Persistence of immunity to varicella in children with leukemia immunized with live attenuated varicella vaccine

To determine the safety and efficacy of varicella vaccine, we studied 437 children in remission from leukemia who were immunized with live attenuated varicella virus. Three hundred one of the patients received two doses of vaccine and 136 received a single dose of vaccine from 1 of 10 lots from two manufacturers. The patients have been followed for an average of three years (range, one to six). Seroconversion occurred in 88 percent of the 437 children after the first dose of vaccine and in 98 percent after one or two doses. The proportions of patients who were seronegative after one, three, and five years were 20, 25, and 30 percent, respectively, with little change over time in the geometric mean titers of specific antibody (6.3, 6.5, and 5.7, respectively). Chickenpox has been documented in 36 vaccinated patients (8 percent) who had 3 to 640 vesicles (mean, 100), mild illness, and no complications. Of the 83 vaccinated patients exposed to varicella within their families, 11 had chickenpox; the attack rate was 14 percent (8 percent among seropositive patients, 29 percent among seronegative patients). There was no relation between the time since vaccination and either the attack rate or the severity of the breakthrough illness. Two doses of vaccine appeared to be no more effective than a single dose. Of the 372 patients receiving maintenance chemotherapy when immunized, 149 (40 percent) had a rash, which was treated with acyclovir in 16 children (4 percent) and became a severe febrile illness in 4. These reactions were not fatal and were all associated with vaccine lots, the use of which has since been discontinued. We conclude that in children in remission from leukemia, varicella vaccine is safe and induces an immunity to chickenpox that persists for more than three years.     

A controlled trial of acyclovir for chickenpox in normal children

BACKGROUND. Chickenpox, the primary infection caused by the varicella-zoster virus, affects more than 3 million children a year in the United States. Although usually self-limited, chickenpox can cause prolonged discomfort and is associated with infrequent but serious complications. METHODS. To evaluate the effectiveness of acyclovir for the treatment of chickenpox, we conducted a multicenter, double-blind, placebo-controlled study involving 815 healthy children 2 to 12 years old who contracted chickenpox. Treatment with acyclovir was begun within the first 24 hours of rash and was administered by the oral route in a dose of 20 mg per kilogram of body weight four times daily for five days. RESULTS. The children treated with acyclovir had fewer varicella lesions than those given placebo (mean number, 294 vs 347; P less than 0.001), and a smaller proportion of them had more than 500 lesions (21 percent, as compared with 38 percent with placebo; P less than 0.001). In over 95 percent of the recipients of acyclovir no new lesions formed after day 3, whereas new lesions were forming in 20 percent of the placebo recipients on day 6 or later. The recipients of acyclovir also had accelerated progression to the crusted and healed stages, less itching, and fewer residual lesions after 28 days. In the children treated with acyclovir the duration of fever and constitutional symptoms was limited to three to four days, whereas in 20 percent of the children given placebo illness lasted more than four days. There was no significant difference between groups in the distribution of 11 disease complications (10 bacterial skin infections and 1 case of transient cerebellar ataxia). Acyclovir was well tolerated, and there was no significant difference between groups in the titers of antibodies against varicella-zoster virus. CONCLUSIONS. Acyclovir is a safe treatment that reduces the duration and severity of chickenpox in normal children when therapy is initiated during the first 24 hours of rash. Whether treatment with acyclovir can reduce the rare, serious complications of chickenpox remains uncertain.     

The incidence of zoster after immunization with live attenuated varicella vaccine. A study in children with leukemia. Varicella Vaccine Collaborative Study Group.

BACKGROUND. The Oka strain of live attenuated varicella vaccine is immunogenic and highly protective, but there has been concern about the risk of zoster after immunization. METHODS. We examined the incidence of zoster, risk factors for it, and measures of immune response in children with leukemia who received the vaccine and in appropriate controls. RESULTS. After a mean follow-up of 4.1 years, zoster was documented in 13 of the 548 vaccinated children with leukemia (2.4 percent). In a subgroup of 96 vaccinated children matched prospectively with 96 children with leukemia who had had natural varicella infections, there were 4 cases of zoster among the vaccinated children and 15 among the controls, for crude incidence rates of 0.80 and 2.46 cases per 100 person-years, respectively (P = 0.01). Of the total of 13 vaccinated children who had zoster, 11 had a skin rash due to varicella-zoster virus, either from the vaccine itself or from breakthrough varicella after household exposure in the period between immunization and the documentation of zoster. In the 268 children who had any type of rash caused by varicella-zoster virus after vaccination, as compared with those who did not have a rash, the relative risk of subsequent zoster was 5.75. For the 21 vaccinated children who received bone marrow transplants, as compared with those who did not, the relative risk of zoster was 7.5. Cell-mediated immunity as assessed by lymphocyte stimulation was lower in 4 children in whom zoster later developed than in 29 controls who had been vaccinated but who did not have zoster (mean stimulation index, 5.1 vs. 23.8; P = 0.0001). CONCLUSIONS. In children with leukemia who receive the live attenuated varicella vaccine, the subsequent incidence of zoster is lower than in children who have natural varicella infections.     

