Herpes Simplex PDF

HERPES SIMPLEX 437 in serum or stool does not eliminate the possibility...

HERPES SIMPLEX 437 in serum or stool does not eliminate the possibility that the person was infected with HEV. TREATMENT: Supportive. Some case reports and case series have indicated that modifica- tion of immunosuppressive medication and/or use of antiviral drugs, such as ribavirin, with or without interferon-alpha, may result in viral clearance in immunocompromised patients with chronic hepatitis E. However, no randomized controlled clinical trials have been performed. ISOLATION OF THE HOSPITALIZED PATIENT: In addition to standard precautions, con- tact precautions are recommended for diapered and incontinent patients for the duration of illness. CONTROL MEASURES: Provision of safe water is the most effective prevention measure. A safe and effective recombinant HEV vaccine has been approved for use by the Chinese Food and Drug Administration but is not approved for use in the United States. The All rights reserved. May not be reproduced in any form without permission from the publisher, except fair uses permitted under U.S. or applicable copyright law. World Health Organization recently published a position paper on hepatitis E vaccine development (www.who.int/wer/2015/wer9018.pdf?ua=1). Herpes Simplex CLINICAL MANIFESTATIONS: Neonatal. In newborn infants, herpes simplex virus (HSV) infection can manifest as: (1) dis- seminated disease involving multiple organs, most prominently liver and lungs, and in 60% to 75% of cases also involving the central nervous system (CNS); (2) localized CNS disease, with or without skin, eye, or mouth involvement (CNS disease); or (3) disease lo- calized to the skin, eyes, and/or mouth (SEM disease). Approximately 25% of cases of ne- onatal HSV manifest as disseminated disease, 30% manifest as CNS disease, and 45% manifest as SEM disease. In the absence of skin lesions, the diagnosis of neonatal HSV in- fection is challenging. More than 80% of neonates with SEM disease have skin vesicles; those without vesicles have infection limited to the eyes and/or oral mucosa. Approxi- mately two thirds of neonates with disseminated or CNS disease have skin lesions, but these lesions may not be present at the time of onset of symptoms. Disseminated infection should be considered in neonates with sepsis syndrome with negative bacteriologic culture results, severe liver dysfunction, consumptive coagulopathy, or suspected viral pneumo- nia. HSV should be considered as a causative agent in neonates with fever (especially within the first 3 weeks of life), a vesicular rash, or abnormal cerebrospinal fluid (CSF) findings (especially in the presence of seizures or during a time of year when enteroviruses are not circulating in the community). Although asymptomatic HSV infection is common in older children, it rarely, if ever, occurs in neonates. Neonatal herpetic infections often are severe, with attendant high mortality and mor- bidity rates, even when antiviral therapy is administered. Mortality rates from neonatal Copyright 2018. American Academy of Pediatrics. herpes increased between 2004 and 2013, compared with the 20 years prior to that. Re- current skin lesions are common in surviving infants, occurring in approximately 50% of survivors, often within 1 to 2 weeks of completing the initial treatment course of paren- teral acyclovir. Initial signs of HSV infection can occur anytime between birth and approximately 6 weeks of age, although almost all infected infants develop clinical disease within the first month of life. Infants with disseminated disease and SEM disease have an earlier age of onset, typically presenting between the first and second weeks of life; infants with CNS EBSCO Publishing : eBook Academic Collection (EBSCOhost) - printed on 8/17/2021 6:25 AM via UNIV OF SOUTH ALABAMA AN: 1809323 ; Kimberlin, David W., Brady, Michael T., Jackson, Mary Anne, Long, Sarah S..; Red Book 2018 : Report of the Committee on Infectious Diseases Account: s4595122.main.emed  438 HERPES SIMPLEX disease usually present with illness between the second and third weeks of life. Children Beyond the Neonatal Period and Adolescents. Most primary HSV childhood infections beyond the neonatal period are asymptomatic. Gingivostomatitis, which is the most com- mon clinical manifestation of HSV during childhood, is caused by HSV type 1 (HSV-1) and is characterized by fever, irritability, tender submandibular adenopathy, and an ul- cerative enanthem involving the gingiva and mucous membranes of the mouth, often with perioral vesicular lesions. Genital herpes is characterized by vesicular or ulcerative lesions of the male or female genitalia, perineum, or both. Until recently, genital herpes most often was caused by HSV type 2 (HSV-2), but HSV-1 