Herpes zoster vaccination efficacy in the long-term care facility population: a qualitative systematic review

Background: The varicella zoster virus (VZV) can reactivate later in life as herpes zoster infection (HZI), a severe disease resulting in painful complications such as post-herpetic neuralgia (PHN). The herpes zoster (HZ) vaccine has been indicated for use among adults 50?years and older for prevention of HZI. Currently, no clinical practice guideline or funding exists specifically for HZ immunization in long-term care facilities (LTCF) for adults age >60 years.

Objectives: This review summarizes the current literature available on the efficacy of HZ vaccine in adults over 60?years old residing in LTCF and evaluates the cost-effectiveness of the HZ vaccine.

Methods: We conducted a literature search in PsycInFO, Embase and MEDLINE databases, and a grey literature search. The search was limited to the last 5?years (January 2013–April 2018). Studies that assessed the efficacy of the HZ vaccine in individuals 60?years old or older and met inclusion criteria were included.

Results: A total of 423 studies were found: 10 studies met inclusion criteria and were deemed relevant to the objectives. All reviewed studies highlighted the efficacy of the HZ vaccine for the LTCF population.

Conclusions: The studies reviewed showed the efficacy of the HZ vaccine in relevant elderly populations residing either in LTCF or in the community including those of advanced age with multiple comorbidities. Consideration can be given to the use of the HZ vaccine for individuals over 60 in LTCF, as well as in the community.     

Post-herpetic neuralgia in older adults: evidence-based approaches to clinical management

Many individuals across the globe have been exposed to the varicella-zoster virus (VZV) that causes chickenpox. After chickenpox has resolved, the virus remains latent in the dorsal root ganglia where it can re-emerge later in life as herpes zoster, otherwise known as shingles. Herpes zoster is a transient disease characterised by a dermatomal rash that is usually associated with significant pain. Post-herpetic neuralgia (PHN) is the term used for the condition that exists if the pain persists after the rash has resolved. Advanced age and compromised cell-mediated immunity are significant risk factors for reactivation of herpes zoster and the subsequent development of PHN. Though the pathophysiology of PHN is unclear, studies suggest peripheral and central demyelination as well as neuronal destruction are involved. Both the vaccine against VZV (Varivax) and the newly released vaccine against herpes zoster (Zostavax) may lead to substantial reductions in morbidity from herpes zoster and PHN. In addition, current evidence suggests that multiple medications are effective in reducing the pain associated with PHN. These include tricyclic antidepressants, antiepileptics, opioids, NMDA receptor antagonists as well as topical lidocaine (lignocaine) and capsaicin. Reasonable evidence supports the use of intrathecal corticosteroids, but the potential for neurological sequelae should prompt caution with their application. Epidural corticosteroids have not been shown to provide effective analgesia for PHN. Sympathetic blockade may assist in treating the pain of herpes zoster or PHN. For intractable PHN pain, practitioners have performed delicate surgeries and attempted novel therapies. Although such therapies may help reduce pain, they have been associated with disappointing results, with up to 50% of patients failing to receive acceptable pain relief. Hence, it is likely that the most effective future treatment for this disease will focus on prevention of VZV infection and immunisation against herpes zoster infection with a novel vaccine.     

