauthors=Brown ZA, Benedetti J, Ashley R, Burchett S, Selke S, Berry S, Vontver LA, Corey L |title=Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor |journal=N. Engl. J. Med. |volume=324 |issue=18 |pages=1247–52 |year=1991 |pmid=1849612 |doi=10.1056/NEJM199105023241804 |url=}}</ref>
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| *The trasmission is by direct contact of the neonate with the virus and the incubation period is 1 to 3 weeks.
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| *The risk of transmission of infection to the neonate from an infected mother is high (30-50%) who have first episode of genital herpes at term and low (<1%) in mothers with prenatal history of recurrent herpes or who have genital HSV during the first and second trimester.<ref name="BrownSelke1997">{{cite journal|last1=Brown|first1=ZaneA.|last2=Selke|first2=Stacy|last3=Zeh|first3=Judy|last4=Kopelman|first4=Jerome|last5=Maslow|first5=Arthur|last6=Ashley|first6=Rhoda L.|last7=Watts|first7=D. Heather|last8=Berry|first8=Sylvia|last9=Herd|first9=Millie|last10=Corey|first10=Lawrence|title=The Acquisition of Herpes Simplex Virus during Pregnancy|journal=New England Journal ofMedicine|volume=337|issue=8|year=1997|pages=509–516|issn=0028-4793|doi=10.1056/NEJM199708213370801}}</ref><ref name="pmid23303485">{{cite journal| author=Pinninti SG, Kimberlin DW| title=Maternal and neonatal herpes simplex virus infections. | journal=Am J Perinatol | year= 2013 | volume= 30 | issue= 2 | pages= 113-9 | pmid=23303485 | doi=10.1055/s-0032-1332802 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23303485 }} </ref><ref name="pmid1849612">{{cite journal| author=Brown ZA, Benedetti J, Ashley R, Burchett S, Selke S, Berry S et al.| title=Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor. | journal=N Engl J Med | year= 1991 | volume= 324 | issue= 18 | pages= 1247-52 | pmid=1849612 | doi=10.1056/NEJM199105023241804 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1849612 }} </ref>
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| ====Timing of infection====
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| *Exposure to the fetus from active genital herpes lesions during delivery, accounts for majority of neonatal herpes simplex cases. <ref name="pmid12517231">{{cite journal| author=Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L| title=Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. | journal=JAMA | year= 2003 | volume= 289 | issue= 2 | pages= 203-9 | pmid=12517231 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12517231 }} </ref>
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| *Intrauterine infection accounts for 5% of cases with neonatal herpes simplex and the infant presents with clinical features at birth.
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| *Postnatal transmission by contact with HSV shed from infected patients. It accounts for 10% of the cases.
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| ====Factors that influence transmission of HSV from the mother to the neonate==== | | ==[[Roseola causes|Causes]]== |
| The factors that influence the transmission of infection include:<ref name="pmid23359576">{{cite journal |vauthors=Kimberlin DW, Baley J |title=Guidance on management of asymptomatic neonates born to women with active genital herpes lesions |journal=Pediatrics |volume=131 |issue=2 |pages=e635–46 |year=2013 |pmid=23359576 |pmc=3557411 |doi=10.1542/peds.2012-3216 |url=}}</ref>
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| *Women with primary infection have higher rate of infection transmission when compared to women with recurrent infection.<ref name="Brown2003">{{cite journal|last1=Brown|first1=Zane A.|title=Effect of Serologic Status and Cesarean Delivery on Transmission Rates of Herpes Simplex Virus From Mother to Infant|journal=JAMA|volume=289|issue=2|year=2003|pages=203|issn=0098-7484|doi=10.1001/jama.289.2.203}}</ref>
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| *Maternal HSV antibody status, women with recurrent infection have IgG antibodies aganist HSV which can protect the fetus from infection.
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| *Prolonged duration of rupture of membranes increases the risk of infection transmission.
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| *Use of scalp electrodes disrupts the integrity of mucocutaneous barrier increasing the risk of transmission.<ref name="pmid7196519">{{cite journal |vauthors=Kaye EM, Dooling EC |title=Neonatal herpes simplex meningoencephalitis associated with fetal monitor scalp electrodes |journal=Neurology |volume=31 |issue=8 |pages=1045–7 |year=1981 |pmid=7196519 |doi= |url=}}</ref>
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| *Vaginal delivery has a higher risk of transmission of infection compared to cesarean section.