now accounts for more than half of all cases in the United States. Most cases of primary genital herpes infection in males and females are asymptomatic, so they are not recognized by the infected person or diagnosed by a health care professional. Eczema herpeticum can develop in patients with atopic dermatitis who are infected with HSV, and can be difficult to distinguish from poorly controlled atopic dermatitis. Examination may reveal skin with punched-out erosions, hemorrhagic crusts, and/or ve- sicular lesions. Pustular lesions attributable to bacterial superinfection also may occur. In immunocompromised patients, severe local lesions and, less commonly, dissemi- nated HSV infection with generalized vesicular skin lesions and visceral involvement can occur. After primary infection, HSV persists for life in a latent form. Reactivation of latent virus most commonly is asymptomatic. When symptomatic, recurrent HSV-1 herpes labi- alis manifests as single or grouped vesicles in the perioral region, usually on the vermilion border of the lips (typically called “cold sores” or “fever blisters”). Symptomatic recurrent genital herpes manifests as vesicular lesions on the penis, scrotum, vulva, cervix, buttocks, perianal areas, thighs, or back. Among immunocompromised patients, genital HSV-2 re- currences are more frequent and of longer duration. Recurrences may be heralded by a prodrome of burning or itching at the site of an incipient recurrence, identification of which can be useful in instituting early antiviral therapy. Conjunctivitis and keratitis can result from primary or recurrent HSV infection. Her- petic whitlow consists of single or multiple vesicular lesions on the distal parts of fingers. Wrestlers can develop herpes gladiatorum if they become infected with HSV-1. HSV in- fection can be a precipitating factor in erythema multiforme, and recurrent erythema multiforme often is caused by symptomatic or asymptomatic HSV recurrences. HSV encephalitis (HSE) occurs in children beyond the neonatal period, in adoles- cents, and in adults, and can result from primary or recurrent HSV-1 infection. One fifth of HSE cases occur in the pediatric age group. Symptoms and signs usually include fever, alterations in the state of consciousness, personality changes, seizures, and focal neuro- logic findings. Encephalitis commonly has an acute onset with a fulminant course, leading to coma and death in untreated patients. Patients who are comatose or semicomatose at initiation of therapy have a poorer outcome. HSE usually involves the temporal lobe, and magnetic resonance imaging is the most sensitive imaging modality to detect this. CSF pleocytosis with a predominance of lymphocytes is typical. Historically, erythrocytes in the CSF were considered suggestive of HSE, but with earlier diagnosis (prior to full mani- festations of a hemorrhagic encephalitis), this finding is rare today. HSV infection also can manifest as mild, self-limited aseptic meningitis, usually asso- ciated with genital HSV-2 infection. Unusual CNS manifestations of HSV include Bell’s EBSCOhost - printed on 8/17/2021 6:25 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  HERPES SIMPLEX 439 palsy, atypical pain syndromes, trigeminal neuralgia, ascending myelitis, transverse myeli- tis, postinfectious encephalomyelitis, and recurrent (Mollaret) meningitis. ETIOLOGY: HSVs are large, enveloped, double-stranded DNA viruses. They are mem- bers of the family Herpesviridae and, along with varicella-zoster virus (human herpesvirus 3), are the subfamily Alphaherpesviridae. Two distinct HSV types exist: HSV-1 and HSV-2. Infections with HSV-1 traditionally involve the face and skin above the waist; however, an increasing number of genital herpes cases are attributable to HSV-1. Infections with HSV-2 usually involve the genitalia and skin below the waist in sexually active adoles- cents and adults. Both HSV-1 and HSV-2 cause herpetic disease in neonates. HSV-1 and HSV-2 establish latency following primary infection, with periodic reactivation to cause recurrent symptomatic disease or asymptomatic viral shedding. Genital HSV-2 infection is more likely to recur than is genital HSV-1 infection. EPIDEMIOLOGY: HSV infections are ubiquitous and can be transmitted from people who are symptomatic or asymptomatic with primary or recurrent infections. Neonatal. The incidence of neonatal HSV infection in the United States is estimated to range from 1 in 2000 to 1 in 3000 live births. HSV is transmitted to a neonate most often during birth through an infected maternal genital tract but can be caused by an ascend- ing infection through ruptured or apparently intact amniotic membranes. Other less com- mon sources of neonatal infection include postnatal transmission from a parent, sibling, or other