Overview
In a steady-state situation, the annual number of vanicella cases occurring in the United States
ap-Varicella:
Complications
and Costs
Stephen R. Preblud, MD
From the Division of Immunization, Center for Prevention Services, Centers for Disease Control, Public Health Service, US Department of Health and Human Services, Atlanta
ABSTRACT. Vanicella (chickenpox) has long been con-sidered a benign, inevitable disease of childhood. Com-plications are generally mild and rarely severe, and yin-tually every individual is infected by adulthood. Infection is associated, however, with a high risk of serious com-plications in certain high-risk groups, such as leukemic children. Concerns about the severity of varicella in this
population have led to the development and testing of a
live, attenuated vaccine. Because of the favorable results thus far available, the vaccine may soon be licensed for use in high-risk individuals. The fact that a vaccine may soon be available has led to an increased interest in the potential benefits of a childhood vanicella vaccine pro-gram. The costs associated with vanicella infection in normal persons without a vanicella vaccination program have been estimated to be approximately $400 million, 95% of which is the cost of caring for a child at home. Vaccination of normal 15-month-old children with a safe and effective vaccine with long-lasting immunity could reduce the cost by 66% and result in a savings of $7 for every dollar spent on the vaccination program. This
assumes that vaccine would be administered only once
with measles, mumps, and rubella vaccine, that there
would be no increase in the number of vanicella cases in older persons who are at increased risk for complications, and that there would be no deleterious effect on the occurrence and severity of herpes zoster. If the assump-tions cited above hold true, then it would appear that
normal children would benefit from prevention of
van-celia by vaccination, not by virtue of the severity of the
disease but rather because of the inevitability of the
disease and its associated expense. Pediatrics 1986;
78(suppl): 728-735.
Vanicella (chickenpox) has long been considered a benign, inevitable disease of childhood. Compli-cations in this population are generally mild, and virtually every individual is infected by adult-hood.”2 Infection is associated, however, with a high risk of serious complications, including death, in
neonates exposed shortly before birth,3’4 adults,”5’6
and immunocompromised persons.7 Concern about
the increased risk of disseminated disease and death in the latter group, especially in leukemic children, has led to the development and testing of a live, attenuated vaccine.3 Because of the favorable results thus far available, the vaccine may soon be licensed for use in high-risk individuals in this country. It is currently licensed for selected use in several European countries.
Although discussion about vaccinating all chil-dren against vanicella infection is not new, the fact that a vaccine may soon be available has led to an increased interest in the potential benefits of a childhood varicella vaccine pnogram.”4#{176} To mea-sure adequately these potential benefits, accurate information on the impact of vanicella on the pop-ulation is needed, as is knowledge of the effective-ness of vaccine in preventing that impact and the potential costs and risks from the vaccine. A pre-vious review attempted to measure the health im-pact associated with childhood vanicella by noting that infection in normal children accounted for
most of the disease burden in this country
an-nually.1 However, there was no attempt to quanti-tate the costs in detail and to measure objectively the potential benefits, ie, reduction in illness and cost, from a childhood vaccination program. The purpose of this paper is to review the complications of vanicella infection, with an emphasis on updating national data,’7 and to summarize the results of a benefit/cost analysis that provides an estimate of the costs associated with varicella and quantitates the benefits of a childhood vaccination program. The details of this benefit/cost analysis have been published elsewhere.18
COMPLICATIONS
Reprint requests to (S.R.P.) Technical Information Services, Center for Pnevention Services, Centers for Disease Control, Atlanta, GA 30333.
proximates the birth cohort. Based on the current number of births (between 3.6 and 3.7 million) and if it is assumed that 95% of vanicella infections are clinically apparent,’9 there are approximately 3.5 million cases annually. Approximately 90% of cases occur in children 1 to 14 years of age, with approx-imately 2% of cases occurring in adults 20 years
of age. Schoolchildren have the highest risk of
infection, with children 5 to 9 years of age alone accounting for 50% to 60% of cases. Primary infec-tion can result in latency of the virus in ganglion tissue. The likelihood of virus reactivation is in-creased by a variety of circumstances, most corn-monly immunosuppression, aging, or in utero ex-posure, and result in herpes zoster, or shingles.20’2’ Based on the estimate of Raggozino et al22 of the annual incidence of herpes zoster (1.3 cases per 1000 person-years), an estimated 300,000 cases oc-cur annually. Because only 5% of persons suffer a
recurrence, approximately 10% of persons can be
expected to experience herpes zoster. The
compli-cations associated with herpes zosten will not be
reviewed here, but the reader is referred to the data of Guess et al23 specifically on children.
