'Definitive' Study: VZV Shot Not Tied to Ischemic Stroke

Vaccination with live, attenuated varicella zoster virus was not associated with an increased risk of ischemic stroke in pediatric patients in the year after they received their vaccination, a retrospective, population-based study of children registered in the Vaccine Safety DataLink shows.

The study is the first to systematically examine the association between varicella zoster virus (VZV) vaccination and ischemic stroke. In previous studies, infection with the wild-type VZV has been associated with ischemic stroke in adults after herpes zoster ophthalmicus and in children after primary infection with the virus (chickenpox). Suspicion of an association between varicella vaccination and ischemic stroke initially arose because of case reports of children with signs and symptoms of ischemic strokes who had been vaccinated with live, attenuated VZV.

In the study of about 3.25 million children who were members of eight medical care organizations that participate in the Centers for Disease Control and Prevention's Vaccine Safety DataLink project, strokes were diagnosed in a significantly lower percentage of children who received at least one varicella vaccination than in those who did not receive the vaccine (0.003% vs. 0.008%), James G. Donahue, D.V.M, Ph.D., of the Marshfield (Wisc.) Clinic Research Foundation and his colleagues reported (Pediatrics 2009;123:e228–34).

Although unvaccinated children had a significantly older mean age than did vaccinated children (7.9 years vs. 1.9 years), because the vaccine was not widely distributed until the late 1990s, adjustment for age did not alter the results of the analysis.

Dr. David Kimberlin, a member of the American Academy of Pediatrics Committee on Infectious Diseases who specializes in varicella, called the study “definitive.” The results show that “using the varicella vaccine can save lives and morbidity among survivors who would have gotten chickenpox, anyway.”

The study “really shows the power of the Vaccine Safety DataLink. It is a phenomenal means by which complications of vaccinations can be assessed, and in this case, ruled out,” Dr. Kimberlin of the division of pediatric infectious diseases at the University of Alabama, Birmingham, said in an interview. He was not involved in the study.

The study included children older than 11 months but younger than 18 years, excluding those diagnosed with infantile cerebral palsy or those who were diagnosed before 11 months of age with stroke, hemiplegia, or hemiparesis. The investigators said that they analyzed the 12 months after vaccination because “reports have suggested that the incidence of stroke rarely exceeds 1 year after VZV infection.”

Within the study period of 1991–2004, the investigators identified 39 children with an inpatient diagnosis of ischemic stroke out of roughly 1.14 million children in the cohort who had received at least one varicella vaccination, compared with 164 diagnoses of stroke in unvaccinated children.

There was no evidence of temporal clustering of the 39 patients who had strokes after vaccination. The risk of stroke was not significantly elevated at any point in time during the 12-month period after vaccination.

The study was funded entirely by the Centers for Disease Control and Prevention.

Three of the investigators reported that they served as a consultant to or received research support from Merck Pharmaceuticals. One of these investigators also has received research support from Novartis, GlaxoSmithKline, Sanofi Pasteur, and MedImmune.

Vaccination with live, attenuated varicella zoster virus was not associated with an increased risk of ischemic stroke in pediatric patients in the year after they received their vaccination, a retrospective, population-based study of children registered in the Vaccine Safety DataLink shows.

The study is the first to systematically examine the association between varicella zoster virus (VZV) vaccination and ischemic stroke. In previous studies, infection with the wild-type VZV has been associated with ischemic stroke in adults after herpes zoster ophthalmicus and in children after primary infection with the virus (chickenpox). Suspicion of an association between varicella vaccination and ischemic stroke initially arose because of case reports of children with signs and symptoms of ischemic strokes who had been vaccinated with live, attenuated VZV.

In the study of about 3.25 million children who were members of eight medical care organizations that participate in the Centers for Disease Control and Prevention's Vaccine Safety DataLink project, strokes were diagnosed in a significantly lower percentage of children who received at least one varicella vaccination than in those who did not receive the vaccine (0.003% vs. 0.008%), James G. Donahue, D.V.M, Ph.D., of the Marshfield (Wisc.) Clinic Research Foundation and his colleagues reported (Pediatrics 2009;123:e228–34).

Although unvaccinated children had a significantly older mean age than did vaccinated children (7.9 years vs. 1.9 years), because the vaccine was not widely distributed until the late 1990s, adjustment for age did not alter the results of the analysis.

