PEDIATRICS Vol. 118 No. 6 December 2006, pp. e1612-e1620 (doi:10.1542/peds.2005-1228)
ARTICLE |
Herpes Simplex Virus Infections in Preterm Infants
Eudowood Neonatal Pulmonary Division, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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OBJECTIVE. Neonatal herpes simplex virus infections cause significant neonatal mortality and morbidity, but the course and prognosis in preterm infants is not well documented. We performed a retrospective review of herpes simplex virus infections at out institution within the first 30 days after birth in infants who were born at <37 weeks to help better define the symptoms and signs of herpes simplex virus infections in preterm infants and to assist in prognosis.
METHODS. Hospital databases were reviewed to identify culture- or polymerase chain reaction–proven cases of herpes simplex virus-1 or herpes simplex virus-2 infections that occurred in preterm newborns between 1989 and 2003. Maternal and neonatal histories, clinical features, and laboratory results were reviewed systematically.
RESULTS. Ten preterm singletons and a set of twins were infected with herpes simplex virus-2 during the first month after birth. No mother had herpes simplex virus lesions at delivery, but a history of genital herpes simplex or other sexually transmitted infections was prevalent among the mothers. Infants presented with either disseminated disease or encephalitis. All infants with disseminated disease (n = 9) died, whereas the 3 infants with encephalitis survived. All infants in the cohort developed respiratory distress, and consistent with the prominence of respiratory symptoms, viral cultures of the respiratory tract were consistently positive. Ten of 12 infants received acyclovir, but despite treatment within 48 hours of symptoms, infants with disseminated disease deteriorated rapidly and died. Two of 3 infants who received high-dosage (60 mg/kg per day) acyclovir survived.
CONCLUSIONS. Herpes simplex virus infections in preterm infants usually present during the first 2 weeks of life with respiratory distress and a high incidence of disseminated disease. Viral respiratory cultures have a high yield for documentation of infection. The morbidity of herpes simplex virus in this population may be attributable to a relatively immature immune system in this population. Additional studies are necessary to delineate the evolution of herpes simplex virus disease in preterm infants and the role of antiviral therapy in mitigating the sequelae of herpes simplex virus infections in this population.
Key Words: herpes simplex virus • newborn • prematurity • acyclovir
Abbreviations: HSV—herpes simplex virus • CSF—cerebrospinal fluid • PCR—polymerase chain reaction • JHH—Johns Hopkins Hospital • STI—sexually transmitted infection • CBC—complete blood count • ETT—endotracheal tube • AST—aspartate aminotransferase • ALT—alanine aminotransferase • CASG—Collaborative Antiviral Study Group • CNS—central nervous system
In the United States, 
1500 neonates develop herpes simplex virus (HSV) infections annually.1 Neonatal infections that are caused by peripartum transmission of HSV are classified into 3 groups: disseminated HSV, which manifests as severe multiorgan dysfunction and has a high mortality risk2; HSV encephalitis, which causes neurologic morbidity among the majority of survivors3; and HSV disease localized to the skin, eye, and/or mouth, which results in significant morbidity and may progress to encephalitis or disseminated disease if left untreated.2 The majority (85%–90%) of neonatal HSV infections are attributable to intrapartum transmission of virus from mother to neonate; increased risk factors include primary maternal infection near the time of labor, prolonged rupture of membranes, use of scalp electrodes, and invasive obstetric procedures.2,4 Early detection of at-risk pregnant women and prompt treatment of infected infants are crucial to reducing the incidence of neonatal HSV. However, 70% of all HSV-infected infants are born to mothers with no clinical history of infection,5 thereby making diagnosis of neonatal HSV infection difficult.