caregiver, most often from a nongenital infection (eg, mouth or hands), and in- trauterine infection causing congenital malformations. The risk of transmission to a neonate born to a mother who acquires primary genital HSV infection near the time of delivery is estimated to be 25% to 60%. In contrast, the risk to a neonate born to a mother shedding HSV as a result of reactivation of infection acquired during the first half of pregnancy or earlier is less than 2%. Distinguishing be- tween primary and recurrent HSV infections in women by history or physical examina- tion alone may be impossible, because primary and recurrent genital infections may be asymptomatic or associated with nonspecific findings (eg, vaginal discharge, genital pain, or shallow ulcers). History of maternal genital HSV infection is not helpful in diagnosing neonatal HSV disease, because more than three quarters of infants who contract HSV in- fection are born to women with no history or clinical findings suggestive of genital HSV infection during or preceding pregnancy and who, therefore, are unaware of their infec- tion. Children Beyond the Neonatal Period and Adolescents. Patients with primary gingivostomatitis or genital herpes usually shed virus for at least 1 week and occasionally for several weeks. Patients with symptomatic recurrences shed virus for a shorter period, typically 3 to 4 days. Intermittent asymptomatic reactivation of oral and genital herpes is common and likely occurs throughout the remainder of a person’s life. The greatest concentration of virus is shed during symptomatic primary infections and the lowest during asymptomatic reactivation. Inoculation of abraded skin occurs from direct contact with HSV shed from oral, genital, or other skin sites. This contact can result in herpes gladiatorum among wrestlers, herpes rugbiorum among rugby players, or herpetic whitlow of the fingers in any exposed person. The incubation period for HSV infection occurring beyond the neonatal period ranges from 2 days to 2 weeks. EBSCOhost - printed on 8/17/2021 6:25 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  440 HERPES SIMPLEX DIAGNOSTIC TESTS: HSV grows readily in traditional cell culture. Special transport me- dia are available that allow transport to local or regional laboratories for culture. Cyto- pathogenic effects typical of HSV infection usually are observed 1 to 3 days after inocula- tion. Methods of culture confirmation include fluorescent antibody staining, enzyme im- munoassays (EIAs), and monolayer culture with typing. Cultures that remain negative by day 5 likely will remain negative. A spin amplification culture method involving centrifu- gation of the specimen onto glass coverslips in small vials (shell vial technique) followed by fluorescent antibody staining of the coverslips and fluorescent microscopy may be used to reduce time to detection to 24 to 48 hours. An alternative, commercially available rapid culture technique known as ELVIS (enzyme-linked, virus-inducible system) uses genet- ically engineered cells to allow for HSV gene expression and detection of infected cells by light microscopy. Sensitivity of culture is highly dependent on proper specimen collection, quality of reagents, and expertise of testing personnel, in addition to the stage of lesion de- velopment, with crusted lesions being less likely to be culture positive. Polymerase chain reaction (PCR) assay usually can detect HSV DNA in CSF from neonates with CNS infection (neonatal HSV CNS disease) and from older children and adults with HSE and is the diagnostic method of choice for CNS HSV involvement. Most of these assays were developed by individual laboratories, and thus, performance varies depending on the individual test. PCR assay of CSF can yield negative results in cases of HSE, especially early in the disease course. In difficult cases in which repeated CSF PCR assay results are negative, histologic examination and viral culture of a brain tissue biopsy specimen is the most definitive method of confirming the diagnosis of HSE. There cur- rently are 2 PCR assays cleared by the US Food and Drug Administration (FDA) for the detection of HSV in CSF; the first is a singleplex assay, and the second is a multiplex as- say that is capable of detection HSV and a number of other bacterial and viral agents of meningitis and encephalitis in CSF. There are limited clinical data on the efficacy of these FDA-cleared assays, and results should be interpreted cautiously. Detection of intrathecal antibody against HSV also can assist in the diagnosis. Viral cultures of CSF from a pa- tient with HSE usually are negative. For diagnosis of neonatal HSV infection, all of the following specimens should be ob- tained for each patient: (1) swab specimens from the mouth, nasopharynx, conjunctivae, and