Management of herpes zoster (shingles) and postherpetic neuralgia

Herpes zoster (HZ) results from recrudescence of varicella zoster virus latent since primary infection (varicella). The overall incidence of HZ is ～ 3/1000 of the population per year rising to 10/1000 per year by 80 years of age. Approximately 50% of individuals reaching 90 years of age will have had HZ. In ～ 6%, a second attack may occur (usually several decades after the first). Patients with HZ can transmit the virus to a non-immune individual causing varicella. HZ is not contracted from individuals with varicella or HZ. Reduced cell-mediated immunity to HZ occurs with ageing, explaining the increased incidence in the elderly and from other causes such as tumours, HIV and immunosuppressant drugs. Diagnosis is usually clinical from typical unilateral dermatomal pain and rash. Prodromal symptoms, pain, itching and malaise, are common. The most common complication of HZ is postherpetic neuralgia (PHN), defined as significant pain or dysaesthesia present ≥ 3 months after HZ. PHN results from damage and secondary changes within components of the nervous system subserving pain. Some motor deficit is common; severe and long-lasting paresis may rarely accompany HZ. More than 5% of elderly patients have PHN at 1 year after acute HZ. Predictors of PHN are, greater age, acute pain and rash severity, prodromal pain, the presence of virus in peripheral blood as well as adverse psychosocial factors. Therapy for acute HZ is intended to reduce acute pain, hasten rash healing and reduce the risk of PHN and other complications. Antiviral drugs are close to achieving these aims but do not entirely remove risk of PHN. Oral steroids show no protective effect against PHN. Adequate analgesia during the acute phase may require strong opioid drugs. Nerve blocks and tricyclic antidepressants (TCAs) may reduce the risk of PHN although firm evidence is lacking. PHN requires thorough evaluation and development of a management strategy for each individual patient. Initial therapy is with TCAs (e.g., nortriptyline) or the anticonvulsant gabapentin. Topical lidocaine patches frequently reduce allodynia. Strong opioids are sometimes required. Topical capsaicin cream is beneficial for a small proportion of patients but is poorly tolerated. NMDA antagonists have not proved beneficial with the exception of ketamine. Transcutaneous Electrical Nerve Stimulation (TENS) may be effective in some cases. HZ is a common condition. Severe complications such as stroke, encephalitis and myelitis are relatively rare whereas sight threatening complications of ophthalmic HZ are more common. PHN is common, distressing and often intractable. Good management improves outcome.     

Management of herpes zoster (shingles) and postherpetic neuralgia

Herpes zoster (HZ) results from recrudescence of varicella zoster virus latent since primary infection (varicella). The overall incidence of HZ is approximately 3/1000 of the population per year rising to 10/1000 per year by 80 years of age. Approximately 50% of individuals reaching 90 years of age will have had HZ. In approximately 6%, a second attack may occur (usually several decades after the first). Patients with HZ can transmit the virus to a non-immune individual causing varicella. HZ is not contracted from individuals with varicella or HZ. Reduced cell-mediated immunity to HZ occurs with ageing, explaining the increased incidence in the elderly and from other causes such as tumours, HIV and immunosuppressant drugs. Diagnosis is usually clinical from typical unilateral dermatomal pain and rash. Prodromal symptoms, pain, itching and malaise, are common. The most common complication of HZ is postherpetic neuralgia (PHN), defined as significant pain or dysaesthesia present >or= 3 months after HZ. PHN results from damage and secondary changes within components of the nervous system subserving pain. Some motor deficit is common; severe and long-lasting paresis may rarely accompany HZ. More than 5% of elderly patients have PHN at 1 year after acute HZ. Predictors of PHN are, greater age, acute pain and rash severity, prodromal pain, the presence of virus in peripheral blood as well as adverse psychosocial factors. Therapy for acute HZ is intended to reduce acute pain, hasten rash healing and reduce the risk of PHN and other complications. Antiviral drugs are close to achieving these aims but do not entirely remove risk of PHN. Oral steroids show no protective effect against PHN. Adequate analgesia during the acute phase may require strong opioid drugs. Nerve blocks and tricyclic antidepressants (TCAs) may reduce the risk of PHN although firm evidence is lacking. PHN requires thorough evaluation and development of a management strategy for each individual patient. Initial therapy is with TCAs (e.g., nortriptyline) or the anticonvulsant gabapentin. Topical lidocaine patches frequently reduce allodynia. Strong opioids are sometimes required. Topical capsaicin cream is beneficial for a small proportion of patients but is poorly tolerated. NMDA antagonists have not proved beneficial with the exception of ketamine. Transcutaneous Electrical Nerve Stimulation (TENS) may be effective in some cases. HZ is a common condition. Severe complications such as stroke, encephalitis and myelitis are relatively rare whereas sight threatening complications of ophthalmic HZ are more common. PHN is common, distressing and often intractable. Good management improves outcome.     

