On 2016 Aug 01, Gary Goldman commented:

The study by Kawail et al demonstrates that HZ incidence has increased over a 60 year period from “0.76 per 1000 person-years (PY) (95% confidence interval [CI], .63–.89) in 1945–1949 to 3.15 per 1000 PY (95% CI, 3.04–3.26) in 2000–2007” with a 2.5% per year rate over the time period after adjusting for age and sex (adjusted incidence rate ratio, 1.025 [95% CI, 1.023–1.026]; P < .001). [1] The authors do not provide an explanation for this increase, yet state, “This increase is unlikely to be due to the introduction of varicella vaccination….”

Unfortunately, Kawail et al do not report details of how widespread the uptake of varicella vaccine was in Olmstead County during 2000-2007. In fact, there were still substantial outbreaks of varicella during 2000 and 2001 (with a period of 9 months that the vaccine was unavailable). Minnesota did not require varicella vaccination for students entering kindergarten and 7th grade who lacked proof of having had chickenpox until 2004. In 1999, based on a CDC National Immunization Survey, varicella vaccine coverage was 61.6% among children aged 19-35 in Minnesota. [2] Approximately 50% of children aged less than 10 years must be vaccinated to effectively reduce exogenous boosting to initiate a noticeable increase in HZ incidence. Likely, only during 2003 through 2007 was varicella vaccination sufficiently widespread in Olmstead County to begin influencing (increasing) HZ incidence rates.

It was first hypothesized by Hope-Simpson [3] that “The peculiar age distribution of zoster may in part reflect the frequency with which the different age groups encounter cases of varicella and because of the ensuing boost to their antibody protection have their attacks of zoster postponed” [3]. However, prior to 1999, only limited studies existed that supported this hypothesis. For example, in 1983, Arvin et al. noted a boost in cell-mediated immunity (CMI) in 71% of adults who were exposed to varicella patients in the family [4]. In 1995, Terada et al. reported that Japanese pediatricians aged 50–69 who received multiple VZV exposures, demonstrated HZ incidence rates one-half to one-eighth that of the general population [5]. Gershon et al. in 1996 showed an immunologic boost that reduced the risk of HZ among leukemic children by reexposure to VZV, either by vaccination or by close exposure to varicella [6]. A 1998 study by Solomon found that pediatricians who had a greater incidence of exposure to VZV had lower rates of HZ than psychiatrists who had the lowest VZV exposure rates [7]. More recent studies by Thomas et al. [8] and Salleras et al. [9] have also demonstrated that re-exposure to VZV via contacts with children was associated with reduction in the risk of HZ in adults. In more recent times, during the varicella vaccination era, additional studies, including those derived from the Antelope Valley Varicella Active Surveillance Project (VASP) in a community with widespread varicella vaccination, have emerged that have provided data that validates Hope-Simpson’s hypothesis. [10-12]. In support of the VASP trends [10-11] between 2000 and 2006, a more recent 2013 study by Guzzetta et al suggests that each episode of exposure to VZV increases protection against HZ and that ‘‘this mechanism may be critical in shaping HZ patterns’’. [12]

Thus, while Kawail et al is unable to provide an explanation for the mean 2.5% annual increase in HZ incidence over six decades, one logical hypothesis for the increase is related to societal changes. Living conditions have gradually changed during the past six decades from multiple generations of families residing in a single household, to more independent living as children aged 18 years and over have increasingly moved out of their parent's home and elderly and sedentary individuals are placed in care facilities. Interesting, a Census Bureau reports, “In 2010, there were 40.3 million people aged 65 and above, comprising 13% of the overall population. (This total is 12 times the number it was in 1900, when this group constituted only 4.1% of the population.)” [13] Thus, due to changing trends in society structure and increases in the elderly population, parents and grandparents generally have fewer opportunities for exogenous boosting of their cell-mediated immunity due to reduced contact to children infected with varicella—giving rise to the steady increase in HZ incidence—especially in decades prior to the varicella vaccination era.

