Original Article
The Effectiveness of the Varicella Vaccine in Clinical Practice
N Engl J Med 2001; 344:955-960March 29, 2001
- Abstract
Background
A live attenuated varicella vaccine was approved for use in the United States in March 1995 and is recommended for all susceptible persons 12 months of age or older.
Methods
To assess the effectiveness of the varicella vaccine, we conducted a case–control study with two controls per child with chickenpox, matched according to both age and pediatric practice. Children with potential cases of chickenpox were identified by active surveillance of pediatric practices in the New Haven, Connecticut, area. Research assistants visited the children on day 3, 4, or 5 of the illness, assessed the severity of the illness, and collected samples from lesions to test for varicella–zoster virus by the polymerase chain reaction (PCR).
Results
From March 1997 through November 2000, data collection was completed for 330 potential cases, of which 243 (74 percent) were in children who had positive PCR tests for varicella–zoster virus. Of the 56 vaccinated children with chickenpox, 86 percent had mild disease, whereas only 48 percent of the 187 unvaccinated children with chickenpox had mild disease (P<0.001). Among the 202 children with PCR-confirmed varicella–zoster virus and their 389 matched controls, 23 percent of the children with chickenpox and 61 percent of the matched controls had received the vaccine (vaccine effectiveness, 85 percent; 95 percent confidence interval, 78 to 90 percent; P<0.001). Against moderately severe and severe disease the vaccine was 97 percent effective (95 percent confidence interval, 93 to 99 percent). The effectiveness of the vaccine was virtually unchanged (87 percent) after adjustment for potential confounders by means of conditional logistic regression.
Conclusions
Varicella vaccine is highly effective as used in clinical practice.
Media in This Article
Table 1
Scale Used to Assess the Severity of Illness.Table 2
Comparison of the Results of PCR and Direct Fluorescent-Antibody Assay for 277 Suspected Cases of Chickenpox.Article Activity
- Article
A varicella vaccine containing live attenuated virus (Oka strain) was developed in Japan in the early 1970s.1 In the United States, the vaccine was approved by the Food and Drug Administration in 1995 and is recommended for persons 12 months of age or older who are susceptible to chickenpox.2
There have been numerous questions about both the use and the effectiveness of varicella vaccine.3 The efficacy of a vaccine as it is used in clinical practice may be different from its efficacy in a clinical trial.4 Much of the evidence on which the licensure of varicella vaccine was based came from a clinical trial that assessed a vaccine with a substantially higher concentration of virus (17,000 plaque-forming units per dose) than is contained in the licensed vaccine (3000 to 9000 plaque-forming units per dose).5 Furthermore, the live attenuated virus is thermolabile, so the vaccine must be kept frozen and its concentration of virus diminishes over time. The duration of effectiveness is a critical issue, yet the clinical trials conducted in normal children assessed the effectiveness of the vaccine for only two years after immunization (or for three years in immunocompromised children).6-8 Longer-term follow-up studies in vaccinated persons have been reported.9,10 The protective concentrations of antibody among vaccinated persons in Japan have persisted for more than 20 years after immunization,11 but this persistence may be due in part to a booster effect from exposure to persons with chickenpox in a country where the vaccine is not used widely12 and where the incidence of chickenpox remains high. We are conducting an ongoing case–control study to assess the effectiveness of the vaccine as it is used in actual practice in the United States.
Methods
Eligibility Requirements
Subjects were healthy children between 13 months and 16 years of age. Children for whom the vaccine is not routinely recommended — those who were immunocompromised because of an underlying illness (e.g., leukemia) or medications (e.g., prednisone) — were excluded. Children with a history of chickenpox were excluded, since varicella vaccine is not recommended for such children.
Children who had received the vaccine within the preceding four weeks were excluded from the study, since it takes two to four weeks for antibodies to develop and about 7 percent of vaccinated persons have a vaccine-associated rash (characterized by a mild exanthem of 6 to 10 lesions that lasts for two to three days) in the first month after vaccination.2 We were interested in assessing the effectiveness of the vaccine against chickenpox and did not wish to include as children with chickenpox children who merely had minor side effects of the vaccine. Similarly, if chickenpox had been incubating at the time of vaccination, disease would have developed within four weeks.
The study was approved by the Human Investigations Committee at Yale University School of Medicine.
Identification, Evaluation, and Classification of Potential Cases
The case group consisted of children in whom chickenpox was suspected who received medical care at the 15 participating pediatric practices in greater New Haven, Connecticut. Potential cases were identified by means of active surveillance. Investigators were notified of all potential cases, regardless of severity, including many cases in children whose illness was managed over the telephone without being evaluated in person by a clinician.
The parents of eligible children were invited to participate in the study, and written informed consent was obtained from a parent, as well as oral consent from the child, when appropriate. A research assistant (who was unaware of the vaccination status of the child) visited the home of each patient with possible chickenpox (ideally on day 3 of the illness, but as late as day 5 when necessary). A parent was interviewed, and the severity of the illness was assessed according to a modified version of a scale used in earlier clinical trials (Table 1Table 1
Scale Used to Assess the Severity of Illness.).7 In addition, a lesion was unroofed with use of a nonheparinized capillary tube in which vesicular fluid was collected to test for the presence of varicella–zoster virus by the polymerase chain reaction (PCR). The base of the lesion was rubbed with a cotton-tipped swab, which was then rubbed on a slide for testing with a direct fluorescent-antibody assay. Material from the swab was analyzed by PCR if vesicular fluid was not available.
