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Prophylaxis Against HAV Infection IG is a sterile preparation of concentrated antibodies (immunoglobulins) made from pooled human plasma processed by cold ethanol fractionation ( 97 ). In the United States, only plasma that has tested negative for a) hepatitis B surface antigen (HBsAg), b) antibody to human immunodeficiency virus (HIV), and c) antibody to hepatitis C virus (HCV) is used to produce IG. In addition, the U.S. Food and Drug Administration (FDA) requires that the process used to produce IG include a viral inactivation step or that final products test negative for HCV RNA by polymerase chain reaction. No transmission of hepatitis B virus, HIV, HCV, or other viruses has been reported from IG for intramuscular administration (IGIM) ( 98,99 ). Anti-HAV titers differ between IG lots, and slightly lower titers have been observed over the past several decades, probably because of the decreasing prevalence of previous HAV infection among plasma donors (100). However, no clinical or epidemiologic evidence of decreased protection has been observed. IG provides protection against hepatitis A through passive transfer of antibody. Both IGIM and IG for intravenous administration (IGIV) contain anti-HAV, but IGIM is the product used for the prevention of HAV infection. The concentrations of anti-HAV achieved following administration of IGIM are below the level of detection of commercially available diagnostic tests (101). When used for preexposure prophylaxis, a dose of 0.02 mL/kg of IG administered intramuscularly (IM) confers protection for <3 months, and a dose of 0.06 mL/kg IG administered IM confers protection for ≤ 5 months (Table 4). When administered within 2 weeks following an exposure to HAV (0.02 mL/kg IM), IG is >85% effective in preventing hepatitis A (102104). Efficacy is greatest when IG is administered early in the incubation period; when administered later in the incubation period, IG often only attenuates the clinical expression of HAV infection (102). IGIM is available in single-use (2-mL) and multidose (10-mL) vials. Some preparations are formulated without a preservative; other preparations include thimerosal as a preservative in a concentration of 100 mg/L. When administration of IGIM is indicated for infants or pregnant women, preparations that do not contain thimerosal should be used. For administration of IGIM, an appropriate muscle mass (i.e., the deltoid or gluteal muscle) should be chosen into which a large volume can be injected by using a needle length appropriate for the person´s age and size (105). If a gluteal muscle is used, the central region of the buttock should be avoided: only the upper outer quadrant should be used, and the needle should be directed anteriorly to minimize the possibility of injury to the sciatic nerve (105). Serious adverse events from IGIM are rare. Anaphylaxis has been reported after repeated administration to persons who have known immunoglobulin A (IgA) deficiency; thus, IGIM should not be administered to these persons (106). Pregnancy or lactation is not a contraindication to IG administration. IG does not interfere in general with the immune response to inactivated vaccines or to oral poliovirus vaccine or yellow fever vaccine. However, IG can interfere with the response to other live, attenuated vaccines (e.g., measles, mumps, rubella vaccine [MMR] and varicella vaccine) when administered as either individual or combination vaccines. Administration of MMR should be delayed for at least 3 months, and varicella vaccine should be delayed for at least 5 months after administration of IG for hepatitis A prophylaxis. IG should not be administered within 2 weeks after the administration of MMR or within 3 weeks after varicella vaccine unless the benefits of IG administration exceed the benefits of vaccination ( 105,107 ). If IG is administered within 2 weeks after administration of MMR or within 3 weeks after administration of varicella vaccine, the person should be revaccinated, but not sooner than 3 months after the IG administration for MMR or 5 months for varicella vaccine ( 105 ). Several inactivated and attenuated hepatitis A vaccines have been developed and evaluated in human clinical trials and in nonhuman primate models of HAV infection (108); however, only inactivated vaccines have been evaluated for efficacy in controlled clinical trials (36,109). The vaccines currently licensed in the United States are HAVRIX ® (manufactured by SmithKline Beecham Biologicals) and VAQTA ® (manufactured by Merck & Co., Inc.). Both are inactivated vaccines. Preparation Inactivated hepatitis A vaccine is prepared by methods similar to those used for inactivated poliovirus vaccine (110,111). Cell-cultureadapted virus is propagated in human fibroblasts, purified from cell lysates by ultrafiltration and exclusion gel chromatography or other methods, formalin inactivated, and adsorbed to an aluminum hydroxide adjuvant; 2-phenoxyethanol is used as a preservative for HAVRIX ®, and VAQTA ® is formulated without a preservative. For HAVRIX, ® the antigen content