Varicella_2001

Canadian Task Force on Preventive Health Care

Structured Abstract

Preventive health care, 2001 update: Use of varicella vaccine in healthy populations

Prepared by S.A. Skull, MBBS, FRACP, FAFPHM, MAppEpid, E.E.L. Wang, MCDM, FRCP(C), with the Canadian Task Force on Preventive Health Care

These recommendations were finalized by the Task Force in June 1999.

Objective
Burden of Suffering
Options
Outcomes

Evidence
Values
Benefits, Harms, and Costs

Recommendations
Validation
Sponsors
Selected References

Objective

The objectives of the review are a) to evaluate the evidence relating to the effectiveness and potential harms of varicella-zoster-virus (VZV) vaccine for the prevention of varicella in healthy individuals, and b) to make recommendations regarding administration of VZV vaccine in healthy populations.

Burden of Suffering

Varicella (chicken-pox) is a common, highly infectious disease characterized by a vesicular eruption accompanied by fever and malaise and caused by varicella zoster virus (VZV). Herpes zoster (shingles), a painful, dermatomal, vesicular rash occurs with reactivation of the virus in approximately 15% of the population. Complications include secondary bacterial infection, pneumonia, encephalitis, hemorrhagic complications, hepatitis, arthritis, and Reye syndrome. While only a small proportion of children experience complications, 10-50% will visit a physician. Most morbidity and mortality occurs in persons > 20 years of age. Mortality from varicella in children under 14 is estimated at 2/100,000. Reporting underestimates actual burden of disease by up to 95%.

Although adults experience only 5% of all varicella cases, severe disease (hospitalizations 18 per 1000) and death (50 per 100,000) are more common than in children and complications occur in just over 1%. Most women of child-bearing age will have immunity to VZV, however, infection in pregnancy can cause congenital varicella syndrome, neonatal varicella and zoster in infancy or early childhood.

Costs due to varicella are mostly attributed to lost parental work days and hospitalization and, although societal costs for uncomplicated varicella in healthy children are less than for complicated cases, uncomplicated cases are responsible for approximately 90% of overall economic burden.

Options

Options for the use of vaccine to prevent varicella in healthy individuals include universal vaccination of healthy infants, catch up vaccination of older children and vaccination of susceptible adolescents and adults.

Outcomes

Outcomes included the incidence of varicella, zoster or adverse outcomes following vaccination.

Evidence

MEDLINE and EMBASE were searched for trials of VZV vaccine in healthy populations published from 1966 to December 1998 using the terms: chicken-pox, vaccination, human. There was no language restriction. Additional articles were identified using the reference lists of these publications, position statements from health organizations, vaccine product information and the Cochrane Library. Selection criteria were used to limit the review to randomised controlled trials or cohort studies of at least one year’s duration with loss to follow-up described.

All evidence was systematically reviewed using the procedures of the Canadian Task Force on Preventive Health Care. The Task Force, comprising expert clinicians and methodologists from a variety of medical specialties, used a standardized evidence-based method for evaluating effectiveness.

Recommendations were graded as:

A Good evidence to support the recommendation that the condition be specifically considered in a PHE.

B Fair evidence to support the recommendation that the condition be specifically considered in a PHE.

C Poor evidence regarding inclusion or exclusion of the condition in a PHE, but recommendations may be made on other grounds.

D Fair evidence to support the recommendation that the condition be specifically excluded from consideration in a PHE.

E Good evidence to support the recommendation that the condition be specifically excluded from consideration in a PHE.

Quality of evidence was rated according to 5 levels:

I Evidence from at least 1 properly randomized controlled trial (RCT).

II-1 Evidence from well-designed controlled trials without randomization.

II-2 Evidence from well-designed cohort or case-control analytic studies, preferably from more than 1 centre or research group.

II-3 Evidence from comparisons between times or places with or without the intervention. Dramatic results in uncontrolled experiments could also be included here.

III Opinions of respected authorities, based on clinical experience, descriptive studies or reports of expert committees.

Values

The 10-member Task Force of experts in family medicine, geriatric medicine, paediatrics, psychiatry and epidemiology used an evidence-based method for evaluating the effectiveness of preventive health care interventions. Recommendations were not based on cost-effectiveness of options. Patient preferences were not discussed.

