The merits of varicella vaccination for varicella non-immune health care workers

Immunity against varicella can be reliably established by history and, if negative, confirmed or refuted by serology. If non-immune, the merits of varicella vaccine for a health care worker (HCW) can be stated clearly: Protection from a disease which may be particularly severe in an adult, and evading the inconvenience (investigation time and possible work restriction) and cost of managing an exposure. This paper discusses implementation of a varicella immunity program for HCWs at Columbia Presbyterian Hospital in Oklahoma City.     

Urticaria following varicella vaccine associated with gelatin allergy

An uncommon reaction to varicella vaccine has been urticaria. Based on two reports of urticaria believed to be due to gelatin in recipients of measles-mumps-rubella vaccine, we suspected gelatin as the cause of generalized urticaria in two children after varicella vaccination. Intradermal testing with gelatin yielded a wheal and flare reaction in both children. We conclude that children known to be allergic to gelatin should not receive Oka/Merck varicella vaccine (VARIVAX).     

Cost-effectiveness of hepatitis A vaccination in healthcare workers

OBJECTIVE: To study the cost-effectiveness of vaccination for hepatitis A. SETTING: Hypothetical analysis of students currently enrolled in medical school in the United States. METHOD: A Markov-based model was developed using data from the literature, actual hospital costs, and an annual discount rate of 5%. The incidence rate was based on the lowest annual rate for the US population during the past decade. RESULTS: Over the lifetimes of students currently in medical school, the model estimated that there would be 286 hepatitis A cases with four deaths and 107 lost years of life. With routine vaccination, these numbers would decrease to 17, 0.3, and 6, respectively. The costs per life-year saved and quality adjusted life-year saved were $58,000 and $47,000, respectively. Serologic screening prior to vaccination was less cost-effective than universal vaccination. If the incidence of hepatitis A was underestimated by a factor of 5, the cost per life-year saved would decrease to $5,500. If the incidence of hepatitis was underestimated by a factor of 10, vaccination would result in a net cost savings. CONCLUSION: We conclude that the cost per life-year saved by routine hepatitis A vaccination was similar to many other standard medical modalities. For routine vaccination of medical students to be cost-saving, the incidence rate for hepatitis A must be at least 10 times higher than the rate presently reported for the general population. Serological screening prior to vaccination was not cost-effective.     

Epidemiologic effects of varicella vaccination

For a plausible range of values for the different efficacy characteristics of the live varicella (Oka) vaccine at different levels of coverage, modeling results suggest that routine immunization of preschool children would greatly reduce the number of primary varicella cases, whereas the shift in age distribution of cases would not result in increased overall morbidity as measured by number of hospitalizations. Although information about some of the vaccine assumptions is scanty, the combinations of assumptions leading to an increase in morbidity seem unlikely. A catch-up program in older children who have not yet had chickenpox will be important. The number and age distribution of the cases in vaccinees are sensitive to assumptions about the vaccine, especially the degree and distribution of partial protection against infection, relative residual infectiousness, and waning of immunity. Responsiveness to boosting by wild-type VZV infection was especially important in reducing the number of older cases. The advantage conferred by responsiveness to boosting depends on the level of transmission. The direct and indirect effects of vaccines and vaccination programs interact. Understanding how a vaccine works at the individual level is important for the vaccinated individual, but it also influences the overall public health benefits of an immunization programs. Lieu et al based a cost-effectiveness analysis of varicella vaccines on this model of varicella dynamics and assumptions about how the vaccines work. Models cannot replace biologic understanding. The purpose of such models is not to predict the number of cases of varicella, but to examine some possible consequences of introducing a vaccine into the routine immunization schedule of preschool children in the United States, effects of different vaccination strategies, and the benefits of a temporary catch-up program for older children. Modeling exercises of this sort force us to formalize our thinking, for instance about the vaccine mechanisms, and to admit our uncertainties, such as about the vaccine efficacy assumptions. Such models also show where more data need to be collected, for example, on boosting and waning of immunity and relative residual infectiousness. Improvements in the design of vaccine efficacy studies are necessary to provide the input to these models for looking at the long-term effects of vaccination programs. Frailty models can be used to analyze the data in the presence of heterogeneities in susceptibility. Waning can also be estimated using appropriate methods. Relative infectiousness of vaccinees with breakthrough cases can be measured by comparing the relative secondary attack rates when the index infected person is vaccinated and when the index infected person is unvaccinated. More studies are needed to understand how to evaluate responsiveness to boosting. Vaccine efficacy studies in the field should be designed to obtain better estimates of residual susceptibility, residual infectiousness, duration of protection, and the effects of boosting by reinfection with wild-type VZV.     