of the final aqueous preparation is determined by reactivity in a quantitative immunoassay for HAV antigen, and final vaccine potency (per dose) is expressed as enzyme-linked immunosorbent assay (ELISA) units (EL.U.). For VAQTA ® , the antigen content is expressed as units (U) of HAV antigen. Vaccine Storage and Shipment Hepatitis A vaccine should be stored and shipped at temperatures ranging from 35.6 F (2 C) to 46.4 F (8 C) and should not be frozen. However, the reactogenicity and immunogenicity of HAVRIX ® after storage at 98.6 F (37 C) for 1 week and the stability profile of VAQTA ® when stored at this temperature for >12 months do not differ from those of vaccines stored at the recommended temperature (112) (Merck & Co., Inc., unpublished data, 1996). Route of Administration, Vaccination Schedule, and Dosage The vaccine should be administered intramuscularly into the deltoid muscle. A needle length appropriate for the person´s age and size should be used (105). HAVRIX ® is available in two formulations, and the formulation differs according to the person´s age: for persons 218 years of age, 720 EL.U. per dose in a two-dose schedule; and for persons >18 years of age, 1,440 EL.U. per dose in a two-dose schedule (Table 5). A pediatric formulation of 360 EL. U. per dose administered in a three-dose schedule is no longer available. VAQTA ® is licensed in two formulations, and the formulation differs according to the person´s age: for persons 217 years of age, 25 U in a two-dose schedule; for persons >17 years of age, 50 U per dose in a two-dose schedule (Table 6). Vaccine Performance Detection of anti-HAV after vaccination Concentrations of antibody achieved after passive transfer by IG or active induction by vaccination are 10100-fold lower than those produced after natural infection and are often below the detection level of commercially available diagnostic assays (101). To measure lower levels of antibody, more sensitive immunoassays have been developed that correlate more closely with neutralizing antibody assays (101). However, these assays have not been reviewed by the FDA and are not approved for any clinical indication. Anti-HAV concentrations are measured in comparison with a World Health Organization reference immunoglobulin reagent and are expressed as milli-International Units per milliliter (mIU/mL). The lower limits of detection are approximately 100 mIU/mL by unmodified, commercially available assays and 10 mIU/mL by more sensitive assays. Thus, a positive anti-HAV result by a standard assay indicates protection. However, after vaccination, persons who are anti-HAV negative by standard assays might still have protective levels of antibody. The absolute lower limit of antibody required to prevent HAV infection has not been defined. In vitro studies using cell-culturederived virus indicate that low levels of antibody (e.g., <20 mIU/mL) can be neutralizing (113). Clinical studies have yielded few data from which a minimum protective antibody level can be derived because vaccine-induced levels of antibody have been high and few infections have been detected among vaccinated persons. Experimental studies in chimpanzees indicate that low levels of passively transferred antibody (<10 mIU/mL) obtained from immunized persons do not protect against infection but do prevent clinical hepatitis and virus shedding (114). To define a protective antibody response, clinical studies conducted with HAVRIX ® have used levels >20 mIU/mL (or >33 mIU/mL in more recent studies) as measured with modified enzyme immunoassays, and studies conducted with VAQTA ® have used levels >10mIU/mL as measured with a modified radioimmunoassay (115,116). Immunogenicity in adults Both licensed vaccines are highly immunogenic in persons aged ≥18 years when administered according to the recommended schedules (116118). Protective antibody levels developed in 94%100% of adults 1 month after the first dose. After the second dose, all persons had protective levels of antibody, with high geometric mean antibody concentrations (GMCs). Few data are available regarding the timing of the appearance of neutralizing anti-body. Among a sample of vaccinated persons, 54%62% were positive for neutralizing antibody 14 days after the first dose, and 94%100% were positive at 1 month (116) (SmithKline Beecham Biologicals, unpublished data, 1994). Immunogenicity in children and adolescents Both vaccines are highly immunogenic when administered to children and adolescents according to a variety of schedules. From 97% to 100% of persons aged 218 years had protective levels of antibody 1 month after receiving the first dose, and 100% had protective levels 1 month after the second dose, with high GMCs (116121). Immunogenicity in infants Available data indicate that hepatitis A vaccine is immunogenic in children aged <2 years who do not have passively acquired maternal antibody. All such infants administered hepatitis A vaccine developed protective anti-body levels, with the final GMCs varying depending on the dosage and schedule (122125). Infants with passively acquired maternal antibody have