VZV Foundation - A Decade Of Leadership In The Fight Against VZV Infections

	The VZV Initiative: Combating the Varicella-Zoster Virus in the United Kingdom Perception Vs. Reality Chickenpox is not simply a mild childhood illness, but a potentially serious infection whose complications result in an estimated 2,000 hospitalizations and 25 deaths in the United Kingdom each year. Shingles is not simply an annoying rash experienced by a small number of elderly persons, but is often a painful rash afflicting nearly 200,000 individuals annually in the United Kingdom, with such potential complications as post-herpetic neuralgia, long-lasting damage to the eye and stroke. Post-herpetic neuralgia, or PHN, is not simply a short-lived, slightly painful sensation, but, rather, damage to the nervous system that may cause severe pain lasting for months or even years after the shingles rash has healed. The majority of people living in the UK will be affected at some time in their lives by one or more of the diseases that are caused by the varicella-zoster virus (VZV). However, public and health professional concern in the UK over VZV infections is often limited while the incidence of cases may be increasing. The Virus That Strikes Twice The varicella-zoster virus (VZV) first strikes as chickenpox or varicella. The most common chickenpox-related complications are bacterial skin infections. However, other complications include inflammation of the brain (encephalitis) or pneumonia, although these are rare in otherwise healthy people, particularly children. Chickenpox is now preventable through vaccination. However, while childhood vaccination against chickenpox is standard in the United States, it is not accepted practice in the United Kingdom. (Further evaluation is required to assist decision making regarding any change of policy in the UK.) Following an episode of chickenpox, the varicella-zoster virus lies dormant, or asleep, in nerve tissues. However, the virus can reactivate, striking a second time as shingles or herpes zoster, an often-painful rash or blisters commonly occurring in a band on one side of the body, or clustered on one side of the face. While current estimates place the annual incidence of shingles in the United Kingdom at 200,000, its incidence is expected to increase due to the growing number of men and women in the two most susceptible population groups: individuals aged 50 and older, and those who have conditions, or are undergoing medical treatments, that weaken their immune systems. These include: HIV infection; chemotherapy or radiation therapy; corticosteroids and transplant operations. It is estimated that 10 to 20 percent of the British population—and 50 percent or more of individuals aged 85 and older—will experience shingles over their lifetime. As the incidence of shingles is rising, treatment of shingles cases may be sub-optimal. Risk factors for development of post-herpetic neuralgia (PHN), a complication of shingles, are now well understood and existing guidelines advise the use of antiviral drugs within 72 hours of rash appearance to reduce duration of PHN for patients at high risk. Cost pressures dictate rational prescription of these drugs. However, the cost of PHN is significant both in terms of personal suffering and health economy. In otherwise healthy individuals, shingles may disappear without major consequence in two to four weeks. But the risk of shingles-related complications increases with age, weakened immunity and lack of appropriate treatment. Chief among these complications is post-herpetic neuralgia, or PHN, the name given to the pain that lingers for months or even years after the shingles rash has healed. The pain of PHN may be sharp, burning, throbbing or stabbing. The skin may be exquisitely sensitive to normally painless stimuli, such as the lightest touch (as from clothing or bed sheets), to the smallest breeze, to changes in temperature (either hot or cold). Pain caused by PHN can interfere with a patient’s daily routines and quality of life, resulting in depression. PHN is remarkably resistant to treatment and may persist for months or years – even for life. Other shingles complications include damage to the eye, if shingles affects the nerves to the eye, which can result in impaired vision, or temporary or permanent blindness. In shingles patients with severely weakened immunity, infections affecting the lungs, central nervous system and brain are possible. The British Dilemma In England and Wales, VZV infections—chickenpox, shingles and PHN—are not notifiable diseases. Therefore, no case reporting is undertaken by the Communicable Disease Surveillance Centre in London (as is the situation for many other diseases in the United Kingdom). This serious limitation on data collection means that the impact on health by the varicella-zoster virus is not well understood by the government, health professionals and the public in general. Perceptions that chickenpox is benign and that shingles is a rare disease of the old ignore the impact of both conditions on patients' health and quality of life. In addition, such perceptions fail to recognise the extent to which health service resources are currently employed in the management of these conditions, especially in vulnerable patients Data on VZV is provided in Scotland via the Centre for Infection and Environmental Health, which has a national reporting system that includes VZV. However, since this is passive and not active surveillance, the data is inconclusive. In the United Kingdom, sentinel general practitioners, via the Royal College of General Practitioners, provide numbers of cases from GPs, but do not produce hospitalization or complication rates. This "soft" data is regarded as merely an indicator for epidemic proportions rather than for data analysis. Currently, there is no organization dedicated to raising awareness and fostering research of VZV infections in the UK. That task has fallen to the world’s only non-profit entity combating VZV—the VZV Research Foundation (VZVRF). Meeting The Challenge: The U.S. Origins of VZVRF In September 1989, Gladys T. Perkin began experiencing severe headaches following cataract surgery. She and her son, Richard T. Perkin, dismissed them as simply post-operative discomfort. However, the