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Clinical Inquiry: is it safe to vaccinate children against varicella while they're in close contact with a pregnant woman?
Abstract
Yes. All healthy children without evidence of immunity to varicella who are living in a household with a susceptible pregnant woman should be vaccinated.
Vesiculopustular eruptions consist of a wide range of diseases from viral and bacterial infections to mechanobullous and immunobullous disorders, all affecting the structural integrity of the skin. The eruptions can be self-limited or life-threatening, necessitating early diagnosis especially in immunocompromised patients. While many similarities exist in the clinical presentation, viral infections can best be detected via viral PCR and differentiation between bacterial infections can allow for prompt appropriate treatment. Immunobullous dermatoses can be differentiated by the region of blister formation, resulting in a variety of clinical patterns. Finally, whereas erythema multiforme and mycoplasma induced rash and mucositis are induced by infections and often self-limited, Steven Johnson syndrome and toxic epidermolysis necrolysis are commonly triggered by medications and can be life-threatening. Recognizing and differentiating between vesiculopustular eruptions is essential to provide appropriate diagnosis and treatment.
National varicella immunization coverage using the current 1-dose immunization strategy has increased among vaccine-eligible children 19 through 35 months of age from 27% in 1997 to 88% by 2005. These high immunization rates have resulted in a 71% to 84% decrease in the reported number of varicella cases, an 88% decrease in varicella-related hospitalizations, a 59% decrease in varicella-related ambulatory care visits, and a 92% decrease in varicella-related deaths in 1- to 4-year-old children when compared with data from the prevaccine era. Despite this significant decrease, the number of reported cases of varicella has remained relatively constant during the past 5 to 6 years. Since vaccine effectiveness for prevention of disease of any severity has been 80% to 85%, a large number of cases of varicella continue to occur among people who already have received the vaccine (breakthrough varicella), and outbreaks of varicella have been reported among highly immunized populations of schoolchildren. The peak age-specific incidence has shifted from 3- to 6-year-old children in the prevaccine era to 9- to 11-year-old children in the postvaccine era for cases in both immunized and unimmunized children during these outbreaks. Outbreaks of varicella are likely to continue with the current 1-dose immunization strategy.
After administration of 2 doses of varicella vaccine in children, the immune response is markedly enhanced, with >99% of children achieving an antibody concentration (determined by glycoprotein enzyme-linked immunosorbent assay) of ≥5 U/mL (an approximate correlate of protection) and a marked increase in geometric mean antibody titers after the second vaccine dose. The estimated vaccine efficacy over a 10-year observation period of 2 doses for prevention of any varicella disease is 98% (compared with 94% for 1 dose), with 100% efficacy for prevention of severe disease. Recipients of 2 doses of varicella vaccine are 3.3-fold less likely to have breakthrough varicella, compared with those who are given 1 dose, during the first 10 years after immunization.
To achieve greater levels of immunity with fewer serosusceptible people, greater protection against breakthrough varicella disease, and reduction in the number of outbreaks that occur nationwide among school-aged populations, a 2-dose varicella immunization strategy is now recommended for children ≥12 months of age.
The safety of administering the live attenuated Oka/Merck varicella vaccine to the well siblings of children with malignancy was evaluated as a strategy for reducing the risk of household exposure to varicella among immunocompromised children. Susceptible well children were eligible for vaccination if the child with malignancy had leukemia, lymphoma, or solid tumor in remission for 3 months or longer. No evidence of vaccine virus transmission was found among 30 children with malignancy whose 37 healthy susceptible siblings were immunized with varicella vaccine. Varicella-zoster virus was not isolated from the oropharyngeal secretions taken from 17 vaccinees or their 14 immunocompromised siblings. None of the 30 immunocompromised children had vaccine-related rashes or showed immunologic evidence of subclinical varicella-zoster virus infection based on testing for varicella-zoster virus IgG antibodies and T-lymphocyte proliferation to varicella-zoster virus. Four healthy vaccinees eventually had mild breakthrough cases of varicella, with transmission to the high-risk sibling in 3 cases. However, even in these families, the immunocompromised children had been protected from household exposure varicella for at least 20 months early in the course of their immunosuppressive treatment.
To examine whether the live varicella vaccine virus is attenuated, we analyzed varicella vaccine-induced contact cases of clinical chickenpox in healthy siblings of immunized children with leukemia. A rash developed approximately 1 month later in 156 children with leukemia who had been vaccinated. Vaccine-type virus was isolated from 25 of these children. Of 88 known susceptible healthy siblings who were exposed to a vaccine with a rash and from whom follow-up information was available, there was evidence of infection in 15 (17%). Of 15 siblings with seroconversion, 11 (73%) also acquired a mild rash with an average of 38 lesions and no accompanying systemic symptoms. Vaccine-type virus was isolated from four of the contact siblings. Tertiary transmission was documented once. Contact siblings with seroconversion were protected during future household exposure to chickenpox, which occurred in four instances. There was a direct relationship between transmission from vaccinees to varicella-susceptible close contacts and the presence and number of skin lesions in children with leukemia after vaccination. We conclude that in the transmission of varicella, the virus probably originates from skin lesions of infected persons and reaches the respiratory tract of those with secondary cases by the airborne route. On the basis of the mildness of the contact illness, the higher-than-normal rate of subclinical primary infection with varicella-zoster virus in contacts, and the lower-than-normal rate of spread of the vaccine virus to susceptible children in the household, we further conclude that the vaccine virus is attenuated. There was no evidence of reversion of the vaccine virus to virulence.
We conducted a double-blind, placebo-controlled efficacy trial of the live attenuated Oka/Merck varicella vaccine among 956 children between the ages of 1 and 14 years, with a negative clinical history of varicella. Of the 914 children who were serologically confirmed to be susceptible to varicella, 468 received vaccine and 446 received placebo. The vaccine produced few clinical reactions and was well tolerated. There was no clinical evidence of viral spread from vaccinated children to sibling controls. Approximately eight weeks after vaccination, 94 per cent of the initially seronegative children who received vaccine had detectable antibody to varicella. During the nine-month surveillance period, 39 clinically diagnosed cases of varicella, 38 of which were confirmed by laboratory tests, occurred among study participants. All 39 cases occurred in placebo recipients; no child who received vaccine contracted varicella. The vaccine was 100 per cent efficacious in preventing varicella in this population of healthy children (P less than 10(-9).
A 12-month-old healthy boy had approximately 30 vesicular skin lesions 24 days after receiving varicella vaccine. Sixteen days later his pregnant mother had 100 lesions. Varicella-vaccine virus was identified by polymerase chain reaction in the vesicular lesions of the mother. After an elective abortion, no virus was detected in the fetal tissue. This case documents transmission of varicella-vaccine virus from a healthy 12-month-old infant to his pregnant mother.