The potential cost-effectiveness of vaccination against herpes zoster and post-herpetic neuralgia

A clinical trial has shown that a live-attenuated varicella-zoster virus vaccine is effective against herpes zoster (HZ) and post-herpetic neuralgia (PHN). The aim of this study was to examine the cost-effectiveness of vaccination against HZ and PHN in Canada. A cohort model was developed to estimate the burden of HZ and the cost-effectiveness of HZ vaccination, using Canadian population-based data. Different ages at vaccination were examined and probabilistic sensitivity analysis was performed. The economic evaluation was conducted from the ministry of health perspective and 5% discounting was used for costs and benefits. In Canada (population = 30 million), we estimate that each year there are 130,000 new cases of HZ, 17,000 cases of PHN and 20 deaths. Most of the pain and suffering is borne by adults over the age of 60 years and is due to PHN. Vaccinating 65-year-olds (HZ efficacy = 63%, PHN efficacy = 67%, no waning, cost/course = $150) is estimated to cost $33,000 per QALY-gained (90% CrI: 19,000-63,000). Assuming the cost per course of HZ vaccination is $150, probabilistic sensitivity analysis suggest that vaccinating between 65 and 75 years of age will likely yield cost-effectiveness ratios below $40,000 per Quality-Adjusted Life-Year (QALY) gained, while vaccinating adults older than 75 years will yield ratios less than $70,000 per QALY-gained. These results are most sensitive to the duration of vaccine protection and the cost of vaccination. In conclusion, results suggest that vaccinating adults between the ages of 65 and 75 years is likely to be cost-effective and thus to be a judicious use of scarce health care resources.     

Prophylaxis of herpesvirus infections in immunocompetent and immunocompromised older patients

In older patients, prophylaxis of herpesvirus infections mainly involves preventing the recurrence of herpes simplex virus (HSV) and complications of herpes zoster in immunocompetent patients, while in immunocompromised patients it is more concerned with the prevention of opportunistic virus reactivation. HSV ocular infection is the most frequent cause of corneal blindness in the US. The effectiveness of aciclovir 400mg twice daily in preventing the recurrence of HSV eye disease in immunocompetent patients has been well demonstrated. The issue of treatment duration for patients with highly recurrent ocular herpes remains unresolved. Post-herpetic neuralgia (PHN) is one of the most common neuralgic illnesses worldwide. Some progress in prevention of PHN has been made with a combination of antiviral therapy (famciclovir or valaciclovir), started within 72 hours of onset of the rash, and analgesic treatment. However, the best prevention of PHN is the prevention of herpes zoster disease, and the varicella vaccine is an option which over the next few years will be tested in clinical trials. For immunocompromised patients of any age, restoring immunity prevents herpesvirus disease, as demonstrated for cytomegalovirus (CMV) in AIDS patients receiving highly active antiretroviral therapy. Specific antiviral therapy during the initial period after transplantation could prevent reactivation of HSV or CMV in seropositive recipients. Whether pre-emptive therapy or prophylaxis with ganciclovir is the optimal approach against CMV remains controversial, and the relative merits and limitations of each approach may guide the choice. In stem cell transplantation, pre-emptive therapy with foscarnet avoids the neutropenia and related complications associated with ganciclovir. In renal transplant recipients, universal prophylaxis of CMV infection with valaciclovir has the same efficacy as ganciclovir. Although it is relatively toxic, cidofovir should be further evaluated because of its in vitro activity against most DNA viruses.     