A lange variety of complications associated with
vanicella infection have been reported in the
literature2327 and reviewed elsewhere.5’6’2#{176} The most common of these is bacterial supeninfection, partic-ularly of the skin. Some other complications in-volving the skin are bullous and hemorrhagic van-cella, localized gangrene, necrotizing fasciitis, and purpura fulminans.
Complications involving the CNS are second only to cutaneous complications. Encephalitis occurs relatively frequently and in two forms. Cerebellar involvement, manifesting as ataxia, accounts for the majority of encephalitis cases, occurs primarily in children, and is associated with a favorable out-come. Diffuse cerebral encephalitis is less common, is more likely to affect adults, and is associated with a high mortality rate (range of 5% to 35%)#{149}528
Another serious associated condition involving the
CNS is Reye syndrome which must be
differen-tiated from diffuse cerebral involvement. Aseptic meningitis, transverse myelitis, and Guillain-Barr#{233} syndrome also can occur.
Pneumonia can be either viral or bacterial. The former is more likely to occur in adults, whereas the latter is more likely to occur in children. In general, children infrequently acquire pneumonia.
Although pneumonia is frequently cited as the
cause of death in adults (reported death rates up to 30%), abnormal chest x-ray film findings are not always associated with symptoms.29 In a study of 110 military recruits with vanicella, 16% had ab-normal chest roentgenographic findings, but cough
and shortness of breath were noted in only 4% and 2%, respectively.
Other infrequent complications include keratitis, conjunctivitis, uveitis, initis, arthritis, appendicitis, glomerulonephnitis, myocanditis,
Henoch-Sch#{246}n-lein purpura, orchitis, thnombocytopenia, and
bleeding diatheses.5’6 Although clinical hepatitis is
relatively uncommon, enzyme elevations are not
unusual.3#{176} It still is not clean whether there is over-lap between vanicella cases with hepatic enzyme elevations and mild cases of Reye syndrome.
Congenital malformations have been reported in
offspring of mothers infected generally within the
first 16 weeks of gestation.3’20’2’ Although there has
been debate about the association between the ob-served malformations and maternal vanicella infec-tion, it is now generally accepted that congenital vanicella infection can result in malformations which include low birth weight, chonionetinitis, mi-cnocephaly, encephalitis, and skin scarring and muscle wasting of the upper and lower extremities. The risk of congenital malformations is not known with certainty, but it is probably low. Based on a
study of 150 women infected in pregnancy and the
birth of one infant who may have been affected, the estimated risk would be <1%.31 As noted previously, infection in uteno also is associated with herpes zosten in childhood, but the actual risk is unknown.
Vanicella infection can result in death. The risk varies greatly depending on the circumstances lead-ing to infection and the host. As discussed below,
there are high-risk groups, but the majority of
deaths occur in normal individuals.
National Data for Complications
There is no comprehensive estimate on the risk of acquiring these complications and little infon-mation about them is available on the national level. However, there are national data on vanicella-associated hospitalizations, encephalitis, Reye syn-drome, and death. The Centers for Disease Control (CDC) receives reports on cases of encephalitis and Reye syndrome, and the National Center for Health Statistics (NCHS) provides information on hospi-tal discharges and deaths due to vanicella. Infor-mation on hospitalizations is also available from the Professional Activities Survey of the
Commis-sion of Professional Hospital Activities (CPHA).
Hospitalizations
Based on Amler’s25 review of NCHS hospital
discharge survey data, there were 6,458
hospitali-zations associated with vanicella annually. As noted
by Guess et al,27 the CPHA estimate of the annual
3,837. The reason for the discrepancy between
NCHS and CPHA data may be related to the type
of hospital included in the samples and the number of discharges actually sampled.