A PCR assay specific for varicella–zoster virus was used to detect the virus and to differentiate the strain contained in the vaccine from wild-type strains.13 In addition, to assess the adequacy of the specimen (since varicella–zoster virus is found in association with cells), all samples that were negative for varicella–zoster virus were tested for a 268-bp region of the β-globin gene that is present in all human cells; a positive result indicated the presence of cellular material in the specimen.13
The investigators who performed the PCR and direct fluorescent-antibody tests and interpreted the results were unaware of each child's vaccination status. The PCR assay was considered positive if the specimen was positive for varicella–zoster virus DNA and all negative controls in the batch were negative. It was considered negative if the specimen was negative for varicella–zoster virus DNA, all positive controls in the batch were positive, and the specimen was positive for β-globin (indicating the presence of amplifiable DNA). The result was considered indeterminate if the specimen was negative for both varicella–zoster virus DNA and β-globin. The results of the direct fluorescent-antibody assay were interpreted as recommended by the manufacturer (Merifluor varicella–zoster virus, Meridian Diagnostics, Cincinnati): specimens with two or more epithelial cells in the smear that exhibited typical apple-green fluorescence were considered positive for varicella–zoster virus. Specimens that were negative but that had less than one cell per high-power (×400) field were considered to be inadequate specimens. Specimens with an adequate number of cells but with fewer than two cells that exhibited immunofluorescence were considered negative. Potential cases of chickenpox were classified on the basis of the PCR results.
Selection of Controls
For each child with a potential case of chickenpox, two controls, matched according to date of birth (within one month) and pediatric practice, were selected. A list of potential controls was generated from the computerized data base of the practice; it consisted of all patients in the practice born between 30 days before and 30 days after the birth of the child with the potential case of chickenpox. A table of random numbers was used to select the order in which potential controls and their parents were contacted, screened for eligibility, and if eligible, invited to enroll in the study.
Collection of Data and Ascertainment of Vaccinations
The medical records of all the children (from all sources of care) were reviewed to obtain information about all previous immunizations. Children for whom there was written documentation that they had received varicella vaccine four weeks or more before the “focal time” — the date of onset of chickenpox or, for the controls, the date of onset in the matched children with chickenpox — were classified as vaccinated. As per current recommendations, children with potential cases of chickenpox and their matched controls who were 13 years of age or older were considered to have been vaccinated if they had received two doses of vaccine at least four weeks before the focal time.
Statistical Analysis
Matched odds ratios for vaccination, with both their associated P values (assessed with the Mantel–Haenszel chi-square test for matched data) and 95 percent confidence intervals, were calculated with the use of True Epistat and SPSS statistical software.14-16 The effectiveness of the vaccine was calculated as 1 minus the matched odds ratio. These estimates were adjusted for the effects of possible confounders with the use of conditional logistic regression.17 The statistical significance of differences among unmatched dichotomous and continuous variables was determined by the Pearson chi-square test and Student's t-test, respectively.15 All P values are two-sided.
To assess whether bias in the selection of controls might have affected the results, we compared the proportion of children with chickenpox who had received the measles, mumps, and rubella (MMR) vaccine with the proportion of controls who had received it. Since the MMR vaccine should have been administered at about the same age as the varicella vaccine and the MMR vaccine should have had no effect on the risk of chickenpox, we expected that there would be no significant difference between the proportion of children with chickenpox and the proportion of controls who had received the MMR vaccine. If there were a significant difference, it would suggest that there had been selection bias (e.g., bias due to differential use of medical care).
We also assessed the effectiveness of the vaccine among the children with potential cases of chickenpox whose PCR test results were either negative for varicella–zoster virus or indeterminate, since the vaccine should not be effective for these patients. To provide additional information to support the accuracy of the classification of potential cases according to the results of the PCR test, parents were called at least 1 month after enrollment and asked whether they knew of anyone in whom chickenpox had developed between 10 and 21 days after having had close contact with the child with a potential case of chickenpox.
Results
Between March 1997 and November 2000, 461 children with suspected cases of chickenpox were identified. Of these, 118 were excluded: a sample from a skin lesion could not be obtained from 10 children; 13 children were identified more than five days after the onset of the rash; 19 had been vaccinated less than four weeks before the onset of the illness; 24 could not be contacted; and 52 children or their parents declined to participate. In addition, complete data were not available for 13 children with potential cases of chickenpox. We enrolled 500 matched controls. Another 675 potential controls were not eligible because they had had chickenpox before the focal time; we were unable to reach the parents of 526 potential controls; and 33 whom we did reach declined to participate.
There were 330 children with potential cases of chickenpox for whom complete data were available. Of these, only 35 percent were seen by a nurse-practitioner or physician. The diagnosis was made over the telephone for the other 65 percent. The results of the PCR tests and the direct fluorescent-antibody assays for the suspected cases of chickenpox are shown in Table 2Table 2
Comparison of the Results of PCR and Direct Fluorescent-Antibody Assay for 277 Suspected Cases of Chickenpox. (the first 53 potential cases were not included in this comparison because the research assistants were learning the proper techniques for obtaining the samples and preparing the slides for the direct fluorescent-antibody assays). Clinically useful results (either positive or negative) were obtained more frequently with the PCR test (258 of 277 [93 percent]) than with the direct fluorescent-antibody assay (203 of 277 [73 percent], P<0.001). The first 100 samples with positive results on the PCR test and the samples from all vaccinated children with chickenpox and a positive PCR result were analyzed to determine the type of varicella–zoster virus. All were wild-type virus.Overall, the PCR test was positive in 243 of the 330 children with potential cases of chickenpox (74 percent). Characteristics of these 243 children are shown in Table 3Table 3
Characteristics of All Children with PCR-Positive Cases of Chickenpox.. The illness was substantially less severe among the children who had received the varicella vaccine. Children with chickenpox who had not received the vaccine were more likely to have a fever and to be treated with an antipyretic (usually acetaminophen).Complete data were available for one or both of the matched controls for 202 of the 243 children with positive results on PCR; estimation of the effectiveness of the varicella vaccine was based on these 202 cases and their 389 controls (Table 4Table 4
Characteristics of Children with Chickenpox and Controls.). The children with chickenpox were substantially less likely than the controls to have received the varicella vaccine (23 percent vs. 61 percent), but there was no difference in the proportions that had received the MMR vaccine (100 percent in both groups). The overall effectiveness of the varicella vaccine is shown in Table 5Table 5
Effectiveness of the Vaccine.. The vaccine was 85 percent effective (95 percent confidence interval, 78 to 90 percent; P<0.001). The vaccine was 97 percent effective (95 percent confidence interval; 93 to 99 percent; P<0.001) against moderately severe and severe disease. The vaccine's effectiveness for children younger than 5 years of age was 79 percent (95 percent confidence interval, 61 to 89 percent; P<0.001); for children 5 to 10 years of age, it was 89 percent (95 percent confidence interval, 80 to 94 percent; P<0.001); and for children older than 10 years of age, it was 92 percent (95 percent confidence interval, 45 to 99 percent; P=0.03).Information about one or two matched controls was available for 40 children with suspected cases of chickenpox whose PCR result was negative and for 19 of those whose PCR result was indeterminate. Among the groups containing a child with chickenpox-like illness but negative PCR results, 29 of 40 children with the suspected cases (72 percent) and 48 of their 74 matched controls (65 percent) had received the varicella vaccine (P=0.53); among the groups containing a child with chickenpox-like illness and indeterminate PCR results, 14 of 19 children with the suspected cases (74 percent) and 23 of their 37 matched controls (62 percent) had received the varicella vaccine (P=0.55). Thus, the vaccine was not effective in preventing illness associated with either negative or indeterminate results on a PCR assay for varicella–zoster virus.