headaches became unbearable and she began complaining of unrelenting pain. A second visit to the doctor, and the appearance of the telltale blisters, resulted in a diagnosis of ophthalmic shingles. The rash disappeared, but the pain reoccurred, only this time it was much more intense. The shingles had progressed to PHN. Mrs. Perkin pleaded with her son to find a way to relieve her suffering, but, not being a doctor and lacking a firm understanding of VZV infections, he was, in essence, a powerless witness to her pain. This was about to change. In 1990, his mother’s condition worsened and, in desperation, Mr. Perkin began a full-time search for any and all information on shingles and PHN. It was a challenging search, since VZV infections are multidisciplinary. Shingles’ origins lie in chickenpox, which is pediatric. Shingles manifests itself on the skin, so it is dermatologic. It involves the nervous system, so it is neurological. It afflicts primarily older individuals, so it is geriatric. It can affect the eye, so it is ophthalmic. It is an infectious disease, so it has public health implications. The pain of acute shingles and PHN can be unrelenting, so it involves the fields of pain medicine and management, and anaesthesia. And even psychology and psychiatry become relevant when one considers the mental and emotional anguish VZV disease often inflicts. Mr. Perkin’s search for knowledge did not yield what he had hoped would be the means to end his mother’s suffering, but, rather, the means to begin an organized effort to focus worldwide attention—and, hopefully, sufficient resources—on VZV. Organization and focus was precisely what was needed in this field. In fact, Mr. Perkin was astonished to learn that, despite significant strides made by scientists worldwide, they were not unified in their efforts. Moreover, there was relatively little research being conducted, largely due to a lack of funding. And shingles and PHN were not top-of-mind among health professionals, government officials and the public, with little awareness of their widespread incidence and potential severity. Motivated by these troubling realities, and the fact that there was no single organization dedicated to VZV infections—a necessity if research and education on the virus was going to proliferate—Mr. Perkin set about trying to remedy this. With the encouragement and counsel of leading scientific and philanthropic minds—chief among them, Anne A. Gershon, M.D., professor of Pediatrics at Columbia University College of Physicians and Surgeons—Mr. Perkin established the VZV Research Foundation in the spring of 1991. The Foundation’s key objectives remain constant: to foster scientific research and to educate the public and healthcare professionals about VZV infections. A Decade of Leadership in the Fight Against VZV 2001 marked the tenth anniversary of the VZV Research Foundation, which is guided by a Board of Directors and has a Scientific Advisory Board and International Committee comprised of more than 50 of the world’s leading experts on VZV—including 14 British scientists. The Foundation is a tax-exempt, nonprofit organization under section 501(c)(3) of the U.S. Internal Revenue Code, identification number 13-3601316. The Foundation must rely on the financial support of individuals, private philanthropies and corporations to fulfill its research and education objectives. In the U.S., gifts to the Foundation are tax deductible to the full extent permitted by law. Since its inception, the VZV Research Foundation has served as an information resource for thousands of VZV sufferers and their families, and to scientific and medical professionals who study or treat the virus. Its primary activities to date include: Sponsorship of international scientific conferences, in addition to scientific symposia, workshops and roundtables at scientific meetings around the world. Provision of twelve, two-year research fellowships totaling more than $1.25 million to: investigate the reasons for the virus’ reemergence; develop new vaccines to prevent chickenpox and shingles in the immunocompromised; and seek new treatments for PHN. Establishment of the VZVRF Ganglia Bank at Columbia University College of Physicians and Surgeons, which will provide scientists with human tissue samples for their VZV studies. Organization of a scientific working group (EuroVar), comprised of European and American scientists, to study the desirability and feasibility of universal vaccination against chickenpox throughout Europe. Development of educational materials for scientists and physicians, including continuing medical education (CME) courses and publication of the proceedings of its scientific conferences. Creation of educational materials and programs for the general public, including: informational booklets; a website (www.vzvfoundation.org); a toll-free, VZV Information Line; a television and radio public service campaign; and public health forums attended by hundreds of shingles and PHN sufferers. Establishment of the VZVRF Scientific Achievement Award honoring scientists who have made important contributions to VZV research. Expanding The Fight To The UK One of the five recipients of the VZVRF Scientific Achievement Award is R. Edgar Hope-Simpson, OBE, FRCGP, a retired, general practitioner in Cirencester with no formal training in research or epidemiology. Yet, he refined the theory that shingles is caused by a reactivation of the chickenpox virus. Furthermore, he hypothesized that the increased incidence and severity of shingles in older people was the result of declining VZV immunity. On February 12, 1999, 40 eminent scientists and physicians from throughout the United Kingdom gathered in Cheltenham to pay tribute to Dr. Hope-Simpson. At that event, several British participants expressed the need for a focused effort to foster VZV research and education in the United Kingdom. Their reasons were many and varied, but they mirrored the factors that led to the Foundation’s formation in the US a decade ago, specifically: the lack of formal organization, unity and focus among scientists in VZV-related fields; the need for greater VZV research, limited by a lack of funding; and little understanding of the widespread incidence and seriousness of VZV disease