The age distribution of the NCHS hospitaliza-tions was: <5 years = 49.2%, 5 to 9 = 26.1%, 10 to
14 = 6.7%, 15 to 19 = 4.5%, and 20 = 13.5%. This
parallels the CPHA data closely. Pneumonia and
other lower respiratory tract conditions were noted for 23.2%, otitis media and other upper respiratory
tract conditions for 14.4%, skin infections for
10.5%, and encephalitis for 9.7% of the NCHS
hospitalizations. Twenty percent of the patients had no complication listed on the discharge sum-mary.
Information on age-specific complications of hos-pitalized children has been reported by Guess et al.23’27 Briefly, young children were most likely to be hospitalized with bacterial skin infections or dehydration, and adults were most likely to have pneumonia. Uncomplicated vanicella accounted for a large proportion of hospitalizations regardless of age.
Encephalitis
Between 1972 and 1983, an average of 48 cases of encephalitis due to vanicella was reported an-nually to CDC (Figure). However, the annual num-bers of encephalitis cases and associated deaths (data not shown) have been decreasing. Whereas an average of 58 encephalitis cases was reported between 1972 and 1979, an average of only 28 cases
was reported between 1980 and 1983 (Table 1).
This decrease was noted for all ages except for those 20 years. As expected, the majority of cases were in children, but a substantial proportion of cases occurred in adults 20 years, 11% and 23.1%, re-spectively, during these two periods.
Overreporting of severe encephalitis cases is in-dicated by the large proportion of cases occurring in adults and by the reported encephalitis death to
1
Year
Figure. Reported number of deaths and cases of en-cephalitis due to vanicella, United States, 1970 to 1983.
TABLE 1. Average Annual Number of Reported
En-cephalitis Cases Due to Vanicella, by Age, United States, 1972 to 1983
Age (yn)
1972
No. %
1980
No. -1983t
%
% Changes
<1 2 2.7 1 0.9 -86.6
1-4 12 22.0 7 25.0 -44.3
5-9 26 46.6 9 35.2 -63.5
10-14 8 14.3 3 13.0 -56.2
15-19 2 3.4 1 2.8 -57.9
20 6 11.0 6 23.1 +1.6
Total 58* 100.0 28t 100.0 -53.1
* Eight-year total = 464 (age data lacking for 18 cases). t Four-year total = 109 (age data lacking for one case). :1:Percentage based on the total number of cases reported during the time period with known age.
§Based on calculated average, not rounded average in Table.
case ratio data. During the 12-year period, the reported death to case ratio was 13.6% (78 deaths and 573 encephalitis cases). The highest encepha-litis death to case ratio occurred in those 20 years (36.5% compared to 7.2% for those <5 years and
11.7% for those 5 to 19 years of age). The higher
ratios in older individuals would be consistent with better reporting of cerebral encephalitis cases than of cerebellar cases.
Reye Syndrome
Between 1977 and 1981, an average of 388 cases of Reye syndrome was reported to CDC annually.32 Approximately 25% of the cases were associated with vanicella. There were 77 such cases in 1981. Recently, the total number of Reye syndrome cases has declined (an average of 203 between 1982 and 1984) with only 26 cases associated with vanicella reported in 1984. Virtually all cases occur in chil-dren and young teenagers. There has been specu-lation that the observed decrease in the number of
Reye syndrome cases reported to CDC may be
related to a change in aspirin use, but this has not been established.32 The provisional 1985 number of cases is only 14.328
Deaths
Between 1970 and 1982, a total of 1,252 deaths
were reported to NCHS, an annual average of 96
deaths (Figure). As noted for reported encephalitis cases, there appears to have been a recent decline
in the number of reported deaths. Between 1970
and 1979 the average was 103 deaths, and the
average was 74 deaths between 1980 and 1982.