According to the available reports of the parents, chickenpox developed within 10 to 21 days in at least one person who had had close contact with a child with chickenpox-like illness in 30 percent (58 of 195) of the PCR-positive cases (including 7 of 43 PCR-positive cases in vaccinated children). By contrast, no parents of any of the 71 children with chickenpox-like illness and negative or indeterminate results on PCR reported any contacts in whom varicella subsequently developed (P<0.001). Similarly, children with chickenpox-like illness and positive results on PCR were more likely to have had known exposure to someone with chickenpox (187 of 243 [77 percent]) than were children with chickenpox-like illness whose PCR result was either negative or indeterminate (22 of 87 [25 percent]; odds ratio, 9.9; P<0.001).
Discussion
These results indicate that the effectiveness of the varicella vaccine as it is used in actual practice is excellent, at least in the short term. Virtually all the vaccinated children in whom chickenpox subsequently developed (all of whom were infected with wild-type virus) had very mild disease. These findings are consistent with those of a study by the Centers for Disease Control and Prevention that show a marked decline in the incidence of chickenpox in areas where the vaccine is widely used,18 as well as with reports of the effectiveness of the vaccine after outbreaks in day-care centers.19-21
It may be too soon to assess the duration of vaccine-induced immunity to chickenpox. Varicella–zoster virus is still circulating in the population, so boosting of vaccine-induced immunity may still occur commonly. However, as the incidence of chickenpox declines, such natural boosting of immunity will become increasingly rare. Because ours is an ongoing study, we expect that, over time, we will be able to detect any waning of immunity that occurs.
By the PCR test, 19 percent of the samples from children in whom chickenpox was suspected were negative and nearly 7 percent had indeterminate results. The hypothesis that these samples were from children who did not truly have chickenpox is supported by the fact that a substantially lower proportion of these children than of the children with PCR-positive cases had had recent exposure to someone with chickenpox. Similarly, none of these children had contacts in whom chickenpox developed within 10 to 21 days of their illnesses (as compared with 30 percent of the children with PCR-positive cases). Most children (65 percent) in whom chickenpox was suspected were given the diagnosis over the telephone and were never seen by a clinician. This information has important public health implications because if these children had not participated in the study, some of them would be believed erroneously to have a history of chickenpox and so would not be given the varicella vaccine even though they remain susceptible to chickenpox.
Because case–control studies like ours are observational rather than experimental, they are especially susceptible to bias. We found that although a much higher proportion of controls than of children with chickenpox had received the varicella vaccine, all the children in the study had received the MMR vaccine, suggesting that selection bias related to the likelihood of vaccination was not an important factor in the study. Far fewer children with PCR-positive cases of chickenpox than their matched controls had received the varicella vaccine. If this difference (which resulted in an estimate of vaccine effectiveness of 85 percent) were due to bias, a similar difference should also have been observed between the children with cases that were negative or indeterminate by PCR and their matched controls. Such a difference would have indicated that the vaccine was also effective against illnesses associated with negative and indeterminate results on a PCR assay for varicella–zoster virus. However, as expected, the vaccine was not effective against these illnesses.
There was some risk that matching according to pediatric practice might bias the results toward the null hypothesis because of overmatching. However, the effectiveness that we found, as well as the substantial variation in the proportion of controls from each practice who had been vaccinated, suggests that possible overmatching did not have a substantial effect.
In summary, the effectiveness of the vaccine was excellent. The great majority of breakthrough cases of chickenpox among vaccinated children were mild. We conclude that, thus far, the varicella vaccine, as it is used in clinical practice, is highly effective.
Supported by a Robert Wood Johnson Foundation Minority Medical Faculty Development Award (to Dr. Vázquez), by grants from the National Institutes of Health (RO1-AI41608, RO1-AI24021, and K24-AI01703), and by a grant to the Yale Children's Clinical Research Center from the General Clinical Research Centers Program of the National Center for Research Resources (MO1-RR06022).