anus (“surface specimens”) for HSV culture (if available) or PCR assay; (2) specimens of skin vesicles for HSV culture (if available) or PCR assay; (3) CSF sample for HSV PCR assay; (4) whole blood sample for HSV PCR assay; and (5) whole blood sample for meas- uring alanine transaminase (ALT). The performance characteristics of PCR assay on skin and mucosal specimens from neonates has not been studied. Positive cultures obtained from any of the surface sites more than 12 to 24 hours after birth indicate viral replication and are, therefore, suggestive of infant infection rather than merely contamination after intrapartum exposure. As with any PCR assay, false-negative and false-positive results can occur. Any of the 3 manifestations of neonatal HSV disease (disseminated, CNS, SEM) can have associated viremia, so a positive whole blood PCR assay result does not define an infant as having disseminated HSV and, therefore, should not be used to determine extent of disease and duration of treatment; likewise, no data exist to support use of serial blood PCR assays to monitor response to therapy. Rapid diagnostic techniques are avail- able, such as direct fluorescent antibody staining of vesicle scrapings or EIA detection of HSV antigens. These techniques are as specific but slightly less sensitive than culture. Radiographs and clinical manifestations can suggest HSV pneumonitis, and elevated EBSCOhost - printed on 8/17/2021 6:25 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  HERPES SIMPLEX 441 transaminase values can suggest HSV hepatitis. Histologic examination of lesions for presence of multinucleated giant cells and eosinophilic intranuclear inclusions typical of HSV (eg, with Tzanck test) should not be performed because of low sensitivity. HSV PCR assay and cell culture are the preferred tests for detecting HSV in genital lesions. The sensitivity of viral culture is low, especially for recurrent lesions, and declines rapidly as lesions begin to heal. PCR assays for HSV DNA are more sensitive and in- creasingly are used in many settings. There are currently several FDA-cleared PCR as- says for the detection of HSV in skin, oral, and genital lesions in adults. Failure to detect HSV in genital lesions by culture or PCR assay does not rule out HSV infection, because viral shedding is intermittent. Both type-specific and type-common antibodies to HSV develop during the first sev- eral weeks after infection and persist indefinitely. Approximately 20% of HSV-2 first epi- sode patients seroconvert by 10 days, and the median time to seroconversion is 21 days with a type-specific enzyme-linked immunosorbent assay (ELISA); more than 95% of people seroconvert by 12 weeks following infection. Although type-specific HSV-2 anti- body usually indicates previous anogenital infection, the presence of HSV-1 antibody does not distinguish anogenital from orolabial infection reliably, because a substantial proportion of initial genital infections and virtually all initial orolabial infections are caused by HSV-1. Type-specific serologic tests can be useful in confirming a clinical diag- nosis of genital herpes caused by HSV-2. Additionally, these serologic tests can be used to evaluate individuals with recurrent or atypical genital tract symptoms with negative HSV culture or PCR evaluations and to manage sexual partners of people with genital herpes. Serologic testing is not useful in neonates. Both laboratory-based assays and point-of-care tests that provide results for HSV-2 antibodies from capillary blood or serum are available. The sensitivities of these glycopro- tein G type-specific tests for the detection of HSV-2 antibody vary from 80% to 98%. The most commonly used test, HerpeSelect 2 ELISA IgG (Focus Diagnostics, Cypress, CA), might be falsely positive at low index values (1.1–3.5). Such low values should be confirmed with another test, such as Biokit (Werfen, Barcelona, Spain) or the Western blot (University of Washington); the HerpeSelect 2 Immunoblot IgG should not be used for confirmation, because it uses the same antigen as the HerpeSelect 2 ELISA IgG. Re- peat testing is indicated if recent acquisition of genital herpes is suspected. The HerpeSe- lect 1 ELISA IgG kit is insensitive. IgM testing for HSV-1 or HSV-2 is not useful, because IgM tests are not type-specific and might be positive during recurrent genital or oral epi- sodes of herpes. TREATMENT: For recommended antiviral dosages and duration of therapy with systemi- cally administered acyclovir, valacyclovir, and famciclovir for different HSV infections, see Non-HIV Antiviral Drugs (p 966). Valacyclovir is an L-valyl ester of acyclovir that is metabolized to acyclovir after oral administration, resulting in higher serum concentra- tions than those achieved with oral acyclovir