Varicella and Varicella Vaccination in South Korea

With continuing occurrence of varicella despite increasing vaccine coverage for the past 20 years, a case-based study, a case-control study, and an immunogenicity and safety study were conducted to address the impact of varicella vaccination in South Korea. Varicella patients under the age of 16 years were enrolled for the case-based study. For the case-control study, varicella patients between 12 months and 15 years of age were enrolled with one control matched for each patient. For the immunogenicity and safety study, otherwise healthy children from 12 to 24 months old were immunized with Suduvax (Green Cross, South Korea). Fluorescent antibody to membrane antigen (FAMA) varicella-zoster virus (VZV) antibody was measured before and 6 weeks after immunization. In the case-based study, the median age of the patients was 4 years. Among 152 patients between 1 and 15 years of age, 139 children received varicella vaccine and all had breakthrough infections. Clinical courses were not ameliorated in vaccinated patients, but more vaccinated patients received outpatient rather than inpatient care. In the case-control study, the adjusted overall effectiveness of varicella vaccination was 54%. In the immunogenicity and safety study, the seroconversion rate and geometric mean titer for FAMA antibody were 76.67% and 5.31. Even with increasing varicella vaccine uptake, we illustrate no upward age shift in the peak incidence, a high proportion of breakthrough disease, almost no amelioration in disease presentation by vaccination, and insufficient immunogenicity of domestic varicella vaccine. There is need to improve the varicella vaccine used in South Korea.     

Latent varicella-zoster viral DNA in human trigeminal and thoracic ganglia

BACKGROUND. Some human herpesviruses become latent in dorsal-root ganglia. Primary infection with the varicella-zoster virus causes chickenpox, followed by latency, and subsequent reactivation leading to shingles (zoster), but the frequency and distribution of latent virus have not been established. METHODS. Using the polymerase chain reaction, we performed postmortem examinations of trigeminal and thoracic ganglia of 23 subjects 33 to 88 years old who had not recently had chickenpox or shingles to identify the presence of latent varicella-zoster viral DNA. Oligonucleotide primers representing the origin of replication of the varicella-zoster virus and varicella-zoster virus gene 29 were used for amplification. RESULTS. Among the 22 subjects seropositive for the antibody to the virus, both the viral origin-of-replication and gene-29 sequences were detected in 13 of 15 subjects (87 percent) in whom trigeminal ganglia were examined and in 9 of 17 (53 percent) in whom thoracic ganglia were examined. Viral DNA was not detected in brain or mononuclear cells from the seropositive subjects. None of three thoracic ganglia from the one seronegative subject contained varicella-zoster viral DNA. CONCLUSIONS. These findings indicate that after primary infection with varicella-zoster virus (varicella), the virus becomes latent in many ganglia--more often in the trigeminal ganglia than in any thoracic ganglion--and that more than one region of the viral genome is present during latency.     

Molecular epidemiology of varicella-zoster virus in East London, England, between 1971 and 1995.

The molecular epidemiology of varicella-zoster virus in London, England, between 1971 and 1995 was examined by using two informative polymorphic markers, variable repeat region R5 and a BglI restriction site in gene 54. Viruses from 105 cases of chickenpox and 144 of zoster were typed. Two alleles of R5, A and B, were found at prevalences of 89 and 6%, respectively. No difference in allele frequency between the zoster and chickenpox cases was found, and no change in the frequencies of these alleles was observed to occur over time. By contrast, a BglI restriction site (BglI+) was found with increasing frequency over time among cases of varicella (P < 0.005) and, to a lesser extent, cases of zoster. The BglI+ polymorphism was strongly associated (P < 0.0005) with zoster in subjects who had immigrated to the United Kingdom from countries with low adult immunity to varicella (LAIV). Sixty-three percent of the subjects with zoster who had emigrated from countries with LAIV carried the BglI+ virus, in contrast to 10% of adults who had grown up in countries with high adult immunity to varicella. The significance of these data, in view of the changing epidemiology of chickenpox, is discussed.     