During these two periods the expected number of
cases and age distribution of reported cases of van-icella did not appreciably change.’6’33
throughout the 13-year period are best illustrated by comparing 1980 to 1982 with 1970 to 1974 data (Table 2). The average number of deaths declined for all ages younger than 15 years. The increase in 15- to 19-year-old individuals is based on a very small number ofdeaths. The increase in the number of deaths in persons 20 years in the face of a decrease in the total number has resulted in a progressive increase in the proportion of deaths occurring in this age group, from 19.9% for 1970 to 1974 to 47.5% for 1980 to 1982.
Fluctuations in the number of reported deaths have been noted previously; therefore, the apparent decline noted during the most recent 3 years for which data are available must be interpreted cau-tiously. If the decline is real, as suggested by the parallel decline in encephalitis cases and associated deaths, it would be consistent with advances in chemotherapy for varicella infections in immuno-compromised children and perhaps early admission to the hospital for suspected Reye syndrome pa-tients, most of whom are otherwise normal chil-dren.26
Risk of Complications Among Different Groups
Immunocompromised Persons. Altered immu-nity, such as that associated with radiation, steroid therapy, cancer chemotherapy, malignancies, and inborn immune deficiencies, is associated with a high risk of serious vanicella infection.5’6’20 The best studied category of high-risk persons has been chil-dren with leukemia or lymphoma. In a report in-volving 60 such children receiving chemotherapy, Feldman et a17 noted that the risk of dissemination and death was 36% and 7%, respectively. The most frequently noted complications were pneumonia, hepatitis, and encephalitis. By contrast, none of eight children with solid tumors died, but the num-ben of children observed was small.
Although immunocompromised persons are at high risk for serious complications from vanicella, they account for few vanicella-related events. It has been estimated that fewer than 0.1 % of all vanicella cases occur in such individuals.’6 The NCHS hos-pital data indicated that only 3.7% of the discharges were associated with a neoplasm and a survey of 105 hospitalizations in a children’s hospital noted that only 17.1% involved an immunocompromised child.26
Finally, death certificate data indicate that a relatively small proportion of deaths are associated with a malignancy.34 Between 1970 and 1978 (the last year for which there are such data), the pro-portion was only 28.6% (5. R. Preblud, unpublished data). However, the proportion of deaths associated with a malignancy increased over time, from 24.2%
for 1970 to 1974 to 34.3% for 1975 to 1978. There
were also marked age-specific differences. Based on data for 1975 to 1978, the proportion of deaths with an underlying malignancy was 0% for infants, 25.6% for those 1 to 14 years old, 42.9% for those 15 to 19 years old, and 50.8% for persons 20 years
old.
Neonates Exposed in Utero. In addition to the risk of congenital malformations and herpes zoster occurring in childhood, data indicate that neonates born within five days of the onset of maternal varicella have a high risk of death resulting from disease manifesting five to ten days after delivery.3’4 The figure most frequently cited is 31%. Although this may be inflated due to biased reporting asso-ciated with retrospectively obtained data, the in-creased risk is thought to be real. These neonates are probably at risk because they are exposed to high titers of virus with little or no protective maternal antibody.
Adults. For uncertain reasons, normal healthy adults are at increased risk for serious
complica-TABLE 2. Average Annual Numb
States, 1970 to 1982
en of Reported Death s Due to Vanicella, by Age, United
Age 1970_1974*
(yr)
No. %II
1975-1979t
No. %II
1980-1982
No. %fl
% Changes
<1 12 10.8
1-4 24 21.2
5-9 44 39.1
10-14 9 8.3
15-19 1 0.7
20 22 19.9
Total 112 100.0
6 5.9
15 16.1
28 29.4
9 9.3
3 3.4
34 35.8
95 99.9
5 7.1
9 12.5
14 18.4
8 10.4
3 4.0
35 47.5
74 99.9
-55.8 -60.6 -68.6 -16.3 +275.0 +59.0 -33.3
* Five-year total = 557
t Five-year total = 472. :1:Three-year total = 223.
§Between 1980 to 1982 and 1970 to 1974; based on calculated average, not rounded average in Table.