and similar serum concentrations as those achieved with intravenous administration of acyclovir. Famciclovir is converted rapidly to penciclovir after oral administration. Table 3.28 shows drugs for treatment of HSV by type of infection. Valacyclovir has been approved by the FDA for the treatment of cold sores (herpes labialis) in pediatric patients 12 years or older. In pediatric patients for whom a solid dosage form of valacyclovir is not appropriate, instructions for preparing a compounded liquid formulation of valacyclovir with a 28-day shelf-life are provided in the drug’s package insert. EBSCOhost - printed on 8/17/2021 6:25 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  442 HERPES SIMPLEX Neonatal. Parenteral acyclovir is the treatment for neonatal HSV infections. The dosage of acyclovir is 60 mg/kg per day in 3 divided doses (20 mg/kg/dose), administered intrave- nously for 14 days in SEM disease and for a minimum of 21 days in CNS disease or dis- seminated disease. All infants with neonatal HSV disease, regardless of disease classifica- tion, should have an ophthalmologic examination and neuroimaging to establish baseline brain anatomy; magnetic resonance imaging is the most sensitive imaging modality but may require sedation, so computed tomography or ultrasonography of the head are ac- ceptable alternatives. 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; in the unlikely event that the PCR result remains positive near the end of a 21-day treatment course, intravenous acyclovir should be administered for another week, with repeat CSF PCR assay performed near the end of the extended treat- ment period and another week of parenteral therapy if it remains positive. Parenteral an- tiviral therapy should not be stopped until the CSF PCR result for HSV DNA is negative. Consultation with a pediatric infectious diseases specialist is warranted in these cases. Infants surviving neonatal HSV infections of any classification (disseminated, CNS, or SEM) should receive oral acyclovir suppression at 300 mg/m2/dose, administered 3 times daily for 6 months after the completion of parenteral therapy for acute disease; the dose should be adjusted monthly to account for growth. Absolute neutrophil counts should be Table 3.28. Recommended Therapy for Herpes Simplex Virus Infectionsa Infection Drugb Neonatal Parenteral acyclovir Keratoconjunctivitis Trifluridinec OR Topical ganciclovir Genital Acyclovir OR Famciclovir OR Valacyclovir Mucocutaneous (immunocompromised or primary Acyclovir gingivostomatitis) OR Famciclovir OR Valacyclovir Acyclovir-resistant (severe infections, Parenteral foscarnet immunocompromised) Encephalitis Parenteral acyclovir a See text and Table 4.10 (p 966) for details. b Famciclovir and valacyclovir are approved by the US Food and Drug Administration for treatment of adults. c Treatment of herpes simplex virus ocular infection should involve an ophthalmologist. EBSCOhost - printed on 8/17/2021 6:25 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  HERPES SIMPLEX 443 assessed at 2 and 4 weeks after initiating suppressive acyclovir therapy and then monthly during the treatment period. Longer durations or higher doses of antiviral suppression do not further improve neurodevelopmental outcomes. Valacyclovir has not been studied for longer than 5 days in young infants, so it should not be used routinely for antiviral sup- pression in this age group. Infants with ocular involvement attributable to HSV infection should receive a topical ophthalmic drug (1% trifluridine or 0.15% ganciclovir) as well as parenteral antiviral therapy. The older topical antiviral agents vidarabine and iododeoxyuridine no longer are available in the United States. An ophthalmologist should be involved in the manage- ment and treatment of acute neonatal ocular HSV disease. Genital Infection. Primary. Oral acyclovir therapy (400 mg, orally, 3 times/day for 7–10 days, or 200 mg, orally, 5 times/day for 7–10 days) shortens the duration of illness and viral shedding. Valacyclovir and famciclovir do not seem to be more effective than acyclovir but offer the advantage of less frequent dosing (famciclovir, 250 mg, orally, 3 times/day for 7–10 days; valacyclovir, 1 g, orally, 2 times/day for 7–10 days). Intravenous acyclovir is indicated for patients with a severe or complicated primary infection that requires hospitalization (5–10 mg/kg, intravenously, every 8 hours for 2–7 days or until clinical improvement is ob- served, followed by oral antiviral therapy to complete the treatment course). Treatment of primary herpetic lesions does not affect the subsequent frequency or severity of recur- rences. Recurrent. Antiviral therapy for recurrent genital herpes can be administered either ep- isodically to ameliorate or shorten the duration of lesions