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Research Paper

Reducing the burden of Herpes Zoster in Italy

Giovanni Gabutti University of Ferrara; Ferrara, ItalyCorrespondence[email protected]
,
Elisabetta Franco University Tor Vergata; Rome, Italy
,
Paolo Bonanni University of Florence; Florence, Italy
,
Michele Conversano LHU Taranto, President of the Italian Society of Hygiene and Preventive Medicine; Taranto, Italy
,
Antonio Ferro LHU17 Veneto; Este-Monselice (Pd), Italy
,
Marzia Lazzari University Tor Vergata; Rome, Italy
,
Stefania Maggi Board of the Italian Society of Gerontology and Geriatrics; Italy
,
Alessandro Rossi Board of the Italian Society of General Medicine; Italy
,
Silvestro Scotti Board of the Italian Federation of General Practitioners; Italy
,
Francesco Vitale University of Palermo; Palermo, Italy
,
Antonio Volpi University Tor Vergata; Rome, Italy
&
Donato Greco Epidemiologist; Rome, Italy
 show all
Pages 101-107 | Received 06 Aug 2014, Accepted 06 Aug 2014, Published online: 01 Nov 2014

Abstract

Herpes Zoster (HZ) is a viral disease with painful neuro-dermatologic manifestations. Incidence increases with age. In Italy, the estimated incidence is 6.3 cases/1000 person/year; hospital admissions are less than 2%, 69% in patients aged over 65 years. The most frequent complication of HZ is Post-Herpetic Neuralgia (PHN) characterized by metameric pain, allodynia, and hyperalgesia. In Italy 20.6% and 9.2% of HZ patients experience PHN after 3 and 6 months, respectively. Available antiviral and analgesic treatments are relatively unsatisfactory in reducing pain and length of the disease. Prevention has recently become possible with the live attenuated vaccine Oka/Merck. Clinical studies show a reduction of 51% in the incidence of the disease, 61% of its burden and 67% of PHN in vaccinees. Protection seems to be long lasting and vaccine safety matches registration requirements. Available evidence suggests that the costs for QALY (less than € 20 000) and avoided cases is favorable. Due to the heavy burden of disease, it is time to offer this vaccination to elderly population.

Introduction

Varicella (chickenpox) is a highly contagious illness sustained by an α Herpes virus called varicella-zoster virus (VZV). Epidemiologically, this is an infection with an endemic-epidemic pattern that only affects humans and is air-transmitted as well as by direct contact with blisters. The causative agent is ubiquitous and mostly affects children; the maximum incidence is seen in the 0 to 14-y-age group.Citation1

A particular characteristic of the causative agent is its ability to infect, during primary infection, skin nervous endings and become latent in nerve sensory ganglia.Citation2 In detail, a replication phase in the penetration site is followed by a viremic phase when VZV spreads to skin and mucosae; the consequent replication leads to the typical rash and infection of nerve sensory ganglia in the epithelium. From here, the virus gains access to sensory ganglia where it remains latent. Reactivation of latent VZV virus, several years or even decades after experiencing primary infection, leads to a typical clinical manifestation called Herpes Zoster (HZ).Citation3

Etiopathogenesis and Immunology

During primary infection, VZV migrates through sensory nerve fibers to corresponding dorsal root nerve ganglia. VZV becomes latent in the ganglia and remains there for the patient lifetime (latency). During the reactivation, nerve ganglia are the site of viral replication with ensuing neuropathic damage to nerve fibers; VZV follows the corresponding sensory ending until it reaches skin branches resulting into clinically evident HZ.Citation4-Citation7 Therefore, HZ can be defined as an acute vesicular dermatitis, with typical unilateral distribution due to the reactivation of VZV acquired during the primary infection usually in pediatric age (chickenpox).Citation8

With regard to immunology, natural VZV infection induces a long-term antibody-mediated and cell-mediated immunity (CMI) against the clinical form of the disease.Citation9 However, natural acquired immunity does not prevent virus latentization nor the possible subsequent reactivation (HZ). The lack of specific anti-VZV antibodies does not necessarily imply susceptibility, since the corresponding CMI can persist.Citation10,Citation11 Approximately 20% of subjects aged >50 y do not show a measurable specific CMI, notwithstanding persistence of specific antibodies and a positive history of varicella.Citation12,Citation13

HZ is strictly related to a reduction in VZV-specific T lymphocytes; a Zoster episode reactivates specific T-cell response.Citation14 Since varicella is an infectious disease that can virtually affect all subjects, especially in the pediatric age, most of the adult population has specific anti-VZV antibodies that are the expression of a previous contact with the infectious agent and has a latent form of VZV.Citation15,Citation16 As a consequence, most of the adult population is potentially susceptible to develop an episode of HZ in its lifetime.