We are indebted to Nancy Holabird, Amy Margolis, and Valerie Parcells for obtaining the data; to Dr. John Leventhal for his critique of the manuscript; and to the practitioners who participated in the study and allowed their patients to participate in it: P. Alvino, F. Anderson, R. Anderson, R. Angoff, B. Balch, G. Bogacki, E. Borsuk, K. Bradford, M. Brochin, N. Brown, C. Butler, C. Canny, M. Carjulo, J. Carlson, J. Cooley-Jacobs, N. Czarkowski, P. Davis, M. Dillaway, C. Dorfman, R. Dorr, G. Draper, D. Durante, O. Ehrlich, T. Etkin, D. Fahey, K. Fearn, B. Freeman, M. Gad, J. Geiger, V. Gerdon, G. Germain, B. Giserman, L. Glassman, E. Gleich, L. Gould, R. Halperin, J. Harper, J. Harwin, A. Hoefer, F. Holmes, J. Hoogstra, C. Keana, K. Kennedy, K. Krieser, E. Lawrence, R. Lebovitz, D. Listman, M.C. Longo, A. Lustbader, C. Mann, F. McKee, A. Meyers, J. Morgan, J. Murphy, P. Murtagh, R. Nolfo, B. Parker, S. Perkins, A. Polletta, M. Porter, D.E. Rana, E. Rice, M. Robert, T. Rose, P. Ryan-Krause, M. Sanyal, R. Seligson, L. Semeraro, E. Smith, E. Springhorn, J. Stein, D. Sullivan, C. Summers, D. Torres, L. Waldman, M. Wakeman, G. Wanerka, C. Wechsler, R. Whelan, E. Wiesner, and J. Zelson.
Source Information
From the Departments of Pediatrics (M.V., E.D.S.) and Epidemiology and Public Health (E.D.S.) and the Children's Clinical Research Center (E.D.S.), Yale University School of Medicine, New Haven, Conn.; and the Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York (P.S.L., A.A.G., K.F., S.P.S.).
Address reprint requests to Dr. Shapiro at the Department of Pediatrics, Yale University School of Medicine, P.O. Box 208064, New Haven, CT 06520-8064.
- References
References
1
Takahashi M ,Otsuka T ,Okuno Y ,Asano Y ,Yazaki T . Live vaccine used to prevent the spread of varicella in children in hospital. Lancet 1974;2:1288-1290
CrossRef | Web of Science | Medline2
Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1996;45:1-36
Medline3
Schaffer SJ ,Bruno S . Varicella immunization practices and the factors that influence them. Arch Pediatr Adolesc Med 1999;153:357-362
Web of Science | Medline4
Clemens JD ,Shapiro ED . Resolving the pneumococcal vaccine controversy: are there alternatives to randomized clinical trials? Rev Infect Dis 1984;6:589-600
CrossRef | Medline5
Weibel RE ,Neff BJ ,Kuter BJ , et al. Live attenuated varicella virusvaccine: efficacy trial in healthy children. N Engl J Med 1984;310:1409-1415
Full Text | Web of Science | Medline6
Weibel RE ,Kuter BJ ,Neff BJ , et al. Live Oka/Merck varicella vaccine in healthy children: further clinical and laboratory assessment. JAMA 1985;245:2435-2439
CrossRef | Web of Science7
Gershon AA ,Steinberg SP ,Gelb L , et al. Live attenuated varicella vaccine: efficacy for children with leukemia in remission. JAMA 1984;252:355-362
CrossRef | Web of Science | Medline8
Johnson CE ,Stancin T ,Fattlar D ,Rome LP ,Kumar ML . A long-term prospective study of varicella vaccine in healthy children. Pediatrics 1997;100:761-766
CrossRef | Web of Science | Medline9
Kuter BJ ,Weibel RE ,Guess HA , et al. Oka/Merck varicella vaccine in healthy children: final report of a 2-year efficacy study and 7-year follow-up studies. Vaccine 1991;9:643-647
CrossRef | Web of Science | Medline10
Clements DA ,Armstrong CB ,Ursano AM ,Moggio MM ,Walter EB ,Wilfert CM . Over five-year follow-up of Oka/Merck varicella vaccine recipients in 465 infants and adolescents. Pediatr Infect Dis J 1995;14:874-879
CrossRef | Web of Science | Medline11
Asano Y ,Suga S ,Yoshikawa T , et al. Experience and reason: twenty-year follow-up of protective immunity of the Oka strain live varicella vaccine. Pediatrics 1994;94:524-526
Web of Science | Medline12
Asano Y . Varicella vaccine: the Japanese experience. J Infect Dis 1996;174:Suppl 3:S310-S313
CrossRef | Web of Science | Medline13
LaRussa P ,Lungu O ,Hardy I ,Gershon A ,Steinberg SP ,Silverstein S . Restriction fragment length polymorphism of polymerase chain reaction products from vaccine and wild-type varicella-zoster virus isolates. J Virol 1992;66:1016-1020
Web of Science | Medline14
Gustafson TL. TRUE EPISTAT manual. 5th ed. Richardson, Tex.: Epistat Services, 1994.
15
Selvin S. Statistical analysis of epidemiologic data. 2nd ed. Vol. 25 of Monographs in epidemiology and biostatistics. New York: Oxford University Press, 1996.
16
SPSS for Windows, release 10.0: user's guide. Chicago: SPSS, 1999.
17
EGRET for Windows: software for the analysis of biomedical and epidemiological studies: user manual. Cambridge, Mass.: Cytel Software, 1999.
18
Seward J ,Peterson C ,Mascola L , et al. Decline in varicella disease: evidence of vaccine impact. Pediatr Res 2000;47:Suppl:276A-276A abstract.
Web of Science19
Izurieta HS ,Strebel PM ,Blake P . Postlicensure effectiveness of varicella vaccine during an outbreak in a child care center. JAMA 1997;278:1495-1499
CrossRef | Web of Science | Medline20
Buchholz U ,Moolenaar R ,Peterson C ,Mascola L . Varicella outbreaks after vaccine licensure: should they make you chicken? Pediatrics 1999;104:561-563
CrossRef | Web of Science | Medline21
Clements DA ,Moreira SP ,Coplan PM ,Bland CL ,Walter EB . Postlicensure study of varicella vaccine effectiveness in a day-care setting. Pediatr Infect Dis J 1999;18:1047-1050
CrossRef | Web of Science | Medline
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1
A. A. Gershon. (2011) The History and Mystery of VZV in Saliva. Journal of Infectious Diseases 204:6, 815-816
CrossRef2
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Wen-Chan Huang, Li-Min Huang, I-Shou Chang, Fang-Yu Tsai, Luan-Yin Chang. (2011) Varicella breakthrough infection and vaccine effectiveness in Taiwan. Vaccine 29:15, 2756-2760
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CrossRef6
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CrossRef7
Anne A. Gershon. 2011. Chickenpox, Measles, and Mumps. , 661-705.