reduced GMCs after vaccination (see Factors Associated with Reduced Immunogenicity on page 22). IgM anti-HAV after vaccination Hepatitis A vaccination can induce IgM anti-HAV that is detectable by standard assays, particularly if the test is conducted soon after vaccination. IgM anti-HAV has been detected 23 weeks after administration of one dose of vaccine in 8%20% of adults (126) (CDC, unpublished data, 1995). However, when tested 1 month after vaccination, only 1% of 311 adults had detectable IgM anti-HAV (127). Efficacy The efficacy of HAVRIX ® was evaluated in a double-blind, controlled, randomized clinical trial conducted in Thailand among approximately 40,000 children 116 years of age living in villages that had high rates of hepatitis A (109). After two doses of vaccine (360 EL.U. per dose) administered 1 month apart, the efficacy of vaccine in protecting against clinical hepatitis A was 94% (95% confidence interval, 79%99%). A double blind, placebo-controlled, randomized clinical trial using VAQTA ® was conducted among approximately 1,000 children 216 years of age living in a New York community that had a high rate of hepatitis A. The protective efficacy against clinical hepatitis A was 100% (lower bound of the 95% confidence interval, 87%) after administration of one dose (25 U) of vaccine (36). Studies of chimpanzees indicate that hepatitis A vaccine can prevent HAV infection if administered shortly after exposure (128). Because the incubation period of hepatitis A can be 50 days, the fact that during a clinical efficacy trial, no cases of hepatitis A occurred in vaccine recipients beginning 17 days after vaccination also suggests a possible postexposure effect (36,45). In a small-randomized trial, investigators found that hepatitis A vaccine was 79% efficacious in preventing IgM anti-HAV positivity after household exposure to hepatitis A when compared with no treatment (129). However, the confidence interval was extremely wide (7%95%) and investigators did not assess the efficacy of the vaccine compared with IG (130). Results of an appropriately designed clinical trial comparing the postexposure efficacy of vaccine with that of IG are needed to determine if hepatitis A vaccine without IG could be recommended to prevent hepatitis A after exposure. Effectiveness in outbreak settings Several studies have examined the effectiveness of hepatitis A vaccine in controlling outbreaks in communities that have high rates of hepatitis A. Administration of hepatitis A vaccine to children aged 216 years during a clinical trial evaluating vaccine efficacy resulted in a substantial decrease in community hepatitis A rates, and ongoing vaccination of young children has prevented expected communitywide outbreaks in subsequent years (36,45). In several Alaskan villages in which hepatitis A outbreaks were occurring, vaccination of children and adolescents and of susceptible adults with one dose of hepatitis A vaccine resulted in a rapid decrease in the number of new cases (42). In addition, in several American Indian communities experiencing outbreaks, early and rapid implementation of childhood hepatitis A vaccination programs stopped the outbreaks (43,44). Ongoing vaccination of young children has continued in these areas, and no further cases have been reported in subsequent years (CDC unpublished data, 1999). In these settings, vaccination was carried out in small, well-defined communities, and in most circumstances, an estimated 70% or more of persons in the target population were vaccinated. Hepatitis A vaccine has been used in several communities that have intermediate rates of hepatitis A and were experiencing outbreaks. In Butte County, California, hepatitis A incidence decreased concurrently with the implementation of a program in which approximately 37% of children aged 212 years were administered one dose of hepatitis A vaccine (53). In Memphis, Tennessee, following a targeted vaccination program in which one dose of vaccine was administered to 52% of eligible children aged 29 years, hepatitis A rates decreased in this target population (54). In two villages in Slovakia, a communitywide outbreak ended 2 months after approximately two thirds of school-age children were administered two doses of vaccine (131). Few data are available regarding the use of hepatitis A vaccine without IG to control outbreaks in day care centers. In one Italian study, hepatitis A vaccine was administered to children and staff of a nursery school and some of their household contacts to attempt to interrupt a 6-week long outbreak (132). Clinical cases among vaccinated children occurred up to 10 days after vaccination, but cases among unvaccinated adult household contacts continued to occur for 2 months. Further study is needed to determine if hepatitis A vaccine can be used alone during day care center outbreaks. Long-term protection Among adults who received three doses of HAVRIX ® (720 EL.U. per dose at 0-, 1-, and 6-month intervals), 100% of those persons had anti-HAV levels >20 mIU/mL 8 years after the initial dose (P. Van Damme, University of Antwerp, Belgium, unpublished