Varicella in Americans from NHANES III: implications for control through routine immunization

At the time of varicella vaccine introduction in the United States, an estimated 4 million episodes of varicella occurred annually. This survey of varicella seroprevalence is the first to describe immunity to a vaccine-preventable disease prior to vaccine introduction in the United States population. The objective of this analysis is to describe patterns of naturally-acquired varicella and understand characteristics associated with infection in the varicella vaccine-naive United States population. A nationally representative cross-sectional health examination survey that included venipuncture was conducted among 21,288 U.S. participants aged 6 years and older from 1988 through 1994. Serologic evidence of varicella-zoster virus infection was measured by enzyme immunoassay of varicella-zoster virus-specific IgG antibody. The seroprevalence of IgG antibody to varicella-zoster virus increased from 86.0% in children aged 6 through 11 years to 99.6% in adults aged 40 through 49 years. Immunity to varicella remained at 99% or higher in Americans aged 50 years and older. Among persons aged 6 through 19 years, non-Hispanic black children were 40% less likely to be seropositive compared with white children (odds ratio [OR], 0.6; 95% confidence interval [CI], 0.4-0.8). Among young adults aged 20 through 39 years, women with a history of live birth (OR, 4.3; 95% CI, 2.1-8.7) and married men (OR, 2.7; 95% CI, 1.2-5.7) were more likely to have naturally-acquired immunity to varicella. This study found that, prior to use of varicella vaccine in the United States, age, race, and marital characteristics were independently associated with naturally acquired varicella. Future varicella serosurveys in Americans will provide essential information to interpret the population impact of varicella vaccine.     

Different genotype pattern of varicella-zoster virus obtained from patients with varicella and zoster in Germany

The general use of the varicella vaccine requires the surveillance of varicella-zoster virus (VZV) strains in patients infected with VZV. This paper reports the data achieved from a prospective study of genotyping VZV in Germany, analyzing the restriction fragment length polymorphism (RFLP) of the open reading frames (ORF) 38, 54, and 62 as well as the polymorphism of the R5 repeat region. The study included 177 patients with varicella. Seventy-eight patients with zoster served as controls. Results revealed that 78% of VZV strains in patients with varicella had the genetic profile of the dominant wild-genotype occurring in Europe and 22% had the markers of African or Asian strains. Varicella patients with the profile of African or Asian strains were significantly younger than patients with varicella caused by the dominant genotype. By contrast, all zoster patients exhibited strains representing the majority of wild-type strains in Europe. In conclusion, VZV strains from patients with varicella have a significantly higher genetic variability than viral strains from zoster patients. Since variants with the markers of African or Asian strains could only be found in young children with chickenpox, the results suggest a changing scene of VZV genotypes in Germany. As reasons, the spread of viruses, which may be imported originally by persons immigrating from warmer climates, or the recombination between wild-and vaccine-type viruses have to be considered.     

Low induction of varicella-zoster virus-specific secretory IgA antibody after vaccination

Breakthrough after varicella vaccination occurs in approximately 2. 6% approximately 18.6% of immunocompetent children, but the reason has not been demonstrated clearly. As a first defense, specific secretory IgA antibody on the mucosa plays an important role in preventing invasion of microorganisms. To examine induction of varicella-zoster virus (VZV) specific secretory IgA after natural infection and vaccination and its booster mechanisms, 143 salivary samples were tested by ELISA. The VZV-secretory IgA values were significantly higher in the matched children after natural chickenpox than in those after vaccination, although the total secretory IgA did not differ between them. Two (7%) of the vaccinees lacked the sIgA antibody. In the elderly and in immunocompromised children, the VZV-secretory IgA values were no lower than those in healthy children, and they did not lack VZV-secretory IgA. The doctors and nurses taking care of patients with chickenpox had higher values than the other groups as did individuals who had had herpes zoster recently. VZV-secretory IgA was thought to be stimulated by exogenous and reactivated endogenous VZV to neutralize VZV with weak activity. These results suggest that low or no induction of VZV-secretory IgA antibody after vaccination may be one of the possible explanations for a breakthrough.     