CrossRef8
Heather T. Keenan, John M. Leventhal. (2010) A Case-Control Study to Evaluate Utah’s Shaken Baby Prevention Program. Academic Pediatrics 10:6, 389-394
CrossRef9
C. S. Toi, D. E. Dwyer. (2010) Prevalence of varicella-zoster virus genotypes in Australia characterized by high-resolution melt analysis and ORF22 gene analyses. Journal of Medical Microbiology 59:8, 935-940
CrossRef10
Gathsaurie Neelika Malavige, Louise Jones, S.D. Kamaladasa, Ananda Wijewickrama, Suranjith L. Seneviratne, Antony P. Black, Graham S. Ogg. (2010) Natural killer cells during primary varicella zoster virus infection. Journal of Infection 61:2, 190-192
CrossRef11
So Hee Kim, Hoan Jong Lee, Su Eun Park, Sung Hee Oh, Seong Yeon Lee, Eun Hwa Choi. (2010) Seroprevalence rate after one dose of varicella vaccine in infants. Journal of Infection 61:1, 66-72
CrossRef12
Z. GAO, H. F. GIDDING, J. G. WOOD, C. R. MacINTYRE. (2010) Modelling the impact of one-dose vs. two-dose vaccination regimens on the epidemiology of varicella zoster virus in Australia. Epidemiology and Infection 138:04, 457
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Marc Brisson, Gurgen Melkonyan, Melanie Drolet, Gaston De Serres, Roseline Thibeault, Philippe De Wals. (2010) Modeling the impact of one- and two-dose varicella vaccination on the epidemiology of varicella and zoster. Vaccine 28:19, 3385-3397
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Silvio Tafuri, Domenico Martinelli, Maria De Palma, Cinzia Germinario, Rosa Prato. (2010) Report of varicella outbreak in a low vaccination coverage group of otherwise healthy children in Italy: the role of breakthrough and the need of a second dose of vaccine. Vaccine 28:6, 1594-1597
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Olga Dulovic, Eleonora Gvozdenovic, Jelena Nikolic, Aleksandra Radovanovic-Spurnic, Natasa Katanic, Dragana Kovacevic-Pavicevic. (2010) Varicella complications: Is it time to consider a routine varicella vaccination?. Vojnosanitetski pregled 67:7, 523-529
CrossRef16
Wolfgang Herr, Bodo Plachter. (2009) Cytomegalovirus and varicella–zoster virus vaccines in hematopoietic stem cell transplantation. Expert Review of Vaccines 8:8, 999-1021
CrossRef17
Georgios Trimis, Stamatis Gregoriou, Dimos Florakis, Dimitrios Rigopoulos. (2009) Can varicella immunization change the course of herpes zoster while herpes zoster vaccine is underway?. Expert Review of Dermatology 4:3, 219-224
CrossRef18
Jia-Feng Wu, Yen-Hsuan Ni, Huey-Ling Chen, Hong-Yuan Hsu, Hong-Shiee Lai, Mei-Hwei Chang. (2009) Humoral immunogenicity to measles, rubella, and varicella-zoster vaccines in biliary atresia children. Vaccine 27:21, 2812-2815
CrossRef19
Moon Kim, Dawn Terashita, Lee Borenstein, Laurene Mascola. (2009) Responding to suspected smallpox cases in the Los Angeles County from 2002 to 2006: identifying areas for education. The American Journal of Emergency Medicine 27:1, 55-62
CrossRef20
Ayşe Kiliç, Emin Ünüvar, Ceren Yilmaz, Ismail Yildiz, Fatma Oğuz, Mujgan Sidal. (2008) The effectiveness of varicella vaccination during an outbreak in a childrens’ day-care center. Vaccine 26:27-28, 3371-3372
CrossRef21
J. OSPINA GIRALDO, D. HINCAPIÉ PALACIO. (2008) Deterministic SIR (Susceptible–Infected–Removed) models applied to varicella outbreaks. Epidemiology and Infection 136:05,
CrossRef22
David E. Michalik, Sharon P. Steinberg, Philip S. LaRussa, Kathryn M. Edwards, Peter F. Wright, Ann M. Arvin, Haley A. Gans, Anne A. Gershon. (2008) Primary Vaccine Failure after 1 Dose of Varicella Vaccine in Healthy Children. The Journal of Infectious Diseases 197:7, 944-949
CrossRef23
Jane F. Seward, Mona Marin, Marietta Vázquez. (2008) Varicella Vaccine Effectiveness in the US Vaccination Program: A Review. The Journal of Infectious Diseases 197:s2, S82-S89
CrossRef24
Sheila Weinmann, Colleen Chun, John P. Mullooly, Karen Riedlinger, Heather Houston, Vladimir N. Loparev, D. Scott Schmid, Jane F. Seward. (2008) Laboratory Diagnosis and Characteristics of Breakthrough Varicella in Children. The Journal of Infectious Diseases 197:s2, S132-S138
CrossRef25
Sophie Hambleton, Sharon P. Steinberg, Philip S. LaRussa, Eugene D. Shapiro, Anne A. Gershon. (2008) Risk of Herpes Zoster in Adults Immunized with Varicella Vaccine. The Journal of Infectious Diseases 197:s2, S196-S199
CrossRef26
Barbara Watson. (2008) Humoral and Cell‐Mediated Immune Responses in Children and Adults after 1 and 2 Doses of Varicella Vaccine. The Journal of Infectious Diseases 197:s2, S143-S146