The diagnosis of bacterial, fungal, or viral infections in the preterm infant is extremely challenging, given that clinical signs and symptoms of illness (eg, apnea, hypoxia, hypotension) may occur secondary to noninfectious causes (eg, patent ductus arteriosus, respiratory distress syndrome). In particular, extremely preterm infants typically have protracted hospitalizations with multiple evaluations for suspected sepsis. Occasionally, a critically ill infant's condition deteriorates, and the diagnosis of viremia (particularly as a result of HSV or enteroviruses) may be entertained hours to days after the onset of symptoms (when bacterial blood and cerebrospinal fluid [CSF] cultures have shown no growth). Preterm infants with HSV have a relative risk for death 3.7 times greater than term infants with HSV6; however, few published descriptions of the initial features of HSV infections in preterm infants are available. Potentially, earlier identification of preterm infants with HSV infections and more rapid treatment with acyclovir could improve their survival by limiting viral dissemination.
We identified a cohort of preterm infants at our institution in the past 15 years with culture-proven HSV infections in the neonatal period. To define better the natural history of herpes simplex viral infections in this group of neonates, we reviewed these cases to identify maternal and infant characteristics that could promote more rapid identification and treatment of preterm infants with potential HSV infections.
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METHODS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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Case Identification
We performed a retrospective review of all culture- and/or polymerase chain reaction [PCR]-proven cases of neonatal HSV infections in preterm infants (<37 weeks) who were hospitalized at Johns Hopkins Hospital (JHH) from 1989 to 2003. The research protocol was approved by the Johns Hopkins University School of Medicine Institutional Review Board. For a case to be considered as a neonatal HSV infection, initial symptoms of the illness had to occur within the first 30 days of life, although the disease could recur or evolve beyond the first month of life. We reviewed the database that is maintained by the Eudowood Neonatal Pulmonary Division (Johns Hopkins University School of Medicine) to identify infants who were admitted to the NICU and were treated for neonatal HSV. In addition, we reviewed virology results (HSV DNA PCR assays from CSF and viral culture results) from a database that is maintained by the Department of Pathology at the Johns Hopkins University School of Medicine. Term infants (defined as infants with a gestational age
37 weeks) and those who were treated for suspected neonatal herpes (without a positive culture or CSF PCR) were excluded from our analysis.
Review of Records
After identification of patients who met inclusion criteria, medical charts were reviewed to identify specific maternal and infant data. Using the infants' charts, multiple maternal medical and social characteristics were examined, including age, parity, medical and surgical histories, history of sexually transmitted diseases, and pregnancy complications. The infants' records also were reviewed to gather neonatal admission information, initial NICU course, age of onset of illness, clinical features at onset of illness, treatment, course of illness, laboratory evaluations, and outcome.
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RESULTS |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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Patient Demographics
Review of the 15-year period at JHH revealed 12 preterm infants from 11 pregnancies who met criteria for inclusion in this retrospective review (Table 1). One case of a documented intrauterine HSV-1 infection was excluded (because the purpose of the study was to identify clinical and laboratory findings in preterm infants without signs of an in utero viral infection). All neonatal infections were with HSV-2, documented by culture. Two of the infants had a positive PCR for HSV DNA (from the CSF) as well as a positive culture. Of the 12 patients, 9 (75%) were male (Table 2). Nine were black (75%) and 3 (25%) were white. Eight (66.7%) of 12 were inborn and directly admitted to the JHH NICU, whereas 3 of the outborn infants were transferred to the NICU from community nurseries shortly after birth. A fourth infant (infant 12) was transferred to the JHH PICU from an outside hospital on day of life 7. Two of the outborn infants (infants 2 and 3) were dizygotic twins who were born at 25 weeks, 4 days. The mean gestational age of our cohort was 27.48 weeks (range: 24.43–35.0 weeks), which was significantly more immature (P < .05) than the population of non–HSV-infected preterm infants who were admitted to the JHH NICU during approximately the same time period (Table 2).
