Sandbox: Reddy: Difference between revisions
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{{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 | | | | 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/end}} | ||
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{{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== | ==Medical Therapy== |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aravind Kuchkuntla, M.B.B.S[2]
Synonyms and keywords:
Overview
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.[1]
Classification
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
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.
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 |
Recurrent infection | Positive for HSV-1 | Positive for HSV-1 |
Positive for HSV-2 | Positive for HSV-2 |
Pathophysiology
Pathogenesis
- 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.[2][3][4]
Timing of infection
- Exposure to the fetus from active genital herpes lesions during delivery, accounts for majority of neonatal herpes simplex cases. [5]
- 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
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.[6]
- 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
- The annual incidence of neonatal herpes is estimated to be 10 cases per 100,000 livebirths.[7]
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
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
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:[8][9]
Congenital Infection | Cardiac Findings | Skin Findings | Ocular Findings | Hepatosplenomegaly | Hydrocephalus | Microcephaly | Intracranial Calcifications | Hearing deficits |
---|---|---|---|---|---|---|---|---|
Congenital Varicella Syndrome | -
|
|
✔ | ✔ | ✔ | |||
Toxoplasmosis | ✔ | ✔ | ✔ | Diffuse intracranial calcifications | ||||
Congenital Syphils | ✔ | |||||||
Rubella | ✔ | ✔ | ✔ | ✔ | ||||
Cytomegalovirus (CMV) | ✔ | ✔ | ✔ | Periventricular calcifications | ✔ | |||
Herpes simplex virus (HSV) | ✔ | ✔ | ✔ | ✔ | ||||
Parvovirus B19 | ✔ |
Natural History, Prognosis and Complications
Natural History
Prognosis
Complications
Diagnosis
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:
Stage of Neonate infection | Specific Findings |
---|---|
HSV Infection |
|
HSV Disease |
|
Treatment
Approach to neonate with suspected HSV infection
Suspicion of HSV infection in asymptomatic neonate | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Establish the infection status of the mother | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
First episode of genital herpes | Positive past history for similar lesions before pregnancy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Signifies the infection can be primary infection, first episode non primary infection or a recurrent infection | Signifies the infection is most likely due to reactivation of the virus | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
❑ Perform maternal serology to differentiate the stages of maternal infection At 24hours of life perform : ❑ HSV surface cultures ❑ CSF analysis and HSV PCR ❑ HSV Blood PCR ❑ Measure serum ALT ❑ Initiate IV Acyclovir 60mg/kg/day in 3 divided doses | At 24 hours of life perform : ❑ Surface cultures ❑ HSV Blood PCR ❑ Donot start Acyclovir if the baby is asymptomatic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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. [10][11][12]
References
- ↑ Hass GM (1935). "Hepato-Adrenal Necrosis with Intranuclear Inclusion Bodies: Report of a Case". Am J Pathol. 11 (1): 127–142.5. PMC 1910753. PMID 19970188.
- ↑ Brown, ZaneA.; Selke, Stacy; Zeh, Judy; Kopelman, Jerome; Maslow, Arthur; Ashley, Rhoda L.; Watts, D. Heather; Berry, Sylvia; Herd, Millie; Corey, Lawrence (1997). "The Acquisition of Herpes Simplex Virus during Pregnancy". New England Journal ofMedicine. 337 (8): 509–516. doi:10.1056/NEJM199708213370801. ISSN 0028-4793.
- ↑ Pinninti SG, Kimberlin DW (2013). "Maternal and neonatal herpes simplex virus infections". Am J Perinatol. 30 (2): 113–9. doi:10.1055/s-0032-1332802. PMID 23303485.
- ↑ Brown ZA, Benedetti J, Ashley R, Burchett S, Selke S, Berry S; et al. (1991). "Neonatal herpes simplex virus infection in relation to asymptomatic maternal infection at the time of labor". N Engl J Med. 324 (18): 1247–52. doi:10.1056/NEJM199105023241804. PMID 1849612.
- ↑ Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L (2003). "Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant". JAMA. 289 (2): 203–9. PMID 12517231.
- ↑ Brown, Zane A. (2003). "Effect of Serologic Status and Cesarean Delivery on Transmission Rates of Herpes Simplex Virus From Mother to Infant". JAMA. 289 (2): 203. doi:10.1001/jama.289.2.203. ISSN 0098-7484.
- ↑ Looker KJ, Magaret AS, May MT, Turner KM, Vickerman P, Newman LM; et al. (2017). "First estimates of the global and regional incidence of neonatal herpes infection". Lancet Glob Health. 5 (3): e300–e309. doi:10.1016/S2214-109X(16)30362-X. PMID 28153513.
- ↑ Neu N, Duchon J, Zachariah P (2015). "TORCH infections". Clin Perinatol. 42 (1): 77–103, viii. doi:10.1016/j.clp.2014.11.001. PMID 25677998.
- ↑ Ajij M, Nangia S, Dubey BS (2014). "Congenital rubella syndrome with blueberry muffin lesions and extensive metaphysitis". J Clin Diagn Res. 8 (12): PD03–4. doi:10.7860/JCDR/2014/10271.5293. PMC 4316306. PMID 25654000.
- ↑ Sheffield JS, Hollier LM, Hill JB, Stuart GS, Wendel GD (2003). "Acyclovir prophylaxis to prevent herpes simplex virus recurrence at delivery: a systematic review". Obstet Gynecol. 102 (6): 1396–403. PMID 14662233.
- ↑ Watts DH, Brown ZA, Money D, Selke S, Huang ML, Sacks SL; et al. (2003). "A double-blind, randomized, placebo-controlled trial of acyclovir in late pregnancy for the reduction of herpes simplex virus shedding and cesarean delivery". Am J Obstet Gynecol. 188 (3): 836–43. PMID 12634667.
- ↑ Scott LL, Hollier LM, McIntire D, Sanchez PJ, Jackson GL, Wendel GD (2002). "Acyclovir suppression to prevent recurrent genital herpes at delivery". Infect Dis Obstet Gynecol. 10 (2): 71–7. doi:10.1155/S1064744902000054. PMC 1784606. PMID 12530483.
Primary infection or First Episode Non-primary infection | Recurrent infection | Reactivation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
HSV Disease | HSV Infection | HSV Infection | ❑ Negative neonate HSV blood PCR ❑ Negative surface culture | ❑ Negative blood HSV PCR ❑ Negative surface culture | ❑ Positive HSV blood PCR ❑ Positive surface culture | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Continue IV Acyclovir based on the extent of the disease (14 to 21 days) Initial CSF PCR was positive repeat lumbar puncture at the end of therapy | Continue IV Acyclovir for 10days to prevent progression | Stop Acyclovir Educate the parents regarding the symptoms of HSV Discharge Re-evaluate at 6weeks | Discharge Educate the parents regarding the symptoms of HSV Re-evaluate at 6 weeks | Perform complete evaluation to determine the extent of the disease | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||