or continuously as suppressive therapy to decrease the frequency of recurrences. Many patients benefit from antiviral therapy, and treatment options should be discussed with patients with recurrent disease. Suppressive therapy has the additional advantage of decreasing the risk of genital HSV-2 transmission to susceptible partners. Acyclovir and valacyclovir have been approved for suppression of genital herpes in immunocompetent adults. Either may be administered orally to pregnant women with first-episode genital herpes or severe recurrent herpes, and acyclovir should be administered intravenously to pregnant women with severe HSV in- fection. Mucocutaneous. Immunocompromised Hosts. Intravenous acyclovir is effective for treatment of mucocuta- neous HSV infections. Acyclovir-resistant strains of HSV have been isolated from im- munocompromised people receiving prolonged treatment with acyclovir. Foscarnet is the drug of choice for acyclovir-resistant HSV isolates. Immunocompetent Hosts. Limited data are available on effects of acyclovir on the course of primary or recurrent nongenital mucocutaneous HSV infections in immunocompetent hosts. Therapeutic benefit has been noted in a limited number of children with primary gingivostomatitis treated with oral acyclovir. A small therapeutic benefit of oral acyclovir therapy has been demonstrated among adults with recurrent herpes labialis. When used as treatment for HSV orolabial disease, a dose of 80 mg/kg per day, in 4 divided doses, for 5 to 7 days, should be used, with a maximum of 3200 mg/day. Famciclovir or valacy- clovir also can be considered. Topical acyclovir is ineffective. A topical formulation of penciclovir (Denavir [Prestium Pharma, Newtown, PA]) and a topical alcohol, docosanol (Abreva [GlaxoSmithKline, Research Triangle Park, NC]), have only limited activity for therapy of herpes labialis and are not recommended. EBSCOhost - printed on 8/17/2021 6:25 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  444 HERPES SIMPLEX In a controlled study of a small number of adults with recurrent herpes labialis (6 or more episodes per year), suppressive acyclovir at a dosage of 400 mg, twice a day, was ef- fective for decreasing the frequency of recurrent episodes. Although no studies of suppres- sive therapy have been performed in children, those with frequent recurrences may bene- fit from daily oral acyclovir therapy, with reevaluation being performed after 6 months to 1 year of continuous therapy; a dose of 30 mg/kg per day, in 3 divided doses, with a max- imum 1000 mg/day, is reasonable to begin as suppressive therapy in children. Other HSV Infections. Central Nervous System. Patients with HSE should be treated for 21 days with intrave- nous acyclovir. For people with Bell palsy, the combination of acyclovir and prednisone may be considered. Ocular. Treatment of eye lesions should be undertaken in consultation with an oph- thalmologist. Several topical drugs, such as 1% trifluridine and 0.15% ganciclovir, have proven efficacy for superficial keratitis. The older topical antivirals vidarabine and iodo- deoxyuridine no longer are available in the United States. Topical corticosteroids admin- istered without concomitant antiviral therapy are contraindicated in suspected HSV con- junctivitis; however, ophthalmologists may choose to use corticosteroids in conjunction with antiviral drugs to treat locally invasive infections. For children with recurrent ocular lesions, oral suppressive therapy with acyclovir may be of benefit and may be indicated for months or even years. ISOLATION OF THE HOSPITALIZED PATIENT: In addition to standard precautions, the following recommendations should be followed. Neonates With HSV Infection. Neonates with HSV infection should be hospitalized and man- aged with contact precautions if mucocutaneous lesions are present. Neonates Exposed to HSV During Delivery. Infants born to women with active genital HSV le- sions should be managed with contact precautions during the incubation period. Some experts believe that contact precautions are unnecessary if exposed infants were born by cesarean delivery, provided membranes were ruptured for less than 4 hours. The risk of HSV infection in infants born to mothers with a history of recurrent genital herpes who have no genital lesions at delivery is low, so special precautions are not necessary. Specific management options for neonates born to women with active genital HSV lesions are de- tailed in “Prevention of Neonatal Infection.” Women in Labor and Postpartum Women With HSV Infection. Women with active HSV lesions should be managed with contact precautions during labor, delivery, and the postpartum period. They should be instructed about the importance of careful hand hygiene before and after caring for their infants. The