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| ===Microscopic Pathology=== | | ==[[Roseola differential diagnosis|Differentiating Any Disease from other Diseases]]== |
| *Tzank Test: Microscopic examination of the skin lesions demonstrate multinucleated gaint cells and eosinophilic intranuclear inclusions.
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| ==Epidemiology and Demographics== | | ==[[Roseola epidemiology and demographics|Epidemiology and Demographics]]== |
| *The annual incidence of neonatal herpes is estimated to be 10 cases per 100,000 livebirths.<ref name="pmid28153513">{{cite journal| author=Looker KJ, Magaret AS, May MT, Turner KM, Vickerman P, Newman LM et al.| title=First estimates of the global and regional incidence of neonatal herpes infection. | journal=Lancet Glob Health | year= 2017 | volume= 5 | issue= 3 | pages= e300-e309 | pmid=28153513 | doi=10.1016/S2214-109X(16)30362-X | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28153513 }} </ref>
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| ==Risk Factors==
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| The cause for neonatal herpes simplex is the presence of active lesions at the time of delivery, therefore all the risk factors which predispose patients to aquire genital herpes are risk factors for developing neonatal disease also. The risk factors include:
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| *Low family income
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| *Minority ethnic group
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| *Longer duration of sexual activity
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| *Past history of other sexually transmitted infections
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| *Multiple sexual partners
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| ==Screening== | | ==[[Roseola risk factors|Risk Factors]]== |
| *Routine HSV screening in pregnancy is not recommended.<ref name="pmid17569194">{{cite journal |vauthors= |title=ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. No. 82 June 2007. Management of herpes in pregnancy |journal=Obstet Gynecol |volume=109 |issue=6 |pages=1489–98 |year=2007 |pmid=17569194 |doi= |url=}}</ref>
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| ==Causes== | | ==[[Roseola screening|Screening]]== |
| The causative pathogen for neonatal herpes simplex is herpes simplex virus. The different types involved in the disease are as follows:
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| *85% of cases are caused by HSV type 1
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| *15% of cases are caused by HSV type 2
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| ==Differentiating Neonatal Herpes Simplex From Other Diseases== | | ==[[Roseola natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| The most important congenital infections, which can be transmitted vertically from mother to fetus are the [[TORCH infections]]. These infections have overlapping features and hence, must be differentiated from neonatal herpes simplex:<ref name="pmid25677998">{{cite journal |vauthors=Neu N, Duchon J, Zachariah P |title=TORCH infections |journal=Clin Perinatol |volume=42 |issue=1 |pages=77–103, viii |year=2015 |pmid=25677998 |doi=10.1016/j.clp.2014.11.001 |url=}}</ref><ref name="pmid25654000">{{cite journal |vauthors=Ajij M, Nangia S, Dubey BS |title=Congenital rubella syndrome with blueberry muffin lesions and extensive metaphysitis |journal=J Clin Diagn Res |volume=8 |issue=12 |pages=PD03–4 |year=2014 |pmid=25654000 |pmc=4316306 |doi=10.7860/JCDR/2014/10271.5293 |url=}}</ref>
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| <small>
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| {| class="wikitable"
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| !Congenital Infection
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| !Cardiac Findings
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| !Skin Findings
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| !Ocular Findings
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| !Hepatosplenomegaly
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| !Hydrocephalus
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| !Microcephaly
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| !Intracranial Calcifications
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| !Hearing deficits
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| |-
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| !Congenital Varicella Syndrome
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| | -
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| *Cicatrical Skin Lesions
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| *Skin Edema
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| *Micropthalmus
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| *Cataracts
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| |✔
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| |✔
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| |✔
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| |-
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| ![[Toxoplasmosis congenital|Toxoplasmosis]]
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| * [[Petechiae]]
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| * [[Purpura]]
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| * [[Maculopapular rash]]
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| * [[Chorioretinitis]]
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| |✔
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| |✔
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| |✔
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| |Diffuse intracranial calcifications
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| |-
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| ![[Congenital Syphils]]
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| * [[Petechiae]]
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| * [[Purpura]]
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| * [[Maculopapular rash]]
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| * [[Chorioretinitis]]
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| * [[Glaucoma]]