TABLE 3. Estimated Age-Specific Vanicella Death to Case Ratios in Persons With No Underlying Malignancy
Age (yn) Cases* Deathst Deaths/100,000
Vanicella Cases
% No. % % Normals No. Nonmal
<1 2.4 73,866 5.7 100.0 5.3 7.2
1-14 91.1 2,803,826 57.0 74.4 39.2 1.4
15-19 4.9 150,810 3.8 57.1 2.0 1.3
20 1.6 49,244 33.5 49.2 15.2 30.9
Total 100.0 3,077,795 100.0 65.7 60.8 2.0
* Based on the average number of births (3,242,974) for 1975 to 1978, the assumption that 99.9% of cases occur in
normal persons, and a 95% clinical attack rate.
t Based on the average number of deaths (92.5) for 1975 to 1978. t Normal = those without a malignancy.
§(92.5 deaths) x (% ofdeaths) x (% normal).
tions. Many reports describe severe infections that
require hospitalization, are complicated by pneu-monia, or result in death.5’6 Pregnancy is believed to increase further the risk of serious vanicella-related complications, but this supposition is not well documented.35 Based on national data, the risk
of hospitalization for adults with vanicella is 14 to
18 hospitalizations per 1,000 vanicella cases as
corn-pared to only one to two per 1,000 for children.”27 The marked discrepancy in the proportion of cases (2%) and deaths (47.5%) occurring in persons 20
years of age is further evidence of the increased
risk. This disproportion in percentage of cases and deaths is true regardless of malignancy status.
Although there are no accurate population
esti-mates on the risk of death in normal healthy adults,
an estimate of the vanicella death to case ratio was derived using the observed age distribution of
re-ported vanicella cases and deaths and the
propor-tion that occur in normal individuals (Table 3). The number of cases was derived by multiplying the age
distribution of reported cases by the estimated
number of cases that actually occur. The latter is based on the birth cohort, 95% of whom become clinically infected and 99.9% who are probably nor-mal. The number of deaths was derived by multi-plying the average number of deaths by both the age distribution and the proportion without a ma-lignancy. Data for 1975 to 1978 (average = 92.5)
were used because this was the latest period with accurate data on malignancy status. During this period, approximately 3 million cases of vanicella would be expected to occur each year. (If the num-ben of deaths reported between 1980 and 1982 (av-erage = 74) is used along with the increase in
expected cases (3.5 million), then lower death to case ratios will be obtained, but the differences by age would remain essentially unchanged.) Based on
this methodology, the estimated vanicella death to
case ratio for normal persons 20 years of age would be 30.9 deaths per 100,000 vanicella cases for the stated time period. (The difference between this figure and a previous estimate of 50/100,000 is
largely due to a revision in the proportion of deaths occurring in persons without a malignancy, 49.2% instead of 84%.1 The latter was based on all deaths
from 1968 to 197036 when the proportion was lower
than that noted in subsequent years. The data were also not age specific.)
Normal Children. The only reports on complica-tions due to vanicella in children involve hospital-ized patients.24’26’27 Thus, estimates on the risk of various complications are inflated because of the nature of the study population. Because data on the
risk of death are available for all of the high-risk
groups mentioned above, it is useful to compare
them with an estimated death to case ratio for
normal children. The estimated vanicella death to
case ratio for normal children 1 to 14 years of age
would be 1.4/100,000 cases of vanicella, or 0.0014%,
using the approach for adults described before
(Ta-ble 3). This risk is only 1/5,000th ofthat of leukemic children (7%).
The calculated death to case ratio for infants is approximately five times that of other children (Table 3). Because most of the infant deaths were not associated with intrauterine exposure, the data suggest that postnatal exposure is responsible for the increased risk of death in this age group.37 However, it is not clear whether the apparent in-creased risk in infants as compared to other chil-dren is real or is simply due to underreporting of cases in infants.
COST OF VARICELLA-BENEFITS OF
PREVENTION
The prior data can be used to estimate the impact
of vanicella in our society. Vanicella infection in
normal children 1 to 14 years of age accounts for approximately 90% of all cases, virtually all Reye
syndrome cases, and 65% to 75% of the
hospitali-zations.’ Based on the latest data on encephalitis,
this population accounts for approximately 70% of
occurred in these individuals. (If one uses the num-ber and age distribution of the deaths reported in
1980 to 1982 and the 1975 to 1978 information on the proportion of deaths occurring in persons with-out a malignancy, then normal children 1 to 14
years of age may have accounted for approximately 30% of all deaths.) Normal children thus account
for a large proportion of the costs associated with vanicella infection in this country. However, an accurate estimate of the costs associated with var-icella illness is needed to measure precisely the potential benefits of a vaccination program.
