SYSTEMATIC REVIEW
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Severe varicella in persons vaccinated with varicella vaccine (breakthrough varicella): a systematic literature review.

INTRODUCTION: Varicella vaccines are highly effective at preventing disease, but varicella may occur among vaccinated persons (termed breakthrough varicella). Breakthrough varicella is generally mild, but severe cases have been reported. The objective of this review is to describe severe breakthrough varicella. Areas covered: We conducted a systematic review of articles published during 1974-2016. A total of 34 articles were included in our review: 21 described breakthrough varicella with disseminated varicella-zoster virus (VZV) infection with other organ involvement in addition to skin (none among two-dose vaccinees); 9 described hospitalized breakthrough varicella without mention of other organ involvement in addition to skin (of which 2 reported 4 two-dose vaccinees); and 4 described both. A total of 52-60 unique breakthrough varicella cases with disseminated VZV infection with other organ involvement in addition to skin reported with the following complications, not mutually exclusive: pneumonia (n = 8-9 cases), neurologic (n = 18-24 cases), hematologic (n = 10-11 cases), ocular (n = 5 cases), renal (n = 2 cases), hepatic (n = 3 cases), secondary infection with bacteremia or sepsis (n = 8 cases), and other complication (n = 4 cases). There were 6 cases of fatal breakthrough varicella. Expert commentary: With >31 million doses distributed annually worldwide since 2007, severe breakthrough varicella can occur but they appear to be uncommon.

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