Epidemiology

HZ is sporadic and occurs all over the year, completely un-related to varicella outbreaks. HZ cannot be transmitted. The only event that may occur is the transmission of the reactivated virus to subjects who had not been previously exposed to the virus; in this case, infected subjects contract varicella. All HZ-infected subjects constantly show a positive history of varicella.Citation17

HZ is painful and unilateral, with a dermatomal distribution in the skin area corresponding to the nervous fiber that originates from a dorsal root ganglion. The most frequent localization is the thoracic segment (50–60%); other possible localizations are the trigeminal (cranial; 10–20% of HZ cases have an ocular localization: ophthalmic HZ), cervical, lumbar and sacral segments.Citation18-Citation21 After the acute phase, 20% of patients can experience complications, while recurrences are relatively rare (1–5%).Citation22 The most fearful complication, being the expression of VZV neurotropism, is Post-Herpetic Neuralgia (PHN). PHN is a painful chronic condition, resistant to a number of treatments, affecting 10 to 20% of patients (some estimates report up to a third of patients) who have experienced an acute HZ episode.Citation23-Citation25

All authors agree that some factors are typically associated with HZ epidemiology, including age, cell-mediated immunity depression, intrauterine exposure to VZV and varicella occurring in early age (<18 months).Citation26,Citation27 Age and CMI depression are strictly related since increasing age leads to CMI decrease. Other authors maintain that also gender, seasonality, race, psychological distress, exposure to immunotoxic agents, mechanical traumas and genetic predisposition can play a crucial role in the development of HZ.

HZ incidence is similar all over the world and its trend is related to population age, with 2 to 3 cases/1000 person/years in the 20–50 y age group up to 5/1000 in the >60 age group, to 6–7/1000 in the 70–80 age group.Citation28,Citation29 It was estimated that over lifetime, at least 25% of the subjects will experience a HZ episode; two thirds of the cases in the world affect subjects aged >50 y. Considering the increase in the elderly and frail population, an increase in the number of cases is foreseen in the future. However, today over 1.7 million HZ cases are estimated to occur globally every year.Citation29

Therefore, immunosenescence plays a crucial role; however, 90% of HZ patients are not specifically immunocompromised. Besides age, HZ risk can be related to other co-morbidities (including diabetes, major depression, stressful events, immunosuppressive therapies) that induce reduced VZV-specific CMI response.Citation30-Citation32

In Europe, 95% of the adult population is estimated to be seropositive for anti-VZV antibodies and thus potentially susceptible to develop HZ in its lifetime.Citation15

In Italy, over 22 million people aged >50 y live; 157 000 new cases of HZ are estimated to occur every year. The annual incidence is 6.3/1000 person-years; 73% of cases affect adult subjects.Citation33

A perspective study performed all over Italy in cooperation with General Practitioners showed that 20.6% and 9.2% of HZ patients aged >50 y had PHN at 3 and 6 months, respectively, notwithstanding an early antiviral treatment (started within 72 h from skin rash onset). Also based on this study, the HZ/PHN burden is confirmed to increase with increasing age and HZ/PHN considerably impact on the patient quality of life.Citation34

Another study on hospital discharge records shows that over the period 1999–2005, 35 328 admissions due to HZ were recorded overall, of which 31 526 regular admissions and 3802 in day-hospital setting. The annual average was 4503 regular admissions and 543 day-hospital admissions, i.e., about 14 admissions/day. In the 1999–2005 period, 61.9% of admissions involved subjects aged ≥65 y and the average stay was 8 days.Citation35 These data, although taking into consideration only hospitalized cases recorded at national level, also confirm the epidemiological impact of HZ and associated complications.

Clinical Overview and Impact on Quality of Life

HZ is clinically characterized by vesicular rash and neuropathic pain with radicular distribution to which loss of sensitivity is often associated. The triad of HZ symptoms includes subjective symptoms, typical unilateral dermatomal rash, and regional painful lymphadenopathy.Citation36

The clinical pattern is usually preceded by a prodromic phase with acute photophobia, pain, headache and general malaise. The acute phase, that appears suddenly, is characterized by rash with a dermatomal distribution, pain, unbearable pruritus and allodynia. The acute phase is usually followed by recovery; however, a number of possible complications, especially neurologic ones, may occur.Citation6

Although HZ skin rash is temporarily disfiguring and quite annoying in a number of patients, the most important issue for patients is undoubtedly pain. HZ is basically a disease of the nervous system, being the most common infectious neurological manifestation.

