On 2016 Sep 15, Gary Goldman commented:

Civen et al report the average HZ incidence of 12.8 cases/100,000 children aged <10 years during 2007 to 2010.¹ Since two different ascertainment sources are available for the reporting of HZ cases—schools (including preschools), and public and private healthcare providers (including hospitals)—capture-recapture techniques could have been employed to determine that the Antelope Valley project had approximately 50% case ascertainment, and thus, the true HZ figure is approximately double that reported. Interestingly, 25.6 cases/100,000, or twice the reported rate closely compares with the rate of 27.4 cases/100,000 (95% C.I. 22.7-32.7) based on 172,163 vaccinated children with overall follow-up of 446,027 person-years among children aged <12 years during 2007-2008 reported by Tseng et al.²

Civen et al report that among 10- to 19-year olds a 63% increasing trend in HZ incidence from 2000 to 2006 was documented; however, “the increased incidence could not be confidently explained.” The authors concede, “the possibility persists that children infected by wild-type VZV experienced increased rates of HZ because they were having fewer opportunities to be exposed to exogenous VZV, leading to reduced immune control of HZ.“¹ The reason that the 63% increasing trend in HZ incidence among 10- to 19-year olds has not been confidently explained is that the methodology utilized by Civen et al did not include stratifying HZ incidence rates by using two widely different cohorts: those vaccinated and those with a history of wild-type (natural) varicella. Computing a single mean HZ incidence rate of a bimodal distribution is statistically invalid and conceals the reality that the HZ incidence rate among children and adolescents with a history of wild-type varicella has an increasing trend.³ By performing such a stratified analysis, Civen et al could have tested the hypothesis that individuals with a prior history of varicella are experiencing increasing HZ incidence due to fewer exogenous exposures, and thus, reduced opportunities for boosting cell-mediated immunity to VZV.^4,5

Civen et al state, “The case for this hypothesis has weakened as studies have found no acceleration in rates of HZ among adults in the United States since the varicella vaccination was introduced, despite the fact that opportunities for varicella exposure have plummeted.” Interestingly, the same Antelope Valley surveillance project did collect HZ cases during 2000-2001 and 2006-2007 that showed statistically significant increases among adults. The Antelope Valley annual summary to the CDC demonstrates that in 2000 and 2001, HZ cases (not ascertainment corrected) reported to the project either maintained or increased in every adult 10-year age category (20–29, 30–39, . . . , 60–69 years), yielding a statistically significant difference. Reported HZ cases among adults aged 20–69 years increased 28.5%—from 158 in 2000 to 203 in 2001 (p <0.042; t = 2.95, df = 4).⁶ Again, HZ incidence rates among adults aged 50 years and older increased from 390/100,000 p-y in 2006 to 470/100,000 p-y in 2007 with a statistically significant rate ratio of 1.2 (95% CI: 1.04–1.40).⁷ A Canadian study by Marra et al concludes that "the incidence of zoster and PHN is increasing with time" and suggests "recent studies have shown an increasing incidence of herpes zoster infection, which may be related to the introduction of varicella vaccination programs in children."⁸

The United States has traded a dramatic reduction in varicella disease which in the prevaccine era accounted for only 25% of the VZV medical costs (i.e., 75% of VZV medical costs were attributed to cases of HZ) for a disproportional increase in HZ costs associated with increasing HZ incidence among adults with a history of wild-type varicella. It is an unfortunate fact that 20 years after the introduction of the varicella vaccine in the US, healthcare officials are still claiming that the mechanism of exogenous boosting “is not well understood” and “the case for this hypothesis has weakened,” when in reality, the data currently exist to understand this biological mechanism first proposed in 1965 by Dr. Robert Edgar Hope-Simpson.⁴ "Rather than eliminating varicella in children as promised, routine vaccination against varicella has proven extremely costly and has created continual cycles of treatment and disease."³

References

[1] Civen R, Marin M. Zhang J. Abraham A, Harpaz R, Mascola L. Bialek S. Update on incidence of herpes zoster among children and adolescents after implementation of varicella vaccination, Antelope Valley, CA, 2000 to 2010. Pediatr Infect Dis J. 2016 Oct; 35(10):1132-1136.Civen R, 2016

