Canada Communicable Disease Report

Final Report of Outcomes from the National Consensus Conference for Vaccine-Preventable Diseases in Canada

June 2005

Disease Summaries

Varicella

Background

The purpose of this session was to review outcomes from the 1999 Consensus Conference on Varicella within the context of recent evidence, to identify issues, and to make recommendations on updating the national goals, recommendations and targets for varicella immunization and disease reduction. Below are highlights of presentations on varicella incidence in the US and Canada.

United States:

(Dr. Jane Seward, CDC)

In the US, following the introduction of the varicella vaccine program in 1995, a decline in 80% to 90% of reported varicella cases was observed. With varicella immunization coverage currently at 85% and climbing for children 19 to 35 months, the US has experienced an 80% reduction in hospitalizations and a significant increase in herd immunity. Rates of varicella as an underlying cause of death have also declined in all ages < 50 years (90% decline in children 1 to 9 years), except among persons > 50 years of age (the cause of death in this group may be herpes zoster, misclassified as varicella). The vaccine has an excellent safety profile, with only rare reported occurrences of serious adverse effects, and has been shown to be more than 95% effective in preventing severe disease and 80% to 85% effective in preventing all disease.

The US varicella immunization program began with a goal of disease reduction of more than 90% in all age groups by 2010, with targeted immunization rates of 90% among children age 19 to 35 months and adolescents aged 13 to 15 years. Current recommendations for varicella vaccine use include one dose for all healthy children aged 12 months to < 12 years, two doses 3 months apart for immunocompromised children, immunization requirements for daycare and school entry, and post-exposure and outbreak control immunization. Among adults, immunization is recommended for health care workers and family contacts of immunocompromised people, individuals at high risk of exposure and transmission, women of childbearing age, and international travellers.

Evidence in the US suggests that a one-dose vaccine program is cost-beneficial or break-even from a medical perspective and a two-dose program is cost-beneficial from a societal perspective. The US is considering elevating the goal of its varicella vaccine program from reduction to elimination (reduction is defined as the absence of endemic disease transmission). A two-dose vaccine policy for children will be needed for improved disease control and elimination. As of mid-June 2005, the Advisory Committee on Immunization Practices (ACIP) had not yet voted on this proposal.

Canada:

(Jeannette Macey, MSc, MA)

The current recommendation of the National Advisory Committee on Immunization (NACI) is "to reduce the incidence, morbidity, and mortality related to varicella, through routinely immunizing children between 12 to 18 months of age and immunizing susceptible older children, adolescents and adults who are at high risk for severe varicella and its complications"⁽⁵⁾. Catch-up priorities include women of childbearing age, postpartum women, immunocompromised individuals, health care workers, teachers and daycare workers, and persons from tropical climates who are still susceptible to varicella. While the US is currently pursuing a goal of varicella elimination, this is not yet a goal in Canada.

Since the introduction of the varicella vaccine in Canada in 1998, there has been a trend toward pre-exposure immunization, with post-exposure immunization also found to be effective. Varicella immunization programs have been introduced in 11 of the 13 jurisdictions for children 12 to 18 months of age, with evidence revealing a link between increased immunization coverage and declining varicella-related hospital admissions across all age groups. Nine provinces and territories have varicella catch-up programs in place, although stages of implementation, standards and coverage vary. There are currently no daycare or school-entry requirements for varicella, and outbreaks are not reported or subject to mandatory investigation. Some jurisdictions follow Canadian Paediatric Society (CPS) guidelines for return to daycare or school following illness, but there is no consistency across the country.

Active varicella surveillance is carried out by the CPS Immunization Monitoring Program Active (IMPACT) which consists of 12 paediatric centres and captures 90% of pediatric tertiary beds across Canada. Still, Canada does not have adequate systems in place for national varicella surveillance. Provinces/territories either report inconsistently or incompletely resulting in under-reporting of disease incidence.

Discussion

Participants agreed that the US experience should serve as the main evidence for decision-making, given the relatively recent introduction of the varicella vaccine in Canada. Discussion ensued on key considerations in the development of updated goals and targets for varicella, with unresolved or "parking lot" issues also flagged. The discussion guide used by participants is attached in Appendix B.

