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Seven viruses cause at least 15% of the total cancer burden. Viral cancers have been described as the "low-hanging fruit" that can be potentially prevented or treated by new vaccines that would alter the course of global human cancer. Kaposi sarcoma herpesvirus (KSHV or HHV8) is the sole cause of Kaposi sarcoma, which primarily afflicts resource-poor and socially marginalized populations. This review summarizes a recent NIH-sponsored workshop's findings on the epidemiology and biology of KSHV as an overlooked but potentially vaccine-preventable infection. The unique epidemiology of this virus provides opportunities to prevent its cancers if an effective, inexpensive, and well-tolerated vaccine can be developed and delivered.

Infection with varicella zoster virus (VZV) causes varicella (chickenpox), which can be severe in immunocompromised individuals, infants and adults. Primary infection is followed by latency in ganglionic neurons. During this period, no virus particles are produced and no obvious neuronal damage occurs. Reactivation of the virus leads to virus replication, which causes zoster (shingles) in tissues innervated by the involved neurons, inflammation and cell death - a process that can lead to persistent radicular pain (postherpetic neuralgia). The pathogenesis of postherpetic neuralgia is unknown and it is difficult to treat. Furthermore, other zoster complications can develop, including myelitis, cranial nerve palsies, meningitis, stroke (vasculopathy), retinitis, and gastroenterological infections such as ulcers, pancreatitis and hepatitis. VZV is the only human herpesvirus for which highly effective vaccines are available. After varicella or vaccination, both wild-type and vaccine-type VZV establish latency, and long-term immunity to varicella develops. However, immunity does not protect against reactivation. Thus, two vaccines are used: one to prevent varicella and one to prevent zoster. In this Primer we discuss the pathogenesis, diagnosis, treatment, and prevention of VZV infections, with an emphasis on the molecular events that regulate these diseases. For an illustrated summary of this Primer, visit: http://go.nature.com/14xVI1.

Background Infants exposed to varicella zoster virus (VZV) in utero ≤5 days before or ≤48 hours after delivery and preterm infants are at high risk for varicella complications. An expanded-access program assessed varicella outcomes after administration of varicella zoster immune globulin (human) (VARIZIG) in a real-world setting. Methods In this open-label, expanded-access program, high-risk infants received ≤125 IU/10 kg of VARIZIG (NCT00338442). VZV outcomes and safety were assessed. Results There were 43 newborns exposed to VZV in utero and 80 preterm infants exposed to VZV; >80% received VARIZIG within 96 hours of reported exposure. When varicella outcomes were available, varicella occurred in 7 of 38 (18%) in utero–exposed newborns and zero of 65 preterm infants. Varicella-related complications were reported in 3 in utero–exposed newborns (3 with >100 lesions, 1 each with encephalitis and pneumonia). Adverse events were reported for 16% of in utero–exposed newborns and 25% of preterm infants, but few were considered related to VARIZIG. There were no deaths attributable to varicella or VARIZIG. Conclusions Varicella incidence and morbidity were low in in utero–exposed infants and zero in preterm infants who received prophylactic VARIZIG. There were few VARIZIG-related safety concerns. [ABSTRACT FROM AUTHOR]

Introduction: Varicella, although a frequently benign childhood disease, nevertheless represents a considerable health burden. WHO recommends including varicella vaccines in universal routine vaccination programs, and maintaining coverage >80%. Many countries have successfully introduced varicella vaccination and have benefited from lower disease burden, but many others have not adopted the vaccine. Reasons include cost commitment for a ‘mild childhood disease’ or concerns that vaccination will shift varicella to older age groups or increase herpes zoster incidence. Areas covered: This literature review summarizes the effectiveness and epidemiological impact of varicella immunization programs. Expert commentary: Varicella vaccines are immunogenic with acceptable safety profiles. One and two dose schedules are highly effective against varicella and large reductions in disease incidence, particularly moderate-severe disease, have been widely reported. There is currently no evidence to suggest that the introduction of varicella vaccination results in a shift of varicella disease burden to older age groups. Although epidemiological studies have shown an increased incidence of herpes zoster since the vaccines were launched, there are many other contributing factors, and indeed, this secular trend was evident before their introduction. In conclusion, varicella vaccination easily fits into existing immunization programs and significantly reduces the often underestimated burden of varicella. [ABSTRACT FROM PUBLISHER]