Chickenpox immunisation in New Zealand

PREVENTION: The appropriate use of varicella vaccine, effective in the prevention of chickenpox, has been considered by a Ministry of Health Working Party in 1996 and 1997, including discussion at a workshop held in Wellington, 26-27 June 1996. The introduction of varicella vaccine into the routine childhood immunisation schedule was not supported at this stage. The use of the only varicella vaccine for which the Minister of Health has given consent for distribution in New Zealand, Varilrix (SmithKline Beecham Limited), in healthy children aged nine months to 13 years inclusive, was supported. Consent has not been given for the use of Varilrix in immunocompromised people or in adults. This report discusses other groups that could be candidates for vaccination, such as children with deteriorating renal function and susceptible health care workers who regularly come into contact with especially vulnerable patients. In these cases, the vaccine would need to be administered on a named patient basis. The use of Varilrix in immunocompromised people was not supported. SURVEILLANCE: Enhanced surveillance of chickenpox and zoster are required in New Zealand. Adverse reactions to Varilrix should be carefully monitored. OUTBREAK CONTROL: There are insufficient data at present to support the use of Varilrix in outbreak control. The frequency, cost and current management of nosocomial outbreaks should be ascertained. This information may also assist in the decision whether to incorporate a varicella vaccine into the routine childhood immunisation schedule in the future.     

Management of the presumed susceptible varicella (chickenpox)-exposed gravida: a cost-effectiveness/cost-benefit analysis

OBJECTIVE: To compare the cost-effectiveness and cost-benefit of different strategies for managing the presumed susceptible varicella (chickenpox)-exposed gravida. METHODS: Three strategies were evaluated: 1) a do-nothing or observation strategy; 2) a testing strategy, in which immune status was assessed and varicella-zoster immune globulin was administered to those who tested nonimmune; and 3) a universal-administration strategy, in which varicella-zoster immune globulin was given to all exposed, presumed susceptible gravidas. Because precise data are unavailable about varicella mortality and hospitalization rates in pregnancy, a range of potential rates was evaluated, from one to greater than 20 times healthy nonpregnant adult rates. The potential efficacy of varicella-zoster immune globulin varied from 1 to 99%. A strategy was defined as cost-effective if it cost less than $50,000 per life-year gained. RESULTS: If the mortality rate from varicella infection in pregnancy was increased fivefold over the nonpregnant healthy adult rate (ie, from 31/100,000 to 155/100,000 cases), efficacy would have to be at least 49% for the immune-testing strategy to be cost-effective. If pregnancy only doubled the varicella mortality rate, then even with perfect efficacy, the immune-testing strategy would not be cost-effective. Under most assumptions, the universal-administration strategy was cost-ineffective when compared with the immune-testing strategy. Similar results were obtained in the parallel cost-benefit analysis, which considered hospitalization costs and rates. The analysis was sensitive to the varicella transmission rate and the discount rate. CONCLUSION: From a cost-effectiveness/cost-benefit standpoint, management based on immune testing is preferable to universal varicella-zoster immune globulin administration when caring for the varicella-exposed gravida with a negative or indeterminate infection history.     