CrossRef27
Dalya Guris, Aisha O. Jumaan, Laurene Mascola, Barbara M. Watson, John X. Zhang, Sandra S. Chaves, Paul Gargiullo, Dana Perella, Rachel Civen, Jane F. Seward. (2008) Changing Varicella Epidemiology in Active Surveillance Sites—United States, 1995–2005. The Journal of Infectious Diseases 197:s2, S71-S75
CrossRef28
Sandra S. Chaves, John Zhang, Rachel Civen, Barbara M. Watson, Tina Carbajal, Dana Perella, Jane F. Seward. (2008) Varicella Disease among Vaccinated Persons: Clinical and Epidemiological Characteristics, 1997–2005. The Journal of Infectious Diseases 197:s2, S127-S131
CrossRef29
Luis Salleras Sanmartí, Monserrat Salleras Redonnet, Andrés Prat, Patricio Garrido, Ángela Domínguez. (2008) Vacunas frente al virus de la varicela zóster. Enfermedades Infecciosas y Microbiología Clínica 26, 29-47
CrossRef30
A. A. Gershon. (2008) Varicella-Zoster Virus Infections. Pediatrics in Review 29:1, 5-11
CrossRef31
C. Azzari, C. Massai, C. Poggiolesi, G. Indolfi, G. Spagnolo, M. De Luca, P. Gervaso, M. de Martino, M. Resti. (2007) Cost of varicella-related hospitalisations in an Italian paediatric hospital: comparison with possible vaccination expenses. Current Medical Research and Opinion 23:12, 2945-2954
CrossRef32
Vu Dinh Thiem, Do Gia Canh, Dang Duc Anh, Jacqueline L. Deen, Lorenz von Seidlein, John D. Clemens, Jan Holmgren. (2007) Response to “Questionable merits of the field trial of an oral killed whole cell cholera vaccine in Vietnam during 1998–2003” Vaccine 2007;25(8):1353–4. Vaccine 25:47, 7981-7983
CrossRef33
Linda M. Niccolai, Lorraine G. Ogden, Catherine E. Muehlenbein, James D. Dziura, Marietta Vázquez, Eugene D. Shapiro. (2007) Methodological issues in design and analysis of a matched case–control study of a vaccine's effectiveness. Journal of Clinical Epidemiology 60:11, 1127-1131
CrossRef34
(2007) Varicella Vaccine. New England Journal of Medicine 356:25, 2648-2649
Full Text35
A Y H Leung, H C H Chow, J S Y Kwok, C K H Lui, V C C Cheng, K-Y Yuen, A K W Lie, R Liang. (2007) Safety of vaccinating sibling donors with live-attenuated varicella zoster vaccine before hematopoietic stem cell transplantation. Bone Marrow Transplantation 39:11, 661-665
CrossRef36
Hassan Vally, Gary K. Dowse, Keith Eastwood, Scott Cameron. (2007) An outbreak of chickenpox at a child care centre in Western Australia. Costs to the community and implications for vaccination policy. Australian and New Zealand Journal of Public Health 31:2, 113-119
CrossRef37
Nicola P. Klein, Bruce Fireman, Andrea Enright, Paula Ray, Steven Black, Cornelia L. Dekker. (2007) A Role for Genetics in the Immune Response to the Varicella Vaccine. The Pediatric Infectious Disease Journal 26:4, 300-305
CrossRef38
Chaves, Sandra S., Gargiullo, Paul, Zhang, John X., Civen, Rachel, Guris, Dalya, Mascola, Laurene, Seward, Jane F., . (2007) Loss of Vaccine-Induced Immunity to Varicella over Time. New England Journal of Medicine 356:11, 1121-1129
Full Text39
Elizabeth Peadon, David Burgner, Michael Nissen, Jim Buttery, Yvonne Zurynski, Elizabeth Elliott, Michael Gold, Helen Marshall, Robert Booy. (2006) Case for varicella surveillance in Australia. Journal of Paediatrics and Child Health 42:11, 663-664
CrossRef40
Ulrich Heininger, Jane F Seward. (2006) Varicella. The Lancet 368:9544, 1365-1376
CrossRef41
Lawrence A. Hunt. 2006. Cytomegalovirus and Varicella-Zoster Virus Vaccines. .
CrossRef42
Hung-Fu Tseng, Hsiu-Fen Tan, Chen-Kang Chang. (2006) Use of National Health Insurance database to evaluate the impact of public varicella vaccination program on burden of varicella in Taiwan. Vaccine 24:25, 5341-5348
CrossRef43
Saro H. Armenian, Jin Young Han, Theresa M. Dunaway, Joseph A. Church. (2006) SAFETY AND IMMUNOGENICITY OF LIVE VARICELLA VIRUS VACCINE IN CHILDREN WITH HUMAN IMMUNODEFICIENCY VIRUS TYPE 1. The Pediatric Infectious Disease Journal 25:4, 368-370
CrossRef44
Maha Almuneef, Ziad A. Memish, Hanan H. Balkhy, Badriyah Alotaibi, Magda Helmy. (2006) Chickenpox complications in Saudi Arabia: Is it time for routine varicella vaccination?. International Journal of Infectious Diseases 10:2, 156-161
CrossRef45
Gabriel Chodick, Shai Ashkenazi, Gilat Livni, Yehuda Lerman. (2006) Increased Susceptibility to Varicella-Zoster Virus among Israeli Physicians and Nurses Born in the Middle-East Region. Journal of Occupational Health 48:4, 246-252
CrossRef46
Anne A. Gershon. 2006. Chickenpox, Measles, and Mumps. , 693-737.