HZ typical manifestations are limited to a specific body area but patient wellbeing is generally compromised.Citation37

Around 20% of patients experience complications. In immunocompromised hosts, the main complication following HZ is pain persistence defined as Post-Herpetic Neuralgia (PHN). PHN is a fearful painful chronic condition, resistant to a number of treatments that affects 10–20% of patients (some estimates report up to a third of patients) who have experienced an acute HZ episode. HZ is an extremely debilitating experience, for the affected subjects, with an impairment of physical, productive, and interpersonal abilities and with psychological effects in case of chronicization of the disease.Citation38 HZ and PHN negatively affect the patient quality of life (QoL); besides suffering due to the typical symptoms of skin lesions and the associated pain, subjects can also have an impaired ability to perform daily activities or maintain social and family relationships. The whole spectrum of symptoms and related functional and social symptoms can cause a chronic alteration in the psychological status of the affected subject.Citation39

The results from two trials, both performed in the United Kingdom, have been published very recently. The first study shows that HZ is an independent risk factor for vascular disease, in particular stroke, TIA and myocardial infarction in HZ subjects aged less than 40 y.Citation40 The second study shows a relationship between HZ and stroke in the 6 months following Zoster appearance. The risk is particularly increased in patients with ophthalmic HZ.Citation41

The objectives of the therapeutic treatments to be used in case of HZ include reducing the extent, the severity and duration of the infection, trying to prevent post-herpetic neuralgia and reduce any possible complications.Citation42

The therapeutic approach includes symptomatic treatments, antibiotics to treat bacterial superinfections, antiviral therapy and nerve blocks.Citation43 The guidelines highlight the importance to start antiviral therapy early, within 72 hours from symptom onset, in order to avoid loss of efficacy.Citation28

Clinical trials show that 20–30% of patients treated within 72 hours have developed post-herpetic neuralgia even so, and a Cochrane review demonstrated that use of antivirals does not prevent PHN.Citation44

PHN is very difficult to treat, though several treatments are available. Briefly, corticosteroids reduce pain intensity, but do not prevent PHN and have several undesirable effects in elderly patients; analgesics can only reduce pain in the acute phase but a limited number of studies on PHN have been performed; antidepressants reduce PHN but are associated with a number of undesirable effects that impact patient QoL; opioids reduce PHN, but are associated with undesirable effects that make them difficult to manage especially in elderly patients; antiepileptics/neuromodulators, i.e., gabapentin and pregabalin, reduce PHN, but do not improve patient Qol; topical analgesics lidocaine and capsaicin have limited efficacy.Citation5,Citation45-Citation49

Prevention: Vaccines Currently Available

The evaluation of the epidemiological impact, the frequent and debilitating complications (especially PHN), the sub-optimal treatments of complications and the costs related to the diagnosis and clinical/therapeutic management of HZ patients (also including costs related to complications and hospitalizations, as well as societal costs) are the rationale and the reason for the search of an adequate preventive measure against this relevant disease. The target of this specific intervention is to reduce the frequency and severity of HZ and related complications by stimulating cell-mediated immunity.

Over the years, varicella vaccines, especially those with a high antigen level, have resulted able to elicit a significant increase in cell-mediated immune response in immunocompetent elderly patients.Citation50-Citation54

Zoster vaccine developed by Merck, and currently available on the market, has an antigen content higher than at least 19,400 PFU (Plaque-Forming Units), i.e., at least 10 times higher than the antigen content in paediatric varicella vaccine.Citation55

High-antigen Zoster vaccine was evaluated in a wide clinical trial called “Shingles Prevention Study” (SPS). SPS was a randomized, double-blind, placebo-controlled trial performed in the United States of America (USA) to establish if vaccination with a single dose of experimental live attenuated Oka/Merck strain vaccine can reduce the incidence and/or severity of HZ and PHN in men and women ≥60 y of age with a negative history of HZ but a positive history of varicella. Overall, 38 546 subjects (19 270 vaccinated and 19 276 treated with placebo) with a mean age of 69 y were enrolled in the study. Overall data on study population showed a reduction of 51.3% in the number of HZ cases, a reduction of 66.5% in PHN cases and a reduction of the overall burden of illness (BOI) of 61.1%.Citation56

After the SPS, other trials on the efficacy and the effectiveness were performed.