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Maternal Prenatal Characteristics
Prenatal maternal data were available for 10 of the 11 mothers. Mean maternal age was 19.8 years (range: 17–23). Seven mothers had at least 1 documented nonherpetic sexually transmitted infection (STI). Two women were positive for Chlamydia trachomatis at delivery, 2 had a history of Chlamydia, 2 had a history of Neisseria gonorrhoeae, and 1 had a history of Trichomonas vaginalis. One woman (the mother of the twins) had an STI of unknown cause noted in the neonatal record. Three of the mothers had a history of genital herpes. All of the mothers were HIV enzyme-linked immunosorbent assay and rapid plasma reagin negative. Use of alcohol, tobacco, and illicit substances was common among mothers (alcohol [n = 4], tobacco [n = 5], marijuana [n = 2], cocaine [n = 1], and heroin [n = 2]). Prenatal care was documented in 8 pregnancies and was highly variable in extent.
Prenatal Complications and Labor
Prenatal and labor information was known for 10 of the 11 pregnancies. One outborn infant's perinatal records were unavailable, but some prenatal information was obtained from the infant's transfer note. Of the remaining 10 pregnancies, all were complicated by preterm labor. Five of the 11 mothers received prenatal steroids. None of the infants was delivered as a result of a maternal indication (eg, preeclampsia). Two of the 11 mothers had a documented intrapartum fever. Eight of 10 mothers received antibiotics during labor, but none of the women had herpetic lesions (identified either before or after delivery) or received intrapartum acyclovir. Rupture of membranes ranged from 0 to 160 hours (median: 9 hours), with 6 of 10 women with documented preterm premature rupture of membranes. Three of the women underwent fetal scalp electrode placement during labor.
Neonatal Admission Data
Eleven of 12 infants in our cohort were admitted either directly from the delivery room or by transfer from another institution shortly after delivery. Infant 12 was discharged from the hospital from a community nursery on day of life 3, admitted to another hospital on day of life 6 for lethargy and poor feeding, and subsequently transferred to the JHH PICU for evaluation of hyperammonemia and liver failure. Apgar scores (available in 11 of 12 cases) ranged from 1 to 7 at 1 minute (median: 4) and from 4 to 8 at 5 minutes (median: 7). Mean birth weight was 1176 g (range: 745–2420 g), significantly less (P = .011) than the weight of preterm infants in the study period without HSV (Table 2). Ten of 12 infants were intubated either in the delivery room or shortly after admission to intensive care.
Signs and Symptoms of Herpetic Infections
Infants displayed a range of clinical features at onset of illness (Table 3) but evidenced a clear, consistent deterioration in clinical status. Overall, the mean age at onset of illness was 8.3 days (SD: 3.5 days; range: 2–13 days). The most common presenting symptoms were respiratory distress (12 of 12), hypotension or poor perfusion (8 of 11 documented), and lethargy (7 of 11 documented). We defined respiratory distress as increased work of breathing, hypopnea, apnea/bradycardia, desaturations, and/or enhanced respiratory support (increased conventional mechanical ventilator settings or a change to high-frequency ventilation). Of the 4 infants who were not noted to be lethargic, 1 was already sedated on the ventilator, making determination of a change in neurologic status difficult. An initial cutaneous rash appeared in only 4 of 12 infants; 3 presented with multiple vesicular or pustular lesions at the onset of illness. In 1 infant, cutaneous disease appeared 5 days after initial symptom onset. Fever (maximal temperature: >38.0°C) appeared in 2 of the infants and hypothermia (minimal temperature: <36.5°C) appeared in 2 infants at onset of symptoms.