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| |✔
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| |-
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| ![[Rubella, congenital|Rubella]]
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| * [[Patent ductus arteriosus (PDA)]]
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| * [[Pulmonary artery stenosis]]
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| * [[Coarctation of the aorta]]
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| * [[Myocarditis]]
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| * [[Petechiae]]
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| * [[Purpura]]
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| * [[Chorioretinitis]]
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| * [[Cataracts]]
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| * [[Glaucoma]]
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| * [[Microphthalmia]]
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| |✔
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| |✔
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| |✔
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| |✔
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| |-
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| ![[Cytomegalovirus (CMV)]]
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| |✔
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| * [[Petechiae]]
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| * [[Purpura]]
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| * [[Chorioretinitis]]
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| |✔
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| |✔
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| |Periventricular calcifications
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| |✔
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| |-
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| ![[Herpes simplex virus (HSV)]]
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| * [[Myocarditis]]
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| * [[Petechiae]]
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| * [[Purpura]]
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| * [[Vesicles]]
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| * [[Chorioretinitis]]
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| |✔
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| |✔
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| |✔
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| |✔
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| |-
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| ![[Parvovirus B19]]
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| | | |
| * [[Myocarditis]]
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| * [[Petechiae]]
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| * [[Subcutaneous]] [[edema]]
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| * [[Chorioretinitis]]
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| * [[Cataracts]]
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| |✔
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| |}
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| </small>
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| ==Natural History, Prognosis and Complications==
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| ===Natural History===
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| <ref name="pmid11483781">{{cite journal |vauthors=Kimberlin DW, Lin CY, Jacobs RF, Powell DA, Frenkel LM, Gruber WC, Rathore M, Bradley JS, Diaz PS, Kumar M, Arvin AM, Gutierrez K, Shelton M, Weiner LB, Sleasman JW, de Sierra TM, Soong SJ, Kiell J, Lakeman FD, Whitley RJ |title=Natural history of neonatal herpes simplex virus infections in the acyclovir era |journal=Pediatrics |volume=108 |issue=2 |pages=223–9 |year=2001 |pmid=11483781 |doi= |url=}}</ref>
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| ===Prognosis===
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| <ref name="pmid3392410">{{cite journal |vauthors=Whitley RJ, Corey L, Arvin A, Lakeman FD, Sumaya CV, Wright PF, Dunkle LM, Steele RW, Soong SJ, Nahmias AJ |title=Changing presentation of herpes simplex virus infection in neonates |journal=J. Infect. Dis. |volume=158 |issue=1 |pages=109–16 |year=1988 |pmid=3392410 |doi= |url=}}</ref>
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| ===Complications===
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| <ref name="pmid9262493">{{cite journal |vauthors=Brown ZA, Selke S, Zeh J, Kopelman J, Maslow A, Ashley RL, Watts DH, Berry S, Herd M, Corey L |title=The acquisition of herpes simplex virus during pregnancy |journal=N. Engl. J. Med. |volume=337 |issue=8 |pages=509–15 |year=1997 |pmid=9262493 |doi=10.1056/NEJM199708213370801 |url=}}</ref>
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| ==Diagnosis== | | ==Diagnosis== |
| | | [[Roseola history and symptoms|History and Symptoms]] | [[Roseola physical examination|Physical Examination]] | [[Roseola laboratory findings|Laboratory Findings]] | [[Roseola electrocardiogram|Electrocardiogram]] | [[Roseola chest x ray|Chest X Ray]] | [[Roseola CT|CT]] | [[Roseola MRI|MRI]] | [[Roseola echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Roseola other imaging findings|Other Imaging Findings]] | [[Roseola other diagnostic studies|Other Diagnostic Studies]] |
| ===History and Symptoms===
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| The onset of symptoms is dependent on the extent of involvement of the disease. Skin, eye mouth disease is the most common presentation and is seen in 50% of patients. Delay in the diagnosis and initiation of treatment results in rapid progression of disease to involve the CNS and other organ systems.<ref name="pmid14726453">{{cite journal |vauthors=Kimberlin DW |title=Neonatal herpes simplex infection |journal=Clin. Microbiol. Rev. |volume=17 |issue=1 |pages=1–13 |year=2004 |pmid=14726453 |pmc=321459 |doi= |url=}}</ref>
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| ====Skin, Eye, Mouth Disease====
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| *The average age of presentation is 10 to 12days of life.