Herpes zoster in eastern Saudi Arabia: clinical presentation and management

BACKGROUND: Herpes zoster (HZ), caused by varicella zoster virus (VZV), initially produces chicken-pox, then the virus lies dormant in the dorsal root ganglia. The virus can reactivate after many years and results in HZ along ganglion's distribution. Old age, trauma, stress, diabetes mellitus, and immune suppression are important risk factors for the reactivation. Herpes zoster is characterized by unilateral radicular pain and vesicular eruption that is generally limited to the dermatome innervated by the affected ganglion. In immunocompromised individuals, disseminated zoster may develop. The aims of therapy in HZ are to control pain or reduce its severity by the use of analgesics, reduce the duration and eruption of new lesions, and prevent complications, particularly postherpetic neuralgia (PHN) by appropriate antiviral therapy. METHODS: All cases of HZ seen in the dermatology clinic at King Fahd Hospital of the University (KFHU) from 1988 to 2006 were included in the study. Their diagnoses were based on the clinical presentation. The following parameters were collected and analyzed: age, sex, nationality, symptoms, dermatomal distribution, complications, coexisting diseases, and disease management. RESULTS: Of 22 749 new cases seen in the dermatology clinic over 18 years, 141 were HZ, with an occurrence of 0.62%. Male to female ratio was 2:1 and the age ranged from 14 months to 80 years. The thoracic dermatomes were the most commonly involved. The most frequent coexisting disease was diabetes mellitus, and the most common complication of HZ was PHN. Most patients with HZ ophthalmicus developed eye complications. CONCLUSION: The occurrence of HZ is 0.62% in patients reporting to the dermatology clinic of the hospital. Males are little more affected than females. The thoracic dermatomes are the most frequently involved. Diabetes mellitus is the most frequent coexisting disease. Postherpetic neuralgia is the most common complication of HZ.     

Universal varicella vaccination: efficacy trends and effect on herpes zoster

In 1995, the Varicella Active Surveillance Project (VASP) was established in Antelope Valley (California), a geographically distinct high-desert community of 300,000 residents, as one of three sites in the nation in a cooperative agreement with the Centers for Disease Control and Prevention (CDC) to collect baseline demographic and clinical data and to monitor trends in varicella (chickenpox) following introduction of varicella vaccine. Herpes zoster (shingles) was added to the active surveillance January 1, 2000. The universal varicella program has proven effective in terms of reducing the number of reported verified varicella cases by 85%, from 2,934 in 1995 to 412 in 2002. Prior to this dramatic reduction, immunologic boosting due to exogenous exposures to wild-type varicella-zoster virus (VZV) in the community (1) caused mean serum anti-VZV levels among vaccines to increase with time after vaccination and (2) served as a mechanism that helped suppress the reactivation of herpes zoster (HZ), especially among individuals with a previous history of wild-type varicella.That immunologic boosting might play a significant role in both varicella and the closely related HZ epidemiology is evidenced by (1) a decline in vaccine efficacy by over 20%, from 95.7% (95% C.I., 82.7% to 98.9%) in 1999 to 73.9% (95% C.I., 57.9% to 83.8%) in 2001 and (2) an unexpectedly high cumulative (2000 to 2003) true incidence rate of 223 (95% C.I. 180-273) per 100,000 person-years (p-y) among children <10 years old with a previous history of varicella. Because capture-recapture methods demonstrate a likely lower bound of 50% underreporting, the actual rate is likely double or 446 per 100,000 p-y, approaching the HZ rate reported among older adults. Other recent studies based on VASP data have mitigated against discovery of the above trends that challenge several initial assumptions inherent to the universal varicella program, namely, (1) a single dose confers long-term immunity and (2) there is no immunologically mediated link between varicella and HZ incidence. As vaccinated children replace those with a prior history of wild-type varicella in the <10 age group, increasing HZ incidence among this cohort will be of less concern in the near future. However, previous scientific studies, including the present preliminary results from active surveillance indicate that HZ may be increasing among adults. It may be difficult to design booster interventions that are cost-effective and meet or exceed the level of protection provided by immunologic boosting that existed naturally in the community in the prelicensure era.     

Tolerability of treatments for postherpetic neuralgia.

