- Deep-sequencing of distinct preparations of the live-attenuated VZV vaccine reveals a conserved core of attenuating SNPs. [JOURNAL ARTICLE]
- J Virol 2016 Jul 20.
The continued success of the live-attenuated varicella zoster virus vaccine in preventing varicella and herpes zoster is well documented, as are many of the mutations that contribute to the attenuation of the vOka virus for replication in skin. At least three different preparations of vOKa are marketed. Here, we show using deep sequencing of seven batches of vOka vaccine (including ZostaVax, VariVax, VarilRix and the Oka/Biken working seed) from three different manufacturers (VariVax, GSK and Biken) that 137 SNP mutations are present in all vaccine batches. This includes six sites at which the vaccine allele is fixed or near-fixation which we speculate are likely to be important for attenuation. We additionally show that despite differences in the vaccine populations between preparations, batch to batch variation is minimal, as is the number and frequency of mutations unique to individual batches. This suggests that the vaccine manufacturing processes are not introducing new mutations and notwithstanding the mixture of variants present, VZV live vaccines are extremely stable.The continued success of vaccinations to prevent chickenpox and shingles, combined with the extremely low incidence of adverse reactions, is testament to the quality of these vaccines. The vaccine itself is comprised of a heterogeneous live-attenuated virus population and thus requires deep sequencing technologies to explore the differences and similarities in the virus populations between different preparations and batches of the vaccines. Our data demonstrate minimal variation between batches, an important safety feature, and provide new insights into the extent of the mutations present in this attenuated virus.
- Analysis of single nucleotide polymorphism among Varicella-Zoster Virus and identification of vaccine-specific sites. [JOURNAL ARTICLE]
- Virology 2016 Jul 1.:277-286.
Varicella-zoster virus (VZV) is a causative agent for chickenpox and zoster. Live attenuated vaccines have been developed based on Oka and MAV/06 strains. In order to understand the molecular mechanisms of attenuation, complete genome sequences of vaccine and wild-type strains were compared and single nucleotide polymorphism (SNP) was analyzed. ORF22 and ORF62 contained the highest number of SNPs. The detailed analysis of the SNPs suggested 24 potential vaccine-specific sites. All the mutational events found in vaccine-specific sites were transitional, and most of them were substitution of AT to GC pair. Interestingly, 18 of the vaccine-specific sites of the vaccine strains appeared to be genetically heterogeneous. The probability of a single genome of vaccine strain to contain all 24 vaccine-type sequences was calculated to be less than 4%. The average codon adaptation index (CAI) value of the vaccine strains was significantly lower than the CAI value of the clinical strains.
- Preparing to introduce the varicella vaccine into the Italian immunisation programme: varicella-related hospitalisations in Tuscany, 2004-2012. [Journal Article]
- Euro Surveill 2016 Jun 16; 21(24)
A universal immunisation programme against varicella in the form of the measles-mumps-rubella-varicella (MMRV) vaccine for toddlers aged 13-15 months was introduced in Tuscany in July 2008. An assessment of the impact of this programme on varicella-related hospitalisations 4 years after its introduction could further support its adoption at a national level. The hospitalisation data were analysed in two periods: pre-vaccination (2004-2007) and vaccination period (2009-2012). The high coverage of the vaccines (84% in 2012) resulted in a significant decline in notifications, from 33,114 (2004-2007) to 13,184 cases (2009-2012), and also of hospitalisations, from 584 (pre-vaccination period) to 325 (vaccination period). The hospitalisation rate was 4.1 per 100,000 (95% confidence intervals (CI): 3.4-4.7) before the introduction of vaccination, which dropped to 2.2 per 100,000 (95% CI: 1.7-2.7) in the vaccination period (hospitalisation risk ratios: 0.54; 95% CI: 0.472-0.619). The reduction was most significant in the youngest age groups. The introduction of universal vaccination has already led to a significant decline in hospitalisations due to varicella after just 4 years of implementation. Hospitalisation rates fell noticeably among younger individuals involved in the vaccination programme. The decrease in hospitalisation rate in the older age groups suggests a possible indirect protection.