Impact of Varicella Vaccine on Varicella-Zoster Virus Dynamics

Summary: The licensure and recommendation of varicella vaccine in the mid-1990s in the United States have led to dramatic declines in varicella incidence and varicella-related deaths and hospitalizations. Varicella outbreaks remain common and occur increasingly in highly vaccinated populations. Breakthrough varicella in vaccinated individuals is characteristically mild, typically with fewer lesions that frequently do not progress to a vesicular stage. As such, the laboratory diagnosis of varicella has grown increasingly important, particularly in outbreak settings. In this review the impact of varicella vaccine on varicella-zoster virus (VZV) disease, arising complications in the effective diagnosis and monitoring of VZV transmission, and the relative strengths and limitations of currently available laboratory diagnostic techniques are all addressed. Since disease symptoms often resolve in outbreak settings before suitable test specimens can be obtained, the need to develop new diagnostic approaches that rely on alternative patient samples is also discussed.     

Outbreak of chickenpox in a Union Territory of North India

Purpose: Primary infection with a varicella-zoster virus (VZV) leads to chickenpox. Though the incidence of the disease has decreased in many developed countries due to the introduction of the varicella vaccine, outbreaks continue to occur in developing countries. Materials and Methods: The present study reports an outbreak of varicella in an urbanised village in the vicinity of Chandigarh City in North India in November 2013. The outbreak was confirmed by the detection of VZV IgM antibodies in serum samples of clinically suspected patients. Vesicular fluid samples were collected from 8 patients with active lesions and tested for VZV DNA by polymerase chain reaction. Blood samples were also collected from 17 healthy controls residing in the same locality and tested for the presence of VZV IgM and IgG antibodies. Results: A total of 18 cases occurred, and the majority of them (67%) were <15 years of age. Of 17 samples collected from patients with the clinically suspected disease, 13 (76.5%) showed the presence of VZV IgM antibodies. Of the healthy controls, 6 were VZV IgM positive and 4 of them developed symptomatic disease on follow-up. VZV DNA was positive in 5/8 (62.5%) of the patients. In one patient, VZV DNA was detected in the absence of an IgM antibody response. Conclusion: The introduction of varicella vaccine in the universal immunisation programme of India may help to prevent these outbreaks; however, the cost-benefit analysis needs to be carried out before making such policies.     

Sixteen Years of Global Experience with the First Refrigerator-Stable Varicella Vaccine (Varilrix™)

Without vaccination, chickenpox (varicella) will affect almost every person in the world during their lifetime. The burden of disease due to varicella is often unrecognized. Varilrix is a varicella vaccine derived from the Oka strain of varicella virus. The vaccine, as a frozen formulation, was licensed for use in 1984 and was the first commercially available varicella vaccine. It subsequently became the first refrigerator-stable varicella vaccine; its development commenced in 1991 and it has been licensed for use since 1994. Varilrix is indicated for use in high-risk groups, potentially immunocompromised individuals, and healthy subjects in many countries. This article reviews data from extensive worldwide experience with the refrigerator-stable version of the vaccine, including information derived from its use in over 10,000 individuals participating in clinical trials investigating its immunogenicity, efficacy, effectiveness, and safety, as well as postmarketing data including its use in universal mass vaccination programs. Sixteen years of clinical and postmarketing experience with the same formulation represents the longest and most extensive experience with a refrigerator-stable varicella vaccine worldwide. Varilrix, in conjunction with the trivalent measles-mumps-rubella vaccine Priorix, has also been the basis for clinical development of the tetravalent measles-mumps-rubella-varicella vaccine (Priorix-Tetra).     

Immunity to varicella zoster virus in children with leukaemia

A total of 46% (32/70) of children with acute lymphoblastic leukaemia presenting to the Hospital for Sick Children had a past history of chickenpox. When their immunity to varicella zoster virus (VZV) was assessed, 75% (24/32) had a positive lymphocyte transformation response to VZV antigen in tissue culture while 78% (25/32) possessed IgG antibody against VZV. Therefore, at least 22% of the children were probably susceptible to infection with VZV inspite of having a history suggestive of chickenpox.Of those with a negative or uncertain history 34% had a positive lymphocyte transformation response, while 55% (21/38) had IgG antibody against VZV. Therefore, about one in two of those with a negative history to VZV had some form of immunity to VZV. Hence, regardless of their VZV infection history, children with leukaemia would need to undergo both cell mediated and humoral immunity tests before they may be considered for immunisation with the live varicella vaccine. From our studies, 34% (24/70) of our patients did not have any evidence of immunity to VZV by either test method. These would be considered for immunisation with the live varicella vaccine.     