Universal immunization of young children with 1 dose of varicella vaccine was recommended in the United States in 1995, and it has significantly decreased the incidence of chickenpox. Outbreaks of varicella, however, are reported among vaccinated children. Although vaccine effectiveness has usually been ~85%, rates as low as 44% have been observed. Whether this is from primary or secondary vaccine failure— or both—is unclear. We tested serum samples from 148 healthy children immunized against varicella in New York, Tennessee, and California to determine their seroconversion rates, before and after 1 dose of Merck/Oka varicella vaccine. The median age at vaccination was 12.5 months; postvaccination serum samples were obtained on average 4 months later. Serum was tested for antibodies against varicella-zoster virus (VZV) by use of the previously validated sensitive and specific fluorescent antibody to membrane antigen (FAMA) assay. Of 148 healthy child vaccinees, 113 (76%) seroconverted, and 24% had no detectable VZV FAMA antibodies. Our data contrast with reported seroconversion rates of 86%-96% by other VZV antibody tests and suggest that many cases of varicella in immunized children are due to primary vaccine failure. A second dose of varicella vaccine is expected to increase seroconversion rates and vaccine effectiveness. [ABSTRACT FROM AUTHOR]

Varivax (varicella virus vaccine live [Oka/Merck]; Merck), a live attenuated varicella vaccine, is indicated for vaccination against varicella in appropriate individuals ⩾12 months of age. The 10-year safety profile for Varivax is described using data submitted to Merck from routine global postmarketing surveillance, combined with information from a Varicella Zoster Virus Identification Program, which uses polymerase chain reaction (PCR) analysis to identify the presence and strain of VZV in selected specimens. There were 16,683 reports worldwide voluntarily submitted to Merck, for an overall reporting rate of 3.4 reports/10,000 doses of vaccine distributed. PCR analysis of vesicular rashes that occurred within the first 2 weeks after vaccination was more likely to identify wild-type varicella-zoster virus (VZV), whereas the presence of Oka VZV was generally associated with vesicular rashes that occurred 15-42 days after vaccination. Reports of breakthrough varicella that occurred >42 days after vaccination were associated with wild-type VZV. Among 697 herpes zoster reports, PCR analysis identified Oka VZV in 57 reports and wild-type VZV in 38 reports. There were no primary neurologic adverse events associated with Oka VZV. Secondary transmission of Oka VZV from vaccine recipients with postvaccination vesicular rashes was identified in 3 susceptible household contacts. Disseminated Oka VZV was identified in 6 immunocompromised patients and 1 patient with Down syndrome. This review has shown that the vaccine is generally safe and well tolerated. [ABSTRACT FROM AUTHOR]

Context: Reports of outbreaks of varicella in highly immunized groups have increased concern about the effectiveness of varicella vaccine. Objective: To assess whether the effectiveness of varicella vaccine is affected either by time since vaccination or by age at the time of vaccination. Design: Case-control study conducted from March 1997 through June 2003. Setting: Twenty different group practices in southern Connecticut. Participants: Case subjects, identified by active surveillance of all practices, consisted of 339 eligible children 13 months or older who were clinically diagnosed as having chickenpox and who also had a polymerase chain reaction (PCR) test result that was positive for varicella-zoster virus DNA. For each case subject, 2 controls were selected, matched by both age and pediatric practice. Main Outcome Measures: The effectiveness of the vaccine, especially the effects of time since vaccination and age at the time of vaccination, adjusted for possible confounders. Results: Although the adjusted overall effectiveness of the vaccine was 87% (95% confidence interval, 81%-91%; P<.001), there was a substantial difference in the vaccine's effectiveness in the first year after vaccination (97%) and in years 2 to 8 after vaccination (84%, P = .003). The vaccine's effectiveness in year 1 was substantially lower if the vaccine was administered at younger than 15 months (73%) than if it was administered at 15 months or older (99%, P = .01), although the difference in effectiveness overall for children immunized at younger than 15 months was not statistically significantly different than for those immunized at 15 months or older (81% vs 88%, P = .17). Most cases of chickenpox in vaccinees were mild. Conclusions: Although varicella vaccine is effective, its effectiveness decreases significantly after 1 year, although most cases of breakthrough disease are mild. If administered at younger than 15 months, the vaccine's effectiveness was lower in the first yea... [ABSTRACT FROM AUTHOR]