High incidence of breakthrough varicella observed in healthy Japanese children immunized with live attenuated varicella vaccine (Oka strain)

In order to know the rate of occurrence of varicella among vaccinees (breakthrough varicella: BV), questionnaire postcards were sent to 593 healthy children who had received varicella vaccine (Oka strain) from March 1987 to December 1989. The questionnaire survey was repeated once a year until January 1996. The annual attack rate from the 1st to 3rd questionnaire was approximately 12%: however, from the 5th to 8th one it was 1-4%. To February 1996, the cumulative attack rate was 157/459 (34.2%). This rate was comparable to that among vaccinees who had confirmed seroconversion; namely, 51/132 (38.6%). These rates are much higher than those reported by other authors. All BV cases were clinically mild; even subjects who had received the vaccine 7 years prior to the disease showed mild symptoms. The high incidence may be partly explained by the regional epidemiology of varicella. The decrease in annual incidence with time after vaccination may be due to the following reasons: some vaccinees remained free from BV owing to reinforcement of their immunity from subclinical infection of varicella-zoster virus (VZV) and others from diminution of opportunity for exposure to VZV with increasing age. Varicella vaccine seems to be effective in modifying the symptoms of varicella, but not potent enough in protecting from VZV infection.     

HIV arthritis

Whether reexposure of varicella-immune persons to varicella-zoster virus would protect against or predispose to development of zoster was analyzed. The rate of zoster in 511 leukemic recipients of varicella vaccine who had 1 or > 1 dose of varicella vaccine and in those who did or did not have a household exposure to varicella was determined. A Kaplan-Meier life-table analysis revealed that the incidence of zoster was lower in those given > 1 dose of vaccine (P < .05). A Cox proportional hazards analysis showed that both household exposure to varicella and receipt of > 1 dose of vaccine were highly protective (P < .01) against zoster. Thus, the risk of zoster is decreased by reexposure to varicella-zoster virus, either by vaccination or by close exposure to varicella.     

Clinical trials of varicella vaccine in healthy children

The Oka varicella vaccine has been tested in clinical trials worldwide in thousands of children. Following licensure in Japan, Korea, Germany, and the United States, the vaccine has been used in several millions of children. The vaccine has been generally well-tolerated with the most common complaints being pain and redness at the injection site and a mild rash following vaccination. The incidence of herpes zoster has not increased in vaccinees and may have decreased. Efficacy rates vary between 65% and 100% depending on the intensity of exposure to natural varicella and the potency of the vaccine. In those few vaccinees who develop MVLS, the rash is generally milder than seen following natural infection (median < 50 versus 300 lesions, respectively, as well as a lower incidence of fever). There has been no evidence to date to indicate waning immunity postvaccination. Studies are in progress in the United States to evaluate whether this will occur and the effect of booster doses of vaccine. It is expected that in countries where there is widespread use of the vaccine in healthy children, disease rates will fall dramatically as will the morbidity and mortality associated with natural varicella in this population.     

The risk of measles, mumps, and varicella among young adults: a serosurvey of US Navy and Marine Corps recruits

OBJECTIVES: To assess the risk of epidemic transmission and to guide immunization policy, the seroprevalence of antibody to measles, mumps, and varicella was determined in a group of young adults. METHODS: A cross-sectional study of 1533 US Navy and Marine Corps recruits was conducted in June 1989. Antibody status was determined with commercially available enzyme-linked immunosorbent assays. RESULTS: Direct sex and race adjustment to the 15- to 29-year-old US population resulted in seronegativity rates of 17.8% for measles, 12.3% for mumps, and 6.7% for varicella. Measles and mumps seronegativity rates were higher among Whites whereas varicella seronegativity was higher among non-Whites. Recruits enlisting from outside the 50 US states, especially those from island territories, were more likely to lack varicella antibody. The sensitivity of a positive history of vaccination or disease in predicting antibody status was less than 90% for all diseases. CONCLUSIONS: These results suggest a continued potential for epidemics, especially of measles, and the need for mandatory immunization policies. Immigrants to the United States, especially those from island territories, may be a high-risk group that could benefit from varicella vaccination.     