In the Antelope Valley VASP, varicella vaccination was widespread in the community with approximately 50% of children aged <10 years vaccinated by 2000. By 2000, exogenous exposures to natural varicella (producing immunologic boosts) were dramatically reduced, especially after a marked decline in varicella seasonality in 1999. After 2 years of active HZ surveillance (2000 and 2001), the number of HZ case reports had maintained or increased in every adult age category except elderly adults aged 70 years and older. Using the paired t-test, there was a statistically significant (p < 0.042; t = 2.95, dF = 4) 28.5% increase in HZ case reports from 158 to 203 from 2000 to 2001 for the population aged 20–69 years. [10] Moreover, the 2007 VASP annual summary to the CDC presents data (not ascertainment corrected) demonstrating a statistically significant increase in HZ incidence rates, from 3.90 to 4.70 per 1,000 p-y in from 2006 to 2007 among adults aged 50 years and older. [11]

Finally, there is a further worrying reason to suspect future increases in HZ incidence. When a child is administered the varicella (or Oka-) strain and then later is exposed to either a child with natural chickenpox or an adult with herpes zoster (almost always due to the reactivation of the natural or wild-type strain), the child harbors two similar but possibly sufficiently heterologous strains--that now are both subject to reactivation. This could potentially double the chances for the reactivation of herpes zoster, or at a minimum, at least increase the chances for reactivation of shingles relative to the pre-varicella vaccination era. [14]

[1] Kawai K, 2016 [2] http://www.cdc.gov/vaccines/imz-managers/coverage/nis/child/index.html [3] HOPE-SIMPSON RE, 1965 [4] Arvin AM, 1983 [5] Terada K, 1995 [6] Gershon AA, 1996 [7] Solomon BA, 1998 [8] Thomas SL, 2002 [9] Salleras M, 2011 [10] Goldman GS, 2013 [11] Goldman GS, 2014 [12] Guzzetta G, 2013 [13] Raphel A. Trends and statistics relating to U.S. seniors, elderly: Census Bureau 2014 report. August 5, 2014. http://journalistsresource.org/studies/society/public-health/trends-statistics-relating-us-seniors-elderly-census-bureau-2014-report [last accessed 07/26/2016] [14] Weinmann S, 2013

On 2016 Aug 01, Gary Goldman commented:

The study by Kawail et al demonstrates that HZ incidence has increased over a 60 year period from “0.76 per 1000 person-years (PY) (95% confidence interval [CI], .63–.89) in 1945–1949 to 3.15 per 1000 PY (95% CI, 3.04–3.26) in 2000–2007” with a 2.5% per year rate over the time period after adjusting for age and sex (adjusted incidence rate ratio, 1.025 [95% CI, 1.023–1.026]; P < .001). [1] The authors do not provide an explanation for this increase, yet state, “This increase is unlikely to be due to the introduction of varicella vaccination….”

Unfortunately, Kawail et al do not report details of how widespread the uptake of varicella vaccine was in Olmstead County during 2000-2007. In fact, there were still substantial outbreaks of varicella during 2000 and 2001 (with a period of 9 months that the vaccine was unavailable). Minnesota did not require varicella vaccination for students entering kindergarten and 7th grade who lacked proof of having had chickenpox until 2004. In 1999, based on a CDC National Immunization Survey, varicella vaccine coverage was 61.6% among children aged 19-35 in Minnesota. [2] Approximately 50% of children aged less than 10 years must be vaccinated to effectively reduce exogenous boosting to initiate a noticeable increase in HZ incidence. Likely, only during 2003 through 2007 was varicella vaccination sufficiently widespread in Olmstead County to begin influencing (increasing) HZ incidence rates.

