Recombination of Globally Circulating Varicella-Zoster Virus.

UNLABELLED: Varicella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpes virus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombine in vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, either in vivo or in vitro during passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade. IMPORTANCE: Although genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the present study, we demonstrate that VZV also frequently undergoes genetic recombination, including strains belonging to the clade containing the vOKA strain.

Use of oral fluid to examine the molecular epidemiology of varicella zoster virus in the United Kingdom and continental Europe.

We investigated oral fluid (OF) as an alternative to sampling of rashes for varicella zoster virus (VZV) genotyping and further characterized VZV clade prevalence in the United Kingdom and Europe. VZV was detected in up to 91% of OF specimens. Paired OF and vesicle fluid samples contained identical VZV clades. While clades 1 and 3 were the most prevalent across the United Kingdom and Europe, in Western Europe, clade 5 viruses were circulating. Viruses from the same outbreak belonged to different clades, but no clade was associated with a severe-disease phenotype. OF is suitable and convenient for large-scale molecular epidemiological studies of VZV.

Varicella vaccination in Europe: are we ready for a universal childhood programme?

Safe and effective vaccines against varicella zoster virus (VZV), the aetiological agent of varicella and shingles, have been available in Europe for the last 5-10 years. The USA has had a universal childhood vaccination policy since 1995 and this has resulted in a dramatic decrease in the incidence, morbidity and mortality related to varicella. The economic and medical burden of VZV has led to discussions regarding both the desirability and feasibility of a similar routine immunisation policy for all European children. This article examines the epidemiology of varicella in Europe and how the data emerging from the USA can be used to achieve adequate prevention of the disease. It looks into the current evidence of the health economic evaluation of universal varicella vaccination and explores the concerns surrounding such a policy, including the postulated impact on the incidence of zoster. In conclusion, the Society of Independent European Vaccination Experts (SIEVE) recommends that the immunisation of susceptible adolescents needs to be urgently implemented, in addition to the current recommendations targeting high-risk patients, their close contacts with a negative history of varicella and seronegative health-care workers. A universal policy, optimally incorporating a two-dose schedule, will be needed to finally reduce the burden of disease of varicella from a societal point of view. The SIEVE recommends the implementation of such a policy as soon as financially and practically possible.

Measles, mumps, and rubella: prevention.

INTRODUCTION: Measles virus causes an estimated 30 million infections and 770,000 deaths a year worldwide, with increased risks of neurological, respiratory, and bleeding complications in survivors. Mumps can cause neurological problems and hearing loss, orchitis with infertility, and pancreatitis. Rubella infection is usually mild, but can lead to fetal death or severe congenital abnormalities if contracted in early pregnancy. The incidence of all three infections has decreased significantly in countries with routine vaccination programmes targeted at these diseases, but decreased vaccination rates are associated with increased risks of infection. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of measles, mumps, and rubella vaccination? We searched: Medline, Embase, The Cochrane Library and other important databases up to July 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 94 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: MMR vaccine, monovalent measles vaccine, monovalent mumps vaccine, and monovalent rubella vaccine.

Measles.

PURPOSE OF REVIEW: The purpose of this review is to summarize important papers concerning measles disease and measles-containing vaccines published in 2004. RECENT FINDINGS: Endemic measles has been successfully controlled in the Americas and, to a lesser extent, in Europe. This has been achieved with a high uptake of two doses of a measles-containing vaccine. Even in industrialized countries, where vaccine uptake is poor, for example Japan, the disease is still a significant cause of morbidity and mortality. Vaccine failure is predominantly due to primary vaccine failure, which may, in part, be genetic in origin and related to HLA type. Measles-containing vaccines have been shown to be associated with febrile convulsions, but there is no strong evidence of a link with atopy. There is considerable evidence that there is no causal relationship with autistic disorders. In spite of this, many parents and some professionals have concerns about the safety of the vaccines, which may lead to their underuse. SUMMARY: It is possible to eliminate measles with a high uptake of two doses of measles-containing vaccine, but concerns about safety persist and need to be tackled. More research is required into how to do this effectively and also to elucidate the causes of vaccine failure.