The study called ZEST (Zoster Efficacy and Safety Trial) evaluated the efficacy of the vaccine against HZ in subjects aged from 50–59 y; efficacy was 70%.Citation57

Within the SPS trial, other efficacy evaluations were performed in the short-term (STPS) as well as in the long-term (LTPS) prevention study. The short-term efficacy was 40%, 60%, and 50% against HZ, PHN and HZ-induced pain, respectively.Citation58

LTPS is currently ongoing; the estimated vaccine efficacy during the sub-study follow-up period was 21% for HZ incidence, 35% for PHN incidence, and 37.3% for the impact of HZ-induced pain.Citation55

Also with regard to effectiveness, short-term and long-term trials are currently ongoing. With regard to short-term effectiveness, an efficacy study has been recently published based on data from the Kaiser Permanente Southern California (KPSC), aimed at assessing the risk of HZ in the general practice setting after vaccine administration. The results have shown an effectiveness of 55% against HZ; the reduced incidence in vaccinees was reported in all age groups, also in subjects with chronic diseases. The study showed an effectiveness of 63% against ophthalmic HZ and 65% against hospitalizations coded as HZ.Citation59

Another retrospective study on subjects enrolled in Medicare aged >60 y (average age 74 y ± 8 y) with immune-mediated diseases (i.e., rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, or ulcerative colitis) showed an effectiveness against HZ equal to 39%.Citation60

With regard to the long-term effectiveness study, a pilot phase started in May 2012 at Kaiser Permanente Northern California (KPNC) and will continue until the end of 2014; two ad interim analyses will be available at the end of 2016 and end 2020 while the final report will be available by the end of 2024.

With regard to safety and tolerability, Zoster vaccine was evaluated in large clinical trials that enrolled and vaccinated over 32 000 adults. Key trials were the Shingles Prevention Study (SPS) in subjects aged ≥60 y (SPS safety sub-study) and the Zoster Efficacy and Safety Trial (ZEST) in subjects aged 50–59 y.Citation56,Citation57 Other clinical trials and post-marketing studies followed. In the SPS, the frequency of serious adverse events, systemic adverse events and hospitalizations was low; the vaccine used did not cause or induce HZ, not even in the weeks immediately following vaccination. In the ZEST study, the most frequent adverse reactions were injection-site adverse reactions (63.9% in the vaccinated group vs. 14.4% in the placebo group), most of which were of moderate intensity.

Taken together, clinical trials show that Zoster vaccine is generally well tolerated, the most commonly reported side effects (occurring in at least 1 in 10 individuals) being reactions at the injection site (redness, swelling, pain and itching) and headache (occurring in at least 1 of 100 and less than 1 of 10 individuals); the rate of zosteriform or varicella-like rashes not localized in the injection site within 42 days postvaccination was similar in the group of vaccinated subjects and in the placebo group and no cases of secondary tranmission of the vaccine virus were reported.Citation61

The analysis of available data in the post-marketing period shows that the overall risk-benefit ratio for Zoster vaccine is favourable and supports claims on the vaccine safety; moreover, no age-related safety issues were reported.Citation62-Citation64

Indications of Use for Zoster Vaccine

In May 2006, Zoster vaccine received FDA marketing approval in the United States and then the early recommendations for its use were issued. In 2006, the vaccine was approved also by the European Medicines Agency (EMA) and it is currently on the market.Citation55

According to the Summary of Product Characteristics (SPC),Citation55 Zoster vaccine is indicated for the prevention of HZ and HZ-related Post-Herpetic Neuralgia (PHN). The vaccine is indicated for immunization of individuals 50 y of age or older and is effective and safe in subjects with a positive history of HZ.Citation65 The vaccine is not indicated for the prevention of primary varicella infection (chickenpox) and should not be used in children and adolescents.

Contraindications include:

  1. history of hypersensitivity to any of the excipients or trace residuals (e.g.,

    • Neomycin)

  2. primary and acquired immunodeficiency due to acute and chronic leukaemias; lymphoma; other conditions affecting the bone marrow or lymphatic system; immunosuppression due to HIV/AIDS; cellular immune deficiencies

  3. immunosuppressive therapy (including high-dose corticosteroids); however, it is not contraindicated for use in individuals who are receiving topical/inhaled corticosteroids or low-dose systemic corticosteroids or in patients who are receiving corticosteroids as replacement therapy

  4. active untreated tuberculosis

  5. pregnancy

Individuals should receive a single dose (0.65 ml) administered subcutaneously, preferably in the deltoid region; the need for a second dose is currently unknown. Contact with disinfectants should be avoided; it is recommended that the vaccine be administered immediately after reconstitution to minimize loss of potency. Reconstituted vaccine should be discarded if it is not used within 30 min.