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Initial laboratory studies included complete blood counts (CBC), serum electrolytes, hepatic enzymes, chest and abdominal radiographs, viral cultures (from CSF, skin, mucosal surfaces [pharynx, rectum, conjunctivae], and endotracheal tube [ETT] secretions) and HSV PCR analysis of the CSF. CBCs at the onset of illness were documented for 11 of 12 infants. Mean initial white blood cell count was 16 633 with a range of 1700 to 42 000. A left shift was seen in 7 of the 8 infants with a differential on the initial CBC. Mean percentage of premature neutrophils (bands, promyelocytes, and myelocytes) was 30.1% (range: 4%–52%). Two of the 11 infants were leukopenic (white blood cell count <5000) at onset of symptoms. Thrombocytopenia (platelet count <150 000) was present often at onset of illness (8 of 11 infants). Mean and median initial platelet counts were 123 and 90, respectively (range: 26–279). Anemia (hematocrit <30%) was present in 1 of 11 infants (mean hematocrit: 36; range: 25–47). Initial aspartate aminotransferase (AST) varied greatly (range: 26–1508 U/L), although the first AST measurement was <100 U/L in all but 2 infants. Subsequent AST values, however, demonstrated a rise in 9 of the 11 infants, with levels >400 U/L in 6 of these infants. Mean and median peak AST levels were 1243 and 485 U/L, respectively. Alanine aminotransferase (ALT) displayed much less elevation and variation, with only 3 infants having an ALT level >100 U/L at any time. Two of these 3 infants displayed a rise in ALT to >800 and 1000, respectively, that paralleled the rise in their AST values. Initial ALT ranged from 4 to 212 U/L with a median of 7 U/L. Mean and median peak ALT levels were 208 U/L and 47 U/L, respectively. Four infants had a minimal rise in total bilirubin (<2.2 mg/dL over baseline), whereas 1 infant demonstrated a rise by 5.4 mg/dL to a maximum of 7.3 mg/dL. Two of 5 tested infants developed direct bilirubin >1.0 mg/dL, with a maximum of 1.7 mg/dL. Of the 11 infants with initial chest radiographs, 10 displayed increased radiographic changes from baseline changes (new infiltrates, atelectasis, or consolidation) as reported by the attending radiologist. Pleural effusions were noted in 3 of these 11 infants.
All infants had at least 1 positive culture for HSV-2 from at least 1 site (Table 4). HSV-1 was not recovered by PCR or culture from any infant. Viral cultures were taken from 1 to 6 sites per patient (median: 3 sites). Of the cultures performed, respiratory tract aspirates or swabs demonstrated the highest yield. All 5 endotracheal cultures (from 5 different infants) were positive (100%). Four of 6 infants tested had a positive HSV culture from the oro- or nasopharynx. Two infants had both positive pharyngeal and ETT cultures. Of the 4 infants with CSF sent for viral culture, 3 (75%) were positive. HSV PCR from the CSF was sent in 2 infants, and both were positive, including the infant with the negative CSF viral culture. Although 4 infants showed vesicles or pustules at the onset of disease, only 3 had cutaneous viral cultures sent, and 2 were positive. Viral recovery from other mucous membranes was low; 1 of 3 conjunctival cultures tested (from different patients) and 1 of 7 rectal cultures tested (from different patients) were positive.
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Acyclovir Therapy
Overall, 10 of 12 infants received acyclovir. Eight of the treated infants received the first dose of acyclovir before growth of HSV in culture. One began acyclovir after culture growth; in 1 case, the status on culture results in relation to acyclovir initiation was unclear. Dosages of acyclovir varied: 2 infants received 20 mg/kg per day, 3 received 30 mg/kg per day, 1 received 40 mg/kg per day, 1 received 45 mg/kg per day, and 3 received 60 mg/kg per day (2 of these survived). The 2 untreated infants died soon after onset of symptoms. Of the 3 infants who survived and completed the course of acyclovir, treatment ranged from 21 to 28 days.
Outcome
Only 3 of the 12 infants survived, with all of the fatal cases in infants with disseminated disease. Of the 3 infants who were born to mothers with a history of HSV, 1 survived. Mean time until death after starting acyclovir was 8.2 days. However, excluding 1 infant who survived for 44 days, the mean time to death after initiation of acyclovir was 3.1 days (range: 1–6 days). Autopsy results were available for only 3 of the 9 deceased infants (Table 5), but all postmortem examinations reflected multiorgan involvement. The infant with extended survival before death (infant 8) initially presented with disseminated disease (hepatitis, respiratory distress, hypoxemia, and hypotension) and survived after a 21-day course of acyclovir at 45 mg/kg per day. The infant was started on an extended course of parenteral steroids (for respiratory failure) while on this dose of acyclovir and was transitioned to a low dosage of prophylactic intravenous acyclovir at 40 days of age. During his second month of life, he developed seizures and encephalomalacia and ultimately succumbed secondary to severe chronic lung disease. Multiple viral cultures (ETT, CSF, and surface) and bacterial cultures that were sent during that time were negative.
