Live-attenuated varicella vaccine was licensed for general use in the United States in 1995, and in Canada in 1999, and it currently is recommended for virtually all healthy individuals who are more than 1 year old and who are susceptible to varicella. This vaccine was developed in the early 1970s by Takahashi, <sup>74 Takahashi M., Otsuka T., Okuno Y. , e al. Live vaccine used to prevent the spread of varicella in children in hospital Lancet 1974 ;  2 : 1288-1290  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> and was licensed for use in Japan in 1989 (Table 1). The wild-type virus was attenuated by passage in various cell cultures, and the vaccine initially was tested in Japan, first in healthy children and then in immunocompromised children. When varicella vaccine first was developed, its use (especially in western countries) was highly controversial, despite many small studies indicating its safety and efficacy.<sup>5 Asano Y., Nakayama H., Yazaki T. , e al. Protection against varicella in family contacts by immediate inoculation with live varicella vaccine Pediatrics 1977 ;  59 : 3-7

Cliccare qui per andare alla sezione Riferimenti, 6 Asano Y., Nakayama H., Yazaki T. , e al. Protective efficacy of vaccination in children in four episodes of natural varicella and zoster in the ward Pediatrics 1977 ;  59 : 8-12

Cliccare qui per andare alla sezione Riferimenti, 46 Izawa T., Ihara T., Hattori A. , e al. Application of a live varicella vaccine in children with acute leukemia or other malignant diseases Pediatrics 1977 ;  60 : 805-809

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The first clinical trials in the United States, therefore, involved varicella-susceptible individuals at high risk to develop severe or fatal varicella, mainly children with leukemia in remission and adults. At that time, in the late 1970s, some children who were being cured of their leukemia were dying from varicella.<sup>24 Feldman S., Hughes W., Daniel C. Varicella in children with cancer: 77 cases Pediatrics 1975 ;  80 : 388-397

Cliccare qui per andare alla sezione Riferimenti</sup> In the United States, it quickly was confirmed that the vaccine was safe and effective for leukemic children.<sup>27 Gershon A. Live attenuated varicella–zoster vaccine Rev Infect Dis 1980 ;  2 : 393

Cliccare qui per andare alla sezione Riferimenti, 32 Gershon A.A., Steinberg S., Gelb L. Live attenuated varicella vaccine: Efficacy for children with leukemia in remission. NIAID Collaborative Varicella Vaccine Study Group JAMA 1984 ;  252 : 355-362

Cliccare qui per andare alla sezione Riferimenti, 33 Gershon A., Steinberg S., Gelb L. Live attenuated varicella vaccine: Use in immunocompromised children and adults. NIAID Collaborative Varicella Vaccine Study Group Pediatrics 1986 ;  78 (S) : 757-762

Cliccare qui per andare alla sezione Riferimenti</sup> Based on this success, early clinical trials in healthy children were expanded and also indicated the safety and efficacy of the vaccine.<sup>50 Kuter B.J., Ngai A., Patterson C.M. , e al. Safety, tolerability, and immunogenicity of two regimens of Oka/Merck varicella vaccine (Varivax®) in healthy adolescents and adults Vaccine 1995 ;  13 : 967-972  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 51 Kuter B.J., Weibel R.E., Guess H.A. , e 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  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 82 Weibel R., Neff B.J., Kuter B.J. , e al. Live attenuated varicella virus vaccine: Efficacy trial in healthy children N Engl J Med 1984 ;  310 : 1409-1415  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 87 White C.J., Kuter B.J., Hildebrand C.S. , e al. Varicella vaccine (VARIVAX) in healthy children and adolescents: Results from clinical trials, 1987 to 1989 Pediatrics 1991 ;  87 : 604-610

Cliccare qui per andare alla sezione Riferimenti</sup> At that point the focus of varicella vaccination shifted from immunocompromised individuals to healthy individuals. The end result of extensive clinical trials during the 1980s and early 1990s was the licensure of varicella vaccine in the United States for healthy children and adults.<sup>49 Krause P., Klinman D.M. Efficacy, immunogenicity, safety, and use of live attenuated chickenpox vaccine J Pediatr 1995 ;  127 : 518-525  [cross-ref]

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