Use of hospitalization and pharmaceutical prescribing data to compare the prevaccination burden of varicella and herpes zoster in Australia

The aims of the study were to compare the burden of varicella and herpes zoster in Australia. No national surveillance exists for varicella or herpes zoster. We used hospital morbidity data from 1993-9 and pharmaceutical prescribing data from 1995-9. In the financial year 1998/99, there were 4718 hospitalizations for zoster compared to 1991 for varicella. For varicella the mean age of patients was 15 years compared to 69 years for zoster. The mean length of stay in hospital was 4.2 days for varicella and 12.7 days for zoster. Varicella accounted for 8396 (3726 with principal diagnosis varicella) bed days compared to 26 266 (5382 with principal diagnosis of zoster) for zoster. The in-hospital case-fatality rate was 0.4% for varicella and 1% for zoster. In 1999, 59 200 community-based cases of zoster were treated with antivirals. We estimate that 157 266 cases of zoster occurred in the community in 1999, a rate of 830 per 100 000 population. Herpes zoster has a higher burden of disease than varicella, and must be a component of disease surveillance in order to determine the full impact of vaccination on the epidemiology of varicella zoster virus (VZV).     

Treatment of acute herpetic neuralgia. A case report and review of the literature

Herpes zoster (shingles) is a viral infection that results from a reactivation of a dormant varicella zoster virus. It has been estimated that more than 300,000 new cases are seen in the United States each year. Several factors influence the incidence of infection, with increasing age being the most consistent. Postherpetic neuralgia is the No. 1 cause of intractable, debilitating pain in the elderly and is the leading cause of suicide in chronic pain patients over the age of 70.     

Modelling the impact of a combined varicella and zoster vaccination programme on the epidemiology of varicella zoster virus in England

This study updates previous work on modelling the incidence of varicella and Herpes Zoster (HZ) following the introduction of childhood vaccination. The updated model includes new data on age-specific contact patterns, as well as data on the efficacy of zoster vaccination in the elderly and allows for HZ among vaccinees. The current study also looks at two-dose varicella childhood programmes, and assesses the combined impact of varicella vaccination in childhood and zoster vaccination of the elderly. The results suggest that a two-dose schedule is likely to reduce the incidence of varicella to very low levels, provided first dose coverage is around 90% and second dose coverage is in excess of 70%. Single dose varicella vaccination programmes are expected to result in large numbers of breakthrough cases. Childhood vaccination is expected to increase the incidence of zoster for more than 40 years after introduction of the programme, the magnitude of this increase being influenced primarily by the duration of boosting following exposure to the varicella zoster virus. Though this increase in zoster incidence can be partly offset by vaccination of the elderly, the effectiveness of this combined strategy is limited, as much of the increase occurs in those adults too young to be vaccinated. Childhood vaccination at intermediate levels of coverage (70% and 60% for first and second dose coverage respectively) is expected to lead to an increase in adult varicella. At high coverage (90% and 80% coverage) this is unlikely to be the case. These results will be used to inform a cost-effectiveness analysis of combined varicella and zoster vaccination programmes.     

The epidemiology of varicella-zoster virus infections: the influence of varicella on the prevalence of herpes zoster.

This paper uses mathematical models and data analysis to examine the epidemiological implications of possible immunologically mediated links between patterns of varicella and herpes-zoster incidence in human communities. A review of previously published reports does not clarify whether or not there is a relationship between the incidence of varicella and the incidence of zoster. However, new analysis of data collected by the Royal College of General Practitioners provides indirect evidence for the hypothesis that a high intensity of varicella transmission suppresses viral reactivation. The significance of this finding for proposed varicella vaccination campaigns is explored by a review of published data on the use of the vaccine. No significant difference is shown to exist between the risk of zoster caused by the vaccine and the wild virus. A mathematical model is then developed to take into consideration the influence of the prevalence of varicella on viral reactivation and the impact of vaccination with attenuated virus, which may be able to recrudesce. Under some conditions, mass application of such vaccines may have the impact of increasing zoster incidence. The results presented here indicate that, before starting any vaccination programme against varicella, its consequences need to be assessed in much more depth.     

Recurrent herpes zoster in the Shingles Prevention Study: Are second episodes caused by the same varicella-zoster virus strain?