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Two of the 3 survivors (infants 3 and 10) had a documented clearance of the CSF (negative HSV PCR or viral culture) after completing a course of intravenous acyclovir therapy. Infant 3 completed 6 months of prophylactic oral acyclovir but developed unilateral glaucoma that required trabeculectomy. Another survivor (infant 10) completed 7 weeks of acyclovir prophylaxis. Within 1 week of ending suppressive therapy, however, she developed recurrent HSV encephalitis (skin vesicle and CSF culture positive for HSV-2) in association with a bacterial gastroenteritis. During the recurrence, the child had a normal head computed tomography scan, electroencephalogram, and ophthalmologic examination but demonstrated significant neurodevelopmental abnormalities (Table 5). At that time, her immunoglobulin levels and T cell subsets were normal; however, HIV serology was not performed. The other survivor (infant 1) had 2 normal neurodevelopmental examinations within the first year of life.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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This study was undertaken to focus specifically on the presentation and evolution of HSV in preterm infants. Other studies of neonatal HSV infections have included preterm infants, but the course of the disease in this unique population was not specifically addressed. An early characterization of HSV infections in mothers and neonates in the United States, which evolved from a prospective, randomized, controlled trial of vidarabine in neonatal HSV,7 included 27 preterm infants, with 21 between 32 and 37 weeks and only 2 infants weighing <1200 g at birth. A Finnish study of 43 neonates with HSV during a 16-year period reported 7 preterm infants (gestational age range: 31–36 weeks), and all had birth weights >1500 g.8 The recent Collaborative Antiviral Study Group (CASG) reports on the natural history of HSV,3 and the trial of high-dosage acyclovir9 also included a relatively large proportion of preterm infants (63 [35%] of 186) with a minimum gestational age of 27 weeks and minimum birth weight of 790 g. Our cohort is unique in that 10 (83%) of 12 infants were born at
27 weeks' gestation, with an equal proportion <1500 g (and 3 [25%] of 12 <800 g) at birth. It is interesting that the mean gestational age and birth weight also were significantly lower in our cohort than in non–HSV-infected preterm infants in our hospital during the same time period. Furthermore, in contrast to the CASG report, which found a sizable percentage of skin, eye, and/or mouth disease among preterm infants (41% in the 1981–1988 cohort and 20% in the 1989–1997 cohort),3 all of our infants had more severe HSV infections. These findings suggest that preterm infants who are infected with HSV (particularly those of lower gestational age) are more likely to develop HSV encephalitis or disseminated HSV disease. Overall, the mean age of onset of symptoms for all infants was 8.3 days. Among the 9 patients with disseminated disease, the mean onset of illness was 8.7 days, consistent with data suggesting that disseminated disease presents within the first 1 to 2 weeks of life.2,3,10 HSV encephalitis typically presents at 2 to 3 weeks of age,2,3 but we found an earlier mean time of onset (7.3 days) in our infants with central nervous system (CNS) involvement alone. However, an association between prematurity and an earlier onset of encephalitis cannot be substantiated given the small number of patients with CNS disease (n = 3) in our cohort. Finally, all of our infants with mucocutaneous lesions had manifestations of CNS or disseminated disease, possibly reflecting the aggressive nature of the infection in this population.
