What are the key principles of preventing viruses – herpes simplex/varicella zoster?

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are usually spread via droplets or contact, which are preventable with good hygienic practices and droplet precautions. VZV, however, can also be transmitted via aerosols from patients with disseminated skin lesions of varicella or herpes zoster (HZ). Prevention of VZV infection is difficult because the incubation period of varicella ranges from 10 to 21 days but the host is infectious 1 or 2 days before and remains so for about 5 days after all the lesions have crusted; patients with HZ have a reactivation of the VZV and are infectious during the vesicular stages of rash.

For patients with localized HZ, standard precautions should be followed and lesions should be covered; for those with disseminated HZ or varicella, standard precautions plus contact and airborne precautions should be followed until lesions are crusted.

A safe varicella vaccine has been available since the 1980s and, in the USA, since 1995; this vaccine is recommended for all non-immune health care workers (HCWs).

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A positive history of varicella is generally considered as proof of immunity; serologic screening before vaccination of HCWs with a negative or uncertain history of varicella is likely to be cost effective. The extension of varicella outbreaks in the health care settings depends on how opportune the control measures are taken.

Clinical trials among adolescents and adults have indicated that acyclovir is well tolerated and effective in reducing the duration and severity of clinical varicella if it is administered within 24 hours of rash onset. Varicella vaccination is essential for outbreak control as demonstrated by studies in children.

Exposed HCWs without evidence of VZV immunity should receive postexposure vaccination as soon as possible. Vaccination within 5 days of exposure may modify the disease if infection occurred. Vaccination 6 or more days after exposure is still indicated because it protects against subsequent exposures. In immunocompromised or pregnant hosts not previously exposed to VZV, varicella-zoster immune globulin within 72 hours of exposure is useful for both prevention of disease and symptomatic relief. Neonates should receive VZIG if maternal varicella rash develops within 7 days either side of delivery. As VZIG is often unavailable, antivirals can be given for prophylaxis to people at high risk who cannot be vaccinated.

HSV transmission can result from people with active lesions or even from mucosal surfaces of asymptomatic people. Herpetic whitlows are an occupational risk mainly for dentists and personnel from intensive care units.

Neonatal HSV infection is usually acquired perinatally from contact with mucosal surfaces from women who have recently acquired the HSV infection, but women with recurrent genital herpes simplex should be informed that the risk of neonatal herpes after vaginal delivery is low when there are no active lesions. Due to reactivation, the risk of HSV disease after allogeneic stem cell transplantation is about 80% without prophylaxis during bone marrow aplasia or in the presence of stomatitis.

What are the key conclusions for available clinical trials and meta-analyses that inform control of viruses – herpes simplex/varicella zoster?

A meta-analysis of studies in children demonstrated that varicella vaccine is useful to control community varicella outbreaks, reducing both contagion and severity of disease. A meta-analysis of studies in children confirms a limited effectiveness of one dose of varicella vaccine and points to waning immunity as an important factor. There are no similar meta-analyses from HCWs or hospitalized or adult patients but inferences are likely valid for them also. A big randomized trial demonstrated that zoster vaccine reduces the burden of illness and post-herpetic neuralgia in people aged over 60 years.

There is insufficient evidence to determine if antiviral prophylaxis reduces the incidence of neonatal herpes, but meta-analyses conclude that antenatal antiviral prophylaxis reduces the risk of clinical HSV recurrence at delivery, cesarean delivery for recurrent genital herpes, and the risk of HSV viral shedding at delivery.

What are the consequences of ignoring key concepts related to control of viruses – herpes simplex/varicella zoster?

By ignoring the need for vaccination at the time of hiring non-immune HCWs, costs associated with varicella control in the health care setting are enormous.

Besides, HCWs with VZV infection can transmit their disease to immunocompromised patients, especially those with cancer, HIV infection, or those undergoing transplantation, causing a severe and protracted, even fatal disease. Exposed, non-immune HCWs who receive any kind of secondary prevention (vaccine, immunoglobulin, or antivirals), should be furloughed. The surveillance of an outbreak must be continued through two incubation periods (42 days) after the rash onset of the last identified case to make sure that the outbreak is over.

Varicella in adults follows a more severe course than in children, with increased risk of complications, such as pneumonia and hemorrhage. The contagion of pregnant HCWs may lead to the congenital varicella syndrome, a rare but devastating disease. HSV mucositis is a severe disease, which occurs in most seropositive patients when acyclovir prophylaxis is not used after allogeneic stem cell transplantation.