It was first hypothesized by Hope-Simpson [3] that “The peculiar age distribution of zoster may in part reflect the frequency with which the different age groups encounter cases of varicella and because of the ensuing boost to their antibody protection have their attacks of zoster postponed” [3]. However, prior to 1999, only limited studies existed that supported this hypothesis. For example, in 1983, Arvin et al. noted a boost in cell-mediated immunity (CMI) in 71% of adults who were exposed to varicella patients in the family [4]. In 1995, Terada et al. reported that Japanese pediatricians aged 50–69 who received multiple VZV exposures, demonstrated HZ incidence rates one-half to one-eighth that of the general population [5]. Gershon et al. in 1996 showed an immunologic boost that reduced the risk of HZ among leukemic children by reexposure to VZV, either by vaccination or by close exposure to varicella [6]. A 1998 study by Solomon found that pediatricians who had a greater incidence of exposure to VZV had lower rates of HZ than psychiatrists who had the lowest VZV exposure rates [7]. More recent studies by Thomas et al. [8] and Salleras et al. [9] have also demonstrated that re-exposure to VZV via contacts with children was associated with reduction in the risk of HZ in adults. In more recent times, during the varicella vaccination era, additional studies, including those derived from the Antelope Valley Varicella Active Surveillance Project (VASP) in a community with widespread varicella vaccination, have emerged that have provided data that validates Hope-Simpson’s hypothesis. [10-12]. In support of the VASP trends [10-11] between 2000 and 2006, a more recent 2013 study by Guzzetta et al suggests that each episode of exposure to VZV increases protection against HZ and that ‘‘this mechanism may be critical in shaping HZ patterns’’. [12]

Thus, while Kawail et al is unable to provide an explanation for the mean 2.5% annual increase in HZ incidence over six decades, one logical hypothesis for the increase is related to societal changes. Living conditions have gradually changed during the past six decades from multiple generations of families residing in a single household, to more independent living as children aged 18 years and over have increasingly moved out of their parent's home and elderly and sedentary individuals are placed in care facilities. Interesting, a Census Bureau reports, “In 2010, there were 40.3 million people aged 65 and above, comprising 13% of the overall population. (This total is 12 times the number it was in 1900, when this group constituted only 4.1% of the population.)” [13] Thus, due to changing trends in society structure and increases in the elderly population, parents and grandparents generally have fewer opportunities for exogenous boosting of their cell-mediated immunity due to reduced contact to children infected with varicella—giving rise to the steady increase in HZ incidence—especially in decades prior to the varicella vaccination era.

In the Antelope Valley VASP, varicella vaccination was widespread in the community with approximately 50% of children aged <10 years vaccinated by 2000. By 2000, exogenous exposures to natural varicella (producing immunologic boosts) were dramatically reduced, especially after a marked decline in varicella seasonality in 1999. After 2 years of active HZ surveillance (2000 and 2001), the number of HZ case reports had maintained or increased in every adult age category except elderly adults aged 70 years and older. Using the paired t-test, there was a statistically significant (p < 0.042; t = 2.95, dF = 4) 28.5% increase in HZ case reports from 158 to 203 from 2000 to 2001 for the population aged 20–69 years. [10] Moreover, the 2007 VASP annual summary to the CDC presents data (not ascertainment corrected) demonstrating a statistically significant increase in HZ incidence rates, from 3.90 to 4.70 per 1,000 p-y in from 2006 to 2007 among adults aged 50 years and older. [11]

Finally, there is a further worrying reason to suspect future increases in HZ incidence. When a child is administered the varicella (or Oka-) strain and then later is exposed to either a child with natural chickenpox or an adult with herpes zoster (almost always due to the reactivation of the natural or wild-type strain), the child harbors two similar but possibly sufficiently heterologous strains--that now are both subject to reactivation. This could potentially double the chances for the reactivation of herpes zoster, or at a minimum, at least increase the chances for reactivation of shingles relative to the pre-varicella vaccination era. [14]

[1] Kawai K, 2016 [2] http://www.cdc.gov/vaccines/imz-managers/coverage/nis/child/index.html [3] HOPE-SIMPSON RE, 1965 [4] Arvin AM, 1983 [5] Terada K, 1995 [6] Gershon AA, 1996 [7] Solomon BA, 1998 [8] Thomas SL, 2002 [9] Salleras M, 2011 [10] Goldman GS, 2013 [11] Goldman GS, 2014 [12] Guzzetta G, 2013 [13] Raphel A. Trends and statistics relating to U.S. seniors, elderly: Census Bureau 2014 report. August 5, 2014. http://journalistsresource.org/studies/society/public-health/trends-statistics-relating-us-seniors-elderly-census-bureau-2014-report [last accessed 07/26/2016] [14] Weinmann S, 2013