With regard to interactions with other products, the vaccine can be administered concomitantly with inactivated influenza vaccine, as separate injections and at different body sites.

Zoster vaccine and 23-valent pneumococcal polysaccharide vaccine should not be given concomitantly because co-administration in clinical trials resulted in reduced immunogenicity of Zoster vaccine. No data are currently available regarding concomitant use with other vaccines; co-administration of Zoster vaccine and anti-viral medications known to be effective against VZV has not been evaluated.

EUnetHTA (European Network of Agencies or national institutions dealing with Health Technology Assessment, HTA) has recently acknowledged the clinical efficacy/effectiveness of Zoster vaccine in the population aged >50 y also highlighting a protection duration up to 10 years.Citation66

Globally, immunization with this vaccine is recommended, with or without public funding, in a number of countries:

1) in USA and Canada, it has been recommended in patients aged 60 y or older, since 2006 and 2010, respectively;

2) in Europe, vaccination is recommended and/or reimbursed:

  1. in Austria since 2007 (cohorts aged over 50 y of age)

  2. in United Kingdom (UK) (cohorts aged 70 y and catch up in cohorts aged 71 to 79 y) since 2010

  3. Germany/Saxony (cohorts aged over 50 y of age) since 2010

  4. Sweden (cohorts aged over 50 y of age) since 2010

  5. Greece (cohorts aged over 60 y at high risk) since 2011

  6. France (cohorts aged 65 to 74 y, catch up in cohorts aged 75 to 79 y) since 2013

A recent cost-efficacy study measured the impact of vaccination in subjects aged ≥65 y and in the 70–79 y age group, concluding that the vaccination is cost-effective.Citation67

In Italy, an economic evaluation study has been performed; it showed that the vaccination program against HZ and PHN is cost-effective from both the societal and third-payer perspectives in subjects aged 60–79 y.Citation68

Expert Recommendations

Herpes Zoster is a relevant public health issue. Over 95% of the adult population is seropositive to specific anti-VZV antibodies and therefore is potentially at risk of developing HZ in its lifetime.

The risk to develop HZ and PHN increases with age and 25% of adults will develop HZ in their lifetime. The risk to develop HZ seems to be related to a decline in cell-mediated immunity (CMI) against VZV virus. HZ clinical pattern and associated acute and chronic pain are debilitating and have a considerable impact on patient quality of life. Treatment options of HZ and PHN are often sub-optimal. Finally, costs for the diagnosis and clinical and therapeutical management of acute HZ, for hospitalizations, complications and societal costs are high. The epidemiological data available in Italy are scientifically robust and consistent with similar data reported in Europe and in the United States. HZ-related suffering is also aggravated by a considerable economic burden: pharmacoeconomic studies estimate an annual cost ranging from 41 to 99 billion Euro in Europe and a cost of 41 million Euro in Italy.

All above mentioned reasons represent the rationale for the prevention of this important infectious disease; the possibility to prevent this disease by means of vaccination is a very interesting perspective.

Zoster vaccine was conceived in order to increase VZV-specific immunity just like a natural case of HZ can increase immunity. Zoster vaccine has a booster effect in immunized subjects by eliciting a significant increase in CMI; this CMI increase can only be obtained by a high-potency vaccine.

The vaccine that is currently available has good immunogenicity, clinical efficacy, effectiveness and safety profiles: briefly, at least half of the cases would be avoided by vaccination with a considerable impact also in terms of reduction of disease severity and complications, mainly post-herpetic neuralgia. Moreover, pharmacoeconomic studies provide evidence of the cost-effectiveness profile of the vaccination that is already recommended, with or without public funding, in a number of countries all over the world.

Based on scientific data, the Public Health best strategy would be to offer the vaccine to the population aged 60–70 y. Aging is the main risk factor for HZ and an age-based strategy would allow to reach also subjects aged over 50 y with chronic diseases, in which the onset of HZ could cause serious complications.

The way the vaccine can be offered to the target population should include a common strategy to progressively ensure an equitable offer compatible with the available resources, being convinced that vaccination is convenient both in terms of quality of life and health economy.