data, 1999). Six years after vaccination, all but one of 313 adults administered two doses of 1,440 EL. U. of HAVRIX ® had anti-HAV levels >20 mIU/mL (133). Protective levels of anti-HAV were still observed in 99% of 549 children evaluated 56 years after receiving VAQTA ® (134). Estimates of antibody persistence derived from kinetic models of antibody decline indicate that protective levels of anti-HAV could be present for ≥20 years (133,135137). Whether other mechanisms (e.g., cellular memory) also contribute to long-term protection is un-known. As has been done for other vaccines, surveillance data and population-based studies are being conducted to monitor the long-term protective efficacy of hepatitis A vaccine and to determine the possible need for a booster dose. In the longest such follow-up reported to date, no cases of hepatitis A have been detected among children followed for 7 years after vaccination (45) (Merck & Co., Inc. unpublished data, 1999). Vaccination schedules According to the licensed schedule, 18-year-old persons should receive the adult dosage of VAQTA ® (Table 6). However, the seroconversion rate among 18-year-old persons administered 25U of VAQTA ® was similar to the rate for those vaccinated with the dosage licensed for this age (i.e., 50 U) (Merck & Co., Inc., unpublished data, 1999). Results of a number of studies indicate that among adults administered hepatitis A vaccine according to a schedule that mixed the two currently licensed vaccines, the proportion who developed protective antibody levels did not differ from that of adults vaccinated according to the licensed schedules, and final GMCs were high (138,139). Although using the vaccines according to the licensed schedule is preferable, given the similar immunogenicity of both vaccines in adults and children, these data indicate that the two brands of hepatitis A vaccine can be considered interchangeable. Limited data are available regarding response to a delayed second vaccine dose. In one study, 97% of 87 persons aged >18 years old who had received one dose of VAQTA ® (50 U) had anti-HAV levels >10 mIU/mL 18 months later. None reported a history of hepatitis A and all responded to a second dose. There was no difference in final GMCs compared with persons vaccinated according to the licensed schedule (Table 6) (Merck & Co., Inc., unpublished data, 1999). In another study, 82% of 51 persons aged 5 months to 39 years who had responded to one dose of HAVRIX ® (720 EL.U. for children aged <18 years; 1440 EL.U. for adults) had anti-HAV levels >20 mIU/mL a mean of 27 months later. None of these persons reported a history of hepatitis A. All of these persons responded to a second dose, with a large boost in GMCs (B. McMahon, Viral Hepatitis Program, Alaska Native Medical Center, Anchor-age, unpublished data, 1999). In a third study, 79% of 124 persons had antibody titers >20 mIU/mL a median of 35 months (range, 2466 months) after receiving the first vaccine dose. All of these persons responded to a second dose; no difference was observed in final GMCs among these persons compared with persons vaccinated according to the recommended schedule (140). Factors associated with reduced immunogenicity The presence of anti-HAV at the time of vaccination appears to blunt the immune response. Administration of IG concurrently with the first dose of hepatitis A vaccine did not decrease the proportion of adults who developed protective levels of antibody compared with adults who had been administered hepatitis A vaccine alone (141,142), but the GMCs of adults who received IG were substantially lower 1 month after completion of the vaccination series than the GMCs of adults who had been administered hepatitis A vaccine alone. However, their antibody levels were at least 100-fold higher than levels considered to be protective. Therefore, the reduced immunogenicity of hepatitis A vaccine that occurs with concurrent administration of IG does not appear to be clinically significant. Reduced vaccine immunogenicity also has been observed in infants who had passively acquired antibody because of prior maternal HAV infection and were administered hepatitis A vaccine according to a number of different schedules (122124). In most studies, all infants developed protective levels of antibody, but the final GMCs were approximately one third to one tenth those of infants born to anti-HAVnegative mothers and vaccinated according to the same schedule. In some studies, administration of hepatitis A vaccine to persons with HIV infection resulted in lower seroprotection rates and antibody concentrations (143,144). In one study, 77% of HIV-infected persons had protective antibody levels after completing the vaccine series, and their final GMCs were considerably lower than those for HIVnegative persons (143). Among HIV-infected men, those who responded to hepatitis A vaccination had significantly more CD4+ T-lymphocytes at baseline (540/mL) compared with those who did not respond (280/mL) (144). Vaccination of adults with chronic liver disease of viral or nonviral etiology produced seroprotection