Varicella Vaccine May Spark CNS Disease, Study Finds

BALTIMORE — Despite the introduction of the varicella vaccine, central nervous system disease continues to be associated with varicella zoster virus and in rare cases can even result from reactivated vaccine strains, a study of 26 California cases shows.

Dr. Barbara Pahud and her colleagues identified 41 varicella zoster virus (VZV)-positive cases within the California Encephalitis Project (CEP), which runs standardized panels of diagnostic tests on specimens from cases of central nervous system (CNS) disease referred by physicians.

Dr. Pahud is a clinical fellow in pediatric infectious diseases at the University of California, San Francisco, and she presented the study findings in a poster at a conference on vaccine research sponsored by the National Foundation for Infectious Diseases.

Four real-time polymerase chain reaction protocols were used to target four vaccine-associated single-base polymorphisms, allowing the identification of VZV-positive specimens and discrimination of vaccine (vOka) from wild- type VZV strains. Cerebral spinal fluid samples were sent to the CDC for genotyping. Additional clinical information was requested for the 26 cases that were successfully genotyped. The median age of this cohort was 46 years; slightly more than half (53%) were white.

"This report includes the fourth documented case of VZV vaccine strain associated with CNS disease, presenting 11 years post immunization [with] meningitis and herpes zoster rash," the researchers wrote.

This strain was found in a previously healthy 12-year-old girl, who presented with meningitis symptoms. Notably, clinical presentation for this case did not differ from that of wild-type varicella-associated CNS disease, "making the diagnosis of vaccine strain reactivation difficult based on clinical presentation alone."

VZV isolates can be divided into three genotypes: European, Japanese, and mosaic. In the United States, the predominant circulating genotype is the European one (82%).

The Oka vaccine strain belongs to the Japanese genotype. Sequencing data from the California cohort show that no one genotype predominates. In addition, the wild- type Japanese strains appear to be more common than has been previously reported.

Varicella-associated CNS reactivation occurs in both immunocompromised and immunocompetent individuals, who might or might not present with herpes zoster (HZ) rash. In this cohort "only 42% of cases presented with an HZ rash. Clinicians should maintain a high index of suspicion in diagnosing VZV in patients with CNS infection, since more often than not, it presents without the characteristic rash of primary varicella or HZ reactivation," the researchers noted.

Four out of the seven pediatric patients had no history of primary varicella disease. Varicella-associated CNS disease in these patients could be secondary to reactivation or caused by a first-time varicella rash, they wrote.

The live attenuated VZV vaccine was introduced in 1996. More than 50 million doses have been distributed in the United States since then. Current recommendations are two doses for children and other healthy people without evidence of immunity.

The study was funded through a subcontract with America's Health Insurance Plans under a contract from the Centers for Disease Control and Prevention.

BALTIMORE — Despite the introduction of the varicella vaccine, central nervous system disease continues to be associated with varicella zoster virus and in rare cases can even result from reactivated vaccine strains, a study of 26 California cases shows.

Dr. Barbara Pahud and her colleagues identified 41 varicella zoster virus (VZV)-positive cases within the California Encephalitis Project (CEP), which runs standardized panels of diagnostic tests on specimens from cases of central nervous system (CNS) disease referred by physicians.

Dr. Pahud is a clinical fellow in pediatric infectious diseases at the University of California, San Francisco, and she presented the study findings in a poster at a conference on vaccine research sponsored by the National Foundation for Infectious Diseases.

Four real-time polymerase chain reaction protocols were used to target four vaccine-associated single-base polymorphisms, allowing the identification of VZV-positive specimens and discrimination of vaccine (vOka) from wild- type VZV strains. Cerebral spinal fluid samples were sent to the CDC for genotyping. Additional clinical information was requested for the 26 cases that were successfully genotyped. The median age of this cohort was 46 years; slightly more than half (53%) were white.

"This report includes the fourth documented case of VZV vaccine strain associated with CNS disease, presenting 11 years post immunization [with] meningitis and herpes zoster rash," the researchers wrote.