mother may wear a clean covering gown to help avoid contact of the infant with lesions or infectious secretions. A mother with herpes labi- alis or stomatitis should wear a disposable surgical mask when touching her newborn in- fant until the lesions have crusted. She should not kiss or nuzzle her newborn until lesions have cleared. Herpetic lesions on other skin sites should be covered. Breastfeeding is acceptable if no lesions are present on the breasts and if active lesions elsewhere on the mother are covered (see Human Milk, p 113). Children With Mucocutaneous HSV Infection. Contact precautions are recommended for pa- tients with severe mucocutaneous HSV infection. Patients with localized recurrent lesions should be managed with standard precautions. Patients With HSV Infection of the CNS. Standard precautions are recommended for patients with infection limited to the CNS. EBSCOhost - printed on 8/17/2021 6:25 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  HERPES SIMPLEX 445 CONTROL MEASURES: Prevention of Neonatal Infection. During Pregnancy. The absence of previous signs and symptoms of genital herpes infec- tions has poor sensitivity in determining the risk of genital HSV infection in a pregnant woman. The American College of Obstetricians and Gynecologists recommends that women with active recurrent genital herpes be offered suppressive antiviral therapy at or beyond 36 weeks of gestation. However, cases of neonatal HSV disease have occurred among infants born to women who received such antiviral prophylaxis. Care of Newborn Infants Whose Mothers Have Active Genital Lesions at Delivery. The risk of trans- mitting HSV to the newborn infant during delivery is influenced directly by the mother’s classification of HSV infection (Table 3.29); women with primary genital HSV infections who are shedding HSV at delivery are 10 to 30 times more likely to transmit the virus to their newborn infants, compared with women with a recurrent infection. With the com- mercial availability of serologic tests that can reliably distinguish type-specific HSV anti- bodies, the means to further refine management of asymptomatic neonates delivered to women with active genital HSV lesions now is possible. The American Academy of Pedi- atrics developed algorithms (Fig 3.5 and 3.6) addressing evaluation and management of asymptomatic neonates following vaginal or cesarean delivery to women with active geni- tal HSV lesions. 1 The algorithms are intended to outline one approach to the manage- ment of these neonates and may not be feasible in settings with limited access to PCR as- says for HSV DNA or to the newer type-specific serologic tests. If, at any point during the evaluation outlined in the evaluation algorithm (Fig 3.5), an infant develops symptoms that could indicate neonatal HSV disease (eg, fever, hypothermia, lethargy, irritability, vesicular rash, seizures, etc), a full diagnostic evaluation should be undertaken and intra- venous acyclovir therapy should be initiated. In applying this algorithm, obstetric and pe- diatric providers will need to work closely with their diagnostic laboratories to ensure that serologic and virologic testing is available and turnaround times are acceptable. In situa- tions in which this is not possible, the approach detailed in the algorithm will have lim- ited, and perhaps no, applicability. Care of Newborn Infants Whose Mothers Have a History of Genital Herpes But No Active Genital Lesions at Delivery. An infant whose mother has known, recurrent genital infection but no genital lesions at delivery should be observed for signs of infection (eg, vesicular lesions of the skin, respiratory distress, seizures, or signs of sepsis) but should not have specimens for surface cultures for HSV obtained at 12 to 24 hours of life and should not receive empiric parenteral acyclovir. Education of parents and caregivers about the signs and symptoms of neonatal HSV infection during the first 6 weeks of life is prudent. Infected Health Care Professionals. Transmission of HSV in hospital nurseries from infected health care professionals to newborn infants rarely has been documented. The risk of transmission to infants by health care professionals who have herpes labialis or who are asymptomatic oral shedders of virus is low. Compromising patient care by excluding health care professionals with cold sores who are essential for the operation of the hospital nursery must be weighed against the potential risk of newborn infants becoming infected. 1Kimberlin DW, Baley J; American Academy of Pediatrics, Committee on Infectious Diseases. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics. 2013;131(2):e635–e646 EBSCOhost - printed on 8/17/2021 6:25 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  446 HERPES SIMPLEX Table 3.29. Maternal Infection Classification by Genital HSV Viral Type and Maternal Serologic Test Resultsa Classification of Maternal PCR/Culture From Maternal HSV-1 and HSV-2 Infection Genital Lesion IgG Antibody Status Documented first-episode pri- Positive, either virus Both negative mary infection Documented first-episode Positive for HSV-1 Positive for HSV-2 AND nonprimary infection negative for HSV-1 Positive for HSV-2 Positive for HSV-1 AND negative for HSV-2 Assumed first-episode (primary Positive for HSV-1 OR Not available or nonprimary) infection HSV-2 Negative OR not availa- Negative for HSV-1 and/or bleb HSV-2, OR not available Recurrent infection Positive for HSV-1 Positive for HSV-1 Positive for HSV-2 Positive for HSV-2 HSV indicates herpes simplex virus; PCR, polymerase chain reaction (assay); IgG, immunoglobulin G. a To be used for women without a clinical history of genital herpes. b When a genital lesion is strongly suspicious for HSV, clinical judgment should supersede the virologic test results for the con- servative purposes of this neonatal management algorithm. Conversely, if, in retrospect, the genital lesion was not likely to be caused by HSV and the PCR assay result/culture is negative, departure from the evaluation and management in this conserva- tive algorithm may be warranted. Health care professionals with cold sores who have contact with infants should cover and not touch their lesions and should comply with hand hygiene policies. Transmission of HSV infection from health care professionals with genital lesions is not likely as long as they comply with hand hygiene policies. Health care professionals with an active herpetic whitlow should not have responsibility for direct care of neonates or immunocompro- mised patients and should wear gloves and use hand hygiene during direct care of other patients. Infected Household, Family, and Other Close Contacts of Newborn Infants. Household members with herpetic skin or mouth lesions (eg, stomatitis, herpes labialis, or herpetic whitlow) should be counseled about the risk of transmission and should avoid contact of their le- sions with newborn infants by taking the same measures as recommended for infected health care professionals, as well as avoiding kissing and nuzzling the infant while they have active lip/mouth lesions or touching the infant while they have a herpetic whitlow. Cases of HSV transmission to the genitalia of male neonates have been reported follow- ing ritual circumcision (metzitzah b’peh) involving mouth suction of the site by the mohel performing the circumcision. Care of People With Extensive Dermatitis. Patients with dermatitis are at risk of developing ec- zema herpeticum. If these patients are hospitalized, special care should be taken to avoid their exposure to HSV. These patients should not be kissed by people with cold sores or touched by people with herpetic whitlow. EBSCOhost - printed on 8/17/2021 6:25 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  HERPES SIMPLEX 447 Fig 3.5. Algorithm for the evaluation of asymptomatic neonates following vaginal or cesarean delivery to women with active genital herpes lesions. Reproduced from Kimberlin DW, Baley J; American Academy of Pediatrics, Committee on Infectious Diseases. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics. 2013;131(2):e635-e646 EBSCOhost - printed on 8/17/2021 6:25 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use  448 HERPES SIMPLEX Fig 3.6. Algorithm for the treatment of asymptomatic neonates following vaginal or cesarean delivery to women with active genital herpes lesions. Reproduced from Kimberlin DW, Baley J; American Academy of Pediatrics, Committee on Infectious Diseases. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics. 2013;131(2):e635-e646 Care of Children With Mucocutaneous Infections Who Attend Child Care or School. Oral HSV in- fections are common among children who attend child care or school. Most of these in- fections are asymptomatic, with shedding of virus in saliva occurring in the absence of clinical disease. Only children with HSV gingivostomatitis (ie, primary infection) who do not have control of oral secretions should be excluded from child care. Exclusion of chil- dren with cold sores (ie, recurrent infection) from child care or school is not indicated. HSV lesions on other parts of the body should be covered with clothing or a bandage, if practical, for children attending school or day care. Additional control measures include avoiding the sharing of respiratory secretions through contact with objects and washing and sanitizing mouthed toys, bottle nipples, and utensils that have come in contact with saliva. EBSCOhost - printed on 8/17/2021 6:25 AM via UNIV OF SOUTH ALABAMA. All use subject to https://www.ebsco.com/terms-of-use