Recombination in tissue culture between varicella-zoster virus strains

Several clinical varicella-zoster virus isolates obtained during testing of a live varicella vaccine had DNA restriction fragment patterns resembling neither vaccine nor wild-type virus [Gelb et al., J Infect. Dis. 155, 633-640, 1987]. One explanation for these isolates was recombination in vivo. To determine if such recombination is likely, two strains of varicella-zoster virus, distinguishable by restriction endonuclease fragment size differences (wild-type strain EF and the OKA vaccine strain), were grown together in tissue culture. After three passages, the mixed infection virus was plaque-purified. DNA from about 13% of the plaque-purified isolates had one or more BglI fragments found in neither parental virus. Hybridization studies showed that isolates containing one of the new BglI fragments were recombinants of the two parental strains. The BglI restriction fragment pattern of these recombinants resembled those of the unusual varicella isolates from individuals either vaccinated with the live attenuated OKA varicella vaccine and later exposed to natural varicella, or simultaneously exposed to both a recent recipient of the vaccine and natural varicella.     

Simian varicella: a model for human varicella-zoster virus infections

Simian varicella virus (SVV) causes a natural varicella-like disease in nonhuman primates. Epizootics of simian varicella occur sporadically in facilities housing Old World monkeys. SVV is antigenically and genetically related to varicella-zoster virus (VZV), the etiologic agent of varicella (chickenpox) and herpes zoster (shingles) in humans. The SVV and VZV genomes are similar in size and structure, share 70%-75% DNA homology and are co-linear with respect to gene organisation. Simian varicella is a highly contagious disease characterised by fever and vesicular skin rash and may progress to pneumonia and hepatitis. Infected monkeys may resolve the disease within 2 weeks although epizootics are sometimes associated with high morbidity and mortality. SVV, like VZV, establishes life-long latent infection, as indicated by detection of viral DNA within neural ganglia. Subsequently, SVV may reactivate to cause secondary disease and spread of the virus to susceptible monkeys. The relatedness of VZV and SVV and the similarities in the clinical symptoms and pathogenesis of human and simian varicella make SVV infection of nonhuman primates an excellent animal model to investigate VZV pathogenesis and latency, and to evaluate potential antiviral strategies.     

Relapsing hemorrhagic varicella

A15 year old boy with a past history of chickenpox in infancy was complicated by lethal varicella during the course of chemotherapy against recurrent acute myeloblastic leukemia. He had received allo-bone marrow transplantation and had overcome a graft-versus-host disease. The skin eruptions were hemorrhagic and progressive during the last 3 weeks, with numerous intranuclear inclusions histologically confirmed in the involved epidermis, hair follicles and endothe-lial cells. lmmunohistochemical and electron microscopic studies confirmed the infection of varicella-zoster virus.     

Serum immunoglobulin A antibody to varicella-zoster virus in subjects with primary varicella and herpes zoster infections and in immune subjects.

Immunoglobulin A (IgA) antibodies to varicella-zoster virus (VZV) were measured in sera from subjects with acute varicella and herpes zoster, VZV-immune subjects remote from infection, and recipients of a live attenuated varicella vaccine, using a solid-phase radioimmunoassay. Primary infection with VZV was associated with early production of IgA antibodies. Among 36 subjects with varicella tested 1 to 5 days after onset, 22 had detectable IgA, and all of the negative sera were obtained before day 3 of the varicella exanthem. VZV IgA was detected in one of three sera obtained more than 60 days after onset of the illness. Four of five sera obtained from subjects within 1 week of the onset of herpes zoster had measurable levels of IgA. Between 1 and 4 weeks after onset of zoster, all 10 subjects tested had detectable IgA to VZV. VZV IgA was detected as late as 63 days after the onset of herpes zoster. Of 10 vaccine recipients, 5 developed VZV IgA which was detected as early as 4 weeks and persisted for as long as 16 weeks after vaccination. VZV IgA was not detected in sera from 42 children who had no detectable IgG antibody to VZV. VZV IgA was found on only 3 of 23 sera from adults who had varicella more than 20 years before.     