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| *The presenting symptoms include: redness and watering of the eye, skin rash and mouth ulcers. <ref name="WuParsons2017">{{cite journal|last1=Wu|first1=Jia Hao|last2=Parsons|first2=Sarah|title=Fatal disseminated neonatal herpes simplex virus type 1 infection in neonates in a forensic setting|journal=Forensic Science, Medicine, and Pathology|volume=13|issue=1|year=2017|pages=99–101|issn=1547-769X|doi=10.1007/s12024-016-9834-5}}</ref>
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| ====CNS Disease====
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| *The average age of presentation is around 16 to 20days of life.
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| *The symptoms include : Irritability, feeding difficulties, weakness of the limbs, seizures and enlarging head.
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| *Majority of the patients with CNS disease have features of SEM.
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| ====Disseminated Disease====
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| *The average age of presentation is 10 to 12 days of life.
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| *The infant presents with symptoms such as difficulty breathing, yellowish skin, distended abdomen,seizures, reduced urine output, bleeding, skin rash.
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| ===Physical Examination===
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| Physical examination findings in neonatal herpes simplex include :
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| | |
| {| border="1"
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| |- | |
| !
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| !'''Clinical Manifestations in neonatal herpes simplex'''
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| |-
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| !'''Skin'''
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| *Vesicular lesions with an erythematous base
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| *Scarring
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| *Aplasia Cutis
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| |-
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| !'''Eye'''
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| *Optic Atrophy
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| *Chorioretinitis
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| *Micropthalmia
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| *Conjunctival erythema
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| |-
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| !'''Mouth'''
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| *Ulcers on the tongue, palate and mouth
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| |-
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| !'''CNS'''
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| *Microcephaly
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| *Irritability
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| *Temperature instability
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| *Hypotonia
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| *Bulging anterior fontanelle
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| |-
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| !'''Disseminated Disease'''
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| |
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| *Jaundice is seen in liver failure
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| *Respiratory Distress
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| *Bulging anterior fontanelle
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| *Features of Disseminated intravascular coagulation such as bleeding and petechiae
| |
| |}
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| | |
| ===Laboratory Findings===
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| ====Diagnosis of maternal genital herpes====
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| *Diagnosis of maternal herpes simplex can be done by PCR assay for HSV DNA and culture for HSV.<ref name="pmid17569194">{{cite journal |vauthors= |title=ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. No. 82 June 2007. Management of herpes in pregnancy |journal=Obstet Gynecol |volume=109 |issue=6 |pages=1489–98 |year=2007 |pmid=17569194 |doi= |url=}}</ref>
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| *PCR assay is the commonly used method for diagnosis as it takes short time for obtaining results. The major limitation of using PCR assay is its availability in remote medical facilities.<ref name="pmid17569194">{{cite journal |vauthors= |title=ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. No. 82 June 2007. Management of herpes in pregnancy |journal=Obstet Gynecol |volume=109 |issue=6 |pages=1489–98 |year=2007 |pmid=17569194 |doi= |url=}}</ref>
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| *Culture for HSV takes 4 to 5 days for results and is dependent on the stage of infection, higher viral load is present in the prodromal and vesicular stage than during the crusting stage affecting the results.<ref name="pmid17569194">{{cite journal |vauthors= |title=ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. No. 82 June 2007. Management of herpes in pregnancy |journal=Obstet Gynecol |volume=109 |issue=6 |pages=1489–98 |year=2007 |pmid=17569194 |doi= |url=}}</ref>
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| *Serological tests distinguish antibodies produced against HSV-1 and HSV-2, therefore help in determining the type of HSV causing the infection.<ref name="pmid17569194">{{cite journal |vauthors= |title=ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. No. 82 June 2007. Management of herpes in pregnancy |journal=Obstet Gynecol |volume=109 |issue=6 |pages=1489–98 |year=2007 |pmid=17569194 |doi= |url=}}</ref>
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| | |
| ====Diagnosis in the Neonate====
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| *Neonates with suspicion for herpes simplex infection must be evaluated for the presence of infection before initiation of empiric treatment with acyclovir. The gold standard for diagnosis is culture for HSV. PCR of CSF should be done in neonates presenting with CNS disease.
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| *The specimens for surface cultures should be collected from multiple areas which include mouth, nasopharynx, conjunctivae, and anus. Skin vesicles should also be sampled for culture and PCR assay.
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| *Sample collection is done at 24 hours of life to eliminate a possible maternal contamination which can result in false positive results. Positive surface cultures indicate viral replication.