Herpes zoster occurs in up to 20% of people infected with varicella-zoster virus, due to reactivation of the virus from latently infected sensory ganglia. Although pain is a typical feature of acute zoster, pain persisting for more than a month after resolution of the rash is less common and is termed postherpetic neuralgia (PHN). The pain associated with PHN is neuropathic in origin and is notoriously difficult to treat. The incidence of herpes zoster and its associated complications both increase with age, so PHN should be seen more commonly in an aging population. Vaccination with live, attenuated varicella vaccine is safe and efficacious, particularly in children. It decreases the incidence of acute varicella and subsequent herpes zoster. Aciclovir is well tolerated, with renal toxicity only at high intravenous doses. Treatment of acute varicella with aciclovir attenuates acute illness but does not prevent herpes zoster. Treatment of herpes zoster with aciclovir or its derivatives minimises symptoms and may reduce the rate of PHN. Foscarnet is an alternative for an aciclovir-resistant virus but its use is limited by renal and CNS toxicity. Corticosteroids reduce acute pain in herpes zoster but do not affect the incidence of PHN. Their use in some patients may be limited by adverse effects such as gastritis and impaired glucose tolerance. Treatment of established PHN is difficult and may require a holistic approach. Tricyclic antidepressants and gabapentin are the systemic agents with the most proven benefit, although opioids such as oxycodone and NMDA receptor antagonists such as ketamine may be useful in some people. Adverse effects from tricyclic antidepressants are common but usually mild, while gabapentin is generally well tolerated. Although effective, the relatively common adverse effects of opioids and ketamine limit their usefulness in treating PHN. Topical treatment with 5% lidocaine patch or capsaicin is of benefit in some patients and is generally well tolerated. Intrathecal methyl prednisolone may be considered for intractable pain but efficacy and safety have not been confirmed.     

Brivudin (bromovinyl deoxyuridine)

Brivudin is an oral thymidine analogue indicated for the early treatment of acute herpes zoster in immunocompetent adults. It has high, selective activity against varicella zoster virus (VZV), inhibiting VZV replication, possibly through competitive inhibition of viral DNA polymerase, or by acting as an alternative substrate to deoxythymidine triphosphate, causing viral DNA strand breakage. In a large, 7-day, phase III trial in immunocompetent patients with herpes zoster, once-daily brivudin 125mg was significantly more effective than oral acyclovir 800mg five times daily in reducing the mean time from start of treatment to last vesicular eruption, and was as effective as acyclovir at healing lesions and alleviating acute zoster-related pain. The likelihood of developing post-herpetic neuralgia (PHN) in immunocompetent patients aged > or =50 years was significantly lower with brivudin than with acyclovir. Brivudin was as effective as oral famciclovir 250mg three times daily in terms of the prevalence of PHN, the time to last vesicular eruption and lesion healing in another large, 7-day, phase III study in immunocompetent patients with herpes zoster. Oral brivudin is generally well tolerated, with a similar tolerability profile to those of oral acyclovir or famciclovir. Nausea was the most commonly reported adverse event.     

Varicella-zoster virus vaccine: a review of its use in the prevention of herpes zoster in older adults

Current strategies for managing herpes zoster show variable efficacy and do not prevent its appearance. Varicella-zoster virus vaccine, or "zoster vaccine" is a more potent form of the varicella-zoster virus vaccine currently approved for use in the prevention of varicella in children. Zoster vaccine decreases the incidence of herpes zoster and burden of illness in adults aged 60 years and older and appears more efficacious in patients aged 60-69 than in those over 70 years. Importantly, the incidence of postherpetic neuralgia is significantly reduced in patients who receive zoster vaccine, irrespective of age or sex. The duration of postherpetic neuralgia is also significantly reduced. Zoster vaccine has a favorable safety profile; most treatment-related adverse events are related to the site of injection. This review summarizes the current data on the clinical efficacy and safety of zoster vaccine in adults aged 60 years and older.     