Preventing perinatal transmission of HIV--costs and effectiveness of a recommended intervention

OBJECTIVE: To calculate the national costs of reducing perinatal transmission of human immunodeficiency virus through counseling and voluntary testing of pregnant women and zidovudine treatment of infected women and their infants, as recommended by the Public Health Service, and to compare these costs with the savings from reducing the number of pediatric infections. METHOD: The authors analyzed the estimated costs of the intervention and the estimated cost savings from reducing the number of pediatric infections. The outcome measures are the number of infections prevented by the intervention and the net cost (cost of intervention minus the savings from a reduced number of pediatric HIV infections). The base model assumed that intervention participation and outcomes would resemble those found in the AIDS Clinical Trials Group Protocol 076. Assumptions were varied regarding maternal seroprevalence, participation by HIV-infected women, the proportion of infected women who accepted and completed the treatment, and the efficacy of zidovudine to illustrate the effect of these assumptions on infections prevented and net cost. RESULTS: Without the intervention, a perinatal HIV transmission rate of 25% would result in 1750 HIV-infected infants born annually in the United States, with lifetime medical-care costs estimated at $282 million. The cost of the intervention (counseling, testing, and zidovudine treatment) was estimated to be $ 67.6 million. In the base model, the intervention would prevent 656 pediatric HIV infections with a medical care cost saving of $105.6 million. The net cost saving of the intervention was $38.1 million. CONCLUSION: Voluntary HIV screening of pregnant women and ziovudine treatment for infected women and their infants resulted in cost savings under most of the assumptions used in this analysis. These results strongly support implementation of the Public Health Service recommendations for this intervention.     

Small bowel injury in gastroschisis: relation to fetal presentation

The study presented here attempts to assess the cost savings attributable to having an on-site corporate medical clinic. For a period of 4 months, employees using the clinic were surveyed regarding: (1) whether they would have used an outside doctor if the corporate medical department clinic were not available, and (2) how many days per year they estimated that they came to work because there was an on-site medical center when they would otherwise have stayed at home. The results indicated that, on average, employees who used the facility saved 3.3 days of absenteeism. That total cost savings was calculated to be $499,212 per year. In addition, 69% of employees indicated that they would have sought attention elsewhere, suggesting that the presence of an on-site medical center does not induce demand. The findings concerning the hidden savings brought about by an on-site medical center are also discussed.     

Varicella zoster virus vaccine--a review

The available published data on the efficacy and safety of a live attenuated varicella vaccine is presented. The data indicate that immunosuppressed leukemic children at high risk for severe varicella can be vaccinated resulting in complete or partial immunity in most children. Vaccination of immunosuppressed children is often associated with fever and rash. There seems to be a decreased risk of herpes zoster in vaccinated leukemic children when compared with a group of naturally infected leukemic children. In order to diminish the risk of varicella zoster virus (VZV) transmission to these high-risk persons family members of these, if susceptible to varicella infection, should be immunized. Although vaccination of healthy children is highly effective and associated with a low frequency of adverse events, vaccination in this group may be questioned due to the benign course of varicella. Due to the more severe VZV-infection seen among non-immune healthy adults, it seems reasonable to offer vaccination to this group. It will, however, require extensive serological testing to identify seronegative individuals. From a theoretical point of view a booster-vaccination to the elderly population, resulting in detectable cell-mediated immunity to VZV, should reduce the risk of herpes zoster. Large placebo-controlled studies are needed to confirm if such an immunization can prevent herpes zoster in this age group.     

Critical value of prevalence for vaccination programmes. The case of hepatitis A vaccination in Spain

Programmes using screening and vaccination are efficient in populations with higher levels of antibodies, while in those with lower levels is more efficient to vaccine the whole target population. The prevalence that makes the cost-effectiveness of vaccination programmes equal to that obtained for programmes using screening and vaccination is defined as the critical value of prevalence p*. In this study, a mathematical procedure to obtain the critical value of prevalence is developed. The formula obtained is used to decide the best vaccination strategy against hepatitis A in Spain. If V is the vaccination cost, S the screening cost, PV the predictive value of a positive test result, D the mean disease cost, A the attack rate in susceptible individuals, E the vaccine efficacy and C the vaccination compliance, the critical value of prevalence is equal to: [formula: see text] The critical value of prevalence obtained for vaccination against hepatitis A in Spain with three doses of vaccine Havrix 720 is 22%. This result show that the optimal decision is to implement vaccination programmes without screening for immunity in individuals aged < 15 years and with screening in those aged > 15 years.     