CrossRef47
Josh Levitsky, Andre C. Kalil, Jane L. Meza, Glenn E. Hurst, Alison Freifeld. (2005) Chicken pox after pediatric liver transplantation. Liver Transplantation 11:12, 1563-1566
CrossRef48
KK Macartney, P Beutels, P McIntyre, MA Burgess. (2005) Varicella vaccination in Australia. Journal of Paediatrics and Child Health 41:11, 544-552
CrossRef49
Gabriel Chodick, Shai Ashkenazi, Gilat Livni, Yehuda Lerman. (2005) Cost-effectiveness of varicella vaccination of healthcare workers. Vaccine 23:43, 5064-5072
CrossRef50
John F. Toney. (2005) Skin manifestations of herpesvirus infections. Current Infectious Disease Reports 7:5, 359-364
CrossRef51
Richard Kent Zimmerman, Melissa Tabbarah, Barbara Bardenheier, Janine E. Janosky, Judith A. Troy, Mahlon Raymund, Barbara P. Yawn. (2005) The 2002 United States varicella vaccine shortage and physician recommendations for vaccination. Preventive Medicine 41:2, 575-582
CrossRef52
Gary Goldman. (2005) Universal Varicella Vaccination: Efficacy Trends and Effect on Herpes Zoster. International Journal of Toxicology 24:4, 205-213
CrossRef53
Sophie Hambleton. (2005) Chickenpox. Current Opinion in Infectious Diseases 18:3, 235-240
CrossRef54
Ami Schattner. (2005) Consequence or coincidence?. Vaccine 23:30, 3876-3886
CrossRef55
Karen S Slobod, Mattia Bonsignori, Scott A Brown, Xiaoyan Zhan, John Stambas, Julia L Hurwitz. (2005) HIV vaccines: brief review and discussion of future directions. Expert Review of Vaccines 4:3, 305-313
CrossRef56
Rivka Sheffer, Danit Segal, Sarit Rahamani, Ilan Dalal, Yifat Linhart, Michal Stein, Tamar Shohat, Eli Somekh. (2005) Effectiveness of the Oka/GSK Attenuated Varicella Vaccine for the Prevention of Chickenpox in Clinical Practice in Israel. The Pediatric Infectious Disease Journal 24:5, 434-437
CrossRef57
Dan Miron, Idit Lavi, Rachel Kitov, Avishag Hendler. (2005) Vaccine Effectiveness and Severity of Varicella Among Previously Vaccinated Children During Outbreaks in Day-Care Centers With Low Vaccination Coverage. The Pediatric Infectious Disease Journal 24:3, 233-236
CrossRef58
Barbara Watson. (2005) Varicella-zoster vaccine in the USA: success for control of disease severity, but what next?. Expert Review of Anti-infective Therapy 3:1, 105-115
CrossRef59
Z. S. Moore, J. F. Seward, B. M. Watson, T. J. Maupin, A. O. Jumaan. (2004) Chickenpox or Smallpox: The Use of the Febrile Prodrome as a Distinguishing Characteristic. Clinical Infectious Diseases 39:12, 1810-1817
CrossRef60
Meirav Mor, Liora Harel, Ernesto Kahan, Jacob Amir. (2004) Efficacy of postexposure immunization with live attenuated varicella vaccine in the household setting—a pilot study. Vaccine 23:3, 325-328
CrossRef61
Jonathan R. Carapetis, Diana M.F. Russell, Nigel Curtis. (2004) The burden and cost of hospitalised varicella and zoster in Australian children. Vaccine 23:6, 755-761
CrossRef62
Arun Chakrabarty, Karl Beutner. (2004) Therapy of other viral infections: herpes to hepatitis. Dermatologic Therapy 17:6, 465-490
CrossRef63
David B. Huang, Jashin J. Wu, Stephen K. Tyring. (2004) A review of licensed viral vaccines, some of their safety concerns, and the advances in the development of investigational viral vaccines. Journal of Infection 49:3, 179-209
CrossRef64
Ana Marli Christovam Sartori. (2004) A review of the varicella vaccine in immunocompromised individuals. International Journal of Infectious Diseases 8:5, 259-270
CrossRef65
Nancy Thiry, Philippe Beutels, Francesco Tancredi, Luisa Romanò, Alessandro Zanetti, Paolo Bonanni, Giovanni Gabutti, Pierre Van Damme. (2004) An economic evaluation of varicella vaccination in Italian adolescents. Vaccine 22:27-28, 3546-3562
CrossRef66
Bernard Rentier, Anne A Gershon. (2004) The Oka varicella vaccines are more equal than different. Vaccine 22:25-26, 3225-3226
CrossRef67
Marietta Vázquez. (2004) Varicella Infections and Varicella Vaccine in the 21st Century. The Pediatric Infectious Disease Journal 23:9, 871-872
CrossRef68
Shaine A Morris, Henry H Bernstein. (2004) Immunizations, neonatal jaundice, and animal-induced injuries. Current Opinion in Pediatrics 16:4, 450-460
CrossRef69
Bernard Rentier, Anne A. Gershon. (2004) Consensus: Varicella Vaccination of Healthy Children. The Pediatric Infectious Disease Journal 23:5, 379-389
CrossRef70
JUSTEN H. PASSWELL, BEATRICE HEMO, YONIT LEVI, REUT RAMON, NURIT FRIEDMAN, LIAT LERNER-GEVA. (2004) Use of a computerized database to study the effectiveness of an attenuated varicella vaccine. The Pediatric Infectious Disease Journal 23:3, 221-226
CrossRef71
EUGENE D. SHAPIRO. (2004) Case-control studies of the effectiveness of vaccines: validity and assessment of potential bias. The Pediatric Infectious Disease Journal 23:2, 127-131
CrossRef72
Marietta V??zquez. (2004) Varicella zoster virus infections in children after the introduction of live attenuated varicella vaccine. Current Opinion in Pediatrics 16:1, 80-84
CrossRef73