Surveillance: Surveillance data do not accurately reflect the disease burden of varicella in Canada due to under-reporting. Data on varicella-related mortality is also lacking. Contributing factors include variations in reporting methods and inadequate laboratory diagnostics; issues aggravated by a national case definition which limits a confirmed case to one in which there is virus isolation or clinical illness and an epidemiological link to a laboratory-confirmed case. As part of a review of the national Notifiable Diseases Reporting System Database (NDRS), case definitions are being updated to reflect actual experience and incorporate epidemiological definitions.

Epidemiology: Data suggest parallels between the Canadian and US experience, including varicella epidemiology in the pre-vaccine era as well as linkages between immunization coverage, varicella cases and other disease-related outcomes.

Breakthrough disease: While varicella immunization has been shown to be highly effective, practitioners and the general public must be made aware that there are isolated cases of vaccine failure or "breakthrough disease" (i.e. most children experience a sero-response, but may not develop sufficient antibodies to mount an adequate response to be completely protected). Breakthrough disease occurs at a rate of 0.7% to 3.0% per year. Available data indicate that a two-dose immunization regimen could noticeably reduce this rate (i.e. a study of varicella antibodies 10 years post-immunization revealed breakthrough rates of 0.7% per year for single-dose vaccinees and 0.2% for two-dose vaccinees).

Participants noted that the term "breakthrough", used only for varicella, implies that the virus is breaking through when, in fact, it refers to a vaccine failure. As such, preference was shown for the term "vaccine-modified varicella" also being considered by the CDC.

Laboratory testing: Several factors impede laboratory testing for varicella. Laboratory diagnostic recommendations for varicella differ from those for measles and rubella. Further, there are no reliable tests for demonstrating serological immunity after varicella zoster virus (VZV) immunization: gpELISA is not commercially available; VZV glycoprotein antigen is only available in limited supply; Immunoglobulin G (ImG) serology screening, while effective with wild varicella infection, is not sensitive enough to demonstrate vaccine-induced immunity; and, relative to other diseases, the Immunoglobulin M (IgM) kinetics of the varicella immune response is not well known.

Immunocompromised people: Immunocompromised persons, who account for 30% to 40% of varicella-related hospital admissions, experience very few complications following Acyclovir treatment; although cases of acyclovir resistance have been reported. The impact of passive prophylaxis with varicella zoster immunoglobulin post-exposure and early implementation of antiviral treatment has significantly reduced morbidity and mortality in immunocompromised populations.

Parking lot issues: A number of issues were identified by participants, but not resolved. Key among these were the incidence of herpes zoster in adults, with participants agreeing to postpone making recommendations for disease reduction goals and targets; and the proposed linking of varicella and measles immunization coverage targets by 2010, which was not supported by participants. With regard to the latter, distinctions between the measles and varicella vaccine programs were noted, in particular the elimination goal and two-dose regimen on which measles coverage targets are based differ significantly from current national recommendations and existing provincial and territorial programs. Participants determined that varicella should be treated as a standalone disease until a measles, mumps, rubella, varicella vaccine (MMRV) is licensed in Canada, at which time linkage of coverage targets could be considered.

Setting goals and recommendations

Participants made the following recommendations for varicella, with the caveat that each be revisited within 5 years to evaluate progress and consider new experience in both the US and Canada.

Goal

Reduce illness and death due to complications from varicella through immunization

Rationale: This goal was proposed following the consensus conference and not voted upon. Development of elimination goal was deemed premature at time of conference.

Disease incidence

Recommendation 1

Achieve a sustained reduction of 70% and 90% in the incidence of varicella by 2010 and 2015 respectively.

Rationale: While desirable, it is premature to establish a goal of varicella elimination in Canada. The proposed targets allow needed time to implement vaccine programs. A one-dose regimen is assumed, with high coverage and attendant herd immunity.

Immunization coverage

Recommendation 2

Achieve and maintain age-appropriate immunization coverage with varicella vaccine in 85% of children by their 2^nd birthday by 2010.

