|
|
| (495 intermediate revisions by 2 users not shown) |
| Line 1: |
Line 1: |
| __NOTOC__ | | __NOTOC__ |
| {{SI}}
| |
| {{CMG}} {{AE}} {{AKI}}
| |
|
| |
|
| {{SK}} | | {{Roseola}} |
| ==Overview==
| | {{CMG}}:{{AE}}{{DAMI}} |
|
| |
|
| ==Historical Perspective==
| |
| *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>
| |
|
| |
|
| ==Classification== | | ==[[Roseola overview|Overview]]== |
| ===Neonatal Herpes Simplex Classification===
| |
| Neonatal herpes simplex is classified based on the organ system involvement in the neonate into the following:
| |
| *'''Disseminated herpes simplex:''' Involving visceral organs such as lung, liver, adrenal glands, skin, eye, and/or brain
| |
| *'''Central nervous system disease:''' Involvement of the CNS with or without skin lesions
| |
| *'''SEM Disease:''' Disease limited to the involvement of skin, eye and mouth
| |
|
| |
|
| ===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 has influence on the management approach.
| |
| {| class="wikitable"
| |
| !Classification of maternal infection
| |
| !PCR / Culture from the genital lesion
| |
| !Maternal HSV-1/ HSV-2 Antibody status
| |
| |-
| |
| |First episode primary infection
| |
| |Positive for either virus
| |
| |Negative for both
| |
| |-
| |
| | rowspan="2" |Recurrent infection
| |
| |Positive for HSV-1
| |
| |Positive for HSV-1
| |
| |-
| |
| |Positive for HSV-2
| |
| |Positive for HSV-2
| |
| |}
| |
|
| |
|
| ==Pathophysiology== | | ==[[Roseola classification|Classification]]== |
|
| |
|
| ===Pathogenesis=== | | ==[[Roseola pathophysiology|Pathophysiology]]== |
|
| |
|
| *The risk of transmission of infection to the neonate from an infected mother is high (30-50%) who have 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>
| | ==[[Roseola causes|Causes]]== |
| ====Timing of infection====
| |
| *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>
| |
| *Intrauterine infection accounts for 5% of cases with neonatal herpes simplex.
| |
| *Postnatal trasmission by contact with HSV shed from infected patients. It accounts for 10% of the cases.
| |
|
| |
|
| ====Factors that influence transmission of HSV from the mother to the neonate==== | | ==[[Roseola differential diagnosis|Differentiating Any Disease from other Diseases]]== |
| The factors which influence the transmission of infection include:
| |
| *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>
| |
| *Maternal HSV antibody status, women with recurrent infection have IgG antibodies aganist HSV which can protect the fetus from infection.
| |
| *Prolonged duration of rupture of membranes increases the risk of infection transmission.
| |
| *Use of scalp electrodes disrupts the integrity of mucocutaneous barrier increasing the risk of transmission.
| |
| *Vaginal delivery has a higher risk of transmission of infection compared to cesarean section.
