Intervention Review

Antiviral agents for treatment of herpes simplex virus infection in neonates

  1. Cheryl A Jones2,
  2. Karen S Walker1,*,
  3. Nadia Badawi1

Editorial Group: Cochrane Neonatal Group

Published Online: 8 JUL 2009

Assessed as up-to-date: 14 MAR 2009

DOI: 10.1002/14651858.CD004206.pub2


How to Cite

Jones CA, Walker KS, Badawi N. Antiviral agents for treatment of herpes simplex virus infection in neonates. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD004206. DOI: 10.1002/14651858.CD004206.pub2.

Author Information

  1. 1

    The Children's Hospital at Westmead, Grace Centre for Newborn Care, Sydney, NSW, Australia

  2. 2

    The University of Sydney, Discipline of Paediatrics and Child Health, Westmead, Sydney, NSW, Australia

*Karen S Walker, Grace Centre for Newborn Care, The Children's Hospital at Westmead, PO Box 4001, Sydney, NSW, 2115, Australia. karenw4@chw.edu.au.

Publication History

  1. Publication Status: New
  2. Published Online: 8 JUL 2009

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Herpes simplex virus (HSV) is a rare but serious neonatal pathogen. Prior to the availability of antiviral drugs the mortality associated with all but localised neonatal infection was high, with 85% of infants with disseminated HSV infection and 50% of infants with encephalitis dying by one year of age. The morbidity in the survivors of multiorgan infection was also high, with up to 50% experiencing long-term neurological sequelae.

Objectives

To determine the effect of antiviral agents in the treatment of neonatal HSV infections on mortality, progression of disease and neurodevelopmental sequelae at approximately one year. The secondary objective was to assess the effect of antiviral agents on major complications associated with the use of these agents including nephrotoxicity and bone marrow suppression.

Search methods

Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2008), MEDLINE (1996 - Nov 2008), EMBASE (1982 - Nov 2008) and reference lists of published trials.

Selection criteria

Randomised and quasi-randomised controlled trials of antiviral therapy in infants less than one month of age with virologically proven HSV infection were included.

Data collection and analysis

Data were extracted and the analyses performed independently by two review authors. Studies were analysed for methodological quality using the criteria of the Cochrane Neonatal Review Group. All data were analysed using RevMan 5.1. When possible, meta-analysis was performed to calculate typical relative risk, typical risk difference, along with their 95% confidence intervals (CI).

Main results

Two eligible studies of a total of 273 infants were included. Both studies were randomized controlled trials. One study treated 63 infants with vidarabine or placebo (Whitley 1980) and the other study treated 210 infants with aciclovir or vidarabine (Whitley 1991).

In the study comparing vidarabine with placebo (Whitley 1980), infants with all forms of neonatal HSV disease were included [disseminated disease, central nervous system (CNS) disease alone, and skin, eye and mouth (SEM) disease].There was no significant reduction in the risk of mortality when analyzed as an entire group; however, mortality was significantly reduced when data from infants with CNS disease or disseminated disease were combined. There was no difference in the rate of neurological abnormalities in survivors at one year when analyzed as an entire group or by disease category.

There was no difference between aciclovir and vidarabine (Whitley 1991) in preventing mortality from neonatal HSV disease, in preventing disease progression, in reducing the incidence of neurological abnormality at one year, or in the incidence of drug-induced renal or bone marrow toxicity. In infants with SEM disease, there was no significant difference in neurological outcome with aciclovir compared vidarabine treatment. Both drugs were well tolerated in the newborn period.

Authors' conclusions

There is insufficient trial evidence to evaluate the effects of antiviral agents with controls or with each other. The rarity of the condition makes effectively powered clinical trials difficult to perform. The efficacy of newer antiviral agents with better bioavailability (e.g. valaciclovir, valganciclovir) for the treatment of neonatal disease needs to be evaluated in randomised trials. The efficacy of oral formulations need to be evaluated as they may be useful for infants with skin, eye or mouth HSV disease or in the treatment of infants with recurrences after the neonatal period.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Antiviral agents for treatment of herpes simplex virus infection in neonates

The virus herpes simplex (herpes) causes a rare but devastating disease in the newborn that can range from skin and eye infection to shock, organ failure, brain infection, and death. Newborn herpes infection is an uncommon complication of active genital herpes in the mother around the time of delivery or after direct contact with a herpes blister ("fever blister", "cold sore") of an infected caregiver. We reviewed five studies conducted to assess the effects of antiviral agents (medications that reduce the spread of virus in the body) on mortality and long-term complications of herpes disease in the newborn. Antiviral agents were shown to reduce mortality from the condition, but the reduction was not statistically significant due to the small number of infants in the study. There was insufficient trial data to guide caregivers regarding the duration of antiviral therapy or dose.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

使用的抗病毒藥物來治療新生兒的單純皰疹病毒感染

對新生兒而言,單純皰疹病毒(herpes simplex virus;HSV)是1種罕見但是卻嚴重的病原體。在能夠取得抗病毒的藥物之前,新生兒感染HSV之死亡率是很高的,有85% 的擴散型HSV感染及50% 的HSV腦炎之嬰兒在1歲之前就死亡。對於多重器官感染的這些倖存者來說,罹病率也是很高的,有高達50% 的比例會有長期的神經系統後遺症。