Live attenuated measles, mumps, rubella, and varicella zoster virus vaccine (Priorix-Tetra)

The live attenuated tetravalent vaccine against measles, mumps, rubella, and varicella zoster viruses (MMRV) is a combination of the measles, mumps, and rubella (MMR) vaccine and the varicella zoster virus vaccine. The immunogenicity after each dose of a two-dose vaccination course of MMRV vaccine was generally similar to that of two doses of separately administered MMR plus varicella zoster vaccines, or a single dose of separately administered MMR plus varicella zoster vaccines followed by a dose of MMR vaccine, in infants aged 9-24 months. In infants aged 9-24 months administered a two-dose course of MMRV vaccine, geometric mean titers for antibodies against all vaccine antigens increased after the second dose relative to the first dose, with the increase being most pronounced for varicella zoster virus antibodies (10- to 21-fold). MMRV as the second vaccination was immunogenic in children aged 5-6 years who had previously received either MMRV or MMR as the first vaccination at 12-24 months of age. The immunogenicity for measles, mumps, rubella, and varicella zoster viruses, in terms of seropositivity and antibody titers, was not altered when MMRV was coadministered with a booster dose of diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b conjugate vaccine in infants aged 12-23 months. Nor was the immunogenicity of the latter vaccine altered by coadministration. The tolerability profile of MMRV vaccine was comparable to that of separately administered MMR plus varicella zoster vaccines or of MMR vaccine alone. Injection-site redness and fever (rectal temperature > or =38degreesC or axillary temperature > or =37.5degreesC) were the most frequent adverse events in both groups.     

临床药师参与1例带状疱疹后神经痛治疗方案分析

带状疱疹后神经痛(postherpetic neuralgia,PHN)为带状疱疹皮疹愈合后由病毒侵入神经所诱发的神经病理性疼痛,是临床中该疾病治疗最常发生且难以控制的并发症.本文中,临床药师对1例带状疱疹后神经痛患者的治疗方案进行分析,从药物使用、联用的角度讨论治疗方案的合理性,体现了临床药师在指导临床诊疗过程中的重...     

Emerging drugs for varicella-zoster virus infections

INTRODUCTION: Varicella-zoster virus (VZV) is the etiological agent of two distinct diseases, varicella (chickenpox) and shingles (herpes zoster). Chickenpox occurs following primary infection, while herpes zoster (usually associated with ageing and immunosuppression) is the consequence of reactivation of the latent virus. Post-herpetic neuralgia is the major complication of shingles. AREAS COVERED: This review will discuss vaccination strategies and the current status of antivirals against VZV. A live attenuated vaccine, Varivax, is available for pediatric varicella while Zostavax was developed to boost VZV-specific cell-mediated immunity in adults older than 60 years and, via this mechanism, to decrease the burden of herpes zoster and pain associated with post-herpetic neuralgia. Despite the availability of a vaccine, there is a need for new antiviral agents. Current drugs approved for the treatment of VZV infections include nucleoside analogs that target the viral DNA polymerase and depend on the viral thymidine kinase. Novel anti-VZV drugs have recently been evaluated in clinical trials, including the bicyclic nucleoside analog FV-100, the helicase-primase inhibitor ASP2151 and valomaciclovir (prodrug of the acyclic guanosine derivative H2G). EXPERT OPINION: New anti-VZV drugs should be as safe as and more effective than acyclovir and its prodrug valacyclovir (current gold standard for the treatment of VZV).     

Zoster vaccine live (Oka/Merck)

A subcutaneously administered, live, high-titre (18,700-60,000 plaque-forming units per dose) varicella zoster virus (VZV) vaccine (zoster vaccine) of the Oka/Merck strain has been evaluated for the prevention of herpes zoster and the reduction of zoster-associated pain in adults aged > or =60 years. Zoster vaccine, when compared with placebo, reduced the burden of herpes zoster illness by 61%, the incidence of herpes zoster by 51% and the incidence of postherpetic neuralgia by 67% during more than 3 years of surveillance. The zoster vaccine caused an initial 1.7-fold rise in VZV antibody titre after 6 weeks that declined progressively over 3 years. Increases in gamma-interferon-secreting peripheral blood mononuclear cells were 2.2-fold greater with the zoster vaccine than with placebo 6 weeks after vaccination. Zoster vaccine was generally well tolerated. The most frequently reported adverse reactions following vaccination were injection-site reactions; the only systemic adverse event with zoster vaccine that differed significantly in incidence from that with placebo was headache.     

Post-herpetic neuralgia – a review of current management and future directions

Introduction: Post-herpetic neuralgia (PHN) is common and treatment is often suboptimal with less than half of patients achieving adequate 50% pain relief. As an area of unmet clinical need and as an archetype of neuropathic pain, it deserves the attention of clinicians and researchers.