Herpes zoster (HZ) is caused by reactivation of varicella zoster virus (VZV) that established latency in sensory and autonomic neurons during primary infection. In the Shingles Prevention Study (SPS), a large efficacy trial of live attenuated Oka/Merck zoster vaccine (ZVL), PCR-confirmed second episodes of HZ occurred in two of 660 placebo and one of 321 ZVL recipients with documented HZ during a mean follow-up of 3.13 years. An additional two ZVL recipients experienced a second episode of HZ in the Long-Term Persistence Substudy. All episodes of HZ were caused by wild-type VZV. The first and second episodes of HZ occurred in different dermatomes in each of these five participants, with contralateral recurrences in two. Time between first and second episodes ranged from 12 to 28 months.One of the five participants, who was immunocompetent on study enrollment, was immunocompromised at the onset of his first and second episodes of HZ.VZV DNA isolated from rash lesions from the first and second episodes of HZ was used to sequence the full-length VZV genomes. For the unique-sequence regions of the VZV genome, we employed target enrichment of VZV DNA, followed by deep sequencing. For the reiteration regions, we used PCR amplification and Sanger sequencing. Our analysis and comparison of the VZV genomes from the first and second episodes of HZ in each of the five participants indicate that both episodes were caused by the same VZV strain. This is consistent with the extraordinary stability of VZV during the replication phase of varicella and the subsequent establishment of latency in sensory ganglia throughout the body. Our observations also indicate that VZV is stable during the persistence of latency and the subsequent reactivation and replication that results in HZ.     

The epidemiology of varicella-zoster virus infections: a mathematical model.

Herpes-zoster is caused by the reactivation of varicella-zoster virus (VZV). In this paper different hypotheses of how this re-emergence of virus comes about are reviewed and discussed. From these hypotheses, and epidemiological data describing the initial transmission of the virus, a mathematical model of primary disease (varicella) and reactivated disease (zoster) in developed countries is derived. The steady-state age distributions of zoster cases predicted by this model are compared with the observed distribution, derived from a review and analysis of published epidemiological data. The model allows differentiation between published hypotheses in which age of host may or may not influence the probability of viral reactivation. The results indicate that the probability of reactivation must increase with age to allow the observed pattern of zoster cases. The basic mathematical model presented provides a conceptual framework, which may be extended to assess possible control programmes.     

Varicella and herpes zoster incidence prior to the introduction of systematic child vaccination in Navarre, 2005-2006

Varicella is an acute and highly contagious disease produced by the varicella-zoster virus, which leaves lasting immunity. Herpes zoster is produced by reactivation of a latent infection of the same virus. The introduction of systematic and free vaccination against varicella in children of 15 months in Navarre from 2007 onwards can be expected to produce important epidemiological changes. For this reason we describe the previous epidemiological situation in the period from 2005 to 2006. We analysed all cases of varicella and herpes zoster registered in the electronic clinical files of primary care, in the database of hospital discharges and in the mortality register. Between 2005 and 2006, 9,908 cases of varicella were diagnosed (8.29 annually per 1,000 inhabitants), with 90% in children under 15 years old. There were 80 hospital admissions (8 for every 1,000 cases), complications in 2.5 out of every 1,000 cases, and there was one death due to this cause (0.1 per 1,000 cases). In the same period, 4,959 cases of herpes zoster were diagnosed (4.15 cases per 1,000 inhabitants), half in people over 55 years old. There were 179 hospital admissions (36 per 1,000 cases), whose average age was 77, and 83 presented complications (16.7 per 1,000 cases). This epidemiological pattern is similar to that found in other places before the introduction of the vaccine.     

The incidence of varicella and herpes zoster in Massachusetts as measured by the Behavioral Risk Factor Surveillance System (BRFSS) during a period of increasing varicella vaccine coverage, 1998–2003

Background  

The authors sought to monitor the impact of widespread varicella vaccination on the epidemiology of varicella and herpes zoster. While varicella incidence would be expected to decrease, mathematical models predict an initial increase in herpes zoster incidence if re-exposure to varicella protects against reactivation of the varicella zoster virus.     