This strain was found in a previously healthy 12-year-old girl, who presented with meningitis symptoms. Notably, clinical presentation for this case did not differ from that of wild-type varicella-associated CNS disease, "making the diagnosis of vaccine strain reactivation difficult based on clinical presentation alone."

VZV isolates can be divided into three genotypes: European, Japanese, and mosaic. In the United States, the predominant circulating genotype is the European one (82%).

The Oka vaccine strain belongs to the Japanese genotype. Sequencing data from the California cohort show that no one genotype predominates. In addition, the wild- type Japanese strains appear to be more common than has been previously reported.

Varicella-associated CNS reactivation occurs in both immunocompromised and immunocompetent individuals, who might or might not present with herpes zoster (HZ) rash. In this cohort "only 42% of cases presented with an HZ rash. Clinicians should maintain a high index of suspicion in diagnosing VZV in patients with CNS infection, since more often than not, it presents without the characteristic rash of primary varicella or HZ reactivation," the researchers noted.

Four out of the seven pediatric patients had no history of primary varicella disease. Varicella-associated CNS disease in these patients could be secondary to reactivation or caused by a first-time varicella rash, they wrote.

The live attenuated VZV vaccine was introduced in 1996. More than 50 million doses have been distributed in the United States since then. Current recommendations are two doses for children and other healthy people without evidence of immunity.

The study was funded through a subcontract with America's Health Insurance Plans under a contract from the Centers for Disease Control and Prevention.

BALTIMORE — Despite the introduction of the varicella vaccine, central nervous system disease continues to be associated with varicella zoster virus and in rare cases can even result from reactivated vaccine strains, a study of 26 California cases shows.

Dr. Barbara Pahud and her colleagues identified 41 varicella zoster virus (VZV)-positive cases within the California Encephalitis Project (CEP), which runs standardized panels of diagnostic tests on specimens from cases of central nervous system (CNS) disease referred by physicians.

Dr. Pahud is a clinical fellow in pediatric infectious diseases at the University of California, San Francisco, and she presented the study findings in a poster at a conference on vaccine research sponsored by the National Foundation for Infectious Diseases.

Four real-time polymerase chain reaction protocols were used to target four vaccine-associated single-base polymorphisms, allowing the identification of VZV-positive specimens and discrimination of vaccine (vOka) from wild- type VZV strains. Cerebral spinal fluid samples were sent to the CDC for genotyping. Additional clinical information was requested for the 26 cases that were successfully genotyped. The median age of this cohort was 46 years; slightly more than half (53%) were white.

"This report includes the fourth documented case of VZV vaccine strain associated with CNS disease, presenting 11 years post immunization [with] meningitis and herpes zoster rash," the researchers wrote.

This strain was found in a previously healthy 12-year-old girl, who presented with meningitis symptoms. Notably, clinical presentation for this case did not differ from that of wild-type varicella-associated CNS disease, "making the diagnosis of vaccine strain reactivation difficult based on clinical presentation alone."

VZV isolates can be divided into three genotypes: European, Japanese, and mosaic. In the United States, the predominant circulating genotype is the European one (82%).

The Oka vaccine strain belongs to the Japanese genotype. Sequencing data from the California cohort show that no one genotype predominates. In addition, the wild- type Japanese strains appear to be more common than has been previously reported.

Varicella-associated CNS reactivation occurs in both immunocompromised and immunocompetent individuals, who might or might not present with herpes zoster (HZ) rash. In this cohort "only 42% of cases presented with an HZ rash. Clinicians should maintain a high index of suspicion in diagnosing VZV in patients with CNS infection, since more often than not, it presents without the characteristic rash of primary varicella or HZ reactivation," the researchers noted.

Four out of the seven pediatric patients had no history of primary varicella disease. Varicella-associated CNS disease in these patients could be secondary to reactivation or caused by a first-time varicella rash, they wrote.

The live attenuated VZV vaccine was introduced in 1996. More than 50 million doses have been distributed in the United States since then. Current recommendations are two doses for children and other healthy people without evidence of immunity.

The study was funded through a subcontract with America's Health Insurance Plans under a contract from the Centers for Disease Control and Prevention.