| |
|
| |
|
| ==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>
| |
| ==Risk Factors==
| |
| 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:
| |
| *Low family income
| |
| *Minority ethnic group
| |
| *Longer duration of sexual activity
| |
| *Past history of other sexually transmitted infections
| |
| *Multiple sexual partners
| |
|
| |
|
| ==Causes== | | ==[[Roseola risk factors|Risk Factors]]== |
| The causative pathogen for neonatal herpes simplex is herpes simplex virus. The different types involved in the disease are as follows:
| |
| *85% of cases are caused by HSV type 1
| |
| *15% of cases are caused by HSV type 2
| |
|
| |
|
| ==Differentiating Neonatal Herpes Simplex From Other Diseases== | | ==[[Roseola screening|Screening]]== |
| 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>
| |
| <small>
| |
| {| class="wikitable"
| |
| !Congenital Infection
| |
| !Cardiac Findings
| |
| !Skin Findings
| |
| !Ocular Findings
| |
| !Hepatosplenomegaly
| |
| !Hydrocephalus
| |
| !Microcephaly
| |
| !Intracranial Calcifications
| |
| !Hearing deficits
| |
| |-
| |
| !Congenital Varicella Syndrome
| |
| |
| |
| | -
| |
| *Cicatrical Skin Lesions
| |
| *Skin Edema
| |
| |
| |
| *Micropthalmus
| |
| *Cataracts
| |
| |✔
| |
| |
| |
| |✔
| |
| |✔
| |
| |
| |
| |-
| |
| ![[Toxoplasmosis congenital|Toxoplasmosis]]
| |
| |
| |
| |
| |
| * [[Petechiae]]
| |
| * [[Purpura]]
| |
| * [[Maculopapular rash]]
| |
| |
| |
| * [[Chorioretinitis]]
| |
| |✔
| |
| |✔
| |
| |✔
| |
| |Diffuse intracranial calcifications
| |
| |
| |
| |-
| |
| ![[Congenital Syphils]]
| |
| |
| |
| |
| |
| * [[Petechiae]]
| |
| * [[Purpura]]
| |
| * [[Maculopapular rash]]
| |
| |
| |
| * [[Chorioretinitis]]
| |
| * [[Glaucoma]]
| |
| |✔
| |
| |
| |
| |
| |
| |
| |
| |
| |
| |-
| |
| ![[Rubella, congenital|Rubella]]
| |
| |
| |
| * [[Patent ductus arteriosus (PDA)]]
| |
| * [[Pulmonary artery stenosis]]
| |
| * [[Coarctation of the aorta]]
| |
| * [[Myocarditis]]
| |
| |
| |
| * [[Petechiae]]
| |
| * [[Purpura]]
| |
| |
| |
| * [[Chorioretinitis]]
| |
| * [[Cataracts]]
| |
| * [[Glaucoma]]
| |
| * [[Microphthalmia]]
| |
| |✔
| |
| |✔
| |
| |✔
| |
| |
| |
| |✔
| |
| |-
| |
| ![[Cytomegalovirus (CMV)]]
| |
| |✔
| |
| |
| |
| * [[Petechiae]]
| |
| * [[Purpura]]
| |
| |
| |
| * [[Chorioretinitis]]
| |
| |✔
| |
| |
| |
| |✔
| |
| |Periventricular calcifications
| |
| |✔
| |
| |-
| |
| ![[Herpes simplex virus (HSV)]]
| |
| |
| |
| * [[Myocarditis]]
| |
| |
| |
| * [[Petechiae]]
| |
| * [[Purpura]]
| |
| * [[Vesicles]]
| |
| |
| |
| * [[Chorioretinitis]]
| |
| |✔
| |
| |✔
| |
| |✔
| |
| |
| |
| |✔
| |
| |-
| |
| ![[Parvovirus B19]]
| |
| |
| |
| * [[Myocarditis]]
| |
| |
| |
| * [[Petechiae]]
| |
| * [[Subcutaneous]] [[edema]]
| |
| |
| |
| * [[Chorioretinitis]]
| |
| * [[Cataracts]]
| |
| |✔
| |
| |
| |
| |
| |
| |
| |
| |
| |
| |}
| |
| </small>
| |
|
| |
|
| ==Natural History, Prognosis and Complications== | | ==[[Roseola natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
| ===Natural History===
| |
| ===Prognosis===
| |
| ===Complications===
| |
|
| |
|
| ==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===
| |
| | |
| ===Physical Examination===
| |
| | |
| | |
| ===Laboratory Findings===
| |
| ====Diagnosis of maternal genital herpes====
| |
| *Diagnosis of maternal herpes simplex can be done by PCR assay for HSV DNA and culture for HSV.
| |
| *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 the availability in remote medical facilities.
| |
| *Culture for HSV is 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.
| |
| *Serological tests distinguish antibodies produced against HSV-1 and HSV-2, therefore helps in determining the type of HSV causing the infection.
| |
| ====Diagnosis in the Neonate====
| |
| 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.