Dr. David Kimberlin, a member of the American Academy of Pediatrics Committee on Infectious Diseases who specializes in varicella, called the study “definitive.” The results show that “using the varicella vaccine can save lives and morbidity among survivors who would have gotten chickenpox, anyway.”

The study “really shows the power of the Vaccine Safety DataLink. It is a phenomenal means by which complications of vaccinations can be assessed, and in this case, ruled out,” Dr. Kimberlin of the division of pediatric infectious diseases at the University of Alabama, Birmingham, said in an interview. He was not involved in the study.

The study included children older than 11 months but younger than 18 years, excluding those diagnosed with infantile cerebral palsy or those who were diagnosed before 11 months of age with stroke, hemiplegia, or hemiparesis. The investigators said that they analyzed the 12 months after vaccination because “reports have suggested that the incidence of stroke rarely exceeds 1 year after VZV infection.”

Within the study period of 1991–2004, the investigators identified 39 children with an inpatient diagnosis of ischemic stroke out of roughly 1.14 million children in the cohort who had received at least one varicella vaccination, compared with 164 diagnoses of stroke in unvaccinated children.

There was no evidence of temporal clustering of the 39 patients who had strokes after vaccination. The risk of stroke was not significantly elevated at any point in time during the 12-month period after vaccination.

The study was funded entirely by the Centers for Disease Control and Prevention.

Three of the investigators reported that they served as a consultant to or received research support from Merck Pharmaceuticals. One of these investigators also has received research support from Novartis, GlaxoSmithKline, Sanofi Pasteur, and MedImmune.

Vaccination with live, attenuated varicella zoster virus was not associated with an increased risk of ischemic stroke in pediatric patients in the year after they received their vaccination, a retrospective, population-based study of children registered in the Vaccine Safety DataLink shows.

The study is the first to systematically examine the association between varicella zoster virus (VZV) vaccination and ischemic stroke. In previous studies, infection with the wild-type VZV has been associated with ischemic stroke in adults after herpes zoster ophthalmicus and in children after primary infection with the virus (chickenpox). Suspicion of an association between varicella vaccination and ischemic stroke initially arose because of case reports of children with signs and symptoms of ischemic strokes who had been vaccinated with live, attenuated VZV.

In the study of about 3.25 million children who were members of eight medical care organizations that participate in the Centers for Disease Control and Prevention's Vaccine Safety DataLink project, strokes were diagnosed in a significantly lower percentage of children who received at least one varicella vaccination than in those who did not receive the vaccine (0.003% vs. 0.008%), James G. Donahue, D.V.M, Ph.D., of the Marshfield (Wisc.) Clinic Research Foundation and his colleagues reported (Pediatrics 2009;123:e228–34).

Although unvaccinated children had a significantly older mean age than did vaccinated children (7.9 years vs. 1.9 years), because the vaccine was not widely distributed until the late 1990s, adjustment for age did not alter the results of the analysis.

Dr. David Kimberlin, a member of the American Academy of Pediatrics Committee on Infectious Diseases who specializes in varicella, called the study “definitive.” The results show that “using the varicella vaccine can save lives and morbidity among survivors who would have gotten chickenpox, anyway.”

The study “really shows the power of the Vaccine Safety DataLink. It is a phenomenal means by which complications of vaccinations can be assessed, and in this case, ruled out,” Dr. Kimberlin of the division of pediatric infectious diseases at the University of Alabama, Birmingham, said in an interview. He was not involved in the study.

The study included children older than 11 months but younger than 18 years, excluding those diagnosed with infantile cerebral palsy or those who were diagnosed before 11 months of age with stroke, hemiplegia, or hemiparesis. The investigators said that they analyzed the 12 months after vaccination because “reports have suggested that the incidence of stroke rarely exceeds 1 year after VZV infection.”

Within the study period of 1991–2004, the investigators identified 39 children with an inpatient diagnosis of ischemic stroke out of roughly 1.14 million children in the cohort who had received at least one varicella vaccination, compared with 164 diagnoses of stroke in unvaccinated children.

There was no evidence of temporal clustering of the 39 patients who had strokes after vaccination. The risk of stroke was not significantly elevated at any point in time during the 12-month period after vaccination.

The study was funded entirely by the Centers for Disease Control and Prevention.

Three of the investigators reported that they served as a consultant to or received research support from Merck Pharmaceuticals. One of these investigators also has received research support from Novartis, GlaxoSmithKline, Sanofi Pasteur, and MedImmune.