Areas covered: This review summarises the epidemiology, pathophysiology, risk factors and clinical features of varicella infection. It describes the current and possible future management strategies for preventing varicella infection and reactivation and for treating PHN.

Expert opinion: A highly successful Varicella Zoster (VZV) vaccine has not been universally adopted due to fears that it may increase Herpes Zoster (HZ) incidence – and thus PHN – in older, unvaccinated generations. This is a controversial theory but advances in the efficacy of vaccines against HZ may allay these fears and encourage more widespread adoption of the VZV vaccine.

Treatment of PHN, as for any neuropathic pain, must be multidisciplinary and multimodal. Advances in sensory phenotyping technology and genomics may allow more individualised treatment. Traditional research methodologies are ill-suited to assess the kind of complex interventions that are necessary to achieve better clinical outcomes in this challenging field.     

Antiviral therapies for herpes zoster infections. Are they economically justifiable?

Antiviral treatment of herpes zoster is controversial because of uncertain benefits and relatively high costs. Most studies show that antiviral therapy lessens acute herpes zoster symptoms and postherpetic neuralgia (PHN). Current clinical recommendations support antiviral treatment of severely symptomatic herpes zoster in all adults, and mild herpes zoster in those 50 or 60 years of age or older. However, it is unclear if these recommended strategies are cost effective. Published studies of herpes zoster costs and the effect of antiviral therapy on costs and quality of life have significant variation in study design and results, as well as many shortcomings in the data. Thus, definitive economic recommendations cannot be made based on the present data. Another approach, which we have used, is to develop a 'reference case' analysis using decision-analysis techniques and the available data to estimate the incremental cost effectiveness of antiviral treatment in patients of differing age and herpes zoster severity. In the baseline analysis, parameter values and assumptions were consistently slightly biased against antiviral use. Effectiveness was measured in quality-adjusted life years (QALYs). We assumed that antiviral treatment did not change PHN risk, but decreased PHN duration in patients older than 50 years. PHN risk increased with age and with acute herpes zoster severity as seen in published data. Mild acute herpes zoster was assumed to have a utility value of 0.9 and severe acute herpes zoster a value of 0.7 on a scale where 0 = death and 1 = perfect health. Treating mildly symptomatic acute herpes zoster cost $US89,200/QALY gained in 40-year-olds, $US47,700/QALY in 60-year-olds and $US40,700/QALY in 70-year-olds (1995 values). Results were most sensitive to variation of antiviral costs (baseline $US134), but changes in acute symptom relief, PHN risk, duration, costs and utility, and antiviral effect on PHN duration increased costs/QALY above $US50,000 in 60- and 70-year-olds in extremes of parameter ranges. However, no variation resulted in treatment of mild illness in 40-year-olds to fall below $US50,000/QALY gained. Treatment of severe acute herpes zoster cost $US29,700, $US18,000 and $US16,500/QALY gained in 40-, 60- and 70-year-olds, respectively. Results were sensitive to variation of antiviral costs (> $US225) and acute symptom relief (< 21%) in 40-year-olds. Based on this analysis, antiviral therapy of herpes zoster seems economically justifiable for mildly symptomatic acute herpes zoster in patients aged 50 years and older, and for severely symptomatic acute herpes zoster in all adults.     