Background papers providing critical appraisal of the evidence and tentative recommendations prepared by the primary author were pre-circulated to the members. Evidence for this topic was presented and deliberated upon in 1- to 2-day meetings from June 1999 to November 1999. Consensus was reached on final recommendations.

Benefits, Harms, and Costs

Health benefits of VZV vaccine were evaluated in terms of a) prevention of varicella morbidity and mortality in children and adults, and b) prevention of zoster due to VZV reactiviation in adults.

The harms of vaccination were evaluated by examining immediate adverse reactions (local reactions, fever, injection site reactions, and rash) and long-term risk for varicella and herpes zoster (transmission of varicella from vaccinees; risk of herpes zoster following vaccination; a shift in varicella cases to an older age group – and more severe disease). Immediate side effects of vaccination appear minimal in both adults and children. Breakthrough varicella and zoster are mild and infrequent. Transmission of vaccine VZV are much less frequent than for natural varicella. The theoretical concern that immunization may lead increase incidence of herpes zoster is not supported. Although vaccination may increase the mean age of varicella, the overall reducation in cases of adult varicella should offset this.

Simulation studies examining both societal and health care costs associated with varicella have all found net cost savings with programs for routine VZV vaccination directed at children aged 15 months. Accuracy of history in those with uncertain or negative history for varicella is an important determinant of cost-effectiveness for VZV vaccination in older subjects. In children under 12 years, vaccination regardless of previous history of varicella appears the most cost-effective approach. The exception is 9-12 year olds with an uncertain history of varicella who should have serotesting prior to vaccination. For adolescents and adults, prior serotesting is likely to be the most cost-effective.

Recommendations

Recommendation grade [A, B, C, D, E] and level of evidence [I, II-1, II-2, II-3, III] are indicated after each recommendation. Citations in support of individual recommendations are identified in the guideline text.

There is good evidence based on effectiveness data to recommend implementing single dose, routine vaccination of children aged 12-15 months and catch-up vaccination of children aged one to 12 years for the prevention of VZV illness [A, I, II-2].
There is fair evidence based on effectiveness and immunogenicity data for the vaccination of susceptible adolescents and adults [B, II-1, II-2]. Two doses given 4-8 weeks apart appear more effective than a single dose based on immunogenicity data in subjects over 12 years.
Further clinical trials would be needed to provide better data on cost-effectiveness, mortality and hospitalization, long-term effectiveness in adults, and to compare the effectiveness of one- versus two-dose regimens in adolescents and adults.
There is insufficient evidence documenting safety of VZV in pregnancy to recommend vaccination in susceptible pregnant women, although risk is likely to be less than for naturally acquired VZV.

Validation

The findings of this analysis were reviewed through an iterative process by the members of the Canadian Task Force on Preventive Health Care. The draft of the report was also externally peer reviewed. It was again peer reviewed as part of the journal publication process.

Selected References

Source Document:

This structured abstract is based on the technical report: Preventive Health Care, 2001 update: Use of varicella vaccine in healthy populations by Skull SA and Wang EEL, with the Canadian Task Force on Preventive Health Care. The full technical report is available by contacting the CTFPHC at ctf@ctfphc.org.

Link to Recommendation Statement of this review

Link to Full Technical Report (in pdf)

Link to Summary Table of Recommendations of this review

Link to Selected References list of this review

Top of Page

CTFPHC Home Page

A	Good evidence to support the recommendation that the condition be specifically considered in a PHE.
B	Fair evidence to support the recommendation that the condition be specifically considered in a PHE.
C	Poor evidence regarding inclusion or exclusion of the condition in a PHE, but recommendations may be made on other grounds.
D	Fair evidence to support the recommendation that the condition be specifically excluded from consideration in a PHE.
E	Good evidence to support the recommendation that the condition be specifically excluded from consideration in a PHE.

I	Evidence from at least 1 properly randomized controlled trial (RCT).
II-1	Evidence from well-designed controlled trials without randomization.
II-2	Evidence from well-designed cohort or case-control analytic studies, preferably from more than 1 centre or research group.
II-3	Evidence from comparisons between times or places with or without the intervention. Dramatic results in uncontrolled experiments could also be included here.
III	Opinions of respected authorities, based on clinical experience, descriptive studies or reports of expert committees.