among the public health and scientific ministries of government, the medical community and the public. Finally, as had been the case in the US, they noted that, in Britain, there was no single organization championing the cause of VZV research and education. Yet, now more than ever, one was needed. In response to the UK scientific community’s requests, in 2000, the Foundation asked a leading British researcher on PHN to spearhead its efforts to establish a formal presence for VZVRF in the UK. Robert W. Johnson, MB, BS, FRCA, a consultant anaesthetist at United Bristol Hospitals and senior lecturer in the University of Bristol agreed and, in turn, established an Executive Committee to help organize a UK Scientific Advisory Board. Members of this "core group" include: Barbara Bannister, MSc, FRCP, of Coppetts Wood Hospital, London; Judith Breuer, MD, FRCPath, of St. Barts and Royal London Hospitals; Nigel Higson, MA, BM, BCh, of Goodwood Court Surgery, Hove, East Sussex; Peter Kennedy, MD, PhD, DSc, of Southern General Hospital, Glasgow; Mike McKendrick, MB, BS, FRCP, of Royal Hallamshire Hospital, Sheffield; and Martin J. Wood, MA, FRCP, of Birmingham Heartlands Hospital. The UK Executive Committee met in London on June 21, 2000 to discuss the establishment of the Foundation in England. It was agreed that the very first task would be to establish a multidisciplinary Scientific Advisory Board. To that end, it was proposed that an organizational meeting be held in late 2001. Other, potential initiatives discussed at that meeting included: Adaptation of the Foundation’s patient and physician booklets for the UK. Launch of a public service and media relations campaign to generate VZV awareness. Development and execution of a major epidemiological study of chickenpox and shingles involving a significant percentage of the British population. Facilitation of United Kingdom-based research and establishment of a clinical and research data standard with the participation of the international scientific community. Creation of an internet-based digest that would survey a wide array of specialist journals for relevant articles and facilitate their summary and review. Involvement of VZVRF in the updating of existing shingles management guidelines. Mr. Perkin also discussed the need to explore the registration of VZVRF as a charitable organization in the UK, including the creation of a domestic Board of Directors. The Way Forward Following a thorough review of the aforementioned, potential initiatives for the UK, Dr. Johnson and his colleagues identified two, crucial initiatives for implementation in the short-term—the first, organizational, the second, research-driven—both of which require funding. I. Formation of a Scientific Advisory Board VZVRF convened an organizational meeting in London on April 17, 2002. Topics discussed included a pilot study on the epidemiology and burden of shingles and post-herpetic neuralgia, funding for which has been generously provided by Pfizer Inc. II. Epidemiological Study of Chickenpox and Shingles VZVRF is proposing a bold initiative that would mark the beginning of formalized tracking of VZV in the UK. Specifically, the Foundation proposes the design and execution of a major study of chickenpox and shingles in parallel over 18 months on a population of approximately 1,000,000. The study would track the burden of diseases in the UK so that there may be appropriate planning for the future healthcare and interventions necessary to reduce the impact of VZV. The UK is ideally suited to such research since chickenpox vaccination has not yet been introduced. The study would be conducted through a network of primary care practices. Its design would be such that it could be repeated at intervals of, for example, ten years, to detect changes in chickenpox and shingles following population changes with regard to age and disease and the introduction of chickenpox vaccination. VZVRF believes the data collected would be relevant and innovative, since it would enable scientists to finally determine the true incidence, and health and economic costs, of VZV infections in the UK. This study would also serve as an impetus and model for similar studies throughout Europe, and its results would significantly relate to the Foundation’s aforementioned, EuroVar working group, which is exploring the desirability and feasibility of universal chickenpox vaccination throughout Europe. Funding for a pilot study has been generously provided by Pfizer Inc. Joining The Fight Against VZV in the UK As referenced earlier, in the UK and throughout the world, the major impediment to the fight against VZV is a lack of sufficient funding. VZV researchers continue to find it difficult to compete for grants with "headliner" diseases such as AIDS, heart disease and cancer. These and other diseases merit as much research money as is available, but so, too, do VZV infections. VZVRF believes that, with a higher level of funding and a focused, interdisciplinary research effort in the UK and worldwide, scientists may finally unravel the reasons for the virus’ reemergence and develop more effective therapeutic and preventive measures for VZV infections and their complications. To that end, the VZV Research Foundation has taken the first step in establishing a formal presence in the United Kingdom. This paper represents a second step, since it serves as a formal request for support from you, as a leader in the UK philanthropic and/or corporate sectors. By providing financial support for the Foundation’s UK Scientific Advisory Board meeting, and for VZV research and education in the UK, you and your organization will be helping to pioneer an effort aimed at sparing future generations of the pain and suffering currently experienced by hundreds of thousands of individuals in the UK, and millions more worldwide. For a formal, request-for-funding proposal, or for further information about VZV infections and the work of the Foundation, please contact: VZV Research Foundation 40 East 72nd Street New York, NY 10021 USA Tel: 212-472-3181 Fax: 212-861-7033 Email: vzv@vzvfoundation.org Thank you for your consideration. The VZV Research Foundation does not practice medicine and no information in this document should be considered medical advice.