Effectiveness of antiviral treatment on acute phase of herpes zoster and development of post herpetic neuralgia: review of international publications

Herpes zoster is due to the reactivation of the virus causing varicella, called varicella-zoster virus. It affects peripheral nerves and causes painful skin and nerve lesions. This pain may last for months, or years after the initial lesions have resolved: post-herpetic neuralgia is the most frequent complication. Antiviral drugs, acting directly on the infectious agent are prescribed to reduce or block viral replication, relieve pain, and shorten symptom duration, especially for people of 50 years of age or more. However, there is currently no systematic collection of data concerning the effectiveness of antiviral drugs administered outside of clinical trials. This review evaluates the effectiveness of antiviral drugs on: (a) the intensity of pain and progression of the rash during the acute phase of herpes zoster, and (b) the frequency, intensity, and duration of post-herpetic neuralgia. During the acute phase, antiviral drugs (acyclovir, valacyclovir and famcyclovir) significantly reduce the intensity of acute pain, accelerate the healing of the vesicular rash, and reduce the duration of viral excretion. According to some authors, these drugs taken at an early stage of the disease would help to prevent the development of post herpetic neuralgia. But for others, there is no convincing evidence that antiviral drugs reduce the risk of painful complications.     

The Nature of Herpes Zoster: A Long-term Study and a New Hypothesis

Dr Hope-Simpson presents a study of all cases of herpes zoster occurring in his general practice during a sixteen-year period. The rate was 3·4 per thousand per annum, rising with age, and the distribution of lesions reflected that of the varicella rash.

It was found that severity increased with age, but that the condition did not occur in epidemics, and that there was no characteristic seasonal variation. A low prevalence of varicella was usually associated with a high incidence of zoster.

Dr Hope-Simpson suggests that herpes zoster is a spontaneous manifestation of varicella infection. Following the primary infection (chickenpox), virus becomes latent in the sensory ganglia, where it can be reactivated from time to time (herpes zoster). Herpes zoster then represents an adaptation enabling varicella virus to survive for long periods, even without a continuous supply of persons susceptible to chickenpox.

     

Zoster Meningitis in an Immunocompetent Child after COVID-19 Vaccination,California, USA

Varicella zoster virus reactivation after COVID-19 vaccination has been reported in older or immunocompromised adults. We report zoster meningitis from live-attenuated varicella vaccine reactivation in an immunocompetent child after COVID-19 vaccination. This type of case is rare; COVID-19 and varicella vaccines remain safe and effective for appropriate recipients in the pediatric population.     

Modeling the impact of one- and two-dose varicella vaccination on the epidemiology of varicella and zoster

In many countries, policymakers are being asked to make recommendations regarding the introduction of a 2-dose varicella vaccination program. The objective of this study was to examine the potential impact of 1-dose versus 2-dose varicella vaccination programs on varicella and zoster incidence, using Canada as an example. We developed a deterministic realistic age-structured model that fits 1- and 2-dose vaccine efficacy, varicella force of infection and zoster incidence. Assuming 90% coverage, the base case model (range: min; max) predicts that 1-dose vaccination will reduce varicella and zoster cases by 64% (14%; 96%) and 5% (−2%; 22%), respectively, over 80-years. Adding a second dose is predicted to reduce varicella and zoster by an additional 22% (0%; 82%) and 6% (0%; 14%), respectively. Most varicella cases prevented by the second dose are breakthrough infections. Although the incremental effectiveness of adding the second dose is highly sensitive to vaccine efficacy and mixing, predictions of the overall benefit of a 2-dose program is relatively robust to model assumptions. Adding a 2-dose program may help guarantee high population-level effectiveness against varicella. However, the incremental benefit of a second dose is highly dependant on the effectiveness of the first dose and its impact on zoster.     

Epidemiology of shingles.

One thousand and nineteen patients with acute varicella zoster viral infection were referred to the physiotherapy department for treatment between 1978 and 1986. Sixty per cent were women and 40% were men with a mean age of 58 years (range 9-96 years). The prevalence varied between 1.3 and 1.6 per 1000 per annum. The left side was affected in 52% while the right was affected in 48%. The thoracic dermatomes were the most commonly affected (56%) followed by cervical (17%), lumbar (10%), sacral (5%), and the trigeminal nerve was infected in 12%. There was a significant seasonal (P less than 0.001) variation in the prevalence of acute varicella zoster virus infection, most common in the summer and least common in the spring. There was no clustering in time and space so that it is unlikely that the varicella zoster virus is infective or that re-exposure to the virus causes reactivation of the latent virus.     