G.M Ginsberg, E Somekh. (2004) Cost containment analysis of childhood vaccination against varicella in Israel. Journal of Infection 48:2, 119-133
CrossRef74
Michiaki Takahashi. (2004) Effectiveness of live varicella vaccine. Expert Opinion on Biological Therapy 4:2, 199-216
CrossRef75
Maha Almuneef, Joanne Dillon, Moustafa F. Abbas, Ziad Memish. (2003) Varicella zoster virus immunity in multinational health care workers of a Saudi Arabian hospital. American Journal of Infection Control 31:6, 375-381
CrossRef76
Marie‐Pierre Préziosi, M. Elizabeth Halloran. (2003) Effects of Pertussis Vaccination on Disease: Vaccine Efficacy in Reducing Clinical Severity. Clinical Infectious Diseases 37:6, 772-779
CrossRef77
J. Dı́ez-Domingo, J. Aristegui, F. Calbo, J. Gonzalez-Hachero, F. Moraga, J. Peña Guitian, J. Ruiz Contreras, A. Torrellas. (2003) Epidemiology and economic impact of varicella in immunocompetent children in Spain.. Vaccine 21:23, 3236-3239
CrossRef78
Swati Y. Bhave. (2003) Controversies in chicken–pox immunization. The Indian Journal of Pediatrics 70:6, 503-507
CrossRef79
(2003) An Outbreak of Varicella despite Vaccination. New England Journal of Medicine 348:14, 1405-1407
Full Text80
Ayman Naseri, William V Good, Emmett T Cunningham. (2003) Herpes zoster virus sclerokeratitis and anterior uveitis in a child following varicella vaccination. American Journal of Ophthalmology 135:3, 415-417
CrossRef81
Nancy Thiry, Philippe Beutels, Pierre Van Damme, Eddy Van Doorslaer. (2003) Economic Evaluations of Varicella Vaccination Programmes. PharmacoEconomics 21:1, 13-38
CrossRef82
Eugene D. Shapiro. (2003) Case-control studies. The Pediatric Infectious Disease Journal 22:1, 85-87
CrossRef83
Margaret A.K. Ryan, Tyler C. Smith, William K. Honner, Gregory C. Gray. (2003) Varicella susceptibility and vaccine use among young adults enlisting in the United States Navy. Journal of Medical Virology 70:S1, S15-S19
CrossRef84
M. Brisson, W.J. Edmunds, N.J. Gay. (2003) Varicella vaccination: Impact of vaccine efficacy on the epidemiology of VZV. Journal of Medical Virology 70:S1, S31-S37
CrossRef85
Adam J. Ratner. (2002) Varicella-related hospitalizations in the vaccine era. The Pediatric Infectious Disease Journal 21:10, 927-930
CrossRef86
Bryce Binstadt, Henry Bernstein. (2002) Current Opinion in Pediatrics 14:4, 498-507
CrossRef87
Mark S. Dworkin, Charles E. Jennings, Jayne Roth‐Thomas, Jo Ellen Lang, Carol Stukenberg, John R. Lumpkin. (2002) An Outbreak of Varicella among Children Attending Preschool and Elementary School in Illinois. Clinical Infectious Diseases 35:1, 102-104
CrossRef88
HENRY R. SHINEFIELD, STEVEN B. BLACK, BRENDA O. STAEHLE, HOLLY MATTHEWS, TAMA ADELMAN, KATHLEEN ENSOR, SHU LI AN CHAN, JOSEPH HEYSE, MARILYN WATERS, CHRISTINA Y. CHAN, S. J. RUPERT VESSEY, KAREN M. KAPLAN, BARBARA J. KUTER. (2002) Vaccination with measles, mumps and rubella vaccine and varicella vaccine: safety, tolerability, immunogenicity, persistence of antibody and duration of protection against varicella in healthy children. The Pediatric Infectious Disease Journal 21:6, 555-561
CrossRef89
M. Brisson, N.J. Gay, W.J. Edmunds, N.J. Andrews. (2002) Exposure to varicella boosts immunity to herpes-zoster: implications for mass vaccination against chickenpox. Vaccine 20:19-20, 2500-2507
CrossRef90
DENIS GETSIOS, J. JAIME CARO, GRACIELA CARO, PHILLIPE DE WALS, BARBARA J. LAW, YVES ROBERT, JEAN-MARIE R. LANCE. (2002) Instituting a routine varicella vaccination program in Canada: an economic evaluation. The Pediatric Infectious Disease Journal 21:6, 542-547
CrossRef91
Paul Rivest, Robert Allard. (2002) The effectiveness of serogroup C meningococcal vaccine estimated from routine surveillance data. Vaccine 20:19-20, 2533-2536
CrossRef92
Sucheep Piyasirisilp, Thiravat Hemachudha. (2002) Neurological adverse events associated with vaccination. Current Opinion in Neurology 15:3, 333-338
CrossRef93
Michael Rothberg, Michael L. Bennish, Jack S. Kao, John B. Wong. (2002) Do the Benefits of Varicella Vaccination Outweigh the Long‐Term Risks? A Decision‐Analytic Model for Policymakers and Pediatricians. Clinical Infectious Diseases 34:7, 885-894
CrossRef94
Susan L. Furth, Barbara A. Fivush. (2002) Varicella vaccination in pediatric kidney transplant candidates. Pediatric Transplantation 6:2, 97-100
CrossRef95
Thomas Fehr, Walter Bossart, Christoph Wahl, Ulrich Binswanger. (2002) Disseminated varicella infection in adult renal allograft recipients: four cases and a review of the literature. Transplantation 73:4, 608-611
CrossRef96
(2001) The Effectiveness of the Varicella Vaccine. New England Journal of Medicine 345:6, 464-465
Full Text97
&NA;. (2001) Varicella vaccine: 'highly effective' for paediatric use in the US. Inpharma Weekly &NA;:1282, 13
CrossRef98
Arvin, Ann M., . (2001) Varicella Vaccine — The First Six Years. New England Journal of Medicine 344:13, 1007-1009
Full Text
