The Safety of Japanese B Encephalitis Vaccine
Abstract & Commentary
Synopsis: A hypersensitivity reaction occurred in 26.7 per 10,000 recipients of Japanese B encephalitis vaccine.
Source: Berg SW, et al. Systemic reactions in U.S. Marine Corps personnel who received Japanese encephalitis vaccine. J Infect Dis 1997;24:265-267.
Because three confirmed cases of japanese b encephalitis occurred in 1991 in U.S. Marine Corps personnel stationed in Okinawa, all 20,000 Marines stationed there were offered Japanese B encephalitis (JE) vaccine. Even though vaccination was "voluntary," the Nakayama-NIH strain JE virus vaccine, currently distributed in the United States by Connaught Laboratories as JE-VAX, was administered to 14,249 Marines. One milliliter of vaccine was administered subcutaneously on days 0, seven, and 30. Recipients were instructed to return if they developed evidence of a hypersensitivity reaction and were also questioned about reactions at the times of their second and third doses.
A hypersensitivity reaction occurred in 38 (0.27%) vaccine recipients, and the overall reaction rate was 26.7 (95% CI, 18.2-35.1) per 10,000 vaccine recipients. The rates per 10,000 vaccine doses after the first, second, and third doses were, respectively, 16.1 (95% CI, 9.5-22.7), 10.3 (4.7-15.9), and 2.0 (0.8-4.8). Seventy-four percent of reactions after the first dose occurred within 48 hours of that dose, while the median interval of reactions after the second dose was 96 hours, with only 31% occurring within the first 48 hours. One reaction occurred 13 days after dose 2.
Of the 38 reactors, 26 (68%) had urticaria (usually generalized) and/or angioedema. Of the 13 reactors with angioedema, 11 had (85%) facial edema, and two of these reported that their tongues felt "thick." Four subjects had wheezing, and in one of these, this was the only abnormality reported. Eleven (29%) reactors had pruritus; six of these also had a non-urticarial rash. Approximately one-third of hypersensitivity reactors also complained of headache, and several had paresthesias, arhtralgia, or low-grade fever.
JE vaccine was inadvertently administered to four individuals who had reacted to an earlier dose. All four again had reactions that occurred within 15 minutes to 72 hours. None of these reactions was life-threatening. Two reactors were admitted to hospital for observation.
One additional individual, not included among the 38 reactors, who had a prior history of anaphylaxis, died approximately 60 hours after receiving a first dose of JE vaccine and 12 hours after receiving a third dose of plague vaccine. No cause for death could be established at postmortem examination.
A nested case-control study found that a history of the following variables associated with an increased likelihood of reacting to JE vaccine: urticaria, rhinitis, and any allergy.
COMMENT BY STAN DERESINSKI, MD, FACP
The authors point out that previous studies, which included only cases of urticaria and angioedema in their case definitions, reported overall reaction rates of 1-15 per 10,000. If a similar case definition is applied to the data reviewed here, the rate drops from 26.7 to 18.2 per 10,000 vaccinees. The authors suggest that their study may have captured more reactors because of their active surveillance.
The use of the vaccine has been limited to some extent in this country because of the nature of United States Public Health Service (USPHS) recommendations for its use, the requirement for multiple doses, and the fear of reactions, particularly delayed anaphylaxis. Because of the occurrence of delayed reactions, it is recommended that the last dose of the series begin at least 10 days prior to departure.
The USPHS recommends that individuals spending at least 30 days in rural endemic areas of endemicity be considered candidates for receipt of the vaccine. In addition, even if their trip is of short duration, travelers with extensive unprotected outdoor evening and nighttime exposure in such areas should also be considered vaccine candidates. British recommendations are much less stringent.
The recommended schedule for primary immunization is that used in the study under review here: 1.0 mL administered subcutaneously on days 0, 7, and 30. When insufficient time is available for this schedule (plus the 10-day interval from the last dose to departure), a compressed schedule, with doses given on days 0, 7, and 14, may be used. Only approximately 80% protection results from the first two doses alone. Consideration may be given to administration of a single booster dose after three years.
Anaphylaxis was not observed in this series, although the case of the unexplained death is worrisome. The concern about reactions to the vaccine must be balanced against knowledge of the potential severity of infection. While most infections are asymptomatic, the case-fatality rate among those who develop clinical illness is reported to be as high as 30%, with frequent neuropsychiatric sequelae in survivors.
A history of urticaria or allergic rhinitis is associated with an increased risk of a hypersensitivity reaction to JE vaccine. Nonetheless, the reaction rate is low, and, as the authors indicate, the major determinant of a recommendation for use of this vaccine should depend primarily upon the risk of exposure to this potentially devastating infection.
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