A benefit to cost model was developed to estimate objectively the costs of vanicella infection in normal persons without a vanicella vaccination program and to measure both the reduction in vanicella-associated disease and costs associated with a vac-cination program targeted for normal children.’8 The model does not include immunocompromised individuals because it is generally accepted that vaccination of this population would be cost-bene-ficial.
The model follows the expected experience of normal individuals from a cohort of 3.5 million individuals from birth to their 30th birthday with-out and with a vaccination program. Vaccine esti-mated to cost $15 would be administered to children at 15 months of age at the same time as the measles, mumps, and rubella vaccine to avoid additional administrative costs.’#{176}’ The model assumes that
90% of the cohort would be vaccinated; that the vaccine would be 90% effective8”2; that there would be no waning immunit?”3 so that only one dose of vaccine would be needed; that vaccine re-actions would be minimal and minor and that se-vere reactions would be rare8”#{176}’2; that the occur-rence, age of onset, and severity of herpes zoster would not be altered39; and that the age-specific epidemiology of the disease would not be adversely affected by the vaccination program. The last as-sumption refers to the possibility of more older individuals, who have an increased risk of serious complications, becoming infected while the pro-gram is in effect than would have been infected if the program were not in effect. This could happen
if there were either unrecognized waning
vaccine-induced immunity on if vaccine coverage was high enough to decrease circulation of the virus but not high enough to produce total protection. The for-men situation would involve an inherent problem with the vaccine, the latter with vaccine delivery.
The events monitored were cases of vanicella, encephalitis, and Reye syndrome and residual de-fects associated with the latter two; physician visits; hospitalizations; medication (antiprunitics and an-tibiotics); and deaths without and with a program.
Costs for both disease and vaccine included medical costs (those associated with physician visits, pre-scniption and oven-the-counter medications,
hospi-talization, and continuing care of disabled persons) and home care costs (lost wages because of absence from work for an individual, most often the parent, to care for an ill person). It was assumed that only
one case occurred in a household at a time, ie, that
multiple cases did not occur in a household
regard-less of the number of susceptible individuals. Costs
associated with lost wages for the patient and loss
of life were not included.
Based on the model, 78% of cases and at least 70% of the other vanicella-related events’8 would be
prevented (Table 4). Because coverage and efficacy were both estimated to be 90%, a reduction of no greater than 81 % (0.90 x 0.90) could have been expected. Without the program, the costs would be
$399,446,960, 95% of which would be associated
with home care costs (Table 4). The costs associ-ated with the program would be $137,396,311:
$93,260,257 for disease that could not be prevented and $44,136,311 for the vaccine. Virtually all of the
latter would be due to the actual cost of the vaccine
itself and not to vaccine reactions which are as-sumed to be very rare. The overall cost savings
would be $262,050,392 ($399,446,960 minus
$137,396,311) for a 66% reduction in costs. The
benefit to cost ratio would be 6.9:1 ([$399,446,960
minus $93,260,257]/$44,136,311). That is, for every
dollar spent, approximately $7 would be saved. Almost all of the costs associated with varicella are not related to traditional medical costs such as
physician visits, medication, and hospitalization
but rather to the costs associated with a sick child whose care at home may result in lost time from work and lost wages. This is consistent with any mild childhood disease. The cost, then, is not re-lated primarily to the severity of the disease but
TABLE 4. Varicella Cases and Costs Withou
a Childhood Vanicella Vaccination Program*
t and With
Parameter Without a With a Reduction
Program Program (%)
No. of cases 3,292,750 729,253 77.9
Costs ($)
Disease
Medical 16,881,227 4,523,165 73.2
Home care 382,565,683 88,737,092
Subtotal 399,446,960 93,260,257
76.8
76.6 Vaccine
Medical 81,125
Home care 45,286
Vaccine 44,009,900
Subtotal 44,136,311
Total 399,446,960 137,396,568 65.6
rather to the lost income resulting from caring for persons with disease.
