Date Published: July 3, 2019
Publisher: Public Library of Science
Author(s): Myron J. Levin, Jennifer M. Duchon, Geeta K. Swamy, Anne A. Gershon, Ray Borrow.
Despite vaccination, there were more than 100,000 annual cases of varicella in the United States in 2013–2014. Individuals at highest risk of developing severe or complicated varicella include immunocompromised people, preterm infants, and pregnant women. Varicella zoster immune globulin (human) (VARIZIG) is recommended by the CDC for postexposure prophylaxis to prevent or attenuate varicella-zoster virus infection in high-risk individuals. Contemporary information on administration of VARIZIG is limited.
This open-label, expanded-access program provided VARIZIG to physician-identified, high-risk participants exposed to varicella. Participants included immunocompromised children/adults, infants (preterm, newborns whose mothers had varicella onset within 5 days before or 2 days after delivery, and those aged <1 year), and pregnant women. VARIZIG (125 IU/10 kg [up to 625 IU]) was administered intramuscularly, ideally within 96 hours, but up to 10 days, postexposure. Incidence of varicella rash and severity (>100 pox, pneumonia, or encephalitis) were assessed up to 42 days after administration.
The varicella outcome population (n = 507) included 263 immunocompromised participants (32 adults, 231 children), 137 pregnant women, 105 infants, and 2 healthy adults with no history of varicella. Varicella incidence was 4.5% in immunocompromised participants, 7.3% in pregnant women, and 11.5% in infants. The incidence of varicella was similar when comparing VARIZIG administration ≤ 96 hours vs > 96 hours (up to 10 days) postexposure in the entire population (6.2% vs. 9.4%, respectively), and also in each subgroup. Of 34 participants with varicella, 5 developed > 100 pox and 1 developed pneumonia and encephalitis. There were no product-related deaths and only 1 serious adverse event (serum sickness) considered probably related to VARIZIG.
Postexposure administration of VARIZIG was associated with low rates of varicella in high-risk participants, regardless of when administered within 10 days postexposure. VARIZIG was well-tolerated and safe in high-risk participants.
Although the incidence of varicella has dropped dramatically in the United States because of varicella vaccination, as of 2014 there remained more than 100,000 annual cases of varicella [1,2]. In addition, there are an estimated 1 million cases of shingles each year in the United States . Exposure of high-risk individuals to varicella-zoster virus (VZV) can result in severe or complicated varicella including pneumonitis, encephalitis, and hepatitis . People at highest risk of developing severe or complicated varicella include non-immune adults, immunocompromised patients [4–8], and preterm infants [4,9,10]. Pregnant women are more likely to develop varicella pneumonia than non-pregnant adults , particularly if they have ≥ 100 pox and are current smokers , although the rate of varicella pneumonia may be lower than previously reported . Children born to pregnant women who develop varicella are at risk of the sequelae of congenital varicella syndrome, depending on when exposure occurs during the pregnancy; however, it is unknown if passive immunization will alter the risk for congenital varicella syndrome [4,7,9,12,14–16]. Newborn infants whose mothers had onset of varicella within 5 days before delivery or within 48 hours after delivery are at especially high risk from severe varicella, presumably because they do not receive protective transplacental VZV antibodies before birth [7,17,18].
Since 2002 , there have been no publications reporting clinical experience with passive immunization to prevent varicella, and the most recent systematic review on the topic was published in 2011 . Because of revised guidelines, confusion between discontinued VZIG and subsequent availability of VARIZIG, and no recent publications, there has been uncertainty about proper management of susceptible individuals exposed to varicella or herpes zoster. In addition, with the increased prevalence of vaccine refusers, the need for passive immunization for high-risk individuals has increased .
This large study conducted in 3 different high-risk populations exposed to varicella, demonstrates that VARIZIG can be safely administered up to 10 days in patients after their exposure to varicella and likely reduces the incidence of varicella. These data are consistent with the current CDC recommendations for the use of hyperimmune globulin to prevent varicella in high-risk populations.