rates similar to those observed in healthy adults (145,146). However final antibody levels were substantially lower for each group of chronic liver disease patients than for healthy adults. In one small study, none of the eight patients who had received a liver transplant responded to hepatitis A vaccination (147). Limited data indicate that age might reduce the immunogenicity of hepatitis A vaccine. In several studies, the proportion of persons aged >40 years who had protective antibody levels was similar to that of persons aged £40 years, but final antibody levels were lower in the older age group (118,148150). Additional factors associated with decreased immunogenicity to other vaccines (e.g., smoking, obesity) have not been evaluated for the currently licensed formulations of hepatitis A vaccine. No data are available pertaining to response rates to revaccination among persons who do not respond to the primary vaccination series. Simultaneous administration with other vaccines Limited data from studies conducted among adults indicate that simultaneous administration of hepatitis A vaccine with diphtheria, poliovirus (oral and inactivated), tetanus, typhoid (both oral and IM), cholera, Japanese encephalitis, rabies, or yellow fever vaccines does not decrease the immune response to either vaccine or increase the frequency of reported adverse events (151153). Studies indicate that hepatitis B vaccine can be administered simultaneously with hepatitis A vaccine without affecting either vaccine´s immunogenicity or increasing the frequency of adverse events (154). Several studies are being conducted among infants and young children to evaluate whether simultaneous administration of hepatitis A vaccine with diphtheria-tetanus-pertussis (DTP), diphtheria-tetanus-acellular pertussis (DTaP), Haemophilus influenzae type b (Hib), hepatitis B, MMR, and oral and inactivated poliovirus vaccines affects the immunogenicity and reactogenicity of these vaccines. Side Effects and Adverse Events Data concerning adverse events are derived from prelicensure clinical studies worldwide, reports following licensure of HAVRIX ® in Europe and Asia, other post-licensure studies, and reports to the national Vaccine Adverse Events Reporting System (VAERS) following licensure of HAVRIX ® and VAQTA ® in the United States. Local reactions Approximately 50,000 persons were administered HAVRIX ® in pre-licensure clinical studies (155). No serious adverse events were attributed definitively to hepatitis A vaccine. Among adults, the most frequently reported side effects occurring within 3 days after the 1,440 EL.U. dose were soreness at the injection site (56%), headache (14%), and malaise (7%). In clinical studies among children, the most frequently reported side effects were soreness at the injection site (15%), feeding problems (8%), headache (4%), and injection-site induration (4%). Approximately 9,200 persons were administered VAQTA ® in prelicensure clinical studies, with no serious adverse events reported among participants ( 156 ). Among adults, the most frequent side effects that occurred within 5 days following vaccination included tenderness (53%), pain (51%), and warmth (17%) at the injection site and headache (16%). Among children, the most common side effects reported were pain (19%), tenderness (17%), and warmth (9%) at the injection site. Serious adverse events An estimated 1.3 million persons in Europe and Asia were vaccinated with HAVRIX ® before the vaccine´s licensure in the United States in 1995. Reports of serious adverse events, without regard to causality, received by the vaccine manufacturer included anaphylaxis, Guillain-Barré syndrome, brachial plexus neuropathy, transverse myelitis, multiple sclerosis, encephalopathy, and erythema multiforme (SmithKline Beecham Biologicals, unpublished data, 1995). Most of these events occurred among adults, and approximately one third occurred among persons receiving other vaccines concurrently. For serious adverse events for which back-ground incidence data were known (e.g., Guillain-Barré syndrome and brachial plexus neuropathy), the rates for vaccine recipients were not higher than would be expected for an unvaccinated population (CDC, unpublished data, 1995). No serious adverse events were reported for approximately 40,000 children who were administered the 360 EL.U. dose of HAVRIX ® in the protective efficacy study (109). In a post-licensure study of 11,417 children and 25,023 adults administered VAQTA ® , no serious adverse events considered to be associated with administration of the vaccine occurred ( 157 ) (Merck & Co., Inc., unpublished data, 1999). From the time hepatitis A vaccine was first licensed in the United States in 1995 through December 1998, >6.5 million doses were administered to the U.S. civilian population, including >2.3 million pediatric doses (SmithKline Beecham Biologicals, unpublished data, 1999, and Merck & Co., Inc., unpublished data, 1999). During this 4-year period, VAERS received 247 reports of unexplained adverse events within 6 weeks after hepatitis A vaccination, including 80 among