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| *Other specimens to be collected include CSF for culture and PCR assay, whole blood for PCR assay and liver function tests.
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| *Whole blood PCR is useful in identifying viremia, but the extent of the disease and response to therapy cannot be related to the result of blood PCR as viremia is present in SEM, disseminated and CNS HSV infections.<ref name="pmid10391175">{{cite journal |vauthors=Diamond C, Mohan K, Hobson A, Frenkel L, Corey L |title=Viremia in neonatal herpes simplex virus infections |journal=Pediatr. Infect. Dis. J. |volume=18 |issue=6 |pages=487–9 |year=1999 |pmid=10391175 |doi= |url=}}</ref>
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| *Based on the laboratory findings HSV manifestation can be differentiated into two types:
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| {| class="wikitable"
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| !Stage of Neonate infection
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| !Specific Findings
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| |- | |
| |HSV Infection | |
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| |
| *Asymptomatic infant
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| *Positive surface culture
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| *Positive HSV blood PCR
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| *Normal CSF analysis
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| *Normal alanine transaminase
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| |-
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| |HSV Disease
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| |
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| *Symptomatic infant ( Presence of SEM, disseminated or CNS HSV features)
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| *Positive surface culture
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| *Positive HSV blood PCR
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| *Positive CSF HSV
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| *Elevated alanine transaminase
| |
| |}
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|
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|
| ==Treatment== | | ==Treatment== |
| ===Approach to neonate with suspected HSV infection===
| | [[Roseola medical therapy|Medical Therapy]] | [[Roseola surgery|Surgery]] | [[Roseola primary prevention|Primary Prevention]] | [[Roseola secondary prevention|Secondary Prevention]] | [[Roseola cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Roseola future or investigational therapies|Future or Investigational Therapies]] |
| {{familytree/start}}
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| {{familytree | | | | | | | | | | | | | A01 | | | | | | | | | | | | | | | | | |A01= Suspicion of HSV infection in asymptomatic neonate}}
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| {{familytree | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | }}
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| {{familytree | | | | | | | | | | | | | B01 | | | | | | | |B01 = Is the present genital herpes lesion the first episode or not }}
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| {{familytree | | | | |,|-|-|-|-|-|-|-|-|^|-|-|-|-|-|-|-|-|.| }}
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| {{familytree | | | | B01 | | | | | | | | | | | | | | | | B02 | |B01= It is the first episode of genital herpes| B02 = Positive past history for similar lesions before pregnancy }}
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| {{familytree | | | | |!| | | | | | | | | | | | | | | | | |!| | }}
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| {{familytree | | | | C01 | | | | | | | | | | | | | | | | C02 | | C01= Signifies the infection can be primary infection, first episode Non-primary infection or a recurrent infection | C02 = Signifies the infection is most likely due to reactivation of the virus}}
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| {{familytree | | | | |!| | | | | | | | | | | | | | | | | |!| | | | |}}
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| {{familytree | | | | D01 | | | | | | | | | | | | | | | | D02 | | | |D01= ❑ Perform maternal serology to differentiate the stages of maternal infection <br>'''AND''' <br> At 24hours of life perform : <br>❑ HSV surface cultures <br>❑ CSF analysis and HSV PCR <br>❑ HSV Blood PCR <br>❑ Measure serum ALT <br>❑ Initiate IV Acyclovir 60mg/kg/day in 3 divided doses | D02 = At 24 hours of life perform : <br>❑ Surface cultures <br>❑ HSV Blood PCR <br>❑ Donot start Acyclovir if the baby is asymptomatic}}
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| {{familytree | | | | |!| | | | | | | | | | | | | | | | | |!| | | | | | }}
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| {{familytree | | | |,|^|-|-|-|-|-|-|-|-|-|.| | | | | | | |`|-|-|.| | |}}
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| {{familytree | | | A01 | | | | | | | | | A02 | | | | | | | | | A03 | | | | | A01= Primary infection or First Episode Non-primary infection | A02 = Recurrent infection | A03 = Reactivation }}
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| {{familytree | |,|-|^|-|-|-|.| | | |,|-|-|^|-|-|-|.| | | |,|-|-|^|-|-|.| }}
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| {{familytree | B01 | | | | B02 | | B03 | | | | | B04 | | B05 | | | | B06 | | | | B01 = HSV Disease | B02= HSV Infection| B03 = HSV Infection| B04 = ❑ Negative neonate HSV blood PCR <br>❑ Negative surface culture| B05 =❑ Negative blood HSV PCR <br> ❑ Negative surface culture | B06= ❑ Positive HSV blood PCR <br>❑ Positive surface culture }}
