Japanese Encephalitis Immunization in South Korea: Past, Present, and Future

Emerging Infectious Diseases. 2000;6(1) 

In This Article

The Future of the Immunization Program

Although the cost-effectiveness of the JE immunization program, including annual boosters, has not been evaluated, JE has been successfully controlled in South Korea for the past 2 decades. Questions remain about the optimum immunization schedule, including appropriate ages for initial vaccination and boosters. The state health authority recommends two doses 4 weeks apart with a booster 1 year later as a primary immunization, and annual boosters thereafter up to 15 years of age. Since the longevity of neutralizing antibody after primary vaccination was not known and seemed short lived, frequent boosters appeared necessary. However, without sound evidence, the total of 14 doses of vaccine until 15 years of age led to concerns about excessive vaccination and increased risk for vaccine adverse effects.

The 1994 report of the cluster of severe adverse systemic effects after JE vaccination prompted medical and social debate[22,23]. A causal association between JE vaccine and the cluster of severe adverse effects has not been clearly established; however, empiric evidence, including the timing of events, characteristics of the adverse reactions, susceptibility, and lack of alternative etiologic agents, indicates a causal relationship. Public concern over adverse reactions led to refusal of the vaccination and a consequent decrease in coverage rate. In response, the National Compensation Program for Vaccine Injury was begun in 1995.

During public debate about the JE immunization schedule, the safety and quality of the domestically produced JE vaccines were questioned. The Advisory Committee of the National Immunization Program announced that the annual booster immunization schedule had become impractical because of the inappropriate administration of the vaccine during the mass immunization in the spring, the need to define the long-term immunity in the elderly (> 65 years of age), poor recognition of adverse effects, the need to guarantee the quality of the vaccine manufactured in South Korea, and public reluctance to receive JE vaccination. The committee agreed that the JE immunization program should be improved with regard to the schedule, age of initial vaccination, booster schedule, and vaccine strain. The annual booster schedule was changed to once every 2 years, and single-dose rather than multidose vials were used, as recommended by the South Korean Society of Pediatricians.

In 1996, a seroprevalence study for plaque-reduction neutralizing antibody (PRNT) was carried out to indirectly evaluate the efficacy of booster vaccination in 311 schoolchildren[24]. The neutralizing antibody titers were found to decrease gradually as the interval between boosters increased (Figure 4A). The seropositivity rate of 98.1%, 99%, and 95.6% at 6, 18, and 30 months, respectively, had declined to 71.4% by 42 months (Figure 4B).

Figure 4. A. Plague-reduction neutralizing antibody titers (pRNT) according to interval since last booster injection with Nadayama vaccine among 311 South Korean children, 1996. B. PRNT antibody seropositivity rate according to the interval since last booster injection.

To replace the inactivated mouse brain-derived vaccine, a clinical trial with a live attenuated SA14-14-2 vaccine, which has been used safely and effectively in >100 million children in China since 1988[25], was conducted in South Korean children in 1997. A preliminary immunogenicity study among South Korean children 1 to 3 years of age indicated a 96% rate of seroconversion in PRNT antibody, with a geometric mean titer (GMT) of 188 after a single primary immunization dose. In children who had been immunized with two or three doses of inactivated Nakayama vaccine, the booster administration of SA14-14-2 vaccine produced an anamnestic response with a GMT of 3,378 in all cases without virus-specific IgM response (Figure 5[26].

Figure 5. Primary or booster neutralizing antibody responses to one dose of Japanese encephalitis SA14-14-2 vaccine in South Korean children, 1997[26].

During the last 10 years, JE has occurred more frequently in adults than in childrentwo-thirds of Korean JE patients were middle-aged adults. Adults are not protected by the current immunization program, probably because of waning immunity. Long-term immunity must be maintained to prevent secondary vaccine failure. A single booster with the live-attenuated SA14-14-2 vaccine might confer long-term immunity for adults and decrease the frequency of vaccination, as well as the risk for vaccine adverse effects.

The national immunization program against JE in children should be continued according to established schedules in South Korea; however, the booster schedule should be adjusted. Surveillance for JE and vaccine adverse reactions should be strengthened to better assess the number of cases and reactions associated with immunization. A new, more advanced vaccine, such as the live attenuated SA14-14-2 vaccine, should be adopted and integrated into the pediatric immunization schedule.

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