children <19 years old and 167 among adults (CDC, unpublished data, 1999). Approximately one third of events involved the concurrent use of other vaccines with hepatitis A vaccine. Thirteen of the events among children (0.6/100,000 vaccine doses distributed) and 85 of the events among adults (1.4/100,000 vaccine doses distributed) were considered serious. These events, without regard to causality, included neurologic, hematologic, and autoimmune syndromes. No reported serious events could be definitively attributed to hepatitis A vaccination. For serious adverse events for which incidence data are available, VAERS reporting rates were not higher than reported background rates (CDC, unpublished data, 1999). For example, published background incidence rates for Guillain-Barré syndrome have ranged from 0.5 to 2.4 cases per 100,000 person-years (158,159). The five Guillain-Barré cases among adult recipients of hepatitis A vaccine represent an estimated incidence of 0.2 cases per 100,000 person-years. In total, >65 million doses of hepatitis A vaccine have been administered worldwide (personal communications, SmithKline Beecham Biologicals, 1999, and Merck & Co., Inc., 1999). Reviews of data from multiple sources for >5 years regarding adverse events did not identify any serious adverse events among children or adults that could be definitively attributed to hepatitis A vaccine or an increase in serious adverse events among vaccinated persons above baseline rates (109,157,160). The safety of the vaccine will continue to be assessed through ongoing monitoring of data from VAERS and other surveillance systems. Any adverse event suspected to be associated with hepatitis A vaccination should be reported to VAERS. VAERS forms can be obtained by calling (800) 822-7967, and information on how to report adverse events can be obtained from the VAERS home page at <http://www.fda.gov/cber/vaers/vaers.htm>. Contraindications and Precautions Hepatitis A vaccine should not be administered to persons with a history of a severe reaction to a prior dose of hepatitis A vaccine or to a vaccine component (e.g., alum, 2-phenoxyethanol [in the case of HAVRIX ®]). The safety of hepatitis A vaccination during pregnancy has not been determined; however, because hepatitis A vaccine is produced from inactivated HAV, the theoretical risk to the developing fetus is expected to be low. The risk associated with vaccination should be weighed against the risk for hepatitis A in women who might be at high risk for exposure to HAV. Because hepatitis A vaccine is inactivated, no special precautions need to be taken when vaccinating immunocompromised persons. Prevaccination Serologic Testing for Susceptibility Antibody production in response to HAV infection results in lifelong immunity to hepatitis A and, presumably, to HAV infection. Vaccination of a person who is immune because of prior infection does not increase the risk for adverse events. In populations that have expected high rates of prior HAV infection, prevaccination testing may be considered to reduce costs by not vaccinating persons who have prior immunity. Testing of children is not indicated because of their expected low prevalence of infection. For adults, the decision to test should be based on a) the expected prevalence of immunity; b) the cost of vaccination compared with the cost of serologic testing (including the cost of an additional visit); and c) the likelihood that testing will not interfere with initiating vaccination. For example, if the cost of screening (including laboratory and office visits) is one third the cost of the vaccine series, then screening potential recipients in populations where the prevalence of infection is likely to be >33% should be cost-effective (161). Persons for whom prevaccination testing will likely be most cost-effective include adults who were either born in or lived for extensive periods in geographic areas that have a high endemicity of HAV infection (Figure 5); older adolescents and adults in certain population groups (i.e., American Indians, Alaskan Natives, and Hispanics); and adults in certain groups that have a high prevalence of infection (e.g., injecting drug users). In addition, the prevalence might be high enough among all older adults to warrant prevaccination testing. For example, the anti-HAV prevalence among persons >40 years of age, determined by NHANES-III testing, is generally >33% (regardless of race/ethnicity or income level). Thus, if the cost of screening is one third the cost of the vaccination series, prevaccination testing of any person >40 years of age would likely be cost-effective. Commercially available tests for total anti-HAV should be used for prevaccination testing. Postvaccination Testing for Serologic Response Postvaccination testing is not indicated because of the high rate of vaccine response among adults and children. In addition, testing methods that have the sensitivity to detect low anti-HAV concentrations after vaccination are not approved for routine diagnostic use in the United States.
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