Recommendation 3

Achieve and maintain age-appropriate immunization coverage with varicella vaccine in 85% of susceptible children by their 7^th birthday by 2010.

Recommendation 4

Achieve and maintain age-appropriate immunization coverage with varicella vaccine in 85% of susceptible adolescents by their 17^th birthday by 2010.

Rationale: These targets are believed to be achievable based on single-dose MMR coverage. Further, it is expected that MMRV will be available by 2010. Targets are consistent with planned national coverage surveys in the specified age cohorts.

Other

Recommendation 5

Decrease varicella-related hospitalization rates by 80% by 2010.

Rationale: Children < 10 years of age are the target of immunization programs and the single largest group hospitalized for varicella-related illness; although significant disease reduction is expected. It is also essential to reduce varicella-related hospitalization rates among older cohorts given rising incidence among these groups. For this reason no age groups have been specified. Active surveillance sites in the US have shown that an 80% reduction in varicella-related hospitalization could be achieved in 5 to 6 years. Similar results are expected in Canada.

Issues: Surveillance systems will be required to monitor older cohorts and populations. Surveillance systems should differentiate between immunocompromised and previously healthy persons and between varicella and herpes zoster.

Recommendation 6

Decrease the number of varicella-related deaths by 80% by 2010.

Rationale: Reductions in varicella-related deaths are expected to parallel reductions in hospitalizations. An 80% to 90% decrease in mortality over baseline is expected among both immunocompromised and healthy populations.

Issues: Small numbers of fatalities may make it difficult to measure target achievement. Further, surveillance should differentiate between immunocompromised and previously healthy persons and between varicella and herpes zoster.

Recommendation 7

Achieve and maintain 100% demonstrated varicella immunity in health care workers, by either history of disease, positive serology or prior immunization; and vaccinate if not immune, unless contraindicated, by 2010.

Rationale: Health care workers (HCW) represent a high-risk group for exposure to varicella, given their close contact with immunocompromised persons and the potential for nosocomial transmission. Some jurisdictions provide publicly funded varicella vaccine for HCW; however there is no national system to assess immunization rates of HCW at the facility level and immunization policy is determined by individual hospitals/facilities. Recent data suggest that improving immunization coverage for HCW reduces costs related to nosocomial transmission and outbreaks.

Issues: Post-immunization varicella serological testing cannot be relied upon because of low-titre levels associated with post-immunization seroconversion and the lack of laboratory tests sensitive enough to detect low levels of antibodies. Scores for antibody negativity also vary.

In the US, the stated outcome of two doses of vaccine is 99% immunity; however, evidence suggests one-third of those vaccinated may lose antibodies over time. A study currently underway in the US involves administering a third vaccine dose to health care workers.

Varicella vaccine should ideally be administered to new HCW at the time of employment. ACIP and NACI do not recommend routine testing post-immunization, however it is important to monitor for varicella among HCW. Days of furlough, cases of disease in HCW, and infection control tools can be used for monitoring. Concerns were raised about implementation (e.g., who is responsible for demonstrating immunity and is there sufficient testing capacity). Another concern is the lack of a common definition of "health care worker".

Recommendation 8a

Screen 100% of pregnant women annually for immunity to varicella, by either history of disease, prior immunization or positive serology, by 2010.

Recommendation 8b

Achieve and maintain immunization coverage with varicella vaccine in 100% of postpartum women without evidence of immunity, unless contraindicated, by 2010.

Rationale: Non-immune pregnant women and their newborns represent a high-risk group for congenital varicella syndrome (CVS), neonatal varicella, and complications from adult disease. Participants agreed that immunization should be offered, not required, for post partum women, although concerns were raised about the feasibility of tracking offers. A note was made that offers of HIV testing are currently tracked.

Issues: Improved prenatal screening is needed. A future goal should be to incorporate varicella into routine prenatal screening, alongside HIV, hepatitis C and rubella.

Vote

Participants achieved consensus on the following updated recommendations for varicella reduction. An overarching goal was also proposed following the meeting.