[2] Tseng HF, Smith N, Marcy SM, Sy LS, Jacobsen SJ. Incidence of herpes zoster among children vaccinated with varicella vaccine in a prepaid health care plan in the United States, 2007, 2008. Pediatr Infect Dis J 2009;28(December(12)):1069–72.Tseng HF, 2009

[3] Goldman GS and King PG. Review of the United States universal varicella vaccination program: Herpes zoster incidence rates, cost-effectiveness, and vaccine efficacy based primarily on the Antelope Valley Varicella active surveillance project data. Vaccine 2013; 31(13): 1680–1694.Goldman GS, 2013

[4] Hope-Simpson RE. The nature of herpes zoster: a long term study and a new hypothesis. Proc R Soc Med 1965; 58: 9–20.HOPE-SIMPSON RE, 1965

[5] Guzzetta G, Poletti P, Del Fava E, Ajelli M, Scalia Tomba GP, Merler S, et al. Hope-Simpson’s progressive immunity hypothesis as a possible explanation for Herpes zoster incidence data. Am J Epidemiol 2013; 177(10): 1134–1142.Guzzetta G, 2013

[6] Maupin T, Peterson C, Civen R and Mascola L. Varicella Active Surveillance Project (VASP). 2000, 2001, Annual Summary. Antelope Valley, County of Los Angeles Department of Health Services (LADHS), Acute Communicable Disease Control, Centers for Disease Control and Prevention (CDC) Cooperative Agreement No. U66/CCU911165-10.

[7] Maupin T, Peterson C, Civen R and Mascola L. Varicella Active Surveillance Project (VASP). 2006, 2007 Annual Summary. Antelope Valley , County of Los Angeles Department of Health Services (LADHS), Acute Communicable Disease Control, Centers for Disease Control and Prevention (CDC) Cooperative Agreement No. 5U01 IP000020-02/5U01 IP000020-04.

[8] Marra F, Chong M and Najafzadeh M. Increasing incidence associated with herpes zoster infection in British Columbia, Canada. BMC Infect Dis. 2016 Oct 20; 16(1):589.Marra F, 2016

On 2016 Sep 15, Gary Goldman commented:

Civen et al report the average HZ incidence of 12.8 cases/100,000 children aged <10 years during 2007 to 2010.¹ Since two different ascertainment sources are available for the reporting of HZ cases—schools (including preschools), and public and private healthcare providers (including hospitals)—capture-recapture techniques could have been employed to determine that the Antelope Valley project had approximately 50% case ascertainment, and thus, the true HZ figure is approximately double that reported. Interestingly, 25.6 cases/100,000, or twice the reported rate closely compares with the rate of 27.4 cases/100,000 (95% C.I. 22.7-32.7) based on 172,163 vaccinated children with overall follow-up of 446,027 person-years among children aged <12 years during 2007-2008 reported by Tseng et al.²

Civen et al report that among 10- to 19-year olds a 63% increasing trend in HZ incidence from 2000 to 2006 was documented; however, “the increased incidence could not be confidently explained.” The authors concede, “the possibility persists that children infected by wild-type VZV experienced increased rates of HZ because they were having fewer opportunities to be exposed to exogenous VZV, leading to reduced immune control of HZ.“¹ The reason that the 63% increasing trend in HZ incidence among 10- to 19-year olds has not been confidently explained is that the methodology utilized by Civen et al did not include stratifying HZ incidence rates by using two widely different cohorts: those vaccinated and those with a history of wild-type (natural) varicella. Computing a single mean HZ incidence rate of a bimodal distribution is statistically invalid and conceals the reality that the HZ incidence rate among children and adolescents with a history of wild-type varicella has an increasing trend.³ By performing such a stratified analysis, Civen et al could have tested the hypothesis that individuals with a prior history of varicella are experiencing increasing HZ incidence due to fewer exogenous exposures, and thus, reduced opportunities for boosting cell-mediated immunity to VZV.^4,5