- [Measles and chickenpox susceptibility among immigrants]. [English Abstract, Journal Article]
- Rev Med Suisse 2016 May 4; 12(517):882-4.
Exposure of immigrants to infectious diseases in their country of origin influences their susceptibility to infections later in life. Susceptibility to certain infections may significantly differs between immigrants depending on their regions of origin. Both measles and chickenpox (varicella) are conditions for which the level of exposure in the country of origin influences the preventive measures that immigrant health providers should propose. Through these two illustrative examples, this article summarizes the practical implications for clinicians who care for immigrants originating from southern countries.
- Varicella Vaccination of Children with Leukemia without Interruption of Maintenance Therapy - A Danish Experience. [JOURNAL ARTICLE]
- Pediatr Infect Dis J 2016 Jun 10.
Varicella zoster virus (VZV) can be fatal or cause severe complications in children with acute lymphoblastic leukemia (ALL). This analysis set out to investigate the morbidity and mortality of VZV vaccination without interruption of maintenance therapy in children with ALL.Files of 73 seronegative children with ALL were examined for data regarding VZV vaccination and infection, and long-term seroconversion was measured. Criteria prior to VZV-vaccination were: 1) seronegative; 2) in complete remission; 3) age ≥ 1.0 year; 4) lymphocyte count ≥ 0.6 x 10/l at time of vaccination; and 5) receiving maintenance therapy.Forty-five children were vaccinated. No child died or experienced serious adverse events due to VZV-vaccination. Nine children developed late chickenpox despite vaccination. Long-term protection was found in 86% of children not receiving acyclovir and 78 % of the entire population. Long-term seroconversion was found in 52% of the children. There were no severe cases of varicella infection. Acyclovir prophylaxis post-vaccination was associated with an increased risk of late chickenpox (HR=5.40,[1.43; 20.41],p=0.01). In contrast, a vaccine-induced rash reduced the risk of late chickenpox (HR=0.08, [0.01; 0.66] p = 0.02). No child had interruption of maintenance therapy at the time of vaccination, but 33% experienced discontinuation of therapy due to vaccine-induced rash. Dexamethasone was associated with an increased risk of vaccine-induced rash (HR=2.9 [1.21; 6.90], p = 0.02).This analysis indicates that VZV-vaccination is feasible and justified in seronegative children with ALL, in countries where VZV-vaccination is not part of the national vaccination program.
- The burden of hospitalisation for varicella and herpes zoster in England from 2004 to 2013. [JOURNAL ARTICLE]
- J Infect 2016 Jun 7.
We aimed to determine the hospital burden of varicella-zoster virus infection (VZV) in England during 2004-2013 to support a future cost-effectiveness analysis of a childhood varicella vaccination programme.We analysed the incidence, duration, outcome and costs of hospitalisations for VZV using the Hospital Episode Statistics (HES) database for the general and immunocompetent population. Mortality in HES was validated using data from the Office for National Statistics (ONS).The average annual incidences of admissions due to varicella and herpes zoster were 7.6 (7.3-7.9) and 8.8 (8.6-9.0) per 100,000, respectively. The immunocompetent population accounted for 93% and 82% of the admissions due to varicella and herpes zoster, respectively. The average yearly number of hospital days was 10,748 (10,227-11,234) for varicella and 41,780 (40,257-43,287) for herpes zoster. The average yearly hospital costs (£2013/14) were £6.8 million (6.4-7.2) for varicella and £13.0 million (12.8-13.4) for herpes zoster. The average annual numbers of deaths identified in HES due to varicella and herpes zoster were 18.5 (14.3-22.8) and 160 (147-172), respectively. Comparison with ONS mortality data indicated a high level of uncertainty.Most of the hospital burden due to VZV-virus in England occurs in the immunocompetent population and is potentially vaccine-preventable.
- [Chickenpox and shingles: one virus, two diseases and current vaccination recommendations in Switzerland]. [English Abstract, Journal Article]
- Ther Umsch 2016; 73(5):247-52.