The benefits from the program in this model are believed to be underestimated because the
propor-tion of normal individuals used in the model was 99% instead of 99.9%, the vaccine is probably of
higher efficacy than 90%,12 and it may cost less than $15. Furthermore, costs associated with illness in persons 30 years who account for a large
num-ben of serious vanicella complications, the
continu-ing care of children with congenital vanicella, and
loss of life were not included. Finally, if the data
suggesting a reduction in the risk of herpes zosten
in leukemic vaccinees should prove to be applicable
to normal vaccinees,39 large additional savings in cost would be realized.’6
The two most significant factors affecting the
model are vaccine and home care costs. Changes in assumptions that affect the medical costs have little
effect on the results of the analysis. If the vaccine cost is reduced to $10 or $5 per dose, then the
benefit to cost ratios would be 10.4:1 and 20.7:1, respectively. Because of the large margin of savings
with the model, changes in the opposite direction
still result in a ratio greater than 1 and a net savings. If the vaccine price is doubled ($30) the
benefit to cost ratio would be 3.5:1. Similarly, if the
home care costs are reduced by as much as two
thirds to account for multiple cases occurring in a household simultaneously, the benefit to cost ratio
would be 2.5:1.
Vaccine costs would obviously increase if lower than expected seroconversion rates or waning of vaccine-induced immunity resulted in a two-dose schedule ($30 plus an added administrative cost of
$25). Ifthe need for an additional dose is recognized before there is a significant effect on the incidence of vanicella in the older population and all individ-uals receive the second dose, the benefit to cost ratio would still be 2.2:1.
Although assumptions regarding vaccine safety,
efficacy, and simultaneous administration with
measles, mumps, rubella vaccine are all based on published information, concern about deleterious
changes in the age-specific epidemiology with a
program cannot yet be directly dispelled. This par-ticular model cannot accommodate the sophisti-cated changes in age-specific risk of infection that might result from unrecognized waning immunity or altered circulation of the virus due to inadequate vaccine coverage rates. However, the benefits as-sociated with the program would be markedly re-duced if there were a significant increase in the number of vanicella cases and related events in older
persons. .
It is important to note, however, that
vaccine-induced antibodies have persisted in normal vacci-nees followed for 3 to 10 years after vaccina-tion.8”3 By analogy with other childhood vacci-nation programs, there has been no observed in-creased risk of infection in olden persons.40’4’ Never-theless, careful surveillance for waning immunity and undesired changes in disease pattern after in-troduction of vaccine will be necessary. However, it is also important to have baseline surveillance data before introduction of vaccine. This fact is
under-scored by the ongoing change in the number and
age distribution of vanicella-nelated encephalitis cases and deaths. Had there been no prevaccine data, the changes might have been misinterpreted to indicate that the vaccine was responsible for the observed increases in the olden age groups.
CONCLUSIONS
Until recently, vanicella has been a “neglected” disease. However, the potential availability of a safe and effective vaccine has led to increased interest
in the epidemiology, virology, immunology, and
health impact of vanicella. There is little doubt that selected high-risk groups would benefit greatly from a vanicella vaccine. The group with highest priority would be persons, especially children, with leuke-mia and possibly other malignancies. Susceptible adults would also benefit from vaccination. In ad-dition to preventing the serious complications seen in this age group, the vaccine could be instrumental in averting the expense and disruption of daily activities associated with nosocomial vanicella.42
Finally, as is the case for mumps vaccination,43 it appears that normal children would benefit from vanicella vaccination, not by virtue of the severity of the disease but rather because of the inevitability of disease and its associated expense. However, important unanswered questions remain about the duration of vaccine-induced immunity, latency of this DNA vaccine virus, and potential adverse changes in the epidemiology of the disease. These
will generate much debate about the use of the
vaccine in normal children.
ACKNOWLEDGMENT
I thank Lois Vernon for providing the latest available data for vanicella-related encephalitis.
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