Matched case-control study of effectiveness of live, attenuated S79 mumps virus vaccine against clinical mumps

Mumps virus infection is a potentially serious viral infection of childhood and early adulthood. In China, live, attenuated S(79) mumps virus vaccine has been licensed for pediatric use since 1990. There has been no assessment of its efficacy. Thus, the objective of this study was to determine the effectiveness of live, attenuated S(79) mumps virus vaccine against clinical mumps. Cases were selected from the China Information System for Disease Control and Prevention during September 2004 to March 2005. Each case was matched to a control by gender, age, and area of residency. In all, 469 cases and 469 controls were enrolled in the study. Vaccination information was obtained from the Children's EPI Administrative Computerized System. Vaccine effectiveness (VE) was calculated for one or two doses of S(79) vaccine, with 95% confidence intervals (CI). VE of mumps virus vaccine for one dose versus none was protection of 86.0% (95% CI, 77.2% to 91.5%) of recipients, and VE was much higher in the first 4 years than in the 5 to 12 years after vaccination. The S(79) vaccine can effectively prevent clinical mumps, and a second dose of mumps virus vaccine is necessary for the protection of children in China.     

Varicella-Zoster virus infections of the nervous system: clinical and pathologic correlates

BACKGROUND: Diseases that present with protean manifestations are the diseases most likely to pose diagnostic challenges for both clinicians and pathologists. Among the most diverse disorders caused by a single known toxic, metabolic, neoplastic, or infectious agent are the central and peripheral nervous system complications of varicella-zoster virus (VZV). METHODS: The pathologic correlates of the neurologic complications of VZV infection, as well as current methods for detecting viral infections, are discussed and presented in pictorial format for the practicing pathologist. RESULTS: Varicella-zoster virus causes chickenpox (varicella), usually in childhood; most children manifest only mild neurologic sequelae. After chickenpox resolves, the virus becomes latent in neurons of cranial and spinal ganglia of nearly all individuals. In elderly and immunocompromised individuals, the virus may reactivate to produce shingles (zoster). After zoster resolves, many elderly patients experience postherpetic neuralgia. Uncommonly, VZV can spread to large cerebral arteries to cause a spectrum of large-vessel vascular damage, ranging from vasculopathy to vasculitis, with stroke. In immunocompromised individuals, especially those with cancer or acquired immunodeficiency syndrome, deeper tissue penetration of the virus may occur (as compared with immunocompetent individuals), with resultant myelitis, small-vessel vasculopathy, ventriculitis, and meningoencephalitis. Detection of the virus in neurons, oligodendrocytes, meningeal cells, ependymal cells, or the blood vessel wall often requires a combination of morphologic, immunohistochemical, in situ hybridization, and polymerase chain reaction (PCR) methods. The PCR analysis of cerebrospinal fluid remains the mainstay for diagnosing the neurologic complications of VZV during life. CONCLUSIONS: Varicella-zoster virus infects a wide variety of cell types in the central and peripheral nervous system, explaining the diversity of clinical disorders associated with the virus.     

Effectiveness of Varicella Vaccination Program in Preventing Laboratory-Confirmed Cases in Children in Seoul,Korea

A universal one-dose varicella vaccination program was introduced in 2005 in Republic of Korea. However, the incidence of varicella in Korea has tripled over the last decade. We conducted a community based 1:1 matched case-control study to assess the effectiveness of one MAV strain-based vaccine and three Oka strain-based vaccines licensed for use in Korea. All cases were children in Seoul, Korea with varicella who were reported to the National Notifiable Disease Surveillance System in Seoul during 2013. The controls were age-matched children with mumps or scarlet fever but no history of varicella. We included 537 cases and 537 controls. The overall effectiveness of one dose of varicella vaccination was 13% (95% confidence interval [CI], −17.3–35.6). Of the four licensed varicella vaccines, only one was highly effective (88.9%; 95% CI, 52.1–97.4). The vaccine effectiveness for the other vaccines were 71.4% (95% CI, −37.5–94.1), −5% (95% CI, −61.9–31.9), and −100% (95% CI, −700–50.0). The overall effectiveness of vaccination was 75.8% (95% CI, 22.8–92.4) in the first year after vaccination and decreased thereafter; the effectiveness became −7.2% (95% CI, −130.9–59.2) in the fourth year after vaccination. Further studies are warranted to investigate reduced effectiveness of varicella vaccines in Korea.