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Immune Response to Varicella After Acyclovir Prophylaxis



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Am Fam Physician. 2000 Feb 15;61(4):1145-1146.

Primary varicella infection can often be prevented or at least limited by administration of the varicella vaccine within 72 hours of exposure to chickenpox or herpes zoster. When timely vaccination is not possible, acyclovir prophylaxis may be an alternative and may be effective even if it is not initiated until seven to 14 days after exposure. Oral acyclovir prophylaxis is thought to keep the varicella infection asymptomatic. However, the degree of immunity to the varicella-zoster virus (VZV) following acyclovir prophylaxis is unknown. To clarify the magnitude of active immunity in this situation, Kumagai and colleagues studied various aspects of the immune response in 15 children six months to five years of age who received oral acyclovir prophylaxis after VZV exposure.

Children in the study had not had chicken-pox or herpes zoster and were exposed to a family member with active varicella. Oral acyclovir was administered in a dosage of 40 mg per kg per day, in four divided doses. Prophylactic therapy was started seven days after exposure and continued for one week. Children were excluded if they had a history of immune deficiency or therapy with cytotoxic or immunosuppressive drugs or immune globulins.

VZV-specific cellular immunity was evaluated by means of the lymphocyte proliferation test (LPT), a skin test reaction to varicella virus antigen four weeks after exposure and determination of VZV-specific IgG antibody. For the skin test, a reaction greater than 5 mm was considered positive. An indirect enzyme-linked immunosorbent assay (ELISA) was used to quantify IgG antibody to VZV. The presence of specific immunity to VZV was defined as a positive result on at least one of the three tests.

Ten of the 13 children who were susceptible to varicella before exposure acquired specific VZV immunity. Each of these 10 children had positive results on the LPT, although the magnitude of the response varied. The stimulation index (the measure for the LPT) ranged from a low of 2.58 to a high of 260.50. A stimulation index of 2.5 or greater was defined as a positive test result. These 10 children did not develop symptoms of varicella. One child did not show an immune response but also had not developed primary varicella by the 34th day after exposure. Two children had the onset of varicella symptoms 19 and 21 days after exposure, suggesting that the acyclovir prophylaxis failed.

Skin test results were positive in seven of 10 children. A fourfold rise in VZV-specific IgG titer by ELISA occurred in three of the 10 children. In four children, antibody activity was detected at baseline, suggesting the presence of maternally acquired antibody. Two children had positive antibody responses to VZV by ELISA on the sixth and 10th days after exposure, indicating that they had acquired specific immunity from asymptomatic infection before the documented exposure.

The authors conclude that cell-mediated immunity to VZV develops following exposure to chickenpox in children who receive acyclovir prophylaxis. The findings corroborate previous studies that have shown acyclovir to be effective in preventing symptomatic chickenpox in children if prophylaxis is initiated seven to 14 days after exposure. In the authors' study, the peak immune response occurred three to five weeks after exposure to VZV, which is the same as that observed in children who contract active infection. The authors state that the varicella vaccine is the first choice for prophylaxis, but acyclovir is an alternative if vaccination is not possible within a few days after exposure. A VZV immune status should be determined in children who receive acyclovir prophylaxis to document immunity and avoid unnecessary administration of varicella vaccine in children with acquired immunity.

Kumagai T, et al. Varicella-zoster virus–specific cellular immunity in subjects given acyclovir after household chickenpox exposure. J Infect Dis. September 1999;180:834–7.


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