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| {{familytree | |!| | | | | |`|-|v|-|'| | | | | | |!| | | |!| | | | | |!| |}}
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| {{familytree | C01 | | | | | | C02 | | | | | | | C04 | | C05 | | | | C06 ||C01=❑ Continue IV Acyclovir based on the extent of the disease (14 to 21 days)| C04=❑ Stop Acyclovir <br>❑ Educate about signs and symptoms of HSV <br>❑ Discharge and re-evaluate at 6weeks | C02 = Continue IV Acyclovir for 10days to prevent progression | C05= ❑ Educate about signs and symptoms of HSV <br> ❑ Discharge and re-evaluate at 6 weeks | C06 = Perform CSF HSV PCR and Alanine Transaminase level}}
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| {{familytree | | | | | | | | | | | | | | | | | | | | | | | |,|-|-|-|-|^|-|-|-|-|.| | }}
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| {{familytree | | | | | | | | | | | | | | | | | | | | | | | G01 | | | | | | | | G02 | G01=❑ Negative CSF PCR <br> ❑ Start IV Acyclovir for 10days| G02 = Positive CSF PCR and Elevated ALT<br>❑ Initiate IV Acyclovir for 14 to 21days}}
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| {{familytree/end}}
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| <small> Algorithm adopted from Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions<ref name="KimberlinBaley2013">{{cite journal|last1=Kimberlin|first1=D. W.|last2=Baley|first2=J.|title=Guidance on Management of Asymptomatic Neonates Born to Women With Active Genital Herpes Lesions|journal=PEDIATRICS|volume=131|issue=2|year=2013|pages=e635–e646|issn=0031-4005|doi=10.1542/peds.2012-3216}}</ref></small>
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| <small>
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| {| class="wikitable"
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| !Classification of maternal infection
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| !PCR / Culture from the genital lesion
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| !Maternal HSV-1/ HSV-2 Antibody status
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| |-
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| |First episode primary infection
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| |Positive for either virus
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| |Negative for both
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| |-
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| | rowspan="2" |Recurrent infection
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| |Positive for HSV-1
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| |Positive for HSV-1
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| |-
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| |Positive for HSV-2
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| |Positive for HSV-2
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| |-
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| | rowspan="2" |First episode Non-primary infection
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| |Positive for HSV-1
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| |Positive for HSV-2
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| |-
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| |Positive for HSV-2
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| |Positive for HSV-1
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| |}
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| </small>
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| ==Medical Therapy==
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| Acyclovir is the only therapeutic agent for the treatment for neonatal HSV and the treatment duration is based on the severity of infection. The current recommendations are as follows:
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| *Start empiric IV acyclovir therapy in all symptomatic infants and infants with suspicion of neonatal HSV or confirmed HSV infection. IV Acyclovir is the recommended regimen and is given at a dose of 20mg/kg every 8 hours.<ref name="urlGenital HSV Infections - 2015 STD Treatment Guidelines">{{cite web |url=https://www.cdc.gov/std/tg2015/herpes.htm |title=Genital HSV Infections - 2015 STD Treatment Guidelines |format= |work= |accessdate=}}</ref>
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| * The duration of acyclovir therapy is dependent on the severity of the infection, it is as follows:
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| **Patients with HSV infection treatment should be continued for 10 days.
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| **Patients with skin, eye, mouth involvement only (SEM) duration of treatment is 14 days.
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| **Patients with CNS and disseminated disease duration of treatment is 21 days.
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| *In patients with a initial positive CSF HSV PCR, repeat lumbar puncture should be performed at the end of therapy to assess the response to therapy. If the CSF PCR is positive at the end of therapy, acyclovir treatment should be extended for a duration of 1week. The results of the repeat lumbar puncture should be negative to stop the therapy.
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| *All patients should receive a 6 month duration acyclovir suppressive therapy 300mg/m²/dose, 3 times a day after IV acyclovir is stopped.