This immunization shows that vaccinations in adults and in elderly people should not be considered separately from those for children and adolescents, but as a fundamental part of a preventive strategy against infectious diseases that should involve all age groups. There is a need for vaccination continuity in all age groups, considering that the increase of coverage rates in adults and elderly subjects necessarily requires an increase in the demand by the community, an optimization of organizational issues as well as a greater awareness by Healthcare Professionals.

Abbreviations:
HZ=

Herpes Zoster

PHN=

Post-Herpetic Neuralgia

VZV=

Varicella Zoster Virus

CMI=

Cell-mediated immunity

QoL=

quality of life

TIA=

Transient Ischaemic Attack

SCP=

summary of product characteristics

SPS=

Shingles Prevention Study

USA=

United States of America

BOI=

burden of illness

ZEST=

Zoster efficacy and safety trial

STPS=

short term prevention study

LTPS=

long term prevention study

KPSC=

Kaiser Permanente Southern California

KPNC=

Kaiser Permanente Northern California

EMA=

European Medicines Agency

EunetHTA=

European Network of Agencies or national institutions dealing with Health Technology Assessment

UK=

United Kingdom

Disclosure of Potential Conflicts of Interest

Giovanni Gabutti received grants from GlaxoSmithKline Biologicals SA, Sanofi Pasteur MSD, Novartis, Crucell/Janssen, and Pfizer for taking part in advisory boards, expert meetings, being a speaker or an organizer of congresses/conferences, and acting as investigator in clinical trials.

Elisabetta Franco received grants to her Institution from Sanofi Pasteur MSD and Pfizer for scientific purposes and was invited as a speaker or an organizer of congresses/conferences from GlaxoSmithKline Biologicals SA, Sanofi Pasteur MSD, Novartis, Crucell/Janssen, and Pfizer.

Paolo Bonanni received grants from GlaxoSmithKline Biologicals SA, Sanofi Pasteur MSD, Novartis, Crucell/Janssen, and Pfizer for taking part in advisory boards, expert meetings, being a speaker or an organizer of congresses/conferences, and acting as promoter of epidemiological studies partially supported by vaccine producers.

Michele Conversano received grants from GlaxoSmithKline Biologicals SA, Sanofi Pasteur MSD, Novartis, for taking part in advisory boards, expert meetings and acting as investigator in clinical trials.

Antonio Ferro received grants from GlaxoSmithKline Biologicals SA, Sanofi Pasteur MSD and Pfizer for taking part in advisory boards, expert meetings, being a speaker or an organizer of congresses/conferences, and acting as investigator in clinical trials.

Marzia Lazzari received grants from Sanofi Pasteur MSD, HPS Srl and Molteni Farmaceutici for taking part in advisory boards, expert meetings and being a speaker of congresses/conferences.

Stefania Maggi received grants from Sanofi Pasteur MSD for taking part in advisory boards and expert meetings.

Alessandro Rossi received grants from GlaxoSmithKline Biologicals SA, Sanofi Pasteur MSD for taking part in advisory boards, expert meetings, being a speaker or an organizer of congresses/conferences.

Silvestro Scotti received grants from Sanofi Pasteur MSD for taking part in advisory boards.

Francesco Vitale received grants from GlaxoSmithKline Biologicals SA, Sanofi Pasteur MSD and Pfizer for taking part in advisory boards, expert meetings, being a speaker or an organizer of congresses/conferences.

Antonio Volpi received grants from GlaxoSmithKline Biologicals SA, Sanofi Pasteur MSD, Menarini and Pfizer for taking part in advisory boards, expert meetings, being a speaker or an organizer of congresses/conferences and acting as investigator in clinical trials.

Donato Greco received consultation fee from Sanofi Pasteur MSD on Herpes Zoster vaccines and received grants for taking part in advisory boards. No other contractual contacts with vaccine producing firms.

Acknowledgements

This paper reports the technical and scientific independent opinion of the group of experts involved in the Advisory Board on Herpes Zoster, promoted by the Sanofi Pasteur MSD Medical and Scientific Department with the purpose of issuing a summary comprehensive report of all available evidence and expert opinions.

The Board would like to thank Marco Ercolani and Stefano Valente of Sanofi Pasteur MSD Medical Department for their scientific support and active cooperation.

Related Research Data

Prevention of Herpes Zoster and its complications: From clinical evidence to real life experience
Source: Informa UK Limited
The Unknown Health Burden of Herpes Zoster Hospitalizations: The Effect on Chronic Disease Course in Adult Patients ≥50 Years.
Source: MDPI AG

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