The high mortality in this cohort may relate to the immaturity of the innate immune system and the absence of transplacentally acquired immunity. Newborns exhibit delayed T-cell proliferation,11 decreased levels of interferons in response to HSV,12,13 and an immature antibody-dependent cellular cytotoxicity response of monocytes and macrophages.2,14,15 This overall impairment of cellular immunity and cytokine production seems to be similar in the preterm infant in comparison with the term infant.16 However, serum immunoglobulin G levels are lower in premature infants relative to term infants,17 because the natural transfer of antibodies does not begin until 20 to 22 weeks' gestation.18 Furthermore, antibody-dependent cellular cytotoxicity–mediating and neutralizing antibodies are reduced in infants with disseminated disease,2,11,19 the most prominent form of HSV infection in our cohort. Therefore, the deficit of an adequate immune response in our infants who were <27 weeks would have contributed to their poor outcome.
Two clinical findings were evident consistently in our patients. First, we found that all 12 of our infants developed clinical and/or radiographic changes in pulmonary function, including increased frequency of apnea and increased ventilatory support. Respiratory symptoms and/or pneumonitis previously has been strongly associated with death among infants with disseminated disease6 and with a poorer prognosis in all neonates with HSV disease.8 In addition, respiratory distress has been reported as a primary complication of HSV in preterm infants.7 Consistent with these data, viral cultures were positive most consistently from endotracheal or nasopharyngeal aspirates in our cohort (9 of 11 samples from 9 infants). Transaminase elevation was the next most common finding, with AST elevation and/or rising levels detected more consistently than changes in ALT. Nine of 11 tested infants had at least 1 AST value >100, 6 of 11 had 1 AST >400, and overall 9 of 11 displayed progressive elevation of AST on repeated testing. These findings suggest that viral respiratory cultures and serial aminotransferase analysis may aid in the diagnosis of HSV in a deteriorating preterm infant.
Although only 4 infants had CSF viral cultures sent, the high percentage of positive cultures (75%) in our cohort is interesting and contrasts with data obtained from older children and adults in whom CSF viral cultures have low yield.20 Recent reviews of HSV CNS infections have suggested a potential value of viral CSF cultures in neonates for detecting HSV (as opposed to adults, children, and infants older than 6 months).10,20 In addition, the recent CASG report found that 17 of 42 infants with CNS HSV involvement (encephalitis or disseminated disease) had a positive viral culture from CSF or brain tissue.3 Conceivably, neonates (particularly preterm neonates) may have decreased ability to isolate viral infection as a result of inherent deficiencies of their immune systems, thereby allowing spread of the virus into the CSF. HSV PCR has been recognized as an important technique in the diagnosis of neonatal HSV infections,21,22 and this test has been available at our institution since 1994. However, recent reviews2,23 suggested that a lack of standardization of the test and variability in specimen collection and maintenance may affect PCR results. Therefore, viral CSF culture may have a role as an adjunct to PCR in the diagnosis of neonatal HSV encephalitis, especially in preterm infants.
A maternal history of primary HSV infection during the third trimester places an infant at high risk for herpes.2 However, initial maternal herpes infections often are completely asymptomatic, and many women whose neonates have herpes have no known history of herpes.1,2,5 In our study, only 3 of 11 mothers had a history of herpes outbreaks, and none of the 11 mothers of these infants had known herpetic lesions at delivery. However, a potentially revealing finding in our cohort is that the majority of mothers had a history of a nonherpetic STI, a finding recently found to be predictive of past HSV-2 infection.24 Therefore, preterm infants who are born to women with an active STI or a history of STIs may be at higher risk for HSV disease as a result of these risk factors.
Two infants did not receive acyclovir in our study, and both died. Of the remaining 10 infants, 8 received acyclovir within 48 hours of symptoms, and 2 of these (both with encephalitis) survived. Both of these infants received high-dosage acyclovir (60 mg/kg per day divided every 8 hours), which demonstrated superior 2-year survival outcomes in infants with disseminated HSV disease.9 It can be speculated that survival in our small cohort may have been higher had all of the infants received high-dosage acyclovir. However, additional work may be necessary to determine an appropriate dosage for low birth weight preterm infants.