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| *Absolute neutrophil count should be monitored at second and fourth week after initiation of suppressive therapy initially and then once monthly.<ref name="EricsonGostelow2016">{{cite journal|last1=Ericson|first1=Jessica E.|last2=Gostelow|first2=Martyn|last3=Autmizguine|first3=Julie|last4=Hornik|first4=Christoph P.|last5=Clark|first5=Reese H.|last6=Benjamin|first6=Daniel K.|last7=Smith|first7=P. Brian|title=Safety of High-Dose Acyclovir in Infants with Suspected and Confirmed Neonatal Herpes Simplex Virus Infections|journal=The Pediatric Infectious Disease Journal|year=2016|pages=1|issn=0891-3668|doi=10.1097/INF.0000000000001451}}</ref>
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| ==Surgical Therapy==
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| There are no surgical measures for the management of neonatal herpes simplex.
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| ==Prevention==
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| ===Primary Prevention===
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| *Women without known genital herpes should be counseled to abstain from vaginal intercourse during the third trimester with partners known or suspected of having genital herpes.<ref name="urlGenital HSV Infections - 2015 STD Treatment Guidelines">{{cite web |url=https://www.cdc.gov/std/tg2015/herpes.htm |title=Genital HSV Infections - 2015 STD Treatment Guidelines |format= |work= |accessdate=}}</ref>
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| *Pregnant women without known orolabial herpes are advised to abstain from receptive oral sex during the third trimester with partners known or suspected to have orolabial herpes.<ref name="urlGenital HSV Infections - 2015 STD Treatment Guidelines">{{cite web |url=https://www.cdc.gov/std/tg2015/herpes.htm |title=Genital HSV Infections - 2015 STD Treatment Guidelines |format= |work= |accessdate=}}</ref>
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| *All pregnant women should be asked about history of genital herpes. At the onset of labor, all women should be questioned carefully about symptoms of genital herpes, including prodromal symptoms, and all women should be examined carefully for herpetic lesions. Women without symptoms or signs of genital herpes or its prodrome can deliver vaginally. Cesarean delivery does not completely eliminate the risk for HSV transmission to the neonate, women with recurrent genital herpetic lesions at the onset of labor should deliver by cesarean delivery to reduce the risk for neonatal HSV infection.<ref name="urlGenital HSV Infections - 2015 STD Treatment Guidelines">{{cite web |url=https://www.cdc.gov/std/tg2015/herpes.htm |title=Genital HSV Infections - 2015 STD Treatment Guidelines |format= |work= |accessdate=}}</ref>
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| *Consistent condom use and avoidance of sexual activity during recurrences.
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| ===Secondary Prevention===
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| *Suppressive acyclovir treatment late in pregnancy reduces the frequency of cesarean delivery among women who have recurrent genital herpes by reducing the frequency of recurrences at term. However, such treatment may not protect against transmission to neonates in all cases. Recommended Regimen : Acyclovir 400 mg orally three times a day OR Valacyclovir 500 mg orally twice a day, beginning from 36weeks of gestation. <ref name="pmid14662233">{{cite journal| author=Sheffield JS, Hollier LM, Hill JB, Stuart GS, Wendel GD| title=Acyclovir prophylaxis to prevent herpes simplex virus recurrence at delivery: a systematic review. | journal=Obstet Gynecol | year= 2003 | volume= 102 | issue= 6 | pages= 1396-403 | pmid=14662233 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14662233 }} </ref><ref name="pmid12634667">{{cite journal| author=Watts DH, Brown ZA, Money D, Selke S, Huang ML, Sacks SL et al.| title=A double-blind, randomized, placebo-controlled trial of acyclovir in late pregnancy for the reduction of herpes simplex virus shedding and cesarean delivery. | journal=Am J Obstet Gynecol | year= 2003 | volume= 188 | issue= 3 | pages= 836-43 | pmid=12634667 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12634667 }} </ref><ref name="pmid12530483">{{cite journal| author=Scott LL, Hollier LM, McIntire D, Sanchez PJ, Jackson GL, Wendel GD| title=Acyclovir suppression to prevent recurrent genital herpes at delivery. | journal=Infect Dis Obstet Gynecol | year= 2002 | volume= 10 | issue= 2 | pages= 71-7 | pmid=12530483 | doi=10.1155/S1064744902000054 | pmc=1784606 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12530483 }} </ref>
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| ==References== | | ==Case Studies== |
| {{reflist|2}}
| | [[Roseola case study one|Case #1]] |