The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community

BACKGROUND: Despite recommendations for annual vaccination against influenza, more than half of elderly Americans do not receive this vaccine. In a serial cohort study, we assessed the efficacy and cost effectiveness of influenza vaccine administered to older persons living in the community. METHODS: Using administrative data bases, we studied men and women over 64 years of age who were enrolled in a large health maintenance organization in the Minneapolis-St. Paul area. We examined the rate of vaccination and the occurrence of influenza and its complications in each of three seasons: 1990-1991, 1991-1992, and 1992-1993. Outcomes were adjusted for age, sex, diagnoses indicating a high risk, use of medications, and previous use of health care services. RESULTS: Each cohort included more than 25,000 persons 65 years of age or older. Immunization rates ranged from 45 percent to 58 percent. Although the vaccine recipients had more coexisting illnesses at base line than those who did not receive the vaccine, during each influenza season vaccination was associated with a reduction in the rate of hospitalization for pneumonia and influenza (by 48 to 57 percent, P < or = 0.002) and for all acute and chronic respiratory conditions (by 27 to 39 percent, P < or = 0.01). Vaccination was also associated with a 37 percent reduction (P = 0.04) in the rate of hospitalization for congestive heart failure during the 1991-1992 season, when influenza A was epidemic. The costs of hospitalization for all types of illness studied were lower in the vaccinated group during 1991-1992 (range of reduction, 47 to 66 percent; P < 0.005) and for acute and chronic respiratory conditions and congestive heart failure in 1990-1991 (reductions of 37 percent and 43 percent, respectively; P < or = 0.05). Direct savings per year averaged $117 per person vaccinated (range, $21 to $235), with cumulative savings of nearly $5 million. Vaccination was also associated with reductions of 39 to 54 percent in mortality from all causes during the three influenza seasons (P < 0.001). CONCLUSIONS: For elderly citizens living in the community, vaccination against influenza is associated with reductions in the rate of hospitalization and in deaths from influenza and its complications, as compared with the rates in unvaccinated elderly persons, and vaccination produces direct dollar savings.     

Risk factors for lack of detectable antibody following hepatitis B vaccination of Minnesota health care workers

OBJECTIVE: To assess the presence of antibody to hepatitis B surface antigen (anti-HBs) at postvaccination testing in Minnesota health care workers receiving recombinant hepatitis B vaccines, and to identify risk factors for lacking anti-HBs following hepatitis B vaccination. DESIGN: Retrospective cohort study. SETTING: Ten acute care hospitals in Minnesota. PARTICIPANTS: A total of 595 health care workers who had received hepatitis B vaccine (Recombivax HB or Engerix-B) between June 1987 and December 1991 and who underwent postvaccination testing for anti-HBs within 6 months after receiving the third dose of vaccine. MAIN OUTCOME MEASURE: Presence or absence of anti-HBs following hepatitis B vaccination. RESULTS: Five variables were independently associated with lacking anti-HBs by multivariate analysis: vaccine brand, smoking status, gender, age, and body mass index. Stratifying by vaccine brand demonstrated that age (P = .01), body mass index (P < .01), and smoking status (P < .01) were associated with lacking anti-HBs only for Recombivax HB recipients; and gender (P = .03) was associated with lacking anti-HBs only for Engerix-B recipients. After controlling for smoking status, age, gender, and body mass index, recipients of Recombivax HB were more likely to lack anti-HBs than recipients of Engerix-B (relative risk, 2.3; 95% confidence interval, 1.1 to 4.7; P = .02). CONCLUSIONS: Results indicate that certain populations of health care workers are at increased risk of not responding to hepatitis B vaccination. Further studies evaluating immunogenicity of currently available recombinant hepatitis B vaccines in persons at high risk for primary vaccine failure are needed.     

