Three serious cholera epidemics have threatened the world during the last 10 years. As a countermeasure against such cholera epidemics, three vaccines, CVD 103-HgR, WC/rBS, and Vietnamese WC, showed good performance. CVD 103-HgR is a recombinant attenuated live vaccine for travelers, and its highly safety and protective efficacy have been demonstrated in volunteers in advanced countries. WC/rBS, which consists of heat- and formalin-killed bacteria and cholera toxin B subunit, protects the vaccinees (>5 years old) from cholera for 6 months. Vietnamese WC, a heat- and formalin-killed vaccine, is inexpensive and effective even for 1 to 5-year-old children. Additionally, irradiated WC vaccines and new serotype (O139) vaccines are being developed. Regarding intestinal immunity, secretory IgA has been mainly examined. In addition, mucosal IgG, as induced by the irradiated WC vaccine, should also be investigated. Development of mucosal adjuvant, such as holotoxin-type mutants of cholera toxin and related Escherichia coli heat-labile enterotoxin, has been actively undertaken. Diverse custom-made vaccines may be one countermeasure for the changing situations in endemic countries or areas and for "barriers" against live vaccines in such areas.

Most of the children who showed systemic immediate-type reactions, including anaphylactic shock, to measles, mumps, rubella, and varicella vaccines had IgE antibodies to gelatin; thus we suspected that the allergic symptoms are caused by gelatin antigen, which is usually included in these live-virus vaccines as a stabilizer. We hypothesized that the anti-gelatin IgE is elicited by immunization with DTaP (diphtheria-tetanus-acellular pertussis) vaccines, which contained a small amount of gelatin as a spillover protein after purification of pertussis toxin. To test this hypothesis, we conducted a case-control study to determine whether children with anti-gelatin IgE had received gelatin-containing DTaP vaccines, and it was indeed found that all such children in the study had immunization histories that included the gelatin-containing DTaP vaccines. Based on these findings, the vaccine manufacturers had removed gelatin from all the DTaP and live-virus vaccines produced in Japan by 2000.

From April to August of 2000, Bacillus spp. were detected in the blood culture of 29 patients in a hospital in Japan. Of these patients, 19 had clinical signs of septicemia; positive culture in the remaining 10 patients was attributed to contamination with skin flora at the site of puncture. Of the 18 strains evaluated, 15 were Bacillus cereus, 2 were Bacillus subtilis, and one was Bacillus licheniformis. The only hospital death observed was that of a patient who had no clinical signs of septicemia at the time of blood sampling. That death is now considered attributable to the underlying neoplasm. The hospital committee for prevention of nosocomial infection concluded after a critical review of the patient records that the cause of septicemia in most cases had been contaminated intravenous lines. To control the situation, the committee recommended the use of a new skin disinfectant, and medical personnel were advised to avoid infusion pauses with interruption of intravenous lines and to replace the caps for the stopcocks with new ones each time the caps were removed. These measures were rigorously observed in addition to the conventional measures for preventing catheter sepsis, and the incidence of septicemia due to the Bacillus spp. declined dramatically thereafter.