Viral skin infections in the elderly: diagnosis and management

Over the past several years, there have been advances in the diagnosis and treatment of cutaneous viral diseases in elderly patients. Herpes zoster is caused by reactivation in adults of the varicella-zoster virus (VZV) that causes chickenpox in children. For many years, aciclovir was the gold standard of antiviral therapy for the treatment of herpes zoster. Famciclovir and valaciclovir are newer antivirals, which offer less frequent administration. Postherpetic neuralgia (PHN) refers to pain lasting 2 months or more after an acute attack of herpes zoster. The pain may be constant or intermittent. The treatment of established PHN may include topical anaesthetics, analgesics, tricyclic antidepressants and anticonvulsants, and nonpharmacological therapy may be used to complement such treatment. Therapeutic strategies to prevent PHN include the use of oral corticosteroids, nerve blocks, and treatment with standard antiviral therapy. The three most recently discovered human herpes viruses (HHV-6, HHV-7 and HHV-8), in common with the other members of the family, may cause a primary infection, establish latent infection in a specific set of cells in their host, and then reactivate if conditions of altered immunity develop. These viruses have been associated with an array of disorders, which are important for the clinician to recognise. Cytomegalovirus (CMV) is a member of the herpesvirus family that is very prevalent worldwide. More than 80% of primary infections and 20% of reactivation-producing symptoms occur in transplant populations. Treatment options include intravenous administration of ganciclovir, foscarnet or cidofovir. Herpes simplex virus (HSV) most commonly affects the genital and perioral regions. In the elderly, HSV infection is typically manifest at the vermilion border of the lip. The main concern of recurrent herpes labialis in the elderly is related to potential autoinoculation of the eye or genital area. Treatment with aciclovir, famciclovir or valaciclovir is indicated for these infections. Molluscum contagiosum is caused by a poxvirus, which produces cutaneous lesions that appear as small, firm, umbilicated papules. Immunocompromised patients often do not respond to the usual destructive therapies, and intravenous or topical cidofovir may be useful in these patients.     

Non‐clinical safety assessment of single and repeated administration of gE/AS01 zoster vaccine in rabbits

HZ/su is an investigational recombinant subunit vaccine for the prevention of shingles, a disease resulting from the reactivation of varicella zoster virus. The vaccine is composed of recombinant varicella zoster virus glycoprotein E (gE), and liposome‐based Adjuvant System AS01. To evaluate the potential local and systemic effects of this vaccine, three studies were performed in rabbits. In the first two studies, rabbits received a single intramuscular (IM; study 1) or subcutaneous (SC; study 2) dose of gE/AS01, AS01 alone (in study 2 only) or saline, and the local tolerance was evaluated up to 3 days after administration. Under these conditions, only local inflammatory reactions at the injection sites were detected by microscopic evaluation. In the third study, gE/AS01, AS01 alone or saline, were injected SC or IM on four occasions at 2 week intervals. General health status, local tolerance, ophthalmology, haematology and blood chemistry parameters were monitored. Macroscopic and microscopic evaluations were performed after termination of the study. The only treatment‐related changes included a transient increase in neutrophils, C‐reactive protein and fibrinogen levels and microscopic signs of inflammation at the injection sites, which are expected observations related to the elicited inflammatory reaction. The SC and IM routes of administration produced similar systemic effects. However, microscopic findings at the injection sites differed. One month after the last injection, recovery was complete in all groups. In conclusion, the single and repeated SC and IM administration of the gE/AS01 vaccine were locally and systemically well‐tolerated in rabbits and support the clinical development of the vaccine. Copyright © 2016 John Wiley & Sons, Ltd.     

Zoster vaccine live

Herpes zoster is a neurocutaneous disease caused by the varicella-zoster virus and is associated with significant morbidity and long-term sequelae in older adults. Until recently, treatment options for these complications have been primarily targeted at disease state management and symptom relief. Zoster vaccine live is the first vaccine approved for the prevention of herpes zoster. The vaccine was approved by the United States Food and Drug Administration for adults aged 60 years or older. Results of the Shingles Prevention Study demonstrated that in older individuals, administration of zoster vaccine live reduces the burden of illness associated with herpes zoster by 61.1%, the frequency of herpes zoster pain and discomfort by 51.3%, and the frequency of postherpetic neuralgia by 66.5%. Overall, adverse events reported in clinical trials of zoster vaccine live were classified as mild. Events that occurred more frequently in zoster vaccine live recipients than in placebo recipients included injection site reactions, headache, respiratory infections, fever, flu syndrome, diarrhea, rhinitis, skin disorders, respiratory disorders, and asthenia. The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recently recommended universal vaccination for those 60 years of age and older, including those who have experienced previous episodes of shingles.