Safety of influenza vaccine in heart transplant recipients

BACKGROUND: Influenza vaccine is recommended for heart transplant recipients, but its administration is often deferred because of anecdotal reports of rejection associated with the vaccine. We evaluated the safety of influenza vaccine in a group of stable heart transplant recipients over a 2-year period. METHODS: During the 1993 to 1994 influenza season, stable heart transplant recipients who had undergone transplantation a minimum of 1 year before study entry were randomized to vaccination with a single dose of influenza vaccine versus no vaccination. Routine endomyocardial biopsies and postvaccination influenza serologic studies were performed between 2 and 6 weeks after enrollment/immunization. During the 1994 to 1995 season, patients were given 2 doses of influenza vaccine, separated by 3 weeks; endomyocardial biopsies and serologic studies were performed between 2 and 6 weeks after the second immunization or enrollment (if control subject). Biopsy results were evaluated with respect to vaccine response, immunosuppressive regimens, and patient demographics. RESULTS: Eighteen patients were enrolled in the single vaccine trial and 10 in the booster vaccine trial. Four of 14 vaccine recipients had biopsy specimens consistent with International Society for Heart and Lung Transplantation grades 2 to 3A as compared with 1 of 14 control subjects (grade 2) (p = .326). All episodes of rejection in the vaccine recipients were asymptomatic and responded to a single course of treatment. Rejection was unrelated to the time from transplantation, doses of immunosuppression, age, or number of doses of or response to vaccine. CONCLUSIONS: Influenza vaccine can be safely administered to most heart transplant recipients but may be associated with low-level histologic rejection.     

Reflex excitability and isometric force production in cerebral palsy: the effect of serial casting

INTRODUCTION: Since 1971 widespread vaccination has limited the number of adenoviral acute respiratory disease (ARD) outbreaks in Army recruits. Increased vaccine costs have recently threatened the continuation of the vaccination program. METHODS: We conducted a cost-effectiveness analysis to assess the consequences of changing the year-round Army adenovirus vaccination program to (1) seasonally targeted vaccine administration (only during the high-risk period) or (2) complete discontinuation of the program from the perspective of total cost to the Army. Costs included vaccination costs and direct and indirect medical and military training costs. Health outcomes were estimated as the number of hospitalizations for ARD prevented. In the reference case, the incidence rate among unvaccinated and vaccinated individuals was 4.06 and 1.5 per 100 person weeks, respectively. Results are expressed for a cohort of 76,171 recruits. RESULTS: In the absence of adenoviral vaccination, a projected 12,370 cases of ARD hospitalization would occur, costing $26.4 million annually. A seasonally targeted program would prevent 7,800 cases of ARD and save $16.1 million over no vaccination. Year-round immunization would not prevent any additional cases but would save $15.5 million over no vaccination. Year-round vaccination would become the cost-effective strategy if ARD incidence during the low-risk months were to increase. CONCLUSION: Vaccination of Army recruits by any schedule was cost-saving due to the high level of prevented disease and averted hospitalizations. Even though a seasonally targeted program provided the greatest cost-savings, year-round vaccination must remain an option due to the potential for adenoviral ARD outbreaks in the low-risk period.     

FIRE (fatty acid synthase insulin-responsive element) and ICE (inverted CCAAT element) regulate fatty acid synthase

Varicella is a highly communicable infection caused by the varicella-zoster virus. Although generally a benign, self-limited disease, varicella infection may be associated with serious complications, especially in older adults and young infants. Live attenuated varicella vaccine was licensed by the U.S. Food and Drug Administration in March 1995. Assessment of varicella immunity status and vaccination of susceptible persons are desirable in all adolescents and adults. Vaccination guidelines stress a systematic review of several factors: neomycin sensitivity, immunosuppressed status, current health and use of medications (particularly corticosteroids), recent use of immune globulin, risk of pregnancy, lactation status and risk of inadvertent transmission to vulnerable contacts.