| |
| *The specimens for surface cultures are collected from multiple areas and include mouth, nasopharynx, conjunctivae, skin vesicles and anus.
| |
| *Other specimens to be collected include CSF for culture and PCR assay, whole blood for PCR assay and liver function tests.
| |
| *Based on the laboratory findings HSV infection is differentiated into two types:
| |
| {| class="wikitable"
| |
| !Stage of Neonate infection
| |
| !Specific Findings
| |
| |- | |
| |HSV Infection | |
| | | |
| *Asymptomatic infant
| |
| *Positive surface culture
| |
| *Positive HSV blood PCR
| |
| *Normal CSF analysis
| |
| *Normal alanine transaminase
| |
| |- | |
| |HSV Disease | |
| | | |
| *Symptomatic infant ( Presence of SEM, disseminated, CNS HSV features)
| |
| *Positive surface culture
| |
| *Positive HSV blood PCR
| |
| *Positive CSF HSV
| |
| *Elevated alanine transaminase
| |
| |} | |
|
| |
|
| ==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}}
| |
| {{familytree | | | | | | | | | | | | | A01 | | | | | | | | | | | | | | | | | |A01= Suspicion of HSV infection in asymptomatic neonate}}
| |
| {{familytree | | | | | | | | | | | | | |!| | | | | | | | | | | | | | | }}
| |
| {{familytree | | | | | | | | | | | | | B01 | | | | | | | |B01 = Establish the infection status of the mother}}
| |
| {{familytree | | | | |,|-|-|-|-|-|-|-|-|^|-|-|-|-|-|-|-|-|.| }}
| |
| {{familytree | | | | B01 | | | | | | | | | | | | | | | | B02 | |B01= First episode of genital herpes| B02 = Positive past history for similar lesions before pregnancy }}
| |
| {{familytree | | | | |!| | | | | | | | | | | | | | | | | |!| | }}
| |
| {{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}}
| |
| {{familytree | | | | |!| | | | | | | | | | | | | | | | | |!| | | | |}}
| |
| {{familytree | | | | D01 | | | | | | | | | | | | | | | | D02 | | | |D01= ❑ Perform maternal serology to differentiate the stages of maternal infection <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}}
| |
| {{familytree/end}}
| |
|
| |
| | |
| {{familytree/start}}
| |
| {{familytree | | | A01 | | | | | | | | | A02 | | | | | | | | | A03 | | | | | A01= Primary infection or First Episode Non-primary infection | A02 = Recurrent infection | A03 = Reactivation }}
| |
| {{familytree | |,|-|^|-|-|-|.| | | |,|-|-|^|-|-|-|.| | | |,|-|-|^|-|-|.| }}
| |
| {{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 }}
| |
| {{familytree | |!| | | | | |`|-|v|-|'| | | | | | |!| | | |!| | | | | |!| |}}
| |
| {{familytree | C01 | | | | | | C02 | | | | | | | C04 | | C05 | | | | C06 ||C01= Continue IV Acyclovir based on the extent of the disease (14 to 21 days) <br> Initial CSF PCR was positive repeat lumbar puncture at the end of therapy | C04= Stop Acyclovir <br> Educate the parents regarding the symptoms of HSV <br> Discharge <br> Re-evaluate at 6weeks | C02 = Continue IV Acyclovir for 10days to prevent progression | C05= Discharge <br> Educate the parents regarding the symptoms of HSV <br> Re-evaluate at 6 weeks | C06 = Perform complete evaluation to determine the extent of the disease}}
| |
| | |
| ==Medical Therapy==
| |
| ==Surgical Therapy==
| |
| | |
| ==Prevention==
| |
| ===Primary Prevention===
| |
| *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.
| |
| *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.
| |
| *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.
| |
| | |
| ===Secondary Prevention===
| |
| *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>
| |
|
| |
|
| ==References== | | ==Case Studies== |
| {{reflist|2}}
| | [[Roseola case study one|Case #1]] |