Population-based incidence of herpes zoster after introduction of a publicly funded varicella vaccination program

Background

Past varicella infection (chicken pox) may reactivate into herpes zoster (shingles). Varicella vaccination leads to a reduction in cases of varicella that may in turn increase herpes zoster rates due to reduction in the immune boosting effect of exposure to varicella zoster virus against varicella reactivation. We assessed the impact of childhood varicella vaccination in Ontario, Canada on zoster incidence and healthcare visits, and established baseline zoster rates prior to zoster vaccine introduction.

Methods

We used population-based, administrative databases to identify zoster incidence and healthcare use from April 1992 to March 2010.

Results

After routine varicella vaccination, zoster incidence rates decreased 29% for children aged 0-9 and changed minimally for other ages. Age-standardized rates of hospitalizations during the study period declined by 53%, while outpatient rates declined by 9%. The annual zoster incidence for those 60 or older was 740 per 100,000.

Conclusions

In the early post-varicella vaccination period, incidence rates of medically attended herpes zoster did not increase for the overall population and decreased moderately for children 9 years and younger, the age group targeted for varicella vaccination.     

FDA approval of an extended period for administering VariZIG for postexposure prophylaxis of varicella

VariZIG (Cangene Corporation, Winnipeg, Canada) is the only varicella zoster immune globulin preparation available in the United States for postexposure prophylaxis of varicella in persons at high risk for severe disease who lack evidence of immunity to varicella and are ineligible for varicella vaccine. VariZIG is available in the United States through an investigational new drug (IND) application expanded access protocol. VariZIG is a purified immune globulin preparation made from human plasma containing high levels of anti-varicella zoster virus antibodies (immunoglobulin G). In May 2011, the Food and Drug Administration (FDA) approved an extended period for administering VariZIG. The period after exposure to varicella zoster virus during which a patient may receive VariZIG, which had been 96 hours (4 days), is now 10 days. VariZIG should be administered as soon as possible after exposure.     

一起医务人员水痘暴发调查分析——一种少见的空气传播方式

 目的 调查分析一起医务人员医院感染水痘暴发事件,分析水痘-带状疱疹病毒医院传播的原因。方法 通过实地访谈、电话问询调查2020年10月5日—12月23日某院重症监护病房（ICU）医务人员人口统计学资料、水痘、带状疱疹相关流行病学史和疫苗接种史,并了解所有ICU住院患者水痘、带状疱疹发生情况及转归,分析其流行病学特征及传播途径。结果 2020年10月26日—12月2日,ICU共报告4例医务人员感染水痘,暴发持续时间为38 d。罹患者均为ICU护理人员,其中本科室护士2例,实习学生1例,轮转护士1例;一代病例1例,二代病例2例,三代病例1例,所有病例均否认其共同居住人员及近期生活中接触水痘或带状疱疹病例。ICU于9月28日—10月20日曾收治1例64岁老年女性带状疱疹后神经痛患者,收治时患者右腰部散在带状疱疹已结痂;首发病例曾在未佩戴手套情况下护理过该患者。在感染病例出疹前72 h使用休息室1的易感者水痘感染率为66.7%,使用休息室2的易感者均未发生感染。此次水痘暴发事件共造成直接经济损失2 725元。结论 首发病例可能是由于未佩戴手套情况下护理1例免疫功能不全的带状疱疹病例引起,续发病例可能是吸入感染病例使用休息室后呼吸道分泌物在室内形成较高浓度的病毒颗粒气溶胶引起的水痘暴发事件。     

The epidemiology of varicella and herpes zoster in The Netherlands: implications for varicella zoster virus vaccination

We studied the epidemiology of varicella (chickenpox) and herpes zoster (shingles) in The Netherlands to assess the desirability to implement routine varicella zoster virus vaccination in The Netherlands. Data on seroprevalence of varicella zoster virus in the general population (1995-1996), consultations of general practitioners for varicella (2000-2002) and herpes zoster (1998-2001) and hospital admissions due to varicella (1994-2001) and herpes zoster (1994-2001) in The Netherlands were analysed. The seropositivity increased sharply with age from 18.4% for both 0- and 1-year-olds, to 48.9%, 59.0%, 75.7% and 93.0% for 2-, 3-, 4- and 5-year-olds, respectively, and varied between 97.5% and 100% for older age groups. The average annual incidence of GP-consultations amounted to 253.5 and 325.0 per 100,000 for varicella and herpes zoster, respectively. The incidence of hospital admission due to varicella and herpes zoster was 1.3 (2.3 including side diagnosis) and 2.7 (5.8) per 100,000, respectively. Whilst for varicella, the incidence of GP-consultations and hospital admissions were highest in childhood, for herpes zoster, these were highest in elderly. Insight into epidemiology of varicella zoster is needed for the assessment of the desirability of introduction of routine varicella zoster vaccination.     