目標

針對死亡率、疾病的進展,以及在大約1歲的時候所發生之神經發展方面的後遺症,評估用的抗病毒藥物來治療新生兒的單純皰疹病毒感染之效果。第二個目標是要評估抗病毒藥物所帶來的嚴重併發症,包括了腎毒性以及骨髓抑制的情況。

搜尋策略

透過搜尋Cochrane Central Register of Controlled Trials (CENTRAL, Cochrane Library, Issue 4, 2008) 、MEDLINE (1996 – 2008年11月) 、EMBASE (1982年2008年11月) 以及已發表試驗之參考資料清單來找出相關試驗。

選擇標準

對於已經受到了病毒學上所證實的單純皰疹病毒感染之年紀不到1個月大的嬰兒們,使用抗病毒藥物之療法的隨機與半隨機對照試驗都會被收集在內。

資料收集與分析

有2位文獻回顧的作者獨立地擷取出資料,並且完成了這些分析。針對方法方面的品質,這些研究都使用了the Cochrane Neonatal Review Group的標準來分析。所有的資料都是使用RevMan 5.1來加以分析。如果有可能的話,就會進行統合分析來計算出典型的相對風險、典型的風險差異,及它們的95% 信賴區間(CI)。

主要結論

當中共收集了包含總數為273名嬰兒的2份合格研究。這2份研究都屬於隨機對照試驗。其中1份研究以vidarabine或是安慰劑來治療63名嬰兒(Whitley 1980),至於另外1份研究則是以aciclovir或是vidarabine來治療210名嬰兒(Whitley 1991)。在這份將vidarabine與安慰劑進行了比較的研究當中(Whitley 1980),新生兒單純皰疹病毒疾病的所有種類都被收集在內【擴散型的疾病、單獨的中樞神經系統(CNS)疾病,以及皮膚、眼睛與嘴巴部位(SEM)的疾病】。當將他們視為1整個群體來進行分析的時候,對於死亡情況的風險而言,並沒有明顯的減少;然而,對於患有中樞神經系統疾病或是擴散型之疾病的嬰兒們而言,當我們將取自於他們的資料合併起來的時候,死亡率就有意義地下降了。對於年紀在1歲時的倖存者而言,將他們視為1整個群體或是根據疾病的分類分開來進行分析的時候,就神經異常的比率來看,當中並沒有差異存在。針對預防新生兒之單純皰疹病毒疾病所帶來的死亡情況、預防疾病惡化、在年紀到達1歲時要減少神經異常的情況發生、或是由藥物所引發的腎臟或是骨髓毒性的情況發生,在aciclovir與vidarabine這兩個藥物之間,並沒有差異存在。在患有皮膚、眼睛與嘴巴部位之疾病的嬰兒們,跟vidarabine的治療比較起來,使用aciclovir所造成的神經結果方面來看,並沒有明顯的差異。在這樣的新生兒時期當中,嬰兒們對於這2種藥物的耐受程度都很高。

作者結論

跟對照組比較起來,或是在藥物之間相互比較起來,並沒有充足的試驗證據可以用來評估抗病毒藥物的效果。對於能夠有效地取得份量的臨床試驗而言,因為難以取得這樣的條件,使得這些試驗在進行時就變得很困難。對於新生兒疾病的治療而言,一些更新型且具有更佳的生物可利用性之抗病毒藥物(例如 valaciclovir、valganciclovir)的功效,還需要隨機化試驗加以評估。對於患有皮膚、眼睛或是嘴巴部位的單純皰疹病毒疾病之嬰兒們,或是對於在新生兒期感染康復之後又產生復發的嬰兒們而言,口服劑型的這些藥物或許會有用處,但還需要評估。

翻譯人

此翻譯計畫由臺灣國家衛生研究院 (National Health Research Institutes, Taiwan) 統籌。

總結

對於新生兒來說,單純皰疹(皰疹)這種病毒會造成罕見但是卻有很大傷害的疾病,這樣的疾病範圍可以從皮膚與眼睛的感染到休克、器官衰竭、腦部感染,以及死亡。母親在接近生產的時候身上帶著活躍性的生殖器官皰疹,或是與某個受到感染之照顧者身上的皰疹水泡(「發燒水泡」、「唇皰疹」)進行過直接接觸之後,就會造成這種不常見的新生兒皰疹感染之併發症。我們檢視過5份研究,而這些研究都是為了評估抗病毒藥物(可以減少病毒在體內散布的藥物)在新生兒的死亡率與長期併發症的影響。抗病毒的藥物顯然可以在這樣的情況下讓死亡率下降,但是因為在這份研究當中的嬰兒數目不夠多,所以這樣的降幅在統計學上並不會很明顯。若是要考量到抗病毒療法的時間長度或是劑量,並沒有足夠的試驗資料可以提供照顧新生兒者有關於抗病毒療法的使用時間長短或是藥物劑量。