Adults, pregnant women, premature babies and immunocompromised persons are at increased risk for varicella complications. Therefore the current Swiss vaccination recommendations against varicella include a general recommendation for 11 to 15 year old adolescents with a negative varicella history, as well as a specific recommendation for risk groups. The goal of both recommendations is to reduce varicella complications in persons most at risk. The vaccine is not universally recommended for all toddlers in Switzerland, while this is the case in some countries such as the United States. Pros and cons of different vaccination strategies, as well as possible short- and long-term effects on herpes zoster incidence are taken into account. In the United States, there was a marked decline in incidence and hospitalisations, but an increased herpes zoster incidence in the short term. Finally, public health aspects of herpes zoster, post-herpetic neuralgia and possible vaccination strategies are outlined.
- [Varicella Zoster infections in adults: beyond shingles?]. [English Abstract, Journal Article, Review]
- Rev Med Suisse 2016 Apr 13; 12(514):738-43.
Chickenpox is a generally benign condition during childhood, but it can cause severe complications when affecting teenage or adult patients. Immunodeficiency and pregnancy are risk factors for disseminated disease with pulmonary, neurological and/or hepatic involvement. Reinfection may be more frequent than previously thought, and management is identical to that of primary infection. The most common manifestation of viral reactivation is shingles, but it can also cause meningitis and vasculopathy, as well as disseminated herpes zoster in the immunocompromised patient. In this article, we will review the clinical manifestations and management of VZV infection in adults.
- The Role of Childhood Infections and Immunizations on Childhood Rhabdomyosarcoma: A Report From the Children's Oncology Group. [Journal Article]
- Pediatr Blood Cancer 2016 Sep; 63(9):1557-62.
Rhabdomyosarcoma (RMS) is a rare, highly malignant tumor arising from primitive mesenchymal cells that differentiate into skeletal muscle. Relatively little is known about RMS susceptibility. Based on growing evidence regarding the role of early immunologic challenges on RMS development, we evaluated the role of infections and immunizations on this clinically significant pediatric malignancy.RMS cases (n = 322) were enrolled from the third trial coordinated by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n = 322) were pair matched to cases on race, sex, and age. The following immunizations were assessed: diphtheria, pertussis, and tetanus (DPT); measles, mumps, and rubella; and oral polio vaccine. We also evaluated if immunizations were complete versus incomplete. We examined selected infections including chickenpox, mumps, pneumonia, scarlet fever, rubella, rubeola, pertussis, mononucleosis, and lung infections. Conditional logistic regression models were used to calculate an odds ratio (OR) and 95% confidence interval (CI) for each exposure, adjusted for maternal education and total annual income.Incomplete immunization schedules (OR = 5.30, 95% CI: 2.47-11.33) and incomplete DPT immunization (OR = 1.56, 95% CI: 1.06-2.29) were positively associated with childhood RMS. However, infections did not appear to be associated with childhood RMS.This is the largest study of RMS to date demonstrating a possible protective effect of immunizations against the development of childhood RMS. Further studies are needed to validate our findings. Our findings add to the growing body of literature, suggesting a protective role of routine vaccinations in childhood cancer and specifically in childhood RMS.
- Herpes zoster and the search for an effective vaccine. [REVIEW, JOURNAL ARTICLE]
- Clin Exp Immunol 2016 May 10.
Primary infection with varicella zoster virus (VZV), an exclusively human neurotrophic alphaherpsesvirus, results in varicella, known more commonly as chickenpox. Like other alphaherpesviruses, VZV establishes latency in the sensory ganglia and can reactivate to cause herpes zoster (also known as shingles), a painful and debilitating disease, especially in elderly and immunocompromised individuals. The overall incidence of herpes zoster in Europe and the United States is three per 1000 people, but increases sharply after 60 years of age to 10 per 1000 people. Zostavax(®) is a vaccine approved by the Federal Drug Administration for the prevention of herpes zoster. Unfortunately, this vaccine reduces the incidence of disease by only 51% and the incidence of post-herpetic neuralgia by 66·5% when administered to those aged 60 and older. Moreover, it is contraindicated for individuals who are immunocompromised or receiving immunosuppressant treatments, although they are at higher risk for herpes zoster compared to immune-competent older individuals. This paper reviews VZV pathogenesis, host responses and current vaccines available to prevent herpes zoster.