Civen et al state, “The case for this hypothesis has weakened as studies have found no acceleration in rates of HZ among adults in the United States since the varicella vaccination was introduced, despite the fact that opportunities for varicella exposure have plummeted.” Interestingly, the same Antelope Valley surveillance project did collect HZ cases during 2000-2001 and 2006-2007 that showed statistically significant increases among adults. The Antelope Valley annual summary to the CDC demonstrates that in 2000 and 2001, HZ cases (not ascertainment corrected) reported to the project either maintained or increased in every adult 10-year age category (20–29, 30–39, . . . , 60–69 years), yielding a statistically significant difference. Reported HZ cases among adults aged 20–69 years increased 28.5%—from 158 in 2000 to 203 in 2001 (p <0.042; t = 2.95, df = 4).⁶ Again, HZ incidence rates among adults aged 50 years and older increased from 390/100,000 p-y in 2006 to 470/100,000 p-y in 2007 with a statistically significant rate ratio of 1.2 (95% CI: 1.04–1.40).⁷ A Canadian study by Marra et al concludes that "the incidence of zoster and PHN is increasing with time" and suggests "recent studies have shown an increasing incidence of herpes zoster infection, which may be related to the introduction of varicella vaccination programs in children."⁸

The United States has traded a dramatic reduction in varicella disease which in the prevaccine era accounted for only 25% of the VZV medical costs (i.e., 75% of VZV medical costs were attributed to cases of HZ) for a disproportional increase in HZ costs associated with increasing HZ incidence among adults with a history of wild-type varicella. It is an unfortunate fact that 20 years after the introduction of the varicella vaccine in the US, healthcare officials are still claiming that the mechanism of exogenous boosting “is not well understood” and “the case for this hypothesis has weakened,” when in reality, the data currently exist to understand this biological mechanism first proposed in 1965 by Dr. Robert Edgar Hope-Simpson.⁴ "Rather than eliminating varicella in children as promised, routine vaccination against varicella has proven extremely costly and has created continual cycles of treatment and disease."³

References

[1] Civen R, Marin M. Zhang J. Abraham A, Harpaz R, Mascola L. Bialek S. Update on incidence of herpes zoster among children and adolescents after implementation of varicella vaccination, Antelope Valley, CA, 2000 to 2010. Pediatr Infect Dis J. 2016 Oct; 35(10):1132-1136.Civen R, 2016

[2] Tseng HF, Smith N, Marcy SM, Sy LS, Jacobsen SJ. Incidence of herpes zoster among children vaccinated with varicella vaccine in a prepaid health care plan in the United States, 2007, 2008. Pediatr Infect Dis J 2009;28(December(12)):1069–72.Tseng HF, 2009

[3] Goldman GS and King PG. Review of the United States universal varicella vaccination program: Herpes zoster incidence rates, cost-effectiveness, and vaccine efficacy based primarily on the Antelope Valley Varicella active surveillance project data. Vaccine 2013; 31(13): 1680–1694.Goldman GS, 2013

[4] Hope-Simpson RE. The nature of herpes zoster: a long term study and a new hypothesis. Proc R Soc Med 1965; 58: 9–20.HOPE-SIMPSON RE, 1965

[5] Guzzetta G, Poletti P, Del Fava E, Ajelli M, Scalia Tomba GP, Merler S, et al. Hope-Simpson’s progressive immunity hypothesis as a possible explanation for Herpes zoster incidence data. Am J Epidemiol 2013; 177(10): 1134–1142.Guzzetta G, 2013

[6] Maupin T, Peterson C, Civen R and Mascola L. Varicella Active Surveillance Project (VASP). 2000, 2001, Annual Summary. Antelope Valley, County of Los Angeles Department of Health Services (LADHS), Acute Communicable Disease Control, Centers for Disease Control and Prevention (CDC) Cooperative Agreement No. U66/CCU911165-10.

[7] Maupin T, Peterson C, Civen R and Mascola L. Varicella Active Surveillance Project (VASP). 2006, 2007 Annual Summary. Antelope Valley , County of Los Angeles Department of Health Services (LADHS), Acute Communicable Disease Control, Centers for Disease Control and Prevention (CDC) Cooperative Agreement No. 5U01 IP000020-02/5U01 IP000020-04.

[8] Marra F, Chong M and Najafzadeh M. Increasing incidence associated with herpes zoster infection in British Columbia, Canada. BMC Infect Dis. 2016 Oct 20; 16(1):589.Marra F, 2016