For Second Varicella Dose, Earlier May Be Better

Four months after receiving one dose of the varicella vaccine only 76% of 148 children showed evidence of seroconversion, suggesting that many pediatric cases of varicella are caused by primary immunization failure, investigators have reported.

"The present findings … strongly support the use of a second dose of vaccine for all children without a history of disease," and the second dose should be given within months, rather than years, of the first, the researchers wrote.

This approach "will probably prevent not only the current phenomenon of isolated outbreaks of breakthrough disease but a subsequent epidemic of serious varicella in vaccinated but unprotected adults," wrote Dr. David E. Michalik of the division of pediatric infectious Diseases at Columbia University Medical Center, New York, and his colleagues (J. Infect. Dis. 2008;197:944–9).

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends that a second dose of varicella vaccine be administered routinely to children. The second dose can be given as soon as 3 months after the first dose.

Writing in an accompanying editorial, Dr. Eugene D. Shapiro of the Yale Center for Clinical Investigation at Yale University, New Haven, Conn., pointed out that the first and second doses of the varicella vaccine are sometimes given at the same time as the MMR vaccine via a combined MMR-varicella (MMR-V) vaccine at 12–15 months and again at 4–6 years.

"If the substantial number of cases of breakthrough varicella is due to primary, rather than secondary, vaccine failure, this timing for the second dose risks leaving a substantial number of children susceptible for several years until they receive the second dose," he wrote (J. Infect. Dis. 2008;197:935–7).

Dr. Michalik and his associates defined primary vaccine failure as the inability to mount a protective immune response after receiving a single dose of vaccine; secondary failure occurred when the demonstrable immune response to vaccination gradually waned over a long period of time.

The researchers conducted the multicenter study to ascertain whether recent reports of breakthrough varicella might represent the higher than expected rates of primary vaccine failure.

Using fluorescent antibody membrane antigen (FAMA) assay, Dr. Michalik and his associates studied the varicella zoster virus (VZV) antibody titers in 148 healthy immunized children before and after they had received one 0.5-mL dose of varicella vaccine. A total of 76% had seroconversion, but 24% showed no detectable VZV FAMA antibodies.

FAMA is considered the preferred method for assessment technique and has a high sensitivity and specificity for VZV antibodies. The seroconversion rates found in this study are significantly lower than those found in other studies (86%–96%) in which flagellar antigen enzyme-linked immunosorbent assay (GP ELISA) was used. The authors noted that the GP ELISA assay can cause false-positive results to occur, which can likely lead to overestimations of the rate of seroconversion.

The median age of participants was 12.5 months, and serum samples were obtained an average of 4 months post vaccination.

In his editorial, Dr. Shapiro stressed that the optimal use of this "effective vaccine" still needs to be determined.

"Because of the limited and conflicting data on which to base recommendations for policy, it is important to obtain additional data to try to clarify whether most breakthrough cases of varicella are due to primary or secondary vaccine failure. The immunogenicity of both monovalent varicella vaccine and of MMR-V vaccine … should be assessed by directly comparing the results of GP ELISA and FAMA assays in the same samples," Dr. Shapiro said.

Four months after receiving one dose of the varicella vaccine only 76% of 148 children showed evidence of seroconversion, suggesting that many pediatric cases of varicella are caused by primary immunization failure, investigators have reported.

"The present findings … strongly support the use of a second dose of vaccine for all children without a history of disease," and the second dose should be given within months, rather than years, of the first, the researchers wrote.

This approach "will probably prevent not only the current phenomenon of isolated outbreaks of breakthrough disease but a subsequent epidemic of serious varicella in vaccinated but unprotected adults," wrote Dr. David E. Michalik of the division of pediatric infectious Diseases at Columbia University Medical Center, New York, and his colleagues (J. Infect. Dis. 2008;197:944–9).

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends that a second dose of varicella vaccine be administered routinely to children. The second dose can be given as soon as 3 months after the first dose.

Writing in an accompanying editorial, Dr. Eugene D. Shapiro of the Yale Center for Clinical Investigation at Yale University, New Haven, Conn., pointed out that the first and second doses of the varicella vaccine are sometimes given at the same time as the MMR vaccine via a combined MMR-varicella (MMR-V) vaccine at 12–15 months and again at 4–6 years.

"If the substantial number of cases of breakthrough varicella is due to primary, rather than secondary, vaccine failure, this timing for the second dose risks leaving a substantial number of children susceptible for several years until they receive the second dose," he wrote (J. Infect. Dis. 2008;197:935–7).