Because of the difficulty of identifying HSV infections early enough in preterm infants to prevent disseminated disease, the inclusion of acyclovir in the regimen of antibiotics that is given to acutely ill preterm neonates may be considered. Recent recommendations suggested using acyclovir only in clinically deteriorating infants who are younger than 1 month and have negative bacterial cultures 48 to 72 hours after the onset of illness.3 However, given the degree to which HSV causes rapid clinical deterioration, a high index of suspicion for possible herpetic infection must be maintained in preterm infants, and the clinician can consider beginning acyclovir if clinical, laboratory, and radiographic findings are suggestive. It remains to be seen whether early initiation of acyclovir can improve mortality in such a vulnerable population.
Consideration of prophylactic acyclovir after treatment of HSV disease also may be entertained in preterm neonates given their innate immune abnormalities and the documented risk for poor neurodevelopmental outcomes in infants with recurrent disease during the first 6 months of life.6 One patient in our cohort (infant 10) developed recurrent HSV encephalitis shortly after discontinuing suppressive acyclovir. However, 2 others (infants 3 and 8) sustained significant morbidity (glaucoma and seizures) while on prophylaxis, although the 5-mg/kg per day regimen that was used for infant 8 is significantly lower than dosing protocols that were reported previously.25,26 Furthermore, recurrent HSV disease was reported previously in a preterm infant who was receiving acyclovir prophylaxis.27 Therefore, benefits and risks of using suppressive therapy are unclear at this time, and routine use of oral acyclovir suppressive therapy (outside of a controlled clinical trial) cannot be recommended.
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CONCLUSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONCONCLUSIONREFERENCES |
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We have described the neonatal and maternal characteristics of a cohort of preterm neonates with HSV infections. For improvement of the outcome of preterm infants who are exposed to HSV in the peripartum period, early recognition of HSV infection in this population of patients is imperative. In addition, determination of the immune response of the preterm infant during and after acyclovir therapy may help to guide the use of treatment therapy and the implementation of suppressive therapy. Finally, long-term neurodevelopmental outcome data are needed to delineate further the natural history of HSV infections in this unique neonatal population.
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ACKNOWLEDGMENTS |
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We are indebted to John K. Boitnott, MD (Department of Pathology, Johns Hopkins University School of Medicine), for performing a laboratory database search to identify infants who were eligible for the study. We also thank Pamela K. Donohue, PA, ScD, Jennifer Shepard, RN, and Elizabeth A. Cristofalo, MD (Eudowood Neonatal Pulmonary Division, Johns Hopkins University School of Medicine), for reviewing the division database for potential cases and for assistance with data analysis. Finally, we thank Alexandra Valsamakis, MD, PhD (Department of Pathology, Johns Hopkins University School of Medicine), for information on use of HSV PCR at the institution.
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FOOTNOTES |
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Accepted Jun 27, 2006.
Address correspondence to W. Christopher Golden, MD, Eudowood Neonatal Pulmonary Division, Johns Hopkins University School of Medicine, 600 N Wolfe St, Nelson Harvey 2-133, Baltimore, MD 21287. E-mail: cgolden{at}jhmi.edu
The authors have indicated they have no financial relationships relevant to this article to disclose.
Dr O'Riordan's current address is St Luke's Regional Medical Center, Neonatal Intensive Care Unit, 190 East Bannock St, Boise, ID 83712.
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PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics
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  P. Lundberg, C. Ramakrishna, J. Brown, J. M. Tyszka, M. Hamamura, D. R. Hinton, S. Kovats, O. Nalcioglu, K. Weinberg, H. Openshaw, et al. The Immune Response to Herpes Simplex Virus Type 1 Infection in Susceptible Mice Is a Major Cause of Central Nervous System Pathology Resulting in Fatal Encephalitis J. Virol., July 15, 2008; 82(14): 7078 - 7088. [Abstract] [Full Text] [PDF]
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