Die Varizellenimpfung in Deutschland

In 2004, a general varicella immunization was introduced in Germany for infants from the age of 11 months, followed by the subsequent recommendation in 2009 of a second vaccine dose. The vaccination is carried out at the same time as the immunization against measles, mumps, and rubella (MMR). Results of the nationwide sentinel surveillance of varicella and herpes zoster implemented by the Varicella Working Group (Arbeitsgemeinschaft Varizellen, AGV) show that the defined goals for varicella immunization (reduction of varicella-related morbidity, complications and hospitalizations) have been reached within a few years owing to the advances in vaccine coverage. Although coverage rates for varicella have not yet reached the same levels as for MMR, varicella immunization seems to have benefited from the established MMR immunization schedule. Moreover, there is no evidence for an adverse effect on the use and acceptance of the MMR vaccine. Lessons learnt in measles epidemiology (such as trends in the incidence of the disease in adolescents and infants), as well as in the history of MMR recommendations, may be useful for the evaluation of future epidemiological changes with respect to varicella and herpes zoster. In view of a rapidly waning immunity against the varicella zoster virus after vaccination with one dose and the lifelong persistence of the virus, achieving a robust and sustainable immunity in the general population seems to be an ambitious goal. However, this accomplishment will be indispensable in preventing breakthrough infections and a shift of varicella to older ages and in avoiding an increase in herpes zoster incidence.     

Specific immunoglobulin responses after varicella and herpes zoster.

The indirect immunofluorescence technique has been used to titrate the specific immunoglobulins in 200 sera from 64 patients with varicella, and 195 sera from 67 patients with herpes zoster. IgG and IgM antibodies were detected in all patients with varicella, and IgA in 59 (92%). All three classes of antibody appeared 2--5 days after the onset of the rash, increased virtually simultaneously and reached maximum titres during the second and third weeks. IgG then declined slowly, but never became undetectable and was still present in five subjects who were retested after 2--4 years; it was present in 88 out of 100 healthy young adults and probably persists indefinitely after varicella. IgA and IgM antibodies declined more rapidly and were not detected in specimens taken more than a year after the illness. IgA, however, may possibly persist in some cases since low titres were found in 8 out of 88 young adults who possessed IgG antibody and had presumably had varicella in the past. IgA responses were significantly weaker in children under the age of 6 years than in older children and adults. Six out of 67 patients with zoster were tested at various times before the onset of the rash: IgG antibody was detected in all. IgG was present in all sera taken after the onset of the rash, increased rapidly after 2--5 days, reached maximum titres during the second and third weeks and then declined slowly. IgA antibody was detected in 66 patients (99%) and IgM in 52 (78%); both types of antibody followed transient courses, as in varicella. Maximum titres of IgG and complement-fixing antibodies were greater after zoster than after varicella, but the differences were not significant. IgA and IgM titres in young adults with zoster were significantly lower than in older patients, and also lower than in young adults with varicella. Increases in varicella-zoster antibody in patients with herpes simplex virus infections consisted mainly of IgG, sometimes IgA, but never IgM.     

Effects of lymphoma on the peripheral nervous system.

Peripheral nervous system abnormalities occur in 5% of patients with lymphoma and have a wide differential diagnosis. Herpes zoster is the commonest cause. Vinca alkaloids are the only drugs used in lymphoma which commonly cause neuropathy. Compression or infiltration of nerve roots by lymphoma is a rare presenting feature but becomes more common with advanced disease. Radiation plexopathy does not usually develop until at least 6 months after irradiation and can be difficult to distinguish from neoplastic infiltration. Either multifocal infiltration of nerves or lymphoma-associated vasculitis may present as a peripheral neuropathy. The incidence of Guillain-Barré (GBS) syndrome, and possibly chronic idiopathic demyelinating polyradiculoneuropathy, appears to be increased in association with lymphoma, especially Hodgkin's disease. Subacute sensory neuronopathy and subacute lower motor neuronopathy have both been reported as paraneoplastic syndromes associated with Hodgkin's disease. Treatment of the underlying lymphoma is only rarely followed by recovery of the associated neuropathy.