Dr. Michalik and his associates defined primary vaccine failure as the inability to mount a protective immune response after receiving a single dose of vaccine; secondary failure occurred when the demonstrable immune response to vaccination gradually waned over a long period of time.

The researchers conducted the multicenter study to ascertain whether recent reports of breakthrough varicella might represent the higher than expected rates of primary vaccine failure.

Using fluorescent antibody membrane antigen (FAMA) assay, Dr. Michalik and his associates studied the varicella zoster virus (VZV) antibody titers in 148 healthy immunized children before and after they had received one 0.5-mL dose of varicella vaccine. A total of 76% had seroconversion, but 24% showed no detectable VZV FAMA antibodies.

FAMA is considered the preferred method for assessment technique and has a high sensitivity and specificity for VZV antibodies. The seroconversion rates found in this study are significantly lower than those found in other studies (86%–96%) in which flagellar antigen enzyme-linked immunosorbent assay (GP ELISA) was used. The authors noted that the GP ELISA assay can cause false-positive results to occur, which can likely lead to overestimations of the rate of seroconversion.

The median age of participants was 12.5 months, and serum samples were obtained an average of 4 months post vaccination.

In his editorial, Dr. Shapiro stressed that the optimal use of this "effective vaccine" still needs to be determined.

"Because of the limited and conflicting data on which to base recommendations for policy, it is important to obtain additional data to try to clarify whether most breakthrough cases of varicella are due to primary or secondary vaccine failure. The immunogenicity of both monovalent varicella vaccine and of MMR-V vaccine … should be assessed by directly comparing the results of GP ELISA and FAMA assays in the same samples," Dr. Shapiro said.

Four months after receiving one dose of the varicella vaccine only 76% of 148 children showed evidence of seroconversion, suggesting that many pediatric cases of varicella are caused by primary immunization failure, investigators have reported.

"The present findings … strongly support the use of a second dose of vaccine for all children without a history of disease," and the second dose should be given within months, rather than years, of the first, the researchers wrote.

This approach "will probably prevent not only the current phenomenon of isolated outbreaks of breakthrough disease but a subsequent epidemic of serious varicella in vaccinated but unprotected adults," wrote Dr. David E. Michalik of the division of pediatric infectious Diseases at Columbia University Medical Center, New York, and his colleagues (J. Infect. Dis. 2008;197:944–9).

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention recommends that a second dose of varicella vaccine be administered routinely to children. The second dose can be given as soon as 3 months after the first dose.

Writing in an accompanying editorial, Dr. Eugene D. Shapiro of the Yale Center for Clinical Investigation at Yale University, New Haven, Conn., pointed out that the first and second doses of the varicella vaccine are sometimes given at the same time as the MMR vaccine via a combined MMR-varicella (MMR-V) vaccine at 12–15 months and again at 4–6 years.

"If the substantial number of cases of breakthrough varicella is due to primary, rather than secondary, vaccine failure, this timing for the second dose risks leaving a substantial number of children susceptible for several years until they receive the second dose," he wrote (J. Infect. Dis. 2008;197:935–7).

Dr. Michalik and his associates defined primary vaccine failure as the inability to mount a protective immune response after receiving a single dose of vaccine; secondary failure occurred when the demonstrable immune response to vaccination gradually waned over a long period of time.

The researchers conducted the multicenter study to ascertain whether recent reports of breakthrough varicella might represent the higher than expected rates of primary vaccine failure.

Using fluorescent antibody membrane antigen (FAMA) assay, Dr. Michalik and his associates studied the varicella zoster virus (VZV) antibody titers in 148 healthy immunized children before and after they had received one 0.5-mL dose of varicella vaccine. A total of 76% had seroconversion, but 24% showed no detectable VZV FAMA antibodies.

FAMA is considered the preferred method for assessment technique and has a high sensitivity and specificity for VZV antibodies. The seroconversion rates found in this study are significantly lower than those found in other studies (86%–96%) in which flagellar antigen enzyme-linked immunosorbent assay (GP ELISA) was used. The authors noted that the GP ELISA assay can cause false-positive results to occur, which can likely lead to overestimations of the rate of seroconversion.

The median age of participants was 12.5 months, and serum samples were obtained an average of 4 months post vaccination.

In his editorial, Dr. Shapiro stressed that the optimal use of this "effective vaccine" still needs to be determined.

"Because of the limited and conflicting data on which to base recommendations for policy, it is important to obtain additional data to try to clarify whether most breakthrough cases of varicella are due to primary or secondary vaccine failure. The immunogenicity of both monovalent varicella vaccine and of MMR-V vaccine … should be assessed by directly comparing the results of GP ELISA and FAMA assays in the same samples," Dr. Shapiro said.