What other information supports the key conclusions of studies of viruses – herpes simplex/varicella zoster e.g., case-control studies and case series?

VZV is highly transmissible to non-immune people as demonstrated by studies in household contacts and case series in hospitals. For HSV-1 and HSV-2, asymptomatic seropositive people with reactivation foster the continued spread and hinder its effective control.

During reactivation, HSV1 appears more transmissible to the neonate than HSV-2, which is a concern, given the rising frequency of genital HSV-1 infection.

Summary of current controversies.

Generally, only standard precautions are applied to patients with localized zoster, although there have been reports of airborne transmission to susceptible HCWs, which has led some authorities to suggest airborne precautions for all patients with active VZV lesions.

Although a positive history of varicella is generally considered proof of immunity, some institutions elect to test all HCWs regardless of disease history, because a small proportion of people with a positive history may be susceptible. There is no established consensus or guideline to offer zoster vaccine to all HCWs aged over 60 years. There is insufficient evidence to determine if antenatal antiviral prophylaxis reduces the risk of neonatal herpes.

What is the role of and impact of viruses – herpes simplex/varicella zoster or infections and the need for control relative to infections at other sites or other specific pathogens?

As they are not common in the healthcare settings, VZV/HSV infections tend to be neglected by professionals who are too busy dealing with problems like those caused by MRSA or MDR gram-negative bacteria.

However, the consequences of infectious outbreaks with VZV/HSV are severe, and costs of control are enormous due to work furloughs, laboratory tests, patient isolation, varicella immune globulin, antivirals, and infection control personnel time. Every health institution must have a plan to prevent VZV/HSV infections and to control them immediately when they have occurred.

Overview of important clinical trials, meta-analyses, case control studies, case series, and individual case reports related to infection control and viruses – herpes simplex/varicella zoster.

See Table I.

Table I.
Study (yr) Type of study Main objective Subjects Main results Other results
Macartney (2008) Meta-analysis of randomized trials on varicella vaccine To assess vaccine effectiveness for post-exposure prophylaxis (<3 days) 110 children from 3 trials Vaccine reduces contagion (18%) as compared with placebo (78%) Vaccine reduces severity of disease
Bayer (2007) Meta-analyses of varicella outbreaks in vaccinated population To assess vaccine effectiveness 3157 children from 14 studies Overall, one-dose vaccine effectiveness, 73% Seven studies suggested a detrimental impact from waning immunity
Oxman (2005) Randomized trial of zoster vaccine against zoster and post herpetic neuralgia To assess effectiveness of herpes vaccine at a median of 3 years 38,546 adults aged over 60 years Vaccine reduces zoster incidence in 51% and post herpetic neuralgia in 67%

Vaccine reduces burden of illness in 61%

Controversies in detail.

Although only standard precautions are applied generally to patients with localized zoster, there have been reports of airborne transmission to susceptible HCWs in such cases, which is why some authorities suggest airborne precautions for all patients with active VZV lesions.

Regardless of varicella history, some institutions elect to perform serology to all HCWs, but most consider positive history a proof of immunity because varicella serology is far from an ideal test.

What national and international guidelines exist related to viruses – herpes simplex/varicella zoster?

In the USA, the IDSA and ACIP guidelines recommend routine, two-dose varicella vaccination for all susceptible HCWs.

The IDSA guideline recommends vaccination of postpartum, non-immune women or if a second dose of varicella vaccine was not administered previously.

The ACIP recommends the new zoster vaccine for all persons aged 60 years or more who have no contraindications, including people with a history of zoster or who have chronic medical conditions.

American and German guidelines recommend passive immunization with anti-VZV immunoglobulin for non-immune stem cell transplantation recipients soon after being exposed to people with active VZV infection.

American and German guidelines recommend acyclovir prophylaxis for all HSV seropositive recipients of allogeneic stem cell transplantation, which should be started on the onset of conditioning and continued until granulocyte recovery or until stomatitis has healed; routine acyclovir prophylaxis is not indicated for seronegative patients even if the donor is positive.

What other consensus group statements exist and what do key leaders advise?

There are no other consensus statements or guidelines regarding post exposure prophylaxis for HSV infections and no controlled clinical trials in humans.